Integrating single-cell and spatial transcriptomics reveals endoplasmic reticulum stress-related CAF subpopulations associated with chordoma progression.

BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.

Corrigendum: Coexpression of HHLA2 and PD-L1 on tumor cells independently predicts the survival of spinal chordoma patients.

[This corrects the article DOI: 10.3389/fimmu.2021.797407.].

Clinicopathological and Prognostic Characteristics in Spinal Chondroblastomas: A Pooled Analysis of Individual Patient Data From a Single Institute and 27 Studies.

STUDY DESIGN: Retrospective pooled analysis of individual patient data. OBJECTIVES: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. METHODS: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. RESULTS: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. CONCLUSION: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

Ca2+ Regulates Autophagy Through CaMKKß/AMPK/mTOR Signaling Pathway in Mechanical Spinal cord Injury: An in vitro Study.

Spinal cord injury (SCI), resulting in damage of the normal structure and function of the spinal cord, would do great harm to patients, physically and psychologically. The mechanism of SCI is very complex. At present, lots of studies have reported that autophagy was involved in the secondary injury process of SCI, and several researchers also found that calcium ions (Ca2+) played an important role in SCI by regulating necrosis, autophagy, or apoptosis. However, to our best of knowledge, no studies have linked the spinal cord mechanical injury, intracellular Ca2+, and autophagy in series. In this study, we have established an in vitro model of SCI using neural cells from fetal rats to explore the relationship among them, and found that mechanical injury could promote the intracellular Ca2+ concentration, and the increased Ca2+ level activated autophagy through the CaMKKß/AMPK/mTOR pathway. Additionally, we found that apoptosis was also involved in this pathway. Thus, our study provides new insights into the specific mechanisms of SCI and may open up new avenues for the treatment of SCI.

Corrigendum: Risk factors for tuberculous or nontuberculous spondylitis after percutaneous vertebroplasty or kyphoplasty in patients with osteoporotic vertebral compression fracture: A case-control study.

[This corrects the article DOI: 10.3389/fsurg.2022.962425.].

Risk factors for tuberculous or nontuberculous spondylitis after percutaneous vertebroplasty or kyphoplasty in patients with osteoporotic vertebral compression fracture: A case-control study.

Objectives: The contributing factors for spondylitis after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) remain unclear. Here, we sought to investigate the factors affecting spondylitis occurrence after PVP/PKP. We also compared the clinical characteristics between patients with tuberculous spondylitis (TS) and nontuberculous spondylitis (NTS) following vertebral augmentation. Methods: Literature searches (from January 1, 1982 to October 16, 2020) using MEDLINE, EMBASE, Google Scholar and Web of science databases were conducted to identify eligible studies according to predefined criteria. The local database was also retrospectively reviewed to include additional TS and NTS patients at our center. Results: Thirty studies from the literature and 11 patients from our local institute were identified, yielding a total of 23 TS patients and 50 NTS patients for analysis. Compared with NTS group, patients in the TS group were more likely to have a history of trauma before PVP/PKP treatment. Univariate analyses of risk factors revealed pulmonary tuberculosis and diabetes were significant factors for TS after PVP/PKP. Analyzing NTS, we found obesity, a history of preoperative trauma, urinary tract infection, diabetes and multiple surgical segments (≥2) were significantly associated with its occurrence following PVP/PKP treatment. Multivariate logistic analyses showed a history of pulmonary tuberculosis and diabetes were independent risk factors for TS after PVP/PKP, while diabetes and the number of surgically treated segments independently influenced NTS development. Conclusions: A history of pulmonary tuberculosis and diabetes were independent risk factors for TS. For NTS, diabetes and the number of surgically treated segments significantly influenced the occurrence of postoperative spinal infection. These data may be helpful for guiding risk stratification and preoperative prevention for patients, thereby reducing the incidence of vertebral osteomyelitis after PVP/PKP.

Incidence and Risk Factors for Cerebrovascular-Specific Mortality in Patients with Colorectal Cancer: A Registry-Based Cohort Study Involving 563,298 Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. METHODS: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from the Surveillance Epidemiology and End Results database, with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general U.S. POPULATION: Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. RESULTS: A total of 563,298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among the competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during the study period. While age, surgery, other/unknown race and tumors located at the transverse colon positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, a more recent year (2001-2015) of diagnosis, a grade II or III CRC, rectal cancer, or multiple primary or distant tumors experienced a lower risk of CVSM. INTERPRETATION: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM that may be helpful for risk stratification and the therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

SERPINA1 is a hub gene associated with intervertebral disc degeneration grade and affects the nucleus pulposus cell phenotype through the ADIRF-AS1/miR-214-3p axis.

Long noncoding RNAs (lncRNAs) and miRNAs have been reported to participate in intervertebral disc degeneration (IDD) progression. However, the key lncRNA-miRNA axis and its corresponding affected hub genes in IDD remain unknown. In this study, weighted gene coexpression network analysis (WGCNA) was first used to determine the key gene cluster and hub genes implicated in IDD progression. The expression levels of ADIRF-AS1, miR-214-3p, and SERPINA1 in nucleus pulposus (NP) tissues were detected. The ADIRF-AS1/miR-214-3p/SERPINA1 axis was identified, and its effects on the proliferation, senescence, and apoptosis of NP cells were investigated in vitro and in vivo. SERPINA1 overexpression in NP cells promoted cell viability and inhibited cell apoptosis and senescence. Moreover, SERPINA1 regulated the IDD grade in rat models. The lncRNA ADIRF-AS1 was downregulated in high-grade degeneration NP tissues and positively correlated with SERPINA1. ADIRF-AS1 overexpression attenuated cellular degenerative changes in NP cells. miR-214-3p directly bound to SERPINA1 and ADIRF-AS1 and negatively regulated ADIRF-AS1 expression. miR-214-3p inhibition exerted similar effects on cellular degenerative changes in NP cells to SERPINA1 or ADIRF-AS1 overexpression. Furthermore, miR-214-3p overexpression partially reversed the effects of ADIRF-AS1 overexpression. Collectively, these data suggest that ADIRF-AS1 overexpression could mitigate IDD by binding to miR-214-3p to upregulate SERPINA1. Additional studies (especially those using an axial loading-induced IDD animal model) will be needed to further validate the role of the ADIRF-AS1/miR-214-3p/SERPINA1 signaling axis in IDD progression.

Clinicopathological and Prognostic Characteristics in Dedifferentiated/Poorly Differentiated Chordomas: A Pooled Analysis of Individual Patient Data From 58 Studies and Comparison With Conventional Chordomas.

BACKGROUND: Currently, the clinicopathological and prognostic characteristics of dedifferentiated chordoma (DC) and poorly differentiated chordoma (PDC) remain poorly understood. In this study, we sought to characterize clinicopathological parameters in a large PDC/DC cohort and determine their correlations with progression-free survival (PFS) and overall survival (OS) of patients. We also attempted to compare clinical features between PDC/DC and conventional chordoma (CC). METHODS: Literature searches (from inception to June 01, 2020) using Medline, Embase, Google Scholar and Wanfang databases were conducted to identify eligible studies according to predefined criteria. The local database at our center was also retrospectively reviewed to include CC patients for comparative analysis. RESULTS: Fifty-eight studies from the literature and 90 CC patients from our local institute were identified; in total, 54 PDC patients and 96 DC patients were analyzed. Overall, PDC or DC had distinct characteristics from CC, while PDC and DC shared similar clinical features. Adjuvant radiotherapy and chemotherapy were associated with both PFS and OS in PDC patients in the univariate and/or multivariate analyses. In the DC cohort, tumor resection type, adjuvant chemotherapy and tumor dedifferentiation components significantly affected PFS, whereas none of them were predictive of outcome in the multivariate analysis. By analyzing OS, we found that surgery, resection type and the time to dedifferentiation predicted the survival of DC patients; however, only surgery remained significant after adjusting for other covariables. CONCLUSIONS: These data may offer useful information to better understand the clinical characteristics of PDC/DC and may be helpful in improving the outcome prediction of patients.

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy.

OBJECTIVE: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients. METHODS: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features. RESULTS: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan-Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance. CONCLUSION: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.

Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients.

Background: Immunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients. Methods: Using multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples. Results: Tumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD-1+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival. Conclusion: These data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.

Development and Validation of a 6-miRNA Prognostic Signature in Spinal Chordoma.

BACKGROUND: Published data have suggested a critical role for microRNA (miRNA) expression in chordoma progression. However, most of these studies focus on single miRNA and no multi-miRNA prognostic signature has been currently established for chordoma. In this study, we sought to develop and validate a 6-miRNA risk score (miRscore) model for survival prediction. METHODS: Medline, Embase, and Google scholar searches (from inception to July 20, 2018) were conducted to identify candidate miRNAs with prognostic value as per predefined criteria. Quantitative RT-PCR was used to measure miRNA levels in 114 spinal chordoma (54 in the training and 60 in the validation cohort) and 20 control specimens. Subsequently, the miRscore was built based on miRNAs data. RESULTS: Literature searches identified six prognostic miRNAs (miR-574-3p, miR-1237-3p, miR-140-3p, miR-1, miR-155, and miR-1290) with differential expression in tumor tissues. Bioinformatical analysis revealed an important regulatory role for miR-574-3p/EGFR signaling in chordoma and showed that the target genes of these prognostic miRNAs were mainly enriched in transcription regulation, protein binding and cancer-related pathways. In both cohorts, the miRscore was associated with surrounding muscle invasion by tumor and/or other aggressive features. The miRscore model well predicted local recurrence-free survival and overall survival, which remained after adjusting for other relevant covariates. Further time-dependent receiver operating characteristics analysis in the two cohorts found that the miRscore classifier had stronger prognostic power than known clinical predictors and improved the ability of Enneking staging to predict outcomes. Importantly, recursive-partitioning analysis of both samples combined separated patients into four prognostically distinct risk subgroups for recurrence and survival (both P < 0.001). CONCLUSIONS: These data suggest the miRscore as a useful prognostic stratification tool in spinal chordoma and may represent an important step toward future personalized treatment of patients.

A four-factor immune risk score signature predicts the clinical outcome of patients with spinal chordoma.

BACKGROUND: Currently, the measurement of immune cells in previous studies is usually subjective, and no immune-based prognostic model has been established for chordoma. In this study, we sought to simultaneously measure tumor-infiltrating lymphocyte (TIL) subtypes in chordoma samples using an objective method and develop an immune risk score (IRS) model for survival prediction. METHODS: Multiplexed quantitative immunofluorescence staining was used to determine the TIL levels in the tumoral and stromal subareas of 114 spinal chordoma specimens (54 in the training and 60 in the validation cohort) for programmed death-1 (PD-1), CD3, CD8, CD20 (where CD is cluster of differentiation), and FOXP3. Flow cytometry was performed to validate the immunofluorescence assay for lymphocyte measurement on an additional five fresh chordoma specimens. Subsequently, the IRS model was built using the least absolute shrinkage and selection operator (LASSO) Cox regression method. RESULTS: Flow cytometry and quantitative immunofluorescence showed similar lymphocytic percentages and TIL subpopulation proportions in the fresh tumor specimens. With the training data, the LASSO model identified four immune features for IRS construction: tumoral FOXP3, tumoral PD-1, stromal FOXP3, and stromal CD8. In both cohorts, a high IRS was significantly associated with tumoral programmed cell death-1 ligand 1 expression, Enneking inappropriate tumor resection, and surrounding muscle invasion by tumor. Multivariate Cox regression and stratified analysis in the two cohorts revealed that the IRS was an independent predictor and could effectively separate patients with similar Enneking staging into different risk subgroups, with significantly different survival rates. Further receiver operating characteristic analysis found that the IRS classifier had a better prognostic value than the traditional clinicopathological factors and compensated for the deficiency of Enneking staging for outcome prediction. More importantly, a nomogram based on the IRS and clinical predictors showed adequate performance in estimating disease recurrence and survival of patients. CONCLUSIONS: These data support the use of the IRS signature as a reliable prognostic tool in spinal chordoma and may facilitate individualized therapy decision making for patients.

Incidence of Subsidence of Seven Intervertebral Devices in Anterior Cervical Discectomy and Fusion: A Network Meta-Analysis.

BACKGROUND: Subsidence is an incapacitating complication in anterior cervical discectomy and fusion (ACDF). However, the debate over which of the intervertebral devices is associated with lower incidence of subsidence remains to be settled. METHODS: Seven dominant techniques comprising cage with plate (CP), iliac bone graft with plate (IP), Zero-profile cage with screws (Zero-P), ROI-C cages with clips (ROI-C), polyether ether ketone cage alone (PCA), iliac crest autogenous graft (ICAG), and titanium cage alone (TCA) were examined. The incidences of subsidence in the different groups were calculated and compared. RESULTS: A total of 30 studies with 2264 patients were identified. Overall, the CP group presented the lowest incidence of subsidence, and its incidence was significantly lower than that in the Zero-P group, the PCA group, the ICAG group, and the TCA group (P < 0.05). The incidence of subsidence in the IP group was significantly lower than that in the PCA group, the ICAG group, and the TCA group (P < 0.05). In single-level ACDF, the CP group presented the lowest incidence of subsidence, and its incidence was significantly lower than that in the PCA group and the TCA group (P < 0.05). No difference was found between single-level and multilevel ACDF and the incidence of subsidence was higher in those undergoing single-level ACDF. CONCLUSIONS: CP and IP resulted in a lower rate of subsidence than cage alone or ICAG. Zero-P and ROI-C cages led to similar subsidence rates with plate. All types of intervertebral device can be applied to both single-level and multilevel ACDF with comparable subsidence rate.

Long-term Results Comparing Cervical Disc Arthroplasty to Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Whether cervical disc arthroplasty (CDA) is superior to anterior cervical discectomy and fusion (ACDF) remains controversial, especially in relation to long-term results. The present study aimed to evaluate the long-term safety and efficiency of CDA and ACDF for cervical disc disease. METHODS: We performed this study according to the Cochrane methodology. An extensive search was undertaken in PubMed, Embase, and Cochrane databases up to 1 June 2019 using the following key words: "anterior cervical fusion," "arthroplasty," "replacement" and "artificial disc". RevMan 5.3 (Cochrane, London, UK) was used to analyze data. Safety and efficiency outcome measures included the success rate, functional outcome measures, adverse events (AE), adjacent segment degeneration (ASD), secondary surgery, and patients' satisfaction and recommendation rates. The OR and MD with 95% confidence interval (CI) were used to evaluate discontinuous and continuous variables, respectively. The statistically significant level was set at P < 0.05. RESULTS: A total of 11 randomized controlled trials with 3505 patients (CDA/ACDF: 1913/1592) were included in this meta-analysis. Compared with ACDF, CDA achieved significantly higher overall success (2.10, 95% CI [1.70, 2.59]), neck disability index (NDI) success (1.73, 95% CI [1.37, 2.18]), neurological success (1.65, 95% CI [1.24, 2.20]), patients' satisfaction (2.14, 95% CI [1.50, 3.05]), and patients' recommendation rates (3.23, 95% CI [1.79, 5.80]). Functional outcome measures such as visual analog score neck pain (-5.50, 95% CI [-8.49, -2.52]) and arm pain (-3.78, 95% CI [-7.04, -0.53]), the Short Form-36 physical component score (SF-36 PCS) (1.93, 95% CI [0.53, 3.32]), and the Short Form-36 mental component score (SF-36 MCS) (2.62, 95% CI [0.95, 4.29]), revealed superiority in the CDA group. CDA also achieved a significantly lower rate of symptomatic ASD (0.46, 95% CI [0.34, 0.63]), total secondary surgery (0.50, 95% CI [0.29, 0.87]), secondary surgery at the index level (0.46, 95% CI [0.29, 0.74]), and secondary surgery at the adjacent level (0.37, 95% CI [0.28, 0.49]). However, no significant difference was found in radiological success (1.35, 95% CI [0.88, 2.08]), NDI score (-2.88, 95% CI [-5.93, 0.17]), total reported AE (1.14, 95% CI [0.92, 1.42]), serious AE (0.89, 95% CI [0.71, 1.11]), device/surgery-related AE (0.90, 95% CI [0.68, 1.18]), radiological superior ASD (0.63, 95% CI [0.28, 1.43]), inferior ASD (0.45, 95% CI [0.19, 1.11]), and work status (1.33, 95% CI [0.78, 2.25]). Furthermore, subgroup analysis showed different results between US and non-US groups. CONCLUSION: Our study provided further evidence that compared to ACDF, CDA had a higher long-term clinical success rate and better functional outcome measurements, and resulted in less symptomatic ASD and fewer secondary surgeries. However, worldwide multicenter RCT with long-term follow up are still needed for further evaluation in the future.

Percutaneous Endoscopic Lumbar Discectomy for Lumbar Disc Herniation with Modic Changes via a Transforaminal Approach: A Retrospective Study.

BACKGROUND: The surgical selection for patients with lumbar disc herniation (LDH) with Modic changes (MCs) is still contentious. Percutaneous endoscopic lumbar discectomy via a transforaminal approach (TF-PELD) as a representative minimally invasive spine surgery technique for LDH has been standardized. However, its efficacy has not been thoroughly described in the patients with LDH with MCs. OBJECTIVES: The goal of this study was to assess the clinical outcomes of TF-PELD in the treatment of LDH and MCs. STUDY DESIGN: Retrospective study. SETTING: Inpatient surgery center. METHODS: From January 2015 to December 2016, 276 patients with LDH showing normal or MCs signals in their bone marrow in our hospital were enrolled in this retrospective study. All patients suffered low back and leg pain because of LDH and underwent the TF-PELD procedure. Clinical outcomes were assessed according to the Visual Analog Scale (VAS) for back pain and leg pain, Oswestry Disability Index (ODI) for functional status assessment, and modified MacNab criteria for patient satisfaction. RESULTS: A total of 182 patients showed normal intensity, 44 patients showed Modic type 1 signals, and 50 patients showed Modic type 2 signals before surgery. The postoperative VAS and ODI scores were significantly improved compared with those preoperatively among the groups. In the Modic type 1 and 2 signals groups, however, the postoperative VAS scores for back pain and ODI scores showed an upward trend with the follow-up time extending. The recurrence rates were 4.4%, 9.1%, and 8.0% in the normal, Modic type 1 and 2 signals groups, respectively. The recurrence rates and satisfaction rates showed no significant difference among the groups at the final follow-up. LIMITATIONS: This study has a small sample size and the follow-up period was too short. There is no comparison with other therapeutic options such as fusion surgery or the lack of any other treatment. CONCLUSIONS: TF-PELD is an option for treatment of patients with LDH even if the patients show MCs. However, the postoperative back pain and functional status have the trend of deterioration with the time extending in patients with MCs, especially in the Modic type 1 signals. KEY WORDS: Modic changes, Modic type 1, Modic type 2, transforaminal percutaneous endoscopic lumbar discectomy, lumbar disc herniation, back pain, recurrence, complication.

The Relationship Between Tumor-Stroma Ratio, the Immune Microenvironment, and Survival in Patients With Spinal Chordoma.

BACKGROUND: Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking. OBJECTIVE: To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome. METHODS: TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed. RESULTS: Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction. CONCLUSION: These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.