Angiogenesis in the uterine cervix

Abstract. Abulafia O, Sherer DM. Angiogenesis in the uterine cervix.
Our objective was to present current data pertaining to angiogenesis of the uterine cervix. We conducted a computerized search to identify relevant studies published in the English language literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, uterine cervix, intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966 through June 1999. In contrast to the cyclic phases of the menstrual cycle of the ovary and endometrium in which angiogenesis plays a significant physiologic role, angiogenesis in the uterine cervix is involved primarily in neoplastic processes. These include intraepithelial disease, human papilloma-related disease, and microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis appears to be a prognostic indicator for overall survival and disease-free survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy such as TNP-470 have been reported and concurrent antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.     

Assessment of pelvic lymph node micrometastatic disease in stages IB and IIA of carcinoma of the uterine cervix

The objective of this study was to assess the frequency of micrometastatic disease (MID) in pelvic lymph nodes (PLNs) in carcinoma of the uterine cervix (CUC) and to determine the risk of recurrence. The PLNs from 289 patients with CUC (IB and IIA) were studied. Each PLN was assessed via immunohistochemistry using a single histologic section (AE1/AE3). Metastatic deposits were measured and the disease status was classified into three groups: 1) absence of metastatic disease (MOD); 2) MID, one or more metastatic PLN with only isolated tumor cells and/or micrometastases (up to 2 mm); and 3) macrometastatic disease (MAD), presence of one or more metastatic PLN with macrometastases (more than 2 mm). Eleven patients (3.8%) were classified as having MID and 37 (12.8%) as having MAD. The 5-year disease-free survival (DFS) rates for MOD, MAD, and MID were 88.7%, 80.4%, and 50.0%, respectively (P < 0.001). The Cox proportional hazards model showed that MID was an independent variable for recurrence when adjusted for MAD, depth of tumor invasion, severity of inflammatory reaction, and use of adjuvant radiotherapy. We conclude that the frequency of MID in PLN was low. However, patients with MID presented a high risk of recurrence and reduced DFS.     

Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune orchitis

Experimental autoimmune orchitis (EAO) is an organ-specific model of autoimmunity characterized by an interstitial lymphomononuclear cell infiltrate as well as sloughing and apoptosis of germ cells. EAO was induced in adult male Sprague–Dawley rats by active immunization with testicular homogenate and adjuvants. Rats injected with saline solution and adjuvants were used as control group. The aim of this work was to study the expression of interleukin-6 (IL-6) and its receptor (IL-6R) in the testis of rats with EAO and analyze whether IL-6 could be involved in germ cell apoptosis. By immunohistochemistry, we detected IL-6 expression in testicular macrophages and Leydig cells of control and EAO rats. Sertoli cells showed IL-6 immunoreactivity in most of the seminiferous tubules of control rats, while a few IL-6⁺ Sertoli cells were found in the testis of rats with EAO. IL-6R immunoreactivity was observed in macrophages, Leydig and germ cells. A significant increase was noted in the number of IL-6R⁺ germ cells in rats with EAO compared to control rats. The content of IL-6 (ELISA) in the conditioned media obtained from testicular macrophages of rats with orchitis was significantly higher than in the control group. By immunofluorescence performed on isolated testicular macrophages, IL-6 was shown to be expressed by monocytes recently arrived from circulation (ED1⁺ cells), while resident macrophages (ED2⁺ cells) were negative. In vitro experiments (trypan blue and MTS assays) showed that IL-6 (50 ng/ml) reduced germ cell viability. We demonstrated also using the TUNEL technique that IL-6 added to cultures of seminiferous tubule segments induced apoptosis of germ cells. Our results suggest that IL-6 and IL-6R may be involved in the pathogenesis of autoimmune orchitis by promoting testicular inflammation and germ cell apoptosis.     

Small cell carcinoma of the cervix

Small cell carcinoma of the cervix is an uncommon aggressive variety of cervical cancer. Between 1982 and 1993, eight cases of this disease were diagnosed at the Queensland Centre for Gynaecological Cancer among 1586 cervical cancers. Treatment results have been poor with one long-term survivor. Literature review suggests that aggressive chemotherapy combined with surgery and/or radiotherapy may improve survival.     

Radiotherapeutic management in carcinoma of the uterine cervix: current status

Despite refinement in the delivery of external radiation and brachytherapy, there has been little improvement in the survival rate of patients with invasive cancer of the uterine cervix in recent years. With advancing stage disease, there is an increase in both local failure and distant metastases. Although recent efforts to improve local control for late stage disease have been encouraging, research efforts should be directed to the identification of new active drugs for radiation sensitization and systemic therapy. Also, due to early detection, therapeutic investigations should focus on the high-risk subsets of patients with early stage disease.     

中药二至天癸颗粒对控制性超排卵周期卵泡液IL-1β、IL-6以及对胚胎质量的影响

目的:探讨补肾中药二至天癸颗粒对提高控制性超排卵所获卵和胚胎质量的作用机理。方法:将66例因输卵管因素行IVF-ET的患者随机分为中药+控制性超排组(实验组,n=33)和控制性超排组(对照组,n=33)。应用双抗体酶联免疫吸附法(ELISA)检测取卵日成熟卵泡卵泡液IL-1β、IL-6水平,移植日采用形态学标准对胚胎进行评分。结果:实验组卵泡液IL-1β水平显著高于对照组(P<0.05);实验组的胚胎评分显著高于对照组(P<0.01);卵泡液IL-1β与移植日胚胎评分呈正相关(P<0.01)。结论:二至天癸颗粒能够改善控制性超排卵周期的胚胎质量,可能与调控卵泡液IL-1β水平有关。     

Minimal deviation adenocarcinoma of the uterine cervix

Background

Precise preoperative diagnosis of minimal deviation adenocarcinoma (MDA) of the uterine cervix is often difficult because the histological features of MDA closely resemble those of normal cervical glands.

Objective

To review the developments in the diagnosis and treatment of MDA over the past 35 years.

Search strategy

We performed a meta-analysis of all case reports published in the English and Chinese languages between 1975 and 2009 that included a histopathologic diagnosis of MDA. Pooled odds ratios and 95% CIs were calculated for comparisons and analyzed.

Results

The histopathologic diagnosis of MDA remains difficult and is currently based on antigen detection by immunohistochemistry. Cytologic assessment and routine biopsy have low detection rates for MDA. Cross-sectional imaging techniques are helpful but a deep cervical biopsy or cervical conization is necessary for a definitive diagnosis. The mean survival is about 5 years for patients with stage I, 38.1 months for patients with stage II, 22.8 months for patients with stage III, and 5.4 months for patients with stage IV MDA.

Conclusion

Early diagnosis and treatment are key to improving prognosis and survival in patients with MDA.     

The basement membrane in the carcinoma in situ of the cervix: A morphological study

A morphological study of the basement membrane in the carcinoma in situ of the cervix has been carried out.Undifferentiated carcinoma in situ that arises usually from the squamocolumnar junction and which extends into the endocervical canal, always shows a continuous and clearly delineated basement membrane, which runs parallel to the basal layer. It has a homogeneous appearance. The hemidesmosomes attached to the lamina propria are quite normal and there are no slender protrusions from basal cells into the lamina propria.Differentiated carcinoma in situ, that originates in the squamous epithelium of the portio, may extend either in the direction of vagina, or towards the endocervical canal. It is always underlined by a basement membrane loosely constituted of irregular or fragmented reticular fibers; it frequently looses its homogeneous appearance and may be dehiscent or duplicated. Basal cells send down small pseudopods or threadlike extensions into the lamina propria.The authors suggest that in the management of carcinoma in situ of the cervix, one should take into consideration the direction of spread and the stroma-invasion potential of the carcinoma. These histologic patterns carry with them a very important morphologic implication, namely ‘cells differentiation’ of the carcinoma.     

Clinical significance of mucin production in post-irradiated cervical carcinoma

Summary Histological sections from 50 patients with clinical stage Ib to stage IIb squamous cell carcinoma of the cervix, initially treated by radiotherapy and followed by Wertheim hysterectomy, were reviewed and stained for mucin. The tissues from 17 (34%) of the patients contained no residual carcinoma. Mucin production was demonstrated in tumour tissue from 18 (55%) of the patients with residual tumour, none of who died of disease during the 5 to 10 years of follow up. Two patients who died of recurrent carcinoma had no mucin production in the post-irradiated tumour tissues. The presence of mucin in irradiated carcinoma of cervix seems to infer a better prognosis and this may prove useful in the follow-up of irradiated carcinomas.     

IL-2、IL-6在HBV母婴传播中的作用

目的探讨IL2、IL6在乙型肝炎病毒(HBV)母婴传播中的作用。方法2002年1月至2003年3月中山大学附属第三医院检测53例HBsAg阳性孕妇和13例正常妊娠孕妇及其新生儿的HBV血清标志物、HBVDNA和IL2、IL6。结果与正常妊娠孕妇比较,孕28～29周时HBsAg阳性孕妇其血IL2水平明显降低,IL6水平明显升高,差异有显著性(P<0.05)。使用HBIG行产前阻断治疗后,HBsAg阳性孕妇的IL2水平上升、IL6水平下降,治疗前后差异有显著性(P<0.05)。HBsAg阳性孕妇未使用药物治疗组和正常妊娠组的IL2、IL6水平,孕28～29周和分娩前比较,差异无显著性(P>0.1)。HBsAg阳性孕妇使用HBIG治疗组和未治疗组,宫内感染率分别为6.25%和28.60%,两组差异有显著性(P<0.05)。结论HBsAg阳性孕妇的IL2、IL6水平失衡。产前应用HBIG可改善HBsAg阳性孕妇的IL2、IL6失衡状态,使其向Th1方向发展,这可能是HBIG阻断HBV宫内感染的机制之一。     

An asymmetric, posterior spacing system for use withmini-ovoids in the treatment of carcinoma of the cervix

Stevens CW, Benjamin I, Epperson RD, Rubin SC, Solin LJ. An asymmetric,posterior spacing system for use with mini-ovoids in the treatment of carcinomaof the cervix. Int J Gynecol Cancer 1997; 7 : 350–354.
Customized brachytherapy implants are an important component of themanagement of patients with carcinoma of the cervix. An asymmetric,posterior-spacing system was designed toimprove the ability to deliver customized brachytherapy implants. This systemattaches to standard mini-ovoids to selectively increase the distance betweenthe ovoids and rectum,thereby reducing the radiation dose to the rectum. The posterior spacing systemis used at the time of tandem and ovoid placements that require mini-ovoids.Minimal operative timeis required, and no loading adjustments are needed. The system can besterilized and re-used. Significant rectal dose reduction in the range of10% to 25% can be achieved.This posterior spacing system has several advantages over typical packing inmini-ovoid applications: (1) Since mini-ovoids are only used in patients withnarrow vaginal vaults,the posterior spacing system provides guaranteed spacing in tight surroundings;(2) The spacing system is rapid to employ, thereby minimizing anesthesia time;(3) The spacingsystem will not slip out of position. The asymmetric posterior spacing systemis useful for patients in whom selective posterior spacing is required toreduce the radiation dose tothe rectum from brachytherapy using tandem and ovoids for the treatment ofcarcinoma of the cervix.     

A short and intensive single-agent cisplatin regimen for recurrent carcinoma of the uterine cervix

Between May 1991 and September 1993, 36 patients with recurrent carcinoma of the uterine cervix were treated with single-agent cisplatin using an intensive regimen of four weekly cycles of 50 mg m⁻² followed in responders by a further four cycles given every fortnight. The response rate was 47% (95% CI: 27–66%), 56% in those with pelvic recurrence, and 38% in those with metastatic disease. All responses but one were seen within 4 weeks of commencing treatment. Three patients (9%) had a complete response, although in two cases this was of short duration. The treatment was moderately well tolerated and the principle toxicities were myelotoxicity and emesis. The median survival was 32 weeks, and the 18-month survival was 13%.
This regimen gives a response rate similar to that seen with more toxic combination chemotherapy regimens such as BIP (bleomycin, ifosfamide and cisplatin). It has the particular advantages of a short duration of treatment and early response, allowing treatment to be stopped after 4 weeks in non-responders. The response rate in pelvic recurrence was better than that seen in most previous chemotherapy trials, particularly as 78% of the evaluable patients with pelvic recurrence had previously received radical radiotherapy to the pelvis.
Weekly, followed by fortnightly cisplatin, is an appropriate palliative treatment for patients with recurrent carcinoma of the uterine cervix for whom chemotherapy is indicated.     

子宫颈小细胞癌——一种特殊类型宫颈癌

目的 了解子宫颈小细胞癌(SCCC)的临床病理与生物学行为特征,探讨其治疗方法。方法回顾性分析6例SCCC患者的临床病理资料及随访记录。结果Ib期Ⅰ例、Ⅱa期2例、Ⅲb期3例。盆腔淋巴结转移2例,肝等器官转移4例,对6例患者采用手术+放疗+化疗或放疗+化疗的综合治疗,2例分别已存活30、20个月,另4例分别存活10、11、13、14个月后死亡。结论 子宫颈小细胞癌与肺小细胞癌的组织病理学和生物学行为特征相似,早期易发生盆腔淋巴结和远处转移,对化学治疗比较敏感。对早期患者应行广泛性子宫切除术+盆腔淋巴结清扫术,术后给予辅助性放疗和化疗;对晚期患者应采用放疗和化疗。     

Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix

Objectives

(1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence.

Study design

This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (IB and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson's χ²-test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan–Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence.

Results

There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p < 0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p = 0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p < 0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p = 0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p = 0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors.

Conclusion

The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted.     

Variations in the distribution of glycosaminoglycans in the uterine cervix of the pregnant woman

A study was made of the modifications of glycosaminoglycans in the uterine cervix and the relationship to gestation. These substances are essential constituents of connective tissue, and a modification of their concentration could affect the physical and chemical characteristics of the cervix.Glycosaminoglycans were extracted from cervical biopsies obtained from pregnant and non-pregnant women. This study showed dermatan sulfate to be quantitatively the most important glycosaminoglycan in the cervix of both the groups studied, and that a significant decrease in the concentration of both dermatan sulfate and chondroitin sulfates occurred in the biopsies obtained just after delivery. This was related to a decrease of collagen in the cervix at the end of gestation, as the proteoglycans containing dermatan sulfate are principally associated with collagen.