Diagnosis, Therapy and Follow-up of Vaginal Cancer and Its Precursors. Guideline of the DGGG and the DKG (S2k-Level, AWMF Registry No. 032/042, October 2018).

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Premenstrual regulation of the pro-angiogenic factor CYR61 in human endometrium.

The pro-angiogenic factor cysteine-rich protein 61 (CYR61/CCN1) mediates different signals in tumorigenesis, angiogenesis and is involved in the pathogenesis of endometriosis. In this study we investigated the temporal and spatial expression pattern in human endometrium during the menstrual cycle and its possible regulation mechanisms in the premenstrual phase. CYR61 transcript expression showed two distinct periods of elevated levels in the proliferative phase and in menstrual effluents. Because the menstrual breakdown of the functionalis is triggered by cytokines, prostaglandins (PGs), as well as hypoxia, we used a benign endometrial cell line to investigate if CYR61 is regulated by these factors. Hypoxic conditions transiently induced CYR61 mRNA levels and enhanced the secretion of the CYR61 protein into the medium. The hypoxia-inducible factor (HIF) 1alpha mediated this effect on CYR61 as evidenced by dimethyloxalylglycine treatment and by HIF1alpha short interfering RNA. CYR61 mRNA expression was further regulated by IL-1, TNFalpha, PGE2, and PGF2alpha. In addition, TNFalpha and PGE2 elevated significantly CYR61 cellular protein levels in well-oxygenated cells but had only a slight effect on the quantity of secreted protein. Moreover, PGE2 combined with hypoxic conditions increased CYR61 mRNA and protein levels synergistically, whereas the combination with TNFalpha abolished the CYR61 levels induced by hypoxia. Together, the up-regulation of CYR61 by hypoxia via HIF1alpha, TNFalpha, and PGE2 could represent possible mechanisms for the CYR61 increase at the onset of menstruation. The opposite effect of TNFalpha combined with hypoxia on CYR61 up-regulation could contribute to a balanced expression level of this angiogenic factor in the endometrium.

TLR3 and TLR4 expression in healthy and diseased human endometrium.

BACKGROUND: Toll-like receptors (TLRs) play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases. METHODS: TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3). The expression studies applied quantitative RT-PCR and immunolabelling of both proteins. RESULTS: TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3). CONCLUSION: Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.

Fertility-preserving treatment in young women with endometrial cancer.

Nonsurgical fertility-preserving treatment of well-differentiated endometrial cancer with systemic progestins has been described for young women who desire to preserve their fertility. The overall response to progestin treatment in 9 retrospective studies is 79% with 79 subsequent live births. Recurrence can be expected in approximately 36-40% of conservatively treated patients who initially responded. Synchronous ovarian cancer has been reported in approximately 9%. However, amongst 162 receiving systemic, continuous treatment with progestins no death caused by cancer has been reported. We review guidelines for diagnosis, treatment and follow-up in young women undergoing conservative treatment for endometrial cancer.

[Surgical management of endometriosis--an overview]. / Operatives Management einer Endometriose--eine Ubersicht.

Laparoscopy is the treatment of choice in the diagnostics of endometriosis. Surgical management of early-stage endometriosis at the time of diagnosis is to be aimed at. Resection of peritoneal endometriosis is essential; coagulation/ablation may be an alternative. In the early stages, pain reduction is as effective as by drug therapy. Surgery improves fertility in these stages. Complete removal of an endometrioma lowers the recurrence rate and improves fertility. In cases of definitive surgical therapy, i.e. hysterectomy and adnexectomy, any accompanying endometriosis focuses have to be carefully resected. When clinically symptomatic, a deep endometriosis has to undergo radical surgery. In these cases, assisted reproduction is usually necessary when such a patient wants to become pregnant. The recurrence rate after complete surgical management of a serious endometriosis is lower compared to drug therapy; pain reduction is more effective. A postoperative drug therapy with GnRH analogues, danazole or gestagen does not improve fertility, the interval to a recurrence is however positively influenced. Hormonal replacement therapy after definitive surgical management has probably no influence on the recurrence rate.