IntroductionThe clinical presentation of endometriosis is extremely varied. Because endometriosis symptoms may overlap with symptoms caused by gastroenterological disorders, this can lead to misdiagnosis and a considerable delay in arriving at the correct diagnosis. The aim was to evaluate the type and duration of endometriosis-related symptoms and to identify predictors for patterns of involvement depending on symptoms. GebFra Science |Originalarbeit 307 Nicolaus K et al. Zyklusabhängige Diarrhö und... Geburtsh Frauenheilk 2020; 80: 307–315 Su pp le m en ta ry M at er ia l – de ut sc hs pr ac hi ge Zu sa tz in fo rm at io n! Zi ti er ba r is t au ss ch lie ß lic h de r en gl is ch sp ra ch ig e A rt ik el . Published online: 2020-03-04

Purpose This study was undertaken to evaluate the prevalence of endometriosis in infertile women of couples with non-male factor infertility. Methods A retrospective validation analysis was carried out of consecutive women of infertile couples with non-male factor infertility who received combined diagnostic hysteroscopy and laparoscopy, in the period from January 2017 to August 2019 in the Department for Gynecology and Reproductive Medicine (n = 300). Type, stage and site of endometriosis were assessed and matched with the occurrence of tubal stenosis. Binary regression analysis was used to estimate the prevalence of endometriosis. Results Endometriosis was diagnosed in 67% (n = 201). Primary infertility (OR 1.76; p = 0.036), dysmenorrhea (OR 2.47; p = 0.002), and a shorter cycle length (OR 0.972; p = 0.036) were independent risk factors for detection of endometriosis in diagnostic hystero-laparoscopy. The most frequent endometriosis sites were pelvic side wall (53.2%) and uterosacral ligaments (41.8%). Patients with endometriosis showed less often a tubal occlusion (34.32% vs. 41.4%; p = 0.205) and presented a lower rate of bilateral obstruction (9.5% vs. 18.8.%, p = 0.024). Women with endometriosis of a Fallopian tube showed a higher rate of tubal occlusion on the same side (right side p = 0.002; left side p = 0.001). Patients with rASRM score III showed the highest rate of tubal obstruction. Conclusions The prevalence of endometriosis in infertile women was higher than expected. The indication for operative infertility diagnostics by minimal invasive techniques should be made much more generous as well as the complete clarification of the causes of female infertility.

PURPOSE:We aimed to assess post-operative complications based on the Clavien-Dindo classification system following routine laparoscopic treatment of all stages of endometriosis.METHODS:A retrospective cohort study was carried out to identify women who underwent laparoscopic complete resection of newly diagnosed endometriosis between 2013 and 2016. 401 patients were identified using hospital database search software, and electronic files were reviewed. The stages of endometriosis had been classified according to the revised score of the American Society of Reproductive Medicine (rASRM) and the Enzian classification in cases of deep infiltrating endometriosis. Post-operative complications were recorded based on the Clavien-Dindo classification. Multivariate regression analysis was used to investigate the impact of the stages of endometriosis and surgical steps on complications.RESULTS:Grade III complications requiring surgical, endoscopic, or radiological intervention occurred in only 1.7% of patients and were significantly associated with rASRM stage IV (OR 1.8). Grade II complications (blood transfusion, total parenteral nutrition) occurred in 18.7% of patients. rASRM stage IV (OR 2.0), hysterectomy (OR 3.2), conversion to laparotomy (OR 11.1), and bowel resection (OR 27.6) were significantly associated with increased risk of grade II complications. rASRM stages I-III did not show an effect on post-operative complications or hospital stay.CONCLUSIONS:Clavien-Dindo complication grading was readily applicable to laparoscopic removal of endometriosis of all stages. Higher Clavien-Dindo grades correctly reflected clinically relevant complications and were associated with deep infiltrating endometriosis, stage IV endometriosis, bowel surgery, or hysterectomy. Clavien-Dindo classification can be recommended for evaluation of laparoscopic endometriosis surgery outcome.

Introduction The clinical presentation of endometriosis is extremely varied. Because endometriosis symptoms may overlap with symptoms caused by gastroenterological disorders, this can lead to misdiagnosis and a considerable delay in arriving at the correct diagnosis. The aim was to evaluate the type and duration of endometriosis-related symptoms and to identify predictors for patterns of involvement depending on symptoms. Material and Method The data of 266 consecutive patients who were operated on in the Endometriosis Center between 1/2016 and 12/2017 after receiving a histologically verified diagnosis of endometriosis were recorded. In addition to recording the clinical parameters, a questionnaire was distributed to the patients, who were asked about their medical history. Infertile patients were grouped together as Group 1 and compared to non-infertile patients (Group 2). Results The response rate for returned questionnaires was 79.47% (182/229). 41.8% of patients reported that they were infertile and 91.8% reported pelvic pain. In more than 1/3 of cases in both groups, more than 10 years passed between the initial symptoms and the final diagnosis (39.4 vs. 37.5%). On average, patients consulted 2.72 (+/- 1.58) resp. 3.08 (+/- 1.72) doctors before they presented to a hospital or were referred for laparoscopic diagnostic workup (p = 0.162). Cycle-related diarrhea (odds ratio 2.707; 95% CI: 1.063-6.895, p = 0.037) and dysmenorrhea (odds ratio 2.278; 95% CI: 1.193-4.348, p = 0.013) were associated with involvement of the pelvic peritoneum, cycle-related dyschezia was associated with rectal involvement by a factor of 4.6 in binary regression analysis (odds ratio 4.659; 95% CI: 1.132-19.186; p = 0.033). Conclusion Cycle-related diarrhea and dysmenorrhea increase the risk probability of peritoneal endometriosis. Dyschezia increases the risk probability of rectal endometriosis.

Purpose The lack of early detection assays and the occurrence of unspecific symptoms are causative for the late diagnosis of EOC. Aberrant DNA methylation of cell-free DNA (cfDNA) in blood may be a potential biomarker for EOC.

To determine risk factors for unexpected coexistent endometriosis in laparoscopic myomectomy for symptomatic uterine leiomyomas.

Das Ovarialkarzinom (OvCa) wird aufgrund von unspezifischer Symptomatik sowie fehlender Früherkennung in > 60% der Fälle im Spätstadium diagnostiziert. Dennoch kann die Bildgebung Raumforderungen im Bauchraum nicht immer differenzieren, wodurch es zu intraoperativen OvCa-Diagnosen kommt. Präoperative Biomarker könnten zu einer Optimierung der Therapieplanung bei unklaren Raumforderungen führen.

Treatment of epithelial ovarian cancer consists of surgery plus platinum-taxane based chemotherapy. Neither prognostic nor predictive serum or tissue markers except BRCA1/2 mutations are available thus precluding individualized treatment. Aim of this study is the identification and validation of DNA-methylation markers with prognostic value. Genome-wide array analyses were used to determine methylation patterns in groups of serous EOC with different outcome (PFS < vs. > 3 years, each n = 6) but comparable clinical parameters. Two hundred and twenty differentially methylated regions in tumor tissue of patients with short vs. long PFS (106 hypo- and 114 hypermethylated regions) were identified. Thirty-five of 37 selected CpG islands were validated by MSP using the same samples as for microarray analyses. Six of these regions were analyzed by targeted next-generation bisulfite-sequencing confirming array and MSP results. Validation experiments with an enlarged patient group of Type II EOC samples (PFS <3 years n = 30; >3 years n = 18) revealed the CpG island of RUNX3 as significantly more often methylated in patients with short PFS (10/30 vs. 0/18; p < 0.01). Marker combinations with significantly different methylation frequencies in patient groups reached an increased sensitivity with equal specificity (RUNX3+CAMK2N1; sens 40%; spec 100%; p < 0.01). RUNX3/CAMK2N1 methylation-positive patients of the array-independent subset (n = 36) showed a significantly lower PFS (p < 0.01) but no other difference in clinical parameters compared to methylation-negative patients. Genome-wide methylation analyses reliably identified markers of potentially prognostic value. Hypermethylation of RUNX3/CAMK2N1 is associated with poor clinical outcome in Type II EOC, also after macroscopic complete resection.

To evaluate fertility, pregnancy and delivery outcomes after laparoscopic myomectomy (LM) during long-term follow-up.

Einführung: In Mitteleuropa beträgt die Inzidenz 12 Fälle pro 100.000 Einwohner/Jahr, bis zu 10% der Melanome treten in erblich belasteten Familien auf. Haupt-Risikofaktor ist die UV-Belastung, toxische oder endokrine Einflüsse wie Kontrazeptiva oder Gravidität werden kontrovers diskutiert (S3 LL 2012).

Einführung: In Mitteleuropa beträgt die Inzidenz für ein Melanom 12 Fälle pro 100.000 Einwohner/Jahr, bis zu 10% der Melanome tretenden erblich belasteten Familien auf. Haupt-Risikofaktor ist die UV-Belastung, toxische oder endokrine Einflüsse wie Kontrazeptiva oder Gravidität werden kontrovers diskutiert (S3 LL 2012).

OBJECTIVE:To evaluate the effectiveness of intraoperatively applied local ropivacaine added to standard analgesic therapy in reducing postoperative pain intensity and opioid requirement under routine hospital conditions. STUDY DESIGN:In this prospective controlled cohort study, 303 consecutive patients receiving a gynaecological laparoscopic intervention at the Jena University Hospital were included. The study cohort (n=168) received, in addition to standard pain management, a port-site (PS) infiltration with ropivacaine prior to incision and intraperitoneal (IP) instillation at the end of surgery. On the first postoperative day patients answered a validated questionnaire, and requirement of rescue analgesics was assessed. RESULTS:Pain intensity was assessed on an 11-point numeric rating scale (NRS) from 0=no pain to 10=most severe pain. Reported pain intensity for movement-related pain was significantly lower (p=.001) in the study group compared with the control group (4.4 (SD 2.4) vs. 5.3 (SD 2.2) respectively). Minimal pain intensity after operation was also significantly lower in the study cohort (2.6 (SD 1.7) vs. 2.1 (SD 1.8), (p=.007)). Significantly fewer patients required rescue opioids for analgesia in the ropivacaine cohort (p=.001). The requested dose of rescue opioid (piritramide) in this cohort was also lower (p=.035) with 6.5mg (SD 4.9) vs. 8.7mg (SD 6.6), and demanded later (p=.001) with 4.3h after surgery vs. 3.1h. Patients in the study cohort experienced less nausea (p=.046). Higher satisfaction scores with pain management were reported in the ropivacaine group 12.7 (SD 2.5) vs. 11.6 (SD 2.8) (p<.001) (16-point NRS with 0=not at all, 15=completely satisfied). CONCLUSION:Addition of pre-emptive port-site plus intraperitoneal ropivacaine to standard postoperative analgesic therapy reduced postoperative pain intensity and opioid consumption in gynaecological laparoscopy.

Hysterectomy for benign conditions can be combined with bilateral salpingectomy to prevent re-intervention for malignant or benign fallopian tube pathologies. The objective of this study was to evaluate the benefit of prophylactic bilateral salpingectomy (PBS) in standard hysterectomy in premenopausal women.

Einleitung: Autoantikörper gegen p53 (p53-AAK) treten bei 20 – 30% der Patientinnen mit serösem Ovarialkarzinom auf, obwohl > 90% dieser Tumore p53-Mutationen aufweisen. Ein besseres Verständnis der Ursachen dieser Diskrepanz ist notwendig, da eine Anwendung von p53-AAK als Verlaufsmarker möglicherweise von klinischer Bedeutung ist.

Fragestellung: Das Ausmaß der operativen Tumorentfernung ist der wichtigste Prognosefaktor bei der Behandlung fortgeschrittener Ovarialkarzinome. Der Serummarker CA125 weist ein Detektionslimit von einem Tumorvolumen > 8 cm3 auf. Somit kann die Präsenz von minimal-residualen Tumorresten nicht sicher bestimmt werden. Ebenso ist eine frühzeitige Diagnose von Rezidiven erschwert. Ebenso kann die präoperative Bestimmung von CA125 keine Auskunft über das Tumorbefallsmusters geben.

Einleitung: Die adjuvante Standard-Chemotherapie bei Ovarialkarzinompatientinnen enthält Platin. Obwohl anfänglich 80% der Patientinnen ein klinisches Ansprechen zeigen, entwickeln die meisten von ihnen ein Pt-resistentes Rezidiv. Bei diesem Prozess sind, neben neu erworbenen genetischen Aberrationen auch epigenetische Veränderungen von Bedeutung. Ziel dieser Studie ist die Untersuchung von Genen, deren Promotor während der in-vitro Pt-Resistenz-Entwicklung im Zellkulturmodell hypermethyliert wird.