Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Cross-sectional study for derivation of a cut-off value for identification of an early versus delayed diagnosis of endometriosis based on analytical and descriptive research methods.

BACKGROUND: Endometriosis is a benign, hormone-dependent, chronic inflammatory gynecological disease accompanied by cyclic and acyclic pelvic pain and other complaints. The long lists of research recommendations in the AWMF guideline (Burghaus et al., Geburtshilfe Frauenheilkd 81:422-46, 2021) and ESHRE Endometriosis Guideline (ESHRE Endometriosis Guideline Development Group, Endometriosis: Guideline of European Society of Human Reproduction and Embryology, 2022) show that there is still a great need for research in all aspects of the disease. Diagnostic delay, defined as the mean time between symptom onset and confirmed diagnosis, is a particular problem associated with endometriosis. Some quantitative and qualitative studies have investigated possible reasons for this. A range of physician-related (Dixon et al., Br J Gen Pract 71:e668-e676, 2021; van der Zanden and Nap, Reprod Biomed Online 32:527-31, 2016) and patient-related factors (Sayer-Jones and Sherman, Health Psychol Behav Med 9:456-79, 2021) as well as stigmatization of the topic of menstruation by society have been identified (Kruckenberg, Frauenarzt 59:2-5, 2018; Seear, Soc Sci Med 69:1220-7, 2009). The consequences of the disease being diagnosed late (or too late) on the course of disease, the quality of life and the costs of the disease have already been documented in studies (Sims Int J Environ Res Public Health 18(15):8210, 2021; Surrey Adv Ther 37:1087-99, 2020). However, a systematically derived cut-off value that clearly distinguishes between short and long delay is still lacking. Therefore, the aim of our study was to derive a threshold value for the definition of a target corridor for endometriosis diagnosis based on descriptive and analytical methods. METHODS: Since our review of the rather sparse publications on diagnostic delay did not yield satisfactory results, we used descriptive statistics and location parameters to calculate a cut-off value for German population data from the EndoCost study. Statistical methods were used for correlation analysis of shortDD versus longDD (correlation analysis and logistic regression) and group membership (discriminant analysis). RESULTS: Five years was identified as the cut-off value that significantly differentiated between shortDD and longDD based on various disease-related variables. This suggests that endometriosis should be definitively diagnosed within less than five years to minimize the risk of an unfavorable course of the disease. CONCLUSION: Our findings confirmed that an early onset of endometriosis-related symptoms is the most important risk factor for a long diagnostic delay. Consequently, adolescent females should receive increased attention as an especially vulnerable group. Evidently, there is an urgent need to develop adequate concepts to improve the endometriosis education and care among this target group.

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.

Splenosis: an uncommon differential diagnosis in gynecology.

Splenosis consists of ectopic functioning splenic tissue that can be located anywhere within the abdomen or pelvis. It is a benign condition usually found incidentally and is usually asymptomatic. The need for therapy is controversial, and treatment is suggested only in symptomatic cases, primarily those related to pelvic or abdominal implants.

Laparoscopic extramucosal partial bladder resection in a patient with symptomatic deep-infiltrating endometriosis of the bladder.

Endometriosis is a complex disease, affecting the urinary tract, mainly the bladder, in 1% to 2% of cases. Thus far, partial cystectomy has been the treatment of choice for long-term relief of symptoms. Here, we describe the case of a 26-year-old patient with deep-infiltrating bladder endometriosis who was completely cured by laparoscopic extramucosal bladder resection. Diagnostic standards and factors affecting the rate of success for this additional option in endometriosis surgery are discussed.

Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions.

BACKGROUND: Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions. METHODS: We obtained biopsies from peritoneal endometriotic lesions (n = 60) and peritoneal sites distant from the endometriotic lesion (n = 60), as well as healthy peritoneum from patients without endometriosis (control tissue, n = 10). These controls were hysterectomy specimens from patients without endometriosis or adenomyosis. Histopathological examination of peritoneal specimens using antibodies against oxytocin receptor (OTR), vasopressin receptor (VPR), smooth muscle myosin heavy chain (SM-MHC), estrogen receptor (ER) or progesterone receptor (PR) was performed. To identify SMC and their level of differentiation, antibodies for smooth muscle actin desmin and caldesmon were used. RESULTS: SMC were detected in all endometriotic lesions. SMC were more abundant in unaffected peritoneum of women with endometriosis (38%) compared with women without endometriosis (6%; P < 0.0001). Depending on the level of differentiation, SMC stained for SM-MHC, OTR, VPR, ER and PR. OTR was only detected in fully differentiated SMC. CONCLUSIONS: Identification of OTR, VPR, ER and PR leads to the hypothesis that the EMaSMC might be functionally active and possibly involved in the generation of pain associated with endometriosis.

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

PURPOSE: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. METHODS: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients' individual HPV-integration sites (vcj-PCR on the basis of NGS). RESULTS: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6-34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8-27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7-20.7%) and predicted ten of fourteen recurrences at six months. CONCLUSIONS: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020).

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

Rare Ectopic Pregnancies - A Literature Review for the Period 2007 - 2019 on Locations Outside the Uterus and Fallopian Tubes.

The majority of ectopic pregnancies (EP) are tubal pregnancies, but other implantation sites outside the uterus and tubes are also found. These rare EP locations present a particular diagnostic and therapeutic challenge. We present an overview of potential very rare locations of ectopic pregnancies, their symptoms, diagnosis and treatment, based on a systematic analysis of case reports. A literature review of the databases PubMed, Livivo and Google Scholar for the period 2007 to 2019 was carried out. A total of 113 publications were included in our review. These studies describe EP implantations in the posterior cul-de-sac, on the uterine serosa and uterine ligaments, in the vicinity of almost all intraperitoneal organs, on the abdominal wall as well as in retroperitoneal sites. The most common presenting symptom was abdominal pain occurring in different locations. The diagnostic procedures included various imaging procedures and/or explorative surgery at different advanced stages of pregnancy. The most common and preferred option was laparotomy for surgical treatment. The placenta was successfully resected in the majority of cases. A rare EP location should be considered when making a differential diagnosis in patients of child-bearing age with abdominal pain.

Histological confirmation of endometriosis in a 9-year-old girl suffering from unexplained cyclic pelvic pain since her eighth year of life.

OBJECTIVE: Endometriosis is considered an estrogen-dependent disease of women in their reproductive age and characterized by the occurrence of stromal cells and endometrial-like glands outside the uterine cavity. PATIENT: A report of a 9-year-old premenarcheal girl who was transferred to the Endometriosis Research Center Berlin-Brandenburg Level III (Academic Teaching Hospital) because of cyclic pelvic pain since her 8th year of life. INTERVENTIONS: History, examination, abdominal ultrasound, laboratory tests, laparoscopic resection of visible lesions. Paraffin-embedded histology (HE staining) and immunohistochemistry. RESULTS: Endometriosis, defined as the presence of stromal tissue and epithelial glands, was confirmed both by HE staining and immunohistochemistry (CD10), respectively. CONCLUSIONS: Young pre- or perimenarcheal girls with chronic/cyclic pelvic pain can have endometriosis, and thus the possibility of endometriosis should be included in the differential diagnosis.

Clinical management and immunohistochemical analysis of umbilical endometriosis.

PURPOSE: To established a strategy for diagnostic and therapeutic management of umbilical endometriosis and to determine the biological character. METHODS: Clinical examination, vaginal and abdominal ultrasound, magnetic resonance imaging of the abdominal wall and laparoscopy were performed on a 42-year-old woman with umbilical endometriosis. Surgery with umbilical reconstruction was performed by a new plastic surgery technique. Immunohistochemical analyses (against Ki 67, estrogen/progestogen receptor, CD10, smooth muscle actin, desmin, caldesmon, von Willebrandt factor, cyclooxygensae-2 and VEGF) were done to characterize the umbilical endometriotic lesion. RESULTS: The extension of the endometriotic lesion necessitated total removal of the umbilicus. Umbilical reconstruction was performed by a new plastic surgery technique. The lesion did express CD10, estrogen and progestogen receptors, and did show a moderate proliferation rate. Furthermore, signs of metaplastic processes such as smooth muscle metaplasia and angiogenesis were detected. The endometriotic lesion was positive not only for smooth muscle actin, caldesmon and desmin, but also for COX-2 and VEGF. CONCLUSION: Based on a case report and a literature review, we discuss the diagnostic and therapeutic management of umbilical endometriosis at our endometriosis research center. Furthermore, our data suggest that the umbilical endometriotic lesion originated from reactivated multipotent cells.

Laparoscopic ovarian cystectomy without bipolar coagulation or sutures using a gelantine-thrombin matrix sealant (FloSeal): first support of a promising technique.

As a important part of endocrine surgery, laparoscopic surgery has become the gold standard for the treatment of benign symptomatic ovarian cysts refractory to medical treatment. In fact, the stripping technique seems to be the most common technique used for ovarian cyst surgery. After stripping the cystic wall, the subsequent bleeding of the ovarian stromal wound ground is usually controlled by bipolar coagulation or/and by suturing. Potentially, the surgery-induced ovarian tissue damage will be increased by heat and/or by sutures. In respect to intraovarian hemostasis, the use of gelantine-thrombin-matrix might protect from additional ovarian tissue damage, which is of great importance for the ovarian reproductive function in woman. For the first time, our data do support a promising laparoscopic technique demonstrating ovarian cystectomy without any bipolar coagulation and/or suturing of ovarian tissue using a gelantine-thrombin-matrix sealant (FloSeal) as a new tool to control post-cystectomy ovarian wound bleeding.