miR-223通过IGF-1R及NFIA调控乳腺癌细胞及破骨细胞功能的研究

目的探索miR-223在乳腺癌骨转移微环境中调控乳腺癌细胞、破骨细胞的功能及其机制。 方法采用micro-CT检测野生型及miR-223基因敲除小鼠股骨骨小梁骨体积分数、骨密度等相关数据,并对股骨组织病理切片染色,观察miR-223缺失对破骨活动影响。利用RANKL诱导RAW 264.7细胞分化为破骨细胞的体外模型,研究miR-223在其中的作用及机制。通过MDA-MB-231细胞实验研究miR-223对乳腺癌细胞增殖、凋亡功能的调控作用及机制。 结果miR-223基因敲除小鼠股骨破骨活动明显活跃;miR-223过表达可以通过NFIA基因抑制RNAKL诱导的破骨细胞分化成熟,还可通过抑制IGF-1R及PI3K/Akt信号通路,抑制乳腺癌细胞增殖并促进其凋亡。 结论miR-223是骨转移微环境中抑制乳腺癌骨转移发生发展的保护性因子,可通过抑制破骨细胞分化成熟、破骨活动、乳腺癌细胞增殖及促进乳腺癌细胞凋亡来调节乳腺癌骨转移微环境。     

血管内皮生长因子C在宫颈癌中的表达及其与淋巴转移的关系

目的分析正常宫颈，宫颈上皮内瘤样病变，无淋巴结转移，有淋巴结转移组的宫颈鳞癌组织中VEGF-C的表达。方法收集84例正常宫颈组织，宫颈上皮内瘤样病变和宫颈鳞癌组织（按有无淋巴转移、分化及临床分期分组）。进行SP免疫组化染色，测定VEGF-C蛋白的表达。结果VEGF-C表达主要位于肿瘤细胞胞浆及胞膜内。它在正常宫颈、CIN及宫颈鳞癌组织中的表达依次增高，有淋巴结转移组较无淋巴结转移组中VEGF-C的表达显著增高。VEGF-C的表达与患者的临床分期无关（P〉0．05），与富颈癌的病理分级呈负相关。结论提示VEGF-C有促进宫颈癌发展、促进淋巴管生成、抑制癌细胞分化的作用。由于VEGF-C与淋巴道转移的密切关系，故可在临床工作中通过检测宫颈癌活检组织中VEGF-C的表达估计其预后，为宫颈癌的治疗提供新策略。     

高清磁共振成像在ⅠB~ⅡB期宫颈癌术前评估中的应用价值

目的 分析高清磁共振成像（MRI）检查在ⅠB~ⅡB期宫颈癌术前评估中的应用价值。方法 回顾性分析2015年3月至2017年6月海军军医大学（第二军医大学）长海医院收治的94例宫颈癌患者的病历资料,所有患者术前均接受盆腔检查,其中58例患者进一步接受常规MRI检查,36例接受高清MRI检查。以术后病理结果为金标准,分析3种检查方法对宫颈癌阴道侵犯和宫旁侵犯的评估效果,计算其准确度、灵敏度和特异度,并采用Kappa检验进行一致性分析。结果（1）盆腔检查评估宫颈癌阴道侵犯的准确度、灵敏度、特异度分别为63.8%（60/94）、53.7%（29/54）、77.5%（31/40）,常规MRI检查的准确度、灵敏度、特异度分别为58.6%（34/58）、48.5%（16/33）、72.0%（18/25）,高清MRI检查的准确度、灵敏度、特异度分别为83.3%（30/36）、76.5%（13/17）、89.5%（17/19）。一致性检验结果显示,盆腔检查、高清MRI检查评估阴道侵犯和术后病理结果的一致性较好（Kappa=0.297、0.664,P=0.002、0.001）。（2）盆腔检查评估宫颈癌宫旁侵犯的准确度、灵敏度、特异度分别为79.8%（75/94）、20.0%（1/5）、83.1%（74/89）,常规MRI检查的准确度、灵敏度、特异度分别为74.1%（43/58）、31.2%（5/16）、90.5%（38/42）,高清MRI检查的准确度、灵敏度、特异度分别为86.1%（31/36）、60.0%（6/10）、96.1%（25/26）。一致性检验结果显示,常规MRI检查和高清MRI检查评估宫旁侵犯与术后病理结果的一致性较好（Kappa=0.251、0.618,P=0.040、0.001）。结论 在ⅠB~ⅡB期宫颈癌术前评估中,高清MRI检查结果与术后病理结果的一致性最好,可作为宫颈癌术前评估的常用方法。     

High external parametrial dose can increase the probability of radiation proctitis in patients with uterine cervix cancer

OBJECTIVE: The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer. METHODS: From May 1993 through December 1996, 191 patients with stage IB-IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44-45 Gy/ 22-25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4-14.4 Gy/ 3-8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2-24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44-45, 50-54, and >54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups. RESULTS: Three-year overall and Grade 2-4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P < 0.0001), respectively. Grade 2-4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2-4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively). CONCLUSION: Regardless of central shielding after 44-45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.     

CT导向下水循环冷却式微波刀消融治疗结直肠癌肝转移瘤

目的探讨CT导向下水循环冷却式微波刀消融治疗技术在结直肠癌肝转移瘤治疗中的意义。方法2007年6月～2008年9月共16例结直肠癌肝转移患者,27个转移灶,其中直径小于3.0cm的病灶共9个,3.0cm～4.0cm者12个,4.0cm～5.0cm者4个,大于5.0cm者2个,平均3.5cm±0.8cm,均采用CT导向下水循环冷却式微波刀消融治疗,术后第1、3个月分别行螺旋CT双期增强扫描评价治疗疗效。结果肿瘤影像学评价,16例患者27例病灶中,完全缓解（complete remission,CR）23个,部分缓解（partial remission,PR）3个,稳定（nochange,NC）1个。全组16例目前全部存活,随访时间最长15个月,最短6个月,近期平均生存期10个月。结论CT导向下水循环冷却式微波刀消融治疗技术是治疗直肠癌肝转移瘤的安全、微创、有效的方法。     

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China

ObjectiveTo investigate the clinical significance of separate lateral parametrial lymph node dissection (LPLND) in improving parametrial lymph node (PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer.MethodsFrom July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1−IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy (CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups.ResultsCompared with CRH group, the rate of laparoscopic surgery was higher (60.3% vs. 15.9%, P<0.001), and the blood transfusion rate was lower (19.0%vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases (96.7%) in the LPLND group, and 270 cases (11.6%) in the CRH group (P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group (median 3vs. 1, P<0.001). The PLN metastases were detected in 25 cases (6.8%) in the LPLND group, and 18 cases (0.8%) in the CRH group (P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio (OR)=228.999, 95% confidence interval (95% CI): 124.661−420.664; P<0.001], but also for PLN metastasis identification (OR=10.867, 95% CI: 5.381−21.946; P<0.001). ConclusionsLPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.     

IA2-IB1期宫颈癌宫旁转移相关因素分析

目的 探讨IA2-IB1期宫颈癌患者宫旁转移的相关因素。方法 回顾性分析168例行手术治疗的IA2-IB1期宫颈癌患者的临床资料,包括年龄、分期、肿瘤直径、血清鳞状细胞癌抗原（squamous cell carcinoma antigen,SCC）数值,肿瘤组织学类型、肿瘤浸润深度、肿瘤细胞分化程度、盆腔淋巴结转移情况、脉管浸润情况、宫旁转移情况等,对宫旁转移的相关因素进行单因素和多因素分析。结果 168例IA2-IB1期宫颈癌患者中9例发生宫旁转移,宫旁转移率为5.4%。单因素分析显示肿瘤直径>2 cm、血清SCC值显著升高、肿瘤肌层浸润深度>1/2肌层、脉管浸润阳性、盆腔淋巴结转移阳性与宫旁转移密切相关（P<0.05）,而年龄、临床分期、肿瘤细胞分化程度、肿瘤组织类型与宫旁转移无关。多因素分析显示肿瘤直径>2 cm、脉管浸润、盆腔淋巴结转移是IA2-IB1期宫颈癌宫旁转移的独立危险因素。结论 IA2-IB1期宫颈癌患者宫旁转移率低,肿瘤直径>2 cm、脉管浸润、盆腔淋巴结转移的患者易发生宫旁转移。     

乳腺癌间质血管密度和肿瘤细胞增殖活性及转移预测的研究

目的 :研究乳腺癌新生间质血管密度、肿瘤细胞增殖活性与临床指标间的相互关系 ,为临床判定肿瘤转移及预后提供新的指标。方法 :采用免疫组化方法对 31例乳腺癌进行了间质血管密度、肿瘤细胞增殖活性的检测。结果 :乳腺癌间质血管密度在淋巴结转移阳性者与淋巴结转移阴性者之间具有显著性差异 (P<0 .0 1 ) ;肿瘤细胞增殖活性随乳腺癌组织学级别的增高而增加 ;乳腺癌肿瘤细胞增殖活性随间质血管密度的增加而具有增高的趋势。结论 :乳腺癌间质血管密度及细胞增殖活性可以成为临床判定转移和预后的指标     

The impact of pelvic retroperitoneal invasion and distant nodal metastases in epithelial ovarian cancer

BackgroundThe absence of disease after debulking surgery is the most important prognostic factor in the treatment of advanced epithelial ovarian cancer (EOC). Occasionally, the presence of extra-abdominal disease complicates the ability to obtain a complete surgery, considering some locations of the metastatic disease as unresectable. The objective of the study was to estimate the survival impact of pelvic retroperitoneal invasion and extrapelvic and aortic distant nodal metastases in EOC patients. The anatomical landmarks of primary cytoreductive surgery will be discussed.Material and methodsWe reviewed data from 116 consecutive Mayo Clinic patients with epithelial ovarian cancer (EOC) stage IIIC and IV, undergoing primary cytoreduction surgery between 1996 and 2000. Univariate and multivariate analysis for patients with positive distant nodes and pelvic retroperitoneal invasion was performed, including 57 patients with no residual disease after surgery. Kaplan–Meier curves were used to estimate the probability of survival.ResultsThe median patient's age was 65 years (range 24–87 years). The 5 years overall survival was 44.8% (range 30.1–57.9 months) and the median length of survival was 39.9 months (range 0.13–60 months, 95% confidence interval: 30.1–57.9). Pelvic retroperitoneal invasion was present in 22 EOC patients (18.9%) and distant positive nodes were noted in 11 (9.5%): suprarenal/celiac (5.2%), inguinal (4.3%) and supraclavicular (0.9%). Univariate and multivariate Cox regression analysis, identified distant positive lymph nodes and pelvic retroperitoneal invasion as factors statistically associated with overall survival (p = 0.002 and p = 0.025, respectively).ConclusionsMetastatic distant nodes and pelvic retroperitoneal invasion are independent prognostic factors for survival in patients with advanced EOC.