The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate.

The choroid plexuses (CPs), located in the brain ventricles, form an interface between the blood and the cerebrospinal fluid named the blood-cerebrospinal barrier, which, by the presence of tight junctions, detoxification enzymes, and membrane transporters, limits the traffic of molecules into the central nervous system. It has already been shown that sex hormones regulate several CP functions, including the oscillations of its clock genes. However, it is less explored how the circadian rhythm regulates CP functions. This study aimed to evaluate the impact of sex hormones and circadian rhythms on the function of CP membrane transporters. The 24 h transcription profiles of the membrane transporters rAbca1, rAbcb1, rAbcc1, rAbcc4, rAbcg2, rAbcg4, and rOat3 were characterized in the CPs of intact male, intact female, sham-operated female, and gonadectomized rats. We found that rAbcc1 is expressed in a circadian way in the CPs of intact male rats, rAbcg2 in the CPs of intact female rats, and both rAbcc4 and rOat3 mRNA levels were expressed in a circadian way in the CPs of intact male and female rats. Next, using an in vitro model of the human blood-cerebrospinal fluid barrier, we also found that methotrexate (MTX) is transported in a circadian way across this barrier. The circadian pattern of Abcc4 found in the human CP epithelial papilloma cells might be partially responsible for MTX circadian transport across the basal membrane of CP epithelial cells.

Choroid plexus papilloma-A case highlighting the challenges of extrapolating pediatric chemotherapy regimens to adult populations.

The treatment of adults who present with rare pediatric tumors is not characterized well in the literature. We report an instance of a 40-year-old African American woman with a diagnosis of choroid plexus carcinoma admitted to the intensive care unit for severe sepsis seven days after receiving chemotherapy consisting of carboplatin (350 mg/m(2) on Days 1 and 2 plus etoposide 100 mg/m(2) on Days 1-5). Her laboratory results were significant for an absolute neutrophil count of 0/µL and blood cultures positive for Capnocytophagia species. She was supported with broad spectrum antibiotics and myeloid growth factors. She eventually recovered and was discharged in stable condition. The management of adults with malignancies most commonly seen in pediatric populations presents substantial challenges. There are multiple age-specific differences in renal and hepatic function that explain the need for higher dosing in pediatric patients without increasing the risk of toxicity. Furthermore, differences in pharmacokinetic parameters such as absorption, distribution, and clearance are present but are less likely to affect patients. It is expected that the pediatric population will have more bone marrow reserve and, therefore, less susceptible to myelosuppression. The extrapolation of pediatric dosing to an adult presents a problematic situation in treating adults with malignancies that primarily effect pediatric patients. We recommend extrapolating from adult treatment regimens with similar agents rather than extrapolating from pediatric treatment regimens to reduce the risk of toxicity. We also recommend the consideration of adding myeloid growth factors. If the treatment is tolerated without significant toxicity, dose escalation can be considered.

The role of chemotherapy and surgical removal in the treatment of Choroid Plexus carcinomas and atypical papillomas.

INTRODUCTION: We performed a retrospective study on clinical assessment, tumor location, radiological imaging, histopathological characteristics, and therapeutic management of 7 patients affected by choroid plexus carcinoma (CPC) or atypical choroid plexus papilloma (ACPP) who have been observed in the last 12 years. METHODS: Four patients fulfilled the criteria for classification as ACPP and three cases as CPC. The median age of the patients at the diagnosis was 42 months (range 3-190 months). Except one older patient (15 years old), all patients were younger than 3 years of age. In all patients affected by ACPP, a total surgical resection was achieved. Two children relapsed 12 and 8 months following radical removal. Both of them underwent adjuvant chemotherapy (carboplatin, cyclophosphamide, etoposide, doxorubicin, and methotrexate); a complete remission was maintained in all cases. In all three patients with CPC, it was impossible to achieve complete resection at first surgery. The response to chemotherapy was variable: in one case, it was complete with complete remission following 6 months; in one case, it was partial with reduction on volume (the patient underwent second-look surgery with complete resection); in the third case, there was no response and the patient progressed and finally died with metastatic disease, 8 months after chemotherapy was started. For children with CPC, the OS was 75% at 6 years. RESULTS: In our series, surgery associated with chemotherapy led to long-term survival in 4/4 patients affected by ACPP and 2/3 patients affected by CPC. Clinical results achieved in our series confirm that our therapeutic regimen is feasible and efficient as a possible adjuvant treatment for both CPC and ACPP. It also suggests that surgery has a pivotal role in the management of most children affected by CPTs.

Preoperative vincristine for an inoperable choroid plexus papilloma: a case discussion and review of the literature.

The authors report the case of a 14-month-old boy with a large right intraventricular choroid plexus papilloma (CPP) for which the first attempt at resection resulted in life-threatening intraoperative hemorrhage. The tumor was unsuitable for embolization, and neoadjuvant ifosfamide, carboplatin, etoposide (ICE) chemotherapy had no effect on tumor size. However, chemotherapy with vincristine, although not impacting on CT perfusion parameters, resulted in a significant decrease in tumor size, enabling complete resection with manageable blood loss. The mechanism underlying the effect of vincristine in this case is uncertain, but it is a treatment strategy that warrants further evaluation for the treatment of CPPs that are not amenable to embolization.

Infantile intracranial neoplasms: characteristics and surgical outcomes of a contemporary series of 21 cases in an Egyptian referral center.

OBJECTIVE: To investigate the demographic, clinical, radiological, pathological and surgical features and outcomes of infantile intracranial neoplasms, the second most common neoplasm in infants. PATIENTS AND METHODS: We conducted a retrospective study in the Department of Pediatric Neurosurgery at the Abo El-Reish Children's Hospital from 2005 to 2008. RESULTS: Out of 451 patients with primary intracranial neoplasms (age 0-14 years), 21 infants (<1 year) underwent surgery, representing 4.7% of total cases. The most common tumor was choroid plexus papilloma (23.8%), followed by teratoma (19%) then astrocytoma and ependymoma (14.3% each). Of the 21 surgical cases, 90% were intra-axial, 80% were in the supratentorial region, and 57% were intraventricular. There was only 1 case of intraoperative mortality (4.8%). Gross total excision was achieved in 65%, debulking in 30%, and biopsy in 5%. Three patients received chemotherapy, but none received radiotherapy. The statistically significant predictors of prognosis were the extent of resection and tumor grade. CONCLUSION: Although the prognosis for infantile intracranial neoplasms is worse than for older children, an overall promising outcome with low operative morbidity and mortality was achieved using gross total excision and appropriate adjuvant chemotherapy as part of a multidisciplinary approach.

Efficacy of multi-staged surgery and adjuvant chemotherapy for successful treatment of atypical choroid plexus papilloma in an infant: case report.

A 12-month-old girl presented with a rare atypical choroid plexus papilloma manifesting as conscious disturbance and vomiting. Magnetic resonance (MR) imaging revealed a well-delineated 5 x 6-cm lobulate mass in the right lateral ventricle. Only partial removal of the tumor was performed because of excessive intraoperative hemorrhage at the first surgery. The histological diagnosis was atypical choroid plexus papilloma. To control the intraoperative hemorrhage, embolization of the feeding artery was performed before the second surgery, and the tumor was macroscopically totally removed. MR imaging disclosed a small residual tumor which showed relatively rapid growth. The patient underwent the third removal 5 months after the second surgery. Two months later, MR imaging showed a cystic lesion with a small nodule adjacent to the midbrain, indicating dissemination of the tumor. The lesion was successfully treated with chemotherapy. Atypical choroid plexus papilloma was recently defined in the classification of the World Health Organization, so clinical data based on these criteria are lacking to establish the therapeutic strategy. Total resection of atypical choroid plexus papilloma is the most reliable treatment at present. However, postoperative chemotherapy should be considered for recurrence or dissemination.

Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study.

Atypical choroid plexus papilloma (APP) represents a novel intermediate-grade subtype of choroid plexus tumor (CPT), the clinical outcome of which has not been described yet. We present the first analysis of a group of APP patients enrolled in the ongoing CPT-SIOP-2000 study of CPTs. A worldwide registration and a randomized trial for those patients who require chemotherapy started in 2000. For APP, maximal surgical resection was recommended. After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses (etoposide and vincristine, combined with either carboplatin or cyclophosphamide). Risk-adapted radiotherapy was given only to patients older than 3 years of age. Of the 106 patients with a centrally confirmed CPT histology, 30 had APP, 42 CPP and 34 CPC. APP patients were significantly younger (median = 0.7 years) than patients with CPP or CPC (both medians = 2.3 years). Complete resection was achieved in 68 (64%) patients (79% in CPP, 63% in APP, and 47% in CPC). Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients. All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease. In the observation group of 15 patients, one event was seen, and all patients were alive. In the treatment group, one patient with a metastasized tumor and incompletely resected APP died. While APP was defined histologically, median percentages of both the Ki-67/MIB-1 proliferation marker and the p53 tumor suppressor protein increased across the three histological subtypes (from CPP to APP and then CPC), suggesting that the subtypes comprise an ordinal categorization of increasingly severe CPT tumors. This ordering was reiterated by clinical outcome in the 92 patients treated per the study protocol, with 5-year EFS rates of 92% in 39 CPP patients, 83% in 24 APP patients, and 28% in 29 CPC patients. A similar ordering was seen when all 106 patients were evaluated for EFS. APP responded favorably to chemotherapy. The intermediate position of APP between CPP and CPC was supported by the clinical data.

Vestibular syndrome due to a choroid plexus papilloma in a ferret.

A 6-year-old, castrated male ferret (Mustela putorius furo) was presented with progressive neurological signs consisting of a right-sided head tilt and ataxia. Neurological examination revealed hemiparesis and absence of proprioception on the right side, consistent with central vestibular syndrome. Measurement of blood glucose excluded hypoglycemia due to insulinoma. Contrast-enhanced computed tomography revealed the presence of an intracranial mass, consistent with either granuloma or neoplasia. Palliative treatment with prednisolone yielded no improvement. At postmortem examination, a final diagnosis of a choroid plexus papilloma originating from the fourth ventricle was made. This is the first report of such a tumor in a ferret.

Treatment factors associated with outcomes in children less than 3 years of age with CNS tumours.

INTRODUCTION: This study aimed to document cognitive outcomes in children treated for brain tumours with surgery and/or chemotherapy before the age of 3 years and to investigate the relationship between treatment factors and cognitive outcome. MATERIALS AND METHODS: Participants were 31 children aged 7-14 years who had been diagnosed and treated for brain tumours under the age of 3 years. Neuropsychological assessment included tests of cognitive functioning (WASI), memory (CMS) and executive functioning (BADS-C). RESULTS AND DISCUSSION: IQ and memory functioning scores were within the normal range but executive function was significantly below the expected level. Lower socio-economic status, younger age at treatment, having undergone more than one surgical intervention, motor problems and speech and language difficulties were found to be related to cognitive functioning. Although this group of children have good outcomes in terms of IQ and memory they have significant difficulties with executive functioning. CONCLUSION: Further research in this area is needed to allow for development of appropriate support packages for those who are most at risk.