MET receptor serves as a promising target in melanoma brain metastases.

The development of brain metastases hallmarks disease progression in 20-40% of melanoma patients and is a serious obstacle to therapy. Understanding the processes involved in the development and maintenance of melanoma brain metastases (MBM) is critical for the discovery of novel therapeutic strategies. Here, we generated transcriptome and methylome profiles of MBM showing high or low abundance of infiltrated Iba1high tumor-associated microglia and macrophages (TAMs). Our survey identified potential prognostic markers of favorable disease course and response to immune checkpoint inhibitor (ICi) therapy, among them APBB1IP and the interferon-responsive gene ITGB7. In MBM with high ITGB7/APBB1IP levels, the accumulation of TAMs correlated significantly with the immune score. Signature-based deconvolution of MBM via single sample GSEA revealed enrichment of interferon-response and immune signatures and revealed inflammation, stress and MET receptor signaling. MET receptor phosphorylation/activation maybe elicited by inflammatory processes in brain metastatic melanoma cells via stroma cell-released HGF. We found phospho-METY1234/1235 in a subset of MBM and observed a marked response of brain metastasis-derived cell lines (BMCs) that lacked druggable BRAF mutations or developed resistance to BRAF inhibitors (BRAFi) in vivo to MET inhibitors PHA-665752 and ARQ197 (tivantinib). In summary, the activation of MET receptor in brain colonizing melanoma cells by stromal cell-released HGF may promote tumor self-maintenance and expansion and might counteract ICi therapy. Therefore, therapeutic targeting of MET possibly serves as a promising strategy to control intracranial progressive disease and improve patient survival.

Tear-drop technique in iliac screw placement: a technical analysis.

BACKGROUND: Instrumentation of the lumbosacral region is one of the more challenging regions due to the complex anatomical structures and biomechanical forces. Screw insertion can be done both navigated and based on X-ray verification. In this study, we demonstrate a fast and reliable open, low exposure X-ray-guided technique of iliac screw placement. METHODS: Between October 2016 and August 2019, 48 patients underwent sacropelvic fixation in tear-drop technique. Screw insertion was performed in open technique by using an X-ray converter angulated 25-30° in coronal and sagittal view. The anatomical insertion point was the posterior superior iliac spine. Verification of correct screw placement was done by intraoperative 3D scan. RESULTS: In total, 95 iliac screws were placed in tear-drop technique with a correct placement in 98.1%. CONCLUSIONS: The tear-drop technique showed a proper screw position in the intraoperative 3D scan and therefore may be considered an alternative technique to the navigated screw placement.

Etiology and Management of Recurrent and Persistent Hemifacial Spasm-A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Despite a 90% success rate, microvascular decompression occasionally fails to resolve hemifacial spasm (HFS), necessitating revision surgery. We investigated recurrent cases to identify underlying causes. METHODS: We evaluated patients at our institution who underwent revision microvascular decompression because of recurrent or persistent HFS, assessing recurrence causes, decompression techniques, complications, and outcomes. Data considered included demographics, preoperative symptoms, disease duration, offending vessel, and magnetic resonance findings. Surgical notes and intraoperative videos were reviewed, and telephone interviews were conducted for recent outcomes. RESULTS: Out of our ongoing series of 493 patients, 43 patients (8.7%) required revision surgery with a patient cohort of 33 females and 10 males. The average symptom duration was 10 years. The median time between primary and revision surgery was 14 months. Thirteen patients (30.2%) underwent initial surgery elsewhere. Adhesions of Teflon pledgets to the facial nerve were the primary cause of nonresolution in 23 patients (53.5%), while in 13 (30.2%), a missed vascular compression was identified. Sixteen patients (37.2%) had sufficient decompression by removing the conflicting pledgets. During 10 revisions (23.3%), additional Teflon pledgets were necessary. After a median follow-up of 67 months after revision surgery, 27 patients (62.8%) reported complete spasm resolution. Six patients (14.0%) had a good outcome with over 90% reduction of their spasms, 3 patients (7.0%) stated a fair outcome (50% improvement), while 7 patients (16.3%) had no improvement. CONCLUSION: According to our results, adhesions of Teflon to the facial nerve may cause HFS recurrence. Therefore, whenever possible, Teflon should be placed without nerve contact between the brainstem and the offending vessel. Using a sling or bridge technique seems to be beneficial because it leaves the facial nerve completely free. Persistent symptoms often result from missed offending vessels in the pontomedullary sulcus indicating the benefit of endoscopic inspection of this area with an endoscope.

Rare clival localization of an eosinophilic granuloma: illustrative case.

BACKGROUND: Eosinophilic granuloma (EG) belongs to the family of Langerhans cell histiocytosis (LCH) and is considered to be a benign disease typically found in children younger than 15 years of age. Here, the authors describe an EG of unusual localization and clinical presentation. OBSERVATIONS: The authors report a 9-year-old girl with an EG presenting as an osteolytic lesion of the clivus. After transsphenoidal resection and histological confirmation, adjuvant chemotherapy was initiated. Presenting signs and symptoms were weight loss, episodic grimacing, and moderate ballism-like movements. After a follow-up-period of 32 months, the patient presented with a total resolution of initial symptoms and no further tumor growth. LESSONS: Although these lesions are rare, one should consider EG as a differential diagnosis when confronted with osteolytic lesions of the clivus.