Concept: Endometrial cancer
Measurement of endometrial thickness is an important tool in the assessment of women with postmenopausal bleeding, but the role of endometrial thickness measurement by ultrasound in asymptomatic women is unclear. The aims of this study were to determine: (1) the normal endometrial thickness measured by ultrasonography, (2) the prevalence of serious endometrial pathology and (3) the sensitivity and specificity of endometrial thickness measurement by transvaginal ultrasonography (TVS) for diagnosing premalignant and malignant endometrial disease in asymptomatic postmenopausal women.
Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer. Here, we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger (SDGE) are potent inhibitors of proliferation of endometrial cancer cells. SDGE, isolated from six different batches of ginger rhizomes, consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC(50) of 1.25 µg/ml. SDGE also enhanced the anti-proliferative effect of radiation and cisplatin. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3. GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE, with the isomers neral and geranial constituting 30-40%. Citral, a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC(50) 10 µM (2.3 µg/ml). Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells. SDGE was more effective in inducing cancer cell death than citral, suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death. SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20-40% decrease in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE. This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax. Inhibitor of p53, pifithrin-α, attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53(neg) SKOV-3 cells. Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer.
The current study sought to assess the role of paraaortic lymphadenectomy (LNE) in females with endometrial cancer. A retrospective analysis of patients diagnosed with endometrial cancer of stage IA to II preoperatively, between 2009 and 2011 was conducted. Patients were included who had suffered from endometrial cancer without preoperative adjuvant therapy and who underwent hysterectomy plus systematic pelvic LNE and paraaortic LNE by laparoscopy or laparotomy. A total of 54 patients who underwent surgery for preoperative endometrial cancer were selected. All patients underwent LNE. The incidences of pelvic and paraaortic lymph node metastases were 11.1% (6/54) and 7.4% (4/54), with a total positive lymph node rate of 14.8% (8/54). In addition, among the 8 positive cases, 5 patients underwent laparotomy and 3 underwent laparoscopy; 3 cases were classified as stage I and 5 as stage II preoperatively. Of these, 7 patients were identified with pathology-related risk factors, including low differentiation or clear cell adenocarcinoma postoperatively. Discordance of pathological differentiation between the pre- and postoperative stages reached 57.1% (4/7). The results revealed the high occurrence of positive lymph nodes in endometrial cancer which demonstrate the importance of systematic LNE. Additonally, no severe complications were caused by LNE besides lymph cysts. In summary, it is neccesary to perform LNE, particularly the removal of the paraaortic lymph node, in patients with endometrial cancers in order to improve postoperative therapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.
OBJECTIVE: To analyze the outcomes of second round of fertility-sparing management using progestin in patients with recurrent endometrial cancer after successful fertility-sparing management using progestin. METHODS: We reviewed 45 patients who had recurrence after achieving complete remission by fertility-sparing management using progestin for presumed stage IA, grade 1, endometrioid adenocarcinoma of the uterus. Of 45 patients, 33 tried progestin re-treatment at recurrence and were included in this study. RESULTS: Recurrent disease was atypical hyperplasia in 13 patients (39%) and grade 1 endometrioid adenocarcinoma in 20 patients (61%) which were confined to the endometrium. Thirty patients (91%) received medroxyprogesterone acetate (dose range, 80-500 mg/day) and three patients (9%) received megestrol acetate (dose range, 80-160 mg/day), with 29 patients receiving a dose of 500 mg/day of medroxyprogesterone acetate. The median duration of treatment was 6 months (range, 3-19 months). Five patients failed to respond to progestin re-treatment and underwent definitive surgical treatment including hysterectomy. Twenty eight patients (85%) showed complete response to progestin re-treatment. The median follow-up time after progestin re-treatment in 28 patients who achieved complete remission was 51 months (range, 24-160 months). During follow-up, five patients had second recurrence after median time interval of 14 months (range, 4-82 months). All patients who tried progestin re-treatment are alive without evidence of disease. CONCLUSION: Progestin re-treatment in patients with recurrent endometrial cancer was effective and safe. Therefore, this can be recommended for young women who still want to preserve fertility at recurrence after complete response to progestin.
Natural estrogen decline leads to vasomotor symptoms (VMS). Hormone therapy alleviates symptoms but increases cancer risk. Effective treatments against VMS with minimal cancer risks are needed. We investigate the effects of a highly bioavailable aglycone rich Red Clover isoflavone treatment to alleviate existing menopausal VMS, assessed for the first time by 24hour ambulatory skin conductance (SC).
There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50-64 y and cervical cancer at age 65-83 y.
Cervical cancer screening usually requires use of a speculum to provide a clear view of the cervix. The speculum is one potential barrier to screening due to fear of pain, discomfort and embarrassment. The aim of this paper is to present and demonstrate the feasibility of a tampon-sized inserter and the POCkeT Colposcope, a miniature pen sized-colposcope, for comfortable, speculum-free and potentially self-colposcopy.
Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis.
Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer.
To assess the impact of cervical screening interval recommendations on cervical cancer incidence and mortality during periods of organized and opportunistic screening in Australia (2-yearly screening interval for organized screening), New Zealand (3 yearly interval for organized screening), and England (3/5 yearly interval for organized screening).