Surgical Management of Brain Metastasis from Esophageal Cancer: A Systematic Review and Single-Center Experience.

BACKGROUND: Brain metastases from esophageal cancer (BMEC) are rare and aggressive, with limited literature on optimal treatment modalities and a standard of care yet to be established. The objective of this study was to systematically review existing literature and perform a retrospective analysis of our institution's patients to evaluate the influence of different treatment modalities on patient outcomes. METHODS: A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and a retrospective review of our institutional experience with BMEC were both conducted. Data based on mean survival,histology, metastasis location, and treatment modality were abstracted. RESULTS: A total of 48 studies representing 136 patients with BMEC were identified, in addition to the 11 patients treated at our institution. There were a total of 100 males (12 unreported), with a median age of 62.2 at diagnosis in our systematic review, along with 8 males with a median age of 62 in our institutional review. Collectively, survival rates observed based on histology were not similar (squamous cell carcinoma: 9.2 months, adenocarcinoma: 13.4 months), however, based on treatment modalities (surgery: 11.6 months, radiation: 10.4 months, chemotherapy: 12.3 months), and metastasis location (supratentorial: 10.5 months, infratentorial: 9.9 months), the survival times were comparable. CONCLUSIONS: Our review suggests that causes of death were often independent of brain metastases highlighting the need for further studies on early detection and prevention of primary esophageal cancer, as well as improved treatment modalities for BMECs.

Pituitary Macroadenoma with Optic Cupping Masquerading as Normal Tension Glaucoma.

When non-glaucomatous disease with disc cupping mimics normal-tension glaucoma (NTG), diagnosis is challenging. The typical optic disc features of glaucomatous disease are often subjective, and often overlap with disc changes in compressive intracranial lesions. Ancillary diagnostic testing such as retinal nerve fiber layer (RNFL) analysis and visual field testing can elevate the index of suspicion of an underlying non-glaucomatous process. We present a case of a nonfunctional macroadenoma coexisting with NTG, although it is unclear if the concurrent brain lesion aggravated or caused it. This case highlights the diagnostic challenge of recognizing optic cupping and non-matching abnormalities in the visual field from a coexisting intracranial lesion, even in the absence of other neurological signs.

Surgically Treated Brain Metastases from Uterine Origin: A Case Series and Systematic Review.

OBJECTIVE: We aimed to describe our institutional case series of 9 surgically treated uterine brain metastases and perform a survival analysis through a systematic review and a pooled individual patient data study. METHODS: This study was divided into 2 sections: 1) a retrospective, single center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising in the uterus with brain metastases and 2) a systematic review of the literature between 1980 and 2021 regarding treatment outcomes of individual patients with intracranial metastasis of uterine origin. Pooled cohort survival analysis was done via univariate and Cox regression multivariable analysis and Kaplan-Meier curves. RESULTS: Final statistical analysis included a total of 124 pooled cohort patients: one hundred fifteen patients from literature review studies plus 9 patients from our institution. Median age at the time of diagnosis was 54 years. Median time from diagnosis of the primary cancer to brain metastasis was 19 months (0-166 months). Surgery and radiotherapy resulted in the highest median OS of 11 months (P < 0.001). Multivariable analyses indicated that the presence of more than one central nervous systemlesion had an increased risk on OS (P = 0.003). Microsurgery, stereotactic radiosurgery, and whole brain radiotherapy remain the evidence-based mainstay applicable to the treatment of multiple brain metastases. CONCLUSIONS: Brain metastases of cancer arising in the uterus appear to result most often in multiple lesions with dismal prognosis. The seemingly most efficacious treatment modality is surgery and radiotherapy. However, this treatment is often not an option when more than 1 or 2 brain lesions are present.

Malignant Transformation of an Intracranial Epidermoid Cyst 25 Years After Initial Surgery: A Case Report and Systematic Review.

OBJECTIVE: We report a unique case of a suspected recurrent intracranial epidermoid cyst (EDC) that was found on pathology to have undergone malignant transformation to squamous cell carcinoma (SCC) approximately 25 years after initial resection. Additionally, we performed a systematic review including 94 studies reporting intracranial EDC to SCC transformation. METHODS: Ninety-four studies were included in our systematic review. PubMed, Scopus, Cochrane Central, and EMBASE were searched in April 2020 for studies regarding histologically confirmed SCC arising within an EDC. Kaplan-Meier estimations were used to estimate time to event including survival, and log rank tests were used to test for significance. All analyses were conducted using STATA 14.1 (StataCorp, College Station, Texas, USA); tests were two-sided, and statistical significance was defined using the alpha threshold of 0.05. RESULTS: The overall median time to transformation was 60 months (95% confidence interval {CI}, 12-96). Transformation time was significantly shorter in the no surgery group (10 months, 95% CI undefined) versus the other 2 groups (60 months, 95% CI, 12-72 in surgery only and 70 months, 95% CI, 9-180 in surgery + adjuvant therapy group, both P < 0.01). Overall survival was significantly longer in the surgery + adjuvant therapy group (13 months, 95% CI, 9-24) versus the other 2 groups (3 months, 95% CI, 1-7 in surgery only and 6 months, 95% CI, 1-12 in the no surgery group, both P < 0.01). CONCLUSIONS: We report a rare case of delayed malignant transformation of an intracranial EDC to SCC, occurring nearly 25 years after initial resection. Transformation time in the no-surgery group was statistically significantly shorter as compared to the surgery only and surgery + adjuvant therapy groups. Overall survival was statistically significantly higher in the surgery + adjuvant therapy group as compared to the surgery only and no surgery groups.

Nuclear respiratory factor 1 transcriptomic signatures as prognostic indicators of recurring aggressive mesenchymal glioblastoma and resistance to therapy in White American females.

PURPOSE: The mechanisms contributing to recurrence of glioblastoma (GBM), an aggressive neuroepithelial brain tumor, remain unknown. We have recently shown that nuclear respiratory factor 1 (NRF1) is an oncogenic transcription factor and its transcriptional activity is associated with the progression and prognosis of GBM. Herein, we extend our efforts to (1) identify influential NRF1-driven gene and microRNA (miRNA) expression for the aggressiveness of mesenchymal GBM; and (2) understand the molecular basis for its poor response to therapy. METHODS: Clinical data and RNA-Seq from four independent GBM cohorts were analyzed by Bayesian Network Inference with Java Objects (BANJO) and Markov chain Monte Carlo (MCMC)-based gene order to identify molecular drivers of mesenchymal GBM as well as prognostic indicators of poor response to radiation and chemotherapy. RESULTS: We are the first to report sex-specific NRF1 motif enriched gene signatures showing increased susceptibility to GBM. Risk estimates for GBM were increased by greater than 100-fold with the joint effect of NRF1-driven gene signatures-CDK4, DUSP6, MSH2, NRF1, and PARK7 in female GBM patients and CDK4, CASP2, H6PD, and NRF1 in male GBM patients. NRF1-driven causal Bayesian network genes were predictive of poor survival and resistance to chemoradiation in IDH1 wild-type mesenchymal GBM patients. NRF1-regulatable miRNAs were also associated with poor response to chemoradiation therapy in female IDH1 wild-type mesenchymal GBM. Stable overexpression of NRF1 reprogramed human astrocytes into neural stem cell-like cells expressing SOX2 and nestin. These cells differentiated into neurons and form tumorospheroids. CONCLUSIONS: In summary, our novel discovery shows that NRF1-driven causal genes and miRNAs involved in cancer cell stemness and mesenchymal features contribute to cancer aggressiveness and recurrence of aggressive therapy-resistant glioblastoma.

Sensitivity to differential NRF1 gene signatures contributes to breast cancer disparities.

PURPOSE: Nuclear respiratory factor 1 (NRF1) drives estrogen-dependent breast tumorigenesis. Herein we examined the impact of NRF1 activity on the aggressiveness and disparate molecular signature of breast cancer in Black, White, Asian, and Hispanic women. METHODS: NRF1 activity by transcription factor target enrichment analysis and causal NRF1-target gene signatures by Bayesian Network Inference with Java Objects (BANJO) and Markov Chain Monte Carlo (MCMC)-based gene order were examined in The Cancer Genome Atlas (TCGA) breast cancer cohorts. RESULTS: We are the first to report increased NRF1 activity based on its differential effects on genome-wide transcription associated with luminal A and B, HER2+ and triple-negative (TN) molecular subtypes of breast cancer in women of different race/ethnicity. We observed disparate NRF1 motif-containing causal gene signatures unique to Black, White, Asian, and Hispanic women for luminal A breast cancer. Further gene order searches showed molecular heterogeneity of each subtype of breast cancer. Six different gene order sequences involving CDK1, HMMR, CCNB2, CCNB1, E2F1, CREB3L4, GTSE1, and LMNB1 with almost equal weight predicted the probability of luminal A breast cancer in whites. Three different gene order sequences consisting of CCNB1 and GTSE1, and CCNB1, LMNB1, CDK1 or CASP3 predicted almost 100% probability of luminal B breast cancer in whites; CCNB1 and LMNB1 or GTSE predicted 100% HER2+ breast cancer in whites. GTSE1 and TUBA1C combined together predicted 100% probability of developing TNBC in whites; NRF1, TUBA1B and BAX with EFNA4, and NRF1 and BTRC predicated 100% TNBC in blacks. High expressor NRF1 TN breast tumors showed unfavorable prognosis with a high risk of breast cancer death in white women. CONCLUSION: Our findings showed how sensitivity to high NRF1 transcriptional activity coupled with its target gene signatures contribute to racial differences in luminal A and TN breast cancer subtypes. This knowledge may be useful in personalized intervention to prevent and treat this clinically challenging problem.

Considering iatrogenic psychosis after malignant glioma resection.

It is generally well known that medial temporal lobe resections have been associated with a variety of postoperative neuropsychiatric disturbances. Most of the neurosurgical literature on psychiatric disturbances after a temporal lobectomy concern patients with a strong history of epilepsy; however, relatively few articles have been reported due to a mesial temporal lobectomy following tumour removal. We report the case of a patient who underwent a gross total resection of a malignant astrocytoma in the temporal lobe who developed transient psychosis. Difficulties in diagnosing and predicting this condition are discussed as along with management considerations.