Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?

Objective

The aims of this study are to investigate the actual time from primary surgery for epithelial ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005–2006, and to compare the survival for groups with early initiation (≤ median TI) and late initiation of adjuvant chemotherapy (> median TI).

Methods

All Danish women who underwent surgery for OC in the period 1 January 2005 to 31 December 2006 and recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR).

Results

The median TI was 32 days (25–75% quartile: 24 days; 41 days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage.The unadjusted HR for death in patients with TI > 32 days compared with TI ≤ 32 days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%).

Conclusions

This nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI > 32 days compared with the reference TI ≤ 32 days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).     

Can radiotherapy be a treatment option for elderly women with invasive vulvar carcinoma without radical surgery?

PURPOSE OF THE INVESTIGATION: To evaluate the impact of radiotherapy after limited surgery in vulvar carcinoma. METHODS: Between March 1980 and January 2000, 22 patients older than 60 years and suffering from invasive vulvar carcinoma were treated with limited surgery and radiotherapy at Gülhane Military Medicine Academy. These are the subjects of this review. RESULTS: The median age of the patients was 67 (range 60 to 78 years). Median follow-up was 35 months (range 12 to 60 months). Local recurrence rate was 18%. Median time to local failure was 12 months (range 8 to 14 months). Two patients with local failure also developed lung metastases. Five-year survival rate was 60% and cause-specific survival rate was 69%. No treatment delay or death related to treatment was observed. CONCLUSIONS: Radiotherapy and conservative surgery can be an alternative to radical surgery with less morbidity in elderly patients.     

Galanin in pregnancy: Is there an association with birth weight and gestational diabetes?

Objective: To review the actions of galanin during pregnancy and to examine the existence of an association between galanin and birthweight as well as with gestational diabetes mellitus (GDM).

Results: Galanin concentrations in maternal circulation are similar in pregnant and nonpregnant status and have been correlated with body mass index (BMI). There is evidence of an association between birthweight and galanin concentrations in amniotic fluid during second trimester and galanin concentrations in umbilical cord at term. Moreover, there is a positive correlation between maternal galanin concentrations and existence of GDM. However, galanin concentrations in fetal circulation have not been correlated with neonatal fat mass. Neonatal galanin concentrations do not differ among uncomplicated pregnancies and those complicated by GDM or intrauterine growth retardation (IUGR).

Conclusions: There is evidence for an association between galanin during pregnancy with birth weight and metabolic processes. Further studies are required in order to elucidate this role. Galanin could serve as a predictor of neonatal body weight, alternations of which contribute to the development of diseases during adulthood.     

Is there an ideal stimulation regimen for IVF for poor responders and does it change with age?

Purpose

To determine whether there is a superior treatment modality for ‘poor’ responders.

Method

Retrospective analysis of three stimulation regimens, with patients stratified based on age, stimulation regime and response in previous cycles (“poor’ responder or “non poor” responder). Fertilisation, embryo utilisation and clinical pregnancy rates were assessed. There were a total of 1,608 cycles in the ‘poor’ responder and 8,489 cycles in the ‘non poor’ responder groups.

Results

In ‘poor’ responders there was no significant difference in fertilisation rate, nor utilisation rate between the three stimulation regimes and no differences in the pregnancy rate/initiated cycle irrespective of age and stimulation regimen in any of the groups. ‘Non poor’ responders had a significantly greater pregnancy rate/initiated cycle for all stimulation regimens in both age groups compared with ‘poor’ responders.

Conclusion

This large retrospective study of ‘poor’ responders has not shown a difference in pregnancy rates/initiated cycle between stimulation regimens.     

Is the plasma anti-Müllerian hormone (AMH) level associated with body weight and metabolic, and hormonal disturbances in women with and without polycystic ovary syndrome?

Objective

The aim of the study was to analyze interrelation between AMH levels and body weight, metabolic, and hormonal status in normal and overweight weight women with and without polycystic ovary syndrome (PCOS).

Study design

Eighty-seven women (54 normal weight and 33 overweight) diagnosed with PCOS and 50 apparently healthy women – Non-PCOS (28 normal weight and 22 overweight) were enrolled. The body weight and height were measured and BMI was calculated. In addition to serum glucose, lipids, androgens, FSH, LH, SHBG and insulin, AMH were assessed in fasting state and free androgens index (FAI) was calculated. The insulin resistance was assessed based on the homeostasis model of assessment-insulin resistance (HOMA-IR).

Results

Plasma AMH levels were similar in normal weight and overweight PCOS groups (9.6 ± 3.5 vs. 11.2 ± 4.5 ng/mL, respectively), and as expected markedly higher than in both Non-PCOS groups (2.5 ± 0.8 and 2.3 ± 0.7 ng/mL, respectively). There were no correlations between BMI and AMH levels in all study groups. A significant positive correlation between HOMA-IR, free testosterone concentrations or FAI and AMH levels were found (R = 0.31, p < 0.001; R = 0.91, p < 0.001 and R = 0.62, p < 0.001, respectively). Moreover, there was positive correlation between total or LDL cholesterol and AMH levels (R = 0.22, p < 0.05 and R = 0.31, p < 0.05, respectively) and a negative one between HDL cholesterol and AMH levels (R = −0.17, p < 0.05) in all study subjects.

Conclusions

The plasma AMH level is associated with insulin resistance but not with BMI per se. Increased circulating AMH level seems to reflect the disturbances of gonadotrophins release in PCOS. It seems that AMH level may be used not only as new surrogate marker of ovarian hyperandrogenism in PCOS but also as a potential new cardiovascular risk factor.     

Features of patients with vulvar dermatoses in dermatologic and gynecologic practice in Turkey: is there a need for an interdisciplinary approach?

AIM: Vulvar dermatoses are very common problems in women and they are associated with significant morbidity. The aims of the present study were to evaluate the features of patients with vulvar diseases in gynecology and dermatology out-patient clinics in Turkey, and to determine the need for a multidisciplinary vulvar clinic in this country. METHODS: A total of 310 patients with vulvar problems as their primary complaints were included in the study. There were 144 women from a dermatology clinic and 166 women from a gynecology clinic. The following factors were recorded for all patients: physical examination findings, menarche age, age at first intercourse, education level, marital status, clinical diagnoses and associated gynecologic problems. RESULTS: There were no significant differences between the two groups when the mean age, menarche age and age at first intercourse were compared (P > 0.05). The number of unmarried women was statistically significantly higher in the dermatology group than in the gynecology group (P < 0.0001). The number of women who graduated from high school and university was also statistically significantly higher in the dermatology group than in the gynecology group (P < 0.01). The frequency of gynecologic problems was statistically significantly higher in the gynecology group than in the dermatology group (P < 0.001); however, dermatologic conditions were the most frequent diagnosis overall (33.54%). Forty patients in the gynecology group were referred to the dermatology clinic. CONCLUSIONS: The approach to patients with vulvar disorders varies from country to country. However, multidisciplinary clinics seem to improve the understanding of vulvar diseases, to make correct diagnoses and to raise patients' quality of life. The need for a multidisciplinary vulvar clinic should not be ignored by the physicians in Turkey.     

Do risk factors for epithelial ovarian cancer have an impact on prognosis? Focus on previous pelvic surgery and reproductive variables

OBJECTIVES: The prognostic impact of risk factors for ovarian cancer development is sparsely explored, but previous sterilisation has been shown to have a negative impact on survival. METHODS: Ovarian cancer cases were from the Danish MALOVA study. Information on previous pelvic surgery as well as reproductive variables was obtained from a personal interview conducted closely after primary surgery. Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for ovarian cancer specific death in relation to previous pelvic surgery and reproductive variables including lifetime number of ovulation years. RESULTS: A total of 295 women with Stage III ovarian carcinomas were identified and followed to death or for a median of 7.3 years (range 5.4-9.5 years). Previously sterilised or hysterectomised women seemed to have a slightly decreased risk of ovarian cancer death (HR = 0.62; 95% CI: 0.36-1.08 and HR = 0.82; 95% CI: 0.55-1.21), although none of these associations reached statistical significance. The prognostic impacts of the individual reproductive variables followed the same pattern as the impact of the variables on ovarian cancer development, although significance was only reached for age at menarche (HR = 0.91 per year; 95% CI: 0.84-0.99). By accumulation of the possible minor effects of the reproductive variables in calculation of the total lifetime number of ovulation years, we found that survival decreased significantly with increasing number of ovulations (HR = 1.53 per 10 years; 95% CI: 1.09-2.14). CONCLUSION: Increasing lifetime number of ovulations was a negative prognostic factor for ovarian cancer specific survival. Previous sterilisation or hysterectomy seemed to be associated with improved survival.     

Is there a role for postoperative treatment in patients with stage Ib2–IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study

Purpose

Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy–radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment.

Patients and methods

This retrospective multicenter study included 333 patients with FIGO stage Ib₂–IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates.

Results

On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p < 0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p = 0.0001). On multivariate analysis, consolidation therapy (p = 0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p = 0.0169) and consolidation therapy (p = 0.0016) were independent prognostic variables for overall survival.

Conclusion

Optimal responders after chemo-surgical treatment for FIGO stage Ib₂–IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment.     

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source

PurposeThe aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation.MethodsWe performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed.ResultsThere were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%).ConclusionsThe use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.     

Is maternal smoking during pregnancy associated with an increased risk of congenital heart defects among offspring? A systematic review and meta-analysis of observational studies

Objective: To investigate the association between maternal smoking during pregnancy and risk of congenital heart defects (CHDs) among offspring.

Methods: PubMed, EMBASE, and Web of Science were searched for eligible studies. The outcomes of interest included risk of any CHD and nine subtypes. We summarized study characteristics and used a random-effects model in meta-analysis, and a two-stage dose–response model was utilized to assess the association between smoking consumption and risk. Statistical heterogeneity was assessed by a chi-squared test of the Cochrane Q statistic and I-squared value. Publication bias was assessed by funnel plots and Egger’s test, and trim and fill method was utilized when publication bias existed.

Results: Forty-three observational epidemiologic studies were included. The pooled risk ratio (RR) of any CHD was 1.11 (95% CI: 1.04, 1.18), but it exhibited substantial statistical heterogeneity (p?I^2?=^?69.0%). In sensitivity analysis, we observed significant associations for atrial septal defect (ASD) and marginally significant associations for septal defects (SPD). The two-stage dose–response analysis showed evidence to support that higher levels of tobacco smoke was associated with an increased risk of septal defects, particularly for ASD and VSD (ventricular septal defect).

Conclusion: Our study presents evidence to support the cardiovascular teratogenic effect of maternal smoking during pregnancy, and their offspring may suffer from approximately a 10% relative increase in the risk of CHDs on average.     

Radical fimbriectomy: a reasonable temporary risk-reducing surgery for selected women with a germ line mutation of BRCA 1 or 2 genes? Rationale and preliminary development

Objective

Bilateral salpingo-oophorectomy (BSO) is the gold standard prophylactic surgery for BRCA1 or 2 mutation carriers. However, due to the resulting early menopause and fertility desires, young women are reluctant to undergo this procedure. In view of the recent literature on ovarian carcinogenesis, we wish to report a novel conceptual surgical procedure we called “radical fimbriectomy.” This procedure is aimed to protect this subset of high-risk women from high-grade serous pelvic carcinoma, while preserving their ovarian function.

Methods

Women with BRCA mutation, who were scheduled for BSO, were informed of the procedure approved by our local review board. Radical fimbriectomy consists of removing all the tube and the fimbrio-ovarian junction, step immediately followed in this developmental phase by completion oophorectomy. Four methods of partial ovarian transsection were prospectively compared: sharp division, stapler, bipolar division and harmonic scalpel. Surgical safety and pathological alterations were assessed. All specimens underwent extensive pathological evaluation using both SEE-FIM protocol and serial sections.

Results

Fourteen women were enrolled in the study. Sharp and EndoGIA^® appeared to be the safest methods of ovarian resection providing the best specimen quality for pathological examination.

Conclusion

We believe this technique could be suggested to young mutation carriers reluctant to undergo BSO. This approach is preferable to no prophylactic surgery at all. However, until the safety and validity of this procedure is confirmed by a multi-institutional study, women who undergo radical fimbriectomy should continue to receive regular multimodal evaluation and be advised of the risks involved until they finally accept secondary castration.