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BACKGROUD: The study objective was to compare three-dimensional and two-dimensional imaging using computer-assisted systems (CASs) in clinical guidance for preoperative surgical planning for middle hepatic tumors in children. METHODS: A retrospective analysis was performed on 23 children who underwent surgery for middle hepatic tumors in our hospital from January 2016 to June 2022. The surgical resection plan was formulated by the operator team using two-dimensional CT images before the operation. Then, the same qualified surgeons conducted an in-depth analysis and formulated the surgical resection scheme for the same pediatric patient using three-dimensional imaging of the middle hepatic tumor. The feasibility of the two schemes was compared and analyzed. RESULT: All the tumors were successfully removed according to the preoperative method developed using three-dimensional imaging. The postoperative short-term follow-up revealed that all patients were doing well. Preoperative plans were revised in 9 cases after evaluating the three-dimensional images due to the disparity between the original plans and the three-dimensional relationship between the tumor and blood vessels, vascular variation, and the volume of remnant liver. CONCLUSIONS: Three-dimensional imaging with a computer-assisted surgery system is superior to two-dimensional imaging in the preoperative planning of pediatric hepatoblastoma.
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Hepatectomia , Imageamento Tridimensional , Neoplasias Hepáticas , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Masculino , Cirurgia Assistida por Computador/métodos , Criança , Tomografia Computadorizada por Raios X/métodos , Pré-Escolar , Hepatectomia/métodos , Cuidados Pré-Operatórios/métodos , Lactente , Adolescente , Estudos de ViabilidadeRESUMO
BACKGROUND: Giant hepatic hemangiomas are rare and can cause serious complications that contribute to a high risk of perinatal mortality. The purpose of this article is to review the prenatal imaging features, treatment, pathology, and prognosis of an atypical fetal giant hepatic hemangioma and to discuss the differential diagnosis of fetal hepatic masses. CASE PRESENTATION: A gravida 9, para 0 woman at 32 gestational weeks came to our institution for prenatal ultrasound diagnosis. A complex, heterogeneous hepatic mass measuring 5.2 × 4.1 × 3.7 cm was discovered in the fetus using conventional two-dimensional ultrasound. The mass was solid and had both a high peak systolic velocity (PSV) of the feeding artery and intratumoral venous flow. Fetal magnetic resonance imaging (MRI) revealed a clear, hypointense T1-W and hyperintense T2-W solid hepatic mass. Prenatal diagnosis was very difficult due to the overlap of benign and malignant imaging features on prenatal ultrasound and MRI. Even postnatally, neither contrast-enhanced MRI nor contrast-enhanced computed tomography (CT) was useful in accurately diagnosing this hepatic mass. Due to persistently elevated Alpha-fetoprotein (AFP), a laparotomy was performed. Histopathological examination of the mass showed atypical features such as hepatic sinus dilation, hyperemia, and hepatic chordal hyperplasia. The patient was ultimately diagnosed with a giant hemangioma, and the prognosis was satisfactory. CONCLUSIONS: When a hepatic vascular mass is found in a third trimester fetus a hemangioma should be considered as a possible diagnosis. However, prenatal diagnosis of fetal hepatic hemangiomas can be challenging due to atypical histopathological findings. Imaging and histopathological assays can provide useful information for the diagnosis and treatment of fetal hepatic masses.
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Hemangioma , Neoplasias Hepáticas , Humanos , Feminino , Gravidez , Hemangioma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Feto/patologia , Diagnóstico Pré-Natal , Imageamento por Ressonância Magnética , Ultrassonografia , Terceiro Trimestre da GravidezRESUMO
Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.
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Neoplasias Hepáticas , Nanopartículas , Cirurgia Assistida por Computador , Humanos , Fototerapia , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Linhagem Celular TumoralRESUMO
PURPOSE: Microfocus computed tomography (micro-CT) has not been widely used at high radiation intensity (industrial micro-CT) in life science fields. In this preliminary study, we investigated its potential value in the detection of micro-hepatic tumors in a mouse model. METHODS: The liver with micro-hepatic tumors was surgically resected en-bloc from mice, and examined with industrial micro-CT and lower intensity micro-CT (small animal micro-CT). The number of hepatic tumors was manually counted on serial images. Then, the accuracy of each technique was determined by preparing matching liver sections and comparing the number of tumors identified in a conventional pathological examination. RESULTS: The number of hepatic tumors evaluated with industrial micro-CT showed high concordance with the results of the pathological examinations (intraclass correlation coefficient [ICC]: 0.984; 95% confidence interval [CI] 0.959-0.994). On the other hand, the number of hepatic tumors evaluated with the small animal micro-CT showed low concordance with the number identified in the pathological examinations (ICC: 0.533; 95% CI 0.181-0.815). CONCLUSION: Industrial micro-CT improved the detection of small structures in resected specimens, and might be a promising solution for life science research.
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Disciplinas das Ciências Biológicas , Neoplasias Hepáticas , Animais , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Camundongos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. MATERIALS AND METHODS: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints. RESULTS: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. CONCLUSION: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%. IMPLICATIONS FOR PRACTICE: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Antígeno Ki-67 , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Somatostatina/uso terapêuticoRESUMO
Multigenerational adverse effects from the environment such as nutrition and chemicals are among important concerns in environmental health issues. Previously, we have found that arsenite exposure of only F0 females during their pregnancy increases hepatic tumors in the F2 males in C3H mice. In the current study, we investigated the association of DNA methylation with the hepatic tumor increase in the F2 males of the arsenite group. Reduced-representation bisulfite sequencing analysis newly identified that DNA methylation levels of regions around the transcriptional start sites of Tmem54 and Cd74 were decreased and the expression of these genes were significantly increased in the hepatic tumors of F2 males of the arsenite group. The associations between DNA methylation in these regions and gene expression changes were confirmed by treatment of murine hepatoma cell lines and hepatic stellate cell line with 5-aza-2'-deoxycytidine. Overexpression of Cd74 in Hepa1c1c7 cells increased Trib3 expression and suppressed the expression of tumor suppressor genes Id3 and Atoh8. Human database analysis using the Cancer Genome Atlas indicated that TMEM54, CD74, and TRIB3 were significantly increased and that ATOH8 was decreased in hepatocellular carcinoma. The data also showed that high expression of TMEM54 and TRIB3 and low expression of ATOH8 were associated with poor survival. These results suggested that an increase in Tmem54 and Cd74 expression via DNA methylation reduction was involved in the tumor increase in the F2 male offspring by gestational arsenite exposure of F0 females. This study also suggested that genes downstream of Cd74 were involved in tumorigenesis.
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Arsenitos/efeitos adversos , Carcinoma Hepatocelular/genética , Metilação de DNA/genética , Neoplasias Hepáticas/genética , Animais , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/induzido quimicamente , Linhagem Celular Tumoral , Feminino , Expressão Gênica/genética , Antígenos de Histocompatibilidade Classe II/genética , Neoplasias Hepáticas/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C3H , GravidezRESUMO
BACKGROUND AND AIMS: Surgical planning in liver resection depends on the precise understanding of the three-dimensional (3D) relation of tumors to the intrahepatic vascular trees. This study aimed to investigate the impact of 3D printing (3DP) technology on the understanding of surgical liver anatomy. METHODS: We selected four hepatic tumors that were previously resected. For each tumor, a virtual 3D reconstruction (VIR) model was created from multi-detector computed tomography (MDCT) and was prototyped using a 3D printer. Forty-five surgical residents were evenly assigned to each group (3DP, VIR, and MDCT groups). After evaluation of the MDCT scans, VIR model, or 3DP model of each tumor, surgical residents were asked to assign hepatic tumor locations and state surgical resection proposals. The time used to specify the tumor location was recorded. The correct responses and time spent were compared between the three groups. RESULTS: The assignment of tumor location improved steadily from MDCT, to VIR, and to 3DP, with a mean score of 34.50, 55.25, and 80.92, respectively. These scores were out of 100 points. The 3DP group had significantly higher scores compared with other groups (p < 0.001). Furthermore, 3DP significantly improved the accuracy of surgical resection proposal (p < 0.001). The mean accuracy of the surgical resection proposal for 3DP, VIR, and MDCT was 57, 25, and 25%, respectively. The 3DP group took significantly less time, compared with other groups (p < 0.005). The mean time spent on assessing the tumor location for 3DP, VIR, and MDCT groups was 93, 223, and 286 s, respectively. CONCLUSIONS: 3D printing improves the understanding of surgical liver anatomy for surgical residents. The improved comprehension of liver anatomy may facilitate laparoscopy or open liver resection.
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Hepatectomia , Imageamento Tridimensional , Neoplasias Hepáticas/cirurgia , Fígado/anatomia & histologia , Modelos Anatômicos , Tomografia Computadorizada Multidetectores , Impressão Tridimensional , Estudos Transversais , Humanos , Laparoscopia , Fígado/diagnóstico por imagem , Fígado/cirurgia , Cuidados Pré-Operatórios/métodos , Estudos ProspectivosRESUMO
Objective: This study aimed to evaluate the risk factors of biloma formation and secondary infection after thermal ablation for malignant hepatic tumors. Patients and methods: A total of 58 patients with 68 bilomas after thermal ablation were recruited as the complication group, and 61 patients with 72 lesions without major complications were selected randomly as the control group. The potential risk factors for biloma formation were analyzed with the chi-square test and multivariate logistic regression analysis. To determine the optimum management method for biloma, patients with secondary infection were included for the subgroup analysis of risk factors. Results: A history of transcatheter arterial chemoembolization (TACE) treatment (odds ratio [OR]: 3.606, 95% confidence interval [CI]: 1.165-11.156, p = .026) and tumor location (OR: 37.734, 95% CI: 13.058-109.034, p = .000) were independent predictors of biloma formation. Among the 58 patients with biloma, 49 (84.5%) showed no symptoms (i.e., the asymptomatic group), while the remaining 9 (15.5%) developed symptoms related to secondary infections (i.e., the symptomatic group). There were significant differences in the history of biliary manipulation (p = .031) between the symptomatic and asymptomatic groups. Conclusion: A history of TACE treatment and the distance from the biliary tract were independent predictors of biloma formation after thermal ablation. Therefore, protecting the bile duct (i.e., cooling of the bile duct and combing thermal ablation with chemical ablation) should be considered for high-risk patients. Moreover, active monitoring and management should be performed for patients with bilomas who underwent biliary surgery before.
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Técnicas de Ablação/efeitos adversos , Ductos Biliares/patologia , Carcinoma Hepatocelular/complicações , Hipertermia Induzida/efeitos adversos , Neoplasias Hepáticas/complicações , Técnicas de Ablação/métodos , Carcinoma Hepatocelular/radioterapia , Feminino , Humanos , Hipertermia Induzida/métodos , Neoplasias Hepáticas/radioterapia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
In the last 2-3 decades, gene therapy represented a promising option for hepatocellular carcinoma (HCC) treatment. However, the design of safe and efficient gene delivery systems is still one of the major challenges that require solutions. In this study, we demonstrate a versatile method for covalent conjugation of glycyrrhizin acid (GL) or glycyrrhetinic acid (GA) to increase the transfection efficiency of Polyethyleneimine (PEI, Mw 1.8K) and improve their targeting abilities of hepatoma carcinoma cells. GA and GL targeting ligands were grafted to PEI via N-acylation, and we systematically investigated their biophysical properties, cytotoxicity, liver targeting and transfection efficiency, and endocytosis pathway trafficking. PEI-GA0.75, PEI-GL10.62 and PEI-GL20.65 conjugates caused significant increases in gene transfection efficiency and superior selectivity for HepG2 cells, with all three conjugates showing specific recognition of HepG2 cells by the free GA competition assay. The endocytosis inhibition and intracellular trafficking results indicated that PEI-GA0.75 and GL10.62 conjugates behaved similarly to SV40 virus, by proceeding via the caveolae- and clathrin-independent mediated endocytosis pathway and bypassing entry into lysosomes, with an energy independent manner, achieving their high transfection efficiencies. In the HepG2 intraperitoneal tumor model, PEI-GA0.75 and PEI-GL10.62 carrying the luciferase reporter gene gained high gene expression, suggesting potential use for in vivo application.
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Carcinoma Hepatocelular/terapia , Técnicas de Transferência de Genes , Terapia Genética/métodos , Ácido Glicirretínico/análogos & derivados , Ácido Glicirrízico/análogos & derivados , Neoplasias Hepáticas/terapia , Polietilenoimina/análogos & derivados , Animais , Endocitose , Feminino , Genes Reporter , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/metabolismoRESUMO
Two cases of hepatocellular carcinoma (HCC) in 2 female captive golden-headed lion tamarins (Leontopithecus chrysomelas) are described. HCC was diagnosed in both, with pulmonary metastasis in one of them. Neoplastic cells were positive for hepatocyte-specific antigen (HSA) by immunohistochemistry, confirming the diagnosis.
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Carcinoma Hepatocelular/veterinária , Leontopithecus , Neoplasias Hepáticas/veterinária , Doenças dos Macacos/diagnóstico , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Doenças dos Macacos/diagnóstico por imagemRESUMO
PURPOSE: Laparoscopic liver resection is increasingly used to treat patients with hepatic tumor. However, during laparoscopic resection, information obtained by palpation using laparoscopic forceps or from intraoperative ultrasonography is extremely limited, which may pose a risk for positive surgical margins. This study aimed to investigate the feasibility and clinical application of near-infrared (NIR) fluorescence imaging to guide laparoscopic liver resection of a liver tumor and secure the surgical margins. METHODS: A preliminary study in 25 patients was conducted. NIR imaging was used intraoperatively during laparoscopic liver resection. The liver tumors were preoperatively labeled by intravenously injecting the patients with indocyanine green dye (0.5 mg/kg), an NIR fluorescence agent. During the surgical procedure, the PINPOINT Endoscopic Fluorescence Imaging System was used to assess the surgical margin by using real-time endoscopic high-definition visible and NIR fluorescence imaging. RESULTS: All tumors were identified and resected laparoscopically by using the PINPOINT system, and all resections successfully secured the surgical margin. The pathological findings of all tumors indicated negative margins, defined as R0. CONCLUSIONS: This technique showed the potential to improve the intraoperative identification and demarcation of tumors. Its use could potentially reduce the number of positive resection margins.
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Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Margens de Excisão , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Corantes/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Verde de Indocianina/administração & dosagem , Laparoscopia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: To explore the value of parameters of multiphase dynamic contrast-enhanced magnetic resonance imaging (MDCE-MRI) in the qualitative diagnosis of hepatic masses. METHODS: Eighty patients with hepatic masses were retrospectively analyzed. All the patients underwent MDCE-MRI at 3.0 T MR before treatment. Mean enhancement time (MET), positive enhancement integral (PEI), a maximum slope of increase (MSI), and a maximum slope of decrease (MSD) were measured. RESULTS: There were significant differences between benign and malignant hepatic masses with respect to MET, PEI, and MSI values. The PEI and MSI values between hemangiomas, hepatocellular carcinomas (HCCs), cholangiocarcinomas, and metastatic tumors had significant differences. The MSD value between metastatic tumors, HCCs, and hemangiomas were significantly different. The area under the curve (AUC) values of the receiver operator characteristic curves for MET, PEI, and MSI were 0.70, 0.72, and 0.80, respectively. The specificity of MET, PEI, and MSI were all 77%, and the sensitivities of MSI was the highest, of which was 82.40%. Logistic regression analysis showed the regression equation to be P = 1/[1 + e0.008 × 1 + 0.007 × 2-6.707], and taking the Youden index maximum points as a diagnostic point was 0.2946. CONCLUSION: Some parameters of MDCE-MRI have significant roles in differentiating hepatic masses.
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Carcinoma Hepatocelular/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Gadolínio DTPA , Hemangioma/patologia , Humanos , Aumento da Imagem/métodos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To determine whether T2*-weighted MRI has the ability to visualize the irradiated liver parenchyma and liver tumor after irradiation to the previously superparamagnetic iron oxide (SPIO)-accumulated liver. MATERIALS AND METHODS: We examined 24 liver tumor-bearing rats. Nine rats (Group 1) received 20 µmol Fe/kg SPIO and subsequent 70-Gy irradiation to the tumor-bearing liver lobe. Four rats (Group 2) received SPIO and sham irradiation. Six rats (Group 3) received saline and irradiation. Finally, five rats (Group 4) received saline and sham irradiation. We acquired sequential 3 Tesla T2*-weighted images of the liver on day 7, and assessed MR image findings including signal intensity of the tumors and tumor-bearing liver lobes. RESULTS: In six rats in Group 1, tumors shrunk by 39-100% (303-0 mm3 ), and severely, well-defined hypointense irradiated areas were observed. In the other two rats, tumors enlarged by 25 and 172% (595 and 1148 mm3 ), and hypointense rings surrounded the tumors. The normalized relative signal intensity of the irradiated areas was significantly lower than that of the tumor (0.53 ± 0.06 versus 0.94 ± 0.06; P < 0.05). The severely, well-defined hypointense areas were not observed in the other groups. Histologically, necrotic regions dominated and minimal nonnecrotic tumor cells remained in irradiated areas. The number of CD68-positive cells was higher in irradiated areas than in nonirradiated areas. CONCLUSION: T2*-weighted MR imaging visualized the irradiated liver parenchyma as markedly, well-defined hypointense areas and liver cancer lesions as hyperintense areas only when SPIO was administered before irradiation. The visualization of the hypointense area was associated with tumor regression after irradiation. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:303-312.
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Dextranos/farmacocinética , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Fígado/diagnóstico por imagem , Fígado/metabolismo , Imagem Multimodal/métodos , Animais , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Meios de Contraste/farmacocinética , Feminino , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Nanopartículas de Magnetita , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Cholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates. RECENT FINDINGS: Cholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation. Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy. Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease. This article provides an overview of cholangiocarcinoma and discusses the current diagnosis and treatment options. While incidence is increasing and more risk factors are being discovered, much more work remains to improve outcomes of this ominous disease.
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Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/terapia , Biomarcadores Tumorais/sangue , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/terapia , Terapia Combinada , Gerenciamento Clínico , Humanos , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Liver resection is the treatment option with the best chance for cure in patients with malignant liver tumors. However, there are concerns regarding postoperative recovery in elderly patients, which may lead to a preference of non-resectional therapies over hepatectomy in this patient population. Although laparoscopic liver resection (LLR) is associated with a faster recovery compared to open hepatectomy, there are scant data on how elderly patients tolerate LLR. The aim of this study was to analyze the perioperative outcomes of LLR in elderly patients with hepatic malignancies, with a comparison to laparoscopic RFA (LRFA). METHODS: A retrospective analysis of a prospective database for liver tumors identified a total of 82 patients older than 65 years who underwent laparoscopic treatment of their liver tumors in a single tertiary care center between 2000 and 2014. These patients were equally distributed into LLR and LRFA treatment arms. RESULTS: Mean age, American Society of Anesthesiologists (ASA) score and tumor type (predominantly metastatic colorectal cancer) were similar in both groups. Patients in the LRFA group had more tumors (2.1 ± 1.8 vs. 1.2 ± 0.6, p < 0.01), whereas tumors were larger in the LLR group (3.8 ± 1.6 vs. 2.8 ± 1.1 cm, p < 0.01). Although the operative time (116 vs. 214 min, p < 0.01) and hospital stay (2.1 vs. 3.4 days, p = 0.010) were shorter for the LRFA versus LLR group, respectively, morbidity (4.8 vs. 7.3 %) and mortality (0 vs. 0 %) were similar. Local recurrence was significantly higher in the LRFA versus LLR group (29 vs. 2.4 %, respectively, p = 0.002). However, there was no statistical difference in disease-free and overall survival between two groups (28 vs. 30 and 51 vs. 54 months, p = 0.443 and 0.768, respectively). CONCLUSIONS: This study showed that LLR was tolerated as well as LRFA in elderly patients with similar comorbidities. We suggest LLR to be considered as an option in selected elderly patients who are deemed poor candidates for open hepatectomy.
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Ablação por Cateter , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Tempo de Internação , Masculino , Recidiva Local de Neoplasia , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD. OBJECTIVE: We aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy. METHODS: We conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial. RESULTS: We identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence. CONCLUSIONS: Several established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.
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AIM: In bipolar radiofrequency ablation (RFA) therapy, insertion of multiple needles at appropriate points on a target is difficult. The aim of our study was to evaluate a simplified method for multi-electrode insertion using a newly developed double-barreled needle guidance system for percutaneous RFA of hepatic tumors. METHODS: RFA using two bipolar electrodes was performed in 15 consecutive patients (nine men, six women; mean age, 72.0 ± 8.2 years) with a solitary small (≤3 cm) hepatic tumor. The first five nodules were treated using the conventional puncture method with the standard attachment, then 10 nodules were ablated using the parallel puncture method with the double-barreled attachment. The times required for double-needle placement and the shapes of the ablated areas were compared between the two puncture methods. RESULTS: The parallel puncture method required a shorter time for double-needle placement than the conventional method (12 s [range, 8-24] vs 96 s [range, 50-240]; P = 0.0003), and allowed continuous observation of the tip of all needles and the size of the ablated area as it increased until completion of the ablation. The method also provided a stable ellipsoidal ablated area. The median height, width and thickness were 30 mm (range, 22-34), 30 mm (range, 21-33) and 20 mm (range, 7-25), respectively, using 20-mm electrodes, and 34 mm (range, 32-41), 36 mm (range, 35-38) and 24 mm (range, 23-24), respectively, using 30-mm electrodes. CONCLUSION: The parallel puncture method may be a feasible procedure for multi-needle RFA therapy.
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AIM: We evaluated the performance of automated tumor-feeder detection (AFD) software using cone-beam computed tomography technology in identifying tumor-feeders of extrahepatic collaterals. METHODS: AFD was prospectively used in superselective transarterial chemoembolization (TACE) or embolization (TAE) of extrahepatic collaterals for 29 hepatocellular carcinomas and one liver metastasis (mean tumor diameter ± standard deviation, 28 ± 15.6 mm) in 25 patients. The detectability of extrahepatic tumor-feeders with non-selective digital subtraction angiography (DSA) and AFD was evaluated and compared using a χ(2) -test. Tumor response of target lesions in each patient at 2-3 months after treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Complications were also evaluated. RESULTS: Of 46 tumor-feeders, non-selective DSA and AFD could identify 26 and 44, respectively (P < 0.001). Regarding the origin of tumor-feeders, both non-selective DSA and AFD could identify 14 of 15, six of seven and two of two tumor-feeders of the right inferior phrenic, omental and right renal capsular artery, respectively. In the cystic and left gastric or right colic artery, AFD could identify 13 of 13 and nine of nine tumor-feeders but non-selective DSA could identify only three of 13 and one of nine, respectively (P < 0.001). Complete response was obtained in 15 patients, partial response in six, stable disease in three and progressive disease in one. No severe complications developed except for right pleural effusion after embolization of the right inferior phrenic artery. CONCLUSION: AFD has a sufficient ability to identify extrahepatic tumor-feeders and may improve the safety and local effects of TACE/TAE of extrahepatic collaterals.
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BACKGROUND: Robotic-assisted liver resection (RALR) was introduced as procedures of overcoming the limitations of traditional laparoscopic liver resection (LLR). The aim of this review was to evaluate the surgical results of RALR from all published studies and the results of comparative studies of RALR versus LLR for hepatic neoplasm. METHODS: Eligible studies involved RALR that published between January 2001 and December 2014 were reviewed systematically. Comparisons between RALS and LLR were pooled and analyzed by meta-analytical techniques using random- or fixed-effects models, as appropriate. RESULTS: In total, 29 studies, involving 537 patients undergoing RALR, were identified. The most common RALR procedure was a wedge resection and segmentectomy (28.67%), followed by right hepatectomy (17.88%), left lateral sectionectomy (13.22%), and bisegmentectomy (9.12%). The conversion and complication rates were 5.59 and 11.36%, respectively. The most common reasons for conversion were bleeding (46.67%) and unclear tumor margin (33.33%). Intracavitary fluid collections and bile leaks (40.98%) were the most frequently occurring morbidities. Nine studies, involving 774 patients, were included in meta-analysis. RALR had a longer operative time compared with LLR [mean difference (MD) 48.49; 95% confidence interval (CI) 22.49-74.49 min; p = 0.0003]. There were no significant differences between the two groups in blood loss [MD 31.53; 95% CI -14.74 to 77.79 mL; p = 0.18], hospital stay [MD 0.13; 95% CI -0.54 to 0.80 days; p = 0.18], postoperative overall morbidity [odds ratio (OR) 0.76; 95% CI 0.49-1.19; p = 0.23], and surgical margin status (OR 0.61; 95% CI 0.33-1.12; p = 0.11); cost was greater than robotic surgery (p = 0.001). CONCLUSION: RALR and LLR display similar safety, feasibility, and effectiveness for hepatectomies, but further studies are needed before any final conclusion can be drawn, especially in terms of oncologic and cost-effectiveness outcomes.
Assuntos
Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Laparoscopia/métodos , Tempo de Internação , Razão de Chances , Duração da Cirurgia , Período Pós-Operatório , Resultado do TratamentoRESUMO
Gestational exposure can affect the F2 generation through exposure of F1 germline cells. Previous studies reported that arsenite exposure of only F0 females during their pregnancy increases hepatic tumors in the F1 males in C3H mice, whose males are predisposed spontaneously to develop hepatic tumors later in life. The present study addressed the effects of gestational arsenite exposure on tumorigenesis of the F2 males in C3H mice. Expression analysis of several genes in the normal livers at 53 and 80 weeks of age clearly showed significant changes in the F2 males obtained by crossing gestational arsenite-exposed F1 (arsenite-F1) males and females compared to the control F2 males. Some of the changes were shown to occur in a late-onset manner. Then the tumor incidence was assessed at 75-82 weeks of age in the F2 males obtained by reciprocal crossing between the control and arsenite-F1 males and females. The results demonstrated that the F2 males born to arsenite-F1 males developed tumors at a significantly higher rate than the F2 males born to the control F1 males, irrespective of exposure of F1 females. Gene expressions of hepatocellular carcinoma markers ß-catenin (CTNNB1) and interleukin-1 receptor antagonist in the tumors were significantly upregulated in the F2 males born to arsenite-F1 males compared to those born to the control F1 males. These results show that arsenite exposure of only F0 pregnant mice causes late-onset changes and augments tumors in the livers of the F2 males by affecting the F1 male offspring.