Despite recent advances in the development of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor is attributed to tumor heterogeneity. To explain this unique chemo- resistance, the concept of cancer stem cells has been evoked. Cancer stem cells, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Here, the author reviews and discusses the cancer stem cell concept.
Cell of origin; Cancer stem cell; Lineage hierarchy
The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS).
Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan-Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors.
Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ≥70 (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were 89.5±4.5% and 70.5±6.9% at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (≤3) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival.
The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.
Brain metastasis; Breast cancer; Gamma Knife radiosurgery; Intrinsic subtype; Treatment outcomes
Microvascular decompression (MVD) for hemifacial spasm (HFS) is a safe and effective treatment with favorable outcomes. The purpose of this study was to evaluate the incidence of delayed cranirve ( VI, VII, and VIII ) palsy following MVD and its clinical courses.
Between January 1998 and December 2009, 1354 patients underwent MVD for HFS at our institution. Of them, 100 patients (7.4%) experienced delayed facial palsy (DFP), one developed sixth nerve palsy, and one patient had delayed hearing loss.
DFP occurred between postoperative day number 2 and 23 (average 11 days). Ninety-two patients (92%) completely recovered; however, House-Brackmann grade II facial weakness remained in eight other patients (8%). The time to recovery averaged 64 days (range, 16 days to 9 months). Delayed isolated sixth nerve palsy recovered spontaneously without any medical or surgical treatment after 8 weeks, while delayed hearing loss did not improve.
Delayed cranial nerve (VI, VII, and VIII) palsies can occur following uncomplicated MVD for HFS. DFP is not an unusual complication after MVD, and prognosis is fairly good. Delayed sixth nerve palsy and delayed hearing loss are extremely rare complications after MVD for HFS. We should consider the possibility of development of these complications during the follow up for MVD.
Delayed facial palsy; Microvascular decompression; Delayed cranial palsy; Delayed hearing loss; Delayed abducens palsy
The aim of this study was to describe a single center's experience in the management of craniopharyngiomas in children over a 15-year period.
The clinical records of pediatric patients treated for craniopharyngiomas between December 1995 and February 2011 were reviewed. Thirty-five pediatric patients diagnosed with craniopharyngioma were treated, and their medical records and imaging data were analyzed retrospectively.
The mean follow-up duration was 76 months (range, 10-195). Overall survival and local control rates at 10 years were 94.7±5.1% and 37.1±11.9%, respectively. The female-to-male ratio was 16 : 19, and the mean age was 8.6 years (range, 1-17). Initially, gross total resection (GTR) was performed in 30 patients; subtotal resection (STR) followed by radiotherapy was performed in 5 patients. Of the 14 cases that showed recurrence after GTR, 5 patients were treated with GTR, 1 with radiation therapy (RT), 4 with gamma knife radiosurgery (GKRS), and 4 with subtotal resection followed by RT. No patients who underwent RT or GKRS had recurrences. Two cases with recurrence after STR followed by RT were treated with GTR. One patient died of hormonal insufficiency 64 months after the first surgery. The overall median time progression was 51.2 months (range, 3-182) : 49.7 months in the patients who underwent GTR and 60.2 months in the patients who underwent STR followed by RT.
If safe resection is possible, GTR at the initial treatment should be attempted to reduce the tumor recurrence. However, if the tumor recurs after the first surgery, RT or GKRS with/without reoperation may be an effective salvage treatment for recurrent craniopharyngioma.
Craniopharyngioma; Microsurgery; Radiotherapy
A set of proteins reflecting the prognosis of patients have clinical significance since they could be utilized as predictive biomarkers and/or potential therapeutic targets. With the aim of finding novel diagnostic and prognostic markers for glioblastoma (GBM), a tissue microarray (TMA) library consisting of 62 GBMs and 28 GBM-associated normal spots was constructed. Immunohistochemistry against 78 GBM-associated proteins was performed. Expression levels of each protein for each patient were analyzed using an image analysis program and converted to H-score [summation of the intensity grade of staining (0–3) multiplied by the percentage of positive cells corresponding to each grade]. Based on H-score and hierarchical clustering methods, we divided the GBMs into two groups (n=19 and 37) that had significantly different survival lengths (p<0.05). In the two groups, expression of nine proteins (survivin, cyclin E, DCC, TGF-β, CDC25B, histone H1, p-EGFR, p-VEGFR2/3, p16) was significantly changed (q<0.05). Prognosis-predicting potential of these proteins were validated with another independent library of 82 GBM TMAs and a public GBM DNA microarray dataset. In addition, we determined 32 aberrant or mislocalized subcellular protein expression patterns in GBMs compared with relatively normal brain tissues, which could be useful for diagnostic biomarkers of GBM. We therefore suggest that these proteins can be used as predictive biomarkers and/or potential therapeutic targets for GBM.
biomarker; therapeutic target; glioblastoma; tissue micro-array; bioinformatics; automated image analysis
The aim of this study was to assess the safety and efficacy of radiation-sterilized allografts of iliac bone and fascia lata from cadaver specimens to repair skull base defects after transsphenoidal surgery.
Between May 2009 and January 2010, 31 consecutive patients underwent endonasal transsphenoidal surgery and all patients received sellar reconstruction using allografts following tumor removal. The allografts were obtained from the local tissue bank and harvested from cadaver donors. The specimens used in our approach were tensor fascia lata and the flat area of iliac bone. For preparation, allografts were treated with gamma irradiation after routine screening by culture, and then stored at -70℃.
The mean follow-up period after surgery was 12.6 months (range, 7.4-16 months). Overall, postoperative cerebrospinal fluid (CSF) leaks occurred in three patients (9.7%) and postoperative meningitis in one patient (3.2%). There was no definitive evidence of wound infection at the routine postoperative follow-up examination or during re-do surgery in three patients. Postoperative meningitis in one patient was improved with the use of antibiotics and prolonged CSF diversion.
We suggest that allograft materials can be a feasible alternative to autologous tissue grafts for sellar reconstruction following transsphenoidal surgery under selected circumstances such as no or little intraoperative CSF leaks.
Endoscopic endonasal approach; Transsphenoidal approach; Allograft; Sellar reconstruction; CSF leak
Recently, combination of surgery and radiation therapy (RT) has been recommended in the treatment of craniopharyngioma. RT could be associated with late complications, including vasculopathy. We report two cases of the moyamoya syndrome seen in children with craniopharyngioma who received RT after surgical resection. Thirty-five patients in pediatric age with craniopharyngioma were surgically treated. Fifteen out of 35 patients underwent surgical resection followed by RT or gamma knife surgery. Two of the 15 were found to have symptoms of transient ischemic attack and were diagnosed as moyamoya syndrome through the cerebral angiography. Age at RT was 4 and 13 years, respectively. The latent period for development of the moyamoya syndrome was 27 months and 3 years, respectively, after RT. The RT dose of both patients was 54 Gy. These two patients received bilateral encephaloduroarteriosynangiosis procedures. We report here these two cases of radiation-induced moyamoya syndrome in pediatric craniopharyngioma. Pediatric patients with craniopharyngioma who received RT should be reminded, during follow-up, about the risk of development of the moyamoya syndrome.
Moyamoya syndrome; Craniopharyngioma; Radiation; Vasculopathy
Intrathecal methotrexate (MTX) therapy combined with whole brain radiotherapy (WBRT) is one of the major treatment modalities for leukemia and lymphoma involving the central nervous system (CNS). The purpose of this study was to retrospectively determine the incidences of leukoencephalopathy and disseminated necrotizing leukoencephalopathy (DNL) following intrathecal MTX therapy for CNS lymphoma or leukemia and to assess the potential risk factors.
Between January 2000 and August 2009, 143 patients with CNS lymphoma or leukemia received intrathecal MTX therapy alone or in combination with WBRT at a single institution. Patients were followed up clinically and radiologically at regular two- or three-month intervals. Medical records were reviewed to obtain information regarding the patients' demographics, medical histories, radiologic characteristics, treatments, and clinical courses.
On follow-up MR images, leukoencephalopathy was found in 95 of 143 patients (66.4%). The median time to develop leukoencephalopathy was 6.6 months. Among those with leukoencephalopathy, four patients showed seven extensive white-matter changes with strongly enhancing lesions demonstrating DNL. Histological confirmation was done in six lesions of three patients and radiological diagnosis alone in one patient. Four lesions spontaneously disappeared on MR images without any treatment, with a mean duration of 14 months before disappearance of DNL.
Leukoencephalopathy is a common phenomenon that occurs following intrathecal MTX therapy; however, DNL occurs at a very low incidence. For newly developed enhancing lesions, consideration for the occurrence of DNL should be taken to avoid unnecessary invasive procedures or therapies.
Leukoencephalopathy; Methotrexate; Intrathecal; Lymphoma; Leukemia
The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain.
From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed.
The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months).
GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy.
Small cell lung carcinoma; Radiosurgery; Gamma knife; Metastasis
We describe here the first case of a concurrent brain abscess caused by Norcardia spp. and semi-invasive pulmonary aspergillosis in an immunocompetent patient. After one year of appropriate antimicrobial therapy and surgical drainage of the brain abscess, the nocardia brain abscess and pulmonary aspergillosis have resolved.
Brain nocardiosis; Semi-invasive pulmonary aspergillosis; Immunocompetent
This paper presents data from a retrospective study of endoscopic third ventriculostomy (ETV) in patients with shunt malfunction and proposes a simple and reasonable post-operative protocol that can detect ETV failure.
We enrolled 19 consecutive hydrocephalus patients (11 male and 8 female) who were treated with ETV between April 2001 and July 2010 after failure of previously placed shunts. We evaluated for correlations between the success rate of ETV and the following parameters : age at the time of surgery, etiology of hydrocephalus, number of shunt revisions, interval between the initial diagnosis of hydrocephalus or the last shunt placement and ETV, and the indwelling time of external ventricular drainage.
At the time of ETV after shunt failure, 14 of the 19 patients were in the pediatric age group and 5 were adults, with ages ranging from 14 months to 42 years (median age, 12 years). The patients had initially been diagnosed with hydrocephalus between the ages of 1 month 24 days and 32 years (median age, 6 years 3 months). The etiology of hydrocephalus was neoplasm in 7 patients; infection in 5; malformation, such as aqueductal stenosis or megacisterna magna in 3; trauma in 1; and unknown in 3. The overall success rate during the median follow-up duration of 1.4 years (9 days to 8.7 years) after secondary ETV was 68.4%. None of the possible contributing factors for successful ETV, including age (p=0.97) and the etiology of hydrocephalus (p=0.79), were statistically correlated with outcomes in our series.
The use of ETV in patients with shunt malfunction resulted in shunt independence in 68.4% of cases. Age, etiology of hydrocephalus, and other contributing factors were not statistically correlated with ETV success. External ventricular drainage management during the immediate post-ETV period is a good means of detecting ETV failure.
Shunt failure; Secondary endoscopic third ventriculostomy; Hydrocephalus
The prognosis for patients with recurrent glioblastomas (GBMs) is dismal, with a median survival of 3–6 months. We performed a phase II trial of low-dose continuous (metronomic) treatment using temozolomide (TMZ) for recurrent GBMs. TMZ-refractory patients with GBM who experienced disease recurrence or progression during or after the cyclic treatment schedule of TMZ after surgery and standard radiotherapy were eligible. This phase II trial included 2 cohorts of patients. The initial cohort, comprising 10 patients, received TMZ at 40 mg/m2 everyday. After this regimen seemed safe and effective, the metronomic schedule was changed to 50 mg/m2 everyday. The second cohort, comprising 28 patients, received TMZ at 50 mg/m2 everyday. The 6-month progression-free survival in all 38 patients was 32.5% (95% CI: 29.3%–35.8%) and the 6-month overall survival was 56.0% (95% CI: 36.2%–75.8%). One patient developed a grade III neutropenia, grade II thrombocytopenia in 3 patients, and grade II increase of liver enzyme (GOT/GPT) in 3 patients. Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis. In a response group, quality of life measured with short form-36 was well preserved, when compared with the pretreatment status. Metronomic treatment of TMZ is an effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.
glioblastoma; metronomic; recurrent
Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC.
Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.
Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).
Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.
It is usually difficult to perform the neuroendoscopic procedure in patients without hydrocephalus due to difficulties with ventricular cannulation. The purpose of this study was to find out the value of navigation guided neuroendoscopic biopsy in patients with peri- or intraventricular tumors without hydrocephalus.
Six patients with brain tumors without hydrocephalus underwent navigation-guided neuroendoscopic biopsy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by chemotherapy and/or radiotherapy as the first line treatment, or establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy.
Under the guidance of navigation, targeted lesion was successfully approached in all patients. Navigational tracking was especially helpful in entering small ventricles and in approaching the third ventricle through narrow foramen Monro. The histopathologic diagnosis was established in all of 6 patients : 2 germinomas, 2 astrocytomas, 1 dysembryoplastic neuroepithelial tumor and 1 pineocytoma. The tumor biopsy sites were pineal gland (n = 2), suprasellar area (n = 2), subcallosal area (n = 1) and thalamus (n = 1). There were no operative complications related to the endoscopic procedure.
Endoscopic biopsy or resection of peri- or intraventricular tumors in patients without hydrocephalus is feasible. Image-guided neuroendoscopic procedure improved the accuracy of the endoscopic approach and minimized brain trauma. The absence of ventriculomegaly in patients with brain tumor may not be served as a contraindication to endoscopic tumor biopsy.
Neuroendoscopy; Navigation; Without hydrocephalus
The purpose of this study was to examine the efficacy and safety of microvascular decompression (MVD) for hemifacial spasm (HFS) in elderly patients.
Between 1997 and June 2008, 1,174 patients had undergone MVD for HFS at our institute. Among these, 53 patients were older than 65 years. We retrospectively reviewed and compared the complication and the cure rates of these patients with those of younger patients.
There were 38 females and 15 males. The mean duration of symptoms of HFS of these patients was 94.6 months (range, 12-360 months), compared with 67.2 months (range, 3-360 months) in the younger group. The overall cure rate in elderly patients who underwent MVD for HFS during this period was 96.2%. Permanent cranial nerve dysfunctions, such as hearing loss and facial palsy, were seen in 2 patients (3.8%, 2/53) in the elderly group and 19 patients (1.7%, 19/1121) in the younger group. The difference in permanent cranial nerve dysfunction between the two groups was not statistically significant. There was no operative mortality in either group.
Microvascular decompression is the most effective surgical modality available for the treatment of HFS. Results of this study indicate that such technique can be performed in the elderly without higher rates of morbidity or mortality. Any patient with HFS, whose general health is acceptable for undergoing general anesthesia, should be considered as a candidate for MVD.
Microvascular decompression; Hemifacial spasm; Elderly patients
Combined hyperative dysfunction syndrome (HDS) defined as the combination of HDSs such as trigeminal neuralgia (TN), hemifacial spasm (HFS) and glossopharyngeal neuralgia (GPN), which may or may not occur simultaneously on one or both sides. We reviewed patients with combined HDS and demonstrated their demographic characteristics by comparing them with those of patients with a single HDS.
Between October 1994 and February 2006, we retrospectively studied a series of 1,720 patients who suffered from HDS and found 51 patients with combined HDSs. We analyzed several independent variables in order to evaluate the prevalence and etiologic factors of combined HDS.
The combined HDS group accounted for 51 of 1,720 (2.97%) patients with HDS; 27 cases of bilateral HFS, 10 cases of bilateral TN and 14 cases of HFS with TN. Their mean age was 52.1 years (range, 26-79 years). There were 5 men and 46 women. Seven patients had synchronous and 44 patients metachronous onset of HDSs. By comparison of combined and single HDS groups, we found that age and hypertension were closely associated with the prevalence of combined HDS (p < 0.05).
This study revealed that combined HDS was very rare. Hypertension and age might be the most important causative factors to evoke combined HDS.
Combined hyperactive dysfunction syndrome; Prevalence; Hemifacial spasm; Trigeminal neuralgia; Etiology
The factors that influence the prognosis of patients with hemifacial spasm (HFS) treated by microvascular decompression (MVD) have not been definitely established. We report a prospective study evaluating the prognostic factors in patients undergoing MVD for HFS.
From January 2004 to September 2006, the authors prospectively studied a series of 293 patients who underwent MVD for HFS. We prospectively analyzed a number of variables in order to evaluate the predictive value of independent variables for the prognosis of patients undergoing MVD. The patients were followed-up at regular intervals and divided into as cured and unsatisfactory groups based on symptom relief. Uni- and multivariate analyses were performed using logistic regression models.
A total 273 of 293 (94.2%) patients achieved symptom relief within one year after the operation. Intraoperatively, the indentation of the root exit zone was observed in 259 (88.5%) patients. Uni- and multivariate analyses revealed that the symptoms at postoperative 3 months (p<0.001) and indentation of the root exit zone (p=0.036) were associated with good outcomes.
The intraoperative finding of root exit zone indentation will help physicians determine the prognosis in patients with HFS. To predict the prognosis of HFS, a regular follow-up period of at least 3 months following MVD should be required.
Hemifacial spasm; Microvascular decompression; Prognosis; Chronology
Hemifacial spasm (HFS) is characterized by tonic clonic contractions of the muscles innervated by the ipsilateral facial nerve. Compression of the facial nerve by an ectatic vessel is widely recognized as the most common underlying etiology. HFS needs to be differentiated from other causes of facial spasms, such as facial tic, ocular myokymia, and blepharospasm. To understand the overall craniofacial abnormalities and to perform the optimal surgical procedures for HFS, we are to review the prevalence, pathophysiology, differential diagnosis, details of each treatment modality, usefulness of brainstem auditory evoked potentials monitoring, debates on the facial EMG, clinical course, and complications from the literature published from 1995 to the present time.
Hemifacial spasm; Microvascular decompression; Craniofacial abnormalities
The authors hypothesized that the placement of the interspinous implant would show a similar clinical outcome to the posterior lumbar interbody fusion (PLIF) in patients having spinal stenosis with mild segmental instability and that this method would be superior to PLIF without significantly affecting degeneration at the adjacent segments. Forty two adult patients having degenerative spinal stenosis with mild segmental instabilit who underwent implantation of Coflex™ (Spine motion, Germany) or PLIF at L4-5 between January 2000 and December 2003 were consecutively selected and studied for one-year clinical outcome. At 12 months after surgery, both groups showed a significant improvement in the visual analogue scale score and Oswestry disability index score for both lower extremity pain and low back pain. However, the range of motion at the upper adjacent segments (L3-4) increased significantly after surgery in the PLIF group, which was not manifested in the Coflex™ group during the follow-up. The authors assumed that interspinous implantation can be an alternative treatment for the spinal stenosis with segmental instability in selected conditions posing less stress on the superior adjacent level than PLIF.
Spinal Stenosis; Outcome
The clinical outcome and prognostic factors of patients with synchronous brain metastases from non-small cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKS) were analyzed. A total of 35 patients with NSCLC underwent GKS as an initial treatment for metastatic brain lesions of synchronous onset. The period of survival and various prognostic factors such as age, gender, performance status, multiplicity of the brain lesions, intracranial tumor volume, and extent of the primary tumor were analyzed. The overall median survival time for this series was 12 months (range 0.75 to 43 months) from the diagnosis. Of the 21 patients who were no longer alive at the conclusion of this study, only 7 (33.3%) died of neurological causes. Multivariate analysis of these data revealed that N stage, whole-brain radiotherapy (WBRT), and chemotherapy were significant predictors for survival (p<0.05). Survival of patients with NSCLC and synchronous brain metastases is mainly dependent upon the progression of the systemic disease, provided that the cerebral lesions are treated adequately with local treatment modalities including radiosurgery. Application of radiosurgery as an initial treatment option and aggressive local and systemic modalities to control extracranial disease may improve survival.
Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Radiosurgery