Breast conserving surgery in combination with intraoperative radiotherapy after previous external beam therapy: an option to avoid mastectomy.

PURPOSE: Mastectomy is the standard procedure in patients with in-breast tumor recurrence (IBTR) or breast cancer after irradiation of the chest due to Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in combination with intraoperative radiotherapy (IORT) is possible. To date, data concerning BCS in combination with IORT in pre-irradiated patients are limited. This is the first pooled analysis of this special indication with a mature follow-up of 5 years. METHODS: Patients with IBTR after external beam radiotherapy (EBRT; treated in two centers) for breast cancer were included. Patients with previous EBRT including the breast tissue due to other diseases were also included. IORT was performed with the Intrabeam™-device using low kV X-rays. Clinical data including outcome for all patients and toxicity for a representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were done including Kaplan-Meier estimates for local recurrence, distant metastasis and overall survival. RESULTS: A total of 41 patients were identified (39 patients with IBTR, 2 with Hodgkin`s disease in previous medical history). Median follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred within 9 weeks. Local recurrence-free survival rate was 89.9% and overall survival was 82.7% at 5 years. Seven patients developed metastasis within the whole follow-up. CONCLUSIONS: BCS in combination with IORT in IBTR in pre-irradiated patients is a feasible method to avoid mastectomy with a low risk of side effects and an excellent local control and good overall survival.

Technologies of cryoprotectant-free vitrification of human spermatozoa: asepticity as criterion of effectiveness.

This review describes 120 years history of technology for cryoprotectant-free cryopreservation of human spermatozoa by direct plunging into liquid nitrogen (vitrification). It is presented an explanation why cryoprotectant-free vitrification for some human ejaculates is better than conventional freezing and vitrification with the presence of cryoprotectants. Special attention is given to the extremely high viability of viruses, bacteria and micoplasmas after cryoprotectant-free cryopreservation in culture medium and even in distilled water. This fact increases the potential risk of disease transmission through liquid nitrogen. It is concretized the concept "asepticity" as obvious parameter for any medical assisted reproduction technology which includes the cooling of cells in liquid nitrogen. It is described the role of nonpermeable compounds of mediums for cryoprotectant-free vitrification: carbohydrates, proteins, lipoproteins, antioxidants. This review summarizes concerned data regarding two groups of different current technologies for cryoprotectant-free vitrification of human spermatozoa: with direct contact of spermatozoa with liquid nitrogen as well as with full isolation of these cells from liquid nitrogen (aseptic technologies).

Use of the fluorescent dye tetramethylrhodamine methyl ester perchlorate for mitochondrial membrane potential assessment in human spermatozoa.

Mitochondrial membrane potential (ΔΨm) is an indicator of sperm quality and its evaluation complements the standard semen analysis. The fluorescent dye JC-1 has been widely used to assess sperm ΔΨm; however, some problems have been detected under certain experimental conditions. Another fluorescent compound, tetramethylrhodamine methyl ester perchlorate (TMRM), has been used in somatic cells and bovine spermatozoa but not in human spermatozoa. TMRM accumulates in hyperpolarised mitochondria and the fluorescence intensity of this compound correlates with ΔΨm. Thus, the aim of this study was to evaluate and validate the usefulness of the fluorescent dye TMRM for measuring sperm ΔΨm. The results showed that TMRM accurately detects sperm populations displaying either high or low ΔΨm. Moreover, TMRM was able to measure sperm ΔΨm under the experimental conditions in which JC-1 had previously presented difficulties. Differences in ΔΨm according to sperm and semen quality were properly detected and a positive correlation between ΔΨm and conventional semen parameters was observed. Finally, a positive correlation was found between the ΔΨm measurement by TMRM and by the widely used JC-1. In conclusion, TMRM is a simple, time-effective method, easy to set in laboratories equipped with flow cytometry technology, and can accurately detect changes in ΔΨm with efficiency comparable to JC-1 without its limitations.

Diagnosis, Therapy and Follow-up Care of Vulvar Cancer and its Precursors. Guideline of the DGGG and DKG (S2k-Level, AWMF Registry Number 015/059, November 2015.

Purpose: This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

Induction of Labour in Late and Postterm Pregnancies and its Impact on Maternal and Neonatal Outcome.

INTRODUCTION: This study aimed to determine the effects of induction of labour in late-term pregnancies on the mode of delivery, maternal and neonatal outcome. METHODS: We retrospectively analyzed deliveries between 2000 and 2014 at the University Hospital of Cologne. Women with a pregnancy aged between 41 + 0 to 42 + 6 weeks were included. Those who underwent induction of labour were compared with women who were expectantly managed. Maternal and neonatal outcomes were evaluated. RESULTS: 856 patients were included into the study. The rate of cesarean deliveries was significantly higher for the induction of labour group (33.8 vs. 21.1 %, p < 0.001). Aside from the more frequent occurrence of perineal lacerations (induction of labour group vs. expectantly managed group = 38.1 % compared with 26.4 %, p = 0.002) and all types of lacerations (induction of labour group vs. expectantly managed group = 61.5% vs. 52.2 %, p = 0.021) in women with vaginal delivery, there were no significant differences in maternal outcome. Besides, no differences regarding neonatal outcome were observed. CONCLUSIONS: Our study suggests that induction of labour in late and postterm pregnancies is associated with a significantly higher cesarean section rate. Other maternal and fetal parameters were not influenced by induction of labour.

New Screening Proposals: the Federal Joint Commission Defines the Parameters for Cervical Cancer Screening from 2018: Statement of the Gynecology Oncology Working Group (AGO).

The Gynecology Oncology Working Group (AGO e. V.) unequivocally welcomes the decision taken by the German Federal Joint Commission (Gemeinsamer Bundesausschuss, G-BA) on March 19, 2015 regarding screening for cervical cancer. AGO is convinced that, in view of recent medical advances, this evidence-based decision will improve screening for cervical cancer.

Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015).

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.

[S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology]. / S3-Leitlinie Diagnostik und Therapie des Zervixkarzinoms.

Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.

Cryopreservation of whole ovine ovaries with pedicles as a model for human: parameters of perfusion with simultaneous saturations by cryoprotectants.

BACKGROUND: The aim of this research was to study the effectiveness of perfusion of intact ovine ovaries with different rates of perfusion and time-period elapsed between extraction of these ovaries and the beginning of perfusion. METHODS: Ovaries were perfused through the arteria ovarica (ovarian arteries) with culture medium supplemented with 5% bovine calf serum, 6% dimethyl sulfoxide, 6% ethylene glycol, 0.15M sucrose, Indian ink, and 100 IU/mL heparin at room temperature (22 degrees C). In the first cycle of experiments, ovaries (n = 96) were perfused for 60 minutes just after extraction of ovaries at the following rates of perfusion (mL/hour): 150, 100, 75, 50, 25, 12.5, and 6.3. In the second cycle of experiments, ovaries (n = 26) were perfused at a rate of 25 mL/hour for 60 minutes after extraction of ovaries and their storage at room temperature for 2, 3, 4, and 5 hours, for groups 1, 2, 3, and, 4, respectively. Successful perfusion of blood vessels was detected visible by a blue coloration of the ovarian tissues. RESULTS: The first cycle of experiments showed that the optimal perfusion rates were 50 mL/hour and 25 mL/hour. In the second cycle of experiments, good perfusion of ovaries was established at a perfusion rate of 25 mL/hour for the ovaries of groups when 2 and 3 hours had elapsed after extraction. CONCLUSIONS: Effective perfusion of ovine intact ovaries with vascular pedicle was established using freezing medium at room temperature at the rate of perfusion of 25 mL/hour or 50 mL/hour. The ovaries must be perfused not later than 3 hours after the death of animals.

Peripartum pubic symphysis separation--Current strategies in diagnosis and therapy and presentation of two cases.

BACKGROUND: During spontaneous vaginal delivery, pubic symphyseal widening is normal. Common changes are reversible after complication-free birth. However, cases of peripartum symphysis separation are rare. There is no consensus in the literature on how to treat pregnancy-related pubic symphysis separation. METHODS: This review used a literature-based search (PubMed, 1900-2013) and analysis of 2 own case reports. Studies with conclusions regarding management were particularly considered. RESULTS: Characteristic symptoms, suprapubic pain and tenderness radiating to the posterior pelvic girdle or lower back, may be noted 48 h after delivery. Pain on movement, especially walking or climbing stairs, is often present. Conservative treatments, such as a pelvic brace with physiotherapy and local interventions such as infiltration, are successful in most cases. Symptom reduction within 6 weeks is the most common outcome, but can take up to 6 months in some cases. Surgical intervention is needed in cases of persistent separation. Anterior plate fixation is offered as a well-known and safe procedure. Minimally invasive SI joint screw fixation is required in cases of combined posterior pelvic girdle lesions. SUMMARY: Postpartum symphyseal rupture can be indicated with the rare occurrence of pelvic pain post-delivery, with sciatica or lumbago and decreased mobility. The diagnosis is made on clinical findings, as well as radiographs of the pelvic girdle. Conservative treatment with a pelvic brace is the gold standard in pre- and postpartum cases of symphysis dysfunction.

Surgical Methods for the Treatment of Uterine Fibroids - Risk of Uterine Sarcoma and Problems of Morcellation: Position Paper of the DGGG.

The appropriate surgical technique to treat patients with uterine fibroids is still a matter of debate as is the potential risk of incorrect treatment if histological examination detects a uterine sarcoma instead of uterine fibroids. The published epidemiology for uterine sarcoma is set against the incidence of accidental findings during surgery for uterine fibroids. International comments on this topic are discussed and are incorporated into the assessment by the German Society for Gynecology and Obstetrics (DGGG). The ICD-O-3 version of 2003 was used for the anatomical and topographical coding of uterine sarcomas, and the "Operations- und Prozedurenschlüssel" (OPS) 2014, the German standard for process codes and interventions, was used to determine surgical extirpation methods. Categorical qualifiers were defined to analyze the data provided by the Robert Koch Institute (RKI), the German Federal Bureau of Statistics (DESTATIS; Hospital and Causes of Death Statistics), the population-based Cancer Register of Bavaria. A systematic search was done of the MEDLINE database and the Cochrane collaboration, covering the period from 1966 until November 2014. The incidence of uterine sarcoma and uterine fibroids in uterine surgery was compared to the literature and with the different registries. The incidence of uterine sarcoma in 2010, standardized for age, was 1.53 for Bavaria, or 1.30 for every 100 000 women, respectively, averaged for the years 2002-2011, and 1.30 for every 100 000 women in Germany. The mean incidence collated from various surveys was 2.02 for every 100 000 women (0.35-7.02; standard deviation 2.01). The numbers of inpatient surgical procedures such as myoma enucleation, morcellation, hysterectomy or cervical stump removal to treat the indication "uterine myoma" have steadily declined in Germany across all age groups (an absolute decrease of 17 % in 2012 compared to 2007). There has been a shift in the preferred method of surgical access from an abdominal/vaginal approach to endoscopic or endoscopically assisted procedures to treat uterine fibroids, with the use of morcellation increasing by almost 11 000 coded procedures in 2012. Based on international statements (AAGL, ACOG, ESGE, FDA, SGO) on the risk of uterine sarcoma as an coincidental finding during uterine fibroid surgery and the associated risk of a deterioration of prognosis (in the case of morcellation procedures), this overview presents the opinion of the DGGG in the form of four Statements, five Recommendation and four Demands.

Erratum: Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015).

[This corrects the article DOI: 10.1055/s-0035-1558120.].

Quality of human spermatozoa: relationship between high-magnification sperm morphology and DNA integrity.

The aim of this work is to establish the relationship between the morphology of Intracytoplasmic Morphologically Selected Sperm Injection (IMSI)-selected spermatozoa and their DNA integrity. The 45 ejaculates were randomly distributed into three treatment groups: normozoospermic, oligoasthenozoospermic and oligoasthenotheratozoospermic samples. The evaluation of DNA integrity was performed using the sperm chromatin dispersion test. It was established that DNA integrity of spermatozoa is strongly dependent on ejaculate quality (P < 0.05). The count of spermatozoa with nonfragmented DNA in normozoospermic samples was high and independent from IMSI-morphological classes (Class 1 versus Class 3, respectively) (P > 0.1). With decreased ejaculate quality, the percentage of spermatozoa with nonfragmented DNA decreased significantly (P < 0.05) independent from morphological class. Nevertheless, the rate of IMSI-selected spermatozoa with fragmented DNA within of Class 1 in normozoospermic (Group 1), in oligoasthenozoospermic (Group 2) and in oligoasthenotheratozoospermic (Group 3) samples was 21.1%, 31.8% and 54.1%, respectively. In conclusion, there is a direct relationship between morphological parameters of spermatozoa and their DNA integrity. However, the IMSI technique alone is not enough for the selection of spermatozoa with intact nuclei.

In vitro perfusion of whole bovine ovaries by freezing medium: effect of perfusion rate and elapsed time after extraction.

BACKGROUND: Cryopreservation and transplantation of the whole ovary with vascular pedicle would be helpful to prevent posttransplantation ischemia. In fact, perfusion of the intact mammalian ovary through arteries and veins is the most technically difficult part of the whole cryopreservation process because of its complexity. It is important to develop the technology of long-time perfusion of intact ovaries by cryoprotectants at low temperatures because it was established earlier that 24-hour cooling to 5 degrees C before cryopreservation is beneficial for the freezing of human ovarian tissue. The aim of this research was to study the effectiveness of perfusion of intact bovine ovaries with different rates of perfusion and elapsed time between extraction of these ovaries and beginning of perfusion. METHODS: Arteria ovarica was cannulated and ovaries were perfused with Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink at room temperature (22 degrees C). In the first cycle of experiments, ovaries (n = 145) were perfused for 60 minutes during 1 to 1.5 hours after extraction of ovaries in the slaughter house at perfusion rates of 150 mL/hour (2.5 mL/minute), 100 mL/hour (1.67 mL/minute), 75 mL/hour (1.25 mL/minute), 50 mL/hour (0.83 mL/minute), 25 mL/hour (0.42 mL/minute), and 12.5 mL/hour (0.21 mL/minute) for groups 1, 2, 3, 4, 5, and 6, respectively. In the second cycle of experiments, ovaries (n = 29) were perfused with a rate of 25 mL/hour (0.42 mL/minute) for 60 minutes during the following time-periods elapsed after extraction of ovaries in the slaughter house: 3 hours (n = 18), 4 hours (n = 5), 5 hours (n = 3), and 6 hours (n = 3) for groups 1, 2, 3, and 4, respectively. Ovaries in luteal and follicular phase of development were distributed randomly into groups. Successful perfusion of blood vessels was detected visibly by a blue coloration of the vascular pedicle and ovarian tissues. The percentage of Indian ink-perfused tissues was detected. The intensity of the vascular leakage and tissue damage was scored microscopically and noted as follows: lack of disruption (-), weak disruption (+), moderate disruption (++), and strong disruption RESULTS: The first cycle of experiments shows that an optimal perfusion rate was established for groups 4 and 5 (50 and 25 mL/hour, respectively). In the second cycle of experiments, good perfusion of ovaries with the perfusion rate of 25 mL/hour was established only for ovaries of group 1 (3 hours after extraction). The effectiveness of perfusion in group 2 (4 hours after extraction) was sharply decreased. CONCLUSIONS: Effective perfusion of bovine intact ovaries with vascular pedicle with freezing medium (6% ethylene glycol + 6% dimethyl sulfoxide + 0.15 M sucrose) at room temperature includes a rate of perfusion 25 or 50 mL/ hour. Ovaries must be perfused no later than 3 hours after the death of animals.

Innovations in Cervical and Endometrial Cancer.

The S2k guideline "Diagnostics and Therapy for Cervical Cancer" published in 2008 is currently being revised to the S3 level. Current developments in epidemiology, surgical therapy, radiochemotherapy and drug therapy will be presented. The S2k guideline "Diagnostics and Therapy for Endometrial Cancer" will also be up-dated this year. The revised recommendations on early diagnosis and diagnostics, therapy for precursors, surgical therapy, adjuvant therapy and therapy for recurrences and metastases will be presented.

Use of Laparoscopy in the Treatment of Endometrial and Cervical Cancer - Results of a 2012 Germany-wide Survey.

Introduction: Endoscopy has begun to play an increasingly important role in the surgical therapy of uterine cancers. To date, there is no data on the use of laparoscopy to treat endometrial cancer (EC) and cervical cancer (CC). Method: A Germany-wide, anonymised survey was done of all gynaecological clinics/endoscopy clinics, using a standardised questionnaire. Results: A total of 128 clinics responded: 16 university clinics (12.5 %), 30 hospitals offering maximum care (23.4 %), 66 general hospitals (51.5 %), 5 outpatient clinics (3,9 %), 4 physicians in private practice affiliated to hospitals (3.1 %) and 7 hospitals (5.4 %) which did not indicate status. Laparoscopy was used in the treatment of 82 % of all EC and 54 % of CC. Surgery for EC was done completely laparoscopically in 58 % of cases and with laparoscopic assistance using a vaginal approach in 32 % of cases. If lymphadenectomy (LNE) was additionally performed, this was done abdominally in 42 % of cases and laparoscopically in 53 %. Cervical cancer was treated by laparoscopic radical hysterectomy (HE) in 44 % of cases and by radical HE using a vaginal approach in 14 %. 4 % of hospitals reported the use of other endoscopic methods (e.g. DaVinci). While the majority of hospitals (43.3 %) treated more than 75 % of EC patients using laparoscopy, in many clinics (38.3 %) less than 25 % of CC patients were treated using endoscopy. Discussion: Laparoscopy is used more often in EC surgery as compared to surgery for CC. However, there are still major differences between hospitals with regard to case numbers, the number of uterine cancers treated using endoscopic surgery, and the type of endoscopic surgery.