Effects of adjuvant chemotherapy and radiation on overall survival in children with choroid plexus carcinoma.

Choroid plexus carcinoma (CPCs) is a rare, malignant, primary brain tumor with a poor prognosis. Currently, there is no consensus on the use of adjuvant therapy, and few large-scale studies focus exclusively on the pediatric population. We performed a comprehensive systematic review of pediatric CPCs to determine the effects of various adjuvant therapy modalities on overall survival (OS). A literature search was performed to identify studies reporting children with CPC who underwent surgical resection. Only patients who had clearly received adjuvant therapy, or were described as not selected for adjuvant therapy were analyzed in our comparison groups. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of different types of adjuvant therapies on OS. A total of 135 children (age ≤ 18 years) with CPC who had known adjuvant therapy status and OS were identified from 53 articles. Kaplan-Meier analysis showed that while adjuvant therapy overall improved OS (p = 0.001), different modes of adjuvant therapies had varying effects on OS (p = 0.034). Specifically, combined chemo-radiotherapy as well as chemotherapy alone improved OS (p = 0.001), but radiation did not (p = 0.129). Multivariate Cox proportional hazard model adjusting for confounding factors showed that combined therapy was associated with better OS compared to chemotherapy alone (HR: 0.291, p = 0.027). Both chemotherapy alone and combined chemo-radiation improved OS independent of age, gender, tumor location and extent of resection, while radiation alone did not.

Gross total resection improves overall survival in children with choroid plexus carcinoma.

Choroid plexus carcinoma (CPC) is a rare, malignant, primary brain tumor with a poor prognosis. While previous reports have shown benefits of aggressive surgery, very few large-scale studies have focused exclusively on the pediatric population, for whom the risks of aggressive surgery must be weighed carefully against the benefits. We performed a comprehensive systematic review of pediatric CPCs to test the effects of gross total resection (GTR) on overall survival (OS) and progression-free survival (PFS). A Pubmed search was performed to identify children with CPC who underwent surgical resection. Only disaggregated clinical cases in which extent of resection was confirmed by CT or MRI were included for analysis. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of extent of resection on OS and PFS. Disaggregated clinical data from a total of 102 pediatric CPC patients (age ≤18 years) with known extent of resection and overall survival were analyzed. GTR was significantly associated with better OS by Kaplan-Meier analysis (logrank p < 0.001). Multivariate Cox regression analysis adjusting for age, gender, tumor location (supratentorial vs. infratentorial), and type of adjuvant therapy (chemotherapy, radiation, and combined therapy), showed that GTR independently increased OS (p = 0.006). While GTR also improved PFS on Kaplan-Meier analysis (p = 0.027), the effect did not meet our criteria for significance in our multivariate Cox model (p = 0.120). GTR improved OS of pediatric CPC and is recommended if it can be safely performed.

Current management of choroid plexus carcinomas.

Choroid plexus carcinoma (CPC) is a World Health Organization (WHO) grade III brain tumor with a poor prognosis that occurs mainly in children. Gross total resection of CPC is highly recommended and is associated with improved overall survival, although it is often associated with increased morbidity. The use of adjuvant therapies has yet to be standardized, although evidence suggests that for patients with incompletely resected CPCs, a combination of chemotherapy and radiation therapy may be beneficial. The use of radiation therapy for younger children (<3 years old) with CPC, however, is not recommended, due to the potential negative neurological sequelae associated with radiation to the developing brain. Given that the majority of CPC patients are young children, questions regarding optimal radiation dose, chemotherapy agents, and how to combine these two adjuvant treatment modalities to achieve the best outcomes remain unanswered. In this paper we summarize the current management of CPC in the literature. Further studies are needed to standardize the treatment paradigm for this malignant brain tumor.

Early radiographic outcomes after anterior cervical discectomy and fusion with anatomic versus lordotic cages.

Background: Anterior cervical discectomy and fusion (ACDF) interbody implants are shaped anatomically, with a convex superior aspect, or lordotically, with an angle and flat surfaces. However, the effect of implant shape on cervical sagittal balance (CSB) is not well described. Methods: Of the 192 cases reviewed from 2018 to 2019, 118 were included with matching pre- and postoperative imaging. Cases were categorized by interbody implant type (anatomic or lordotic) and number of levels fused (1-level, 2-level, etc.). SurgiMap was used to measure cervical lordosis (CL), C2-C7 sagittal vertical axis (cSVA), T1 slope (T1S), and T1S minus CL (T1S-CL) on pre- and postoperative imaging. Pre- and postoperative parameters were compared within and between each cohort. Change in CL (ΔCL), cSVA (ΔcSVA), and T1S-CL (ΔT1S-CL) were calculated as the difference between pre- and postoperative values and were compared accordingly (1) anatomic versus lordotic and (2) 1-level versus 2-level versus 3-level fusion. Results: Thirty-nine (33.1%), 57 (48.3%), and 22 (18.6%) cases comprised the anatomic, lordotic, and mixed (anatomic and lordotic) groups, respectively. ACDFs improved CL and T1S-CL by 5.71° (p<.001) and 3.32° (p<.01), respectively. CL was improved in the lordotic (5.27°; p<.01) and anatomic (4.57°; p<.01) groups, while only the lordotic group demonstrated improvement in T1S-CL (3.4°; p=.02). There were no differences in ΔCL (p=.70), ΔcSVA (p=.89), or ΔT1S-CL (p=.1) between the groups. Two- and 3-level fusions improved CL by 7.48° (p<.01) and 9.62° (p<.01), and T1S-CL by 4.43° (p<.01) and 5.96° (p<.01), respectively. Conclusions: Overall, ACDFs significantly improved CL and T1S-CL however, there were no differences in CSB correction between the anatomic and lordotic groups. Two- and 3-level fusions more effectively improved CL (vs. single-level) and T1S-CL (vs. 3-level). These results suggest that implants should continue to be personalized to the patient's anatomy, however, future research is needed to validate these findings and incorporate the effects of preoperative deformities.

Surgical outcomes in choroid plexus papillomas: an institutional experience.

Choroid plexus papillomas (CPPs) are rare, indolent lesions that comprise less than 0.5 % of intracranial tumors. We sought to assess the long-term outcomes and associated surgical complications at our institution. A review of the University of California, San Francisco (UCSF) Brain Tumor Research Center (BTRC) database was performed to identify a cohort of patients treated for CPP from 1997 to 2011. Patients were grouped based on tumor location and extent of resection. Outcomes including progression-free survival and surgical complications were assessed. We identified 24 patients (16 female, 8 male) ranging in age from 6 months to 55 years (median 29 years) treated at our institution. Tumors were found in the following locations: 16 (67 %) fourth ventricle/cerebellopontine angle; 7 (29 %) lateral ventricle; 1 (4 %) third ventricle. Gross total resection (GTR) was achieved in 20 patients (83 %) with subtotal resection (STR) in 4 (17 %). Median follow-up time was 2.8 years with 3 recurrences identified at 1.6, 3.3, and 8.5 years. Extent of resection and tumor location were not associated with recurrence. There was one new permanent neurologic deficit detected after surgery. All patients were alive at most recent follow-up. Attempted gross total resection is the standard treatment for CPPs and generally associated with excellent outcomes. Since recurrences are rare, even among patients who undergo STR, radiation may be reserved for cases of tumor progression. This modern experience at a tertiary care center performed exclusively during the MRI-era demonstrates that CPPs can be safely removed with minimal morbidity and good tumor control.

Histologic grade and extent of resection are associated with survival in pediatric spinal cord ependymomas.

PURPOSE: Prognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS). METHODS: A comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included. RESULTS: A total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR) = 0.248, p = 0.022). Moreover, older age (HR = 0.818, p = 0.026), GTR (HR = 0.042, p = 0.013), and anaplastic grade (HR = 19.847, p = 0.008) demonstrated a significant association with OS in a multivariate model. CONCLUSIONS: Among pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.

Development of multidisciplinary, evidenced-based protocol recommendations and implementation strategies for anterior lumbar interbody fusion surgery following a literature review.

The anterior lumbar interbody fusion (ALIF) procedure involves several surgical specialties, including general, vascular, and spinal surgery due to its unique approach and anatomy involved. It also carries its own set of complications that differentiate it from posterior lumbar fusion surgeries. The demonstrated benefits of treatment guidelines, such as Enhanced Recovery after Surgery in other surgical procedures, and the lack of current recommendations regarding the anterior approach, underscores the need to develop protocols that specifically address the complexities of ALIF. We aimed to create an evidence-based protocol for pre-, intra-, and postoperative care of ALIF patients and implementation strategies for our health system. A 12-member multidisciplinary workgroup convened to develop an evidence-based treatment protocol for ALIF using a Delphi consensus methodology and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for rating the quality of evidence and strength of protocol recommendations. The quality of evidence, strength of the recommendation and specific implementation strategies for Methodist Health System for each recommendation were described. The literature search resulted in 295 articles that were included in the development of protocol recommendations. No disagreements remained once the authors reviewed the final GRADE assessment of the quality of evidence and strength of the recommendations. Ultimately, there were 39 protocol recommendations, with 16 appropriate preoperative protocol recommendations (out of 17 proposed), 9 appropriate intraoperative recommendations, and 14 appropriate postoperative recommendations. This novel set of evidence-based recommendations is designed to optimize the patient's ALIF experience from the preoperative to the postoperative period.

Neuroanatomical correlation of the House-Brackmann grading system in the microsurgical treatment of vestibular schwannoma.

Avoidance of facial nerve injury is one of the major goals of vestibular schwannoma (VS) surgery because functional deficits of the facial nerve can lead to physical, cosmetic, and psychological consequences for patients. Clinically, facial nerve function is assessed using the House-Brackmann grading scale, which also allows physicians to track the progress of a patient's facial nerve recovery. Because the facial nerve is a peripheral nerve, it has the ability to regenerate, and the extent of its functional recovery depends largely on the location and nature of its injury. In this report, the authors first describe the facial nerve anatomy, the House-Brackmann grading system, and factors known to be predictors of postoperative facial nerve outcome. The mechanisms and pathophysiology of facial nerve injury during VS surgery are then discussed, as well as factors affecting facial nerve regeneration after surgery.

Candida Auris Urinary Tract Infection in a Nursing Home Patient With Multicomorbidities.

Candida (C.) auris is an opportunistic ascomycetous budding yeast that has been emerging as an invasive, multidrug-resistant pathogen over the past 11 years since its discovery. Candida auris infection has raised considerable attention in public health organizations due to its rising number of cases, virulence, and unique resistance to commonly used mycofungal therapy. This case follows a 64-year-old male with multiple comorbidities from the nursing home presenting with polybacterial sepsis along with a urinary tract infection growing Candida auris. Along with treatment for sepsis, the patient was placed on the Centers for Disease Control and Prevention's (CDC's) recommended regimen of micafungin to eradicate C. auris infection and isolation precautions. Cases should be approached carefully and reported to public agencies such as the CDC and state health department.

A Meta-Analysis on the Effects of Hydroxychloroquine on COVID-19.

Introduction Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world with a large medical and economic impact. On March 12, 2020, the World Health Organization (WHO) classified SARS-CoV-2 as a pandemic. As a result of this worldwide public health crisis, politicians, elected officials, and healthcare professionals emergently began trialing hydroxychloroquine (HCQ) in efforts to treat and prevent the transmission of the virus. This meta-analysis was performed to assess the effects of HCQ on patients with COVID-19. Methods  This meta-analysis adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMA) guidelines. Selected articles published between December 2019 and July 2020 were found utilizing the following search engines: PubMed, Google Scholar, Cochrane Library, DisasterLit, Clinicaltrials.gov, Medrxiv, and Embase. Two independent physician reviewers screened eligible articles that met the inclusion and exclusion criteria of the analysis. The outcome measures analyzed were mortality rate, rate of disease progression/improvement, rate of disease severity, and adverse effects of treatment. Six out of 14 studies that met the study's eligibility criteria were selected and further analyzed, with a total of 381 participants (n= 381). Conclusion From the studies analyzed, it was found that groups treated with HCQ had an overall mortality rate that was 2.5 times greater than that of the control group. HCQ treated patients had higher rates of adverse clinical outcomes and side effects compared with the control populations. Lastly, there was a 1.2 times higher rate of improvement in the group of HCQ treated patients with mild to moderate symptoms as compared to the control group.

Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I.

Ca(2+)-permeable AMPA receptors (CP-AMPARs) at central glutamatergic synapses are of special interest because of their unique biophysical and signaling properties that contribute to synaptic plasticity and their roles in multiple neuropathologies. However, intracellular signaling pathways that recruit synaptic CP-AMPARs are unknown, and involvement of CP-AMPARs in hippocampal region CA1 synaptic plasticity is controversial. Here, we report that intracellular infusion of active CaM-kinase I (CaMKI) into cultured hippocampal neurons enhances miniature EPSC amplitude because of recruitment of CP-AMPARs, likely from an extrasynaptic pool. The ability of CaMKI, which regulates the actin cytoskeleton, to recruit synaptic CP-AMPARs was blocked by inhibiting actin polymerization with latrunculin A. CaMK regulation of CP-AMPARs was also confirmed in hippocampal slices. CA1 long-term potentiation (LTP) after theta bursts, but not high-frequency tetani, produced a rapid, transient expression of synaptic CP-AMPARs that facilitated LTP. This component of TBS LTP was blocked by inhibition of CaM-kinase kinase (CaMKK), the upstream activator of CaMKI. Our calculations show that adding CP-AMPARs numbering <5% of existing synaptic AMPARs is sufficient to account for the potentiation observed in LTP. Thus, synaptic expression of CP-AMPARs is a very efficient mechanism for rapid enhancement of synaptic strength that depends on CaMKK/CaMKI signaling, actin dynamics, and the pattern of synaptic activity used to induce CA1 LTP.

Dominant role of the GluR2 subunit in regulation of AMPA receptors by CaMKII.

GluR1 and GluR2 subunits compose AMPA receptors (AMPARs) in the mature hippocampus, and both the GluR1 subunit and Ca2+/calmodulin-dependent protein kinase II (CaMKII) are required for synaptic plasticity, memory and learning. Although GluR1 phosphorylationby CaMKII is preserved, the functional regulation of AMPARs by phosphorylation is lost in the presence of the GIuR2 subunit. Our findings define a previously unknown, dominant role of the GluR2 subunit in signaling mediated by CaMKII at AMPARs.

Bidirectional regulation of cytoplasmic polyadenylation element-binding protein phosphorylation by Ca2+/calmodulin-dependent protein kinase II and protein phosphatase 1 during hippocampal long-term potentiation.

Induction of hippocampal long-term potentiation (LTP) requires activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), whereas maintenance of LTP additionally requires protein synthesis. We recently reported that CaMKII stimulates protein synthesis in depolarized hippocampal neurons through phosphorylation of the mRNA translation factor cytoplasmic polyadenylation element-binding protein (CPEB), and this phosphorylation is rapidly reversed by protein phosphatase 1 (PP1). Protein synthesis-dependent late-phase LTP (L-LTP) in the hippocampus requires calcium influx through the NMDA-type glutamate receptor (NMDA-R) to activate CaMKII as well as concomitant inhibition of PP1 mediated by protein kinase A. Therefore, we investigated the regulation of CPEB phosphorylation during L-LTP. Pharmacological stimulation of the NMDA-R in hippocampal slices to produce chemical long-term depression induced a brief dephosphorylation of CPEB. Modest LTP induction (once at 100 Hz), which induces a protein synthesis-independent early-phase LTP (E-LTP), resulted in a transient phosphorylation of CPEB. However, stronger stimulation (four times at 100 Hz), known to induce protein synthesis-dependent L-LTP, elicited a prolonged phosphorylation of CPEB. Furthermore, CPEB phosphorylation correlated with phosphorylation of PP1 inhibitor dopamine- and cAMP-regulated phosphoprotein, a known substrate for protein kinase A. These results evoke the hypothesis that bidirectional regulation of CPEB phosphorylation by CaMKII and protein phosphatases may serve as a mechanism to convert E-LTP into protein synthesis-dependent L-LTP by stimulating protein synthesis and thereby stabilizing synaptic enhancement.

Prognosis by tumor location in adults with intracranial ependymomas.

Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the meta-analysis. Patients presented at a mean of 8.2months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p<0.001) and OS (p=0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p=0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.

Surgical outcomes in spinal cord ependymomas and the importance of extent of resection in children and young adults.

OBJECT: Ependymomas are a common type of CNS tumor in children, although only 13% originate from the spinal cord. Aside from location and extent of resection, the factors that affect outcome are not well understood. METHODS: The authors performed a search of an institutional neuropathology database to identify all patients with spinal cord ependymomas treated over the past 20 years. Data on patient age, sex, clinical presentation, symptom duration, tumor location, extent of resection, use of radiation therapy, surgical complications, presence of tumor recurrence, duration of follow-up, and residual symptoms were collected. Pediatric patients were defined as those 21 years of age or younger at diagnosis. The extent of resection was defined by the findings of the postoperative MR images. RESULTS: A total of 24 pediatric patients with spinal cord ependymomas were identified with the following pathological subtypes: 14 classic (Grade II), 8 myxopapillary (Grade I), and 2 anaplastic (Grade III) ependymomas. Both anaplastic ependymomas originated in the intracranial compartment and spread to the spinal cord at recurrence. The mean follow-up duration for patients with classic and myxopapillary ependymomas was 63 and 45 months, respectively. Seven patients with classic ependymomas underwent gross-total resection (GTR), while 4 received subtotal resection (STR), 2 received STR as well as radiation therapy, and 1 received radiation therapy alone. All but 1 patient with myxopapillary ependymomas underwent GTR. Three recurrences were identified in the Grade II group at 45, 48, and 228 months. A single recurrence was identified in the Grade I group at 71 months. The mean progression-free survival (PFS) was 58 months in the Grade II group and 45 months in the Grade I group. CONCLUSIONS: Extent of resection is an important prognostic factor in all pediatric spinal cord ependymomas, particularly Grade II ependymomas. These data suggest that achieving GTR is more difficult in the upper spinal cord, making tumor location another important factor. Although classified as Grade I lesions, myxopapillary ependymomas had similar outcomes when compared with classic (Grade II) ependymomas, particularly with respect to PFS. Long-term complications or new neurological deficits were rare. Among patients with long-term follow-up, those who underwent GTR had a recurrence rate of 20% compared with 40% among those with STR or biopsy only, suggesting that extent of resection is perhaps a more important prognostic factor than histological grade in predicting PFS, which has been suggested by other data in the literature. Given the relative paucity of these lesions, collaborative multiinstitutional studies are needed, and such efforts should also focus on molecular and genetic analysis to refine the current classification system.

The role of epidermal growth factor-like module containing mucin-like hormone receptor 2 in human cancers.

G-protein coupled receptors (GPCRs) are among the most diverse and ubiquitous proteins in all of biology. The epidermal growth factor-seven span transmembrane (EGF-TM7) subfamily of adhesion GPCRs is a small subset whose members are mainly expressed on the surface of leukocytes. The EGF domains on the N-terminus add significant size to these receptors and they are considered to be among the largest members of the TM7 family. Although not all of their ligands or downstream targets have been identified, there is evidence implicating the EGF-TM7 family diverse processes such as cell adhesion, migration, inflammation, and autoimmune disease. Recent studies have identified expression of EGF-TM7 family members on human neoplasms including those of the thyroid, stomach, colon, and brain. Their presence on these tissues is not surprising given the ubiquity of GPCRs, but because their functional significance and pathways are not completely understood, they are of tremendous clinical and scientific interest. Current evidence suggests that expression of certain EGF-TM7 receptors is correlated with tumor grade, confers a more invasive phenotype, and increases the likelihood of metastatic disease. In this review, we will discuss the structure, function, and regulation of these receptors. We also describe the expression of these receptors in human cancers and explore their potential mechanistic significance.

Prognosis by tumor location in adults with spinal ependymomas.

OBJECT: Ependymomas are primary central nervous system tumors that occur more frequently in the spines of adults than they do there in children. Previous studies consist mainly of retrospective single-institutional experiences or case studies. In this study, a comprehensive literature review was performed on reported cases of spinal ependymoma treated with resection to determine whether tumor location along the spinal axis conveys important prognostic information. METHODS: A PubMed search was performed to identify all papers that included data on patients with spinal ependymoma. Only cases involving adult patients who underwent ependymoma resection with a clearly reported tumor location were included for analysis. Tumor locations were separated into 6 groups: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus + cauda equina. Kaplan-Meier survival and Cox regression analyses were performed to determine the effect of tumor location on progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 447 patients who underwent resection of spinal ependymomas with clearly indicated location of tumor were identified. The most common locations of spinal ependymomas were the cervical (32.0%) and conus + cauda equina (26.8%) regions. The thoracolumbar and cervicomedullary regions had the fewest tumors (accounting for, respectively, 5.1% and 3.4% of the total number of cases). The conus + cauda equina and thoracolumbar regions had the highest percentage of WHO Grade I tumors, while tumors located above these regions consisted of mostly WHO Grade II tumors. Despite the tendency for benign grades in the lower spinal regions, PFS for patients with spinal ependymomas in the lower 3 regions (thoracic, thoracolumbar, conus + cauda equina) was significantly shorter (p < 0.001) than for those with tumors in the upper regions (cervicomedullary, cervical, cervicothoracic), but the difference in OS did not achieve statistical significance (p = 0.131). CONCLUSIONS: Spinal ependymomas along different regions of spinal axis have different characteristics and clinical behaviors. Tumor grade, extent of resection, and PFS varied by tumor location (upper vs lower spinal regions), while OS did not. Recurrence rates were higher for the lower spinal cord tumors, despite a greater prevalence of lower WHO grade lesions, compared with upper spinal cord tumors, suggesting that tumor location along the spinal axis is an important prognostic factor.

CD97 is a multifunctional leukocyte receptor with distinct roles in human cancers (Review).

G-protein coupled receptors (GPCRs) represent the most diverse and biologically ubiquitous protein receptors. The epidermal growth factor seven-span transmembrane (EGF-TM7) family consists of adhesion GPCRs with a diverse functional repertoire. CD97 is the most broadly expressed member with roles in cell adhesion, migration and regulation of intercellular junctions. CD97 is also expressed in a variety of human malignancies including those of the thyroid, stomach, colon and brain. CD97 confers an invasive phenotype and has been shown to correlate with tumor grade, lymph node invasion, metastatic spread and overall prognosis. More recently, CD97 was found to signal through Gα12/13, resulting in increased RHO-GTP levels. Proven roles in tumor invasion and signaling make CD97 an exciting novel therapeutic target. In this review, we will discuss the structure and function of this receptor, with a specific focus on its mechanistic significance in neoplastic diseases.

Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

Spinal ependymomas: benefits of extent of resection for different histological grades.

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p<0.001), grade I and II tumors did not differ significantly in outcomes following surgery. Overall, gross total resection (GTR, 68.7%, 114/166) provided significantly improved progression-free survival (PFS, p<0.001) and overall survival (OS, p=0.022) compared to the subtotal resection group. Surprisingly, the highest GTR rate was achieved for grade II tumors (78.8%, 78/99; p<0.001) followed by grade I (58.9%, 33/56) and grade III tumors (27.3%, 3/11). Interestingly, PFS was significantly improved by GTR for grade II tumors (p<0.001), but not for grade I (p=0.705). Similar trends, although not statistically significant, were found for OS. Our results show that while GTR provides the best overall outcomes, GTR is most effective for classic grade II ependymomas, but not for grade I ependymomas. Despite having a lower WHO grade, myxopapillary ependymomas have a lower GTR rate, and benefit less from GTR.