RESUMO
A 33-year-old male presented with sudden onset of dysarthria. MRI showed a single round lesion containing hematomas in varying stages combined with venous malformation in the superior midline portion of the midbrain, indicating a midbrain cavernous angioma. Serial follow-up MRI revealed enlargement of the angioma concomitant with worsening of the dysarthria, ataxia, and intention tremor. Preoperative MRI suggested that the angioma consisted of a cystic hemorrhagic lesion with an 18-mm diameter without hydrocephalus. Since the angioma was located just beneath the floor of the midline portion of the third ventricle, we chose an anterior interhemispheric transcallosal transforaminal approach. After callosotomy, the foramen of Monro was widened by dissecting the choroidal fissure, enabling entry into the third ventricle. The lower part of the massa intermedia was cut;the median floor of the third ventricle was dissected and the angioma was removed. After the surgery, only a transient complication of seesaw nystagmus was observed, caused by damage to the interstitial nucleus of Cajal. As the anterior interhemispheric transcallosal transforaminal approach does not damage both forces, this technique may be a safe and useful approach for superior medial midbrain lesions, located just beneath the floor of the third ventricle.
Assuntos
Hemangioma Cavernoso , Hidrocefalia , Terceiro Ventrículo , Adulto , Humanos , Ventrículos Laterais , Masculino , MesencéfaloRESUMO
Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence. We investigated radiological imaging; the interval between the two surgeries; and immunohistochemistry of CD3, CD4, CD8, CD20, CD68, FOXP3, and PD1. We implanted BCNU wafers in 41 newly diagnosed glioblastoma patients after approval of the wafer in Japan. Of them, 14 underwent surgery at recurrence and tissue was obtained from around the wafers. The interval between the first and second surgeries ranged from 63 to 421 days. The wafer could be observed on magnetic resonance imaging at up to 226 days, whereas intraoperatively the biodegraded material of the wafer could be found at up to 421 days after the initial surgery. Immunohistochemical analysis demonstrated that CD8+ and CD68+ cells were significantly increased, but FOXP3+ cells did not increase, after wafer implantation compared to tissue from cases without wafer implantation. MRI data and immune cells, as well as interval between surgeries and immune cells, demonstrated positive correlation. These results helped us to understand the bioactivity of bioengineered materials and to establish a new approach for immunotherapy.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Carmustina/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Implantes Absorvíveis , Adulto , Idoso , Biomarcadores Tumorais/imunologia , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/cirurgia , Criança , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Glioblastoma/imunologia , Glioblastoma/cirurgia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: One of the most serious complications of stereotactic biopsy is postoperative symptomatic hemorrhage due to injury to the basal perforating arteries such as the lenticulostriate arteries neighboring the basal ganglia lesions. OBJECTIVES: A new target-planning method was proposed to reduce hemorrhagic complications by avoiding injury to the perforating arteries. METHODS: Three-dimensional 3-T time-of-flight (3D 3-T TOF) imaging was applied to delineate the basal perforating arteries such as the lenticulostriate arteries. The incidence of postoperative hemorrhage in basal ganglia cases was compared between a new method using 3D 3-T TOF and a conventional target-planning method based on contrast-enhanced T1-weighted magnetic resonance images obtained by 1.5-T scanning. RESULTS: 3D 3-T TOF imaging could delineate the basal perforating arteries sufficiently in target planning. No postoperative hemorrhage occurred with the new method (n = 10), while 6 postoperative hemorrhages occurred with the conventional method (n = 14). The new method significantly reduced the occurrence of postoperative hemorrhages (p = 0.017). CONCLUSIONS: 3D 3-T TOF MR imaging with contrast medium administration provides useful information about the perforating arteries and allows safe stereotactic biopsy of basal ganglia lesions.
Assuntos
Artérias/lesões , Gânglios da Base/patologia , Biópsia/efeitos adversos , Hemorragias Intracranianas/prevenção & controle , Lesões do Sistema Vascular/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias/diagnóstico por imagem , Gânglios da Base/diagnóstico por imagem , Criança , Feminino , Humanos , Imageamento Tridimensional , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/etiologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Adulto JovemRESUMO
BACKGROUND: Gliomas adjacent to the corticospinal tract (CST) should be carefully resected to preserve motor function while achieving maximal surgical resection. Modern high-field intraoperative magnetic resonance imaging (iMRI) enables precise visualization of the residual tumor and intraoperative tractography. We prospectively evaluated the extent of resection and distance between the tumor resection cavity and CST using 3-T iMRI combined with motor evoked potentials (MEP) in glioma surgery. METHODS: Participants comprised patients who underwent surgery for solitary supratentorial glioma located within 10 mm of the CST. All cases underwent surgery using neuronavigation with overlaid CST under MEP monitoring. The correlation between distance from CST and transcortical MEP amplitude was calculated using Spearman rank correlation. RESULTS: Among the 63 patients who underwent surgery, 27 patients were enrolled in the study. Gross total resections were achieved in 26 of the 27 cases. Volumetric analysis showed the extent of resection was 98.6%. Motor function was stable or improved in 24 patients (Stable/Improved group) and deteriorated in 3 patients (Deteriorated group). All patients in the Deteriorated group showed motor deficit before surgery. Mean intraoperative minimal distance was significantly longer in the Stable/Improved group (7.3 mm) than in the Deteriorated group (1.1 mm; P < 0.05). MEP amplitude correlated with minimal distance between the resection cavity and CST (R = 0.64). CONCLUSIONS: Resection of gliomas adjacent to CST with a navigation system using 3-T iMRI could result in an ultimate EOR >98%. The combination of intraoperative tractography and MEP contributes to maximal removal of motor-eloquent gliomas.
Assuntos
Potencial Evocado Motor , Glioma , Imageamento por Ressonância Magnética , Neuronavegação , Tratos Piramidais , Humanos , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/cirurgia , Glioma/cirurgia , Glioma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética/métodos , Idoso , Potencial Evocado Motor/fisiologia , Neuronavegação/métodos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Estudos Prospectivos , Adulto Jovem , Monitorização Intraoperatória/métodos , Monitorização Neurofisiológica Intraoperatória/métodos , Neoplasias Supratentoriais/cirurgia , Neoplasias Supratentoriais/diagnóstico por imagemRESUMO
In-stent thrombosis (IST) after carotid artery stenting (CAS) is a rare but potentially devastating complication. We present a case of early IST after CAS despite sufficient antiplatelet therapy in a patient with bladder cancer. A 77-year-old man under preventive triple antiplatelet therapy underwent CAS without any intra- or periprocedural complications. However, the patient developed a large asymptomatic IST 6 days after CAS. Anticoagulant therapy with argatroban was reintroduced to treat IST concomitant with antiplatelet agents. Subsequently, the IST shrank and disappeared without any thrombotic symptoms. Malignancy is regarded as an acquired thrombophilic condition associated with a significant risk of thrombosis. In the field of coronary stents, cancer is associated with a significant increasing risk of IST. The cause of IST in our case was possibly related in hypercoagulable state because of the patient's cancer. Attention for IST should be paid in CAS cases with these risk factors, and repeated examination is recommended.
Assuntos
Carcinoma/complicações , Estenose das Carótidas/cirurgia , Inibidores da Agregação Plaquetária/uso terapêutico , Stents/efeitos adversos , Trombose/etiologia , Neoplasias da Bexiga Urinária/complicações , Idoso , Estenose das Carótidas/complicações , Humanos , MasculinoRESUMO
Gaucher disease (GD) causes the accumulation of glucocerebrosides in various organs, resulting in hepatosplenomegaly, anemia, decreased platelet counts, and bone disorders. Glucosylsphingosine accumulates in the brain and causes central nervous system (CNS) disorders. GD can be classified into types I (without CNS disorders), II, and III. Substrate reduction therapy (SRT) is an oral therapy that improves patients' quality of life; however, its effect on type III GD is unknown. We administered SRT to GD types I and III patients and found it effective. Malignancy is a late complication of GD, but this is the first report of Barrett adenocarcinoma.
Assuntos
Doença de Gaucher , Humanos , Doença de Gaucher/tratamento farmacológico , Qualidade de Vida , Pirrolidinas/uso terapêutico , GlucosilceramidasRESUMO
RATIONALE: Infections that spread to the pterygomandibular muscle can be misdiagnosed as temporomandibular disorder (TMD) because of the resulting difficulty in opening the mouth. Importantly, infection of the pterygomandibular space can extend to the skull base in the early stages, and a delay in therapeutic intervention can lead to severe complications. PATIENT CONCERNS: A 77-year-old Japanese man with trismus after pulpectomy was referred to our department. This case report describes a rare instance of meningitis with septic shock caused by an odontogenic infection, initially misdiagnosed as TMD due to similar symptoms, leading to life-threatening complications. DIAGNOSIS: The patient was diagnosed with sepsis and meningitis resulting from cellulitis in the pterygomandibular space caused by iatrogenic infection after pulpectomy of the right upper second molar. INTERVENTIONS: After emergency hospitalization, the patient developed septic shock and required blood purification. Subsequently, abscess drainage and extraction of the causative tooth were performed. However, the patient developed hydrocephalus secondary to meningitis and underwent ventriculoperitoneal shunting to alleviate the condition. OUTCOMES: The infection was controlled and the patient level of consciousness improved following treatment for hydrocephalus. The patient was transferred to a hospital for rehabilitation on the 106th day of hospitalization. LESSONS: Infections of the pterygomandibular space may be misdiagnosed as TMD, owing to the main symptoms of restricted mouth opening and pain on mouth opening. A prompt and appropriate diagnosis is crucial because these infections can lead to life-threatening complications. A detailed interview, along with additional blood tests and computed tomography (CT) scans, can aid in making an accurate diagnosis.
Assuntos
Diagnóstico Diferencial , Erros de Diagnóstico , Meningite , Transtornos da Articulação Temporomandibular , Humanos , Masculino , Idoso , Choque Séptico/etiologia , Meningite/complicações , Meningite/diagnóstico , Transtornos da Articulação Temporomandibular/diagnósticoRESUMO
BACKGROUND: Nonconvulsive status epilepticus (NCSE) requires prompt diagnosis and treatment, particularly after neurosurgical procedures for cerebral damage. Here, the authors reported an extremely rare case of suprasellar arachnoid cyst presenting with NCSE after cyst fenestration with transsphenoidal surgery, which was associated with pneumocephalus. OBSERVATIONS: A 61-year-old man presented with visual impairment and was diagnosed with a suprasellar arachnoid cyst on magnetic resonance imaging (MRI). The patient received cyst fenestration with endonasal transsphenoidal surgery. His visual symptoms improved immediately after the operation; however, on postoperative day 3, semicoma appeared and was prolonged. The patient was diagnosed with NCSE due to pneumocephalus based on MRI and electroencephalography (EEG) findings. The administration of antiepileptic drugs (AEDs) improved his clinical symptoms and the abnormal findings on MRI and EEG. LESSONS: This is the first case of NCSE with pneumocephalus after transsphenoidal surgery for a suprasellar arachnoid cyst. Pneumocephalus due to cerebrospinal fluid leakage can cause NCSE. Arterial spin labeling perfusion imaging and diffusion-weighted imaging are as useful for differentially diagnosing NCSE as EEG and AED tests.
RESUMO
We report here a rare case of adult-onset multiloculated hydrocephalus (MLH) after Cryptococcal meningitis. A 63-year-old man had Cryptococcal ventriculitis in 2011, and he recovered with treatment of antimycotic drugs. However, he was admitted again because of disorientation and amnesia, and brain MRI showed dilation of the inferior horn of the left lateral ventricle. He underwent a ventriculoperitoneal shunt (VPS) for noncommunicating hydrocephalus in 2019, and the disorientation and amnesia improved. One year after the VPS, he was admitted because of urinary dysfunction and gait disturbance. Brain MRI showed dilation of the bilateral anterior horns of the lateral ventricles. He underwent an additional VPS into the space in 2020, and urinary dysfunction and gait disturbance improved. This case was supposed that the symptom in agreement with the dilated ventricle by MLH was shown.
Assuntos
Ventriculite Cerebral , Hidrocefalia , Meningite Criptocócica , Amnésia , Ventriculite Cerebral/diagnóstico por imagem , Ventriculite Cerebral/tratamento farmacológico , Ventriculite Cerebral/etiologia , Confusão , Encefalite , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Masculino , Pessoa de Meia-Idade , Mielite , NeoplasiasRESUMO
A typical teratoid/rhabdoid tumors (AT/RT) are highly malignant embryonal tumors in children that are associated with inactivation of the integrase interactor 1 (INI1) gene. Several adult cases of AT/RT have been reported, which were characterized by the sellar occurrence and predominantly occurred in females with INI1 mutation variants. However, clinical and genetic features are poorly understood in this unusual entity. We experienced a case of a 45-year-old female with sellar AT/RT presenting diplopia, who underwent subtotal removal of the tumor by the endoscopic endonasal transsphenoidal approach. Pathological diagnosis was AT/RT with INI1 inactivation on immunohistochemistry. Subsequently, multiple lung metastases were confirmed on fluorodeoxyglucose positron emission tomography (FDG-PET). Although she received postoperative chemoradiotherapy, she died of cerebrospinal fluid dissemination. Autopsy revealed cerebrospinal dissemination and lung metastasis of AT/RT. Biallelic alterations in the INI1 gene were identified by direct sequencing, harboring on different alleles (compound heterozygous mutations) was observed, which is the potential genetic pattern in adult AT/RT. Literature review indicated that lung metastasis frequently occurs in sellar AT/RTs, which is accompanied by cavernous sinus invasion. These observations suggested that cavernous sinus invasion causes haematogenous metastasis to the lung in sellar AT/RT. We discuss clinical and pathological features in adult sellar AT/RT to improve understanding of this unique entity.
RESUMO
BACKGROUND: The utility of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status as a prognostic marker in patients with glioblastoma (GBM) has been established. However, the number of CpG sites that must be methylated to cause transcriptional silencing remains unclear, and no significant consensus exists on the optimal method of assessing MGMT methylation. We developed a new high-performance liquid chromatography (HPLC) method that enables accurate analysis of DNA methylation levels using long PCR products. In the present study, we analyzed the MGMT methylation status of 28 isocitrate dehydrogenase-wild-type GBMs treated with temozolomide using ion-exchange HPLC and set the optimal cutoff values. RESULTS: We designed three primers for separate regions (regions 1-3) that had 21 to 38 CpGs for PCR and validated the MGMT promoter methylation status using frozen samples. There was a strong correlation between HPLC and bisulfite sequencing results (R = 0.794). The optimal cutoff values for MGMT methylation in HPLC were determined to allow differentiation of patient prognosis by receiver operating characteristic curve analysis. The cutoff values were 34.15% for region 1, 8.84% for region 2, and 36.72% for region 3. Kaplan-Meyer curve analysis estimated that the most differentiated prognosis was enabled in the setting of 8.84% methylation of MGMT in region 2. Progression-free survival and overall survival were significantly longer for patients in this setting of region 2 methylation (p = 0.00365 and p = 0.00258, respectively). CONCLUSIONS: The combination of our HPLC method and the original primer setting provides a new standard method for determination of MGMT methylation status in patients with GBM and is useful for refining MGMT-based drug selection.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/genética , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/genética , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/patologia , Ilhas de CpG , Metilação de DNA , Epigenômica , Feminino , Glioblastoma/diagnóstico , Glioblastoma/tratamento farmacológico , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Prognóstico , Intervalo Livre de Progressão , Proteínas Repressoras/genética , Temozolomida/uso terapêuticoRESUMO
OBJECTIVE: Maximal safe resection prolongs the survival of patients with glioblastoma (GB). However, whether total resection of the enhanced lesion is pursued or abandoned depends on preoperative judgments based on the findings of magnetic resonance imaging (MRI). Anatomically, medial temporal tumor tends to invade toward the temporal stem, insula, and basal ganglia, representing tumor with high surgical risk. In the present study, we describe the key radiologic features of medial temporal GB to achieve extent of resection. METHODS: We reviewed all GB cases located in the temporal lobe (tGB) treated between April 2013 and March 2018 at Kitasato University Hospital. On the basis of MRI, tGB was simply classified into 3 groups: medial tGB and nonmedial tGB, and medial tGB was further subdivided into invading type and mimicking type. We focused on the resectability of medial tGB. RESULTS: Twenty-seven patients with tGB were identified. Twenty were included in the nonmedial tGB, and 7 were in the medial tGB. All medial tGB seemed to invade into the basal ganglia and/or the lenticulostriate arteries, but detailed examination revealed 2 types of tumor, invading type (3 cases) and mimicking type (4 cases). The invading type had true involvement of the basal ganglia and/or lenticulostriate arteries, whereas the mimicking type had no involvement of these structures. This new classification is highly effective, as the former is unresectable, but the latter is totally resectable. CONCLUSIONS: Medial tGB is a challenging tumor for maximal safe resection, so our classification will help to identify cases of removable medial tGB.
Assuntos
Gânglios da Base/diagnóstico por imagem , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/classificação , Glioblastoma/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Idoso , Gânglios da Base/cirurgia , Neoplasias Encefálicas/cirurgia , Diagnóstico Diferencial , Feminino , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Estudos Retrospectivos , Lobo Temporal/cirurgiaRESUMO
BACKGROUND: Wrap-clipping is one of the recommended treatments for ruptured blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA). However, the long-term clinical and angiographic outcomes of this procedure have not yet been elucidated. The present study examined the long-term efficacy of wrap-clipping using a polytetrafluoroethylene membrane, an ideal wrapping material, for BBAs. METHODS: The data from 9 patients with ruptured BBAs treated at our institutes from 2007 to 2016 were retrospectively analyzed. Wrap-clipping was performed with advanced monitoring techniques, including fluorescence video angiography and endoscopy. Angiographic follow-up was achieved using 3-dimensional computed tomography angiography or digital subtraction angiography. Clinical outcomes were assessed using the modified Rankin scale. RESULTS: Wrap-clipping was performed without any permanent morbidity in all patients. Endoscopy visualized accurate margins of the aneurysmal pathological wall with high magnification and revealed the position of the clip blades and the surrounding perforators in the dead angles of the microscope. Fluorescence video angiography could confirm the blood flow of the ICA and the surrounding arteries. Regrowth of the aneurysm owing to the presence of a neck remnant occurred 1 month after treatment in 1 case that was repaired surgically. However, no other recurrence of BBAs or progression of ICA stenosis was observed by angiography with a mean follow-up period of 37 months. No repeat rupture or ischemic complications occurred, and all patients had a modified Rankin scale score of 0 with a mean follow-up period of 61 months. CONCLUSION: Wrap-clipping using a polytetrafluoroethylene membrane for ruptured BBAs is a useful and acceptable procedure with long-term effectiveness. The effectiveness of this method can be ensured using modern monitoring methods.
Assuntos
Aneurisma Roto/cirurgia , Dissecação da Artéria Carótida Interna/cirurgia , Aneurisma Intracraniano/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Instrumentos Cirúrgicos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/instrumentaçãoRESUMO
OBJECTIVE: We previously disclosed that damage to the subependymal arteries (SEAs) caused by coagulation of the choroid plexus at the atrium can result in infarction within the lateral posterior choroidal artery territory, followed by hemiparesis. The present study describes the intraoperative anatomical findings of the SEAs and choroid plexus at the atrium, which were verified only by a few cadaveric studies. METHODS: Locations of the SEA and descending motor pathway were determined with the neuronavigation system and subcortical electrical stimulation in 8 cases of periatrial brain tumor. Indocyanine green videoangiography was performed to verify the blood flow in the choroid plexus and SEAs. RESULTS: Intraoperative visualization of the SEAs was performed successfully in all patients. The neuronavigation system and subcortical electrical stimulation mapping demonstrated that these SEAs penetrated into the descending motor pathway. Indocyanine green depicted the blood flow of the SEAs entering the wall of the lateral ventricle and adjacent brain parenchyma. The blood flow directions between the SEAs and choroid plexus were not uniform, because the SEAs were filled ahead of the choroid plexus in 3 cases, whereas the choroid plexus was filled first in the other 2 cases. CONCLUSIONS: Manipulations to the inner side of the choroid plexus at the transition from the atrium to the body of lateral ventricle can damage the SEAs. Not only coagulation of the SEAs themselves, but also coagulation of choroid plexus itself may reduce the blood flow in the SEAs, resulting in ischemic complications at descending motor pathway.
Assuntos
Plexo Corióideo/irrigação sanguínea , Plexo Corióideo/diagnóstico por imagem , Monitorização Intraoperatória/métodos , Tratos Piramidais/irrigação sanguínea , Tratos Piramidais/diagnóstico por imagem , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Criança , Plexo Corióideo/cirurgia , Feminino , Humanos , Ventrículos Laterais/irrigação sanguínea , Ventrículos Laterais/diagnóstico por imagem , Ventrículos Laterais/cirurgia , Masculino , Pessoa de Meia-Idade , Tratos Piramidais/cirurgia , Cirurgia Vídeoassistida/métodosRESUMO
OBJECT Indoleamine 2,3-dioxygenase (IDO), a key enzyme of tryptophan (Trp) metabolism, is involved in tumor-derived immune suppression through depletion of Trp and accumulation of the metabolite kynurenine, resulting in inactivation of natural killer cells and generation of regulatory T cells (Tregs). It has been reported that high expression of IDO in cancer cells is associated with suppression of the antitumor immune response and is consistent with a poor prognosis. Thus, IDO may be a therapeutic target for malignant cancer. The authors have recently shown that IDO expression is markedly increased in human glioblastoma and secondary glioblastoma with malignant change, suggesting that IDO targeting may also have therapeutic potential for patients with glioma. The aim of this study was to investigate the antitumor effect of IDO inhibition and to examine the synergistic function of IDO inhibitor and temozolomide (TMZ) in a murine glioma model. METHODS Murine glioma GL261 cells and human glioma U87 cells were included in this study. The authors used 3 mouse models to study glioma cell growth: 1) a subcutaneous ectopic model, 2) a syngeneic intracranial orthotopic model, and 3) an allogenic intracranial orthotopic model. IDO inhibition was achieved via knockdown of IDO in GL261 cells using short hairpin RNA (shRNA) and through oral administration of the IDO inhibitor, 1-methyl-l-tryptophan (1-MT). Tumor volume in the subcutaneous model and survival time in the intracranial model were evaluated. RESULTS In the subcutaneous model, oral administration of 1-MT significantly suppressed tumor growth, and synergistic antitumor effects of 1-MT and TMZ were observed (p < 0.01). Mice containing intracranially inoculated IDO knockdown cells had a significantly longer survival period as compared with control mice (p < 0.01). CONCLUSIONS These results suggest that IDO expression is implicated in immunosuppression and tumor progression in glioma cells. Therefore, combining IDO inhibition with standard TMZ treatment could be an encouraging therapeutic strategy for patients with malignant glioma.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Dacarbazina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Glioma/tratamento farmacológico , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Triptofano/análogos & derivados , Animais , Linhagem Celular Tumoral , Dacarbazina/farmacologia , Sinergismo Farmacológico , Feminino , Técnicas de Silenciamento de Genes , Glioma/enzimologia , Glioma/imunologia , Glioma/patologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , RNA Mensageiro/metabolismo , Análise de Sobrevida , Temozolomida , Resultado do Tratamento , Triptofano/farmacologia , Carga TumoralRESUMO
We describe a rare case where a patient developed intracranial pial arteriovenous (AV) fistula due to dural tenting. The patient was a 63-year-old woman who had undergone neck clipping for an unruptured middle cerebral artery (MCA) aneurysm. The surgery was performed without any problems and her postoperative course was uneventful. Two weeks after cerebral angiography operation revealed a pial AV fistula fed by the right MCA and drained into the vein of Trolard through the Sylvian vein which had not existed before surgery. Being diagnosed as de novo pial AV fistula, surgical repair was performed. The AV fistula was located just beneath the dural tenting. The fistulous point was confirmed with fluorescein video angiography and obliterated using a clip. Although rare, we should pay attention to the AV fistula due to dural tenting as the complications of cranial surgery.
Assuntos
Malformações Vasculares do Sistema Nervoso Central/etiologia , Veias Cerebrais , Dura-Máter , Aneurisma Intracraniano/cirurgia , Pia-Máter/irrigação sanguínea , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Angiografia Cerebral , Craniotomia , Feminino , Angiofluoresceinografia , Humanos , Pessoa de Meia-Idade , Reoperação , Gravação em VídeoRESUMO
Neck clipping of a large middle cerebral artery aneurysm was performed using a newly developed surgical microscope integrated with modules for both indocyanine green (ICG) and fluorescein videoangiography. During surgery, ICG and fluorescein videoangiography by intra-arterial or intravenous injection were safely carried out without interrupting the surgical procedure. Based on the findings obtained from the case, we evaluated the differences between the dyes and the injection routes. With intra-arterial injection, fluorescein offered sharper contrast images and was better at depicting fine arteries than ICG. Patchy staining of vessel walls was observed in intravenous fluorescein videoangiography, while it was not evident in ICG. Intra-arterial injection method had a great advantage in the rapid clearance of the dyes, which allowed us to perform repeated videoangiography within a short period, and was useful in detecting incomplete clipping in this case; however, catheter insertion requires additional work and carries a potential risk. Use of a microscope integrated for both ICG and fluorescein videoangiography would be another method for repeated evaluation. Namely, alternate use of the dyes enables us to perform videoangiography in a short time even via intravenous injection.