Optimal primary management of bulky stage IIIC ovarian, fallopian tube and peritoneal carcinoma: Are the only options complete gross resection at primary debulking surgery or neoadjuvant chemotherapy?

OBJECTIVE: To explore the impact of primary debulking surgery (PDS) to minimal but gross residual disease (RD) in women with bulky stage IIIC ovarian, fallopian tube, or primary peritoneal cancer. METHODS: We retrospectively reviewed all patients with the aforementioned diagnosis who underwent PDS at our institution from 01/2001-12/2010. Those with disease of non-epithelial histology or borderline tumors were excluded. Clinicopathologic data were abstracted, and appropriate statistical tests were used. RESULTS: We identified 496 eligible patients. Median age was 62years; 91% had disease of serous histology. Patients were grouped by RD status: no gross RD, 184 (37%); RD of 1-5mm, 127 (26%); RD of 6-10mm, 54 (11%); and RD >10mm, 131 (26%). With a median follow-up of 53months, the median progression-free survivals (PFS) were: 26.7, 20.7, 16.2, and 13.6months, respectively (p<0.001). The median overall survivals (OS) were 83.4, 54.5, 43.8, and 38.9months, respectively (p<0.001). Among patients with RD following PDS, those with RD of 1-10mm had improved PFS (p<0.001) and OS (p=0.001) compared with those with RD >10mm. Patients with RD 1-10mm who received intravenous/intraperitoneal (IV/IP) chemotherapy were younger and had prolonged OS compared with those solely exposed to IV chemotherapy (p<0.001 and p=0.002, respectively). CONCLUSIONS: PDS to no gross RD was associated with the longest PFS and OS. However, cytoreduction to 1-10mm of RD was also associated with better survival outcomes compared with cytoreduction to >10mm of RD. We conclude that PDS remains an appropriate option for patients with a high likelihood of achieving RD 1-10mm, especially for younger patients who can receive IV/IP chemotherapy after PDS.

Robotically Assisted Laparoscopic Ovarian Transposition in Women with Lower Gastrointestinal Cancer Undergoing Pelvic Radiotherapy.

BACKGROUND: Pelvic radiotherapy (RT) is a standard component of the management for patients with locally advanced rectal cancer or squamous cell carcinoma of the anus. Pelvic RT leads to permanent and irreversible ovarian failure in young women. This study aimed to determine the effectiveness of robotically assisted laparoscopic ovarian transposition (OT) before RT in women with rectal or anal cancer who wanted to preserve normal ovarian function. METHODS: The study reviewed the medical records of all patients treated at our institution from August 2009 to October 2014 who received robotically assisted laparoscopic OT for rectal or anal cancer before RT. Clinical and hormonal data were abstracted to determine ovarian function. RESULTS: The study identified 22 women with rectal (n = 20) or anal (n = 2) cancer. The median age of the women was 39 years (range 26-45 years). For one patient, OT was technically not feasible. The postoperative course was uneventful in all but one case. Follow-up data on ovarian function were unavailable for 3 patients. The median times from RT initiation to the last gynecologic or hormonal evaluation were 9 months (range 5-47 months) and 10.5 months (range 5-47 months), respectively. At the last gynecologic or hormonal follow-up visit, ovarian function was preserved in 12 (67%) of 18 evaluable patients, including 9 (90%) of 10 patients 40 years of age or younger and 3 (38%) of 8 patients older than 40 years (P = 0.07). CONCLUSIONS: Robotically assisted laparoscopic bilateral OT is safe and can lead to preservation of ovarian function in two-thirds of patients with low gastrointestinal cancer undergoing pelvic RT. It should be considered in this setting, especially for women age 40 years or younger, to avoid premature menopause and its associated sequelae.

The role of miRNAs in endometrial cancer.

miRNAs are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Since their discovery, miRNAs have been associated with every cell function including malignant transformation and metastasis. Endometrial cancer is the most common gynecologic malignancy. However, improvement should be made in interobserver agreement on histological typing and individualized therapeutic approaches. This article summarizes the role of miRNAs in endometrial cancer pathogenesis and treatment.

The contribution of sildenafil (Viagra) to ovarian stimulation with gonadotropins in a woman with poor ovarian response.

We aim to present the first case of a pregnancy achieved by administering sildenafil (Viagra) to a woman not responding to controlled ovarian hyperstimulation (COH) with the sole use of gonadotropins. A 37-year-old woman underwent COH, as part of an intracytoplasmic sperm injection (ICSI) cycle, with the combination of r-FSH and HMG for 13 d, without evidence of follicular growth. The addition of oral sildenafil at a dose of 50 mg per day for a total of five doses improved the ovarian response and resulted in the retrieval of 10 oocytes. Three embryos were transferred to the uterine cavity resulting in a successful pregnancy and, eventually, the delivery of a healthy neonate. Conclusively, the use of sildenafil as an adjunct to COH protocols may enhance ovarian response in a woman with poor ovarian response (POR) and merits further research.

The immunomodulatory and anti-apoptotic effect of dexamethasone in imminent preterm labor: an experimental study.

The study was designed to investigate the effect of dexamethasone (DEX) on the latency period to delivery in a murine model of preterm labor. To this purpose, pregnant mice were randomly assigned in groups: the control group received water for injection (n=20), the preterm labor group was injected with lipopolysaccharide (LPS) (n=22), while the glucocorticoids group was administered DEX either 1h before (n=17) or after (n=7) lipopolysaccharide. In a first set of experiments animals were monitored to record perinatal outcomes. In another set of experiments, the remaining animals were sacrificed eight h after interventions. Fetuses were homogenized to measure tumor necrosis alpha in supernatants. Maternal splenocytes were isolated and stimulated for cytokine production. Serum of mice was incubated with donor cells from healthy pregnant and non-pregnant animals to induce apoptosis. LPS induced preterm labor but treatment or pretreatment with DEX delayed parturition exerting a favorable impact on survival of delivered fetuses. DEX inverted the increase of fetoplacental tumor necrosis alpha levels. Serum of LPS-stimulated mice induced apoptosis of splenocytes of either pregnant or non-pregnant healthy mice; this was reversed after incubation of splenocytes with serum coming from DEX pre-treated mice. The presented findings suggest that DEX administered either as pre-treatment or treatment prolonged gestation and promoted neonatal survival in a sterile murine model of preterm labor. These favorable outcomes were closely linked to alterations in both immune and apoptotic responses of animals.

Controversies in the management of endometriomas in patients undergoing assisted reproduction.

INTRODUCTION: The presence of an endometrioma has been proposed to affect the ovarian function in a negative way. Our aim was to present the key evidence on multiple aspects of endometriomas' management in subfertile couples scheduled for assisted reproduction technologies (ART). MATERIALS AND METHODS: A critical review of the existing literature was performed focusing on the need of endometrioma treatment prior to ART, the relevant options, the potentially participating surgeon's characteristics and the socioeconomic perspective. RESULTS: To date, we have no definitive data to suggest whether the damage to the ovaries observed in women with endometriomas may be related to the mere presence of the cyst, the surgical procedure to remove it, the combination of the two, or factors currently unknown. Moreover, there is no conclusive evidence that, for subfertile couples, removal of endometriomas increases the chance of having a baby. The uncertainty regarding the best treatment strategy and factors such as the limited number of tertiary centers for laparoscopic surgery throughout the world seems to further complicate the decision. CONCLUSIONS: Until research addresses the current "grey areas", the management of endometriomas in patients undergoing ART should be individualized and take into consideration numerous parameters.

How and when human chorionic gonadotropin curves in women with an ectopic pregnancy mimic other outcomes: differences by race and ethnicity.

OBJECTIVE: To investigate the hCG profiles in a diverse patient group with ectopic pregnancy (EP) and to understand when they may mimic the curves of an intrauterine pregnancy (IUP) or spontaneous abortion (SAB). DESIGN: Retrospective cohort study. SETTING: Three university hospitals. PATIENT(S): One hundred seventy-nine women with symptomatic pregnancy of unknown location. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Slope of log hCG; days and visits to final diagnosis. RESULT(S): Of women with an EP, 60% initially exhibited an increase in hCG values, with a median slope of 32% increase in 2 days; 40% of subjects initially had an hCG decrease, with the median slope calculated as a 15% decline in 2 days. In total, the hCG curves in 27% of women diagnosed with EP resembled that of a growing IUP or SAB. Of the EP hCG curves, 16% demonstrated a change in the direction of the slope of the curve. This was more common in African Americans and less evident in Hispanics. Furthermore, it was associated with more clinical visits and days until final diagnosis. CONCLUSION(S): The rate of change in serial hCG values can be used to distinguish EP from an IUP or SAB in only 73% of cases. The number of women who had a change in direction of serial hCG values was associated with race and ethnicity.

A short narrative review of the feasibility of adopting mild ovarian stimulation for IVF as the current standard of care.

INTRODUCTION: Mild ovarian stimulation has been conceived, proposed and implemented in clinical practice as a safer and cheaper alternative to conventional strategies of controlled ovarian hyperstimulation in preparation for in vitro fertilization (IVF). Our aim was to summarize the key evidence on this topic and explore its possible role as the standard treatment option for women undergoing IVF. MATERIALS AND METHODS: A short narrative review of the existing literature, with emphasis on mild ovarian stimulation clinical and cost effectiveness, as well as treatment limitations. RESULTS: Numerous studies highlight mild ovarian stimulation's favorable characteristics with respect to oocyte/embryo quality, reduced patient risk, and ease of intervention. There is, however, a need for high-quality laboratory environment. Limitations regarding poor responders, older women, or those seeking ovarian stimulation for non-infertility indications should also be considered. Finally, outcomes on the cumulative success rates and the cost effectiveness of mild ovarian stimulation remain inconclusive. CONCLUSION: Mild ovarian stimulation protocols for IVF should currently be implemented only in carefully selected populations. Further research is needed to clarify the remaining controversies in this IVF approach.

Ovarian stimulation and embryo banking for fertility preservation in a woman with severe mixed connective tissue disease: Is it safe?

OBJECTIVE: To report the first case of using assisted reproductive technologies (ART) for fertility preservation in a patient with mixed connective tissue disease (MCTD), secondary pulmonary hypertension (PH) and antiphospholipid syndrome (APS). DESIGN: Case-report and review of the literature. SETTING: Academic infertility practice and tertiary care center. PATIENT(S): A 25-year-old woman with MCTD, complicated with PH and APS, who was scheduled for gonadotoxic therapy INTERVENTION(S): Controlled ovarian hyperstimulation, egg retrieval, embryo banking. MAIN OUTCOME MEASURE(S): Successful ART cycle leading to embryo banking without worsening her underlying disease. RESULT(S): Following successful embryo cryopreservation, the patient experienced respiratory failure and other severe complications, resulting in a prolonged hospital stay. CONCLUSION(S): Controlled ovarian hyperstimulation for embryo banking in women with MCTD, PH and APS may pose a risk for potentially catastrophic complications. A multidisciplinary approach to these patients is necessary to optimize the outcomes of such procedures. More data are needed regarding the safety of fertility preservation technologies in patients with complex medical diseases.