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Clinical and Translational Medicine Oct 2023Skull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and...
BACKGROUND
Skull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and recurrent lesions remain poorly understood, impeding development of effective treatment approaches.
METHODS
To obtain an understanding of the differences in single cells between primary and recurrent chordomas, we performed single-cell RNA sequencing and T-cell/B-cell receptor (BCR) sequencing. This allowed us to delineate the differences between the two types of tumour cells, tumour-infiltrating lymphocytes, myeloid cells, fibroblasts and B cells. Copy number variants (CNVs) were detected and compared between the tumour types to assess heterogeneity. Selected samples were subjected to immunohistochemistry to validate protein expression. Fluorescence in situ hybridisation experiments, Transwell assays and xenograft mouse models helped verify the role of fibronectin 1 (FN1) in chordoma.
RESULTS
Promoting natural killer (NK) cell and CD8_GZMK T-cell function or inhibiting the transformation of CD8_GZMK T cells to CD8_ZNF683 T cells and promoting the transformation of natural killer T (NKT) cells to NK cells are promising strategies for preventing chordoma recurrence. Additionally, inhibiting the M2-like activity of tumour-associated macrophages (TAMs) could be an effective approach. Antigen-presenting cancer-associated fibroblasts (apCAFs) and dendritic cells (DCs) with high enrichment of the antigen-presenting signature were enriched in primary chordomas. There were fewer plasma cells and BCR clonotypes in recurrent chordomas. Remarkably, FN1 was upregulated, had more CNVs, and was more highly secreted by tumours, macrophages, CD4 T cells, CD8 T cells and fibroblasts in recurrent chordoma than in primary chordoma. Finally, FN1 enhanced the invasion and proliferation of chordomas in vivo and in vitro.
CONCLUSION
Our comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.
Topics: Humans; Animals; Mice; Chordoma; Fibronectins; Neoplasm Recurrence, Local; Treatment Outcome; Skull Base Neoplasms; Head and Neck Neoplasms; Skull Base; Tumor Microenvironment
PubMed: 37784253
DOI: 10.1002/ctm2.1429 -
Hormones (Athens, Greece) Mar 2024Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH)... (Review)
Review
Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH) concentrations, may occur as part of a hereditary syndromic disorder or as a non-syndromic disease. The associated syndromic disorders include multiple endocrine neoplasia types 1-5 (MEN1-5) and hyperparathyroidism with jaw tumor (HPT-JT) syndromes, and the non-syndromic forms include familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), familial isolated hyperparathyroidism (FIHP), and neonatal severe hyperparathyroidism (NS-HPT). Such hereditary forms may occur in > 10% of patients with PHPT, and their recognition is important for implementation of gene-specific screening protocols and investigations for other associated tumors. Syndromic PHPT tends to be multifocal and multiglandular with most patients requiring parathyroidectomy with the aim of limiting end-organ damage associated with hypercalcemia, particularly osteoporosis, nephrolithiasis, and renal failure. Some patients with non-syndromic PHPT may have mutations of the MEN1 gene or the calcium-sensing receptor (CASR), whose loss of function mutations usually cause FHH1, a disorder associated with mild hypercalcemia and may follow a benign clinical course. Measurement of the urinary calcium-to-creatinine ratio clearance (UCCR) may help to distinguish patients with FHH from those with PHPT, as the majority of FHH patients have low urinary calcium excretion (UCCR < 0.01). Once genetic testing confirms a hereditary cause of PHPT, further genetic testing can be offered to the patients' relatives and subsequent screening can be carried out in these affected family members, which prevents inappropriate testing in normal individuals.
Topics: Infant, Newborn; Humans; Hyperparathyroidism, Primary; Calcium; Hypercalcemia; Adenoma; Fibroma; Hyperparathyroidism; Jaw Neoplasms
PubMed: 38038882
DOI: 10.1007/s42000-023-00508-9 -
Magyar Onkologia Mar 2024Despite the advanced medical and radiation therapy, the role of surgical resection of brain neoplasms still remains indisputable. The maximal safe resection of benign... (Review)
Review
Despite the advanced medical and radiation therapy, the role of surgical resection of brain neoplasms still remains indisputable. The maximal safe resection of benign brain tumors may result in complete recovery of the patient. Surgery of malignant tumors can resolve mass effect, improve the neurological condition of the patient providing the possibility for further complex oncotherapy based on molecular level histopathology results. The advances in technical and multidisciplinary environment of brain tumor surgery facilitate more radical and safer resection resulting in better outcomes and preservation of quality of life, even in case of tumors which were considered inoperable until recently. In this review we present the recent technical innovations used in brain tumor surgery and discuss the surgical strategy of the most common tumor types (gliomas, meningiomas, cranial nerve tumors and brain metastases). The surgical management of complex skull base tumors, pituitary tumors, as well as neuro-endoscopic surgery and pediatric brain tumors are discussed in other papers of this special issue.
Topics: Adult; Humans; Brain Neoplasms; Meningeal Neoplasms; Meningioma; Neurosurgical Procedures; Quality of Life; Skull Base Neoplasms
PubMed: 38484372
DOI: No ID Found -
JPMA. the Journal of the Pakistan... Dec 2023Skull base chrodomas are slow growing neoplasms usually located along the midline. They display a locally invasive nature with possibilities of extracranial metastasis.... (Review)
Review
Skull base chrodomas are slow growing neoplasms usually located along the midline. They display a locally invasive nature with possibilities of extracranial metastasis. Presentation is usually late and depends upon the location and extent of the tumour. Management aims at gross total resection via open microsurgical or endoscopic approach followed by adjuvant radiotherapy. Prognosis may be good for the classical and chondroid subtypes but remains poor for de-differentiated type.
Topics: Humans; Chordoma; Prognosis; Radiotherapy, Adjuvant; Head and Neck Neoplasms; Skull Base Neoplasms; Skull Base; Treatment Outcome
PubMed: 38083943
DOI: 10.47391/JPMA.23-103 -
Oral and Maxillofacial Surgery Clinics... Aug 2023Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are... (Review)
Review
Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are most affected by PNS, and their connections are reviewed. MRI is the most sensitive modality for detecting PNS, and their anatomy and interconnections are reviewed. MRI is the most sensitive modality for detecting PNS, and imaging features of PNS and important imaging checkpoints are reviewed. Optimal imaging protocol and techniques are summarized as well as other entities that can mimic PNS.
Topics: Humans; Cranial Nerve Neoplasms; Neoplasm Invasiveness; Head and Neck Neoplasms; Skull Base; Magnetic Resonance Imaging
PubMed: 37005170
DOI: 10.1016/j.coms.2023.02.004 -
Journal of Surgical Oncology Dec 2023Intraoperative frozen section histopathology (IFSH) in sinonasal and skull base surgery although widely used is not well studied. (Review)
Review
BACKGROUND
Intraoperative frozen section histopathology (IFSH) in sinonasal and skull base surgery although widely used is not well studied.
METHODS
We reviewed a database of sinonasal and anterior skull base tumors, between 1973 and 2019, and identified 312 suitable operative cases. Clinicopathologic data was collected and analyzed, in addition to descriptive data for histopathological reports classified as "ambiguous," or "limited/insufficient-quality/quantity."
RESULTS
Overall, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IFSH were 90.2%, 97.5%, 94.2%, 95.6%, and 95.2%, respectively. IFSH for adenocarcinoma, salivary carcinoma, and SCC all demonstrated a better clinical utility with a sensitivity of 90% or greater, while it was less than 90% for esthesioneuroblastoma, melanoma, and sarcoma. Other factors such as unclear reporting, poor quality specimens, or limited quality specimens were shown to lower diagnostic performance. Based on limitations identified, we proposed a novel IFSH reporting algorithm to improve IFSH in sinonasal and skull base surgery.
CONCLUSIONS
IFSH is an accurate and clinically useful technique in sinonasal and skull base surgery patients; however, limitations exist.
Topics: Humans; Skull Base Neoplasms; Frozen Sections; Adenocarcinoma; Nose Neoplasms; Nasal Cavity
PubMed: 37650809
DOI: 10.1002/jso.27429 -
La Revue Du Praticien May 2024
Topics: Humans; Ameloblastoma; Jaw Neoplasms
PubMed: 38833232
DOI: No ID Found -
No Shinkei Geka. Neurological Surgery Mar 20243D printers have been applied in bone-based surgeries, including craniofacial, plastic, oral, and orthopedic surgeries. The improved capabilities of diagnostic imaging... (Review)
Review
3D printers have been applied in bone-based surgeries, including craniofacial, plastic, oral, and orthopedic surgeries. The improved capabilities of diagnostic imaging equipment and 3D printers have enabled the development of more precise models, and research on surgical simulations and training in the field of neurosurgery is increasing. This review outlines the use of 3D printers in neurosurgery at our institution in terms of modeling methods and surgical simulations. Modeling with the powder-sticking lamination method using plaster as the material allows drilling, which is a surgical procedure. Therefore, it is useful for simulating skull base tumors, such as petrosectomy in a combined transpetrosal approach or anterior clinoidectomy in an orbitozygomatic approach. The color coding of each part of the model facilitates anatomical understanding, and meshed tumor modeling allows deep translucency. As shown above, the 3D printer's modeling ingenuity allows for useful surgical simulations for each case.
Topics: Humans; Printing, Three-Dimensional; Models, Anatomic; Neurosurgical Procedures; Craniotomy; Skull Base Neoplasms
PubMed: 38514114
DOI: 10.11477/mf.1436204909 -
Journal of Neuro-oncology Oct 2023Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve... (Meta-Analysis)
Meta-Analysis Review
Assessing survival outcomes and complication profiles following surgical excision and radiotherapy as interventions for skull base chordoma: a systematic review of operative margins and surgical approaches.
INTRODUCTION
Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. Nonetheless, due to the rarity of this pathology (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series. Furthermore, radiotherapeutic treatments investigated to date have proven largely ineffective.
METHODS
Accordingly, we performed a systematic review in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorical variables including GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Additionally, we pooled eligible studies for formal meta-analysis to compare outcomes by surgical approach (lateral versus midline). Statistical analyses were performed using R Studio 'metafor' package or Cochrane Review Manager. Furthermore, meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values < 0.05 to be statistically significant.
RESULTS
Following the systematic search and screen, 55 studies published between 1993 and 2022 reporting data for 2453 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [95% CI: 0.5418; 0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, I value indicated notable heterogeneity across the 55 studies [I = 56.3% (95%CI: 44.0%; 65.9%)]. With respect to operative margins, the rate of GTR was 0.3323 [95% CI: 0.2824; 0.3909], I = 91.9% [95% CI: 90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [95% CI: 0.4596; 0.5808], I = 93.1% [95% CI: 91.6%; 94.4%]. The most common complication was CSF leak (5.4%). In terms of survival outcomes, 5-year OS rate was 0.7113 [95% CI: 0.6685; 0.7568], I = 91.9% [95% CI: 90.0%; 93.5%]. 10-year OS rate was 0.4957 [95% CI: 0.4230; 0.5809], I = 92.3% [95% CI: 89.2%; 94.4%], which was comparable to the 5-year PFS rate of 0.5054 [95% CI: 0.4394; 0.5813], I = 84.2% [95% CI: 77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [95% CI: 0.4075; 0.6010], I = 14.9% [95% CI: 0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The relative risk for mortality in the midline group versus the lateral approach group did not indicate any substantial difference in survival according to laterality of approach (-0.93 [95% CI: -1.03, -0.97], I = 95%, (p < 0.001).
CONCLUSION
Overall, these results indicate good 5-year survival outcomes for patients with skull base chordoma; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate. Furthermore, mortality rates among patients undergoing midline versus lateral skull base approaches appear to be equivocal.
Topics: Female; Humans; Male; Adult; Middle Aged; Retrospective Studies; Chordoma; Cranial Fossa, Posterior; Prognosis; Skull Base Neoplasms; Head and Neck Neoplasms; Treatment Outcome
PubMed: 37880419
DOI: 10.1007/s11060-023-04477-2 -
Journal of Neurosurgery Nov 2023Chordomas are rare bone neoplasms characterized by a high recurrence rate and no benefit from any approved medical treatment to date. However, the investigation of...
OBJECTIVE
Chordomas are rare bone neoplasms characterized by a high recurrence rate and no benefit from any approved medical treatment to date. However, the investigation of molecular alterations in chordomas could be essential to prognosticate, guide clinical decision-making, and identify theranostic biomarkers. The aim of this study was to provide a detailed genomic landscape of a homogeneous series of 64 chordoma samples, revealing driver events, theranostic markers, and outcome-related genomic features.
METHODS
The authors conducted whole-exome sequencing (WES), targeted next-generation sequencing, and RNA sequencing of 64 skull base and spinal chordoma samples collected between December 2006 and September 2020. Clinical, histological, and radiological data were retrospectively analyzed and correlated to genetic findings.
RESULTS
The authors identified homozygous deletions of CDKN2A/2B, PIK3CA mutations, and alterations affecting genes of SWI/SNF chromatin remodeling complexes (PBRM1 and ARID1A) as potential theranostic biomarkers. Using matched germline WES, they observed a higher frequency of a common genetic variant (rs2305089; p.(Gly177Asp)) in TBXT (97.8%, p < 0.001) compared to its distribution in the general population. PIK3CA mutation was identified as an independent biomarker of short progression-free survival (HR 10.68, p = 0.0008). Loss of CDKN2A/2B was more frequently observed in spinal tumors and recurrent tumors.
CONCLUSIONS
In the current study, the authors identified driver events such as PBRM1 and PIK3CA mutations, TBXT alterations, or homozygous deletions of CDKN2A/2B, which could, for some, be considered potential theranostic markers and could allow for identifying novel therapeutic approaches. With the aim of a future biomolecular prognostication classification, alterations affecting PIK3CA and CDKN2A/2B could be considered as poor prognostic biomarkers.
Topics: Humans; Prognosis; Chordoma; Spinal Neoplasms; Precision Medicine; Retrospective Studies; Neoplasm Recurrence, Local; Biomarkers; Skull Base Neoplasms; Skull Base; Class I Phosphatidylinositol 3-Kinases
PubMed: 37029667
DOI: 10.3171/2023.1.JNS222180