"Paradoxical" findings of tumor vascularity and oxygenation in recurrent glioblastomas refractory to bevacizumab.

Anti-angiogenic therapy induces the apparent normalization of vascular structure, decreases microvessel density (MVD), and improves tumor oxygenation in glioblastomas (GBMs). Six initial and recurrent tumor pairs after bevacizumab (Bev) treatment were compared with GBMs from nine patients resected under neoadjuvant Bev treatment with regard to histological characteristics; MVD; MIB-1 index; and expression of vascular endothelial growth factor (VEGF) and its receptors, hypoxia markers (hypoxia-inducible factor 1 alpha, carbonic anhydrase 9), and nestin as a marker of glioma stem-like cells. In recurrent tumors post-Bev treatment, while the MVD remained low compared with the paired initial tumors (pre-Bev tumors), the expression of hypoxic markers were increased and were even higher in expression compared with the paired pre-Bev tumors in three of the six cases. MIB-1 indices were similar among the initial GBMs, neoadjuvant group, and recurrent tumors post-Bev treatment. The nestin-positive cell ratio of the post-Bev recurrent tumors was as high as that of the pre-Bev tumors. The expression of VEGF and VEGFR1 was increased in the post-Bev recurrent tumors in three and four cases, respectively, compared with the paired pre-Bev tumors. In the majority of Bev-refractory GBMs, tumor hypoxia was present with a paradoxical decrease in MVD. These findings suggest that re-activation of tumor angiogenesis is not initially involved in the acquisition of resistance to Bev.

A case report of surgical management of hemangiopericytoma at the foramen magnum.

BACKGROUND: Hemangiopericytoma (HPC) is a highly vascularized mesenchymal tumor known for its high rates of recurrence and metastasis. The extent of tumor removal is known to be the most trustful prognostic factor. Skull base HPCs are challenging to treat because of the difficulty of the surgical approach and proximity to vital vascular and neuronal structures. We successfully treated a case of HPC at the ventral foramen magnum through surgical gross tumor removal via a far-lateral transcondylar approach. CASE DESCRIPTION: A 38-year-old male complained of neck pain and bilateral paresthesia of his shoulders for 2 months, for which he was referred to our hospital. A magnetic resonance image (MRI) showed a 20 mm diameter mass at the ventral foramen magnum, which compressed his medulla oblongata. The tumor was gross totally removed via a far-lateral transcondylar approach. During the surgery, marked bleeding disturbed the surgical field until the main feeding artery from the direction of the dura mater was coagulated and cut. A relatively wide surgical field and a transcondylar approach were helpful to control the bleeding. The pathological examination revealed the tumor to be a HPC. After an uneventful recovery period of 9 days, the patient was discharged without neurological sequelae. CONCLUSION: We successfully and completely removed an HPC near the foramen magnum, employing a wide surgical field and a transcondylar approach to help control bleeding. When the tumor is suspected preoperatively to be a hemangiocytoma or vascular-rich tumor, a surgical approach that can secure a wide surgical field should be selected.

A case of glioblastoma resected immediately after administering bevacizumab: consideration on histopathological findings and safety of surgery.

Surgery after administering bevacizumab should be carefully considered particularly because of wound healing concerns. A 27-year-old man presented with multiple tumor recurrences after gross total removal of a left temporal oligodendroglioma (1p/19q-noncodeleted). Whole brain radiotherapy with concomitant temozolomide and bevacizumab was immediately prescribed; however, the patient's condition deteriorated because of brain herniation. Three days after administering bevacizumab, an emergency tumor removal with external decompression and a ventriculo-peritoneal shunt was performed. The surgery and postoperative clinical course were uneventful. On histopathological examination, the tumor showed findings such as tumor vessel thrombosis, numerous interstitial red blood cells, and cells with degraded, fragmented nuclei possibly suggesting apoptosis, which could be attributable to bevacizumab. Performing craniotomy shortly after administering bevacizumab is not recommended; however, it can still be safely performed as long as surgery and wound management is carefully performed. Vessel thrombosis might be among the mechanisms of action of bevacizumab.

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

BACKGROUND: Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. CASE DESCRIPTION: A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. CONCLUSIONS: In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed.

Significant antitumor response of disseminated glioblastoma to bevacizumab resulting in long-term clinical remission in a patient with encephalocraniocutaneous lipomatosis: A case report.

The prognosis of recurrent and disseminated glioblastoma is very poor. Bevacizumab is an effective established therapy for recurrent glioblastoma following treatment with radiotherapy plus temozolomide. However, the efficacy of bevacizumab is limited to prolonging progression-free survival, without significant prolongation of the overall survival. We herein report a case of glioblastoma in a 32-year-old female patient with encephalocraniocutaneous lipomatosis (ECCL) that had disseminated following surgical resection and subsequent treatment with temozolomide and radiation therapy. The disseminated tumors disappeared completely after five courses of bevacizumab therapy. Surprisingly, the patient has remained in clinical remission for >2.5 years after dissemination by continuing this therapy. To the best of our knowledge, this is the first case of long-time clinical remission following glioblastoma dissemination and treatment with bevacizumab. In the present case, bevacizumab exerted an atypically strong antitumor effect against disseminated glioblastoma after multidisciplinary treatments had already been applied. Moreover, this is the first report of ECCL associated with a malignant brain tumor.