Enabling an unimpeded surgical approach to the skull base in patients with cranial hyperostosis, exemplarily demonstrated for craniometaphyseal dysplasia

Craniometaphyseal dysplasia is an extremely rare, genetic bone-remodeling disorder. Comparable to osteopetrosis, fibrous dysplasia, and other infrequent conditions, craniometaphyseal dysplasia is characterized by progressive diffuse hyperostosis of the neuro- and viscerocranium. Affected patients present with a pathognomonic dysmorphia: macrocephalus, hypertelorism, bulky facial skeleton, and a prominent mandible. Progressive thickening and petrification of the craniofacial bones can continue throughout life, often resulting in neurological symptoms due to obstruction of the cranial nerves in the foramina and therefore immediately requiring neurosurgical interventions to avoid persistent symptoms with severe impairment of function. Treatment is largely infeasible given the lack of suitable tools to perform a craniotomy through the gross calvarial bone. In this paper, the authors present a complete process chain from the CT-based generation of an individual patient's model displaying his pathology to optimized preoperative planning of the skull's shape with a thickness of about 6-7 mm. For concise verification of the surgical plan in an operating room environment, a 3D real-time navigation prototype system was utilized. To guarantee realization of the surgery in a reasonable time frame, the mechanical tools were preoperatively selected for optimizing the ablation rate in porcine and bovine bone, which were comparable to that in the patient. This process chain was developed in a modular way, so that it could be easily adopted completely or partially for other surgical indications. A 21-year-old man was treated according to this sophisticated concept. Skull bone more than 50 mm thick in some regions was reduced to physiological thickness. The patient was thus in a stage that neurosurgical interventions could be performed with a regular risk within a reasonable time of treatment.     

Targeting the epidermal growth factor receptor in non-small-cell lung cancer: Who,which, when,and how?

Aberrations in the signaling cascade of the epidermal growth factor receptor are common to several solid tumors. Compounds aimed at targeting this pathway have been approved for use by the US Food and Drug Administration for lung, head and neck, pancreas, and colorectal carcinomas. Unfortunately, only the minority of patients treated with this class of agents will have responses or improvements in survival. This article reviews the data on agents that exploit tumor dependency on epidermal growth factor receptor cascade and describes the knowledge on how to discern the appropriate patient population for receiving these agents.     

红细胞多态性的基因分型

红细胞多态性在DNA水平的分型是输血医学的重大进展,其将对输血服务产生重大影响.最近,国际输血协会和国际血液学标准化委员会就此问题组织三次研讨会结果表明,可为分子血型基因分型设定非常高的标准.随着基因分型用于红细胞多态性研究的报道迅速增加,引起了国际论坛对其进展评价的关注.为了获得必要的信息,该领域的专家被问及以下问题:     

Flat adenoma in colon: Two decades of debate

The existence of flat adenomas in the colon is well recognized. Whether they represent a distinct disease with a pathogenetic pathway different from that of the classical adenoma-carcinoma sequence in colorectal tumorigenesis and have higher malignant potential remains a matter of debate. To review the epidemiology, clinical features, detection and management of flat and depressed (non-polypoid) colonic neoplasm, we performed a thorough literature review on studies focusing on the prevalence, histological features, genetics, detection and treatment of flat and depressed (non-polypoid) colonic neoplasm. A high percentage of severe dysplasia in flat colonic adenomas has not been consistently demonstrated. Their malignant potential appears to be size-dependent. Flat adenomas are found to have a lower incidence of major genetic abnormalities involved in the classical adenoma-carcinoma sequence and that has raised suspicions that they may have a different pathogenesis. The depressed type of colorectal carcinoma is uncommon but shows more aggressive behavior. More advanced colonoscopic techniques, such as chromoendoscopy, may enhance the detection of small and inconspicuous colonic neoplastic lesions that lack a protruding configuration. It is essential for endoscopists to appreciate the existence and clinical significance of flat and depressed colonic lesions as an important variant of colonic neoplasms so that the goal of reducing colorectal carcinoma incidence by polypectomy can be better achieved.     

Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia

Background  

Microglia are considered a major target for modulating neuroinflammatory and neurodegenerative disease processes. Upon activation, microglia secrete inflammatory mediators that contribute to the resolution or to further enhancement of damage in the central nervous system (CNS). Therefore, it is important to study the intracellular pathways that are involved in the expression of the inflammatory mediators. Particularly, the role of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and glycogen synthase kinase-3 (GSK-3) pathways in activated microglia is unclear. Thus, in the present study we investigated the role of Akt and its downstream pathways, GSK-3 and mTOR, in lipopolysaccharide (LPS)-activated primary rat microglia by pharmacological inhibition of these pathways in regard to the expression of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1) and to the production of prostaglandin (PG) E₂ and PGD₂.