Avoidance of ischemic complications after resection of a brain lesion based on intraoperative real-time recognition of the vasculature using laser speckle flow imaging.

OBJECTIVE To avoid ischemic complications, it is important to consider the arteries in resection planning for lesions such as a vascular intraparenchymal tumor and arteriovenous malformation. Here, the clinical application of laser speckle flow imaging (LSFI) as a complementary method for the management of mass lesion-related arteries during surgery was evaluated. METHODS LSFI was performed in 12 patients with mass lesion-related arteries and brain tumor or arteriovenous malformation. The portable LSFI device was centered over the surgical field, and the relative cerebral blood flow (CBF) before and after the temporary interruption of the arteries was measured through continuous recording. CBF fluctuations permitted the classification of 3 kinds of artery-a feeding artery (FA), a "passing through" artery (PA), and a combined FA and PA (FA+PA)-based on decreased relative CBF in the inner resection area and unchanged CBF in the surrounding area (FA), unchanged CBF in the inner area and decreased CBF in the surrounding area (PA), or decreased CBF in both areas (FA+PA). This information allowed the appropriate management of these arteries and avoidance of postoperative ischemic complications. RESULTS Good visualization of CBF in the surgical field and relative CBF measurements in the regions of interest were achieved in real time with excellent spatiotemporal resolution. In 11 patients (92%) and 20 regions of interest, a decline in CBF was observed after temporary interruption of the FA (n = 8), PA (n = 2), and FA+PA (n = 2) types. There was a significant average reduction in CBF of 15.3% ± 29.0%. There were no ischemic complications, and only 1 patient had a postoperative ischemic lesion caused by resection through an artery that could not be viewed by LSFI due to a positional problem. CONCLUSIONS LSFI permits noninvasive and rapid intraoperative real-time recognition of mass lesion-related vasculature. This information can be used to avoid ischemic complications as a procedure complementary to neurophysiological monitoring.

A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population.

Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLC-enriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy.

Pathological features of highly invasive glioma stem cells in a mouse xenograft model.

Glioma stem cells (GSCs) may be a source of tumor progression and recurrence after multimodal therapy, because of their high invasive potential. The purpose of this study was to compare the invasive and migratory properties of GSCs and non-GSCs and examine the distribution of these cells in a mouse xenograft model. Three GSC lines, G144, Y02, and Y10, cultured from human glioblastoma, were used in the study. Matrigel-invasion assays of infiltration and time-lapse studies of migration were performed for comparison of the GSCs with the corresponding differentiated non-GSC lines. Cells were also transplanted into mouse brain and the different distribution of GSCs and non-GSCs was examined in the tumor xenograft model. All 3 GSC lines had greater invasion and migration ability than the corresponding non-GSCs. In vivo, GSCs infiltrated more widely than non-GSCs and reached the contralateral hemisphere via the corpus callosum in the early stage of tumorigenesis. GSCs also primarily penetrated the subventricular zone (SVZ). GSCs have high invasive potential and tend to be present in the outer tumor bulk and infiltrate the contralateral hemisphere via the corpus callosum, in addition to penetrating the SVZ.

Characteristics of intraoperative abnormal hemodynamics during resection of an intra-fourth ventricular tumor located on the dorsal medulla oblongata.

Abnormal hemodynamics during extirpation of a para-medulla oblongata (MO) tumor is common and may be associated with direct vagal stimulation of the medullary circuit. However, resection of tumors on the dorsal MO may also induce hemodynamic instability without direct vagal stimulus. The objective of this study was to examine the characteristics of hemodynamic instability unrelated to vagal stimulus during dissection of an intra-fourth ventricular tumor with attachment to the dorsal MO. A retrospective analysis was performed in 13 patients. Abnormal hemodynamics were defined as a > 20% change from the means of the intraoperative mean arterial pressure (MAP) and heart rate (HR). Relationships of intraoperative hemodynamics were evaluated with various parameters, including the volume of the MO. Six patients (46.2%) had intraoperative hypertension during separation of the tumor bulk from the dorsal MO. The maximum MAP and HR in these patients were significantly greater than those in patients with normal hemodynamics (116.0 ± 18.0 mmHg versus 85.6 ± 6.5 mmHg; 124.3 ± 22.8 bpm versus 90.5 ± 14.7 bpm). All six cases with abnormal hemodynamics showed hemodynamic fluctuation during separation of the tumor bulk from the dorsal MO. The preoperative volume of the MO in these patients was 1.11 cc less than that in patients with normal hemodynamics, but the volume after tumor resection was similar in the two groups (5.23 cc and 5.12 cc). This suggests that the MO was compressed by the conglutinate tumor bulk, with resultant fluctuation of hemodynamics. Recognition of and preparation for this phenomenon are important for surgery on a tumor located on the dorsal MO.

Yolk sac tumor of the bilateral basal ganglia in a patient with Down syndrome.

We report a case of intracranial yolk sac tumor in a 17-year-old girl with Down syndrome who presented with left slowly progressive hemiparesis. Initial magnetic resonance imaging (MRI) showed a small area of ill-defined abnormal signal intensity without a mass in the bilateral basal ganglia. These findings progressed very slowly for 2 years, but then the lesion rapidly progressed to a huge mass on MRI 4 months after the previous scan. The patient subsequently underwent a blood examination and endoscopic biopsy, and was finally diagnosed with yolk sac tumor. Standard platinum-based chemotherapy and radiotherapy were performed as soon as practicable. The frequency of solid cancer in patients with Down syndrome is generally lower than that in individuals without this disorder. Brain tumor is also rare in Down syndrome, but half of these cases are germ cell tumors. Moreover, slowly progressive non-tumor-like lesions in the basal ganglia may also be germ cell tumors. Therefore, MRI signal abnormalities in the basal ganglia in patients with Down syndrome require careful and frequent follow-up scans based on the possibility of a germ cell tumor that may exhibit rapid growth.

[Lung cancer incidentally detected at the treatment of pneumothorax ; report of two cases].

We report 2 cases of lung cancer incidentally detected following pneumothorax. Case 1:A 40-year-old man complaining of dyspnea was admitted with right pneumothorax. Chest computed tomography (CT) after chest drainage showed a cavitary nodule with pleural indentations in the right lower lobe. It was indicated at surgery that pneumothorax was caused by perforation of the tumor into the pleural cavity. Right lower lobectomy was performed because the pathological diagnosis of the nodule was a large cell carcinoma. The final histopathological diagnosis was stage II A (pT2aN1M0). The patient died of recurrence 14 months after surgery. Case 2:A 47-year-old man who admitted with right pneumothorax was found to have a nodule with pleural indentations closely a bulla at the apex of the right lung by chest CT after chest drainage. Pneumothorax was indicated to be caused by rupture of the bulla at surgery. Right upper lobectomy was performed because the pathological diagnosis of the nodule was a squamous carcinoma. The final histopathological diagnosis was stage I A (pT1bN0M0). The patient is alive at 2 years after the operation without recurrence. Lung cancer detected following pneumothorax which was caused by perforation of the tumor is generally considered to have poor prognosis. Whereas, prognosis of lung cancer incidentally detected following pneumothorax depends on its staging.

Intracranial yolk sac tumor in a patient with Down syndrome.

The authors report a rare case of intracranial yolk sac tumor in a 13-year-old boy with Down syndrome who presented with left hemiparesis. Admission MR imaging revealed a tumor in the right basal ganglia. Serum α-fetoprotein was markedly elevated. Yolk sac tumor was diagnosed radiologically and serologically. The standard therapy for intracranial yolk sac tumor is platinum-based chemotherapy with concomitant radiotherapy. However, the authors used reduced-dose chemotherapy and asynchronized radiotherapy because of the well-known low tolerance of patients with Down syndrome to chemotherapy. This treatment was successful with no complications. Blood cancers are frequently associated with Down syndrome, whereas solid tumors occur less frequently in these patients, and the risk of chemoradiotherapy is unclear. The results indicate that dose-reduction therapy can be effective for treatment of a brain tumor in a patient with Down syndrome.

[Mediastinal goiter; report of a case].

A 76-year-old female was admitted to our hospital because of an abnormal shadow on chest computed tomography (CT) which showed the tumor extending from left lower end of the thyroid to the aortic window along the left side of the trachea, indicating the retrosternal goiter. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were within normal ranges. The tumor was resected through cervical collar incision and median sternotomy. The pathological diagnosis was an adenomatous goiter. The patient was discharged without complications.

[Catamenial pneumothorax; report of a case].

A 39-year-old woman was referred to our hospital because of pneumothorax related to menstruation. Chest X-ray showed right pneumothorax. Right thoracoscopy revealed 3 fenestrations on the diaphragm. Partial resection of the diaphragm including these lesions were performed. Intrathoracic minocycline was applied expecting pleural adhesion after surgery. Histopathological examination confirmed the presence of endometriosis on the resected diaphragm.

Stereotactic radiosurgery/radiotherapy for pituitary adenomas: a review of recent literature.

The recent clinical results are reviewed of stereotactic radiosurgery/radiotherapy for the treatment of pituitary adenomas. The outcomes of pituitary adenomas treated by stereotactic radiosurgery/radiotherapy with gamma knife, CyberKnife, or linear accelerator (LINAC) radiosurgery were evaluated from articles published after 2004. Each study was evaluated for the number of patients, radiosurgical parameter (marginal dose), length of follow up, tumor growth control, rate of hormonal normalization in secretary adenomas, and adverse events. After gamma knife radiosurgery, the tumor reduction rates varied from 42.3% to 89% in non-secreting adenomas. However, the tumor control rates in non-secreting adenomas were more than 90% in most studies. In growth hormone-secreting adenomas, the rates of insulin-like growth factor-1 normalization ranged from 36.9% to 82%. In adrenocorticotropin-secreting adenomas, the rates for 24-hour urine free cortisol normalization ranged from 27.9% to 54%. In prolactin-secreting adenomas, the prolactin normalization ranged from 17.4% to 50%. New hormonal deficits ranged from 0% to 34%. New visual deficits were relatively low. The number of patients treated with CyberKnife and LINAC radiosurgery/radiotherapy was small and follow-up periods were relatively short compared to those with gamma knife treatment, but the clinical outcomes after these therapies were similar to those after gamma knife therapy. Image-guided stereotactic radiosurgery/radiotherapy with the gamma knife, CyberKnife, or LINAC system is effective and safe against pituitary adenomas. Careful long-term follow up of the patients is necessary because of long-term anti-tumor effects and delayed adverse events.

Vaccine therapy with dendritic cells transfected with Il13ra2 mRNA for glioma in mice.

OBJECT: The Il13ra2 gene is often overexpressed in brain tumors, making Il13ra2 one of the vaccine targets for immunotherapy of glioma. In this study, using a mouse glioma model, the authors tested the hypothesis that vaccination using dendritic cells transfected with Il13ra2 mRNA induces strong immunological antitumor effects. METHODS: A plasmid was constructed for transduction of the mRNAs transcribed in vitro into dendritic cells. This was done to transport the intracellular protein efficiently into major histocompatibility complex class II compartments by adding a late endosomal/lysosomal sorting signal to the Il13ra2 gene. The dendritic cells transfected with this Il13ra2 mRNA were injected intraperitoneally into the mouse glioma model at 3 and 10 days after tumor cell implantation. The antitumor effects were estimated based on the survival rate, results of histological analysis, and immunohistochemical findings for immune cells. RESULTS: The group treated by vaccination therapy with dendritic cells transfected with Il13ra2 mRNA survived significantly longer than did the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing CD4+ and CD8+ T cells were found in the group vaccinated with dendritic cells transfected with Il13ra2 mRNA. CONCLUSIONS: These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with Il13ra2 mRNA for the treatment of malignant glioma.

Continuous hypertension and tachycardia after resection of a hemangioblastoma behind the dorsal medulla oblongata: relationship to sympathetic overactivity at the neurogenic vasomotor center.

A very rare case of continuous hypertension and tachycardia after excision of a cerebellar hemangioblastoma at the dorsal medulla oblongata is presented. This 21-year-old man was admitted to the authors' hospital with a headache and dizziness. Radiological examination revealed a tumor located behind the dorsal medulla oblongata and compressing it substantially. The tumor was completely resected, but after the surgery the patient experienced prolonged hypertension and tachycardia. Postoperative MR imaging showed a small injury at the dorsocaudal medulla that was located at the caudal site of the nucleus of the tractus solitarius (NTS). Because the NTS has been reported to play a central role in cardiovascular regulation along with the rostral ventrolateral medulla, the authors considered it possible that the NTS injury was the cause of the prolonged elevation of sympathetic tone.

Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma.

Subpopulations of tumorigenic cells have been identified in many human tumors, although these cells may not be very rare in some types of cancer. Here, we report that medulloblastomas arising from Patched-1-deficient mice contain a subpopulation of cells that show a neural precursor phenotype, clonogenic and multilineage differentiation capacity, activated Hedgehog signaling, wild-type Patched-1 expression, and the ability to initiate tumors following allogeneic orthotopic transplantation. The normal neural stem cell surface antigen CD15 enriches for the in vitro proliferative and in vivo tumorigenic potential from uncultured medulloblastomas, supporting the existence of a cancer stem cell hierarchy in this clinically relevant mouse model of cancer.

Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens.

Human brain tumors appear to have a hierarchical cellular organization suggestive of a stem cell foundation. In vitro expansion of the putative cancer stem cells as stable cell lines would provide a powerful model system to study their biology. Here, we demonstrate routine and efficient derivation of adherent cell lines from malignant glioma that display stem cell properties and initiate high-grade gliomas following xenotransplantation. Significantly, glioma neural stem (GNS) cell lines from different tumors exhibit divergent gene expression signatures and differentiation behavior that correlate with specific neural progenitor subtypes. The diversity of gliomas may, therefore, reflect distinct cancer stem cell phenotypes. The purity and stability of adherent GNS cell lines offer significant advantages compared to "sphere" cultures, enabling refined studies of cancer stem cell behavior. A proof-of-principle live cell imaging-based chemical screen (450 FDA-approved drugs) identifies both differential sensitivities of GNS cells and a common susceptibility to perturbation of serotonin signaling.

Benign fibrous histiocytoma of the skull with increased intracranial pressure caused by cerebral venous sinus occlusion.

The authors present a very rare case of benign fibrous histiocytoma of the skull with increased intracranial pressure caused by sinus occlusion. A 33-year-old woman was referred for investigation of a right occipital protrusion with tenderness and double vision. She had only mild divergence insufficiency and bilateral papilledema neurologically. Imaging findings showed that the skull tumor was located at the right occipital bone with bone disruption and a compressed right sigmoid sinus. When planning the resection, caution was required to spare the collateral flow so as to manage the intracranial pressure. Immunohistochemical analysis showed that the tumor was positive for CD68, alpha1-antichymotrypsin, and alpha1-antitrypsin. From these findings, the tumor was diagnosed as a primary benign fibrous histiocytoma of the skull.

Cause of hematic cysts of the orbit: increased fibrinolysis and immunohistologic expression of tissue plasminogen activator.

PURPOSE: Hematic cysts of the orbit are relatively uncommon. These cysts expand gradually, leading to progressive orbital symptoms. To clarify the cause of hematic cyst, especially the mechanisms leading to its gradual expansion, we investigated the immunohistologic expression of tissue-type plasminogen activator (tPA), a key enzyme of fibrinolysis, in cases of hematic cysts. DESIGN: Retrospective small case series. PARTICIPANTS: Three patients with hematic cyst of the orbit were studied. METHODS: Three surgically removed hematic cysts were studied from a histologic perspective, including immunohistochemistry for tPA. The cyst content was also analyzed chemically. MAIN OUTCOME MEASURES: The pathologic features of hematic cyst of the orbit, expression of tPA in the cyst wall, and coagulation-fibrinolytic factors in the content of the cyst. RESULTS: The cyst wall was composed of dense collagen fibers lacking an epithelial lining and contained many fine capillary- or venule-like vessels. Hemosiderin-laden macrophages were observed among the collagen fibers. Strong immunoreactivity for tPA was revealed in the endothelial cells of the vessels in the cyst wall. Chemical analysis of the cyst content revealed a marked delay in the activated partial thromboplastin time and prothrombin time, a low fibrinogen concentration, and high concentrations of the D-dimer and tPA-plasminogen activator inhibitor-1 complex. CONCLUSIONS: Our findings indicate that blood coagulation and hemostasis occur first and that fibrinolysis occurs second in hematic cysts. Gradual expansion of the cyst may be due to hyperfibrinolysis resulting from oversecretion of tPA from the endothelial cells in the cyst wall, thus impairing normal hemostasis. Hemorrhage may then recur, resulting in enlargement of the hematic cyst. These mechanisms are similar to those occurring in chronic subdural hematomas. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

[MALT-type lymphoma of lacrimal gland: case report].

A 72-year-old female presented with a lump in the left superior-lateral eyelid. The magnetic resonance imaging showed a well-delineated mass in the left lacrimal gland. The tumor was isointense on both the T1 and T2 weighted images, and it was homogenously enhanced with Gd-DTPA. Surgery via the trans-cranial approach revealed a pinkish and elastic-hard tumor. Total resection was successfully performed. The hematoxilyn-eosin staining of the surgical specimen showed a dense infiltrate of lymphocytes, which were composed predominantly of small lymphocytes, centrocyte-like cells, monocytoid cells, and occasionally transformed lymphocytes. The immunohistochemical findings for CD20, CD3, UCHL-1, CD23, CD5, cyclinD1, and bcl-2 were compatible with Mucosa Associated Lymphoid Tissue (MALT)-type lymphoma. The patient received local radiation therapy (30 Gy/15 fractions). She remained in complete clinical remission of the disease about one and a half years after treatment.

Antitumor effects of vaccination with dendritic cells transfected with modified receptor for hyaluronan-mediated motility mRNA in a mouse glioma model.

OBJECT: The receptor for hyaluronan-mediated motility (RHAMM) is frequently overexpressed in brain tumors and was recently identified as an immunogenic antigen by using serological screening of cDNA expression libraries. In this study, which was conducted using a mouse glioma model, the authors tested the hypothesis that vaccination with dendritic cells transfected with RHAMM mRNA induces strong immunological antitumor effects. METHODS: The authors constructed a plasmid for transduction of the mRNAs transcribed in vitro into dendritic cells, which were then used to transport the intracellular protein RHAMM efficiently into major histocompatibility complex class II compartments by adding a late endosomal-lysosomal sorting signal to the RHAMM gene. The dendritic cells transfected with this RHAMM mRNA were injected intraperitoneally into the mouse glioma model 3 and 10 days after tumor cell implantation. The antitumor effects of the vaccine were estimated by the survival rate, histological analysis, and immunohistochemical findings for immune cells. Mice in the group treated by vaccination therapy with dendritic cells transfected with RHAMM mRNA survived significantly longer than those in the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing T cells activated by CD4+, CD8+, and CD25+ were found in the group vaccinated with dendritic cells transfected with RHAMM mRNA. CONCLUSIONS: These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with RHAMM mRNA for the treatment of malignant glioma.

Improvement of functional outcome after radical surgery in glioblastoma patients: the efficacy of a navigation-guided fence-post procedure and neurophysiological monitoring.

This retrospective study investigated the functional outcomes of patient with glioblastoma receiving radical surgery before and after the adoption of the navigation-guided fence-post (NGFP) procedure and neurophysiological monitoring. We investigated 42 glioblastoma patients receiving radical surgery in our institute between 1980 and 2005. Of the 42 patients, 18 patients from 1980 to 1996 (1st term) underwent radical surgery without navigation system guidance, NGFP, or neurophysiological monitoring; 11 patients from 1997 to 2002 (2nd term) underwent surgery with simple navigation system guidance but without NGFP procedure or neurophysiological monitoring, and 13 patients from 2003 to 2005 (3rd term) underwent surgery with the NGFP procedure and neurophysiological monitoring as appropriate. There were no significance differences between any of the three term groups in age, gender, preoperative KPS score, or 'surgical staging for glioma' according to the difficulty of surgery. The rates of 95% or greater volume reduction in each term were 38.9%, 54.5% and 76.9%. The rates of morbidity were 38.9%, 18.1% and 0%. The change in KPS scores (delta KPS) before and after the perioperative period in each term were -16.1 +/- 6.6 SEM, -9.0 +/- 5.8 SEM and +8.5 +/- 3.7 SEM, respectively. The delta KPS in the 3rd term was significantly better than those of 1st and 2nd terms (P < 0.01, Kruskal-Wallis rank test). The rate of patients who were discharged to home and who resumed daily useful life without assistance was 38.9%, 63.6% and 84.6% in each term, respectively. The mean survival times in each term were 9.9, 14.0 and 16.8 months. The introduction of the NGFP procedure and neurophysiological monitoring in glioblastoma radical surgery improved the functional outcome of patients.