1.Construction of ceRNA Network and Analysis of Key mRNA and Immune Function for Bladder Urothelial Carcinoma Based on Bioinformatics
Bo SHAO ; Jin WANG ; Shui WAN ; Kaixiu WU ; Shen TIAN ; Yichen DU ; Danxia CHEN ; Yuanyuan MA
Journal of Modern Laboratory Medicine 2024;39(1):29-35,66
Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P<0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P<0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.
2.Associations between the diet-related inflammation indices and digestive system cancer:a narrative review of epidemiological studies
Jing-Yu TAN ; Yan ZHANG ; Jun CHEN ; Dan-Ni YANG ; Yi-Xin ZOU ; Wan-Shui YANG ; Yong-Bing XIANG
Fudan University Journal of Medical Sciences 2024;51(3):404-414
The inflammatory effect of dietary is strongly related to the development of cancer,therefore,the diet-related inflammatory index was developed as a methodological tool to investigate the relationship between dietary,inflammation and tumors.In this paper,we summarized the results on diet-related inflammatory indices and common cancers of the digestive system based on relevant cancer epidemiological studies.The available epidemiological evidence suggests that pro-inflammatory diet is associated with an increased risk of gastrointestinal malignancies,with the strongest association with colorectal cancer,followed by esophageal and gastric cancers,and then pancreatic cancer,and the least evidence of studies with liver cancer.Among these studies,the level of evidence for esophageal cancer is lower than colorectal cancer,the study of gastric cancer has gender differences and problems in adjusting for confounders,and the study of pancreatic cancer has heterogeneous results.In view of the current research progress and deficiencies,prospective studies or population-based cohort studies,as well as strengthening nutritional epidemiological studies related to common tumors such as liver cancer could be considered in the future.This review is expecting to provide basic information and scientific basis for strengthening the related healthy eating behavior promotion in the prevention and control of digestive system tumors.
3.Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien TSAI ; Chung-Feng HUANG ; Ming-Lun YEH ; Meng-Hsuan HSIEH ; Hsing-Tao KUO ; Chao-Hung HUNG ; Kuo-Chih TSENG ; Hsueh-Chou LAI ; Cheng-Yuan PENG ; Jing-Houng WANG ; Jyh-Jou CHEN ; Pei-Lun LEE ; Rong-Nan CHIEN ; Chi-Chieh YANG ; Gin-Ho LO ; Jia-Horng KAO ; Chun-Jen LIU ; Chen-Hua LIU ; Sheng-Lei YAN ; Chun-Yen LIN ; Wei-Wen SU ; Cheng-Hsin CHU ; Chih-Jen CHEN ; Shui-Yi TUNG ; Chi‐Ming TAI ; Chih-Wen LIN ; Ching-Chu LO ; Pin-Nan CHENG ; Yen-Cheng CHIU ; Chia-Chi WANG ; Jin-Shiung CHENG ; Wei-Lun TSAI ; Han-Chieh LIN ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Jee-Fu HUANG ; Chia-Yen DAI ; Wan-Long CHUNG ; Ming-Jong BAIR ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(3):468-486
Background/Aims:
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods:
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results:
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
4.Clinical characteristics, ultrasonic diagnosis, treatment and outcomes of eosinophilic fasciitis: a retrospective single-center analysis of 45 cases.
Jin Shui YANG ; Yue Hua WAN ; Jiang Lin ZHANG ; Jian ZHU
Journal of Southern Medical University 2023;43(1):145-152
OBJECTIVE:
To evaluate the clinical features, laboratory and imaging results, treatment and outcomes of eosinophilic fasciitis (EF) and assess the value of ultrasound in the diagnosis of EF.
METHODS:
We retrospectively analyzed the clinical data of 45 patients with EF treated in our center from January 1, 2006 to February 28, 2022. The consistency between the diagnoses of EF based on ultrasound and MRI findings was assessed.
RESULTS:
In the 45 EF patients (male/female ratio 3.5:1), the age of onset ranged from 16 to 64 years with a mean disease course of 22.6 months. The average time from symptom onset to diagnosis was 16 months. The most common possible trigger of the disease was vigorous exercise (10/45), causing symmetrical lesions in the limbs, most commonly in the forearms (86.7%) and lower legs (80%). Clinical features of EF included subcutaneous swelling and induration (95.6%), arthralgia and arthritis (55.6%), groove sign (42.2%), hand joint contractures (42.2%), skin pigmentation (37.8%), and peau d'orange appearance (13.3%). Eosinophilia was found in 31 patients (68.9%). Hypergammaglobulinemia was seen in 23/44 (52.3%) and positive antinuclear antibodies in 9 (20%) of the patients. Twentyone of the patients were treated with high-dose methylprednisolone (≥200 mg daily for 3 to 5 consecutive days), and compared with the patients who did not receive this treatment, these patients more frequently experienced relapse before admission, had more extensive involvement, and had a higher rate of hypergammaglobulinemia without fever, but these differences were not statistically significant. Of the 31 patients (68.9%) with follow-up data (for a median of 3.2 years [range 0.2-15.9]), complete remission was achieved in 12 (38.7%) patients, and the accumulative complete remission rate was 44.1% at 5.5 years. No specific baseline characteristics or immunosuppressants were found to correlate with the treatment response. A total of 26 patients underwent both ultrasound and MRI examination, and the Kappa value of the diagnostic results between ultrasound and MRI was 0.91.
CONCLUSION
EF is characterized by symmetrical subcutaneous swelling and induration in the limbs, accompanied by eosinophilia and hypergammaglobulinemia. Glucocorticoid is effective for treating EF. Ultrasound examination can identify thickening of subcutaneous fascia for an early diagnosis of EF.
Humans
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Female
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Male
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Infant
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Child, Preschool
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Retrospective Studies
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Hypergammaglobulinemia
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Eosinophilia
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Ultrasonography
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Hand
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Contracture
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Treatment Outcome
5.Amyloid arthropathy with joint flexion contracture as the initial manifestation:a report of 5 cases and literature review
Yue-Hua WAN ; Jin-Shui YANG ; Yu-Rong ZHAO ; Kun-Peng LI ; Zheng ZHAO ; Jing-Yu JIN ; Jian ZHU
Medical Journal of Chinese People's Liberation Army 2023;48(12):1451-1456
Objective To report 5 cases of amyloid arthropathy with joint flexion contracture as the first manifestation,and perform a literature review to improve the understanding of the disease.Methods Retrospective analysis of the clinical manifestations,laboratory and imaging results clinical data of patients with immunoglobulin light chain(AL)amyloidosis related amyloid arthropathy with joints flexion contracture as the first manifestation at the Department of Rheumatology and Immunology,the First Medical Center of People's Liberation Army General Hospital from January 2012 to February 2022.Meanwhile searching the database(CNKI,Wanfang Data,PubMed),excluding myeloma-associated amyloid arthropathy,and analyzing the literature results comprehensively.Results There were a total of 5 patients with amyloid arthropathy with joint flexion contracture as the initial manifestation in this center,including 4 males and 1 female.By February 2022(searching CNKI,Wanfang Data and PubMed),two eligible patients were selected,all males.A total of 7 patients were included with male-to-female ratio of 6:1.The median age was 30-year-old(range from 19 to 73).Spine and limb joints were involved,especially finger joints(7 cases,100%).Soft tissue was involved in 5 patients(71.4%),carpal tunnel syndrome in 4 patients(57.1%),giant tongue in 3 patients(42.9%),shoulder pad sign in 2 patients(28.6%),muscle swelling in 2 patients(28.6%).Five patients were misdiagnosed as rheumatoid arthritis(RA)and 1 patient was misdiagnosed as spondyloarthritis(SpA).The median time of delayed diagnosis was 24 months(2-204 months).The laboratory results showed that 3 patients(42.9%)were positive for immunoelectrophoresis,all of which were λ light chain.Only 1 patient was positive for HLA-B27,while the other patients were negative for autoantibodies and rheumatoid factors.Only 1 patient had elevated C reactive protein(CRP)and erythrocyte sedimentation rate(ESR).Ultrasound examination of the lesion site of 5 patients(71.4%)showed hypoechoic area around the joint,thickening of ligaments or periarticular tenosynovitis.Five patients(71.4%)underwent X-ray examination,of which 4 patients had no bone destruction,1 patient had soft tissue swelling with bone erosion and subchondral cyst.MRI was performed in 5 patients(71.4%),in which low signal on T1 weighted image,medium signal on T2 weighted image and edema signal on peripheral tendon sheath were seen in 1 patient.One patient(14.3%)underwent emission computed tomography(ECT)without abnormal uptake.Conclusion Joint flexion contracture may be the first sign of amyloid arthropathy.Vigilance for amyloid arthropathy is warranted when there is associated soft tissue involvement,negative autoantibodies,and imaging showing no joint destruction but surrounding soft tissue abnormalities.
6.Survival of children with recurrent medulloblastoma undergoing sequential therapy: an analysis of 101 cases.
Yan-Ling SUN ; Jing-Jing LIU ; Shu-Xu DU ; Wan-Shui WU ; Li-Ming SUN
Chinese Journal of Contemporary Pediatrics 2021;23(2):164-168
OBJECTIVE:
To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens.
METHODS:
A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis.
RESULTS:
Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) (
CONCLUSIONS
As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.
Cerebellar Neoplasms/therapy*
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Child
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Humans
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Medulloblastoma/therapy*
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Neoplasm Recurrence, Local
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Retrospective Studies
;
Survival Rate
7.Multi-Omics and Its Clinical Application in Hepatocellular Carcinoma: Current Progress and Future Opportunities.
Wan-Shui YANG ; Han-Yu JIANG ; Chao LIU ; Jing-Wei WEI ; Yu ZHOU ; Peng-Yun GONG ; Bin SONG ; Jie TIAN
Chinese Medical Sciences Journal 2021;36(3):173-186
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the fourth leading cause of cancer related death worldwide. China covers over half of cases, leading HCC to be a vital threaten to public health. Despite advances in diagnosis and treatments, high recurrence rate remains a major obstacle in HCC management. Multi-omics currently facilitates surveillance, precise diagnosis, and personalized treatment decision making in clinical setting. Non-invasive radiomics utilizes preoperative radiological imaging to reflect subtle pixel-level pattern changes that correlate to specific clinical outcomes. Radiomics has been widely used in histopathological diagnosis prediction, treatment response evaluation, and prognosis prediction. High-throughput sequencing and gene expression profiling enabled genomics and proteomics to identify distinct transcriptomic subclasses and recurrent genetic alterations in HCC, which would reveal the complex multistep process of the pathophysiology. The accumulation of big medical data and the development of artificial intelligence techniques are providing new insights for our better understanding of the mechanism of HCC via multi-omics, and show potential to convert surgical/intervention treatment into an antitumorigenic one, which would greatly advance precision medicine in HCC management.
Artificial Intelligence
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Carcinoma, Hepatocellular/therapy*
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Gene Expression Profiling
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Humans
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Liver Neoplasms/genetics*
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Prognosis
8.Predictive values of the combination of Friedman stage and sleep oximetry done early after surgery in predicting the treatment outcomes of uvulopalatopharyngoplasty.
Bing Wan DONG ; Jun Bo ZHANG ; Shui Fang XIAO
Journal of Peking University(Health Sciences) 2020;52(2):281-284
OBJECTIVE:
To explore the predictive values of the combination of preoperative data, including medical history and physical examination, and results of sleep oximetry performed early after the surgery (one week) in predicting the treatment outcomes of uvulopalatopharyngoplasty (UPPP) in adult patients with obstructive sleep apnea hypopnea syndrome (OSAHS).
METHODS:
All the patients who were diagnosed with OSAHS, underwent UPPP treatment and had complete follow-up data in our institution between Jan 2013 and May 2016 were enrolled in our study. The pre-operative data of these patients, including age, physical examination, and polysomnography (PSG) data, were all exactly collected for analysis. All these patients had received the evaluation of subjective efficacy scale and the sleep oximetry test in early post-operative days (within one week). The long-term efficacy evaluations including PSG and subjective efficacy scale were all finished at least three months after the surgery.
RESULTS:
In the research 61 patients were finally studied, including 25 responders (41.0%) and 36 non-responders (59.0%). Regression analysis revealed that the pre-operative Friedman stage and early post-operative oxygen desaturation index of ≥4% (ODI4) were found to be independently predictive parameters for the UPPP treatment outcomes (P<0.05). The ROC curve analysis was used to estimate the predictive values of ODI4 to the treatment outcomes, and it was calculated with an area under the curve of 0.822. Using the ODI4 of 15 as the cutoff value, the sensitivity and specificity of that calculated were up to 0.778 and 0.760 respectively. The response rate among the patients with an early post-operative ODI4 of <15 was 70.4%, which was significantly higher than that of the patients with an early post-operative ODI4 of ≥15, whose response rate was 17.6% (P<0.05). The similar results could also be obtained in the patients with pre-operative Friedman stage II (87.5% vs.25.0%) and Friedman stage III (33.3% vs. 6.7%).
CONCLUSION
The combination of early post UPPP operation oximetry parameters, especially ODI4, and pre-operative Friedman stage could be used in better evaluating the potential surgical outcomes of UPPP.
Adult
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Humans
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Oximetry
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Palate
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Pharynx
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Polysomnography
;
Treatment Outcome
9.Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis.
Wan-Shui WU ; Jing-Jing LIU ; Yan-Ling SUN ; Si-Qi REN ; Xiao-Guang QIU ; Shu-Xu DU ; Chun-De LI ; Li-Ming SUN
Chinese Journal of Contemporary Pediatrics 2020;22(6):589-594
OBJCTIVE:
To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis.
METHODS:
A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018.
RESULTS:
The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade.
CONCLUSIONS
Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.
Antineoplastic Combined Chemotherapy Protocols
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Child
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Combined Modality Therapy
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Disease-Free Survival
;
Humans
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Neuroectodermal Tumors, Primitive
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Prognosis
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Retrospective Studies
10.Risk factors for recurrence within 2 years in children with medulloblastoma.
Jing-Jing LIU ; Yan-Ling SUN ; Shu-Xu DU ; Chun-De LI ; Xiao-Jun GONG ; Miao LI ; Wan-Shui WU ; Li-Ming SUN
Chinese Journal of Contemporary Pediatrics 2019;21(8):761-765
OBJECTIVE:
To investigate the risk factors for recurrence of medulloblastoma (MB) within 2 years and their influence on progression-free survival (PFS).
METHODS:
A retrospective analysis was performed for the clinical data of 123 children with MB who were admitted from January to December, 2017. According to the presence or absence of recurrence, they were divided into recurrence group with 30 children and non-recurrence group with 93 children. The risk factors for recurrence within 2 years were analyzed, and PFS was compared between the children with different risk factors.
RESULTS:
Large-cell/anaplastic type and M stage were risk factors for MB recurrence within 2 years. The risk of recurrence in the children with M+ MB was 3.525 times that in those with M0 MB, and the risk of recurrence in the children with large-cell/anaplastic MB was 3.358 times that in those with classic MB (P<0.05). The survival analysis showed that the median PFS time was 20 months in the children with M+ MB, and the 20-month PFS rate was 50% ± 11% in the children with M+ MB and 81% ± 5% in those with M0 MB (P<0.05). The 20-month PFS rate was 80% ± 5% in the children with classic MB, 65% ± 10% in those with desmoplastic/nodular MB, 86% ± 13% in those with MB with extensible nodularity, and 36% ± 20% in those with large-cell/anaplastic MB (P<0.05).
CONCLUSIONS
Recurrence is an important influencing factor for the prognosis of MB, and M+ stage and large-cell/anaplastic MB are risk factors for recurrence. Children with such risk factors tend to have a low PFS rate.
Cerebellar Neoplasms
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Child
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Humans
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Medulloblastoma
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Neoplasm Recurrence, Local
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Prognosis
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Recurrence
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Retrospective Studies
;
Risk Factors

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