Craniotomy for cerebellar hemangioblastoma excision in a patient with von Hippel–Lindau disease complicated by uncontrolled hypertension due to pheochromocytoma

INTRODUCTION: This report describes a patient with Von Hippel–Lindau (VHL) syndrome and uncontrolled hypertension due to pheochromocytoma who underwent craniotomy for the excision of a cerebellar hemangioblastoma combined with a laparoscopic adrenalectomy. CASE REPORT: A 31-year-old man presented with severe headache. MRI showed areas of abnormal enhancement in the left cerebellum that were determined to be hemangioblastoma with mass effect and obstructive hydrocephalus. His blood pressure rose abruptly and could not be controlled. CT of the abdomen revealed bilateral suprarenal tumors, and the patient was diagnosed as having VHL syndrome.On the third day, he presented with increasing headache, a decreased level of consciousness, and hemiparesis. We were not able to perform an craniotomy because abdominal compression in the prone or sitting position resulted in severe hypertension. We performed ventricular drainage to control his ICP. On the fifth day, we first performed a bilateral laparoscopic adrenalectomy to control ICP and then moved the patient to the prone position before performing a craniotomy to remove the left cerebellar hemangioblastoma. DISCUSSION & CONCLUSION: In patients with pheochromocytoma, the effects of catecholamine oversecretion can cause significant perioperative morbidity and mortality, but these can be prevented by appropriate preoperative medical management. When carrying out an excision of cerebellar hemangioblastomas in patients with intracranial hypertension complicated by abnormal hypertension due to pheochromocytoma whose blood pressure is not sufficiently controlled, tumor resection of the pheochromocytoma prior to cerebellar hemangioblastoma excision in the same surgery may prevent increased ICP and reduce perioperative risk

Continued-Maintenance Therapy for PCNSL

Background. PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS). Methods. In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months. Results. In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT

Navigation-Guided fence-post catheter

Background : Navigation system devices have been developed to allow precise resection of brain tumor. The fence-post catheter techniques that use a navigation system have been used in many neurosurgery centers. However, an exclusive catheter for the fence-post catheter techniques have not been made, and substituted silicon tube of the cerebral ventricle drainage or a Nelaton catheter is widely used. Objective : In this brief technical note, we describe a new fence-post catheter with steel tip device that was designed for more precise tissue resection and is useful in tumor resection. Methods : The newly designed fence-post catheter helps to visually gauge the accurate depth from the tumor bottom during tumor resection. Furthermore, the catheter tip has moderate weight and is made of a non-magnetic material. Results : Using our fence-post catheter, which has a metal part at the tip of the tube (length, 13 mm), operators can clearly notice that they are getting closer to base of the tumor by checking the metal part during the resection of deep tumors. Conclusion : Our newly developed fence-post tube enables easy confirmation of the distance to deep-tissue regions and improves the degree of safety during tumor removal

Metastatic tumor to the orbital cavity

Metastatic tumors to the orbit of the eye, especially from primary carcinomas of the uterine cervix are very rare. A 64-year-old woman with a history of carcinoma of the uterine cervix presented with right eye pain and blepharoptosis for 2 weeks. Magnetic resonance imaging revealed a mass at the right orbital apex. Surgical extirpation was performed due to severe pain. Postoperative pathology demonstrated a poorly differentiated squamous cell carcinoma. The origin was ultimately considered to be the carcinoma of the uterine cervix. In conclusion, this report describes a rare case of a metastatic tumor at the orbital apex derived from the cervix of the uterus

アクセイ シンケイ コウシュ ニ タイスル チュウセイシ ホソク リョウホウ : コンゴウ ビーム ネツチュウセイシ ト ネツガイチュウセイシ ビーム オ モチイタ アタラシイ チリョウ センリャク

The purpose of this study was to clarify the clinical interim results of boron neutron capture therapy (BNCT) using mixed epithermal-and thermal neutron beams in patients with malignant glioma. The mixed neutron beam for BNCT has been used clinically since 1998. Its great advantage consists of its greater ability than the pure thermal neutron beam to reach sites deep from the brain surface. Sixteen patients with malignant glioma (glioblastoma n=14, anaplastic ependymoma n=1, PNET n=1) underwent mixed epithermal-and thermal neutron beam treatment between 1998 and 2003. They included 2 children younger than 3 years. Sodium borocaptate (Na2B12H11SH, BSH ; 80-100 mg/kg) was administered intravenously at 12-15 hr before neutron irradiation. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the he protocol used between 1997 and 2000 (Protocol A) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B) ; it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. In both protocols, the maximum vascular radiation dose to the brain surface is not to exceed 15 Gy. Of the 12 patients, 8 were treated according to Protocols A and 4 according to Protocol B. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to four glioblastoma patients (Protocol C). Of the 8 patients treated under Protocol A, 7 died (dissemination n=4, local recurrence, infection, unknown causes, n=1 each). Of the 4 patients treated under Protocol B, 2 died. Concerning the adverse effects of BNCT, Protocol B resulted in higher complication rates with respect to both acute and delayed radiation injury. The estimated median survival time after diagnosis and after BNCT in all patients were 16.7 and 14.6 months, respectively. In 8 patients of Protocol A, the estimated median survival time after diagnosis was 16.0 months ; 1-year and 2-year survival rate were 75.0% and 12.5%, respectively. On the other hand, in 8 patients in Protocol B and C, the estimated median survival time after diagnosis was 15.5 months ; 1-year and 2-year survival rate were 80.0% and 53.3%, respectively. Our limited clinical evaluation suggests that BNCT could achieve local control of glioblastomas at the primary site and that possible dose escalation is limited. While the dose escalation can contribute to the improvement of survival rate, it results in the radiation injury. We conclude that not only the radiation dose at the target point, but also the distribution of neutron flux in the radiation field may contribute to the cure of glioblastoma by BNCT. Computation-assisted dose planning can contribute to improved clinical results following BNCT and to the prevention of cerebrospinal fluid dissemination. We will introduce pure epithermal neutron beam instead of mixed neutron beam in the near future. It has greater advantage than mixed neutron beam to deep-seated glioma because it has a peak in neutron flux at 2-3 cm depth from the brain surface. The dose-planning system and pure epithermal neutron beam can lead to further improvements in the clinical outcomes and the avoidance of adverse effects in brain tumor patients subjected to BNCT

The risk of hemorrhage in stereotactic biopsy

Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy

Perfusion MRI for brain tumors

Purpose : To compare data on brain tumors derived from intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) imaging with multiple parameters obtained on dynamic susceptibility contrast (DSC) perfusion MRI and to clarify the characteristics of IVIM and ASL perfusion data from the viewpoint of cerebral blood flow (CBF) analysis. Methods : ASL-CBF and IVIM techniques as well as DSC examination were performed in 24 patients with brain tumors. The IVIM data were analyzed with the two models. The relative blood flow (rBF), relative blood volume (rBV) corrected relative blood volume (crBV), mean transit time (MTT), and leakage coefficient (K2) were obtained from the DSC MRI data. Results : The ASL-CBF had the same tendency as the perfusion parameters derived from the DSC data, but the permeability from the vessels had less of an effect on the ASL-CBF. The diffusion coefficient of the fast component on IVIM contained more information on permeability than the f value. Conclusion : ASL-CBF is more suitable for the evaluation of perfusion in brain tumors than IVIM parameters. ASL-CBF and IVIM techniques should be carefully selected and the biological significance of each parameter should be understood for the correct comprehension of the pathological status of brain tumors

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma : Comparison of clinical results obtained with BNCT and conventional treatment

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months ; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide

Research and surgery for brain AVMs

Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler–Martin grade AVMs with low morbidity

FKBP5 regulation on anti-PD-1 therapy

Background. Antitumor therapies targeting programmed cell death-1 (PD-1) or its ligand-1 (PD-L1) are used in various cancers. However, in glioblastoma (GBM), the expression of PD-L1 varies between patients, and the relationship between this variation and the efficacy of anti-PD-1 antibody therapy remains unclear. High expression levels of PD-L1 affect the proliferation and invasiveness of GBM cells. As COX-2 modulates PD-L1 expression in cancer cells, we tested the hypothesis that the COX-2 inhibitor celecoxib potentiates anti-PD-1 antibody treatment via the downregulation of PD-L1. Methods. Six-week-old male C57BL/6 mice injected with murine glioma stem cells (GSCs) were randomly divided into four groups treated with vehicle, celecoxib, anti-PD-1 antibody, or celecoxib plus anti-PD-1 antibody and the antitumor effects of these treatments were assessed. To verify the mechanisms underlying these effects, murine GSCs and human GBM cells were studied in vitro. Results. Compared with that with each single treatment, the combination of celecoxib and anti-PD-1 antibody treatment significantly decreased tumor volume and prolonged survival. The high expression of PD-L1 was decreased by celecoxib in the glioma model injected with murine GSCs, cultured murine GSCs, and cultured human GBM cells. This reduction was associated with post-transcriptional regulation of the co-chaperone FK506-binding protein 5 (FKBP5). Conclusions. Combination therapy with anti-PD-1 antibody plus celecoxib might be a promising therapeutic strategy to target PD-L1 in glioblastoma. The downregulation of highly-expressed PD-L1 via FKBP5, induced by celecoxib, could play a role in its antitumor effects