Immunohistochemical study in dural arteriovenous fistula and possible role of ephrin-B2 for development of dural arteriovenous fistula

Background Although there were several clinical and experimental studies discussing the pathogenesis of dural arteriovenous fistula (DAVF), the pathological process leading to intracranial DAVF so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors for the development of DAVF and to study the biological activity of this uncommon lesion.Methods We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from 6 patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors FIk-1 and Fit-1, ephrin-B2, MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques.Results A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/6 cases. VEGF stained positive in all of the available specimens (6/6). FIk-1 showed a positive immunoreaction in only 2/6 cases and Fit-1 in 4/6 cases. Ephrin-B2 was expressed in the majority (5/6) of the cases.Conclusions These results support the hypothesis that DAVFs might be acquired dynamic vascular malformations with low biological activity. Vascular growth factors like VEGF and ephrin-B2 might play a pivotal role in the formation of DAVF.     

ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis

Experts discussed the definition, natural history, pathologic features, pathogenesis, electroclinical, neurophysiological, neuropsychological, structural and functional imaging findings, as well as surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). After a long-lasting consensus process the ILAE Commission Neurosurgery of epilepsy accepted the resulting conclusions as state-of-the art report on MTLE-HS. The majority of contributors considered MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity.     

Utility of FDG-PET in differential diagnosis of benign and malignant fractures in acute to subacute phase

OBJECTIVE: To evaluate the usefulness of positron emission tomography with [fluorine-18] 2-deoxy-2-fluoro-D-glucose (FDG-PET) for early differential diagnosis of benign and malignant fractures. MATERIALS AND METHODS: Among 1,164 patients who had received FDG-PET between January 1999 and December 2000, 20 patients were found to have an acute fracture on review of clinical charts and/or radiologic images taken within one month before or after FDG-PET examination. The fractures were finally diagnosed by clinical follow up of at least five months duration. Standardized uptake values (SUV) for the benign and malignant bone lesions were calculated and compared. RESULTS: Ten of the 20 patients were finally diagnosed to have a benign fracture, nine patients to have a malignant fracture, and one patient to have both a benign and a malignant fracture at different locations. A statistically significant difference in the SUV was found between the benign group (SUV: 1.36 +/- 0.49) and the malignant group (SUV: 4.46 +/- 2.12) (p = 0.0006, the nonparametric Mann-Whitney U test). CONCLUSIONS: FDG-PET can be a useful method for early differentiation between acute benign and metastatic fractures. Our retrospective study indicates that an acute benign fracture itself does not show significant FDG uptake.     

Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors

Many different pathological and biological variables which characterize breast carcinomas have been found to be associated. The aim of this work was to analyze the complex relationship among these parameters. The pathologic, biologic, and clinical characteristics of a series of primary breast carcinomas from 676 patients were retrospectively investigated. Multiple correspondence analysis of 13 factors revealed clustering of eight pathobiologic variables, that is histologic grade, necrosis, lymphoid infiltration, number of mitoses, cerbB2 overexpression, p53, progesterone receptor, and bcl2 expression. An index for each tumor calculated on the basis of these eight factors served to distinguish two different tumor phenotypes, designated A and B. Phenotype A is represented by tumors sharing most of the biologic features of normal breast tissues: indeed, these tumors are characterized by a relatively high degree of differentiation, low proliferation, no necrosis or leukocyte infiltration, and no gene alterations. By contrast, phenotype B is quite divergent from the normal tissue because of its poor differentiation, high proliferation, frequent gene alterations and evidence of a host immune reaction. As regards the disease progression, these two subsets showed marked differences: phenotype A tumors had a low recurrence rate per year that remained constant over time and affected more frequently elderly patients, whereas group B tumors showed high aggressivity in the first years after surgery followed by a low longterm recurrence rate and were more frequently seen in younger patients. These data suggest that breast carcinoma consists of two different subsets that can be identified on the basis of pathobiologic features.     

小婴儿病理性黄疸77例分析

目的：为探讨引起小婴儿的病理性黄疸发病相关因素,以指导治疗和诊断,避免误诊。方法：小婴儿的黄疸77例进行分析。结果：其中母乳性黄疸61例（占79.2%）,巨细胞病毒感染5例（占6.4%）,婴儿肝炎综合症者3例（占3.8%）。先天性甲状腺功能低下1例（占1.2%）,乙型肝炎1例（1.2%）,其他疾病6例（占7.8%）。结论：认为新生儿后期的黄疸,虽然主要是母乳性黄疸,但其他一些疾病也可引起黄疸,要注意鉴别,避免误诊和漏诊。     

附件囊肿病理特征的B超诊断

96例应用超声显象仪(B超)诊断的附件囊性肿块,经病理证实,分别为炎性肿抉,非赘生性、良性和恶性肿瘤。根据声象图上的特征可分为六型:单纯型、多房型、厚壁型、均质型、混合型和声衰减型。本文描述其声象图表现与病理特征之间的关系。表现为低或中等强度的均质性回声的囊肿,是粘液性囊腺瘤的特征,本文共4例。8例声衰减型囊肿,均为良性畸胎瘤皮样囊肿型。而6例恶性囊肿,均为伴有腹水的混合型囊肿。本组病理定性诊断符合率达85％,定位符合率94％。     

Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk,locally advanced prostate cancer

BACKGROUND:

Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high‐risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).

METHODS:

Thirty‐one patients with high‐risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b‐3 or serum prostate‐specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER‐2/neu was performed on prechemotherapy and postchemotherapy prostate tissue.

RESULTS:

The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty‐nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI.

CONCLUSIONS:

No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity. Cancer 2009. © 2009 American Cancer Society.     

血管生成拟态研究进展

血管生成拟态(VM)是近年来发现的一种与经典的肿瘤血管生成途径完全不同、不依赖机体内皮细胞的全新肿瘤微循环模式.它描述了在高度侵袭性肿瘤组织中通过肿瘤细胞的自身变形和基质重塑形成类似血管样的通道,通过这种结构有利于肿瘤组织获取营养、侵袭和转移.血管生成拟态的提出为肿瘤研究和治疗提供了新思路.     

Extrapolation: Experience gained from original biologics

Biologicals undergo modifications throughout their commercial lifecycle. Major changes can unintentionally magnify their inherent physicochemical variability. Although trials comparing the pre- and the post-change versions have been requested occasionally, analytical comparison is the most sensitive approach to anticipating clinical equivalence. Therefore, it may be concluded, by means of ‘extrapolation’, that non-identical versions of a given biologic will behave equally in all indications. Despite the lessons learned with original biologics, there are still controversies around the approval of biosimilars through extrapolation. Here, a comprehensive analysis of scattered information allows for an account of cases of original biologic versions approved in some indications with no patient trials involved. Healthcare professionals can be reassured that inasmuch as extrapolation has proven valid for new versions of original biologics, the same holds for biosimilars.