Utility of a scoring system for differentiating cancer-associated stroke from cryptogenic stroke in patients with cancer.

BACKGROUND: The commonest type of ischemic cerebral stroke in patients with cancer is cryptogenic stroke (CRS), the majority of which are considered cancer-associated strokes (CAS) caused by multiple microemboli associated with hypercoagulation, known as Trousseau syndrome. However, detection of microemboli and diagnosing CAS is difficult. We have therefore developed a scoring system for diagnosing CAS. METHODS: We retrospectively examined data of patients with cancer and stroke between 2006 and 2017. We identified risk factors for CRS, assigned them one or two points, and calculated total scores (Trousseau score) for each patient. We used overall survival after stroke (OSs) to validate the utility of the system. RESULTS: In 181 consecutive strokes, CRS was the commonest type (43.6%) and had a short OSs (median 56 days). We identified the following five risks for CRS: high D-dimer concentration (≥ 10.0 µg/mL) and lesions in multiple territories (two points each); and active cancer, low platelet count (150,000/µL>) and female sex (one point each). Trousseau score ≥ 3 indicated CAS (50.3%), which had a median OSs of 50 days. Only CAS (hazard ratio 3.44 [2.34-5.10], P < 0.0001) and poor performance status (3 or 4) (2.27 [1.50-3.39], P = 0.0002) were risk factors for OSs; CRS was not. OSs of patients with non-CAS/CRS was significantly longer than that of those with CAS/CRS (404.5 days vs. 47 days, P = 0.0114), whereas OSs of CAS/non-CRS was much shorter than that of non-CAS/non-CRS (53 days vs. 547 days, P < 0.0001). CONCLUSION: Trousseau scores simply and clearly identify CAS.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

BACKGROUND: The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. METHODS: Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. RESULTS: Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. CONCLUSION: Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Levetiracetam versus phenytoin for seizure prophylaxis during and early after craniotomy for brain tumours: a phase II prospective, randomised study.

OBJECTIVE: Phenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period. METHODS: Patients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15-18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events. RESULTS: One hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2). CONCLUSIONS: Prophylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period. TRIAL REGISTRATION NUMBER: UMIN13971.

Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations.

BACKGROUND: The brain is a frequent site of metastases from non-small-cell lung cancer (NSCLC). We analyzed the frequency of brain metastases (BMs) from NSCLC in the era of magnetic resonance images, and evaluated the correlation between epidermal growth factor receptor (EGFR) mutations and BMs among East Asian patients. METHODS: Frequency, number, and size of BMs, and survival of 1,127 NSCLC patients were retrospectively reviewed. Mutation status of EGFR was evaluated in all cases, and its association with BMs was statistically evaluated. RESULTS: EGFR mutations were found for 331 cases (29.4 %). BM was the cause of primary symptoms for 52 patients (4.6 %), and found before initiation of treatment for 102 other patients (9.1 %); In addition to these 154 patients, 107 patients (9.5 %) developed BMs, giving a total of 261 patients (23.2 %) who developed BMs from 1,127 with NSCLC. BM frequency was higher among EGFR-mutated cases (31.4 %) than EGFR-wild cases (19.7 %; odds ratio: 1.86; 95 % confidence interval (CI) 1.39-2.49; P < 0.001). BMs from EGFR-mutated NSCLC were small, but often became disseminated. EGFR mutations accounted for 39.9 % of BMs, but patient survival after BMs was significantly longer for EGFR-mutated cases than for EGFR-wild cases (hazard ratio: 2.23; 95 % CI 1.62-3.10; P < 0.001). CONCLUSIONS: Patients with EGFR-mutated NSCLC were more likely to develop BMs, but apparently also survived longer after BMs.

Favorable long-term outcome of low-grade oligodendrogliomas irrespective of 1p/19q status when treated without radiotherapy.

Despite the accumulating evidences of high chemosensitivity especially in anaplastic oligodendrogliomas with loss of chromosomes 1p and 19q, the optimal management strategy for low-grade tumors using the 1p/19q information remains controversial. We have treated all low-grade oligodendrogliomas by a chemotherapy-preceding strategy without radiotherapy, and here we analyzed the survival outcomes of 36 consecutive patients in relation to 1p/19q status. The treatment protocol was as follows: (1) simple observation after gross total resection, and (2) modified PCV chemotherapy for postoperative residual tumors or recurrence after total resection. The 1p and 19q status were analyzed by fluorescence in situ hybridization. The median follow-up period was 7.5 years and no patient was lost during the follow-up periods. 1p/19q co-deletion was observed in 72% of the patients, and there was no significant association between 1p/19q co-deletion and chemotherapy response rate. The 5- and 10-year progression-free survival (PFS) rate was 75.1 and 46.9%, respectively, and the median PFS was 121 months for 1p/19q-deleted tumors and 101 months for non-deleted tumors (log-rank test: P = 0.894). Extent of surgery did not affect PFS (P = 0.685). In contrast, the elder patients (>50) had significantly shorter PFS (P = 0.0458). Recurrent tumors were well controlled by chemotherapy irrespective of 1p/19q status, and 35 out of 36 patients survived without receiving radiotherapy. The 5- and 10-year overall survival rates were 100 and 93.8%, respectively. Two of the patients in their sixties (29%) suffered from severe cognitive dysfunctions and marked brain atrophy following chemotherapy alone. These results show that low-grade oligodendrogliomas could be successfully treated by surgical resection and nitrosourea-based chemotherapy alone without radiotherapy irrespective of 1p/19q status.

Urokinase-targeted fusion by oncolytic Sendai virus eradicates orthotopic glioblastomas by pronounced synergy with interferon-ß gene.

Glioblastoma multiforme (GM), the most frequent primary malignant brain tumor, is highly invasive due to the expression of proteases, including urokinase-type plasminogen activator (uPA). Here, we show the potential of our new and powerful recombinant Sendai virus (rSeV) showing uPA-specific cell-to-cell fusion activity [rSeV/dMFct14 (uPA2), named "BioKnife"] for GM treatment, an effect that was synergistically enhanced by arming BioKnife with the interferon-ß (IFN-ß) gene. BioKnife killed human GM cell lines efficiently in a uPA-dependent fashion, and this killing was prevented by PA inhibitor-1. Rat gliosarcoma 9L cells expressing both uPA and its functional receptor uPAR (9L-L/R) exhibited high uPA activity on the cellular surface and were highly susceptible to BioKnife. Although parent 9L cells (9L-P) were resistant to BioKnife and to BioKnife expressing IFN-ß (BioKnife-IFNß), cell-cell fusion of 9L-L/R strongly facilitated the expression of IFN-ß, and in turn, IFN-ß significantly accelerated the fusion activity of BioKnife. A similar synergy was seen in a rat orthotopic brain GM model with 9L-L/R in vivo; therefore, these results suggest that BioKnife-IFNß may have significant potential to improve the survival of GM patients in a clinical setting.

Endoscopic endonasal skull base reconstruction using a nasal septal flap: surgical results and comparison with previous reconstructions.

The objective of this study is to evaluate the usefulness and reliability of endoscopic endonasal skull base reconstructions using a nasal septal flap. This study is designed as a retrospective review. Between April 2005 and November 2009, we performed 32 endoscopic endonasal skull base reconstructions for closure of large dural defects. Eleven patients underwent reconstructions using fat grafts or the fascia lata (non-flap group). Twenty one patients underwent reconstructions using a nasal septal flap with a balloon catheter (flap group). Incidence of postoperative cerebrospinal fluid (CSF) leaks and perioperative insertion rate of external lumbar drain (ELD) were compared between the two groups. Postoperative CSF leaks occurred in two patients (9.5%) in the flap group. Three patients (27.3%) presented CSF leaks in the non-flap group. The rate of insertion of ELD was 81.8% in the non-flap group. In the flap group, one patient (4.8%) should be placed with ELD postoperatively. The incidence of postoperative CSF leaks in the flap group was lower than in the non-flap group, whereas the rate of insertion of ELD in the non-flap group was higher than in the flap group. Endoscopic endonasal skull base reconstruction using a nasal septal flap without ELD seems to be useful and reliable for ventral skull base defects after endoscopic endonasal approaches as compared with our previous single-layer reconstructions using free fat grafts or fascia lata. The long-term effectiveness of nasal septal flaps to prevent intracranial complications should be confirmed.

[Endoscopic endonasal surgery for extrasellar tumors: case presentation and its future perspective].

BACKGROUND AND OBJECTIVES: Endoscopic endonasal transsphenoidal surgery has been performed because of its advantages such as less invasive surgical management and more aggressive tumor removal of extrasellar lesions. In 2003, we began endoscope-assisting surgery. In 2006, we completely switched to the endoscopic endonasal approach without microscope or nasal specula. Today, we report endoscopic pituitary and skull base surgery in our institute. The endonasal approach via the sphenoid ostium was carried out without nasal specula. Postoperative nasal packing was basically not needed in such cases. In cases with meningiomas, craniopharyngiomas and giant pituitary adenomas, which needed intra-dural procedure, nasal procedures such as middle nasal conchotomy, posterior ethmoidectomy and skull base techniques such as optic canal decompression and removal of the planum sphenoidale were carried out to gain the wider operative field toward anterior skull base and lower clivus. Navigation and US-Doppler were essential. Angled endoscope attained more successful removal of tumor under direct visualization extending into the cavernous sinus (GH secreting ademomas) and lower clivus (chordoma). In the case of CSF (cerebrospinal fluid) leakage during operation, a newly designed balloon catheter was placed in the sphenoid sinus to fix the abdominal fat and fibrin glue at the leakage point. In recent cases, dural opening has been sutured. In the combination of such techniques, a lumbar drainage system to prevent postoperative CSF rhinorrhea became needless in many cases. Angled suction tips, single-shaft coagulation tools and slim and longer holding forceps, all of which were newly designed for endoscopic surgery, were essential for smoother procedure. Endonasal endoscopic pituitary surgery has resulted in less invasive transsphenoidal surgery since no postoperative nasal packing is needed and there is less dependency on lumbar drainage. Although better techniques to prevent postoperative CSF leakage needs to be developed, this endoscopic pituitary surgery will become more common and will become a standard procedure. Endoscopic skull base surgery has enabled more aggressive removal of extrasellar tumors with the aid of nasal and skull base techniques. This endoscopic skull base surgery is more highly specialized, needs special techniques and surgical training. Selection of patients is also important. This also needs collaboration with ENT (ear, nose, throat) doctors. To be acknowledged as a safe and successful procedure in skull base surgery, this complex procedure may be preferably carried out only in center hospitals, which deal with many patients with a skull base lesion.

Feasibility study of finalizing the extended adjuvant temozolomide based on methionine positron emission tomography (Met-PET) findings in patients with glioblastoma.

In the management of patients with newly diagnosed glioblastoma, there is no standard duration for adjuvant temozolomide treatment. This study aimed to assess the feasibility of finalizing adjuvant temozolomide treatment on the basis of methionine uptake in methionine positron emission tomography (Met-PET). We conducted a retrospective review of glioblastoma patients who underwent more than twelve cycles of temozolomide (extended temozolomide) treatment after resection and concomitant chemoradiotherapy with no evidence of recurrence on MRI. In addition to the methionine uptake value at the completion of extended temozolomide, local and distant recurrence and progression-free survival were also analyzed. Forty-four patients completed the extended temozolomide treatment. Among these, 18 experienced some type of tumor recurrence within one year. A Tmax/Nave value of 2.0 was the optimal cut-off value indicating progression. More than 80% of the patients with low methionine uptake completed the temozolomide treatment, and subsequent basic MRI observations showed no recurrence within one year after Met-PET. Subgroups with high uptake (≥2.0), even with continuation of temozolomide treatment, showed more frequent tumor progression than patients with low uptake (<2.0) who completed the extended temozolomide treatment (p < 0.001, odds ratio 14.7, 95% CI 3.46-62.3). The tumor recurrence rate increased in stepwise manner according to methionine uptake. Finalization of the extended temozolomide treatment on the basis of low uptake value was feasible with a low recurrence rate. Compared to MRI, Met-PET shows better ability to predict tumor progression in long-term glioblastoma survivors with extended temozolomide use.

Ceritinib Treatment for Carcinomatous Meningitis with a Secondary Mutation at I1171T in Anaplastic Lymphoma Kinase.

The mechanisms underlying anaplastic lymphoma kinase (ALK) resistance have not been well investigated in clinical practice. We herein report the case of a lung cancer patient with carcinomatous meningitis who had an ALK I1171T resistance mutation revealed by direct DNA sequencing of the cerebrospinal fluid after treatment with cytotoxic chemotherapy, crizotinib, and alectinib. I1171T is considered to be sensitive to ceritinib. Although ceritinib was not effective initially, we chose ceritinib again after whole-brain radiotherapy and ventriculoperitoneal shunting. Although the response duration was short, spinal magnetic resonance imaging revealed a marked response. The identification of an acquired ALK resistance mutation will aid in choosing the optimum sequence therapy.

Clinical significance of the 2016 WHO classification in Japanese patients with gliomas.

In this study, we retrospectively compared the prognostic value of the 2016 WHO classification with the former classification in 387 patients with glioma treated at our institution. According to the new classification, diagnoses included oligodendroglioma with isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion (5.4%), anaplastic oligodendroglioma with IDH mutation and 1p/19q co-deletion (3.4%), diffuse astrocytoma IDH-mutated (3.9%), anaplastic astrocytoma IDH-mutated (2.8%), glioblastoma IDH-mutated (7.8%), glioblastoma IDH-wildtype (58.4%), diffuse midline glioma H3 K27M mutation (2.6%), oligodendroglioma NOS (1.3%), anaplastic oligodendroglioma NOS (0.8%), diffuse astrocytoma IDH-wildtype (2.8%), and anaplastic astrocytoma IDH-wildtype (10.9%). The prognoses of IDH-mutated astrocytomas clearly varied according to tumor grade. However, we identified no survival difference between IDH-wildtype anaplastic astrocytomas and glioblastomas; additionally, these tumors showed similar gene expression profiles. After exclusion of those without 1p/19q co-deletion, patients with oligodendroglial tumors showed excellent survival regardless of tumor grade. Our evaluation of chromosomal aberrations suggests that the MAPK/PI3K pathway plays a role in acquired malignancy of astrocytic tumors, whereas TP53 participates in tumorigenesis. We suspect the RB pathway also plays a role in tumorigenesis of IDH-mutated gliomas. The new WHO classification more clearly reflects the tumorigenesis of gliomas and improves the prognostic power of classification.

The influence of carmustine wafer implantation on tumor bed cysts and peritumoral brain edema.

The development of perifocal edema and tumor bed cyst has been reported after implantation of biodegradable carmustine wafers for the treatment of malignant gliomas. We retrospectively evaluated these changes in a series of patients; 19 consecutive patients with malignant glioma who received carmustine wafer implantation at our hospital from January 2013 through July 2013, and 28 patients who underwent surgery prior to our institution's initiation of carmustine wafer implantation, as historical controls. The volume of the tumor bed cyst and perifocal edema was calculated on MRI acquired at four time points: ⩽72hours after surgery for baseline, and at 1-4, 5-8, and 9-12weeks after surgery. The volume of the tumor bed cyst in the wafer group increased significantly relative to the control group at all time points (p=0.04). Opening of the ventricle was inversely correlated with enlargement of the tumor bed cyst in the wafer group (p=0.04). The change in the volume of perifocal edema in the wafer group was not significantly different (p=0.48), but exhibited a considerable increase in patients with anaplastic oligodendroglioma relative to glioblastoma patients in the wafer group (p=0.01). We demonstrated significant enlargement of the tumor bed cyst volume after carmustine wafer implantation, as well as the development of marked perifocal edema in patients with anaplastic oligodendroglioma.

Epilepsy in patients with gliomas: incidence and control of seizures.

Brain tumor-related epilepsy (BTRE) is a unique condition that is distinct from primary epilepsy. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. From a database of 121 consecutive patients with supratentorial gliomas treated at Chiba Cancer Center from 2006-2012, the incidence and control of seizures before and after surgery were retrospectively evaluated. Epilepsy occurred in 33.9% of patients before surgery. All patients received prophylactic anti-epileptic drugs (AED) during surgery; however, seizures occurred in 9.1% of patients within the first postoperative week. During follow-up, seizures occurred in 48.3% of patients. The overall incidence of seizures was 73.7% in patients with World Health Organization Grade II gliomas, 66.7% in those with Grade III and 56.8% in those with Grade IV gliomas. Levetiracetam was very well tolerated. However, carbamazepine and phenytoin were poorly tolerated because of adverse effects. AED were discontinued in 56 patients. Fifteen of these patients (26.8%) had further seizures, half occurring within 3 months and 80% within 6 months of AED withdrawal. No clinical factors that indicated it was safe to discontinue AED were identified. The unpredictable epileptogenesis associated with gliomas and their excision requires prolonged administration of AED. To maintain quality of life and to safely and effectively control the tumor, it is necessary to select AED that do not adversely affect cognitive function or interact with other drugs, including anti-cancer agents.

Methionine Uptake and Required Radiation Dose to Control Glioblastoma.

PURPOSE: The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. METHODS AND MATERIALS: Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. RESULTS: MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P = .005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P < .0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 × MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. CONCLUSIONS: Target delineation based on MET-PET was demonstrated to be feasible for radiation therapy treatment planning. MET-PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions.

Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma.

PURPOSE/OBJECTIVES: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m(2)/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m(2)/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. RESULTS: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. CONCLUSIONS: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.

Comparison of intensity modulated radiotherapy and dynamic three-dimensional conformal radiotherapy with regard to dose distribution and sparing of organs at risk.

Dose escalation to the target while sparing the organs at risk near the lesion has been difficult over the last decade. However, recent radiotherapy techniques can deliver more sophisticated doses to the target. This study evaluated whether intensity modulated radiotherapy can deliver more homogeneous and conformal doses to the target than dynamic three-dimensional conformal radiotherapy while sparing organs at risk near the lesion in 13 patients with central nervous system tumors and other tumors around the central nervous system. Dynamic three-dimensional conformal radiotherapy and intensity modulated radiotherapy plans were calculated and dose distributions were compared for all patients with regard to the planning target volume and organs at risk. The plan of intensity modulated radiotherapy was significantly superior to that of dynamic three-dimensional conformal radiotherapy in target dose conformity (p = 0.0006) and organs at risk sparing (p = 0.0257). Intensity modulated radiotherapy could deliver more homogeneous and conformal doses to the target than dynamic three-dimensional conformal radiotherapy with sparing organs at risk near the lesion and may improve local control of radioresistant tumors via dose escalation.

Endoscopic endonasal trans-sphenoidal optic nerve decompression for traumatic optic neuropathy--technical note.

The endoscopic endonasal trans-sphenoidal approach can decompress the traumatized and swollen optic nerve without brain retraction. Three cases of traumatic optic neuropathy (TON) were treated by this endoscopic approach. We performed 58 endoscopic endonasal trans-sphenoidal approaches in 52 patients between April 2006 and December 2007. Three patients, 2 men and a woman aged 42-66 years, with TON were treated by endoscopic endonasal trans-sphenoidal optic nerve decompression. Adequate decompression of the optic canal was observed in all three patients. Two experienced improved visual function, but the third did not. No surgical complications were observed in any patient. We were able to reach the optic canal above the opticocarotid recess near the orbit. Endoscopic endonasal trans-sphenoidal optic canal decompression using a navigation system may be a safe and effective surgical strategy in carefully selected patients with TON.

Endoscopic endonasal pituitary and skull base surgery.

Here we describe the procedures of endoscopic pituitary and skull base surgery in our institute. We also review the literature to reveal recent advances in this field. Endonasal approach via the sphenoid ostium was carried out for pituitary lesions without the nasal speculum. Postoperative nasal packing was basically not needed in such cases. For meningiomas, craniopharyngiomas, and giant pituitary adenomas, which required intra-dural procedures, nasal procedures such as middle nasal conchotomy and posterior ethmoidectomy, and skull base techniques such as optic canal decompression and removal of the planum sphenoidale were carried out to gain a wider operative field. Navigation and ultrasonic Doppler ultrasonography were essential. Angled endoscopes allowed more successful removal of tumors under direct visualization extending into the cavernous sinus and lower clivus. If cerebrospinal fluid (CSF) leakage occurred during operation, the dural opening was covered with a vascularized mucoseptal flap obtained from the nasal septum. Lumbar drainage system to prevent postoperative CSF rhinorrhea was frequently not required. Angled suction tips, single-shaft coagulation tools, and slim and longer holding forceps, all of which were newly designed for endoscopic surgery, were essential for smoother procedures. Endonasal endoscopic pituitary surgery allows less invasive transsphenoidal surgery since no postoperative nasal packing and less dependence on lumbar drainage are needed. Endoscopic pituitary surgery will be more common and become a standard procedure. Endoscopic skull base surgery has enabled more aggressive removal of extrasellar tumors with the aid of nasal and skull base techniques. Postoperative CSF leakage is now under control due to novel methods which have been proposed to close the dural defect in a water-tight manner. Endoscopic skull base surgery is more highly specialized, so needs special techniques and surgical training. Patient selection is also important, which needs collaboration with ear, nose, and throat specialists. As a safe and successful procedure in skull base surgery, this complex procedure should be carried out only in specialized hospitals, which deal with many patients with skull base lesions.

Selection of chemotherapy for glioblastoma expressing O(6)-methylguanine-DNA methyltransferase.

The therapeutic benefit of nitrosoureas or temozolomide for glioblastoma is limited mainly by O(6)-methylguanine-DNA methyltransferase (MGMT) expression. The aim of this study was to evaluate the effectiveness of various anticancer drugs for MGMT-positive glioblastoma. Seventy-four glioblastoma patients were administered various anticancer drugs according to drug sensitivity testing. For the individualization, drug-induced apoptosis was quantified by flow cytometry in the primary culture of surgically resected tumor cells. The MGMT protein expression was analyzed by immunohistochemistry. The median survival of the patients receiving the individualized chemotherapy was 19.4 months (95% CI, 15.9-22.1). The patients with negative MGMT immunostaining had significantly longer survival than those with positive MGMT immunostaining [median survival, 22.3 months (95% CI, 17.6-27.0) vs. 15.1 months (95% CI, 13.4-16.8); p=0.0188]. For MGMT-positive tumors, the platinum agents and the taxanes were more frequently selected for administration than the other categories of anticancer agents. The patient survival period of MGMT-positive glioblastomas treated with the platinum agents or the taxanes [median survival, 20.1 months (95% CI, 18.0-22.7)] was significantly longer than that of MGMT-positive tumors treated with nitrosoureas (p=0.0026), and was equivalent to that of MGMT-negative glioblastomas (p=0.3047). These results suggest that the platinum agents and the taxanes offer the best probability to be effective against immunohistochemically MGMT-positive glioblastomas.