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1.
PeerJ ; 11: e15546, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37744240

RESUMEN

Background: Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods: We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results: We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Humanos , Niño , Neoplasias de la Tiroides/genética , Carcinoma Neuroendocrino/genética , Agresión , Microambiente Tumoral/genética
2.
Front Pediatr ; 10: 1055729, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36467495

RESUMEN

As a neuroendocrine tumor derived from the neural crest, neuroblastoma (NB) is the most common extracranial solid tumor in children. The prognosis in patients with low- and intermediate-risk NB is favorable while that in high-risk patients is often detrimental. However, the management of the considerably large proportion of high-risk patients remains challenging in clinical practice. Among various new approaches, oncolytic virus (OV) therapy offers great advantages in tumor treatment, especially for high-risk NB. Genetic modified OVs can target NB specifically without affecting normal tissue and avoid the widespread drug resistance issue in anticancer monotherapy. Meanwhile, its safety profile provides great potential in combination therapy with chemo-, radio-, and immunotherapy. The therapeutic efficacy of OV for NB is impressive from bench to bedside. The effectiveness and safety of OVs have been demonstrated and reported in studies on children with NB. Furthermore, clinical trials on some OVs (Celyvir, Pexa-Vec (JX-594) and Seneca Valley Virus (NTX-010)) have reported great results. This review summarizes the latest evidence in the therapeutic application of OVs in NB, including those generated in cell lines, animal models and clinical trials.

3.
Front Oncol ; 12: 893206, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860547

RESUMEN

Sialoblastoma (SBL) is an infrequent embryonal malignant tumor originating from the salivary gland, resembling primitive salivary gland anlage, whereas hepatoblastoma (HB) is the most common pediatric liver malignancy. The simultaneous occurrence of both tumors is extremely rare. Here we reported a case of a 6-month-old infant diagnosed with synchronous SBL and HB. The patient received neoadjuvant chemotherapy followed by surgical resection. Fresh tissues of both tumors were collected before and after chemotherapy, which were further profiled by whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). WES analysis revealed potential somatic driver mutation PIK3CA p.Glu454Lys for SBL and canonical mutation CTNNB1 p.Ser45Pro for HB. No shared somatic variants or common copy number alterations were found between SBL and HB primary tumor samples. Though scRNA-seq, single-cell atlases were constructed for both tumors. SBL may recapitulate a pre-acinar stage in the development of salivary gland, including basaloid, duct-like, myoepithelial-like, and cycling phenotypes. In the meantime, HB was composed of tumor cells resembling different stages of the liver, including hepatocyte-like, hepatic progenitor-like, and hepatoblast-like cells. After chemotherapy, both tumors were induced into a more mature phenotype. In terms of transcriptional signatures, SBL and HB showed enhanced expression of epithelial markers KRT8, KRT18, and essential embryo development genes SDC1, MDK, indicating the disruption of normal embryo epithelium development. Finally, heterozygous deleterious germline mutation BLM and FANCI were identified which could predispose the patient to higher cancer risk. It partially explained the reason for the co-occurrence of SBL and HB. Taken together, we provided valuable resources for deciphering cellular heterogeneity and adaptive change of tumor cells after chemotherapy for synchronous SBL and HB, providing insights into the mechanisms leading to synchronous pediatric tumors.

4.
Front Pediatr ; 9: 625451, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34079779

RESUMEN

Objectives: Biliary atresia (BA) is a rare neonatal liver disease of which the early diagnosis remains a challenge for clinicians. Our center has established a nomogram diagnostic model based on clinical characteristics and liver function characteristics. We aim to develop and validate a nomogram that includes additional ultrasound and finds hepatobiliary abnormality with better BA early screening performance. Methods: In this single-center, retrospective cohort analysis, 1,001 neonatal obstructive jaundice (NOJ) patients between 2012 and 2015 were enrolled. Multivariable analysis was used to identify clinical characteristics, laboratory liver function characteristics, and ultrasonic features that may early screen BA. A nomogram was developed to predict the probability of BA using multiple logistic regression analysis. This nomogram was subsequently validated using another cohort of 501 NOJ patients between 2015 and 2017. Calibration curve analysis and decision curve analyses were performed to evaluate and interpret the nomogram's clinical benefits. Results: Gender, direct bilirubin (DB), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), fasting gallbladder visibility, fasting gallbladder filling, and common bile duct visibility were found to have profound statistical significance between the BA and non-BA groups (P < 0.05). The significant features were used to build the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) value of the novel nomogram (0.87) was superior to those of the former nomogram (0.83) and GGT alone (0.81) in the prediction of BA. The calibration curve revealed a close resemblance between the predicted and actual BA probabilities. Also, the net benefit from the decision curve analysis (DCA) of the nomogram (0.54) was superior to those of the former nomogram (0.49) and GGT alone (0.45) at 80% of threshold possibility. Conclusions: The nomogram has demonstrated better performance for BA screening by including additional information of the US finding, holding a promising future as a non-invasive method for BA patients.

5.
World J Clin Cases ; 7(16): 2287-2301, 2019 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-31531322

RESUMEN

BACKGROUND: Perioperative shivering is clinically common during cesarean sections under neuraxial anesthesia, and several neuraxial adjuvants are reported to have preventive effects on it. However, the results of current studies are controversial and the effects of these neuraxial adjuvants remain unclear. AIM: To evaluate the effects of neuraxial adjuvants on perioperative shivering during cesarean sections, thus providing an optimal choice for clinical application. METHODS: A systematic review and network meta-analysis were conducted following the PRISMA (Preferred Reported Items for Systematic Review and Meta-analysis) guidelines. Analyses were performed using Review Manager 5.3 and Stata 14.0. We searched PubMed, EMBASE, Web of Science, and Cochrane Central databases for eligible clinical trials assessing the effects of neuraxial adjuvants on perioperative shivering and other adverse events during cesarean sections. Perioperative shivering was defined as the primary endpoint, and nausea, vomiting, pruritus, hypotension, and bradycardia were the secondary outcomes. RESULTS: Twenty-six studies using 9 neuraxial adjuvants for obstetric anesthesia during caesarean sections were included. The results showed that, compared with placebo, pethidine, fentanyl, dexmedetomidine, and sufentanil significantly reduced the incidence of perioperative shivering. Among the four neuraxial adjuvants, pethidine was the most effective one for shivering prevention (OR = 0.15, 95%CI: 0.07-0.35, surface under the cumulative ranking curve 83.9), but with a high incidence of nausea (OR = 3.15, 95%CI: 1.04-9.57) and vomiting (OR = 3.71, 95%CI: 1.81-7.58). The efficacy of fentanyl for shivering prevention was slightly inferior to pethidine (OR = 0.20, 95%CI: 0.09-0.43), however, it significantly decreased the incidence of nausea (OR = 0.34, 95%CI: 0.15-0.79) and vomiting (OR = 0.25, 95%CI: 0.11-0.56). In addition, compared with sufentanil, fentanyl showed no impact on haemodynamic stability and the incidence of pruritus. CONCLUSION: Pethidine, fentanyl, dexmedetomidine, and sufentanil appear to be effective for preventing perioperative shivering in puerperae undergoing cesarean sections. Considering the risk-benefit profiles of the included neuraxial adjuvants, fentanyl is probably the optimal choice.

6.
BBA Clin ; 6: 125-130, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27761414

RESUMEN

Symptoms of early hepatocellular carcinoma (HCC) often go unnoticed, so more than half of patients with primary HCC are diagnosed after their disease has already reached an intermediate or advanced stage, or after portal hypertension has appeared. While hepatic resection is widely recognized as a first-line therapy to treat very early or early HCC, its use in treating intermediate or advanced HCC or HCC involving portal hypertension remains controversial. Here we review PubMed-indexed literature covering the use of hepatic resection for such patients. The available evidence strongly suggests that, as a result of improvements in surgical techniques and perioperative care, hepatic resection can benefit many patients with intermediate or advanced HCC or with HCC associated with portal hypertension.

7.
J Clin Epidemiol ; 70: 4-16, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26117439

RESUMEN

OBJECTIVES: To assess the overall qualities of published surgical meta-analysis and predictive factors for high qualities. STUDY DESIGN AND SETTING: All meta-analyses pertinent to surgical procedures published in year 2013 were selected from PubMed and EMBASE. The characteristics of the included meta-analyses were collected, and their reporting and methodologic qualities were assessed by the PRISMA (27 items) and AMSTAR (11 items) checklists, respectively. Independent predictive factors associated with these two qualities were evaluated by univariate and multivariate analyses. RESULTS: Hundred ninety-seven meta-analyses representing 10 surgical subspecialties were included. The mean PRISMA and AMSTAR adherences (by items) were 22.2 ± 2.4 and 7.8 ± 1.2, respectively, and a positive linear correlation was found between them with an R(2) of 0.793. Those meta-analyses conducted by the first authors having meta-analysis publication previously had significantly higher reporting and methodologic qualities than those who did not (P = 0.002 and P = 0.001). Meanwhile, there were also significant differences in these two qualities between studies published in Q1-ranked and (Q2 + Q3)-ranked journals as rated by the SCImago indicator (P < 0.001 and P < 0.001). On multivariate analyses, region of origin (non-Asia vs. Asia), publishing experience of first authors (ever vs. never), rank of publishing journals (Q1 vs. Q2 + Q3), and preregistration (presence vs. absence) were independently associated with superior reporting and methodologic qualities. CONCLUSIONS: The reporting and methodologic qualities of current surgical meta-analyses remained suboptimal, and first authors' experience and ranking of publishing journals were independently associated with both qualities. Preregistration might be an effective measure to improve the quality of meta-analyses, which deserves more attention from future study conductors.


Asunto(s)
Difusión de la Información , Metaanálisis como Asunto , Publicaciones Periódicas como Asunto , Edición , Procedimientos Quirúrgicos Operativos , Humanos , Proyectos de Investigación
8.
World J Surg ; 38(4): 947-57, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24258262

RESUMEN

OBJECTIVE: The aim of this study was to investigate the prognostic value of tumor size alone on long-term survival and recurrence after curative resection for solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion. METHODS: A single-center cohort of 615 patients with solitary HCC (a single tumor, without macroscopic vascular invasion or distant metastasis) undergoing curative hepatic resection from 2002 to 2010 was retrospectively studied. Using 2.0, 3.0, 4.0, 5.0, 8.0, and 10.0 cm as cut-off values of tumor size, the overall survival (OS) and recurrence-free survival (RFS) rates were compared between the groups of patients with tumor size up to a certain cut-off value and the groups of patients with tumor size above that cut-off value. Thus, multiple comparisons were done. The prognostic factors of OS and RFS were evaluated using univariate and multivariate analyses. RESULTS: The median tumor size of all HCCs was 4.0 cm (range 0.9-22.0 cm). The in-hospital mortality rate was 1.0 %, and the overall morbidity rate was 22.3 %. The 1-, 3-, and 5-year OS rates were 96.0, 79.8, and 69.9 %, and the corresponding RFS rates were 83.6, 72.7, and 57.2 %, respectively. On univariate analyses, the 1-, 3-, and 5-year OS and RFS rates were significantly different between the individual two groups of patients as divided by the aforementioned different cut-off values of tumor sizes (all p < 0.05). However, when tumor size was put as a continuous variable into multivariate analysis, it was no longer an independent prognostic factor of OS or RFS after curative resection. CONCLUSIONS: Tumor size did not independently affect long-term survival and recurrence after curative resection of solitary HCC without macroscopic vascular invasion. Therefore, there is no size limit that precludes hepatic resection for solitary HCC, provided the tumor is resectable.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Carga Tumoral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Niño , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
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