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BACKGROUND: Glioblastoma usually recurs locally and extracranial metastases are rare. Most patients with extracranial metastases experience recurrence of the primary intracranial tumor. Lymph node metastases are often detected based on lymphadenopathy or symptoms caused by other metastatic sites. CASE PRESENTATION: Herein, we report a case of glioblastoma with lymph node metastasis in which the patient was asymptomatic but exhibited gradually increasing C-reactive protein levels prior to becoming febrile 9 months after the initial C-reactive protein increase. Diagnosis of lymph node metastasis that was delayed because the patient had a fever of unknown origin, no signs of infection, and the primary intracranial tumor did not recur. Chest computed tomography indicated supraclavicular, mediastinal, and hilar lymphadenopathy, and biopsy identified lymph node metastasis of glioblastoma. This is the fifth reported case of lymph node metastasis without intracranial recurrence. CONCLUSIONS: C-reactive protein levels may be a diagnostic marker for lymph node metastasis in patients with glioblastoma. Further evaluation is needed to elucidate the role of CRP in glioblastoma with lymph node metastasis.
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Neoplasias Encefálicas , Glioblastoma , Linfadenopatia , Humanos , Metástase Linfática/patologia , Proteína C-Reativa , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Linfonodos/patologiaRESUMO
Introduction Boron neutron capture therapy (BNCT) is a biologically targeted, cell-selective particle irradiation therapy that utilizes the nuclear capture reaction of boron and neutron. Recently, accelerator neutron generators have been used in clinical settings, and expectations for developing new boron compounds are growing. Methods and Results In this study, we focused on serum albumin, a well-known drug delivery system, and developed maleimide-functionalized closo-dodecaborate albumin conjugate (MID-AC) as a boron carrying system for BNCT. Our biodistribution experiment involved F98 glioma-bearing rat brain tumor models systemically administered with MID-AC and demonstrated accumulation and long retention of boron. Our BNCT study with MID-AC observed statistically significant prolongation of the survival rate compared to the control groups, with results comparable to BNCT study with boronophenylalanine (BPA) which is the standard use of in clinical settings. Each median survival time was as follows: untreated control group; 24.5 days, neutron-irradiated control group; 24.5 days, neutron irradiation following 2.5 h after termination of intravenous administration (i.v.) of BPA; 31.5 days, and neutron irradiation following 2.5 or 24 h after termination of i.v. of MID-AC; 33.5 or 33.0 days, respectively. The biological effectiveness factor of MID-AC for F98 rat glioma was estimated based on these survival times and found to be higher to 12. This tendency was confirmed in BNCT 24 h after MID-AC administration. Conclusion MID-AC induces an efficient boron neutron capture reaction because the albumin contained in MID-AC is retained in the tumor and has a considerable potential to become an effective delivery system for BNCT in treating high-grade gliomas.
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Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Glioma , Albuminas , Animais , Boro/uso terapêutico , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/tratamento farmacológico , Glioma/patologia , Humanos , Maleimidas , Ratos , Distribuição TecidualRESUMO
Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl-closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)-a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21-24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26-36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25-37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28-40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.
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Terapia por Captura de Nêutron de Boro/métodos , Boro/química , Boro/uso terapêutico , Receptores de Folato com Âncoras de GPI/metabolismo , Glioma/patologia , Terapia de Alvo Molecular , Animais , Boro/farmacocinética , Compostos de Boro/química , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Glioma/metabolismo , Glioma/radioterapia , Humanos , Masculino , Ratos , Distribuição TecidualRESUMO
The novel bisphosphonate (BP) disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. We investigated the systemic effects of this compound on bone loss induced by ovariectomy (OVX) in adult rats. Micro-computed tomography revealed that MPMBP increased bone mass and density in both the metaphysis and diaphysis, and improved the structural properties important for mechanical strength of osteoporotic bone. Sequential bone labeling with tetracycline and calcein indicated that MPMBP decreased longitudinal growth of the primary spongiosa (PS), but stimulated cortical bone formation in the diaphysis. MPMBP increased type I collagen accumulation in the PS, and decreased the number and size of adipocytes in the bone marrow, suggesting inhibition of increased bone marrow adipogenesis induced by OVX. Furthermore, MPMBP reduced the number of bone resorbing cathepsin K-positive osteoclasts induced by OVX. These results suggest that MPMBP could improve bone loss induced by estrogen deficiency. Both stimulation of bone formation and inhibition of bone resorption might play a role in the increase in bone mass and bone density after MPMBP treatment.
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Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Difosfonatos/farmacologia , Tíbia/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Colágeno Tipo I/metabolismo , Feminino , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Ovariectomia/efeitos adversos , Ratos Sprague-Dawley , Tíbia/diagnóstico por imagem , Tíbia/fisiologia , Microtomografia por Raio-XRESUMO
Enantiomerically pure 3-methyl-ß-proline was synthesized using an asymmetric phase-transfer-catalyzed alkylation of a cyanopropanoate to establish the all-carbon stereogenic center. The catalytic activity of 3-methyl-ß-proline in the Mannich-type reaction between a glyoxylate imine and ketones/aldehydes was subsequently investigated. The catalyst was designed and found to be more soluble in nonpolar organic solvents relative to the unsubstituted ß-proline catalyst, and as a result allowed for added flexibility during optimization efforts. This work culminated in the development of a highly anti-diastereo- and enantioselective process employing low catalyst loading.
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Prolina/análogos & derivados , Propano/química , Alquilação , Catálise , Estrutura Molecular , Prolina/síntese química , Prolina/química , Propano/análogos & derivadosRESUMO
BACKGROUND: Pituitary apoplexy (PA) is characterized by sudden headache, vomiting, visual dysfunction, anterior lobe dysfunction, and endocrine disorder due to bleeding or infarction from a pituitary adenoma. PA occurs in approximately 0.6-10% of pituitary adenomas, more commonly in men aged 50-60 years, and more frequently in nonfunctioning and prolactin-producing pituitary adenomas. Further, asymptomatic hemorrhagic infarction is found in approximately 25% of PA. OBSERVATIONS: A pituitary tumor with asymptomatic hemorrhage was detected on head magnetic resonance imaging (MRI). Thereafter, the patient underwent head MRI every 6 months. After 2 years, the tumor was enlarged and visual dysfunction was noticed. The patient underwent endoscopic transnasal pituitary tumor resection and was diagnosed with a chronic expanding pituitary hematoma with calcification. The histopathological findings were very similar to those of chronic encapsulated expanding hematoma (CEEH). LESSONS: CEEH associated with pituitary adenomas gradually increases in size, causing visual dysfunction and pituitary dysfunction. In case of calcification, total removal is difficult due to adhesions. In this case, calcification developed within 2 years. A pituitary CEEH, even when showing calcification, should be operated on, as visual function can be fully recovered.
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BACKGROUND: Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated. METHODS: Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used. TSPO expression was evaluated in the F98 rat glioma model. Boron uptake was assessed in three rat glioma cell lines and in the F98 rat glioma model. In vitro and in vivo neutron irradiation experiments were performed. RESULTS: DPA-BSTPG was efficiently taken up in vitro. The brain tumor has 16-fold higher TSPO expressions than its brain tissue. The compound biological effectiveness value of DPA-BSTPG was 8.43 to F98 rat glioma cells. The boron concentration in the tumor using DPA-BSTPG convection-enhanced delivery (CED) administration was approximately twice as high as using BPA intravenous administration. BNCT using DPA-BSTPG has significant efficacy over the untreated group. BNCT using a combination of BPA and DPA-BSTPG gained significantly longer survival times than using BPA alone. CONCLUSION: DPA-BSTPG in combination with BPA may provide the multi-targeted neutron capture therapy against HG.
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The aim of this study was to evaluate the influence of skin distortion due to surgical positioning on the clinical accuracy of the navigation system. The distance errors were measured in four fiducial markers (anterior, posterior, right, and left of the head) after the registration of the navigation system. The distance errors were compared between the surface-merge registration (SMR) method using preoperative imaging and the automatic intraoperative registration (AIR) method using intraoperative imaging. The comparison of the distance errors were performed in various surgical positions. The AIR method had the significant accuracy in the lateral markers than the SMR method (lateral position, 3.8 mm vs. 8.95 mm; p < 0.0001; prone position, 4.5 mm vs. 13.9 mm; p = 0.0001; 5.2 mm vs. 11.5 mm; p = 0.0070). The smallest distance errors were obtained close to the surgical field in the AIR method (3.25-3.85 mm) and in the forehead in the SMR method (3.3-8.1 mm). The AIR method was accurate and recommended for all the surgical positions if intraoperative imaging was available. The SMR method was only recommended for the supine position, because skin distortion was frequently observed in the lateral region.
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Neoplasias Encefálicas , Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos , Decúbito Ventral , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgiaRESUMO
Boron neutron capture therapy (BNCT) is a high-LET particle radiotherapy clinically tested for treating malignant gliomas. Boronophenylalanine (BPA), a boron-containing phenylalanine derivative, is selectively transported into tumor cells by amino acid transporters, making it an ideal agent for BNCT. In this study, we investigated whether the amino acid 5-aminolevulinic acid (ALA) could sensitize glioma stem cells (GSCs) to BNCT by enhancing the uptake of BPA. Using human and mouse GSC lines, pre-incubation with ALA increased the intracellular accumulation of BPA dose-dependent. We also conducted in vivo experiments by intracerebrally implanting HGG13 cells in mice and administering ALA orally 24 h before BPA administration (ALA + BPA-BNCT). The ALA preloading group increased the tumor boron concentration and improved the tumor/blood boron concentration ratio, resulting in improved survival compared to the BPA-BNCT group. Furthermore, we found that the expression of amino acid transporters was upregulated following ALA treatment both in vitro and in vivo, particularly for ATB0,+. This suggests that ALA may sensitize GSCs to BNCT by upregulating the expression of amino acid transporters, thereby enhancing the uptake of BPA and improving the effectiveness of BNCT. These findings have important implications for strategies to improve the sensitivity of malignant gliomas to BPA-BNCT.
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Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Glioma , Humanos , Animais , Camundongos , Ácido Aminolevulínico/farmacologia , Boro , Glioma/radioterapia , Células-Tronco Neoplásicas , Compostos de Boro , Neoplasias Encefálicas/radioterapiaRESUMO
Septum pellucidum cyst is rare and is defined as a fluid-filled space between the lateral ventricles; it has a width of 10 mm or more. In this case report, a surgical patient of symptomatic septum pellucidum cyst (SPC) in extreme age is described. To the best our knowledge, this is the first report of an extremely aged patient with symptomatic SPC that was successfully treated using a flexible neuroendoscope. An 85-year-old male complained of gradually worsening gait disturbance, dementia, and urinary incontinence without headache and was admitted to our hospital. MRI revealed a huge cyst between the lateral ventricles as well as ventricle dilatation with periventricular hyperintensity in T2-weighted image. The patient was diagnosed with symptomatic hydrocephalus with SPC and underwent neuroendoscopic fenestration of the cyst with the use of a flexible endoscope without cerebrospinal fluid shunt placement. Immediately after the surgery, the patient's gait disturbance and dementia were dramatically improved. In extremely aged patients, SPC tended to develop with idiopathic normal pressure hydrocephalus-like symptoms, including gait disturbance without increasing intracranial pressure, sensorimotor disturbances, and psychological disorders. Neuroendoscopic cyst fenestration with the use of a flexible scope for SPC is a less-invasive procedure and should be considered even for extreme elderly symptomatic patients.
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Spinal intramedullary metastasis is an extremely rare event that occurs in advanced cancer. The surgical indications for spinal intramedullary metastasis are highly limited because of surgical difficulty and poor prognosis. In this technical case report, we present a rare case of spinal intramedullary metastasis from the lung that recurred late after local radiation to the spinal cord. The patient progressively experienced relapsed buttock pain and developed gait and urination disorders late after treatment for lung cancer. Imaging examinations suggested the recurrence of spinal intramedullary metastasis in the conus medullaris. Systemic examinations revealed no apparent recurrence in other organs, including the primary lung lesions. Gross total resection of the tumor within the conus medullaris was safely performed using the unilateral posterolateral (PLS) approach and by addition of the contralateral PLS approach. To the best of our knowledge, this is the first case in which a spinal intramedullary metastatic tumor was successfully removed using a bilateral PLS approach.
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Adenocarcinoma , Neoplasias Pulmonares , Neoplasias da Medula Espinal , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgiaRESUMO
Giant cell tumor (GCT) of bone is essentially benign but locally aggressive, and the rate of local recurrence is high when the resection is not enough. En bloc resection is recommended as an ideal solution for GCT to decrease the risk of local recurrence, but it remains challenging for cervical GCT. In this technical case report, we present a case of extensively infiltrating GCT of the cervical spine completely encasing the vertebral artery (VA) on one side. The tumor was distributed to layers A-D, sectors 3-8 based on the Weinstein-Boriani-Biagini staging. Combined posterior and anterior surgical approach for the cervical spine was successfully performed and followed by postoperative adjuvant pharmacological therapy. This kind of multimodal management may be one of the solutions for advanced cervical GCT.
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Tumores de Células Gigantes , Neoplasias da Coluna Vertebral , Neoplasias do Colo do Útero , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgia , Feminino , Tumores de Células Gigantes/patologia , Células Gigantes/patologia , Humanos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgiaRESUMO
Spinal intramedullary tumors such as ependymoma or vascular lesions such as cavernous malformation are often at risk of intramedullary hemorrhage. Surgical procedures involving the high cervical spinal cord are often challenging. This technical note included four patients who presented with acute, subacute, or gradual onset of spinal cord dysfunction associated with intramedullary hemorrhage at the C1 or C1/2 level of the high cervical spine. The mean age was 46.3 years (16-74 years). All patients underwent posterior spinal cord myelotomy of the posterior median sulcus or posterolateral sulcus. It was not to exceed the caudal opening of the fourth ventricle (foramen of Magendie) and was assumed to be as high as the caudal medulla oblongata. Total removal of the intramedullary ependymoma or cavernous malformation occurred in three of four cases, and the remaining case had subtotal removal of the ependymoma. None of the patients showed postoperative deterioration of the neurological condition. Pathological examination of all cases revealed intramedullary hemorrhage was associated with ependymoma or cavernous malformation. Posterior spinal myelotomy should be limited to the caudal opening of the fourth ventricle (foramen of Magendie), that is the caudal medulla oblongata, to avoid the significant deterioration after surgery.
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Neoplasias do Sistema Nervoso Central , Ependimoma , Neoplasias da Medula Espinal , Doenças Vasculares da Medula Espinal , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgia , Ependimoma/complicações , Ependimoma/diagnóstico por imagem , Ependimoma/cirurgia , Hemorragia , Humanos , Pessoa de Meia-Idade , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgiaRESUMO
Background: Although the tap test for patients with suspected idiopathic normal pressure hydrocephalus (iNPH) is still often performed as part of the preoperative evaluation, it is true that some studies have reported the limitations of the tap test, claiming that it does not provide the additional information for appropriate patient selection for surgery. We aimed to determine whether a better method of pre- and post-tap test assessment could lead to appropriate patient selection for shunting. Methods: We performed the tap test as part of the preoperative evaluation in all 40 patients who underwent lumboperitoneal shunt surgery for iNPH from April 2021 to September 2021. We retrospectively analyzed the patient data. We examined whether a comprehensive evaluation of the effect of the tap test using the Functional Gait Assessment (FGA) and Global Rating of Change (GRC) scales would identify a wider range of patients who would benefit from shunt surgery than the 3-m Timed Up and Go test (TUG) alone. Results: Assuming a prevalence of 1% for iNPH, the TUG had a sensitivity of 0.23, specificity of 0.71, positive likelihood ratio of 0.79, and negative likelihood ratio of 1.09. When improvement in either the FGA or the GRC was used as a criterion for the validity of the tap test, the sensitivity was 0.88, specificity was 0.17, positive likelihood ratio was 1.06, and negative likelihood ratio was 0.71. Conclusion: Improvement in either the FGA or the GRC is a more sensitive criterion for the effectiveness of the tap test for the gait aspect than the TUG. Since the negative likelihood ratio is lower than that for the TUG alone, it is more appropriate to exclude patients with neither FGA nor GRC improvement from surgical indications than to exclude surgical indications based on a negative TUG.
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[This corrects the article DOI: 10.3389/fneur.2022.846429.].
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A catalytic asymmetric allylation of 3,4-dihydroisoquinoline was carried out with allyltrimethoxylsilane-Cu as the nucleophile in the presence of DTBM-SEGPHOS as the chiral ligand to afford corresponding chiral 1-allyltetrahydroisoquinoline derivatives in good yield and stereoselectivity. The allyl adduct thus obtained was applied to the synthesis of several isoquinoline alkaloids such as crispine A and homolaudanosine. The reaction was further used for the synthesis of the isoquinoline moiety of schulzeine A.
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Alcaloides/química , Alcaloides/síntese química , Isoquinolinas/química , Isoquinolinas/síntese química , Catálise , Cobre/química , Ligantes , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos de Organossilício/química , EstereoisomerismoRESUMO
3-Decyl-ß-proline, which has a highly lipophilic substituent, was synthesized, and its catalytic activities in Michael addition using water as the solvent were investigated. The decyl substituent promoted the reaction by hydrophobic interactions to afford the Michael adduct in a high yield and with high diastereoselectivity under low catalyst loading.
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BACKGROUND: Calcifications in pituitary adenomas are rare, being found in only 5.4%-25% of reported cases. These are divided into eggshell-like calcifications around the tumor and nodular calcifications at the center of the tumor, the latter of which are called "pituitary stones" (PSs). OBSERVATIONS: The authors report the case of a 60-year-old male with a nonfunctional pituitary adenoma with PSs and asymptomatic ventricular dilatation who presented with spontaneous cerebrospinal fluid (CSF) rhinorrhea and rapid visual aggravation without an increase in tumor size over the course of 4 years. After endoscopic transnasal surgery, his visual acuity immediately improved temporarily. It was believed that the increased intracranial pressure due to secondary hydrocephalus resulted in visual aggravation; thus, a ventriculoperitoneal (VP) shunt was created. After creation of the VP shunt, the patient's visual acuity improved gradually and completely. Histological findings showed that adenoma cells were observed among the lamellar bone trabeculae. To the best of the authors knowledge, this is the first report of osteoid metaplasia-type PSs in nonfunctioning pituitary adenoma. LESSONS: PSs formed near the sellar floor and caused spontaneous CSF rhinorrhea due to direct mechanical stress on the dura mater and optic nerves, which may have caused meningitis and secondary hydrocephalus that resulted in visual impairment independent of tumor size.
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BACKGROUND: The development of effective boron compounds is a major area of research in the study of boron neutron capture therapy (BNCT). We created a novel boron compound, boronophenylalanine-amide alkyl dodecaborate (BADB), for application in BNCT and focused on elucidating how it affected a rat brain tumor model. METHODS: The boron concentration of F98 rat glioma cells following exposure to boronophenylalanine (BPA) (which is currently being utilized clinically) and BADB was evaluated, and the biodistributions in F98 glioma-bearing rats were assessed. In neutron irradiation studies, the in vitro cytotoxicity of each boron compound and the in vivo corresponding therapeutic effect were evaluated in terms of survival time. RESULTS: The survival fractions of the groups irradiated with BPA and BADB were not significantly different. BADB administered for 6 h after the termination of convection-enhanced delivery ensured the highest boron concentration in the tumor (45.8 µg B/g). The median survival time in the BADB in combination with BPA group showed a more significant prolongation of survival than that of the BPA group. CONCLUSION: BADB is a novel boron compound for BNCT that triggers a prolonged survival effect in patients receiving BNCT.