Expression of 67-kDa laminin receptor was associated with tumor progression and poor prognosis in epithelial ovarian cancer

Objective

67-kDa laminin receptor (67LR) has been identified as a prognostic biomarker for a variety of human cancers. We investigated the clinical significance of 67LR expression and its functional role in epithelial ovarian cancer (EOC).

Methods

67LR expression was evaluated by immunohistochemistry in 62 patients with EOC. We assessed the correlation of 67LR expression with clinical characteristics. In vitro experiment was performed for 67LR with inhibition using siRNA to evaluate its role in cell survival, apoptosis, and invasion in EOC cells.

Results

67LR was predominantly expressed on the cell membrane in the majority of EOC samples (45/62, 73%). 67LR expression was significantly correlated with advanced stage (P = 0.001). Patients with 67LR expression had shorter progression-free survival among all the patients (P = 0.010) and in particular among patients with advanced stages (P = 0.046). When 67LR expression was inhibited by siRNA in EOC cells (HeyA8 and A2780), there was a significant decrease of cell proliferation and invasion as well as increase of apoptosis.

Conclusion

These findings suggest that 67LR expression may play an important role in tumor progression into advanced stage with poor prognosis in EOC and down-regulation of 67LR on tumor cells may be a therapeutic target in those patients.     

Three-dimensional power Doppler imaging in the diagnosis of polycystic ovary syndrome

Objective

To determine the role of three-dimensional (3D) power Doppler imaging in the diagnosis of polycystic ovary syndrome (PCOS).

Methods

Pulsatility index (PI) and resistance index (RI) of the uterine artery and ovary were measured by two-dimensional (2D) Doppler imaging, while vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured by 3D power Doppler in 25 patients with PCOS and 25 women with normal menstrual cycles used as a control group.

Results

Uterine artery PI and RI were significantly higher (P < 0.001) and ovarian PI and RI were significantly lower (P < 0.001) in women with PCOS compared with controls. Ovarian VI and VFI were significantly higher in women with PCOS compared with the control group (P < 0.001).

Conclusion

3D power Doppler indices were higher in women with PCOS than in the control group and were positively correlated with 2D color Doppler indices, and clinical and hormonal parameters. High 3D power Doppler indices may be useful as one of the diagnostic criteria for PCOS.     

Interaction between preoperative CA-125 level and survival benefit of neoadjuvant chemotherapy in advanced epithelial ovarian cancer

Objective

This study aims to determine whether neoadjuvant chemotherapy (NAC) has survival benefit in selected patients with advanced epithelial ovarian cancer (EOC) who have high risk of suboptimal cytoreduction which is represented by high serum CA-125 level.

Methods

We retrospectively reviewed records of 314 patients with EOC including 94 patients who received NAC. After stratification by preoperative CA-125 levels, the progression-free survival (PFS) was compared between the NAC group and the primary debulking surgery (PDS) group.

Results

The NAC group had more FIGO stage IV disease (P < 0.001) and higher CA-125 levels (P < 0.001). Although suboptimal resection rate was higher in the PDS group (50% vs. 18%, P < 0.001), however, NAC was not associated with increased PFS in multivariate Cox analysis (P = 0.334). Nevertheless, after stratification according to CA-125 levels, NAC showed survival benefit in the subgroup with high CA-125 levels (> 2000 U/ml; HR 0.62, P = 0.037).

Conclusion

Our preliminary data suggests the possible interaction between CA-125 levels and survival benefit of NAC. The randomized trial data about NAC should be stratified by the reproducible and relevant criteria such as preoperative serum CA-125 level to elucidate true survival benefit of NAC in ovarian cancer.     

Concomitant surgical correction of occult stress urinary incontinence by TOT in patients with pelvic organ prolapse

Objectives

To assess the post-operative urinary incontinence states of pelvic organ prolapse cases operated on with concomitant trans-obturator tape (TOT) procedure.

Study design

Urodynamic evaluation of 79 patients with pelvic organ prolapse, before and after operation, while reducing the prolapsed organs by ring forceps placed bilaterally on the anterolateral sulcuses avoiding urethral compression. According to urodynamic tests, 25 patients were diagnosed as having occult stress urinary incontinence.

Results

Post-operative overactive bladder, stress urinary incontinence and mixed incontinence were found in three (12%), two (8%) and one (4%) patients of the occult stress urinary incontinence group, respectively. The corresponding numbers were six (11%), five (9%) and three (6%) in the continent group. No significant difference was found between the groups in terms of post-operative overactive bladder symptoms, stress urinary incontinence and mixed incontinence (Kruskal-Wallis test, X² = 0.52, p = 0.820).

Conclusions

This retrospective study suggests that a complete pre-operative urodynamic evaluation, including urodynamic tests at the time of POP reduction by placing ring forceps on the anterolateral sulcuses, is an efficient method for the diagnosis of occult symptomatic stress urinary incontinence (SUI). Prospective randomized studies are needed to establish the benefits and the risks of concomitant prophylactic surgery in patients with pelvic organ prolapse.     

Insulin resistance, dyslipidemia, and metabolic syndrome in women with polycystic ovary syndrome

Objective

To investigate the association of insulin resistance with dyslipidemia and metabolic syndrome (MBS) in women with polycystic ovary syndrome (PCOS).

Methods

Fasting glucose (G), insulin (I), and lipid levels were measured in 50 infertile women with PCOS. A fasting G/I ratio of 4.5 or less (n = 29) defined insulin resistance (IR).

Results

The mean levels of total cholesterol (P < 0.001), low-density lipoprotein (P = 0.02), and triglycerides (P < 0.001) were significantly higher and the mean levels of high-density lipoprotein were significantly lower (P < 0.001) in the IR group. The prevalence of MBS (P = 0.02) and obesity (P = 0.04), hypertension (P = 0.02), fasting hyperglycemia (P = 0.03), low high-density lipoprotein levels (P = 0.02), and hypertriglyceridemia (P = 0.02) were also significantly higher in the IR group.

Conclusion

Insulin resistance is associated with dyslipidemia and MBS in women with PCOS. Lifestyle modification and insulin-sensitizing agents should be part of the management plan.     

Doppler analysis of uterine perfusion and ovarian stromal blood flow in polycystic ovary syndrome

Objective

To investigate blood flow velocity in the ovarian stromal artery and uterine artery in women with polycystic ovary syndrome (PCOS) and to correlate these velocities with clinical and biochemical parameters.

Methods

A prospective study was carried out in 55 patients with PCOS and 42 age-matched women who did not have PCOS. Clinical, biochemical, and hormonal characteristics, and utero-ovarian Doppler ultrasound blood flow parameters were determined, and correlations between the parameters were evaluated.

Results

Ovarian stromal blood flow was higher (P < 0.01) and uterine perfusion was lower (P < 0.01) in women with PCOS compared with women who did not have PCOS. Ovarian stromal artery pulsatility index (PI) was inversely correlated with levels of dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor-1, and with the luteinizing hormone/follicle-stimulating hormone ratio. There was a positive correlation between uterine artery PI and DHEAS level.

Conclusion

Doppler analysis of the uterine and intraovarian arteries may provide additional information about the etiopathogenesis of PCOS and partly explain the clinical implications of the condition.     

Intensity-modulated radiation therapy for advanced cervical cancer: a comparison of dosimetric and clinical outcomes with conventional radiotherapy

Objective

The aim of this study is to evaluate the dosimetry, efficacy and toxicity of reduced field intensity-modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer.

Methods

From August 2005 to August 2010, 60 patients with stage IIB-IIIB cervical cancer underwent reduced field IMRT (RF-IMRT group) and 62 patients treated with conventional radiotherapy (c-RT group) were enrolled. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver a dose of 30 Gy firstly, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30 Gy boost. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. The tumor coverage and normal tissue avoidance were evaluated. Treatment response, toxicities and survival were assessed.

Results

The mean dose delivered to the planning target volume was significantly higher in RF-IMRT group than in c-RT group (61.5 vs. 50.8 Gy, P = 0.046). IMRT plans yielded better dose conformity to the target and better sparing of the rectal, bladder and small intestine. The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (CR: 87.7% vs. 88.3%, P = 0.496; PR: 7.0% vs. 6.7%, P = 0.440). No significant differences were found between treatment groups for 1 year, 3 year, and 5 year overall survival (OS) levels, although the latter approached statistical significance in favor of IMRT, while a significantly higher progression-free survival (PFS; P = 0.031) was seen for IMRT.

Conclusions

RF-IMRT yields improved dose distributions, with lower toxicities, while providing comparable clinical outcomes. The increased PFS may be an advantage.     

Comparison of the efficacy and adverse effects of nifedipine and indomethacin for the treatment of preterm labor

Objective

To compare the effectiveness and adverse effects of nifedipine versus indomethacin in the treatment of preterm labor.

Methods

In a randomized clinical trial, 79 women with labor pain at 26-33 weeks of gestation were treated with either oral nifedipine (n = 40) or rectal indomethacin (n = 39).

Results

Twenty-three (59%) women in the indomethacin group, and 10 (25%) in the nifedipine group did not respond to treatment (P = 0.002). None of the 16 and 30 women remaining in the indomethacin and nifedipine groups, respectively, delivered during the subsequent 48 hours. Of these remaining women, 1 (6.25%) in the indomethacin group and 4 (13.3%) in the nifedipine group delivered between 48 hours and 7 days (P = 0.162). For the women who responded to treatment, the mean gestational age at time of delivery was 238.5 ± 19.4 days and 246.4 ± 15.4 days in the nifedipine and indomethacin groups, respectively (P = 0.182). Seventeen (42.5%) women in the nifedipine group, and 11 (28.2%) in the indomethacin group showed adverse effects (P = 0.184).

Conclusion

Indomethacin was less effective than nifedipine for the fast treatment of preterm labor. For women who responded to treatment within 2 hours, however, the delaying of delivery by indomethacin was similar to that by nifedipine.     

High-intensity focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva

Objective

To assess the efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with non-neoplastic epithelial disorders of the vulva.

Method

We reviewed 41 cases of lichen sclerosus, 38 cases of squamous cell hyperplasia, and 17 mixed cases treated by HIFU from April 2004 to July 2008 at the Women's Hospital of Zhejiang University School of Medicine. Biopsy specimens were assessed with light microscopy before and after treatment.

Results

Pruritus and signs of vulvar lesions were dramatically improved following HIFU treatment, without severe complications, and 90.23% of the patients were cured or had their symptoms improved 6 months after treatment. On light microscopy, pigmentation and epithelial structures were recovered and dermal lymphocytic infiltration was reduced. The response rates were lower and complication rates higher among lichen sclerosus than among squamous cell hyperplasia cases (P < 0.05 for both).

Conclusion

Treatment with HIFU may be safe and effective in cases of vulvar dystrophy.     

Immunohistochemical expression of Annexin A2 and S100A proteins in patients with bulky stage IB-IIA cervical cancer treated with neoadjuvant chemotherapy

Objective

Abnormal expression of Annexin A2 and S100A proteins has been reported to induce sensitivity/resistance to chemotherapy in a variety of cancers. The aim of this study was to evaluate the significance of Annexin A2 and S100A protein expression to predict response to neoadjuvant chemotherapy and prognostic significance of these protein expressions in bulky stage IB-IIA cervical cancer patients.

Methods

Paired tumor samples (pre- and post-chemotherapy) were obtained from 68 patients who were treated with cisplatin-based neoadjuvant chemotherapy and radical hysterectomy at our hospital from 2006 to 2011. The expression of Annexin A2 and S100A proteins was analyzed by immunohistochemistry.

Results

Thirty-six patients were identified as chemotherapy-response and 32 were non-response. (a). Protein expression in tumor cells: (1). Exposure of tumor cells to chemotherapy results in a change of Annexin A2 and S100A expression (P < 0.05). (2). Annexin A2, S100A8 and S100A9 protein expression correlates with tumor response to chemotherapy (P < 0.05). (b). Protein expression in stromal cells: (1). Expression of Annexin A2, S100A8 and S100A9 was increased, but S100A2 and S100A4 was decreased after exposure to chemotherapy (P < 0.05). (2). Only S100A4 expression was associated with response to chemotherapy (P < 0.05). Multivariate analysis revealed that tumor size (P = 0.022), differentiation (P = 0.000), Annexin A2 expression in stromal cells (P = 0.009), and S100A8 expression in tumor cells (P = 0.008) were independent prognostic factors for progression-free survival of cervical cancer patients.

Conclusions

Expression of some of the measured proteins in tumor and stromal cells correlates with chemotherapy exposure, response to therapy, and progression-free survival.     

First trimester ultrasound estimation of gestational age in pregnancies conceived after in vitro fertilization

Objective

To evaluate BPD as an alternative to CRL for the estimation of gestation age in late first trimester pregnancies (between 9th and 13th gestational weeks), and to construct a first trimester reference chart of fetal BPD growth.

Study design

A prospective study that compared the gestational age estimated by BPD and CRL with the IVF gestational age in 167 first trimester pregnancies (127 singletons, 40 twins).

Results

Both BPD and CRL correlated well with the IVF gestational age (GA) from 9th to 13th gestation weeks. When comparing the difference of the GA (in days) estimated from the two respective ultrasound parameters versus the GA based on IVF (oocyte retrieval day +14 days), BPD estimations had a significantly lower mean difference than CRL (0.013 vs. 0.746; p < 0.01), as well as a lower standard deviation (2.414 vs. 3.008; p < 0.05). In addition, the 95% limits of agreement between the BPD estimated GA and IVF GA were also smaller than CRL estimated GA versus IVF GA (−4.719 to 4.745 vs. −5.149 to 6.641).

Conclusion

Biparietal diameter shares similar accuracy with crown rump length in late first trimester ultrasound estimation, with additional advantages of lower random measurement errors.     

Pregnancy outcomes and ultrasonographic diagnosis in patients with histologically-proven placental chorioangioma

Objective

To evaluate pregnancy outcome and ultrasound diagnosis in patients with histologically-confirmed placental chorioangioma.

Study design

Placentas with histological diagnosis of chorioangioma were identified and medical charts were reviewed for findings of ultrasound examinations. Pregnancy outcomes were compared with all singleton deliveries without chorioangioma in the same time period.

Main outcome measures

Primary outcome was Neonatal Intensive Care Unit admission rate. Secondary outcome was ultrasound detection rate of chorioangioma.

Results

Among 14,725 singleton deliveries, 23 placentas were diagnosed with chorioangioma (0.16%). The control group included all singleton deliveries without chorioangioma (n = 14702). Neonates in the study group were more likely to be admitted to the Neonatal Intensive Care Unit (OR = 4.45) and to have smaller birth weight (p = 0.006). Only 2 of 7 larger chorioangiomas (≥2 cm) with available ultrasound reports were identified by ultrasound (29% detection rate). All cases demonstrated normal fetal growth and wellbeing.

Conclusion

Chorioangiomas are not always identified by routine prenatal sonography. Even in the absence of ultrasonic abnormalities, neonatal morbidity, as measured by NICU admission rate, is increased.     

The effects of ritodrine and magnesium sulfate on maternal and fetal Doppler blood flow patterns in women with preterm labor

Objective

To determine the effects of ritodrine and magnesium sulfate on maternal-fetal blood flows.

Study design

A total of 85 pregnant women between 26th and 36th weeks with preterm labor, and 83 healthy pregnant women were included. Patients in the study group were randomly assigned to receive either ritodrine (with the addition of verapamil) (n = 46) or magnesium sulfate (n = 39). Blood flow examinations on the umbilical artery (UA), middle cerebral artery (MCA), bilateral uterine arteries (Ut.A) and ductus venosus (DV) were performed before and 48 h after initiating therapy.

Results

UA pulsatility index (PI) significantly differed in women receiving tocolysis compared to controls after 48 h. DV PI increased in women receiving MgSO₄, whereas it decreased in the ritodrine and control groups. Ut.A values did not significantly change after 48 h in the groups.In women between the 26th and 32nd weeks, UA, MCA and DV PI did not significantly change after 48 h in the three groups. However, in women between the 32nd and 36th weeks UA and MCA PI significantly differed in the treatment groups compared to controls after 48 h. DV PI increased in women receiving MgSO₄, whereas it decreased in the ritodrine and control groups.

Conclusions

MgSO₄ and ritodrine affect blood flow patterns after 48 h in some maternal-fetal vessels. These effects on blood flow are particularly significant in women between 32nd and 36th weeks. The effects of both drugs on fetal and maternal Doppler flows seem similar, except the increased resistance to flow in DV in women receiving MgSO₄.     

Expression of human leukocyte antigen-G and its correlation with interleukin-10 expression in cervical carcinoma

Objective:

To determine human leukocyte antigen (HLA)-G and interleukin (IL)-10 expression and the relationship between HLA-G expression and clinicopathologic features in patients with cervical cancer.

Method:

Tissue samples were obtained from 40 patients with cervical cancer and 15 control patients with a normal cervix. Quantitative real-time RT-PCR for mRNA and western blot analysis for protein expression were used.

Result:

Both HLA-G and IL-10 mRNA expression in cervical cancer tissues was significantly greater than normal controls (P < 0.001, P = 0.005). Protein expression of HLA-G and IL-10 in the cancer group was also significantly greater than in the controls (P < 0.001, P = 0.021). There was an inverse relationship between FIGO stage and HLA-G mRNA expression (P = 0.046).

Conclusion:

HLA-G and IL-10 might play an important role in cancer progression of the cervix. High HLA-G mRNA expression may be related to early carcinogenesis since it was associated with early-stage cervical cancer.     

Oral misoprostol versus intracervical prostaglandin E2 gel for active management of premature rupture of membranes at term

Objective

To compare the efficacy and safety of oral misoprostol with intracervical prostaglandin E2 (PGE2) gel for the active management of premature rupture of membranes (PROM) at term.

Methods

Women with pregnancies between 37 and 42 weeks presenting with PROM at term and a Bishop score of 5 or less were randomly assigned to receive either a 4-hourly oral dose of 50 µg of misoprostol up to a maximum of 3 doses or 2 applications of intracervical PGE2 gel at a 6-hour interval. Oxytocin was given if labor had not started after 12 hours.

Results

Twenty women in the misoprostol group (n = 31) delivered within 12 hours compared with 5 in the PGE2 group (n = 30) (P < 0.001). The induction-to-delivery interval in the misoprostol group was shorter than in the PGE2 gel group (615 min vs 1070 min; P < 0.001). The mode of delivery was comparable between the 2 groups (P = 0.821). Abnormalities in uterine contractions and neonatal outcomes were also comparable. The requirement for oxytocin was lower and patient satisfaction was better in the misoprostol group.

Conclusion

Oral misoprostol is a safe and efficacious alternative to intracervical PGE2 gel in the active management of PROM at term.     

Maternal serum protein S forms in pregnancies complicated by intrauterine growth restriction

Objectives

The clinical relevance of protein S deficiency in pregnant women remains controversial. Major debate exists regarding which parameter (total protein S antigen, free protein S antigen or functional protein S) should be evaluated in order to define protein S deficiency. The present study aimed to identify which of these parameters correlate with intrauterine growth restriction (IUGR).

Study design

A retrospective case-control study of women with IUGR (n = 27) and healthy controls (n = 123) in the third trimester of pregnancy.

Results

The maternal serum of women in the IUGR group had significantly lower levels of functional and free protein S compared with the control group: 54.07 ± 24.72% vs 65.20 ± 17.95% (p < 0.005) and 42.88 ± 11.01% vs 56.64 ± 13.30% (p < 0.0001), respectively. No significant correlation was found between total protein S and IUGR.

Conclusions

Levels of functional and free protein S are correlated with IUGR.     

The effect of “breathable” panty liners on the female lower genital tract

Objective

To evaluate whether the use of “breathable” panty liners (BPLs) alters the normal vaginal flora, increases the incidence of bacterial vaginosis and/or vaginal candidiasis, or causes vulvar irritation.

Methods

A randomized controlled trial assessed the vaginal ecosystem of women without complaints of vaginal discharge. The study group (n = 53) wore BPLs for 10-12 hours each day for 75 consecutive days, whereas the control group (n = 54) wore only their usual underwear. At each of 6 visits during 3 menstrual cycles, participants underwent gynecologic examination with colposcopic evaluation and pH measurement, in addition to assessment of vaginal microbial flora, intensity of inflammatory processes, and presence of vaginal candidiasis/bacterial vaginosis in Gram-stained smears.

Results

After 75 consecutive days of BPL use, 40/44 (90.9%) and 42/44 (95.5%) women reported no complaints of vaginal discharge or vulvar itching/burning, respectively. There was no significant difference between the study group and the control group with regard to positive vaginal fungus cultures (5/44 [11.4%] vs 8/50 [16.0%]; P = 0.7848) or bacterial vaginosis (3/44 [6.8%] vs 2/50 [4.0%]; P = 0.7974) at the end of the study period.

Conclusion

After 75 days of BPL use, there was no significant increase in vulvovaginal candidiasis, bacterial vaginosis, vulvovaginal irritation, or vulvovaginal inflammation.     

Effect of a pelvic floor muscle training program on gynecologic cancer survivors with pelvic floor dysfunction: a randomized controlled trial

Objective

To investigate the effects of a pelvic floor rehabilitation program (PFRP) on pelvic floor function and quality of life (QoL) in gynecological cancer survivors in a prospective, randomized, controlled trial.

Methods

Thirty-four patients with gynecological cancers recruited between July 2009 and December 2009 were randomly allocated into two groups: a PFRP group (n = 17), who participated in a 4-week PFRP exercise program, and a non-PFRP group (n = 17), who received the usual health care. The pelvic floor strength, the motor evoked potentials (MEPs) elicited by sacral and transcranial magnetic stimulation, the pelvic floor questionnaire, and the scores on two QoL questionnaires, (QLQ)-C30 and QLQ-CX 24, from the European Organization for Research and Treatment of Cancer (EORTC) were evaluated to assess changes in pelvic floor function and QoL before and after the exercise program.

Results

Twenty four patients (12 from each group) completed the exercise program. The PFRP group improved in pelvic floor strength (mean difference (MD) = 14.22, t₉ = 2.389, P = 0.036) and sexual functioning. The PFRP group also improved in physical and sexual function compared with the non-PFRP group.

Conclusions

The results suggest that the PFRP improved pelvic floor dysfunction and QoL of gynecological cancer patients. A larger randomized controlled trial is planned.