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Τρίτη 8 Ιουνίου 2021

Recurrent Sphenocavernous Meningioma

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1725941

A case of a recurrent sphenocavernous meningioma is presented. The patient is a 42-year-old male who presented with an episode of transient right-sided numbness. A magnetic resonance imaging (MRI) revealed a large left sphenocavernous meningioma. The patient underwent a frontotemporal craniotomy for tumor resection. Near total resection was achieved with minimal residual in the left cavernous sinus (CS) and orbital apex. The pathology was consistent with meningioma, World Health Organization (WHO) grade I. A follow-up MRI was done 9 months after surgery and showed a growth of the residual tumor, which was treated with intensity modulated radiotherapy. Tumor growth was detected on serial imaging over a 4-year period. Surgical resection was offered. A left frontotemporal craniotomy with pretemporal transcavernous approach was performed. The bone flap was reopened and the dura was opened in a Y-sha ped fashion. The roof of the optic canal was drilled off, and the falciform ligament was opened to decompress the optic nerve. The tumor was disconnected from the anterior clinoid region (the anterior clinoid process was eroded by the tumor) and reflected off the wall of the lateral CS. Tumor was adherent to the V2 fascicles (the lateral CS wall was resected in the first surgery) and was sharply dissected off. Gross total resection was achieved. The pathology was consistent with meningioma, WHO grade I. The patient had an unremarkable postoperative course without any new neurological deficits.The link to the video can be found at: https://youtu.be/KVBVw_86JqM.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Cochlear Implantation in Vestibular Schwannoma: A Systematic Literature Review

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0040-1715606

Objective Ipsilateral cochlear implantation (CI) in vestibular schwannoma (VS) has been an emerging trend over the last two decades. We conducted the first systematic review of hearing outcomes comparing neurofibromatosis 2 (NF2) and sporadic VS undergoing CI. A comparison of the two populations and predictor of outcome was assessed. This is an update to a previously presented study. Data Sources Systemic data searches were performed in PubMed NCBI and Scopus by an academic librarian. No restrictions based on the year of publication were used. Study Selection Studies were selected if patients had a diagnosis of NF2 and a CI placed in the affected side with reports of hearing outcome. Two independent reviewers screened each abstract and full-text article. Data Extraction Studies were extracted at the patient level, and the assessment of quality and bias was evaluated according to the National Institutes of Health Quality Assessment Tool. Main Outcome Measures Outcome predictors were determined by using the chi-square test and Student's t-test. Results Overall, most CI recipients functioned in the high-to-intermediate performer category for both sporadic and NF2-related VS. Median AzBio (Arizona Biomedical Institute Sentence Test) was 72% (interquartile range [IQR]: 50) in NF2 patients and 70% (IQR: 7.25) in sporadic patients. Larger tumor size predicted a poorer final audiometric outcome. Conclusions Categorization of hearing outcome into superior performance and inferior performance based on sentence recognition revealed a generally good hearing outcome regardless of treatment or patient population. Select patients with sporadic and NF2 VS may benefit from CI.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation

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Eur Arch Otorhinolaryngol. 2021 Jun 8. doi: 10.1007/s00405-021-06924-0. Online ahead of print.

ABSTRACT

PURPOSE: For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCTSECO) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based c ochlear implantation.

METHODS: Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCTSECO) of patients with and without implanted electrodes.

RESULTS: Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCTSECO with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCTSECO compared to MSCT.

CONCLUSION: The combination of fpVCTSECO and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.

PMID:34101009 | DOI:10.1007/s00405-021-06924-0

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Health-related quality of life in adults with profound postlingual hearing loss before and after cochlear implantation

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Eur Arch Otorhinolaryngol. 2021 Jun 8. doi: 10.1007/s00405-021-06866-7. Online ahead of print.

ABSTRACT

PURPOSE: In clinical trials and everyday medical practice, health-related quality of life (HRQoL) measures are increasingly being used. That is, in addition to the usual biological health assessment, the impact of disease and treatment on the patient's functioning in the physical, mental, and social areas is an important parameter. The aim of this study was to assess HRQoL before and after using a cochlear implant (CI) in adults with profound hearing loss.

METHODS: There were 104 patients who qualified for the study. All gave informed and free consent. The study involved adults with bilateral hearing loss above 81 dB HL and rated according to the World Health Organization (WHO) classification scheme as having profound hearing loss (which includes deafness). In each participant, the hearing loss was postlingual, that is, it occu rred after speech and language had developed. The assessment of quality of life (AQoL-8D) questionnaire was used to assess the health-related quality of life in the study participants.

RESULTS: Quality of life significantly increased (p < 0.001) after cochlear implantation in almost all domains (except the pain dimension). The mean increase in overall quality of life was 0.16, the greatest improvement was found in the dimensions senses (mean change of 0.17) and self-worth (mean change of 0.16).

CONCLUSION: Cochlear implantation improves the health-related quality of life of the postlingually deaf.

PMID:34101007 | DOI:10.1007/s00405-021-06866-7

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The use of melatonin for auditory brainstem response audiometry in children with comorbidities

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Eur Arch Otorhinolaryngol. 2021 Jun 8. doi: 10.1007/s00405-021-06923-1. Online ahead of print.

ABSTRACT

PURPOSE: In this study, the efficacy and feasibility of melatonin in young children with and without comorbidities, undergoing auditory brainstem response audiometry (ABR) was evaluated. The aim of this study was primarily to evaluate the use of melatonin for ABR investigations in children with comorbidities. Second, the efficacy of melatonin was evaluated based on several factors like sleep-onset latency, sleep duration, frequency of awakenings as well as adverse events.

METHODS: Click-induced ABR tests were performed at the outpatient clinic between January, 2018 and August, 2020. Investigations were considered successful when binaural testing was completed. A dose of melatonin depending on age, 5 mg for children younger than 6 years and 10 mg if older than 6 years, was administered after placement of electrodes.

RESULT S: 131 children were included in this study. 87% of all ABR investigations were performed successfully. Comorbidities such as neurodevelopmental disorders or developmental delays were present in 70% of all children. There was no significant difference in age (p = 0.36) or gender (p = 0.97) between the success and failed group. In addition, comorbidities were equally distributed between both groups. Mean sleep duration was 38 (SD 21) min and sleep-onset latency was 28 (SD 20) min No adverse events were documented.

CONCLUSION: Melatonin is effective for ABR examinations in infants and children with and without comorbidities. Furthermore, it allows for sequential testing in those at risk for progressive hearing loss. Clear instructions to caregivers and expertise of audiologists are a prerequisite for optimal outcomes.

PMID:34101008 | DOI:10.1007/s00405-021-06923-1

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Δευτέρα 7 Ιουνίου 2021

The dual functions of Rab11 and Rab35 GTPases-regulation of cell division and promotion of tumorigenicity

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Am J Cancer Res. 2021 May 15;11(5):1861-1872. eCollection 2021.

ABSTRACT

The broad studies of cancer have led researchers to the creditable understanding of biological and environmental factors that make benign cells to become malignant, as well as the developmental aspects of the tumour cells, known as the "hallmarks of cancer". However, additional research is needed to uncover the features of cancer biology, which would allow to design new and more effective treatment strategies for cancer patients. Since RabGTPases and their effectors are frequently altered in cancer, their role in a regulation of cell division leading to the acquisition of cancer cell-like phenotype has drawn a lot of attention from different research groups in recent years. Both, Rab11 and Rab35 belong to a superfamily of small monomeric GTPases that regulate a diverse array of cellular functions. Lately, Rab11 and Rab35 were declared as oncogenic, and because of their association with abundant cellular functions, a linkage to the induction of cancer, has been proposed. Although the clear connection between the improper regulation of Rab11 or Rab35 and the initiation of tumorigenicity has only beginning to emerge, in this review we will discuss the newest findings regarding the participation of RabGTPases in a control of cell division and promotion of tumorigenesis, trying to link the actual function to the cancer causality.

PMID:34094658 | PMC:PMC8167671

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MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2

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Am J Cancer Res. 2021 May 15;11(5):2159-2173. eCollection 2021.

ABSTRACT

MiR-22 has been demonstrated to inhibits tumor growth in several cancers. However, its function in the tumor microenvironment is still unclear, especially for T cell differentiation. Here, miR-22 expression in the circulating T cells from hepatocellular carcinoma (HCC) patients and healthy controls was analyzed with quantitative polymerase chain reaction (qPCR). Diethylnitrosamine (DEN)/phenobarbital (PB)-mediated primary HCC and Hepa1-6 subcutaneous tumor mouse models were established and subjected to lenti-miR-22 injection. Mice immunoreconstituted with miR-22-overexpressing T cells were employed to investigate the antitumor effect of miR-22 in mice. Luciferase assay, immunofluorescent staining, in vitro Th17 cell differentiation assay, and rescue experiments were employed to investigate the mechanism underlying the miR-22-mediated regulation of Th17 cell differ entiation and liver tumor growth. Results confirmed the dramatic downregulation of miR-22 expression in malignant tissues and circulating T cells from patients with HCC. MiR-22 expression correlated with good prognosis of patients. Overexpression of miR-22 impaired the DEN/PB-induced primary HCC formation and the growth of Hepa1-6 subcutaneous tumors by promoting Th17 differentiation. Injection of miR-22-overexpressing T cells in irradiated mice resulted in the inhibition of Hepa1-6 subcutaneous tumor growth via Th17 differentiation promotion. MiR-22 could directly bind to Jarid2, which played an important role during the miR-22-mediated regulation of Th17 differentiation. Taken together, our study expands the understanding of miR-22 function and provides a therapy target for HCC.

PMID:34094675 | PMC:PMC8167680

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The role of iron homeostasis and iron-mediated ROS in cancer

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Am J Cancer Res. 2021 May 15;11(5):1895-1912. eCollection 2021.

ABSTRACT

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments.

PMID:34094660 | PMC:PMC8167679

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HMGA1 induces EZH2 overexpression in human B-cell lymphomas

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Am J Cancer Res. 2021 May 15;11(5):2174-2187. eCollection 2021.

ABSTRACT

EZH2 is an enzymatic subunit of PRC2, an epigenetic regulator that triggers the methylation of the histone H3 lysine 27 silencing the transcription of several genes. EZH2 has a critical role in cancer progression, since its overexpression has been associated with increased cancer cell invasiveness, drug resistance and poor patient survival. However, the mechanisms accounting for EZH2 overexpression in cancer remain still unclear. Intriguingly, also HMGA protein overexpression is a feature of many human malignancies and correlates with the presence of metastases and a poor outcome. The HMGA proteins, including HMGA1 and HMGA2, belong to the architectural transcription factors that play a key role in the organization of chromatin structure. Here, we report a statistically significant correlation between HMGA1 and EZH2 expression in human lymphomas. We demonstrate th at HMGA1 is able to bind EZH2 promoter and induce its activity. Consistently, silencing of HMGA1 expression results in the downregulation of the EZH2 levels leading to a decreased proliferation and migration rate of human lymphoma cell lines. Therefore, these data identify HMGA1 as an EZH2 activator, suggesting a novel molecular mechanism contributing to EZH2 overexpression in human malignancies and a synergism of these proteins in cancer progression.

PMID:34094676 | PMC:PMC8167683

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Background, applications and challenges of radiogenomics in genitourinary tumor

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Am J Cancer Res. 2021 May 15;11(5):1936-1945. eCollection 2021.

ABSTRACT

Genitourinary tumors are groups of tumors with high complexity and heterogeneity. For long-term monitoring, biomarkers that can be used in detection, grading and treatment response assessment are needed. With rapid development in imaging technology and cancer genomics, radiogenomics, the combination of "radiology" and "genomics", has emerged as a powerful tool in oncology practice in recent years because imaging can provide some information that genomic test cannot as gene expression and mutation status are usually evaluated on a small portion of the tumor and are usually not powerful enough to reflect tumor heterogeneity. Radiogenomics investigates the correlations between imaging features and gene expression of a disease, especially in oncologic diseases. It aims to detect the disease's mutation status and supplement genomic analysis based on imaging analysis, p roviding additional findings for diagnosis, treatment decisions, evaluation of treatment response and prognosis prediction of the disease. Recent years have seen an increase in the number of studies investigating the application of radiogenomics in genitourinary tumors. Many studies have shown promising results. However, there still exist limitations and challenges. In this review, we will summarize recent applications of radiogenomics in genitourinary tumors and discuss limitiations, challenges and future directions of radiogenomics.

PMID:34094662 | PMC:PMC8167692

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Role of kruppel-like factor 8 for therapeutic drug-resistant multi-organ metastasis of breast cancer

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Am J Cancer Res. 2021 May 15;11(5):2188-2201. eCollection 2021.

ABSTRACT

Metastasis and drug resistance are intertwined processes that are responsible for the vast majority of patient deaths from breast cancer. The underlying mechanisms remain incompletely understood. We previously demonstrated that KLF8 activates CXCR4 transcription in metastatic breast cancer. Here, we report a novel role of KLF8-CXCR4 signaling for converting single organ metastasis into multiple organ metastasis associated with chemotherapeutic resistance. We show that KLF8 expression in metastatic breast cancer cells can be over-induced by chemotherapeutic drugs. Analysis of data from large-cohorts of patients indicates that post-chemotherapy there is a close correlation between the aberrant high levels of KLF8 and CXCR4 and that this correlation is well associated with drug resistance, metastasis, and poor prognosis. To mimic their aberrant high levels, we overex pressed KLF8 or CXCR4 in a human breast cancer cell line known to metastasize only to the lungs after intravenous injection in nude mice. As expected, these cells become more resistant to chemotherapeutic drugs. Surprisingly, these KLF8 or CXCR4 overexpressing cells, even implanted orthotopically, metastasized extensively to multiple organs particularly the CXCL12-rich organs. Tube formation assay, Ki67 staining and Western blotting revealed that KLF8 or CXCR4 overexpression enhanced angiogenesis involving increased expression and secretion of VEGF protein. We also found that KLF8 or CXCR4 overexpression strongly enhanced formation of filopodium-like protrusions and proliferation via CXCR4 stimulation in a 3D culture model mimicking the colonization step of metastasis. Taken together, these results suggest that the chemo-induction of KLF8 upregulation be critical for drug resistance and systemic metastasis through enhanced tumor angiogenesis and colonization via CXCR4 over-activatio n and that KLF8-CXCR4 signaling axis may be a new therapeutic target for drug-resistant breast cancer metastasis.

PMID:34094677 | PMC:PMC8167685

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