A practical guide to the evaluation of benign endometrial conditions in biopsy and curettage material

Sampling of the endometrium, via biopsy or dilation and curettage, is an important diagnostic tool in a wide variety of clinical scenarios, ranging from infertility and abnormal uterine bleeding to cancer surveillance in high-risk populations. This review describes the most common methods for endometrial sampling used currently and discusses the issue of specimen adequacy from an evidence-based perspective. It also focuses on select benign conditions involving the endometrium in the setting of abnormal uterine bleeding, ranging from anatomic/structural lesions to patterns indicative of a dysfunctional menstrual cycle. The topic of endometrial sampling evaluation in the context of recurrent pregnancy loss is also discussed, with insights on documentation of endometrial changes during the ovulatory phase and the diagnosis of endometritis.     

不同照射方式下核黄素-A波紫外线兔巩膜胶原交联术对兔巩膜成纤维细胞生物力学特性的影响

目的　研究不同照射方式下核黄素-A波紫外线兔巩膜胶原交联术对兔巩膜成纤维细胞生物力学特性的影响。方法　取健康新西兰大白兔24只，随机将兔平均分为A、B两组，每组选取左眼为实验眼，右眼为对照眼。麻醉后暴露左眼鼻上方巩膜。在该处巩膜滴加5-磷酸核黄素5 min后，用波长为370 nm的紫外线灯照射。A组的照射时间为30 min，能量密度为3.0 mW·cm^-2；B组的照射时间为9 min，能量密度为10.0 mW·cm^-2。照射期间，每2 min滴加1次5-磷酸核黄素溶液，以保持巩膜的湿润。术后60 d，处死实验兔，培养实验眼交联部位及对照眼相应部位的巩膜成纤维细胞，用细胞微管吸吮实验检测巩膜成纤维细胞的杨氏模量、表观黏性。结果　A、B两组实验眼巩膜细胞的杨氏模量、表观黏性均较各自对照眼显著增强，差异均有统计学意义（均为P＜0.05）；而A、B两组实验眼间、及对照眼间巩膜细胞的杨氏模量、表观黏性差异无统计学意义（均为P＞0.05）。以上结果表明，交联术后巩膜细胞的黏弹性发生了明显的变化，黏弹性显著升高。而两种照射方式之间巩膜细胞的黏弹性无显著差异。结论　两种不同的照射方式，均能使巩膜成纤维细胞的生物力学性能发生显著增强，而两种照射方式之间并未见明显的差别。     

Principles of chemotherapy and radiotherapy

The current management of all gynaecological malignancy requires complex multidisciplinary investigation and discussion, leading to multi-modality treatment. The delivery of systemic therapy or radiotherapy can have different aims depending on the type of cancer, clinical context and patient wishes. This review explores the systemic treatment options and radiotherapy that form part of the standard management of this group of tumours and looks at current research that may help shape the treatment of the future.     

Pharmacodynamics of combined estrogen–progestin oral contraceptives: 4. Effects on uterine and cervical epithelia

ABSTRACT

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.

Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 μg), medium- (30 μg), low- (20 μg), ultralow- (15 μg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.

Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.

Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.

In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.     

Noncatalytic PTEN missense mutation predisposes to organ-selective cancer development in vivo

Inactivation of phosphatase and tensin homology deleted on chromosome 10 (PTEN) is linked to increased PI3K–AKT signaling, enhanced organismal growth, and cancer development. Here we generated and analyzed Pten knock-in mice harboring a C2 domain missense mutation at phenylalanine 341 (Pten^FV), found in human cancer. Despite having reduced levels of PTEN protein, homozygous Pten^FV/FV embryos have intact AKT signaling, develop normally, and are carried to term. Heterozygous Pten^FV/+ mice develop carcinoma in the thymus, stomach, adrenal medulla, and mammary gland but not in other organs typically sensitive to Pten deficiency, including the thyroid, prostate, and uterus. Progression to carcinoma in sensitive organs ensues in the absence of overt AKT activation. Carcinoma in the uterus, a cancer-resistant organ, requires a second clonal event associated with the spontaneous activation of AKT and downstream signaling. In summary, this PTEN noncatalytic missense mutation exposes a core tumor suppressor function distinct from inhibition of canonical AKT signaling that predisposes to organ-selective cancer development in vivo.     

Antibody persistence and booster response following MenACWY-CRM vaccination in children as assessed by two different assay methods

BackgroundThe quadrivalent meningococcal conjugate vaccine MenACWY-CRM has been shown to be immunogenic and well-tolerated in infants and toddlers. We evaluated antibody persistence for up to 4 years after vaccination with MenACWY-CRM in the first years of life and response to a booster dose administered at 60 months of age.MethodsThis was phase 3b, open-label, multicenter extension trial (NCT01148017). We assessed by hSBA and rSBA the persistence of antibody responses to serogroups ACWY in 203 healthy 60-month-olds receiving 4 doses of MenACWY-CRM during infancy (ACWY-4 group), or 2 doses at 12/13 and 15 months or 1 dose at 18 months of age (ACWY-2 group). We administered a MenACWY-CRM dose to 224 primed and 45 naïve 60-month-olds and evaluated safety and antibody response 1 month later.ResultsAntibody persistence measured by both assays was higher in primed than naïve 60-month-olds. The percentages of primed children with hSBA titers ≥8 was low for serogroup A (6–25%) and moderate for serogroups C (27–43%), Y (69–74%) and W (56–69%). For all serogroups, hSBA antibody geometric mean titers (GMTs) tended to be higher in the ACWY-2 than the ACWY-4 group. Post-booster/single dose, ≥96% of primed and ≥73% of naïve children had hSBA titers ≥8 against each serogroup, and hSBA GMTs were higher in primed children. The booster dose was well-tolerated and no safety concern was identified. We further assessed persistence using rSBA across different age groups and detected no overall correlation between rSBA and hSBA titers.ConclusionsPrimary vaccination of infants/toddlers with MenACWY-CRM resulted in moderate antibody persistence against serogroups C, W and Y for up to 4 years after the last priming dose. Regardless of priming schedule, a MenACWY-CRM booster dose at 60 months of age induced a robust immune response against all serogroups and was well-tolerated in all children.     

国产弹性蛋白酶浸泡法构建兔腹主动脉瘤及其随访

目的采用国产猪胰弹性蛋白酶溶液主动脉周浸泡法构建兔腹主动脉瘤(AAA)模型,并随访其长期稳定性。方法 24只新西兰兔随机分成两组,实验组(n=12)用10μL浓度为10 U/μL国产猪胰弹性蛋白酶溶液浸润主动脉近分叉处血管段30 min,对照组用10μL 0.9%氯化钠溶液浸润30 min。术前和术后5、15、40、100、150 d分别经耳缘静脉造影测量主动脉内径。术后5、15、150 d造影后每组分别处死4只兔作苏木精-伊红(HE)、弹力纤维EVG染色和免疫组化染色。结果实验组术后5 d均形成AAA,主动脉直径100 d内基本稳定,150 d时明显缩小;组织学上术后5 d血管壁严重破坏、结构紊乱,可见红细胞渗出和炎性细胞浸润,弹力纤维和平滑肌细胞明显减少甚至消失,15 d时血管结构规整,可见部分残留弹力纤维,未见炎性细胞,150 d时管腔变窄,内膜过度增生,可见大量平滑肌细胞增生和紊乱的新生弹力纤维。对照组均未见AAA形成,病理学无明显变化。结论国产猪胰弹性蛋白酶溶液浸泡法可诱导兔AAA形成,操作简单、安全、有效。该模型有自愈倾向,但100 d内基本稳定,有助于AAA机制研究。