HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status.

OBJECTIVES: To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy. METHODS: Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios. RESULTS: 9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p < 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p < 0.001. CONCLUSIONS: Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.

The Clearance of Serum Human Epididymis Protein 4 Following Primary Cytoreductive Surgery for Ovarian Carcinoma.

OBJECTIVE: The aim of this study was to examine the clearance of serum human epididymis protein 4 (HE4) in the immediate postoperative period in patients undergoing maximal effort cytoreductive surgery for ovarian carcinoma. METHODS: The study was performed at a tertiary gynecologic oncology center. The surgery was performed by accredited gynecological oncologists. RESULTS: Preoperative and serial postoperative venous blood samples at 4, 8, 24, 48, 72, 96, and 120 hours were taken from 10 sequential patients. Pretreatment HE4 is considered elevated at greater than 70 pmol/L. Human epididymis protein 4 was greater than 70 pmol/L in 7 patients, including all patients with high-grade serous carcinoma. Patients with preoperative elevation of serum HE4 and complete cytoreduction cleared more than 80% of serum HE4 in the first 4 hours and more than 88% within 5 days of surgery. One patient with incomplete cytoreduction of high-grade serous carcinoma had 66% clearance at 4 hours and a plateau thereafter. CONCLUSIONS: Human epididymis protein 4 derived from ovarian carcinoma had a short half-life of less than 4 hours in the circulation when cytoreductive surgery was complete. Sustained low HE4 following surgery could be a useful indicator of the completeness of cytoreduction. Plateau or rise in serum HE4 could suggest persistent disease. Comparison of values on day 1 and day 4 or 5 might have value in assessing the completeness of cytoreduction.

Retroperitoneal 'uterus-like mass' of cervical origin.

We report a rare case of a retroperitoneal uterus-like mass communicating with the endocervix, which presented as abdominal pain and bloating associated with severe irregular vaginal and postcoital bleeding. Our patient did not have any structural abnormalities of the urogenital system or otherwise, which makes a müllerian defect unlikely in our case. Based on the diagnostic criteria for the choristoma, that theory would be excluded here as the mass communicated with the endocervix. This strengthens the theory of metaplasia, under the effect of oestrogen and accelerated by the hyperoestrogenic state of pregnancy as the most likely postulate for our patient. Although the uterus-like mass is not commonly reported, it should be considered as a possible differential for pelvic masses.

Role of radiomics as a predictor of disease recurrence in ovarian cancer: a systematic review.

Ovarian cancer is associated with high cancer-related mortality rate attributed to late-stage diagnosis, limited treatment options, and frequent disease recurrence. As a result, careful patient selection is important especially in setting of radical surgery. Radiomics is an emerging field in medical imaging, which may help provide vital prognostic evaluation and help patient selection for radical treatment strategies. This systematic review aims to assess the role of radiomics as a predictor of disease recurrence in ovarian cancer. A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Studies meeting inclusion criteria investigating the use of radiomics to predict post-operative recurrence in ovarian cancer were included in our qualitative analysis. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. Six retrospective studies met the inclusion criteria, involving a total of 952 participants. Radiomic-based signatures demonstrated consistent performance in predicting disease recurrence, as evidenced by satisfactory area under the receiver operating characteristic curve values (AUC range 0.77-0.89). Radiomic-based signatures appear to good prognosticators of disease recurrence in ovarian cancer as estimated by AUC. The reviewed studies consistently reported the potential of radiomic features to enhance risk stratification and personalise treatment decisions in this complex cohort of patients. Further research is warranted to address limitations related to feature reliability, workflow heterogeneity, and the need for prospective validation studies.

Plasminogen activator inhibitor 1 is associated with high-grade serous ovarian cancer metastasis and is reduced in patients who have received neoadjuvant chemotherapy.

Introduction: High-grade serous ovarian cancer (HGSOC) is the most prevalent and deadliest subtype of epithelial ovarian cancer (EOC), killing over 140,000 people annually. Morbidity and mortality are compounded by a lack of screening methods, and recurrence is common. Plasminogen-activator-inhibitor 1 (PAI-1, the protein product of SERPIN E1) is involved in hemostasis, extracellular matrix (ECM) remodeling, and tumor cell migration and invasion. Overexpression is associated with poor prognosis in EOC. Platelets significantly increase PAI-1 in cancer cells in vitro, and may contribute to the hematogenous metastasis of circulating tumor cells (CTCs). CTCs are viable tumor cells that intravasate and travel through the circulation-often aided by platelets - with the potential to form secondary metastases. Here, we provide evidence that PAI-1 is central to the platelet-cancer cell interactome, and plays a role in the metastatic cascade. Methods: SK-OV-3 cells where PAI-1 had been silenced, treated with healthy donor platelets, and treated with platelet-conditioned medium were used as an in vitro model of metastatic EOC. Gene expression analysis was performed using RNA-Seq data from untreated cells and cells treated with PAI-1 siRNA or negative control, each with and without platelets. Four cohorts of banked patient plasma samples (n = 239) were assayed for PAI-1 by ELISA. Treatment-naïve (TN) whole blood (WB) samples were evaluated for CTCs in conjunction with PAI-1 evaluation in matched plasma. Results and discussion: Significant phenotypic changes occurring when PAI-1 was silenced and when platelets were added to cells were reflected by RNA-seq data, with PAI-1 observed to be central to molecular mechanisms of EOC metastasis. Increased proliferation was observed in cells treated with platelets. Plasma PAI-1 significantly correlated with advanced disease in a TN cohort, and was significantly reduced in a neoadjuvant chemotherapy (NACT) cohort. PAI-1 demonstrated a trend towards significance in overall survival (OS) in the late-stage TN cohort, and correlation between PAI-1 and neutrophils in this cohort was significant. 72.7% (16/22) of TN patients with plasma PAI-1 levels higher than OS cutoff were CTC-positive. These data support a central role for PAI-1 in EOC metastasis, and highlight PAI-1's potential as a biomarker, prognostic indicator, or gauge of treatment response in HGSOC.

Synchronous uterine artery embolization and laparoscopic myomectomy for massive uterine leiomyomas.

Uterine leiomyomas remain the commonest cause of menorrhagia and frequently cause pressure symptoms. Management of leiomyomas depends on the presenting symptoms, size, location, number of myomas, and the patient's desire to retain her uterus, fertility, or both. We present the first case of laparoscopic myomectomy for a fibroid measuring 30cm in maximum diameter.

Intravenous leiomyomatosis: the first reported case of intraoperative intracaval embolisation of tumour to the right atrium.

Intravenous leiomyomatosis is extremely rare. This case describes a 42-year-old woman who presented with abdominal distension, cyclical bloating and urinary retention. Preoperative imaging showed a multilobulated uterine mass. Following multidisciplinary team discussion, a complete staging surgery consisting of midline laparotomy, total hysterectomy and bilateral salpingo-oophrectomy was performed. Intraoperatively, a large multilobulated uterine mass was noted with engorgement of the infundibulopelvic ligaments due to intravascular extension of tumour. On removal of the uterus, the patient desaturated and became hypotensive. Intraoperative transoesophageal echocardiography revealed mass extending from the inferior vena cava (IVC) into the right atrium (RA). The cardiothoracic surgical team retrieved a worm-like mass extending from the IVC into the RA. Histopathological examination diagnosed a large uterine leiomyoma with intravenous leiomyomatosis. The mass from the RA was a bland spindle cell tumour which matched the uterine mass histopathologically. Intravenous leiomyomatosis is a rare variant of uterine leiomyoma. Although intracardiac extension has been described, this is the first case of intraoperative embolisation of pelvic tumour to the RA at hysterectomy.

Risk reduction surgery (RRS) for tubo-ovarian cancer in an Irish gynaecological practice: an analysis of indications and outcomes.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most common tubo-ovarian cancer. The fallopian tube harbours the precursor lesion: serous tubal intraepithelial carcinoma (STIC). Bilateral salpingo-oophorectomy is an effective risk-reducing surgical (RRS) strategy for breast cancer susceptibility gene mutation carriers (BRCAm). The value of RRS in those without defined genetic risk is unknown but these women represent a substantial cohort in prophylactic surgical practice. METHODS: This is a retrospective review of RRS at an Irish university teaching hospital. RESULTS: One hundred and thirty women underwent RRS; group 1 = 46 BRCAm; group 2 = 19 BRCAm negative/65 genetic status unknown. Group 1 had one occult HGSC. Group 2 had no STIC or cancers and were older and more likely to have hysterectomy and benign pathology. Other pathologies included serous tubal intraepithelial lesions (STIL) (2), p53 signatures (2), endometriosis (6), fibroids/adenomyosis (4) and atypical endometrial hyperplasia (1). CONCLUSION: More than 60% of women undergoing RRS were BRCAm negative or untested. Counselling of high-risk women without defined germline mutations remains a challenge for gynaecologists because the likelihood of removing STIC lesions or occult invasive cancer is low. Removal of coincidental pathology may give added value to RRS in these women.