NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine.

Deciphering the molecular pathways associated with N-methyl-D-aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain-derived models that are amenable to studying the neurobiology of schizophrenia may contribute to filling the gaps left by the widely employed animal models. Here, we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK-801 on human brain slice cultures obtained from adult donors submitted to respective neurosurgery. Initially, we demonstrated that MK-801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass-spectrometry-based proteomics and systems biology in silico analyses, we found that MK-801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology, including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid, and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK-801-induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset, we identified potential modulators of the MK-801-induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia. This dataset is publicly available and may be helpful in further studies aimed at evaluating the effects of MK-801 and antipsychotics in the human brain.

Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Progressive chronic calvarial osteomyelitis in rhino-orbital mucormycosis associated with COVID-19.

We describe two cases of extensive indolent calvarial osteomyelitis after rhino-orbital-mucormycosis in diabetic patients previously diagnosed with COVID-19. Both patients presented with acute rhino-orbital symptoms about one month after being diagnosed with COVID-19. Treatment with intravenous liposomal Amphotericin B and prompt radical surgical debridement was instituted, but calvarial osteomyelitis ensued and persisted chronically despite maintenance of antifungal therapy and partial debridement of necrotic calvarial bone. The patients were discharged to continue antifungal therapy on a day-hospital regime. After more than 8 months of treatment, they remain with radiological signs of osteomyelitis but with no symptoms or intracranial extension of the infection. Calvarial indolent osteomyelitis secondary to mucormycosis is extremely rare, and little is known regarding its treatment. We believe it can be controlled with medical treatment and partial bony debridement although more studies are necessary to better define therapy.

Searching for a paradigm shift in the research on the epilepsies and associated neuropsychiatric comorbidities. From ancient historical knowledge to the challenge of contemporary systems complexity and emergent functions.

In this review, we will discuss in four scenarios our challenges to offer possible solutions for the puzzle associated with the epilepsies and neuropsychiatric comorbidities. We need to recognize that (1) since quite old times, human wisdom was linked to the plural (distinct global places/cultures) perception of the Universe we are in, with deep respect for earth and nature. Plural ancestral knowledge was added with the scientific methods; however, their joint efforts are the ideal scenario; (2) human behavior is not different than animal behavior, in essence the product of Darwinian natural selection; knowledge of animal and human behavior are complementary; (3) the expression of human behavior follows the same rules that complex systems with emergent properties, therefore, we can measure events in human, clinical, neurobiological situations with complexity systems' tools; (4) we can use the semiology of epilepsies and comorbidities, their neural substrates, and potential treatments (including experimental/computational modeling, neurosurgical interventions), as a source and collection of integrated big data to predict with them (e.g.: machine/deep learning) diagnosis/prognosis, individualized solutions (precision medicine), basic underlying mechanisms and molecular targets. Once the group of symptoms/signals (with a myriad of changing definitions and interpretations over time) and their specific sequences are determined, in epileptology research and clinical settings, the use of modern and contemporary techniques such as neuroanatomical maps, surface electroencephalogram and stereoelectroencephalography (SEEG) and imaging (MRI, BOLD, DTI, SPECT/PET), neuropsychological testing, among others, are auxiliary in the determination of the best electroclinical hypothesis, and help design a specific treatment, usually as the first attempt, with available pharmacological resources. On top of ancient knowledge, currently known and potentially new antiepileptic drugs, alternative treatments and mechanisms are usually produced as a consequence of the hard, multidisciplinary, and integrated studies of clinicians, surgeons, and basic scientists, all over the world. The existence of pharmacoresistant patients, calls for search of other solutions, being along the decades the surgeries the most common interventions, such as resective procedures (i.e., selective or standard lobectomy, lesionectomy), callosotomy, hemispherectomy and hemispherotomy, added by vagus nerve stimulation (VNS), deep brain stimulation (DBS), neuromodulation, and more recently focal minimal or noninvasive ablation. What is critical when we consider the pharmacoresistance aspect with the potential solution through surgery, is still the pursuit of localization-dependent regions (e.g.: epileptogenic zone (EZ)), in order to decide, no matter how sophisticated are the brain mapping tools (EEG and MRI), the size and location of the tissue to be removed. Mimicking the semiology and studying potential neural mechanisms and molecular targets - by means of experimental and computational modeling - are fundamental steps of the whole process. Concluding, with the conjunction of ancient knowledge, coupled to critical and creative contemporary, scientific (not dogmatic) clinical/surgical, and experimental/computational contributions, a better world and of improved quality of life can be offered to the people with epilepsy and neuropsychiatric comorbidities, who are still waiting (as well as the scientists) for a paradigm shift in epileptology, both in the Basic Science, Computational, Clinical, and Neurosurgical Arenas. This article is part of the Special Issue "NEWroscience 2018".

Midface distraction osteogenesis using a modified external device and 3D virtual simulation: technical note.

INTRODUCTION/BACKGROUND: Distraction osteogenesis (DO) with an external distraction device such as the rigid external distraction frame has become an established method for treating midface hypoplasia in faciocraniosynostosis. It allows for greater advancement of the midface in comparison with traditional Le Fort III osteotomies, associated or not with fronto-orbital osteotomies (Le Fort IV). However, the forward movement of the bone segments may not always be performed obeying an ideal distraction vector, resulting in asymmetries, anterior open bite, and loosening of screws. In addition, the cost of the distraction devices is significant and may preclude their routine use in developing countries. METHOD: We present an alternative device and method for craniofacial advancement in a clinical case of Crouzon's syndrome. RESULTS: A 3D virtual simulation of the distraction vector and a modified external device were used in the current case. CONCLUSION: The alternative external device in this case proved to be safe, effective, and reliable.

Intraoperative breast radiotherapy: survival, local control and risk factors for recurrence.

BACKGROUND: Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. AIM: To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. MATERIALS AND METHODS: 147 patients treated with a median follow up of 6.9 years (0.1â¿¿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p â¿¤ 0.05 was considered statistically significant. RESULTS: Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). CONCLUSIONS: IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

The role of coagulopathy on clinical outcome following traumatic brain injury in children: analysis of 66 consecutive cases in a single center institution.

INTRODUCTION: Head injury is a significant economic, social, and medical problem in developing countries and remains one of the leading causes of pediatric morbidity and mortality. The association of traumatic brain injury and coagulopathy in children is linked with an increase in mortality and poor functional outcomes. However, its impact on long-term outcome has not been discussed in the literature so far. OBJECTIVES: The aim of this paper was to investigate the effect of coagulopathy diagnosed by routine laboratory tests on neurological outcome following traumatic brain injury in children. METHODS: A retrospective review was carried out using medical records of children with a traumatic brain injury admitted at a level I trauma center, between January 2013 and December 2016, submitted to any neurosurgical procedures. Statistical analysis was performed accordingly to identify factors predicting unfavorable or favorable outcomes at 1- and 6-month follow-ups. Data regarding age, gender, trauma mechanism, Glasgow Coma Scale at admission and at discharge, highest and lowest stable intracranial pressure, serum glucose and coagulation assessment, radiological findings, and length of stay were analyzed. RESULTS: We identified 66 children with surgical head trauma. Mean age was 10.9 years (ranges from 3 months to 17 years), with male predominance (77.3%). Common mechanisms were road traffic accidents (66.7%), falls (19.7%), and blunt trauma (10.6%). Brain edema was detected in 68.2% of the patients, surgical fractures or intracranial bleeding in 75.8%. ICP monitoring was performed in 24.2% of the patients, and of these, 18.7% underwent consecutive decompressive craniectomy. Mean length of in-patient treatment was 16.3 ± 28.2 days. At 1- and 6-month follow-ups, favorable outcome was detected in 71.2 and 78.7% of the patients, respectively. The mortality rate was 12.1%. Routine coagulation assessments such as prothrombin time, fibrinogen levels, and thrombocyte count upon admission were potential prognostic variables identified. CONCLUSIONS: The present study concluded that a trauma-related coagulopathy is an important predictor of unfavorable neurological outcome following TBI in pediatric patients. Initial GCS score, age, and neuroradiological findings, such as severe brain edema and different types of intracranial bleeding, correlated with GOS in the first 6 months following TBI. Sustained intracranial hypertension also predicted unfavorable outcome and death in this series.

Breast cancer after thoracic radiotherapy in young patients: what does the radiologist need to know?

Radiation-induced secondary tumors constitute a rare complication of radiation therapy and typically occur in or near the irradiated area. Women who undergo thoracic radiotherapy before 30 years of age have a significantly greater lifetime risk of developing breast cancer than do those in the general population. It is recommended that a patient who has previously received thoracic radiotherapy with a radiation dose ≥ 10 Gy subsequently undergo annual screening with mammography and magnetic resonance imaging, beginning eight years after the initial treatment or when the patient has reached 25 years of age (whichever comes later). The treatment of secondary breast cancer in this population should be individualized and should be discussed with a multidisciplinary team to avoid toxicity related to the treatment of the primary cancer.

Os cânceres secundários induzidos por radiação são complicações raras da radioterapia e geralmente ocorrem na área tratada ou próximo a ela. Mulheres com menos de 30 anos de idade tratadas com radioterapia torácica têm risco significativamente aumentado de desenvolver câncer de mama ao longo da vida, em comparação com a população em geral. Para as pacientes tratadas com irradiação torácica com dose igual ou superior a 10 Gy é recomendado rastreamento anual com mamografia e ressonância magnética iniciando oito anos após o tratamento, desde que este início seja após 25 anos de idade. O tratamento do câncer de mama secundário nessa população deve ser individualizado e discutido com equipe multidisciplinar, para evitar toxicidade relacionada ao tratamento do câncer primário.

Involved-Field Radiation Therapy for Patients With Unresectable Pancreatic Adenocarcinomas: Failure Pattern Analysis.

Introduction Unresectable pancreatic tumors are frequently diagnosed. Initial treatment is carried out with chemotherapy. Eventually, in selected cases, radiotherapy may be used to improve local control rates and relieve the symptoms. The volume of radiotherapy treatment fields is the subject of controversy in the literature. The use of involved fields with the gross tumor volume encompassing the primary tumor and lymph nodes considered clinically positive is associated with a lower rate of side effects, but can lead to a higher rate of regional loco failures, especially in regional lymph nodes. The purpose of this article is to analyze the failure pattern of chemotherapy and involved-field radiation therapy (IFRT) for treating patients with unresectable pancreatic adenocarcinomas. Methods Clinical records of thirty consecutive patients treated from March 2016 to June 2020 for unresectable pancreatic adenocarcinoma were analyzed. The patients were treated with initial systemic chemotherapy (median: 6 cycles) with regimens based on gemcitabine or oxaliplatin-irinotecan (folfirinox/folfox) followed by radiotherapy (total dose of 50-54 Gy/with fractionation of 2 Gy/day). The patients were treated with IFRT. Local failure (LF) was defined as an increase in radiographic abnormality within the planning target volume (PTV). Elective nodal failure (ENF) was defined as recurrence in any lymph node region outside the PTV. Any other failure was defined as distant failure (DF). Results The median age of the patients was 68 years (range: 44-80 years); 20 patients (66.7%) were men, and 11 (36.6%) and 19 (63.4%) patients presented with tumors of stage II and III, respectively. Most patients (63.3%) had tumors in the pancreatic head. The median survival was 17.2 months. Tumor recurrences were classified as LF, DF, LF and DF in 7 (23.3%), 17 (56.7%), and 5 (16.7%) patients, respectively. Only one patient (3.3%) had both LF and ENF. No severe side effects related to radiotherapy were reported. Conclusion The use of IFRT did not cause a significant amount of ENF, besides presenting low morbidity, which is of special importance for patients with locally advanced tumors or low performance status. The predominant failure pattern was distant metastases.

Outcomes of decompressive craniectomy for malignant middle cerebral artery stroke in an academic hospital in Brazil.

BACKGROUND: Ischemic stroke is an important cause of death in the world. The malignant middle cerebral artery infarction (MMCAI) has mortality as high as 80% when clinically treated. In this setting, decompressive craniectomy is a life-saving measure, in spite of high morbidity among survivors. OBJECTIVE: To evaluate the outcomes of patients with MMCAI treated with decompressive craniectomy in a Brazilian academic tertiary stroke center. METHODS: A prospective stroke database was retrospectively evaluated, and all patients treated with decompressive craniectomy for MMCAI between January 2014 and December 2017 were included. The demographics and clinical characteristics were evaluated. The functional outcome, measured by the modified Rankin Scale (mRS), was assessed at hospital discharge, after 3-months and 1-year of follow-up. RESULTS: We included 53 patients on the final analysis. The mean age was 54.6 ± 11.6 years and 64.2% were males. The median time from symptoms to admission was 4.8 (3-9.7) hours and the mean time from symptoms to surgery was 36 ± 17 hours. The left hemisphere was the affected in 39.6%. The median NIHSS at admission was 20 (16-24). The in-hospital mortality was 30.2%. After a median of 337 [157-393] days, 47.1% of patients had achieved favorable outcome (mRS ≤ 4) and 39.6% had died. CONCLUSION: Decompressive craniectomy is a life-saving measure in the setting of MMCAI, and its effects remains important in the scenario of a middle-income country in real-world situations.

ANTECEDENTES: O acidente vascular cerebral (AVC) isquêmico é uma causa importante da morte em todo o mundo. O infarto maligno da artéria cerebral média (IMACM) tem mortalidade de até 80% quando tratado clinicamente. Nesse contexto, a craniectomia descompressiva é uma medida salvadora de vidas, apesar da alta morbidade entre os sobreviventes. OBJETIVO: Avaliar os desfechos dos pacientes com IMACM tratados com craniectomia descompressiva em um centro acadêmico terciário de AVC no Brasil. MéTODOS: Um banco de dados prospectivo de AVC foi avaliado retrospectivamente e todos os pacientes tratados com craniectomia descompressiva para IMACM entre janeiro de 2014 e dezembro de 2017 foram incluídos. As características clínicas e demográficas foram avaliadas. Os desfechos funcionais, medidos pela escala modificada da Rankin (mRS), foram avaliados na alta hospitalar, após 3 meses e após 1 ano de seguimento. RESULTADOS: Foram incluídos 53 pacientes na análise final. A idade média foi 54,6 ± 11,6 anos e 64,2% eram homens. A mediana do tempo dos sintomas à admissão foi 4,8 (3­9,7) horas e o tempo médio dos sintomas à cirurgia foi 36 ± 17 horas. O hemisfério esquerdo foi o afetado em 39,6%. A pontuação na escala de AVC do National Institute of Health (NIHSS) à admissão foi 20 (16­24). A mortalidade hospitalar foi 30,2%. Após uma mediana de 337 (157­393) dias, 47,1% dos pacientes tinham atingido um desfecho favorável (mRS ≤ 4) e 39,6% tinham morrido. CONCLUSãO: Craniectomia descompressiva é uma medida salvadora de vidas no contexto do IMACM e seus efeitos permanecem importantes no cenário de um país em desenvolvimento em situação de vida real.

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.

Impact of cranial stereotactic radiotherapy associated with immunotherapy with nivolumab and ipilimumab on overall survival in patients with melanoma brain metastases: a real-world evidence.

PURPOSE: To evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting. METHODS/PATIENTS: The study was performed by using TriNetX, a global health network dataset of electronic medical records from patients in 49 healthcare organizations. We queried for patients with specific terms between January 2016 and December 2020 and run a propensity score matching (PSM) analysis. OS was estimated by Kaplan-Meier and log-rank test was applied. RESULTS: After initial query and PSM, 114 patients were selected in each cohort. Median OS was 327 days in CNI and not reached in the CNI + SRT cohort, with OS probability of 54.4 and 40.9%, respectively (log-rank P = .0057). CNI + SRT was associated with significantly decreased mortality (HR, 0.57; 95% CI 0.377-0.853; proportionality P = .0034). CONCLUSIONS: This real-world analysis showed that CNI + SRT led to an improvement in OS compared to CNI.

Postmastectomy Radiation Therapy Bolus Associated Complications in Patients Who Underwent 2-stage Breast Reconstruction.

Purpose: This study aimed to evaluate the association of bolus and 2-stage breast reconstruction complications, and whether the dosimetric advantage translates into improvements in local control. Methods and Materials: We retrospectively analyzed data from 2008 to 2019 of women who underwent a mastectomy and a planned 2-stage breast reconstruction, followed by adjuvant radiation therapy. We reviewed all data from medical records and radiation plans regarding patient characteristics, diagnoses, surgeries, complications, pathology, staging, systemic therapy, radiation therapy, and outcomes, and compared complication rates according to bolus usage. Results: A total of 288 women, age 25 to 71 years, were included in the study. Of these women, 6 were treated with daily bolus and 19 with alternate days bolus, totaling 25 of 288 patients (8.7%) in the bolus group. A total of 226 patients (78.5%) had the second stage performed. The median follow-up time was 61 months. The rates for 5-year overall survival and locoregional control were both 97%, and the metastasis-free rate was 83%. In the first stage, 6.25% of patients in the entire cohort had an infection and 4.2% had implant loss. Daily bolus significantly increased the risk of expander infection (hazard ratio [HR]: 10.3; 95% confidence interval [CI], 1.7-61.8) and loss (HR: 13.89; 95% CI, 2.24-85.98), but alternate-day bolus showed a nonsignificant increase for expander infection (HR: 1.14; 95% CI, 0.14-9.295) and loss (HR: 1.5; 95% CI, 0.19-12.87). Bolus was not associated with second-stage complications or local-regional failure. Local infection and implant loss were more frequent in the second than in the first stage (5.2% vs 10.2% and 4.2% vs 12.8%, respectively). Conclusions: Skin bolus significantly increased first-stage breast reconstruction complications (infection and reconstruction failure). Despite the small sample size and the need for future studies, these findings need to be taken into consideration when planning treatment and reconstruction, and recommendations should be individualized.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Epidemiological features of meningiomas: a single Brazilian center's experience with 993 cases.

BACKGROUND: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their geographical and ethnic characteristics need to be known, in order to enable rational treatment. OBJECTIVE: To investigate clinical and epidemiological aspects in a series of patients with meningiomas. METHODS: Retrospective analysis on the demographic profile, location and histopathology of 993 patients with meningiomas (768 operated and 225 not operated). RESULTS: Meningiomas represented 43.8% of the primary CNS tumors; 6.8% were multiple tumors (14.7% with neurofibromatosis 2) and 0.6% were radiation-induced tumors. The mean ages were 53.0 and 63.9 years for operated and non-operated patients and the female/male ratios were 3.2:1 and 6.3:1. Diagnosis was made later among females. The peak incidences were in the 6th and 7th decades respectively for operated and non-operated patients. The incidence was low at early ages and higher among patients aged 70+ years. The meningiomas were intracranial in 96.5% and most were WHO grade I (88.9%) and transitional. In the spinal canal (3.5%), they occurred mainly in the dorsal region (all grade I; mostly transitional). The racial distribution was 1.0% in Asian-Brazilians, 87% in Caucasians and 12% in African-Brazilians. 83.4% and 51.6% of the patients were estimated to be recurrence-free at 10 and 20 years, and the mortality rate was 3%. CONCLUSIONS: Most of the demographic data were similar to what has been observed in other western centers. Differences were higher incidence of meningiomas, female and older predominance in non-operated patients, predominance in Caucasian, and higher association with neurofibromatosis 2.

Pediatric Skull Base Tumors: A Management Challenge.

CONTEXT: Skull base tumors are varied in children and are particularly challenging to pediatric neurosurgeons, with few papers in the literature describing the evolution, complications, and outcome. The authors evaluated long-term outcomes in children submitted to skull base tumor surgery and performed a literature review. AIMS: The aim of this study was to analyze surgical results, complications, and outcomes, on comparison with previous publications. MATERIALS AND METHODS: A retrospective analysis of children undergoing surgery at a single institution between 2000 and 2018 for lesions of the cranial base was carried out. In addition, a literature review was carried out describing a total of 115 children operated on for skull base tumors. STATISTICAL ANALYSIS: Chi-squared and Fisher's exact tests were performed to compare the distribution of categorical variables and a nonparametric Mann-Whitney U test was used to perform intergroup comparisons of continuous variables. RESULTS: Seventeen children ranging in age from 8 months to 17 years (mean, 10.9 years) underwent skull base approaches. Tumor types included schwannoma, meningioma, chondroid chordoma, mature teratoma, epidermoid cyst, hemangiopericytoma, rhabdomyosarcoma, myofibroblastic inflammatory tumor, fibromyxoid sarcoma, Crooke's cell adenoma, ossifying fibroma, osteoblastoma, nasopharyngeal angiofibroma and Ewing's sarcoma. Gross total resection was achieved in 6 patients (35.3%), 12 patients (70.6%) had benign histology, and 5 patients (29.4%) had a malignant tumor. Transient postoperative cerebrospinal fluid leak affected only one patient. Thirteen children (76.4%) had a residual neurological deficit at last follow-up evaluation. Three (17.6%) surviving patients received adjuvant therapy. The rate of recurrence or lesion progression was 17.6%. CONCLUSIONS: Skull base tumors in children present a therapeutic challenge because of their unique pathological composition and can lead to considerable morbidity and mortality in pediatric age.

Surgical management of embolized jugular foramen paragangliomas without facial nerve transposition: Experience of a public tertiary hospital in Brazil.

BACKGROUND: Jugular foramen paragangliomas (JFP) treatment represents a challenge for surgeons due to its close relationship with facial nerve (FN), lower cranial nerves (LCN), and internal carotid artery. Due to its hypervascularization, preoperative tumor embolization has been indicated. METHODS: Retrospective analysis of the clinical evolution of 26 patients with JFP class C/D previously embolized treated through infratemporal/cervical access without FN transposition. RESULTS: Total and subtotal resections were 50% each, regrowth/recurrence were 25%, and 23%, respectively, and mortality was 3.9%. Postoperatively, 68.4% of patients had FN House and Brackmann (HB) Grades I/II. New FN deficits were 15.4% post embolization and 30.7% postoperatively. Previous FN deficits worsened in 46.1%. Tumor involved the FN in 30.8% and in 62.5% of them these nerves were resected and grafted (60% of them had HB III). Lateral fall, ear murmur, and vertigo improved in all patients. Tinnitus improved in 77.8% and one patient developed tinnitus after surgery. Hearing loss did not improve, eight partial hearing loss remained unchanged and four worsened. New postoperative LCN deficits were 64.3%. Postoperative KPS between 80 and 100 dropped 8.3%. Two patients with secretory paragangliomas with arterial hypertension difficult to control had better postoperative blood pressure control. CONCLUSION: Although still with significant morbidity due to FN and LCN injuries, the treatment of patients with JFP Fisch C/D has good long-term results. Surgical techniques without FN transposition have less intraoperative nerve damage, lower rates of total resection, and higher recurrence. Preoperative embolization of JFP reduces the intraoperative blood loss but can cause FN deficit.

Clinical Prognostic Factors for Patients With Esophageal Cancer Treated With Definitive Chemoradiotherapy.

Background Treatment with definitive chemoradiotherapy (CRT) is the best option for patients with locally advanced esophageal tumors considered unresectable or for patients without clinical conditions to undergo surgical treatment. Technological advances in radiotherapy in the last decades have made treatment more accurate with less toxicity, and the association with more effective systemic treatment has been gradually improving survival rates. Aim Evaluate clinical prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with esophageal cancer treated with definitive radiotherapy (RT) and chemotherapy (ChT). Material and methods The clinical records of 60 patients treated from April 2011 until December 2019 with esophageal cancer considered unresectable and/or without clinical conditions for surgery, treated with definitive CRT, were analyzed. All patients had upper digestive endoscopy (UDE) with positive biopsy, neck, chest, and abdominal CT scan, and 18F-fluorodeoxyglucose positron-emission tomography (PET-CT). Patients were followed with physical examination and CTs every three months in the first and second years and every six months from the third year of follow-up. UDE was made every three to six months after the end of the treatment or in suspicion of tumor recurrence. PET-CT was also performed in the follow-up when clinically necessary. Local and regional failure (LRF) was defined as abnormalities in the image tests within the planning target volume (PTV) and/or positive biopsy on UDE. Any other failure was defined as a distant failure (DF). PFS was defined in the record of the first tumor recurrence site and OS in the death record from the date of the start of treatment. Results The median age of the patients was 66 years (range: 33 to 83 years) and 46 patients (76.7%) were male. Squamous cell carcinoma (SCC) was the most frequent histological type (85%). Most patients had tumors located in the mid-thoracic esophagus (53.3%) and stage III or IV (59.9%). All patients were treated using 3D (76.7%) or intensity-modulated radiotherapy (IMRT; 23.3%). The median total dose was 50.4Gy (41.4-50.4). All patients received platinum-based ChT concomitant with RT. The most common regimen used was carboplatin and paclitaxel, with a median of five cycles. With a median follow-up of 19 months, the median PFS and OS were 10 and 20 months, respectively. LRF and DF as the first site of failure were observed in 22 (36.6%) and 26 (43.3%) patients, respectively. In the univariate analysis, tumor length lower than 2.6 cm, gross tumor volume (GTV) volume lower than 28 cm3, clinical tumor stages T1 and T2, clinical node stage N0, clinical prognostic stage groups I and II, and complete response to treatment, were statistically significant factors for better PFS and OS. In the multivariate analysis, the presence of clinical nodal stage N0 was related to better PFS (p=0.02). Conclusion Node clinical status was the most important clinical factor for PFS. Despite all the technical progress observed in radiotherapy, treatments concomitant with platinum-based chemotherapy are associated with high levels of LRF and DF. New strategies in systemic therapy and radiotherapy are necessary for improving outcomes.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms.

OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Malignant Phyllodes Tumor of the Breast: A Practice Review.

INTRODUCTION: Phyllodes tumor (PT) of the breast, particularly malignant phyllodes tumor (mPT), is a rare fibroepithelial neoplasm. A complex diagnosis is based on pathologic, radiologic, and clinical findings, with controversies about what is the best therapeutic strategy. OBJECTIVE: Our objective was to provide an overview of the clinical, pathologic, and therapeutic aspects of this rare tumor. CONCLUSIONS: mPT is a rare presentation of breast cancer and a challenge in clinical practice. A multidisciplinary approach should take into account some aspects like pathogenic mutations and hereditary syndromes. Oncologic surgery is the fundamental approach, and the use of adjuvant therapies is still controversial due to the lack of clinical trials. Treatment recommendations should be individualized according to patient risk and preferences. Prospective studies are fundamental to clarifying the best treatment for these tumors.