基于数字组织病理图像的肿瘤与微环境相互作用风险模型在口咽癌症中的预后研究

数字组织病理学全幅图像为计算机化的定量分析提供新的机遇。越来越多的研究表明,肿瘤微环境中的免疫细胞与癌变细胞的相互作用是一项重要的预后指标。HPV+口咽癌症是头颈部常见的恶性肿瘤,目前对其没有很好的预后指标。利用计算机图像处理和模式识别技术,从数字组织病理学全幅图像中定量提取细胞核形态,并利用其特征去度量肿瘤微环境与癌变区域相互作用的程度,构建口咽癌症复发风险模型。实验数据来自华盛顿大学医学中心的病理学档案,是连续回顾性收集的234名口咽癌患者手术切除的组织病理学切片及其相应的跟踪数据。研究发现:利用图像定量分析构建口咽癌症复发风险模型,能够显著地区分复发与非复发病患,其100次5折交叉验证的分类结果的平均AUC达到0.67±0.02;对病患分别进行单变量(HR(95%CI)=1.76(0.99～3.13),P=0.0352)及多变量生存分析((HR(95%CI)=3.27(1.12～5.46),P=0.039)),结果说明肿瘤微环境与癌变区域相互作用高的口咽癌症病患相比于相互作用低的病患,有更低的复发风险及更长的生存期。研究揭示计算机定量度量的肿瘤微环境中的免疫细胞与癌变细胞的相互作用,有望作为一个独立的预后指标来指导口咽癌症病患的治疗疗程。     

Modified Histopathological Protocol for Poly-ɛ-Caprolactone Scaffolds Preserving Their Trabecular,Honeycomb-like Structure

Poly-ɛ-caprolactone (PCL) is now widely studied in relation to the engineering of bone, cartilage, tendons, and other tissues. Standard histological protocols can destroy the carefully created trabecular and honeycomb-like architecture of PCL scaffolds, and could lead to scaffold fibers swelling, resulting in the displacement or compression of tissues inside the scaffold. The aim of this study was to modify a standard histopathological protocol for PCL scaffold preparation and evaluate it on porous cylindrical PCL scaffolds in a rat model. In 16 inbred Wag rats, 2 PCL scaffolds were implanted subcutaneously to both inguinal areas. Two months after implantation, harvested scaffolds were first subjected to μCT imaging, and then to histopathological analysis with standard (left inguinal area) and modified histopathological protocols (right inguinal area). To standardize the results, soft tissue percentages (STPs) were calculated on scaffold cross-sections obtained from both histopathological protocols and compared with corresponding µCT cross-sections. The modified protocol enabled the assessment of almost 10× more soft tissues on the scaffold cross-section than the standard procedure. Moreover, STP was only 1.5% lower than in the corresponding µCT cross-sections assessed before the histopathological procedure. The presented modification of the histopathological protocol is cheap, reproducible, and allows for a comprehensive evaluation of PCL scaffolds while maintaining their trabecular, honeycomb-like structure on cross-sections.     

The protective impact of adapted trimebutine maleate-loaded nanostructured lipid carriers for alleviating the severity of acute colitis

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues such as high adverse effects of released drugs, insufficient drug amount at diseased areas, and unintentionally premature drug release to noninflamed GIT regions. Herein, the goal of this work was to convert trimebutine maleate (TMB) into nanostructured lipid carriers (NLC) in order to improve its protective effects in ulcerative colitis. NLC of TMB was prepared by the hot homogenization followed by ultra-sonication method. A full 4²-factorial design was used to estimate the produced TMB-NLC. The study design included the exploration of the impact of two independent variables namely lipid mix amount and ratio (glyceryl mono stearate and capryol 90), surfactant concentration (0.5, 1, 1.5, and 2%), on the particle size, polydispersity index, and the entrapment efficiency (EE%). The protective activity of F9 was examined through macroscopical scores, histopathological changes, immunohistochemical localization of tumor necrosis factor-α (TNF-α) and examination of oxidative stress such as reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) against acetic acid-induced colitis in rats. Consistent with our expectations, the orally administered optimized formula (F9) alleviated the severity of colitis in acetic acid-induced rat model of colitis likely owing to the controlled release compared to free TMB. We aimed to develop TMB-loaded NLC for the treatment of acute colitis with the goal of providing a superior drug safety profile over long-term remission and maintenance therapy.     

肘关节滑膜性骨软骨瘤病术后复发影像学表现1例

目的：原发性滑膜骨软骨瘤病又称滑膜软骨化生,非常罕见,是发生在关节囊、滑囊和腱鞘滑膜的慢性关节病,非常罕见,病因不明,可能与外伤有关。结果好发于30~50岁男性,以膝关节发生率最高,占68.99%,其次为髋关节、肩关节、肘关节、踝关节等,常单侧关节发病,双侧少见。结论临床表现为受累的关节肿胀,疼痛明显,关节穿刺可抽出积液。以手术治疗为主,需摘除关节腔内游离体,同时需广泛切除病变的滑膜,该病复发率较高。     

Congenital lung malformations in the second trimester: prenatal ultrasound diagnosis and pathologic findings

PURPOSE: To correlate prenatal sonographic diagnosis of cystic lung malformations with fetopathologic findings after termination of pregnancy. METHODS: We retrospectively analyzed the data of 16 terminated cases in which a cystic lung lesion was diagnosed pre- or postnatally. RESULTS: On average, prenatal diagnosis was established on the 21(st) gestational week (range, 19-26 weeks). The cause of termination was severe polyhydramnios in 4 cases, nonimmune fetal hydrops in 4 cases, other congenital malformation in 5 cases (renal malformation, 2 cases; congenital diaphragmatic hernia, 3 cases), and obstetrical conditions (intrauterine death, placental abruption, spontaneous abortion) in 3 cases. In 11 cases, congenital cystic adenomatoid malformation (CCAM) was the presumptive prenatal diagnosis. Autopsy confirmed the prenatal diagnosis in 6 of them, while in the other 5 cases, an enteric cyst, a laryngeal atresia, an unidentified tumor, a pulmonary hypoplasia, and an extralobar pulmonary sequestration were found on histologic examination. On the other hand, the autopsy revealed CCAM in those 5 cases in which other malformations were suggested prenatally. CONCLUSION: The prenatal sonographic diagnosis of CCAM is difficult. Our cases emphasize the important role of fetopathology even today in the verification of prenatal diagnosis based on sonographic examinations.     

活检术前应用皮质醇对原发性中枢神经系统淋巴瘤病理诊断的影响

目的研究活检术前应用皮质醇是否会影响原发性中枢神经系统淋巴瘤的病理诊断。方法回顾分析2005年2月至2011年2月期间73例经立体定向活检诊断为原发性中枢神经系统淋巴瘤患者的资料。结果 73例淋巴瘤患者中,39例（53.4%）在活检术前应用皮质醇;10例（73;13.7%）未得出阳性结果,再次行立体定向活检或开颅被证实为原发性中枢神经系统淋巴瘤,其中5例（39例）术前应用过皮质醇（12.8%）,5例（34例）未使用皮质醇（14.7%）（P=1.0）。结论活检术前应用皮质醇对大部分原发性中枢神经系统淋巴瘤患者而言不影响其病理诊断。     

Utility of high-resolution computed tomography for predicting risk of sputum smear-negative pulmonary tuberculosis

Background

To diagnose sputum smear-negative pulmonary tuberculosis (PTB) is difficult and the ability of high-resolution computed tomography (HRCT) for diagnosing PTB has remained unclear in the sputum smear-negative setting. We retrospectively investigated whether or not this imaging modality can predict risk for sputum smear-negative PTB.

Methods

We used HRCT to examine the findings of 116 patients with suspected PTB despite negative sputum smears for acid-fast bacilli (AFB). We investigated their clinical features and HRCT-findings to predict the risk for PTB by multivariate analysis and a combination of HRCT findings by stepwise regression analysis. We then designed provisional HRCT diagnostic criteria based on these results to rank the risk of PTB and blinded observers assessed the validity and reliability of these criteria.

Results

A positive tuberculin skin test alone among clinical laboratory findings was significantly associated with an increase of risk of PTB. Multivariate regression analysis showed that large nodules, tree-in-bud appearance, lobular consolidation and the main lesion being located in S1, S2, and S6 were significantly associated with an increased risk of PTB. Stepwise regression analysis showed that coexistence of the above 4 factors was most significantly associated with an increase in the risk for PTB. Ranking of the results using our HRCT diagnostic criteria by blinded observers revealed good utility and agreement for predicting PTB risk.

Conclusions

Even in the sputum smear-negative setting, HRCT can predict the risk of PTB with good reproducibility and can select patients having a high probability of PTB.