Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes.

Background: Proinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In the current study, we sought to investigate the prognostic value of TLS-associated chemokines/cytokines (TLS-kines) expression levels in melanoma patients by performing serum protein and tissue transcriptomic analyses, and to then correlate these data with patients clinicopathological and TME characteristics. Methods: Levels of TLS-kines in patients' sera were quantitated using a custom Luminex Multiplex Assay. The Cancer Genomic Atlas melanoma cohort (TCGA-SKCM) and a Moffitt Melanoma cohort were used for tissue transcriptomic analyses. Associations between target analytes and survival outcomes, clinicopathological variables, and correlations between TLS-kines were statistically analyzed. Results: Serum of 95 patients with melanoma were evaluated; 48 (50%) female, median age of 63, IQR 51-70 years. Serum levels of APRIL/TNFSF13 were positively correlated with levels of both CXCL10 and CXCL13. In multivariate analyses, high levels of serum APRIL/TNFSF13 were associated with improved event-free survival after adjusting for age and stage (HR = 0.64, 95% CI 0.43-0.95; p = 0.03). High expression of APRIL/TNFSF13 tumor transcripts was significantly associated with improved OS in TCGA-SKCM (HR = 0.69, 95% CI 0.52-0.93; p = 0.01) and in Moffitt Melanoma patients (HR = 0.51, 95% CI: 0.32-0.82; p = 0.006). Further incorporation of CXCL13 and CXCL10 tumor transcript levels in a 3-gene index revealed that high APRIL/CXCL10/CXCL13 expression was associated with improved OS in the TCGA SKCM cohort (HR = 0.42, 95% CI 0.19-0.94; p = 0.035). Melanoma differentially expressed genes positively associated with high APRIL/CXCL10/CXCL13 tumor expression were linked to tumor infiltration by a diverse array of proinflammatory immune cell types. Conclusion: Serum protein and tumor transcript levels of APRIL/TNFSF13 are associated with improved survival outcomes. Patients exhibiting high coordinate expression of APRIL/CXCL10/CXCL13 transcripts in their tumors displayed superior OS. Further investigation of TLS-kine expression profiles related to clinical outcomes in larger cohort studies is warranted.

Transcervical approach to oropharyngeal synovial sarcoma: a case report.

Aim: Synovial sarcomas (SS) are malignant tumors rarely arising in the head and neck region. In most of these cases, the tumor arises in the cervical or hypopharyngeal region, and extremely rarely in the oropharynx. Case report: Herein, we report the case of a 22-year-old male oropharyngeal SS patient presented with breathing difficulty and dysphagia. The management plan included an emergency tracheostomy, followed shortly by transcervical resection of the oropharyngeal sarcoma tumor, the pectoralis major myocutaneous flap was used for pharyngeal reconstruction, followed by adjuvant radiotherapy resulting in more than 5 years disease-free survival. Conclusion: SS arising in the oropharynx are extremely rare. Transcervical resection coupled with adjuvant radiotherapy warrants enhanced locoregional control in advanced oropharyngeal cases.

Genomic and Transcriptomic Predictors of Response to Immune Checkpoint Inhibitors in Melanoma Patients: A Machine Learning Approach.

Immune checkpoint inhibitors (ICIs) became one of the most revolutionary cancer treatments, especially in melanoma. While they have been proven to prolong survival with lesser side effects compared to chemotherapy, the accurate prediction of response remains to be an unmet gap. Thus, we aim to identify accurate clinical and transcriptomic biomarkers for ICI response in melanoma. We also provide mechanistic insight into how high-performing markers impose their effect on the tumor microenvironment (TME). Clinical and transcriptomic data were retrieved from melanoma studies administering ICIs from cBioportal and GEO databases. Four machine learning models were developed using random-forest classification (RFC) entailing clinical and genomic features (RFC7), differentially expressed genes (DEGs, RFC-Seq), survival-related DEGs (RFC-Surv) and a combination model. The xCELL algorithm was used to investigate the TME. A total of 212 ICI-treated melanoma patients were identified. All models achieved a high area under the curve (AUC) and bootstrap estimate (RFC7: 0.71, 0.74; RFC-Seq: 0.87, 0.75; RFC-Surv: 0.76, 0.76, respectively). Tumor mutation burden, GSTA3, and VNN2 were the highest contributing features. Tumor infiltration analyses revealed a direct correlation between upregulated genes and CD8+, CD4+ T cells, and B cells and inversely correlated with myeloid-derived suppressor cells. Our findings confirmed the accuracy of several genomic, clinical, and transcriptomic-based RFC models, that could further support the use of TMB in predicting response to ICIs. Novel genes (GSTA3 and VNN2) were identified through RFC-seq and RFC-surv models that could serve as genomic biomarkers after robust validation.

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma.

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.

An in Depth Look Into Intracranial Abscesses and Empyemas: a Ten-year Experience in a Single Institute.

Background: As the incidence of intracranial infections increase due to diagnostic procedures improvement, more real-life data is needed to reach a more solid informed management approach. Objective: This study aims to describe and analyse clinical features of intracranial abscesses patients treated at a tertiary hospital in North Jordan during a 10-year period. Methods: We retrospectively identified 37 patients treated at King Abdullah University Hospital (KAUH) from 2011 to 2020 in Irbid, North Jordan. Treatment consisted of either aspiration, open craniotomy excision (OCE) or conservative therapy. Extracted variables included demographic data such (age, gender), clinical presentation, lab findings, radiological findings as well as management plan. Retrieved data was compared between the patients who underwent a single operation and those who underwent reoperation after the initial procedure. Results: Thirty-seven patients with 55 intracerebral abscesses were identified, 29 of whom had intraparenchymal brain abscesses, 4 patients had epidural empyema, and 4 had subdural empyema. The mean age was 28.8 (± 20.7) years, with a male predominance (78.4%). Sixteen patients underwent open craniotomy excision (OCE), 14 patients were treated by aspiration and 7 patients were treated conservatively. When comparing the single operation and the reoperation groups, there was no statistically significant difference across variables. Conclusion: Our study presents valuable insight from a tertiary hospital in north Jordan on intracranial abscesses and empyemas. Our findings confirm that good recovery can be established after aspiration or OCE in the majority of patients. Similar results were obtained when comparing the SOP and the ROP groups.

Buckling of the Ligamentum Flavum as a Rare Complication of Anterior Cervical Corpectomy and Fusion: A Case Report

Introduction and Importance Neurological deterioration due to buckling of the ligamentum flavum (LF) is an uncommon complication after anterior cervical corpectomy or discectomy with fusion. Case Presentation In this report, we present the case of a 66-year-old male who underwent anterior cervical partial corpectomy of C5 and discectomy of prolapsed C5- C6 with fusion. Postsurgery, the patient displayed signs of neurological deterioration. Upon immediate cervical magnetic resonance imaging (MRI), posterior canal stenosis and severe compression with cord signal due to LF buckling were detected. A posterior laminectomy procedure and canal decompression at the C5-C6 level with bone fusion were performed. Clinical Discussion Patient presented with walking difficulty, then walking disability, followed by bilateral upper and lower limb paresthesia with burning sensation. Examination showed ⅘ muscle strength in both handgrips. Further investigation showed brisk deep tendon reflexes, positive Hoffman sign unilaterally, equivocal Babinski sign, and progressive quadriparesis. Magnetic resonance imaging showed mild and diffuse building of some cervical discs, with spinal cord progression. We performed an anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF); a titanium mesh with plates and screws was used for fusion, with removal of a calcified and herniated subligamentous disc. Postoperatively, upper and lower limb strength deteriorated; immediate cervical and thoracic MRI showed LF buckling, which caused canal stenosis and severe compression. Urgent posterior laminectomy and canal decompression with bone fusion was scheduled on the same day. The patient underwent physiotherapy and regained upper and lower limb strength and his ability to walk. Conclusion This indicates the possibility of neurological deterioration as a result of LF buckling, whichmay be a result of LF thickening accompanied by hyperextension in the cervical region. In this regard, immediate imaging following signs of neurological complications after anterior cervical corpectomy or discectomy warrants early detection, which results in a better prognosis.

Giant versus regular parathyroid adenoma: A retrospective comparative study.

BACKGROUND: A fraction of Parathyroid Adenoma (PTA) is considered giant if they weigh more than 3.5 g. There is no clear consensus whether this subgroup has a distinct clinical or biochemical presentation that could have implications on PTA localization and management. In this study, we investigate the difference between regular and giant PTA patients regarding their clinical and laboratory findings as well as their postoperative outcomes. MATERIALS AND METHODS: Clinical and PTA-related data were retrospectively retrieved from all patients undergoing parathyroidectomy from 2010 to 2019 at our hospital. RESULTS: A total number of 84 PTA (Females 76.2%) patients were included, of which 24 (28.6%) qualified as a giant with a mean weight of 7.86 g and the rest were regular adenomas (71.4%) with a mean weight of 1.45 g. Giant adenomas were more likely to present at a younger age compared to regular adenoma patients, (44.4 vs 50.8, P = 0.053, D = 0.470). Preoperative PTH levels were significantly higher in the giant PTA group (650.8 vs 334.2 pg/mL, P = 0.044, r = 0.22). Hospital stay was on average 1.6 days longer in giant PTA patients compared to regular PTA patients. CONCLUSION: Giant PTA compromised a significant percentage of all adenomas, which was higher than what is reported in the literature and might reflect a delay in diagnosis and lack of screening tests. Both giant and regular adenomas seem to run a similar clinical course, yet biochemical abnormalities in PTH levels may have a predictive value for adenoma weight.