Antiangiogenic strategies in medulloblastoma: reality or mystery

Medulloblastoma is the most common malignant brain tumor of childhood. Surgery, radiation therapy, and chemotherapy successfully cure many patients, but survivors can suffer long-term toxicities affecting their neurocognitive and growth potential; furthermore, there is no curative therapy in up to 30% of cases, mainly because of our incomplete understanding of many of the underlying molecular and cellular processes. Angiogenesis is a hallmark of the progression of medulloblastoma and, over the last years, investigators have sought to develop effective and less toxic antiangiogenic strategies, including the inhibition or destruction of abnormal blood vessels using either antiangiogenic or vascular disrupting agents. However, the results are conflicting principally because of the complex biology of tumor vasculature and the irregular geometry of the vascular system in real space. In addition, current targets of antiangiogenic therapy, such as vascular endothelial growth factor (VEGF), are thought to be critical for both physiologic and pathologic angiogenesis, and clinical side effects of anti-VEGF therapy are beginning to emerge. We here review the state-of-the-art concerning antiangiogenic targets for medulloblastoma treatment, and discuss the complexity of the vascular system that intrinsically limits the efficacy of current strategies.     

Cerebrospinal fluid leaks in extended endoscopic transsphenoidal surgery: covering all the angles

Following extended endoscopic transsphenoidal approach (EETSA), cerebrospinal fluid (CSF) leak rate has been reported in the range of 5–50 %. Novel closure techniques, such as the nasoseptal flap and other multilayered repairs improved the outcomes significantly but took most of our focus. Little attention, however, was given to other aspects of the equation such as nasal support—to support the heavy weight of such repairs—and lumbar drains. These are important because they diminish the forces acting on both sides of the repair, hence covering all the angles. We reviewed data of 98 consecutive patients who underwent an EETSA between 1999 and 2014. We analyzed the rates of CSF leak throughout the years and with every modification added to our closure technique. Common pathologies encountered were invasive adenomas, meningiomas, chordomas, and craniopharyngiomas. CSF leak occurred overall in five patients (5.1 %). The nasoseptal flap decreased the rate of CSF leak but not significantly (P = 0.112), while placing a nasal trumpet to support our repair resulted in significant decrease in CSF leak rate (P = 0.0013). In the last 2 years of our series, when all modifications took place and all angles were covered, there was one leak in 35 cases (2.8 %). A protocol that covers all the angles by a good multilayered repair (regardless of its type and materials) while diminishing the forces acting on both sides of the repair leads to a minimal rate of CSF leak. No principle alone is effective individually.     

Factors Affecting Oncologic Outcomes of 90Y Radioembolization of Heavily Pre-Treated Patients With Colon Cancer Liver Metastases

Introduction

The purpose of this study was to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogram for OS.

鸭子α-干扰素基因表达及多样性分析

目的：采用分子杂交及ＰＣＲ方法，分析鸭α－干扰素基因的表达及多态性。方法：从鸭外周血分离出的单核细胞在体外经ＰＨＡ（５ｕｇ／ｍｌ）刺激不同时间后，提取总ＲＮＡ。以ＲＴ－ＰＣＲ方法检测鸭α－干扰素（ＤｕＩＦＮ－α）ｍＲＮＡ表达状况。引物根据最近公布的ＤｕＩＦＮ－α基因序列设计。从鸭外周血单核细胞中提取的基因组ＤＮＡ经限制性内切酶ＢａｍＨＩ，ＨｉｎｄⅢ，ＰｓｔＩ，ＸｂａＩ消化后，以公布的ＤｕＩＦＮ－α序列为探针，采用Ｓｏｕｔｈｅｒｎ杂交分析ＤｕＩＦＮ－α基因的多样性。结果：在未经ＰＨＡ刺激的鸭外周血单核细胞（ＰＢＭＣｓ）中，未检测到ＤｕＩＦＮ－α表达；ＰＨＡ刺激４ｈ后，即可检测到ＤｕＩＦＮ－α表达，一直持续到２４ｈ，基因组ＤＮＡ限制性内切酶多态性分析表明，ＰｓｔＩ酶切后，出现片段大小各异的杂交信号，提示ＤｕＩＦＮ－