宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性

目的探讨宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。方法选择2018年1月至2019年1月间在我院确诊为原发性宫颈癌的患者50例作为宫颈癌组,在我院诊断为宫颈糜烂的患者78例作为宫颈糜烂组,同期在我院进行体检的健康女性100例作为正常对照组。对比3组研究对象的阴道微生态失调率、高危型HPV感染率以及宫颈癌组、宫颈糜烂组患者宫颈病灶组织中宫颈癌相关增殖基因(Prdx4、Nek2、Fhit、BLCAP)mRNA表达量的差异。采用Pearson检验分析宫颈癌患者阴道微生态失调率与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。结果宫颈癌组、宫颈糜烂组患者的阴道微生态失调率、高危型HPV感染率高于正常对照组,其中宫颈癌组患者这两项指标水平高于宫颈糜烂组(均P0.05)。宫颈癌组患者宫颈病灶组织中Prdx4、Nek2 mRNA表达量高于宫颈糜烂组,Fhit、BLCAP mRNA表达量低于宫颈糜烂组(均P0.05)。相关性分析发现,宫颈癌患者阴道微生态失调率与高危型HPV感染率呈正相关,与癌基因(Prdx4、Nek2)mRNA表达量呈正相关,与抑癌基因(Fhit、BLCAP)mRNA表达量呈负相关(均P0.05)。结论宫颈癌患者阴道微生态失调率较高,可能与高危型HPV感染及癌细胞增殖旺盛密切相关。     

Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks

E. K. J. Risse, J. P. Holierhoek, E. M. Meijer‐Marres, E. Ouwerkerk‐Noordam and M. E. Boon Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks Objective: The purpose of this study was to reduce the number of diagnoses of atypical glandular cells (AGC). Residual material from the cervical ThinPrep® samples (Hologic, Marlboruogh, MA, USA) was used for cell blocks (CB) and immunohistochemistry (IHC). Methods: In 2007 there were 87 patients (0.12% of tests) with AGC on liquid‐based cytology (LBC) in the Leiden Cytology and Pathology Laboratory (LCPL) using the Bethesda System 2001 (TBS). CB with IHC was used for 26 of these cases. The vials still containing the brush (Cervex‐Brush^® Combi) were placed in a shaker for 10 minutes to dislodge the material trapped between the bristles. The residual sampling fluid was used to prepare paraffin sections (Shandon Cytoblock^®) stained with Papanicolaou and immunostaining. Results: Four of five cases with AGC not otherwise specified (NOS) were diagnosed with CB/IHC as benign mimics (endometrium, tubal metaplasia, follicular cervicitis, microglandular hyperplasia) and one of four with AGC‐favour neoplasia (FN) (endocervical polyp). In one of five cases with AGC‐NOS and in two of seven with AGC‐FN, CIN3 was found on subsequent histological biopsy. Of six cases diagnosed as adenocarcinoma in situ (AIS) on LBC with CB/IHC the diagnosis was confirmed in four; one was adenocarcinoma and one glandular atypia. Of eight cases diagnosed as adenocarcinoma on cytology and CB/IHC, the diagnosis was confirmed in three. The other five cases were found to be one each of AIS, squamous cell carcinoma, CIN3, CIN2 with glandular atypia, and cervical endometriosis. Conclusions: By reducing the number of benign mimics of AGC, we achieved a high proportion (16/26; 61.5%) of neoplastic or preneoplastic lesions (glandular or squamous) on histological outcome potentially avoiding colposcopy. Histological biopsy verification by the gynaecologist is needed for final diagnosis of AGC‐FN, AIS and adenocarcinoma.     

显微镜下减压联合前路Zero-P治疗颈椎病的早期临床疗效分析

目的:探讨前路颈椎显微镜辅助下精准减压联合前路椎间隙Zero-P融合器置入治疗颈椎病的早期临床疗效。方法:回顾性分析2016年6月至2018年1月我院收治的43例颈椎病患者,处理节段共73个;患者均行显微镜辅助颈椎前路减压、髓核切除、Zero-P置入融合内固定术。记录患者手术节段、手术时间,术中失血量及并发症。手术前,术后1个月、3个月、6个月、末次随访时的颈部及上肢疼痛视觉模拟评分(Visual Analogue Scale,VAS)、颈部日本骨科协会评分(Japanese Orthopedic Association,JOA)和颈椎残障功能指数(Neck Disability Index,NDI),并采用配对t检验对不同时间点的评分进行分析,评估临床疗效。并同期行颈椎X线、CT及MRI检查,测量和评估椎间隙高度、颈椎Cobb角的改变情况和邻近节段异位骨化形成(Adjacent Level Ossification Development,ALOD)。结果:所有患者术后均获得随访,随访时间12-18个月,平均(14.9±2.2)个月。平均手术时间(82.2±20.9)min,失血量(91.5±33.7) m L;未发生神经和血管损伤等严重并发症。与术前相比,患者术后1个月、3个月、6个月及末次随访时的VAS评分、JOA评分、NDI评分、椎间隙高度及Cobb角均明显改善,差异有统计学意义(P0.05)。但术后随访时间点比较,差异无统计学意义(P0.05)。术后出现轻度吞咽困难2例,中度和重度吞咽困难各1例。随访期间,所有患者均获椎间骨性融合,未发生Zero-P融合器松动、滑脱或断裂,椎体未出现继发性骨折。结论:显微镜辅助颈椎前路椎间盘切除、Zero-P融合器置入治疗颈椎病,能够精准的去除神经脊髓组织的压迫,术后短期和中期临床疗效良好,同时显微镜下止血、术中出血少;视野清晰、手术安全性高。     

Focus: Personalized Medicine: Simultaneously Detection of 50 Mutations at 20 Sites in the BRAF and RAS Genes by Multiplexed Single-Nucleotide Primer Extension Assay Using Fine-Needle Aspirates of Thyroid Nodules

Fine-needle aspiration (FNA) is commonly used for primary evaluation of thyroid nodules. Twenty to 30 percent of thyroid nodules remain indeterminate after FNA evaluation. Studies show the BRAF p.V600E to be highly specific for papillary thyroid carcinoma (PTC), while RAS mutations carry up to 88 percent positive predictive value for malignancy. We developed a two-tube multiplexed PCR assay followed by single-nucleotide primer extension assay for simultaneous detection of 50 mutations in the BRAF (p.V600E, p.K601E/Q) and RAS genes (KRAS and NRAS codons 12, 13, 19, 61 and HRAS 61) using FNA smears of thyroid nodules. Forty-two FNAs and 27 paired formalin-fixed, paraffin-embedded (FFPE) tissues were tested. All BRAF p.V600E-positive FNA smears (five) carried a final diagnosis of PTC on resection. RAS mutations were found in benign as well as malignant lesions. Ninety-two percent concordance was observed between FNA and FFPE tissues. In conclusion, our assay is sensitive and reliable for simultaneous detection of multiple BRAF/RAS mutations in FNA smears of thyroid nodules.     

两种高危型HPV检测技术诊断宫颈病变的临床价值比较

目的:比较酶切信号放大法(Cervista)与导流杂交基因芯片技术(Hybri Ma)检测高危型人乳头状瘤病毒(HR-HPV)诊断宫颈上皮内瘤变2级或2级以上(CIN2+)的临床价值。方法:随机选择288例2012年3月至2013年1月在哈尔滨医科大学附属第一医院妇科门诊进行新柏氏液基细胞学检查的年龄在20~65岁的宫颈细胞学检测未明确意义的不典型鳞状细胞(ASCUS)的患者,采用Cervista技术与Hybri Ma技术进行高危型HPV检测,并对入组的患者行阴道镜下宫颈活组织检查。以病理学诊断结果为金标准,比较Cervista技术与Hybri Ma技术诊断宫颈上皮内瘤变2级或2级以上(CIN2+)的敏感度、特异度及ROC曲线。结果:在入组的288例患者中,Cervista技术和Hybri Ma技术检出高危型HPV的阳性率分别为49.31%和51.39%(P0.05),其诊断CIN2+的敏感度分别为95.65%和91.30%(P0.05),特异度分别为59.50%和56.20%(P0.05),阳性预计值分别为30.99%和28.38%(P0.05),阴性预计值分别为98.63%和97.14%(P0.05)。两组ROC曲线下面积分别为0.776和0.738(P0.05)。结论:Cervista技术与Hybri Ma技术诊断CIN2+的临床价值相当。     

Determination of Ki67 Growth Fraction and Oestrogen Receptors In Screen-Detected Breast Cancer Using Cytological Preparations

Oestrogen receptor (ER) status of 77 cases of screen-detected breast cancer has been determined using cytological preparations. In 48% ER status was positive, which was the same proportion as that formed in a control group of age-matched patients with symptomatic breast carcinoma. Since the screen-detected group contained more low grade tumours, the percentage of ER-positive cases would be expected to be higher. the reasons for the discrepancy are discussed. Ki67 score has been determined for 41 cases of screen-detected cancer. Ki67 score showed a positive correlation with histological tumour grade and a negative correlation with ER status. However, there was no correlation with tumour size or lymph node status. the Ki67 scores in the screen-detected cancers were essentially similar to those found in an age-matched symptomatic group, but the very low scores were only found in the screened group.     

Necrotic Debris In Thyroid Aspirates: A Feature of Follicular Carcinoma of the Thyroid

Fine needle aspirates from 44 follicular thyroid tumours (30 adenomas, 14 carcinomas) have been studied. All aspirates contained neoplastic cells in follicular and trabecular arrangements. The individual tumour cells showed varying degrees of anisonucleosis and nuclear pleomorphism. Colloid was scanty or absent from all smears. Granular or filamentous necrotic material was observed in both biopsies and smears from one moderately and two poorly differentiated follicular carcinomas, but in none of the adenomas. This suggests that necrotic debris may be a feature of follicular carcinoma of the thyroid.     

A study of oxidative stress in cervical cancer- an institutional study

Cervical cancer is the second most common cause of cancer-related death among women worldwide, especially in developing countries. Oxidative stress has been associated with cervical cancer. Many studies demonstrated that the low level of antioxidants induces the production of free radicals that cause lipid peroxidation, DNA, and protein damage leading to mutations that favors malignant transformation. This is a case-control institutional study conducted to evaluate the level of oxidative stress in cervical cancer patients and the age-matched healthy controls. We measured level of TBARS expressed as MDA, activity of SOD and GSH level by the spectrophotometric method, and level of 8-OHdG was estimated using a competitive sandwich ELISA assay. Our results showed a significant increase in the level of lipid peroxidation in group IV when compared to the control, group II and group III (p < 0.001). The activity of SOD was also significantly higher in group IV when compared to the control group (p < 0.001), group II (p < 0.001), and group III (p < 0.001). The level of GSH was also significantly lower in group IV when compared to the control group (p < 0.01), group II (p < 0.01), and group III (p < 0.01). The level of 8-OHdG was significantly higher in group IV than in the other groups (p < 0.01). The results suggest that oxidative stress is involved in the pathogenesis of cervical cancer, which is demonstrated by an increased level of lipid peroxidation and higher levels of 8-OHdG and an altered antioxidant defense system.     

High TMPRSS4 expression is a predictor of poor prognosis in cervical squamous cell carcinoma

Objective The aim of this study was to clarify the clinical role of TMPRSS4 expression in cervical squamous cell carcinoma (CSCC) and to investigate the role of TMPRSS4 in predicting outcomes of patients with CSCC. Methods The retrospective study enrolled 87 patients diagnosed with CSCC between 2004 and 2006. TMPRSS4 expression in CSCC was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. The impact of TMPRSS4 expression on 5-year disease-free survival (DFS) and 5-year overall survival (OS) was assessed by Kaplan–Meier analysis and Cox proportional hazards modeling. Results The high expression of TMPRSS4 was 63.2% in 87 patients with CSCC, and 17.5% in 40 patients with benign cervical disease (P < 0.001). High TMPRSS4 expression was significantly associated with tumor grade (P = 0.005), lymph node metastasis (P = 0.004), and deep cervical stromal invasion (P = 0.025). Patients with high expression of TMPRSS4 had shorter OS and DFS than those with low expression (P = 0.0205 and P = 0.0318, respectively). In multivariate Cox regression analysis, high expression of TMPRSS4 was a potential prognostic indicator for OS (P = 0.041) and DFS (P = 0.015). Conclusion Our findings suggest that TMPRSS4 might play an important role in the progression of CSCC. TMPRSS4 could be a potential prognostic marker of CSCC.