Search

Standard treatment for patients with craniosynostosis is cranial remodeling surgery. If diagnosed early, minimally invasive surgery, such as suturectomy, is a good alternative, although it is sometimes difficult to diagnose craniosynostosis early because premature suture closure is not always radiologically obvious. In this study, we present two cases of five-month old infants who were conservatively treated for positional brachycephaly without any obvious premature suture closure on CT, who later developed progressive tower-like skull deformity despite conservative treatment for positional skull deformity. Both their fathers showed similar skull deformities. They underwent suturectomy at the site of the lambda, followed by molding helmet therapy based on a diagnosis of craniosynostosis. Histopathological specimens obtained from the resected sutures showed irregularly narrowed suture structure and ossification and fibrous tissue proliferation within it, supporting the diagnosis. The infants’ postoperative course was uneventful. The cephalic index of both the cases improved postoperatively. Conservative therapy-resistant progressive occipital skull deformity can sometimes lead to secondary craniosynostosis, even if CT does not show premature suture closure.

Objective: Retethering is not an unusual operation for a congenital lumbosacral dysraphic spinal lesion. The present study aimed to assess a new surgical technique for preventing retethering. Surgical technique: After untethering the spinal cord, the pia mater or scar tissue at the caudal end of the conus medullaris is anchored to the ventral dura mater loosely using 8-0 thread, and the dura mater is closed directly. This technique is called ventral anchoring. Results: Ventral anchoring was performed in 15 patients (aged 5 to 37 years old, average age: 12.1 years old) between 2014 and 2021. All but one patient showed improvement or stabilization of the preoperative symptoms. No complication directly related to the procedure was observed. Postoperative MRI demonstrated that the dorsal subarachnoid space was restored in 14 patients but was undetectable or absent in three patients on follow-up MRI. No patients have experienced a recurrence of the tethered cord syndrome during the follow-up period. Conclusion: Ventral anchoring is effective for restoring the dorsal subarachnoid space after untethering the spinal cord. This preliminary study suggested that ventral anchoring has the potential to prevent the postoperative recurrence of tethered cord syndrome in patients with a congenital lumbosacral dysraphic spinal lesion.

A 50-year-old man and a 69-year-old woman with consciousness disturbance were diagnosed to have suffered from subarachnoid hemorrhage (SAH) involving the posterior fossa. In both cases, the initial 3D CT angiogram failed to reveal the SAH source in the vertebrobasilar system. Delayed 3D rotational angiography revealed aneurysms on unfamiliar aberrant arteries. One was a dissecting aneurysm located between the proximal part of the posterior inferior cerebellar artery and the distal part of the intracranial vertebral artery. It was trapped and resected; the patient subsequently presented with lateral medullary symptoms. The other aneurysm was between the distal posterior and the distal anterior inferior cerebellar artery. It was successfully embolized; there were no complications. We think that the aberrant aneurysm-harboring vessels encountered in these two patients were primitive arteries on or adjacent to the vertebrobasilar paramedian longitudinal axis and that they persisted past the embryologic stage. Such aneurysms arising from unfamiliar persistent arteries beside the brainstem are extremely rare but must be considered when the SAH source is not detected in the trunk of the vertebrobasilar system.

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, or Carmustine) wafers are intraoperatively implantable wafers used to achieve local tumor control. There is scarce data about the behavior of wafers in the long-term follow-up of implanted cases. We reviewed the data of 64 patients with newly diagnosed glioblastoma treated by surgery, BCNU wafers, radiation therapy, and temozolomide administration. This cohort included 55 patients who presented first recurrence, and 49 of them showed tumor progression to death. The MR imaging of each patient at the terminal stage and an autopsy case were used to elucidate the tumor progression pattern after the wafer implantation. We subdivided the first recurrence pattern into local, distant, and multifocal based on MR imaging or into infield, outfield, and marginal based on the radiation field. The first recurrence pattern was 33 patients (60%) with local, 13 (24%) with distant, and nine (16%) with multifocal recurrence, or 38 patients (69%) with infield, 13 (24%) with outfield, and four (7%) with marginal. The median and mean time intervals between MR imaging at the terminal stage and death were 2.0 and 2.3 months, respectively. Of note, 13 patients with first distant recurrence had no obvious radiological local tumor progression even at the terminal stage. Long-term follow-up after BCNU wafer implantation revealed that patients with first distant recurrence had long-lasting local tumor control until the terminal stage.

BACKGROUND Nonocclusive mesenteric ischemia (NOMI) causes intestinal necrosis due to irreversible ischemia of the intestinal tract. The authors evaluated the incidence of NOMI in patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysms, and they present the clinical characteristics and describe the outcomes to emphasize the importance of recognizing NOMI. OBSERVATIONS Overall, 7 of 276 consecutive patients with SAH developed NOMI. Their average age was 71 years, and 5 patients were men. Hunt and Kosnik grades were as follows: grade II, 2 patients; grade III, 3 patients; grade IV, 1 patient; and grade V, 1 patient. Fisher grades were as follows: grade 1, 1 patient; grade 2, 1 patient; and grade 3, 5 patients. Three patients were treated with endovascular coiling, 3 with microsurgical clipping, and 1 with conservative management. Five patients had abdominal symptoms prior to the confirmed diagnosis of NOMI. Four patients fell into shock. Two patients required emergent laparotomy followed by second-look surgery. Four patients could be managed conservatively. The overall mortality of patients with NOMI complication was 29% (2 of 7 cases). LESSONS NOMI had a high mortality rate. Neurosurgeons should recognize that NOMI can occur as a fatal complication after SAH.

The exact location of the leg motor area is still in debate due to the lack of landmarks such as 'precentral knob' in the medial cortex. This study tried to identify the leg motor area based on intraoperative neurophysiological data and neuroimaging techniques.Intraoperative data of somatosensory evoked potential (SEP) elicited by tibial nerve stimulation and motor evoked potential (MEP) of the leg muscles induced by direct cortical stimulation were recorded using subdural electrodes placed in the medial cortex. We displayed the neurophysiological data on the individual MR images and the MNI52.Definite N40-P40 phase reversal was observed with the shallow grooves in the medial cortex in 5 cases. Leg MEP was successfully obtained in all 12 cases preserving the leg motor function. Superimposed SEP and leg MEP data on the MNI152 indicated the leg motor area was predominantly located in the posterior two-thirds between the vertical lines passing through the anterior commissure and the posterior commissure (VCP).Our study revealed the location of the leg motor area and the presence of the 'medial central sulcus' in the medial cortex.The VCP can be useful landmark to identify the sensorimotor border in the medial cortex.

Opening the ventricular system during glioblastoma surgery is often necessary, but the consequent effect on the tumor microenvironment of glioblastoma remains unknown. Implantation of carmustine wafer enables direct drug delivery to the tumor site; however, the exact mechanism of the wafer's biodegradation process is unclear, and the available data is limited to in vivo non-human mammalian studies. We hypothesized that the ventricular opening affects the degradation process of the wafer and the glioblastoma tumor microenvironment.This study included 30 glioblastoma patients. 21 patients underwent carmustine wafer implantation during initial surgery. All patients underwent repeated surgical resection upon recurrence, allowing for pathological comparison of changes associated with wafer implantation. Immunohistochemical analyses were performed using CD68, TMEM119, CD163, IBA1, BIN1, and CD31 antibodies to highlight microglia, macrophages, and tumor vascularity, and the quantitative scoring results were correlated with clinical, molecular, and surgical variables, including the effect of the ventricular opening.The carmustine wafer implanted group presented significantly less TMEM119-positive microglia within the tumor (P = 0.0002). Simple and multiple regression analyses revealed that the decrease in TMEM119-positive microglia was correlated with longer intervals between surgeries and opened ventricular systems. No correlation was observed between age, methylated O6-methylguanine DNA methyltransferase promoter expression, and the extent of surgical resection.Our study findings strongly suggest that biomaterials may possess immunomodulation capacity, which is significantly impacted by the ventricular opening procedure. Furthermore, our data highlights the pathophysiological effects of the ventricular opening within the surrounding human brain, especially after the wafer implantation.

Although the synchronous occurrence of testicular seminoma and systemic sarcoidosis has been reported, that of intracranial germinoma and systemic sarcoidosis is unknown. A 26-year-old man presented with symptoms of panhypopituitarism and consciousness disturbance. Imaging demonstrated a large nodule in the upper right lung field and swelling of multiple bilateral pulmonary and mediastinal lymph nodes in addition to the bifocal pineal and suprasellar tumors with obstructive hydrocephalus. The pathological diagnosis of the intracranial bifocal tumors was pure germinoma, whereas that of the mediastinal lymph nodes was epithelioid granuloma. Three courses of chemotherapy using carboplatin and etoposide were administered, followed by whole ventricle irradiation. The intracranial tumors completely disappeared, but the lung nodule and mediastinal lymph nodes progressed. Whole-body fluorine-18-fluorodeoxyglucose positron emission tomography demonstrated accumulation in the mediastinal lymphadenopathy, lung masses, and multiple lymph nodes of the whole body. Transbronchial lung biopsy revealed epithelioid granuloma with multinucleated giant cells. In conjunction with the high blood concentration of angiotensin-converting enzyme and soluble interleukin-2 receptor, these findings established a diagnosis of sarcoidosis. This is the first report of synchronous occurrence of intracranial germinoma and sarcoidosis. Such coexistence is extremely rare, but we should mind that sarcoidosis can occur with intracranial germinoma.

The characteristic features of plasticity and heterogeneity in glioblastoma (GB) cells cause therapeutic difficulties. GB cells are exposed to various stimuli from the tumor microenvironment and acquire the potential to resist chemoradiotherapy. To investigate how GB cells acquire stem cell-like phenotypes, we focused on ribosomal proteins, because ribosome incorporation has been reported to induce stem cell-like phenotypes in somatic cells. Furthermore, dysregulation of ribosome biogenesis has been reported in several types of cancer. We focused on ribosomal protein S6, which promotes sphere-forming ability and stem cell marker expression in GB cells. We expect that investigation of dysregulation of ribosome biogenesis and extra-ribosomal function in GB will provide new insights about the plasticity, heterogeneity, and therapeutic resistance of GB cells, which can potentially lead to revolutionary therapeutic strategies.

BACKGROUND The authors report a rare case of coexistence of dural arteriovenous fistula (DAVF) and arteriovenous malformation (AVM), with a common trunk drainer from both DAVF and AVM in the left anterior cranial fossa (ACF) with simple DAVF in the right ACF. OBSERVATIONS A 63-year-old female presented with seizure. Cerebral angiography showed bilateral DAVFs in the ACF and AVM in the left frontal lobe. A dilated frontal vein acted as a simple drainer of the right DAVF. In contrast, a dilated vein with large varix was the common drainer of both the left DAVF and the AVM. During surgery, indocyanine green videoangiography was performed with direct observation. In the left ACF, the drainer occlusion of the DAVF resulted in partial shrinkage of the varix and decreased distal blood flow. Additional main feeder occlusion of the AVM could decrease the blood flow further, but not completely because of the residual pial supplies for the AVM. Finally, the nidus of the AVM with varix was removed by en bloc resection. LESSONS Neurosurgeons should be aware of the coexistence of DAVF and AVM with a common trunk drainer. Only simple occlusion of the drainer from DAVF is not sufficient, so removal of the AVM is essential.

BACKGROUIND Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. OBSERVATIONS The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2′-deoxyguanosine positivity, suggesting the presence of oxidative stress. LESSONS LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.

Background: Rosette-forming glioneuronal tumor (RGNT) is a rare tumor that arises primarily in the posterior fossa, with molecular features of FGFR1 mutation. A previous study reported that brainstem RGNT accounts for only 2.7% cases; therefore, midbrain RGNT is infrequent. Case Description: The authors encountered two cases of RGNT located in the midbrain tegmentum (Case 1: 23-year-old woman and Case 2: 18-year-old boy), both exhibiting similar cystic components with gadolinium-enhanced cyst walls on preoperative magnetic resonance imaging, surgically resected through the occipital transtentorial approach. Histological findings in both cases comprised two characteristic architectures of neurocytic and glial components, typical of RGNT. Molecular assessment revealed no FGFR1 mutation in the initial specimen, but revealed FGFR1 K656E mutation in the recurrent specimen in Case 1 and showed no FGFR1 mutation but showed TERT C228T mutation in Case 2. Neither case revealed IDH1/2, BRAF, H3F3A K27, H3F3A G34, or HIST1H3B K27 mutations. DNA methylation-based classification (molecularneuropathology.org) categorized both cases as RGNT, whose calibrated scores were 0.99 and 0.47 in Cases 1 and 2, respectively. Conclusion: Midbrain tegmentum RGNTs exhibited typical histological features but varied FGFR1 statuses with TERT mutation. RGNT in rare locations may carry different molecular alterations than those in other common locations, such as the posterior fossa.

The patient was a 79-year-old woman with a left breast mass. Magnetic resonance imaging showed a cystic mass with a diameter of 10×8 cm and an ulcer in the upper outer quadrant and the nipple-areola region of the left breast. Intracystic carcinoma was thus suspected. A mass with a diameter of 1 cm was found in the upper outer quadrant of the right breast. Needle biopsy revealed that a cystic mass in the left breast was diagnosed as a malignant phyllodes tumor. A mass in the right breast was diagnosed as Luminal A breast cancer. The clinical tumor stage was T1N0M0. Computed tomography showed no enlarged bilateral axillary lymph nodes. In the left breast, mastectomy was performed with extensive skin excision above the tumor. In the right breast, partial mastectomy was performed with sentinel lymph node biopsy. On postoperative pathological examination, the diagnosis of left breast tumor was triple-negative spindle-cell carcinoma. The pathological tumor stage was diagnosed as T4bNxM0. Taking into consideration treatment according to breast cancer stage and age, we selected 4 courses of weekly-paclitaxel, endocrine therapy, irradiation to the left chest wall, and irradiation to the residual right breast. The preoperative diagnosis was malignant phyllodes tumor. The postoperative diagnosis was switched from malignant phyllodes tumor to spindle-cell carcinoma. It was therefore difficult to determine the presence or absence of additional resection and postoperative treatment regimens. Even though the preoperative diagnosis was a malignant phyllodes tumor, surgical procedures such as sentinel lymph-node biopsy should be considered, taking into account the possibility of breast cancer.

Granulomatous mastitis is a chronic inflammatory disease of unknown causes that forms a breast mass and may be difficult to distinguish from breast cancer on imaging studies. The patient was a woman in her 50's. Needle biopsy was performed for a mass in the upper outer quadrant of the right breast and revealed granulomatous mastitis. Breast magnetic resonance imaging showed that the tumor was malignant. Taking into account that there is a difference between histologic findings and imaging findings and that surgery after steroid therapy for granulomatous mastitis is more likely to cause complications, we decided to perform lumpectomy. The definitive pathological diagnosis was a triple negative, pT1cN0cM0 medullary carcinoma. Postoperative adjuvant chemotherapy was performed. The absence of axillary lymph-node metastasis was confirmed by right axillary sentinel lymph-node biopsy. Radiotherapy was performed on the preserved breast region. Even if granulomatous mastitis is diagnosed, biopsy should be repeated while paying attention to biopsy methods if there is a difference between pathological findings and image findings.

Cerebral amyloid angiopathy-related inflammation(CAA-RI)is a rare condition thought to be caused by an inflammatory response to amyloid beta(Aβ)protein in the walls of the small arteries and capillaries of the cerebral cortex. A 73-year-old female presented with left hemiparesis and dysarthria. Fluid-attenuated inversion recovery(FLAIR)imaging disclosed progressive enlargement of infiltrative white matter abnormalities in the right temporo-occipito-parietal lobes. Interestingly, digital subtraction angiography(DSA)demonstrated early venous filling. Pathological examination of the biopsy specimen demonstrated lymphocytes infiltration surrounding the blood vessels and in the thickened walls with amyloid-beta deposition. The diagnosis given was CAA-RI. The patient was successfully treated with high dose corticosteroids and clinical improvement was associated with shrinkage of the high intensity lesion on FLAIR imaging. Early venous filling resolved on the follow-up DSA. Most patients with CAA-RI can be treated with corticosteroids. However, the clinical condition will worsen without appropriate treatment. Early diagnosis is the key. If an expanding disease of the white matter appears in an elderly patient, we should exclude other cerebrovascular diseases by DSA, followed by biopsy without delay. The present case demonstrated that early venous filling on DSA may appear until inflammation is resolved by the treatment of CAA-RI.

TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) is an atypical manifestation of multicentric Castleman's disease. Although overproduction of interleukin-6, vascular endothelial growth factor, and other cytokines may partially explain the pathophysiology of this rare syndrome, the precise mechanisms underlying the renal dysfunction associated with the condition remain unclear. Here, we describe a case of a 69-year-old male with TAFRO syndrome. He was treated with immunosuppressive agents and his renal function improved. Tapering of immunosuppressive agents resulted in a deterioration of renal function and an elevation of C-reactive protein. After 20 months of treatment, the patient died from tuberculous peritonitis and gastrointestinal bleeding. An autopsy revealed miliary tuberculosis, mediastinal lymphadenopathy, and gastric ulcers. Renal histopathology showed a membranoproliferative glomerulonephritis-like appearance. Almost all glomeruli showed lobular formations with mesangial proliferation and duplication of glomerular capillary walls on light microscopy. Immunofluorescence showed deposition of C1q and IgM along the glomerular capillary walls. Electron microscopy showed mesangial expansion and widening of the subendothelial space with a large number of electron-dense deposits. The glomerular lesions might be characteristic of TAFRO syndrome, and were regarded as the main cause of the patient's renal dysfunction.

We herein report the case of a 52-year-old man with stage IV lung adenocarcinoma. The patient was negative for epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated protein-like 4 (EML4) /anaplastic lymphoma kinase (ALK) rearrangement. He was treated with nivolumab as a third-line chemotherapy. After four cycles of nivolumab treatment, a partial response was observed in the brain and at the primary tumor site. Nivolumab treatment has been continued for 11 months without progression. Immunohistochemistry revealed that the programmed death-ligand 1 (PD-L1) expression was 0% (according to the tumor proportion score). Our case indicates that the efficacy of programmed cell death 1 inhibitors is not solely predicted by the PD-L1 status, and that immune checkpoint inhibitors might be effective for the treatment of central nervous system metastasis.

A 67-year-old male presenting with left exophthalmos and progressive visual disturbance was referred to our department. Tumors at the supraclavicular fossa and dorsal femoral region were resected at ages 27 and 45 years. His father and son had both been diagnosed with spinal tumors, and his son's tumor was pathologically diagnosed as a schwannoma. Brain MRI of his son demonstrated no intracranial tumor. Brain MRI of the patient revealed a multilobular tumor of 2 cm diameter compressing the optic nerve medially within the left muscle cone, and no other intracranial tumors. However, large masses lateral to the pharynx and intercostal nerve, as well as multiple spinal tumors were detected. Transcranial total resection of the intraorbital tumor was performed. The pathological diagnosis was consistent with a schwannoma. These clinical characteristics fulfilled the diagnostic criteria of familial schwannomatosis. The postoperative course was uneventful. His visual dysfunction and eye movement disorder resolved completely. The intraorbital tumor was believed to originate from the lacrimal nerve. Sequencing of all exons foriSMARCB1/iandiLZTR1/iusing DNA extracted from the tumor did not reveal any mutations. This case is the third report on familial schwannomatosis in Japan.

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

The patient was a 50-year-old woman. She had been diagnosed with bilateral breast tumors at another hospital 5 years previously and was followed up every 2 months. Ultrasonography showed hypoechoic masses in her breasts. The largest tumor in the right breast was 15mm in diameter and located in region A, while that in the left breast was 8mm in diameter and located in region B. Magnetic resonance imaging(MRI)showed multiple bilateral breast tumors. The largest tumor was 12mm in diameter and was suggestive of breast cancer. Core needle biopsies(CNB)of the largest tumors in both breasts were performed. Intraductal papilloma(IDP)and low-grade intraductal papillary carcinoma were diagnosed in the right and left breasts, respectively, on immunohistochemical staining. We performed left nipple-sparing mastectomy with sentinel lymph node biopsy and right tumor excision for diagnoses of carcinoma of the left breast(cTisN0M0)and IDP of the right breast. The histopathological diagnosis of the left breast tumor was pT1aN0M0, triple negative breast cancer with extensive intraductal components, and that of the right breast tumor was IDP with atypical ductal hyperplasia. Chemotherapy was administered postoperatively. Several studies have reported that peripheral IDP often coexists with or follows the development of carcinoma. Therefore, we should also closely follow-upthe patient's right breast.

Glioblastoma multiforme (GBM) contains heterogenous population of cells including a small population of GBM stem cells (GSCs), which potentially cause therapeutic resistance and tumor recurrence. GSCs harbored in special microenvironments, such as perinecrotic niche, perivascular niche, border niche. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. Stemness and chemo-radioresistance was promoted by not only additional mutation, but also microenvironment of GBM cells. Previously, we had reported that growth factors and cytokines secreted by oligodendrocyte lineage cells and macrophages/microglia induce stemness and chemo-radioresistance into GBM cells. Recently, Ito et al. reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans-differentiation toward multipotency. Ribosomal proteins exist intra- and extracellularly. There is a possibility that ribosomal proteins promote stemness into cancer cells, we focused on 40S ribosomal protein S6 (RPS6), which is related to cell proliferation in lung and pancreatic cancer, but not reported in GBM. RPS6 was significantly upregulated in high-grade glioma. SiRNA-mediated RPS6 knock-down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and stemness marker expression, such as Nestin and Sox2. RPS6 overexpression enhanced the tumorsphere potential of GSCs. Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data indicated that RPS6 was predominant detected at GSC niches, concurrently with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC-predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemo-radioresistance and GBM recurrence. These results suggested that intercellular communications through growth factors, cytokines, and ribosomes are regarded as new treatment targets of GBM.

Background: If the brain tumor is suspected to be a primary central nervous system lymphoma (PCNSL) on radiological findings, it is general to perform biopsy to obtain the pathological diagnosis. Glioblastomas (GBs) must be distinguished from PCNSLs. In addition to commonly used contrast-enhanced T1-weighted imaging, diffusion-weighted image (DWI), and apparent diffusion coefficient (ADC) value, the following characteristics of PCNSLs were reported to be essential for this purpose: 1) no increase in blood flow on perfusion images obtained by the arterial spin labeling (ASL) method; 2) less microbleeding on T2*-weighted images (T2*). However, we experienced some exceptional cases. Purpose: To clarify the histopathological features of PCNSLs those had atypical radiological findings. Method: 62 consecutive PCNSL cases (40 males, 22 females, mean age 65.4 years, range 35–84) treated in our department from April 2013 to March 2020 were retrospectively analyzed. We compared the following features between 47 biopsy cases showing typical image findings as PCNSLs (Group A) and 15 surgically resected cases with atypical findings (Group B), 1) number of blood vessels per hyper 10 fields, 2) occupying area of blood vessels per unit area, 3) immunoreactivity of vascular endothelial growth factor (VEGF), and 4) germinal center B-cell (GCB) subtype. Results: In Group A, the number of blood vessels in the tumor was 39.3 on average, and the area occupied by blood vessels was 3.8%. In Group B, the former was 133.2, and the latter was 9.9%. There was no significant difference in VEGF expression and GCB subtype. Conclusion: In PCNSLs showing with high blood flow and microbleeds, the blood vessels were rich and partial bleeding was confirmed histologically. We should analyze much more cases to set the threshold both of the ADC value and the absolute value of blood flow calculated by the ASL method to distinguish between PCNSLs and GBs.

Background Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare clinical entity. We report an unusual case of intraparenchymal bifrontal CAPNON coexisting with interhemispheric lipoma and agenesis of the corpus callosum. Case Description A 64-year-old woman presented with slight weakness of her left leg. Computed tomography and magnetic resonance imaging showed massive nodular intraparenchymal calcifications at both sides of the interhemispheric lipoma associated with partial agenesis of the corpus callosum. Enhancement was observed at the periphery and within the calcification. Massive perifocal edema was also demonstrated. The enhanced lesion with calcification was partially resected. Histologic analysis of the resected specimen disclosed nodular calcification with fibro-osseous components and histiocytic reaction, consistent with CAPNON. A high ratio of M2 macrophages was observed among the infiltrating macrophages. 11C-methionine positron emission tomography demonstrated high uptake of the tracer at the lesion corresponding to the calcified lesion on computed tomography. Postoperatively, massive perifocal edema was decreased and maintained without progression for a year. Conclusions The high M2 macrophage activity verified by histopathologic analysis suggests that CAPNON is not a silent but a more active, tumefactive disease involving the immune response. This hypothesis may be supported by the high uptake of 11C-methionine positron emission tomography.

We report our experience with a patient with breast cancer who showed recurrence in the nipple skin 5 years and 10 months after a breast-preserving surgery. The patient was a woman, and was 65-years old at the time of initial surgery. Breast-preserving surgery and axillary lymph-node dissection were performed for left breast cancer. Invasive ductal carcinoma of the breast(pT3N0M0)was triple-negative, and the patient postoperatively received adjuvant chemotherapy. Left breast pain developed 5 years and 6 months after surgery. Computed tomography showed no evidence of recurrence, and the symptoms resolved after treatment with non-steroidal anti-inflammatory drugs(NSAIDs). After 3 months, however, the left nipple had enlarged to about 1.5 cm, and the surrounding skin was red and painful. Treatment with NSAIDs was thus resumed. After 1 week, redness of the nipple skin and pain were improved. However, the nipple had enlarged to twice its normal size. Nipple skin biopsy was subsequently performed, and revealed adenocarcinoma invading the skin. Left axillary lymph-node metastasis was suspected, but there was no evidence of metastasis to other sites or recurrence. Conservative total mastectomy with axillary lymph-node dissection was thus performed. The histopathological diagnosis was the recurrence of invasive ductal carcinoma, arising mainly in the reticular layer of the dermis. Chemotherapy was administered postoperatively. There has been no evidence of recurrence as of 1 year after surgery.

The patient was a 51-year-old woman with a mass in the left breast.At the first presentation, she had abdominal distension and liver dysfunction.Mammography showed a category 5 mass in the left breast and a category 4, unstructured region in the right breast.Pathological examination revealed bilateral, invasive ductal carcinomas.Stage II B disease(clinical T2N1M0)was diagnosed in the left breast, and Stage I disease(clinical T1N0M0)was diagnosed in the right breast.Computed tomography revealed a massive uterine myoma compressing the inferior vena cava.Liver dysfunction was suspected to be caused by these factors.Preoperative chemotherapy was scheduled to treat breast cancer.A gynecologist stated that "uterine myoma is unlikely to cause liver dysfunction" and refused to perform a hysterectomy.However, we diligently negotiated with him to avoid chemotherapy-induced venous thrombosis and pulmonary infarction; eventually, a hysterectomy(3.6 kg)was performed. After surgery, liver function was normal.Subsequently, breast cancer could be safely and adequately treated.In patients who have benign disease, as well as malignant tumors, treatment of the malignant tumors is generally given the highest priority.However, there are cases when the treatment of benign disease has priority over the treatment of malignant tumors.It is therefore important to intensively discuss such cases with physicians from other departments.

The carmustine (BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. Biomaterials to treat cancers hold therapeutic potential; however, how they behave inside the tumor microenvironment requires further study. We previously investigated the tumor microenvironment after BCNU wafer implantation, and found that CD68-positive macrophage was significantly introduced around the wafer (Shibahara et al. J Neurooncol 2018). Recent studies demonstrated the importance of tumor-associated macrophage (TAM). However, we could not clarify whether the increased macrophage around the wafer was pro-tumor or anti-tumor phenotype. In the present study, we immunohistochemically examined expressions of CD68, IBA1, CD163, TMEM119, BIN1, CD31, and VEGF to investigate TAM after the wafer implantation. Quantitative evaluation revealed that CD68+ cells were significantly increased (P = 0.0009), whereas TMEM119+ cells were significantly decreased (P = 0.0081) after wafer implantation compared to tissue from cases without wafer implantation. CD163, a known marker of poor prognosis in glioblastoma, did not differ with and without wafer implantation. Among factor analyzed, BCNU wafer did not induce protumor TAM, but reduced microglial marker, TMEM 119. In addition to the aspect of chemotherapy, BCNU wafer may have potential to modify the tumor microenvironment such as TAM.

Pseudopalisades (Ps) around necrotic foci are severely hypoxic and overexpress hypoxia-inducible factor (HIF) in glioblastoma (GBM). Hypoxic regions have been proposed as one of several distinct niches for cancer stem cells (CSCs) in GBM, but little is known about the association between Ps features and CSC properties. Herein, we focused on the biological role of Ps lesions. In clinical cases of GBM, expression of hypoxia-related molecules including HIF-1α, Glut-1, p27(Kip1), and pAkt was significantly increased in perinecrotic Ps lesions compared with nonnecrotic areas and perinecrotic lesions lacking Ps features. Significantly higher expression levels of several CSC-related markers, including CD133, Sox2, CD44s, and aldehyde dehydrogenase (ALDH) 1, were also observed in Ps lesions, which were positively correlated with expression of hypoxia-related molecules and pAkt. Ps lesions also showed increased number of apoptotic cells and decreased bcl-2 and survivin expression compared with the surrounding tissue. Short-term exposure of astrocytoma cell lines to cobalt chloride, which is known to mimic the effect of hypoxia, caused an increase in expression of both hypoxia- and CSC-related markers, in line with increases in the ALDH(high) cell population and number of spheroids. Inhibition of endogenous Akt by LY294002 resulted in decreased expression of Sox2, ALDH1, and CD133, leading to enhancement of cobalt chloride-mediated apoptotic events due to altered ratio of bcl-2 to bax expression. These findings suggest that Ps lesions within GBM may serve as a specialized hypoxic niche, in which the HIF-1α/pAkt axis is activated, in response to severe hypoxia.

Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence. We investigated radiological imaging; the interval between the two surgeries; and immunohistochemistry of CD3, CD4, CD8, CD20, CD68, FOXP3, and PD1. We implanted BCNU wafers in 41 newly diagnosed glioblastoma patients after approval of the wafer in Japan. Of them, 14 underwent surgery at recurrence and tissue was obtained from around the wafers. The interval between the first and second surgeries ranged from 63 to 421 days. The wafer could be observed on magnetic resonance imaging at up to 226 days, whereas intraoperatively the biodegraded material of the wafer could be found at up to 421 days after the initial surgery. Immunohistochemical analysis demonstrated that CD8+ and CD68+ cells were significantly increased, but FOXP3+ cells did not increase, after wafer implantation compared to tissue from cases without wafer implantation. MRI data and immune cells, as well as interval between surgeries and immune cells, demonstrated positive correlation. These results helped us to understand the bioactivity of bioengineered materials and to establish a new approach for immunotherapy.

The carmustine (BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. Biomaterials to treat cancers hold therapeutic potential; however, how they behave inside the tumor microenvironment requires further study. We previously investigated the tumor microenvironment after BCNU wafer implantation, and found that CD68-positive macrophage was significantly introduced around the wafer (Shibahara et al. J Neurooncol 2018). Recent studies demonstrated the importance of tumor-associated macrophage (TAM). However, we could not clarify whether the increased macrophage around the wafer was pro-tumor or anti-tumor phenotype. In the present study, we immunohistochemically examined expressions of CD68, IBA1, CD163, TMEM119, BIN1, CD31, and VEGF to investigate TAM after the wafer implantation. Quantitative evaluation revealed that CD68-positive cells were significantly increased (P = 0.0009), whereas TMEM119-positive cells were significantly decreased (P = 0.0081) after wafer implantation compared to tissue from cases without wafer implantation. CD163, a known marker of poor prognosis in glioblastoma, did not differ with and without wafer implantation. Among factor analyzed, BCNU wafer did not induce protumor TAM, but reduced microglial marker, TMEM119. In addition to the aspect of chemotherapy, BCNU wafer may have potential to modify the tumor microenvironment such as TAM.

Uterine carcinosarcomas (U-CSs) are considered monoclonal in origin, but little is known about the mechanisms for establishment of heterologous sarcomatous components. Here, we examine the functional roles of nuclear factor κB (NF-κB)/p65 and Sox9 in the transcriptional regulation of alpha-1 type II collagen (COL2A1), a hallmark of chondrogenesis, during morphologic change in the direction of the chondrocytic phenotype. In 32 cases of U-CS, both phosphorylated p65 and Sox9 expression were colocalized in Col2A1-positive sarcomatous components, particularly in cartilaginous elements, with strongly positive correlation (ρ = 0.72, P = .005). A positive association of Col2A1 expression between protein (immunohistochemistry) and messenger RNA (in situ hybridization) assays was evident in sarcomatous components, whereas 9 cases also showed distinct positive signals for the messenger RNA without protein expression in carcinomatous elements, probably through a posttranscriptional and/or posttranslational modulation mechanism. In the Ishikawa endometrial cancer line, overexpression of p65 could activate transcription of COL2A1 promoter-intron reporters through binding to specific NF-κB sites in the first intron, along with up-regulation of Sox9. Exogenous induction of Sox9 also caused an increase in transcription of COL2A1, in contrast to a repression of the p65-mediated COL2A1 transcription, suggesting the existence of a negative feedback loop. These data, therefore, suggest that NF-κB/p65 signaling, as well as Sox9, may contribute to changes in the morphology of U-CS cells toward the chondrocytic phenotype through modulation of COL2A1 transcription.

The patient was a 68-year-old woman who received neo-adjuvant chemotherapy(4 courses of weekly paclitaxel plus bevacizumab and 4 courses of 5-fluorouracil epirubicin, and cyclophosphamide)for cT1N1M0, Stage II A right-sided triplenegative breast cancer(TNBC). Right breast-conserving surgery with axillary lymph-node dissection was performed. The postoperative pathological diagnosis was a complete response. Six months after surgery, the patient developed lower and right-sided back pain. Detailed examination revealed multiple metastases to the liver, bone, lymph nodes of the mediastinum, and bile duct. The recurrence was treated with biweekly paclitaxel plus bevacizumab. The patient's pain dramatically improved. However, the duration of the response was only 3 months. The patient received eribulin as a second-line treatment, but did not respond and subsequently died. TNBC is considered to have relatively good outcomes if a pathological complete response(pCR)is obtained after preoperative chemotherapy. However, recurrence occurred after only 6months in our patient. In patients with TNBC, physical examinations and simple laboratory tests should be performed every 1 to 2 months after surgery, even if a pathological complete response is obtained. We used paclitaxel plus bevacizumab to treat recurrence of TNBC. Although this treatment did not prolong overall or disease-free survival, the patient temporarily responded, and her quality of life was maintained. Further studies are needed to elucidate the pathogenesis of TNBC and to develop more effective treatments.

FilGAP, a Rac‐specific Rho‐GTPase‐activating protein (GAP), acts as a mediator of Rho/ROCK‐dependent amoeboid movement, and its knockdown results in Rac‐driven mesenchymal morphology. Herein, we focused on the possible roles of FilGAP expression in astrocytomas. In clinical samples, FilGAP expression was significantly increased in grade (G) II astrocytomas as compared to normal astrocytes, but its expression strongly decreased in a grade‐dependent manner, and was positively associated with isocitrate dehydrogenase 1 (IDH1) mutations and inversely to cytoplasmic Rac1. Patients with astrocytoma showing a high FilGAP score had favorable overall survival as compared to the low score patients. Multivariate Cox regression analysis also showed that a high FilGAP score was a significant and independent favorable prognostic factor. Moreover, patients with high FilGAP score and IDH1 mutant‐type astrocytomas had significantly the best Overall survival (OS) and Progression‐free survival (PFS), in contrast to the patients with low FilGAP score and wild‐type IDH1 tumors who had the worst prognosis. In GIV tumors (GBM: glioblastomas), elongated tumor cells with low FilGAP expression were frequently observed in tumor core lesions, whereas the rounded cells with abundant expression were found in the peripheral areas adjacent to non‐neoplastic brain tissues. In an astrocytoma cell line, suppression of endogenous FilGAP expression by siRNAs caused an increased proportion of mesenchymal elongated cells, probably through increased Rac1 activity. These findings suggest that FilGAP, as well as IDH1 status, may be useful for predicting the behavior of astrocytomas. In addition, the FilGAP/Rac1 axis may serve as an important regulator of tumor progression in GBMs, probably through alteration of cell morphology.

Object The transvenous approach via the inferior petrosal sinus (IPS) is commonly used as the most appropriate for carotid-cavernous fistula (CCF) or cavernous sinus sampling. However, sometimes the IPS is not accessible because of anatomical problems and/or complications, therefore an alternative route is needed. In this paper, the authors present and discuss the utility of a transvenous approach to the cavernous sinus via the inferior petrooccipital vein. Methods Four patients, 3 with dural CCFs and the other with Cushing disease, in whom endovascular surgical attempts failed using a conventional venous approach via the IPS, underwent a transvenous approach to the cavernous sinus via the inferior petrooccipital vein (IPOV). One dural CCF case had only cortical venous drainage, the second CCF also mainly drained into the cortical vein with slight inflow into the superior ophthalmic vein and inferior ophthalmic vein, and the third demonstrated drainage into the superior and inferior ophthalmic veins and IPOV. Results In all cases, the cavernous sinus could be accessed successfully via this route and without complications. Conclusions The transvenous approach to the cavernous sinus via the IPOV should be considered as an alternative in cases when use of the IPS is precluded by an anatomical problem and there are no other suitable venous approach routes.

Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection, using 5-aminolevulinic acid (5-ALA), is among the most valuable tools for determining tumor removal area. However, PPIX fluorescence is not necessarily achieved during an operation visually even when 5-ALA is used, and we do not know until tumor exposure to the excitation light of the ultraviolet region whether PPIX fluorescence has been achieved. When a particular biopsy and frozen section diagnosis is made, the reason for lack of PPIX fluorescence in the tissue cannot be judged. We do not know whether the tumor fails to fluoresce or no fluorescence is seen because it is not the main body of the tumor. We investigated whether the presence or absence of tumor fluorescence could be predicted by examining urinary porphyrin before surgery, at the time of intraoperative fluorescence diagnosis using 5-ALA. The urine of brain tumor patients 2 hours after 5-ALA administration was irradiated with a 405 ± 1 nm laser light. The patients were divided into a fluorescent urine group and negative fluorescent urine group. Red fluorescence was observed in response to the 405 ± 1 nm laser beam for all tumors in the fluorescent urine group. Clear red fluorescence was not observed even with 405 ± 1 nm laser beam irradiation in any tumors in the negative fluorescent urine group. Preoperative prediction of the intraoperative fluorescence of PPIX can be achieved by observation of urine 2 hours after 5-ALA administration with exposure to a 405 ± 1 nm laser light.

The aim of this retrospective study was to investigate the efficacy of saireito for bilateral chronic subdural hematomas (B-CSDH). Between April 2006 and March 2010, a total of 18 patients undergoing unilateral burr hole drainage for B-CSDH took part in a controlled clinical study. Postoperative status of the nonsurgical side was subsequently evaluated, with (n = 10) and without (n = 8) saireito administration. Two in the saireito-treated group patients and four in the control group patients ultimately required contralateral surgical intervention. The remainder, including eight saireito-treated hematomas, resolved without further surgery, generally within eight weeks of the surgical side procedure. However, two of the four resolving control lesions took longer to regress. The hydragogue and anti-inflammatory/steroid-evoking properties ascribed to saireito may facilitate hematoma resolution. After unilateral surgery for B-CSDH, saireito administration may prevent symptomatic deterioration of a contralateral low-density CSDH, preempting subsequent surgery.

The transvenous approach via the superior ophthalmic vein (SOV) is an available approach for carotid cavernous fistula (CCF), especially in the event that there is no other suitable approach route to the fistula. Surgical exposure of the peripheral roots of the SOV is commonly used; however, often, the SOV is often not accessible because of anatomical problems and/or complications. In this paper, we present and discuss our original direct-puncture approach to the extraconal portion of the SOV.An attempt on three patients with traumatic CCF failed with the transarterial approach and the conventional venous approach via the inferior petrosal sinus; therefore, the patients were treated with the direct-puncture approach to the extraconal portion of the SOV using two-dimensional digital subtraction angiography with local anesthesia.All cases that had tortuous and partially stenotic division of the SOV were treated successfully with this approach and without complications.This approach will become an alternate approach, especially when the peripheral roots of the SOV are focally narrowed and tortuous, making it impossible to insert a catheter.

The effects of consumption of grapefruit juice on the pharmacokinetics of conventional low-dose simvastatin in Japan were investigated. In a randomized cross-over study with two phases, 10 healthy volunteers ingested grapefruit juice 400ml or water for 2 days. On day 3, a single 5mg dose of simvastatin was administered with grapefruit juice 200ml or water. Plasma concentrations of HMG-CoA reductase inhibitor were determined up to 8 h thereafter. Grapefruit juice increased the area under the plasma concentration-time curves from 0 to 8 h of total HMG-CoA reductase inhibitor 1.7- fold (p=0.002) and that of active HMG-CoA reductase inhibitor 1.7-fold (p=0.024). However, the peak concentrations (Cmax) and Tmax of total and active HMG-CoA reductase inhibitors were not significant influenced.Consumption of grapefruit juice with low-dose simvastatin thus resulted in mild increase of the plasma HMG-CoA reductase inhibitor, so that the pharmacokinetic interaction can be labeled as of weak CYP3A type.

We report a rare case of a traumatic aneurysm which developed after clipping surgery with review of the relevant literature. Endovascular treatment using coiling and stent assistance taking into account technical considerations is described. Monitoring of the aneurysmal pressure showed marked decrease immediately after the stent emplacement.

A 55-year old female was referred to the Department of Neurosurgery, Kitasato Hospital, because of a hearing impairment. Neuroimaging revealed a typical meningioma attached to the falx in the right frontal region. During surgery, an encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the falx was completely removed by an interhemispheric approach. On light microscopy, many of the tumor cells contained eosinophilic inclusions with single or multiple vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were eccentric. There were no signs of malignancy in the specimen. Electron microscopy revealed that most of the eosinophilic inclusions were composed of filaments measuring 12 nm in diameter. There have been several reports of benign meningiomas with eosinophilic inclusions composed of intermediate filaments. The microscopic differences between these types of tumor and rhabdoid meningiomas are very subtle, and it is important the two types of tumors are not confused. Benign meningiomas with eosinophilic inclusions comprising intermediate filaments, for example the tumor described in this report, have been diagnosed as granulofilamentous meningiomas, which is a subtype of benign meningioma.

The transvenous approach via the inferior petrosal sinus (IPS) is commonly used as the most appropriate for carotid-cavernous fistula (CCF) or cavernous sinus sampling. However, sometimes the IPS is not accessible because of anatomical problems and/or complications, therefore an alternative route is needed. In this paper, the authors present and discuss the utility of a transvenous approach to the cavernous sinus via the inferior petrooccipital vein.Four patients, 3 with dural CCFs and the other with Cushing disease, in whom endovascular surgical attempts failed using a conventional venous approach via the IPS, underwent a transvenous approach to the cavernous sinus via the inferior petrooccipital vein (IPOV). One dural CCF case had only cortical venous drainage, the second CCF also mainly drained into the cortical vein with slight inflow into the superior ophthalmic vein and inferior ophthalmic vein, and the third demonstrated drainage into the superior and inferior ophthalmic veins and IPOV.In all cases, the cavernous sinus could be accessed successfully via this route and without complications.The transvenous approach to the cavernous sinus via the IPOV should be considered as an alternative in cases when use of the IPS is precluded by an anatomical problem and there are no other suitable venous approach routes.