Pharma Update Genitalkarzinome

Ovarian cancer

In early stage ovarian cancer chemotherapy containing platinum is recommended. In an advanced or recurrent situation combined chemotherapy with carboplatin/paclitaxel (area under the curve AUC5 175 mg/m²) is indicated. The vascular endothelial growth factor (VEGF) targeting agent bevacizumab can prolong the progress-free interval. For the treatment of platinum-sensitive ovarian cancer the preferred agents are carboplatin/gemcitabine, carboplatin/paclitaxel and carboplatin/caelyx. Platinum-resistant recrudescence primarily indicates a monochemotherapy and the recommended therapeutic options are polyethylene glycol (PEG) liposomal doxorubicin/topotecan/gemcitabine/paclitaxel.

Cervical cancer

A combined radiochemotherapy containing cisplatin is considered to be the standard of care in neoadjuvant and adjuvant treatment as well as in recurrent situations. Neoadjuvant dose-dense chemotherapy improves the 5-year survival rate and reduces overall mortality. Adjuvant chemotherapy only is not indicated. In a recurrent or metastasized situation for radiation-naive patients radiochemotherapy is indicated. The only approved regimen in Germany is a combination of cisplatin and topotecan. Results of the GOG 240 trial confirmed an enhancement of the progress-free survival with addition of the antibody bevacizumab.

Endometrial cancer

Of all endometrial cancer patients 20?% are considered to be high risk patients. The recurrence rate is 50?%. According to the current German S2K guidelines in all patients presenting with a TNM stage Ib G3, II and III as well as all serous or small cell endometrial carcinomas, platinum chemotherapy with carboplatin/paclitaxel (AUC5 175 mg/m²) is indicated sequential to radiation. In the palliative situation local surgical treatment or radiation is the main option. A possible combination with either gestagens or cytostatic therapy depends on the hormone receptor status.

Vulvar cancer

Radiochemotherapy is indicated in inoperable situations, extensive recrudescence or in non-in sano resected patients. In metastasized patients the use of a combined chemotherapy is criticized due to the high toxicity and low response rate.     

Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma

Purpose

Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC.

Methods

A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150?mg/m²), epirubicin (50?mg/m²) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175?mg/m²) and carboplatin (AUC 5).

Results

TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p?=?0.017 for progression-free survival and p?=?0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p?=?0.55 for progression-free survival and p?=?0.63 for overall survival).

Conclusions

TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.     

Polycystic ovarian syndrome and congenital uterine anomalies: the hidden common player

Objective

To study the association between polycystic ovary syndrome (PCOS) and congenital uterine (Müllerian) anomalies in infertile patients. The ultimate aim was to check for a common factor linking both reproductive health problems.

Design

A prospective observational study.

Setting

Tertiary referral infertility center.

Subjects and methodology

3,900 infertile patients were included. The diagnoses of PCOS and uterine anomalies were made. Patients with or without PCOS were correlated to the presence or absence of uterine anomalies and statistically assessed.

Main outcome measures

Study of the prevalence of PCOS/uterine anomalies in the studied population and the ratio of coexistence.

Results

The prevalence of PCOS in the studied cohort was 10.48 %. 409 (10.48 %) patients were confirmed to have PCOS, while 204 (5.23 %) were with confirmed uterine anomalies. Of the patients with confirmed PCOS, almost one-third (n = 149, 31.4 %) had uterine anomalies, while in patients with confirmed uterine anomalies, almost three-fourths (n = 149, 73 %) had PCOS.

Conclusions

There is evident association between PCOS and uterine anomalies in infertile patients. We suggest a genetic rather than a developmental defect to be a possible common player for the development of both PCOS and uterine anomalies.     

Post-treatment follow-up procedures in cervical cancer patients previously treated with radiotherapy

Purpose

We investigated the role of physical examination, CT scan, chest X-ray, and Pap smear in the routine follow-up program for cervical cancer patients previously treated with radiotherapy.

Methods

The records of women who had developed recurrent cervical cancer after radiotherapy were retrospectively reviewed. The optimal procedure for the detection of recurrence was evaluated according to the disease-free interval (DFI). Survival analysis was performed based on the Kaplan?CMeier method and comparisons between groups were made using the log-rank test.

Results

A total of 146 recurrent cervical cancer patients were included in our database. The majority of recurrences were diagnosed either by symptoms, physical examination, or CT scan. The patients whose recurrent disease was detected by Pap smear, physical examination, or CT scan had a significantly longer survival than those detected by symptoms. When analyzed according to DFI, physical examination, and CT scan led to the detection of recurrence in patients with a DFI of 1?C5?years. In contrast, chest X-ray and Pap smear only had a clinical impact on the diagnosis of recurrence in patients with a DFI of 1?C2?years.

Conclusions

Chest X-ray and Pap smear can be routinely performed for the first 2?years after radiotherapy, but can be omitted or used sparingly thereafter.     

MR imaging evaluation of fibroid clearance following open myomectomy for massive/multiple symptomatic fibroids

Purpose

To evaluate the technical success of total fibroid clearance at open myomectomy for massive and/or multiple symptomatic fibroids using MR imaging (MRI) as the imaging modality.

Methods

The study group comprised 27 women [mean age 37.4?±?6.9?years (range 27–53)] who underwent open myomectomy for the treatment of massive/multiple symptomatic fibroids at our institution between January 2009 and April 2010. Myomectomy was performed with the intention of achieving complete fibroid clearance. Pre- and postmyomectomy MRI was performed to assess changes in uterine volume and fibroid burden. Periprocedural data (including blood loss and complications) and relief of clinical symptoms at follow-up were also recorded.

Results

The mean time to MRI and clinical follow-up was 10?months (range 6–15?months). The mean uterine volume premyomectomy was 795?±?580?cc and postmyomectomy was 123?±?70?cc (p?<?0.001). The mean percentage reduction in uterine volume was 80.3?% (range 43.0–98.1?%). Of the 10/27 (37.0?%) women with residual fibroids at follow-up: 7 patients had fibroids measuring up to 1?cc in volume, 3 patients had fibroids measuring up to 6?cc. Postoperative adnexal seromas were observed in 6/27 (22.2?%) patients. The clinical success rates of myomectomy amongst the 22/27 (81?%) responders were: 73?% for menorrhagia, 64?% for pain, and 36–64?% for mass-related symptoms.

Conclusions

Using MRI, we have confirmed that open myomectomy can achieve total or near-total fibroid clearance in the majority of patients with massive and/or multiple fibroids.     

Women’s well-being after Manchester procedure for pelvic reconstruction with uterine preservation: a follow-up study

Purpose

This study describes the outcomes of a modified Manchester procedure on the quality of life and sexual functioning of women with elongation of the uterine cervix with or without pelvic organ prolapse (POP).

Methods

Data on medical and demographic variables were collected from medical files and then women were invited to for follow-up examination and data collection.

Results

Follow-up data were collected from 53 out of 87 women who underwent reconstructive surgery with modified Manchester procedure (60.9% of the women). Prior the surgery, all women in this sample (n?=?53) were medically examined and found to have uterine cervix elongation, 40/53 (75.4%) women also had cystocele, 10/53 women (18.8%) had uterine prolapse and 8/53 women (15.1%) had rectocele (all stages II–IV). On follow-up examination, all the cervical stumps were satisfactorily situated, recurrent cystocele was found among 12/53 women (22.6%) women; 13/53 (24.5%) had rectocele; and none of these women had uterine prolapse. Women with POP (cystocele and rectocele) (24/53) had less operative satisfaction (p?=?0.004), lower quality of life (p?p?=?0.03) compared to women without POP (29/53).

Conclusion

The modified Manchester procedure including reconstructive surgery for women with cervix elongation, with or without POP, prevented recurrent uterine prolapse and was well received in terms of patient’s satisfaction, quality of life, and sexual function.     

Polymorphisms in genes HSD17B1 and HSD17B2 and uterine leiomyoma risk in Chinese women

Purpose

To evaluate the association of HSD17B1 and HSD17B2 gene polymorphisms with uterine leiomyoma in Chinese women.

Methods

121 Chinese women with clinically diagnosed uterine leiomyoma and 217 healthy normal Chinese women were investigated to compare three single nucleotide polymorphisms (SNPs) (rs605059 and rs676387 of HSD17B1 gene and rs8191246 of HSD17B2 gene) by polymerase chain reaction?Crestriction fragment length polymorphism and DNA sequencing method.

Results

All the SNPs were polymorphisms in Chinese women. Frequencies of rs605059 AA genotype and A allele were significantly increased in patients with uterine leiomyoma compared to healthy controls (GG vs. AA, OR 0.40, 95?% CI 0.20?C0.82; G vs. A, OR 0.68, 95?% CI 0.50?C0.94).

Conclusion

The results suggest that the genotype of HSD17B1 rs605059 may play a role in the tumourgenesis of uterine leiomyoma.     

Comparison of uterine artery Doppler in pregnant women with thrombophilia treated by LMWHs and without thrombophilia

Objective

The aim of this study was to use uterine artery Doppler ultrasonography to investigate the cases of women with thrombophilia who used LMWH during the 18?C22-week period of gestation.

Methods

This retrospective study was conducted at our university between January 2005 and July 2010. 64 patients were treated with low-dose LMWHs (enoxaparine 40?mg) from the beginning of pregnancy until 36?weeks of gestation. Fifty control subjects were also included in this study. Transabdominal ultrasound examination and bilateral uterine artery Doppler measurements pulsatility index (PI), resistive index (RI), and systole/diastole measurement (S/D) were performed during the 18?C22-weeks period of gestation.

Results

No significant differences were found between the groups with respect to maternal age or gestational age at the time of uterine artery Doppler. However, the mean PI (1.07?±?0.46 for LMWH group and 0.91?±?0.31 for control, p?=?0.036) and the mean RI (0.59?±?0.12 for LMWH group and 0.54?±?0.10 for control, p?=?0.021) were significantly higher in the trombophilia group.

Conclusion

Women with trombophilia still have an increased mean PI and RI, as determined by uterine artery Doppler ultrasonography during the 18-22-week period of gestation, even if they use LMWH.     

Efficacy of PET/CT to exclude leiomyoma in patients with lesions suspicious for uterine sarcoma on MRI

Objective

To analyze the efficacy of positron emission tomography/computed tomography (PET/CT) for the diagnosis of uterine sarcoma.

Clinical characteristics,pathological reevaluation,surgical management and adjuvant therapy of patients with endometrial stromal tumors

Purpose

To review a single-center experience over a 27-year period in the management of endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) for insight into clinical characteristics, pathological diagnosis, surgical practice, adjuvant therapy and clinical outcome.

Materials and methods

This was a retrospective study of women with histologically proven ESS and UES who were treated at the Department of Obstetrics and Gynecology, University of Tuebingen, Germany, between 1983 and 2010. Available tumor tissue, as well as inpatient and ambulatory records were reviewed; follow-up and survival data were ascertained.

Results

The study sample comprised ten patients with ESS and seven patients with UES. Primary surgical treatment consisted of total hysterectomy in nine patients (90.0 %) with ESS and six patients (85.7 %) with UES; one patient (10.0 %) with ESS and one patient (14.3 %) with UES underwent debulking surgery. All patients (100 %) from the ESS group and six patients (85.7 %) from the UES group underwent bilateral salpingo-oophorectomy. Seven women (70.0 %) with ESS and six women (85.7 %) with UES underwent lymphadenectomy. Median DFS was 83.8 months (95 % CI 80.6–87.0) and median OS was 232.6 (95 % CI 49.3–415.9) for patients with ESS; median DFS was 12.9 months (95 % CI 0–284.1) and median OS was 17.6 (95 % CI 0–37.0) for patients with UES. There was no significant difference in DFS between patients with ESS as compared with patients with UES. However, patients with ESS had a significantly better OS when compared to patients with UES (p = 0.011).

Conclusion

ESS and UES are very rare uterine neoplasms. Surgery consisting of total hysterectomy with or without bilateral salpingo-oophorectomy is the most important treatment-element in patients with ESS or UES.     

Evaluation of SprayShield™ Adhesion Barrier in a single center: randomized controlled study in 15 women undergoing reconstructive surgery after laparoscopic myomectomy

Objective

The objective of this study was to evaluate the safety and efficacy of SprayShield? Adhesion Barrier in preventing and/or reducing postoperative adhesion during gynecological surgery.

Design

This was a prospective, controlled, blinded, and randomized study. Patient blinding was performed intraoperatively. Subjects were randomly assigned to the SprayShield? or the control group in a 2:1 ratio.

Setting

The study was conducted at the Clinic of Gynaecology and Obstetrics, at the University Hospital for Gynecology in Germany.

Patients

Fifteen patients participated in this study; nine patients were assigned to the SprayShield? and six patients to the control group.

Interventions

During first operation (FLL) in the SprayShield? group, the agent was applied to all myomectomy suture lines. Patients in the control group did not receive any anti-adhesion treatment, only good surgical practice. A second-look laparoscopy (SLL) was performed 8–12 weeks after myomectomy to evaluate adhesion formation.

Main outcome measures

Main outcome measures were incidence, severity, and extent of uterine adhesions.

Results

No significant differences were found between the two study groups.

Conclusions

SprayShield? is easy to use. No serious adverse event related to SprayShield? was observed. Efficacy data are inconclusive regarding the performance of SprayShield?. Further studies are needed to better understand this performance.     

The outcome of Manchester–Fotergill operation for uterine decensus repair: a single center experience

Purpose

The aim of this study was to evaluate the clinical characteristics, peri- and post-operative outcomes, and clinical effectiveness of the Manchester–Fothergill (MF) procedure for uterine descensus as a uterine-sparing surgery.

Methods

In this study, 49 patients underwent the MF procedure as a uterine-sparing surgery for uterine descensus during 2008–2012 in the Department of Urogynecology at Kanuni Sultan Süleyman Research and Teaching Hospital, Istanbul, Turkey.

Results

Medical records and follow-up data were collected from 24 of the 49 patients (48.9 %). The mean age was 49.3 ± 9.1 years, and parity 3.6 ± 1.5; 41.6 % were post-menopausal; 6 patients (25 %) had grade II, and 18 (75 %) had grade III uterine prolapse; 95.8 % had associated cystoceles, and 79.1 % had associated rectoceles; 66.6 % complained of urinary incontinence. On follow-up examination, the cervical stumps were satisfactorily situated in 23 of 24 patients, and recurrent prolapse was seen in 1 patient (4.1 %). Bladder perforation was repaired at the time of the operation in 1 patient, and one complained of post-operative urinary retention.

Conclusion

The MF procedure is a viable option to surgically correct uterine descent while preserving the uterus to treat recurrent prolapse with a low complication rate and low morbidity.     

c-kit/CD 117 positive cells in the myometrium of pregnant women and those with uterine endometriosis

Purpose

Abnormal myometrial motility may play a role in the pathogenesis of endometriosis. Uterine contractility is a major contribution to labour. Myometrial motility might be controlled by CD 117-positive uterine smooth muscle cells.

Methods

Myometrial tissues from 8 cases with uterine endometriosis, 9 pregnant uteri (31.1?±?8.7?weeks of gestation), 10 cases from non-pregnant pre-menopausal and 9 cases from post-menopausal women were immunohistochemically evaluated using a polyclonal antibody against c-kit/CD 117. The number of CD 117 positive cells was counted within 10 microscopic high power fields (×400) and compared with the clinical diagnoses.

Results

Overall, a mean number of 15.7 (range 0?C43) CD 117-positive cells within the myometrium was seen. Significant highest count occurred in the myometrium of non-pregnant pre-menopausal women without uterine endometriosis (30.78?±?9.52), followed by post-menopausal women (15.5?±?8.37) and those with uterine endometriosis (9.98?±?4.9; p????0.01). The lowest count of CD 117-positive cells was seen in pregnant uteri (4.09?±?2.33; p?Conclusions The lowest count of CD 117-positive cells was seen in the myometrium of pregnant women suggesting a role of preventing premature uterine contractility. There is no increase of CD 117-positive cells in the myometrium of women affected by uterine endometriosis.     

An audit about labour induction, using prostaglandin, in women with a scarred uterus

Objectives

Induction of labour after a previous caesarean section is still controversial. We aim to analyse, in a population of women who have a uterine scar, the maternal, foetal and neonatal complications in relation to the mode of labour and delivery.

Study design

Retrospective analysis of collected data from all the singleton deliveries of patients with a scarred uterus (N?=?798), admitted to the hospital between August 2006 and March 2009. Outcomes: maternal and perinatal complications.

Results

Among 798 singleton deliveries, 36.1?% had a spontaneous labour, 12.6?% a prostaglandin-induced labour and 2.9?% an ocytocin-induced labour, and 48.4?% had an elective caesarean section. The chance of delivering vaginally was respectively 84.4?% for those who had a spontaneous labour, 75.2?% for those who were induced using prostaglandin, 82.6?% after induction using ocytocin. There were eight uterine ruptures, four after spontaneous labour (1.4?%), two after prostaglandin induction (2?%) and two at the time of an iterative caesarean section (0.5?%). There were no differences between groups, except the risk of haemorrhage (17.4?% after spontaneously induced labour, 34.8?% after ocytocin, 17.8?% after prostaglandin and 44.6?% after iterative caesarean section; p?<?0.005) and the neonatal admissions when analysed by intention to treat only (8.3?% after spontaneously induced labour, 9.1?% after ocytocin, 12?% after prostaglandin and 16.8?% after iterative caesarean section; p?<?0.009).

Conclusion

Although no increase in maternal or perinatal outcome was observed in relation to prostaglandin-induced labour after caesarean section, this study is too underpowered to exclude an increased risk.     

Changes in endometrial receptivity in women with Asherman’s syndrome undergoing hysteroscopic adhesiolysis

Objective

To determine whether there is any improvement in the endometrial receptivity in infertile women with Asherman??s syndrome undergoing hysteroscopic adhesiolysis.

Materials and methods

This was a prospective observational clinical analysis of 40 infertile patients who underwent hysteroscopic adhesiolysis for Asherman??s syndrome in a tertiary level hospital. Endometrial thickness and blood flow impedance of the uterine spiral artery by transvaginal color pulsed Doppler ultrasound was measured post-menstrual on day 2/3 and post-menstrual on day 21 pre- and post-hysteroscopic adhesiolysis or at a randomly chosen time in patients with amenorrhea.

Results

The age of the patients was 18?C36?years (mean 29.2?years). The mean duration of infertility was 6.9?years. There were 27 (67.5?%) women with primary infertility and 13 (32.5?%) had secondary infertility. 22 (55?%) women had had genital tuberculosis in the past. A significant improvement in the endometrial thickness was observed on day 2 (p?p?p?Conclusions A significant improvement in the endometrial thickness was observed post-adhesiolysis. A high blood flow impedance of spiral artery perhaps impairs growth of the endometrium making it unsuitable for successful implantation.     

A randomized controlled trial for cervical priming using vaginal misoprostol prior to hysteroscopy in women who have only undergone cesarean section

Purpose

To evaluate the efficacy of misoprostol administrated vaginally on cervical priming and its complications prior to diagnostic or operative hysteroscopy in women who have undergone at least one cesarean section and who have never delivered vaginally before and/or had other transcervical procedure.

Methods

A total of 55 patients undergoing hysteroscopy for various intra-uterine lesions were included in this study and were randomly allocated to two groups finally. Thirty patients in the study group were given 200?μg misoprostol vaginally 12?h before the procedure, whereas 25 patients in the control group did not receive any cervical priming. The countered outcome included the cervical width detected with Hegar dilatators and complication rates.

Results

Mean cervical width was greater in the study group (6.6?±?1.3) than in the control group (5.1?±?0.9). Complications and failure rates were lower in the study group.

Conclusion

Application of 200?μg misoprostol vaginally 12?h before hysteroscopy softens the cervix, reduces cervical resistance and consequently the need for cervical dilatation, with only mild side effects.     

Habituelle Aborte

Frequency

Recurrent miscarriages affect 1?% of couples trying to conceive.

Risk factors and treatment

Proven risk factors are chromosomal balanced translocations, large uterine septums, insufficiently treated hypothyroidism and diabetes mellitus, and antiphospholipid syndromes (APS). Treatments are genetic counseling, uterine septum resection, endocrine therapy of hypothyroidism and diabetes, and heparin plus acetylsalicylic acid in APS. Other risk factors are under discussion but due to insufficient data, clinical relevance could not yet be proved.

Recommendations

Medical societies have formulated evidence-based recommendations to diagnose and treat recurrent miscarriages; however, these are not uniform. Thus, several recommendations must be considered in individual cases. Medically and economically useful diagnostic and therapeutic procedures, which have not yet definitely been proven, might also be necessary.     

Cisplatin can be safely administered to ovarian cancer patients with hypersensitivity to carboplatin

Objective

Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy.

Hyaluronan binding assay does not predict pregnancy rates in IUI cycles in couples with unexplained infertility

Purpose

There are very few reports in the literature about the conservative surgical approach of large uterine myoma. The individualization of the surgery approach, the technical expertise and skill of the surgeon, the use of modern technologies/facilities could offer the optimal individualized treatment.

Methods

We performed a conservative combined surgical approach consisting of open laparoscopy myomectomy followed by laparotomy for the treatment of a very large uterine myoma of the anterior uterine wall in a 27-year-old non-pregnant woman with a history of progressive abdominal distension and symptoms related to abdomen pressure and constipation.

Results

The myoma weighted 12.010?kg. The postoperative course was good and 20?months after surgery, the patients had a successful pregnancy with a spontaneous delivery at the 39th week of a healthy baby weighting 3.260?kg.

Conclusions

In the case reported here, the careful pre-surgical evaluation, the technical expertise and skill of the surgeon, the choice of a combined approach with laparoscopy and open surgery and the use of modern surgical instruments have enabled us to achieve a significant result: the preservation of the anatomical integrity of the uterus and adnexa which allowed a successful natural pregnancy with spontaneous delivery.