Initiation of ovarian stimulation independent of the menstrual cycle: a case-control study.

PURPOSE: In the GnRH-antagonist protocol, ovarian stimulation with gonadotropins typically commences on cycle day 2 or 3. Initiation of ovarian stimulation with a spontaneously occurring menstruation, however, poses significant organizational challenges for treatment centres and patients alike. It has previously been demonstrated in the context of fertility preservation that initiation of stimulation in the luteal phase is feasible in terms of retrieval of mature oocytes for cryopreservation. Herein, we report the extension of this concept to a routine IVF setting with the aim of establishing an ovarian stimulation protocol, which can be utilized independent of menstruation. Because of asynchrony of endometrium and embryo in such a setting, all fertilized oocytes have to be cryopreserved for a later transfer. METHODS: This was a prospective, case-control study (trial registration: NCT00795041) on the feasibility of starting ovarian stimulation in a GnRH-antagonist protocol in the luteal phase. Inclusion criteria were: IVF or ICSI; 18-36 years; ≤3 previous IVF/ICSI attempts; BMI 20-30 kg/m(2); regular cycle (28-35 days); luteal phase progesterone >7 ng/ml at initiation of stimulation. Exclusion criteria were: PCOS, endometriosis ≥AFS III°, unilateral ovary, expected poor response. Stimulation was performed with highly purified uFSH (Bravelle®) 300 IU/day and 0.25 mg/day GnRH-antagonist starting on cycle day 19-21 of a spontaneous menstrual cycle and commencing until hCG administration when three follicles ≥17 mm were present. All 2PN stage oocytes were vitrified for later transfers in programmed cycles. Feasibility was defined as the achievement of ongoing pregnancies progressing beyond the 12th gestational week in at least 2/10 study subjects (primary outcome). Secondary outcomes were gonadotropin consumption per oocyte obtained, stimulation duration, and fertilization rates. Study subjects were matched in a 1:3 ratio with concomitantly treated control cases of similar age, BMI, and duration of infertility who were treated in a conventional GnRH-antagonist protocol with 150-225 rFSH or HP-HMG/day. RESULTS: The study group consisted of ten subjects, mean age 31.4 years, BMI 25.4 kg/m(2), of which one had fertilization failure. Mean stimulation duration was 11.7 (SD 1.6) vs. 9.1 (SD 1.3) days, mean cumulative FSH dose was 3,495.0 (SD 447.5) vs. 2,040.5 (SD 576.2) IU, and mean number of oocytes was 8.8 (SD 5.0) vs. 10.0 (SD 5.4) in study vs. control group, respectively. Per follicle ≥10 mm, the cumulative FSH dose was 274.5 (SD 130.8) IU vs. 245.2 (SD 232.3) IU in study and control groups, respectively. Cumulative ongoing pregnancy rates were 1/10 (10 %) and 6/30 (20.0 %) in study and control group, respectively (difference: 10 %, 95 % confidence interval of the difference: -29.2-22.2 %, p = 0.47). Fertilization rate was similar between groups, with 63.5 % (SD 32.9) in the study and 61.3 % (SD 26.7) in the control group, respectively. Serum estradiol levels were significantly lower on the day of triggering final oocyte maturation with 1,005.3 (SD 336.2) vs. 1,977.4 pg/ml (SD 1,106.5) in study and control group, respectively. Similarly, peak estradiol biosynthesis per growing follicle ≥10 mm was lower in the study group (134 pg/ml, SD 158.4 vs. 186.7 pg/ml, SD 84.7). CONCLUSIONS: Per retrieved oocyte, a nearly threefold higher dose of FSH had to be administered when ovarian stimulation had been initiated in the luteal phase. Furthermore, the present study casts doubt on the efficacy of initiating ovarian stimulation in the luteal phase in terms of pregnancy achievement. Thus, this concept is currently not feasible for routine use, and it should also be explored further before using it at larger scale in the context of emergency stimulation for fertility preservation.

Are there changes in characteristics and therapy of young patients with early-onset breast cancer in Germany over the last decade?

PURPOSE: The objective of the study is to investigate recent changes in patient characteristics and treatment procedures of young breast cancer patients over the last 10 years in Germany. METHODS: The study describes the data of 518 patients who were treated adjuvantly between 2008 and 2011 and participated in a resident mother-child program for rehabilitation (cohort II). The data includes TNM-categories, biology of tumor and therapies. This population is compared to a cohort of 535 patients, who were treated between 2002 and 2006 (cohort I). Characteristics and treatment of cohort II are compared with a normally age distributed cohort. RESULTS: 51.5 % of the patients in cohort II were diagnosed with tumor category pT1, 36.9 % pT2, 4.4 % pT3 and 1.2 % pT4. 3.3 % had merely DCIS. 58.1 % of the patients were pN0, 28.4 % pN1 and 13.5 % had a more intense manifestation of lymph nodes. 45.8 % of the tumors showed a grading classified as G3, 69.3 % were estrogen and progesterone hormone receptor positive and 21.8 % Her2 positive. 24.5 % of the examined patients showed a triple negative carcinoma. 66.2 % of the patients with pT1 or pT2 underwent breast-conserving surgery. Overall 19.2 % of the women received mastectomy only and 17.4 % received mastectomy with subsequent reconstruction. 98.6 % of the patients received axillary surgery, 87.6 % chemotherapy. Overall, 21.0 % of the patients received their chemotherapy in connection with clinical studies. 88.0 % of the patients with hormone receptor positive tumors received endocrine therapy, 25.5 % of them with GnRH-analogs. In comparison with cohort I the tumors in cohort II were detected with a higher proportion of negative lymph nodes (48.8 %/58.1 %, p = 0.008) and G1 grading (4.9/5.6 %, p = 0.001). On the other hand the percentage of triple negative tumors increased from 21.0 % to 24.5 % (p = 0.018). Operative therapy has adjusted to a more moderate way. Breast-conserving therapy with pT1 and pT2 increases from 57.3 % to 66.2 % (p = 0.006), sentinel lymph node biopsy only from 24.5 % to 47.5 % (p[Symbol: see text]0.001) over the years. The percentages of chemotherapy, radiation, endocrine therapy and antibody therapy with positive receptor have stayed stable over the last decade. Comparing cohort II with a normally age distributed group (DMP II 2007-2009) the young patients have still a much lower portion of negative lymph nodes (58.1 %/67.9 %) and positive hormone receptor status (69.3 %/85.1 %). The percentage of a high grading G3 is 45.8 % in cohort II versus 24.7 % in DMP II. The portion of breast-conserving therapy with pT1 is with 68.9 versus 82.2 % still comparatively low. Young patients received more axillary surgery (98.6 %/81.5 %) but less endocrine therapy with hormone receptor positive tumors (93.3 %/94.7 %). CONCLUSION: Young breast cancer patients in Germany can still be regarded as a special group. Although tumors are now more often detected before reaching the lymph nodes than 10 years ago, an even bigger percentage is triple negative. Operative treatment has improved to a less aggressive way. Still operative and medical treatments have to be chosen after very careful evaluation.

Total laparoscopic hysterectomy without uterine manipulator at big uterus weight (>280 g).

METHODS: The retrospective study included the total laparoscopic hysterectomy without uterus manipulator at big uterus >280 g (Group A), proceeding the same technique as known to show feasibility and safety of its technique, compared with a randomized patient group of a uterus weight below 280 g (Group B). Statistical measurement was proceeded in typical clinical parameters. RESULTS: No statistical differences in age, body mass index, further abdominal surgery, blood loss, and hospital stay were observed. Operating time was significantly different favouring the uterus below 280 g (111.74 min Group A/90.68 min Group B). No increase in intra- or postoperative complications in both groups was observed. CONCLUSION: Total hysterectomy at big uterus (>280 g) is safe and feasible. Statistical analysis shows a significant shorter operating time only in one parameter (Group B). The technique of hysterectomy without uterus manipulator offers a surgical advancement also at vaginal stenosis, early staged cervix, or endometrial cancer and exhibits an opportunity for laparoscopic advancement in these cases too.

Blood loss after caesarean section: depending on the management of oxytocin application?

PURPOSE: Oxytocin donation in caesarean section is used to reduce postpartum blood loss. Cardiovascular side effects such as tachycardia, hypotension and decreased cardiac output are known and seem to depend on the way of application, whereas the blood loss is said to be similar. We aimed to examine that extent of haemorrhage in our own patients. METHOD: In July 2011, the perioperative oxytocin management was changed and the postpartum was oxytocin bolus abolished. Retrospectively, we reviewed the pre- and postpartum haemoglobin in all women who had undergone caesarean section in the year 2011 at the University Hospital of Schleswig-Holstein, Campus Luebeck. RESULTS: We found a significantly higher blood loss in those patients who were treated without oxytocin bolus but only with oxytocin infusion (-10.5 vs. -9 g/dl). CONCLUSION: We recommend to do further studies to clarify the advantage and contraindications of using oxytocin boluses and until to use the oxytocin bolus again in healthy patients but to avoid it in patients with cardiovascular risk.

Incidence of testicular malignancies and correlation to risk factors in a TESE population of subfertile men.

INTRODUCTION: In recent years, researchers have postulated a decreasing fertility potential of males and a rising incidence of testicular malignancies. MATERIALS AND METHODS: In this retrospective observational diagnostic multicenter study, 302 patient files of subfertile men whose testes were biopsied for TESE procedure were analysed. All patients referred to reproductive medicine centres in Northern Germany and they were identified by the cycle data collected by the German IVF register. A total of 280 patients (436 cycles) treated for intracytoplasmatic sperm injection after TESE procedures were eligible to be analysed. RESULTS: Our findings: 13.0% overall paternity rate before TESE procedure, 45.9% smokers, maldescensus testis was found on occasion (12.9%), and mumps orchitis previously occurred to 10 patients (3.6%). The tumour incidence rate at the time of testicle biopsy was 1.81% (= 5 pts.). Two of these patients had an anamnesis for maldescensus testis and one patient acquired mumps orchitis in childhood. CONCLUSION: Our data even reflects that tumour patients express an interest in having children after completion of cancer treatment, presenting four patients who had testicular biopsies after a previous malignancy. Moreover, there is evidence suggesting that environmental factors are causative for the trends in occurrence of male reproductive health problems. Within our highly selected population, the testicular tumour incidence rate is 100-fold higher than in a standard population. Supposing that the incidence rate of testicular malignancies among infertile men continues to increase in comparison to the incidence rate of the general male population, one has to count on an incremental number of males suffering from subfertility and testicular tumours.

Characteristics and therapy of premenopausal patients with early-onset breast cancer in Germany.

PURPOSE: The objective of the study is to investigate what kind of tumors young, premenopausal breast cancer patients in Germany show at diagnosis and how they are treated adjuvantly in comparison with a normally distributed cohort. METHODS: The study describes the data of 535 patients who were treated adjuvantly between 2002 and 2006 and participated in a resident mother-child program for rehabilitation (Groemitz cohort). The data includes TNM categories, biology of tumor and therapies. This population is being compared to an age-heterogeneous cohort from the state of Schleswig-Holstein and the DMP-report of the state of North Rhine-Westphalia. RESULTS: 45.8 % of the patients were diagnosed with tumor category pT1, 37 % pT2, 7.3 % pT3 and 1.9 % pT4. 5 % had merely DCIS. 48.8 % of the patients were pN0, 31.4 % pN1 and 17.4 % had a more intense manifestation of lymph nodes. 43.5 % of the tumors showed a grading classified as G3, 64.3 % were estrogen and progesterone hormone receptor positive and 26.2 % Her2 positive. 21 % of the examined cohort members/patients showed a triple negative carcinoma. 59.1 % of the patients with pT1 underwent breast-conserving surgery, 56.1 % of those with pT2 and 25.6 % of those with pT3. Overall 31.0 % of the women received mastectomy and 14.8 % received mastectomy with subsequent reconstruction. 97.6 % of the patients received axillary surgery, 89.9 % chemotherapy. Overall 23.7 % of the patients received their treatment in connection with clinical studies. 95.3 % of the patients with hormone receptor positive tumor received endocrine therapy, 61.3 % of them with GnRH-analogs. In comparison with the OVIS and DMP cohorts patients of the Groemitz cohort were on average 20 years younger. Their tumors were of bigger size and had more often reached the axillary lymph nodes (pN0 48.8 % Groemitz/62.0 % OVIS/66.7 % DMP). The hormone receptor status was more often negative (35.7/16.6/16.5 %) and tumor grading higher (G3 43.5/29.0/28.5 %). Surgery was more extensive even with small tumors (breast conserving surgery with tumor stage pT1 59.1/81.2/77.6 %) and axillary surgery was performed more often in the young collective (97.6/89.3/62.5 %). More patients of the young collective received chemotherapy (89.9/58.4 %/unknown) and more patients of the young collective with hormone receptor positive tumor received endocrine therapy (95.3/77.4/90.6 %). CONCLUSION: Our study shows that young breast cancer patients in Germany can be regarded as a special group. At the time of diagnosis the tumor has frequently reached a more advanced stage, and carcinomas are more aggressive. Operative and medical treatment will often be more aggressive.

Follicular fluid high-density lipoprotein-associated sphingosine 1-phosphate (S1P) promotes human granulosa lutein cell migration via S1P receptor type 3 and small G-protein RAC1.

Coordinated migration and progesterone production by granulosa cells is critical to the development of the corpus luteum, but the underlying mechanisms remain obscure. Sphingosine 1-phosphate (S1P), which is associated with follicular fluid high-density lipoprotein (FF-HDL), was previously shown to regulate ovarian angiogenesis. We herein examined the effects of S1P and FF-HDL on the function of granulosa lutein cells. Both FF-HDL and S1P induced migration of primary human granulosa lutein cells (hGCs) and the granulosa lutein cell line HGL5. In addition, FF-HDL but not S1P promoted progesterone synthesis, and neither of the two compounds stimulated proliferation of granulosa lutein cells. Polymerase chain reaction and Western blot experiments demonstrated the expression of S1P receptor type 1 (S1PR1), S1PR2, S1PR3, and S1PR5 but not S1PR4 in hGCs and HGL5 cells. The FF-HDL- and S1P-induced granulosa lutein cell migration was emulated by FTY720, an agonist of S1PR1, S1PR3, S1PR4, and S1PR5, and by VPC24191, an agonist of S1PR1 and S1PR3, but not by SEW2871 and phytosphingosine 1-phosphate, agonists of S1PR1 and S1PR4, respectively. In addition, blockade of S1PR3 with CAY1044, suramine, or pertussis toxin inhibited hGC and HGL5 cell migration toward FF-HDL or S1P, while blockade of S1PR1 and S1PR2 with W146 and JTE013, respectively, had no effect. Both FF-HDL and S1P triggered activation of small G-protein RAC1 and actin polymerization in granulosa cells, and RAC1 inhibition with Clostridium difficile toxin B or NSC23766 abolished FF-HDL- and S1P-induced migration. The FF-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of the corpus luteum.

Ovarian stimulation: from basic science to clinical application.

Treatment for infertility, including ovarian stimulation, was first introduced almost 100 years ago. At this time, radiation therapy became an established treatment, and it was only some decades later that the problem of radiation-induced cancer emerged. Non-human gonadotrophins, such as pregnant mare serum gonadotrophin (PMSG), and human pituitary gonadotrophins (HPG), were commonly used for hormonal stimulation procedures. However, use of PMSG led to antibody formation, and it was therefore only useful for the first treatment cycle. HPG produced good results, but its use came to an end in the late 1980s when it was linked to the development of Creutzfeldt-Jakob disease. The first hormonal product from human menopausal urine to be used was human menopausal gonadotrophin (HMG), followed later by purified preparations of this product. All of these preparations contained a high percentage of unknown urinary proteins, which interfered with batch-to-batch consistency. This changed with the introduction of recombinant gonadotrophins, produced from an immortalized/standardized mammalian cell line (CHO). More recent developments include the introduction of long-acting gonadotrophin formulations. The development of gonadotrophin-releasing hormone (GnRH) analogues and more recently the use of GnRH antagonists has helped to improve ovarian stimulation protocols by optimizing their efficacy, and making them easier to administer.

Intensified ovarian stimulation in a GnRH antagonist protocol with agonist triggering: a prospective, clinical feasibility study.

The threat of severe ovarian hyperstimulation syndrome (OHSS) and the increase in discomfort for the patient has limited the feasibility of maximizing the oocyte yield per treatment cycle. A gonadotrophin-releasing hormone (GnRH) antagonist protocol with agonist triggering and vitrification of all 2PN oocytes can eliminate the risk of OHSS. This prospective, single-centre, cohort study in 30 good-responder IVF patients ≤ 36 years reports the feasibility of arbitrarily intensifying stimulation in a GnRH antagonist protocol in terms of tolerability, safety and efficacy. Ovarian stimulation was performed with 225-375IU FSH, induction of final oocyte maturation with 0.2mg GnRH agonist followed by vitrification of all 2 pronuclear (2PN) oocytes and repetitive vitrified-warmed embryo transfer cycles. Main outcomes were severe OHSS incidence, tolerability, assessed by a questionnaire, and cumulative live birth rate. On average, 17 oocytes were retrieved (range 4-42) and 8.4 oocytes at the 2PN stage were cryopreserved (range 3-22). No case of severe OHSS was observed (0%, 95 CI 0-11.4%). Tolerability was good. The cumulative live birth rate per patient undergoing at least one vitrified-warmed embryo transfer was 26.9% (7/26, 95% CI 13.7-46.1%). This approach can be explored in future larger-sized controlled studies.

Emerging gonadotropin-releasing hormone agonists.

INTRODUCTION: Gonadotropin-releasing hormone agonist analogs (GnRHa) are peptides that mimic the action of gonadotropin-releasing hormone (GnRH) and are used to suppress subsequent sex steroid production. Although the analogs are a rather defined group of drugs, there have been developments in the past decades and there is still ample room for improvement. New therapeutic strategies in the use of GnRHs are discussed. AREAS COVERED: Major points of discussion include: i) the use of concomitant treatment of early breast cancer in premenopausal estrogen-positive and -negative patients, ii) the use of GnRHa for fertility preservation in young female patients with malignant diseases and iii) the use of GnRH analogs in assisted reproduction. The manuscript provides a better understanding of GnRH agonists as well as an explanation of their major indications, biochemical pathways and concluding therapeutic strategies. Recent results from international meetings and debates are described to explain current controversies. EXPERT OPINION: This paper highlights the need for more complex GnRH analogs. In the next few years, there will be longer acting GnRHas that may improve adherence. New therapeutic targets in oncological concepts may go beyond fertility preservation and focus on the antiproliferative effects of GnRH analogs.

Laparoendoscopic single-site surgery (LESS) - is it feasible in gynecological surgery?

Increases in technical expertise in gynecological surgery and advances in surgical instrumentation have led to the development of laparoendoscopic single-site surgery (LESS). Between March and September 2009, 24 patients underwent adnexal surgery at our institution with laparoendoscopic single-site surgery. The LESS technique was performed using the TriPort through an umbilical incision of 10 mm and bent laparoscopic instruments. We furthermore compared the LESS technique with a control group of 24 patients operated consecutively in the same period and for the same procedures with conventional multiport laparoscopy. Comparing the two techniques we found differences between the operation time and mean hospital stay. The surgeon must master the use of novel bent instruments in close proximity to each another. The LESS technique for benign adnexal surgery is technically feasible and safe, representing a reproducible alternative to conventional multiport laparoscopy.

miRNA expression profiling in formalin-fixed and paraffin-embedded placental tissue samples from pregnancies with severe preeclampsia.

AIMS: Micro RNAs (miRNAs) are small, single-strand RNAs, playing an important role in post-transcriptional gene regulation. The placenta is considered to play a key role in pathogenesis of preeclampsia. The purpose of this study was to demonstrate deregulation of miRNAs in placentas with preeclampsia using formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: Expression levels of 162 miRNAs were measured in FFPE placental tissues (5 with severe preeclampsia, 5 from a control group) using a quantitative qPCR based technique. RESULTS: Six miRNAs were more than 2-fold over-expressed in severe preeclampsia: let-7b, miRNA-302*, miRNA-104, miRNA-128a, miRNA-182* and miRNA-133b. Gene ontology analyses were performed using the algorithms "TargetScanS", "microRNA", and "PicTar". CONCLUSIONS: Two of the up-regulated miRNAs (miRNA-182* and miRNA-133b) are putative regulators of the transcript variants 1 and 2 of the BCL2-like gene, which controls apoptosis. miRNA-182* is also a probable angiogenesis regulator via angiogenin and VEGF-B. Apoptosis and angiogenesis are major mechanisms presumed to be involved in the pathogenesis of preeclampsia. Moreover, usability of qPCR technique based miRNA profiling for FFPE tissues was proofed. Hence FFPE tissue is the most widely used material for retrospective clinical studies, this method has a great property for future investigations in placenta research.

Coexistent parathyroid adenoma and thyroid papillary carcinoma in pregnancy.

BACKGROUND: Primary hyperparathyroidism in pregnant women is a rare antenatal complication. Maternal symptoms include nephrolithiasis, bone disease, pancreatitis, hyperemesis, muscle weakness, mental status changes, and hypercalcemic crisis. Fetal complications comprise intrauterine growth retardation, low birth weight, preterm delivery, intrauterine fetal death, postpartum neonatal titanic crisis, and permanent hypoparathyroidism. CASE: A 23-year-old gravida was referred to our clinic with severe hyperemesis and weight loss at 32 gestational weeks. She was diagnosed with primary hyperparathyroidism because of parathyroid adenoma and treated with surgery where a synchronous thyroid papillary carcinoma was detected. After right parathyroidectomy and right subtotal lobectomy of the thyroid, the patient was stable and laboratory and clinical findings normalized. The fetus' state was monitored via reassuring non-stress cardiotocography and repeated sonographic exams until birth. Delivery was induced at 35 weeks of gestation because of preeclampsia. CONCLUSION: Parathyroid adenoma in pregnancy is a rare maternal condition with potential impact on the advancing pregnancy. Generally, a surgical approach is recommended with thorough inspection of the thyroid gland so that any irregular structure might be removed during the same surgical intervention for diagnostic reasons. In this reported case, a coexistent papillary carcinoma of the thyroid was detected accidentally and removed successfully.

Bridge-1 is expressed in human breast carcinomas: silencing of Bridge-1 decreases Smad2, Smad3 and Smad4 expression in MCF-7 cells, a human breast cancer cell line.

PURPOSE: The aim of the study was to investigate the expression of Bridge-1 in human breast carcinomas, and to determine the in vitro regulation of Bridge-1 by activin A and the influence of Bridge-1 on activin A signaling in the human breast cancer cell line MCF-7. METHOD: Bridge-1 expression in human breast carcinomas was shown after staining paraffin slides with a specific antibody against Bridge-1. To gain insight into Bridge-1 function, immortalized, human breast cancer cells (MCF-7 cell line) were stimulated with activin A and the expression of Bridge-1 was analyzed by real-time PCR and Western blot. Next, Bridge-1 was downregulated via siRNA treatment in MCF-7 cells and the expression of Bridge-1, Smad2, 3 and 4 was investigated by real-time PCR and Western blot. RESULTS: Human breast carcinoma cells showed nuclear and cytoplasmic localization of Bridge-1. Activin A stimulation of the immortalized human breast adenocarcinoma cell line MCF-7 showed an increase in Bridge-1 expression by real-time PCR and Western blot. Downregulation of Bridge-1 by Bridge-1-siRNA resulted in a decreased expression of Smad2, 3 and 4 of up to 50% compared to the treatment with non-targeting siRNA. CONCLUSIONS: This study is the first to demonstrate the expression of Bridge-1 in human breast carcinomas. Bridge-1 expression is increased by activin A stimulation and itself seems to influence activin A signaling by affecting the expression of Smad2, 3 and 4.

Does acetic acid influence the non-dysplastic Pap smear?

OBJECTIVE: Acetic acid tests are commonly performed for colposcopic evaluation of the cervix. However, it is unclear whether the acetic acid influences normal Papanicolaou (Pap) smear results. METHODS: Patients were routinely seen in our outpatient department between April and May 2009. Two Pap smears were performed in 50 patients. One smear was done before, the other after the acetic acid test. The smears were evaluated by an experienced cytologist. He did not know whether the smear was done with or without acetic acid. RESULTS: In a normal smear, there was no influence of acetic acid on the cytologic result. In two patients, a smear of Pap III [Bethesda, atypical squamous cells of undetermined significance (ASCUS)] was seen before acetic acid test. This changed to Pap IIID [Bethesda, low-grade squamous epithelial lesions (LSIL)] after acetic acid test. CONCLUSIONS: The acetic acid test does not seem to alter the result of the non-dysplastic smear. In contrast to this, a dysplastic smear seems to be influenced by the acetic acid. This should be evaluated in a further investigation.

Standardized technique of laparoscopic pelvic and para-aortic lymphadenectomy in gynecologic cancer optimizes the perioperative outcomes.

INTRODUCTION: The main objective of this study is to illustrate the effectiveness and the safety of standardized technique of laparoscopic lymphadenectomy (LNE), newly introduced in a University Hospital, in patients with gynecologic malignancy. MATERIALS AND METHODS: A cohort of 104 patients with gynaecologic malignancies (71 with endometrial and 33 with cervical cancer), who underwent laparoscopic pelvic with or without para-aortic LNE between September 2008 and March 2010, were analyzed. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy (TLH & BSO) was the standard approach for patients with endometrial cancer (n = 71), while laparoscopic (nerve sparing) radical hysterectomy (n = 29), laparoscopic-assisted radical vaginal hysterectomy (n = 2) and radical trachelectomy was the treatment for patients with cervical cancer. All LNE were performed by a learning team under the supervision of an expert surgeon, familiar with the technique. RESULTS: The median number of pelvic lymph nodes yielded was 22 (range 16-34) and of para-aortic 14 (range 12-24). The mean operative time ± standard deviation for pelvic LNE for each side was 29 ± 17 and 64 ± 29 min for para-aortic LNE. The overall complication rate was 7.6% (n = 8). Two patients were reoperated laparoscopically, one because of postoperative hemorrhage and the other because of lymphocyst formation; laparoconversion was not necessary. DISCUSSION: Laparoscopic lymphadenectomy performed by a learning team with standardized technique is effective with adequate number of harvested nodes, in acceptable operative time and with low rate of perioperative complications.

Successful application of vacuum-assisted closure therapy for treatment of mastitis-associated chronic breast wounds.

INTRODUCTION: Although non-puerperal mastitis is rare and its cause is rather unclear, the number of patients diagnosed with this defect is increasing. In some cases, standard therapy fails and it progresses to a chronic disease. Vacuum-assisted closure (VAC) therapy has shown good results in healing complex wounds. PATIENTS AND METHODS: The goal of this study was to evaluate our experiences with VAC therapy and to answer the question whether or not should be accepted as an effective treatment in healing chronic wounds caused by non-puerperal mastitis. Retrospectively, we identified five patients with a non-puerperal mastitis chronic wound that was treated using VAC and report on their outcome. RESULTS: We reached both wound control and closure of the breast wounds in all patients. CONCLUSION: According to our findings, the VAC therapy can be considered when managing challenging breast wounds, particularly when other therapeutic options have failed. The role of VAC therapy as a primary therapeutic option has not yet been evaluated.

Obesity decreases the chance to deliver spontaneously.

PURPOSE: To evaluate the impact of maternal obesity on labour, intrapartual assessment and delivery. METHODS: Retrospective cohort analysis of n = 11,681 deliveries supervised between 01 January 2000 and 31 December 2009. Results were analysed dividing the patients into two main groups according to their body mass index (BMI): group 1, control: BMI 18-24.9 and group 2 BMI, test >25. Subgroups were built: (0) BMI 25-29.9, (I) BMI 30-34.9, (II) BMI 35-39.9, (III) BMI >40. Exclusion criteria were defined as: delivery <37 + 0 weeks p.m., multiple pregnancy, comorbidity other than GDM, abnormal presentation, BMI <18.5, and incomplete data. The main outcome parameter was defined as secondary caesarean delivery rate and mode of delivery. RESULTS: N = 8,379 patients met the inclusion criteria and were divided in two groups: 1, n = 4,464 patients and 2, n = 3,915. Basic maternal characteristics including foetal vital parameters were equal in all groups. GDM occurred more frequently in obese patients (P < 0.001). For the main outcome parameter a significant decrease in the rate of spontaneous delivery between control/test groups (72-66%, P < 0.001) and control/I-III groups (72 vs. 50%, P < 0.001) could be observed. The rate of secondary c-section increased significantly according to a higher BMI (>40: OR 2.5, 95% CI 1.84-3.61, χ (2) P < 0.001). The groups showed no difference in the rate of injuries during delivery though foetal birth weight increased significantly with a higher BMI (3,412-3,681 g; P < 0.001). CONCLUSION: Obesity decreases the chance to deliver spontaneously. Moreover, the obese patient suffers from a significantly longer trial of labour (7.9 vs. 9.5 h) and an elevated risk of surgical delivery.

Spontaneous uterine rupture at the 21st week of gestation caused by placenta percreta.

PURPOSE: To describe the management of a ruptured uterus caused by placenta percreta in the 21st week of gestation. METHODS: We present a case report of a 33-year-old patient with a ruptured uterus in the 21st week of gestation who presented at the Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck. Therapeutic management was performed by laparoscopy, and consecutive laparotomy and hysterectomy. RESULTS: A 33-year-old patient presented with severe abdominal pain in the 21st week of gestation at the department of abdominal surgery. A laparoscopy was performed to exclude appendicitis. There was about one liter of blood in the peritoneal cavity and a small, bleeding lesion in the fundus uteri was found which was coagulated. The blood was evacuated and the patient returned to department of gynecology. One hour after the first operation, the patient developed signs of hypovolemic shock and ultrasound showed absent fetal heart beat. An immediate laparotomy was performed and a ruptured uterus was detected. The fetus was removed and a hysterectomy performed. Pathology results showed a placenta percreta. After a few days in hospital and transfusion of 4 liters of blood the patient was discharged in a healthy condition. CONCLUSIONS: In a pregnant woman with severe abdominal pain even in the 21st week of gestation a placenta percreta has to be considered as a differential diagnosis. If there is no evidence of other causes, laparoscopy may help to confirm the diagnosis and hysterectomy is a life saving intervention.