scholarly journals Transcriptomic Analysis Identified Two Subtypes of Brain Tumor Characterized by Distinct Immune Infiltration and Prognosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xilin Shen ◽  
Xiaoli Wang ◽  
Hongru Shen ◽  
Mengyao Feng ◽  
Dan Wu ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
Cox Model ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Cancer Type ◽  
Immune Infiltration ◽  
Therapeutic Benefits ◽  
Log Rank Test

BackgroundBrain tumor ranks as the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from receiving therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction.MethodsWe developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods, including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses, were employed.ResultsWe identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound-healing, and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 – 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 – 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation, and co-deletion of 1p and 19q. This finding was validated in six datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6).ConclusionsWe identified two distinctive subtypes of brain tumor with different immune infiltration signatures, which might be helpful as an independent prognosticator for brain tumor.

scholarly journals Transcriptomic Analysis Identified two Subtypes of Brain Tumor Characterized by Distinct Immune Infiltration and Prognosis

2021 ◽  
Author(s):  
Xilin Shen ◽  
Hongru Shen ◽  
Mengyao Feng ◽  
Dan Wu ◽  
Yichen Yang ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
Cox Model ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Cancer Type ◽  
Immune Infiltration ◽  
Therapeutic Benefits ◽  
Log Rank Test

Abstract Background Brain tumor ranks the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction.Methods We developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses were employed.Results We identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound healing and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 – 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 – 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation and co-deletion of 1p and 19q. This finding was validated in 6 datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6).Conclusions We identified two distinctive subtypes of brain tumor with different immune infiltration signatures and prognosis. Our finding is helpful for better understanding of brain tumor and has potential clinical utilities.

CDKN2A or CDKN2B homozygous deletion with high-immune infiltration as a favorable prognostic factor for lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20543-e20543
Author(s):  
Benxu Tan ◽  
Yonghong Chen ◽  
Lei Xia ◽  
Xian Yu ◽  
Yusheng Huang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Homozygous Deletion ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Immune Infiltration ◽  
Log Rank Test ◽  
Significant Difference ◽  
Wild Group

e20543 Background: CDKN2A and CDKN2B both acted as tumor suppressor genes by regulating the cell cycle, which in humans were located at chromosome 9, band p21.3. The frequencies of homozygous deletion (HomDel) in CDKN2A and CDKN2B in lung adenocarcinoma (LUAD) were 12.5% and 12.1%, respectively. However, the genomic, immunogenomic features and impact on the prognosis of LUAD patients with CDKN2A/B HomDel were still unclear. Methods: The cohort of this study was from The Cancer Genome Atlas (TCGA). A total of 508 LUAD patients, including 99 CDKN2A/B HomDel (homdel) and 509 CDKN2A/B wild (wild). This study explored the difference of genomic and immunogenomic landscape between homdel and wild by analysis of whole-exome sequencing (WES) and RNA sequencing data. Results: The most frequently mutated genes were TP53, TTN, MUC16, and CSMD3. Their frequencies in homdel and wild are 46% and 48%, 43% and 46%, 35% and 41%, 33% and 38%, respectively. There was no significant difference of tumor mutational burden (TMB) between homdel and wild (median TMB, 133 in homdel vs 177 in wild; Wilcoxon test, p = 0.11), and clinical characteristics including age, gender, smoking history, and tumor stage were not significantly different between homdel and wild. Homdel had a shorter overall survival (OS) than wild (Log-rank test, p = 0.04, Hazard Ratio: 0.7, 95% CI: 0.49-1.02), but there was no significant difference in progression-free survival (PFS) (Log-rank test, p = 0.05, Hazard Ratio: 0.73, 95% CI: 0.51-1.04). We used single sample gene set enrichment analysis (ssGSEA) to calculate the enrichment score (ES) of 25 immune-related pathways such as antigen presentation and T cell-mediated immunity, and then used the consensus clustering algorithm (ConsensusClusterPlus) to cluster homdel and wild respectively, and both clustered into low and high immune infiltration groups. For the high immune infiltration and low immune infiltration in homdel and wild, high immune infiltration had a longer OS (Log-rank test, p = 0.009, Hazard Ratio: 2.19, 95% CI: 1.22-3.94) and PFS (Log-rank test, p = 0.044, Hazard Ratio: 1.8, 95% CI: 1.01-3.2) than low immune infiltration in homdel. However, there was no significant heterogeneity between high and immune infiltration in terms of PFS (Log-rank test, p = 0.28, Hazard Ratio: 1.21, 95% CI: 0.87-1.68) and OS (Log-rank test, p = 0.96, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) in the wild group, the wild group had longer OS than homdel group with low immune infiltration (Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI: 0.29-0.88), while had the same OS with homdel with high immune infiltration, irrespective of immune infiltration. And so was PFS (Log-rank test, p = 0.005, Hazard Ratio: 0.48, 95% CI: 0.27-0.82). Conclusions: CDKN2A/B homdel was an unfavorable prognostic factor for LUAD, but which with high immune infiltration might improve patient survival time.

scholarly journals Predictive impact of PVL assessments on clinical outcomes in patients undergoing TAVR

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
M Kibler ◽  
C Sato ◽  
J Heger ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cox Regression ◽  
Adenosine Diphosphate ◽  
Rank Test ◽  
Multicenter Studies ◽  
Cox Regression Analysis ◽  
Paravalvular Leakage ◽  
Transcatheter Aortic Valve ◽  
Log Rank Test ◽  
Cerebrovascular Events

Abstract Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (<25) and CT-ADP (>180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI <25 and CT-ADP >180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI <25, and CT-ADP >180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

scholarly journals Tumor Volume Reduction Rate to Induction Chemotherapy Is a Prognostic Factor for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Retrospective Cohort Study

2021 ◽  
Author(s):  
Chi-hsien Huang ◽  
Ting-Chun Lin ◽  
Ming-Yu Lien ◽  
Fu-Ming Cheng ◽  
Kai-Chiun Li ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Cox Regression ◽  
Reduction Rate ◽  
Volume Reduction ◽  
Cancer Site ◽  
Rank Test ◽  
Primary Cancer ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Tumor Volume Reduction

Abstract BackgroundAim of this study was to evaluate the prognostic of tumor volume reduction rate (TVRR) status post induction chemotherapy (IC) in LA-HNSCC.MethodsPatients with newly diagnosed LA-HNSCC from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received IC as TPF (taxotere, platinum, fluorouracil) followed by daily definitive intensity-modulated radiotherapy (IMRT) for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate of the primary tumor (TVRR-T) and lymph node (TVRR-N) was measured and calculated by contrast-enhanced CT images at diagnosis, and one month after final IC cycle, and analyzed though a univariate and multivariate Cox regression model.ResultsNinety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%) and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In univariate Cox regression analysis, the TVRR-T as the only variable showed a significant difference for disease-free survival (DFS) (hazard ratio [HR] 0.77, 95% confidence interval (CI) 0.63 to 0.96; P = 0.02), aside from cancer site, RECIST, age and IC dose. In multivariate Cox regression analysis, The TVRR-T was also an independently significant prognostic factor for DFS (HR 0.77, 95% CI 0.62 to 0.97; P = 0.02). At a cutoff value using TVRR-T of 50% in Kaplan-Meier survival analysis, the DFS was significant higher with TVRR-T ≥ 50% group (log-rank test, p = 0.024), and also a trend of improved OS. (log-rank test, p = 0.069).ConclusionsTVRR-T was related to improved DFS and trend of improved OS. Other factors including patient’s age at diagnosis, the primary cancer site, and RECIST, were not significantly related to DFS.

scholarly journals Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways

2019 ◽  
Vol 28 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Bai Ji ◽  
Hongqiao Cai ◽  
Yahui Liu
Keyword(s):  
Liver Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Rank Test ◽  
P Value ◽  
Rna Seq ◽  
Cox Regression Analysis

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.

scholarly journals Identification and Validation of Immune-Related LncRNA Prognostic Signature for Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Guomin Wu ◽  
Qihao Wang ◽  
Ting Zhu ◽  
Linhai Fu ◽  
Zhupeng Li ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Clinical Features ◽  
Cox Regression ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Immune Infiltration

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.

scholarly journals Silent infarct is a risk factor for infarct recurrence in adults with sickle cell anemia

Neurology ◽  
2018 ◽  
Vol 91 (8) ◽  
pp. e781-e784 ◽  
Author(s):  
Lori C. Jordan ◽  
Adetola A. Kassim ◽  
Manus J. Donahue ◽  
Meher R. Juttukonda ◽  
Sumit Pruthi ◽  
...  
Keyword(s):  
Risk Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Cox Regression ◽  
Brain Mri ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Rank Test ◽  
Event Analysis ◽  
Log Rank Test

ObjectiveBecause of the high prevalence of silent cerebral infarcts (SCIs) in adults with sickle cell anemia (SCA) and lack of information to guide treatment strategies, we evaluated the risk of recurrent SCIs and overt stroke in adults with SCA with preexisting SCI.MethodsThis observational study included adults with SCA (HbSS or Sβ0 thalassemia) aged 18 to 40 years. Participants received 3-tesla brain MRI and a detailed neurologic examination. Time-to-event analysis assessed those with or without baseline SCI and with new or progressive infarcts. The incidence rate of new events was compared by log-rank test. Univariable Cox regression assessed the association of SCI with infarct progression.ResultsAmong adults with SCA with 2 MRIs and at least 6 months between MRIs (n = 54, mean interval = 2.5 years), 43% had SCI at baseline. Of participants with baseline SCI, 30% had new or progressive SCI over 2.5 years compared to 6% with no SCI at baseline; no participant had an overt stroke. New SCIs at follow-up were present in 12.9 per 100 patient-years with existing SCI compared with 2.4 per 100 patient-years without prior SCI (log-rank test, p = 0.021). No statistically significant differences were seen among those with or without baseline SCI in use of hydroxyurea therapy, hydroxyurea dose, or other stroke risk factors. The presence of SCI was associated with increased hazard of a new or progressive infarct (hazard ratio 5.27, 95% confidence interval 1.09–25.51, p = 0.039).ConclusionsSilent infarcts in adults with SCA are common and are a significant risk factor for future silent infarcts.

miR-181 Expression is Associated With The Prognosis in Lung Cancer.

2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Suppressor Gene ◽  
Rank Test ◽  
High Morbidity ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Cancer Tissues

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.

scholarly journals Reopening of an obstructed third ventriculostomy: long-term success and factors affecting outcome in 215 infants

2015 ◽  
Vol 15 (4) ◽  
pp. 399-405 ◽  
Author(s):  
Paul J. Marano ◽  
Scellig S. D. Stone ◽  
John Mugamba ◽  
Peter Ssenyonga ◽  
Ezra B. Warf ◽  
...  
Keyword(s):  
Cox Regression ◽  
Operation Time ◽  
Cox Proportional Hazards Model ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Third Ventriculostomy ◽  
Time To Failure ◽  
Factors Affecting ◽  
Log Rank Test

OBJECT The role of reopening an obstructed endoscopic third ventriculostomy (ETV) as treatment for ETV failure is not well defined. The authors studied 215 children with ETV closure who underwent successful repeat ETV to determine the indications, long-term success, and factors affecting outcome. METHODS The authors retrospectively reviewed the CURE Children's Hospital of Uganda database from August 2001 through December 2012, identifying 215 children with failed ETV (with or without prior choroid plexus cauterization [CPC]) who underwent reopening of an obstructed ETV stoma. Treatment survival according to sex, age at first and second operation, time to failure of first operation, etiology of hydrocephalus, prior CPC, and mode of ETV obstruction (simple stoma closure, second membrane, or cisternal obstruction from arachnoid scarring) were assessed using the Kaplan-Meier survival method. Survival differences among groups were assessed using log-rank and Wilcoxon methods and a Cox proportional hazards model. RESULTS There were 125 boys and 90 girls with mean and median ages of 229 and 92 days, respectively, at the initial ETV. Mean and median ages at repeat ETV were 347 and 180 days, respectively. Postinfectious hydrocephalus (PIH) was the etiology in 126 patients, and nonpostinfectious hydrocephalus (NPIH) in 89. Overall estimated 7-year success for repeat ETV was 51%. Sex (p = 0.46, log-rank test; p = 0.54, Wilcoxon test), age (< vs > 6 months) at initial or repeat ETV (p = 0.08 initial, p = 0.13 repeat; log-rank test), and type of ETV obstruction (p = 0.61, log-rank test) did not affect outcome for repeat ETV (p values ≥ 0.05, Cox regression). Those with a longer time to failure of initial ETV (> 6 months 91%, 3–6 months 60%, < 3 months 42%, p < 0.01; log-rank test), postinfectious etiology (PIH 58% vs NPIH 42%, p = 0.02; log-rank and Wilcoxon tests) and prior CPC (p = 0.03, log-rank and Wilcoxon tests) had significantly better outcome. CONCLUSIONS Repeat ETV was successful in half of the patients overall, and was more successful in association with later failures, prior CPC, and PIH. Obstruction of the original ETV by secondary arachnoid scarring was not a negative prognostic factor, and should not discourage the surgeon from proceeding. Repeat ETV may be a more durable solution to failed ETV/CPC than shunt placement in this context, especially for failures at more than 3 months after the initial ETV. Some ETV closures may result from an inflammatory response that is less robust at the second operation.

Sign in / Sign up

Export Citation Format

Share Document