Ovarian serous adenocarcinoma identified during IVF: diagnostic approach, surgical management, and reproductive outcome

BACKGROUND: To present a diagnostic evaluation and treatment strategy for serous adenocarcinoma of the ovary discovered during an in vitro fertilisation (IVF) sequence, and report on reproductive outcome after tumour resection and embryo transfer. CASE PRESENTATION: Cycle monitoring in IVF identified an abnormal ovarian lesion which was subjected to ultrasound-guided needle aspiration. Cytology suggested malignancy, and unilateral oophorectomy was performed after formal staging. After surgery, the patient underwent an anonymous donor oocyte IVF cycle which established a viable twin intrauterine pregnancy. No recurrence of cancer has been detected in the >72 month follow-up interval; mother and twin daughters continue to do well. CONCLUSION: Suspicious adnexal structures noted during controlled ovarian hyperstimulation for IVF warrant assessment, and this report confirms the role of aspiration cytology in such cases. If uterine conservation is possible, successful livebirth can be achieved from IVF if donor oocyes are utilised, as described here

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Return Migration to Mexico: Does Health Matter?

We use data from three rounds of the Mexican Family Life Survey to examine whether migrants in the United States returning to Mexico in the period 2005–2012 have worse health than those remaining in the United States. Despite extensive interest by demographers in health-related selection, this has been a neglected area of study in the literature on U.S.-Mexico migration, and the few results to date have been contradictory and inconclusive. Using five self-reported health variables collected while migrants resided in the United States and subsequent migration history, we find direct evidence of higher probabilities of return migration for Mexican migrants in poor health as well as lower probabilities of return for migrants with improving health. These findings are robust to the inclusion of potential confounders reflecting the migrants’ demographic characteristics, economic situation, family ties, and origin and destination characteristics. We anticipate that in the coming decade, health may become an even more salient issue in migrants’ decisions about returning to Mexico, given the recent expansion in access to health insurance in Mexico

MyD88 expression and survival (Kaplan-Meier curves: median survival time shown in months).

<p>MyD88 positive tumours (n = 12) had significantly reduced progression-free survival (A) and overall survival (B) (p = 0.018 and p = 0.008, respectively).</p

Heterogeneous expression of monoclonal anti-TLR4.

<p>A: variable staining observed in adjacent epithelium within a benign serous cystadenoma (20x). B: focal strong staining within a serous carcinoma (40x).</p

The effect of silencing MyD88 and TLR4 mRNA on the chemoresponsive properties of SKOV-3 cells.

<p>SKOV-3 cells were left untransfected (Unt), transfected with negative control siRNA (siNeg), MyD88 targeting siRNA (siMyD88) or TLR4 targeting siRNA (siTLR4). The transfected cells were incubated for 72 hrs before either harvesting for mRNA analysis (A), for protein analysis (B) or treatment with paclitaxel (C). (A) MyD88 and TLR4 mRNA expression levels were evaluated by TaqMan RT-PCR. MyD88 and TLR4 mRNA expression was normalised to that of an endogenous control, B2M, and calibrated to that of untreated cells to establish the relative percentage of mRNA expression (n = 3, mean +SD). (B) MyD88 and TLR4 mRNA expression levels were evaluated by western blot analysis. GAPDH was used as a loading control. (C) Transfected cells were either left untreated, treated with DMSO (vehicle control) or 3.5 nM of paclitaxel (IC25). 48 hrs post treatment, cell viability was assessed by means of the CCK-8 assay. % cell viability rate was calculated by comparing the absorbance values for the vehicle control to the corresponding paclitaxel treated samples. Results are expressed as mean +SD, n = 3; *p<0.05, **p<0.01 (un-paired Student's t-test).</p

TLR4/MyD88 and progression-free survival (Kaplan-Meier curves; median survival shown in months).

<p>TLR4 (A) or MyD88 (B) negative cases had significantly better PFS (15 & 18 months longer; p<0.05).</p