FEMaLe: The use of machine learning for early diagnosis of endometriosis based on patient self-reported data-Study protocol of a multicenter trial.

INTRODUCTION: Endometriosis is a chronic disease that affects up to 190 million women and those assigned female at birth and remains unresolved mainly in terms of etiology and optimal therapy. It is defined by the presence of endometrium-like tissue outside the uterine cavity and is commonly associated with chronic pelvic pain, infertility, and decreased quality of life. Despite the availability of various screening methods (e.g., biomarkers, genomic analysis, imaging techniques) intended to replace the need for invasive surgery, the time to diagnosis remains in the range of 4 to 11 years. AIMS: This study aims to create a large prospective data bank using the Lucy mobile health application (Lucy app) and analyze patient profiles and structured clinical data. In addition, we will investigate the association of removed or restricted dietary components with quality of life, pain, and central pain sensitization. METHODS: A baseline and a longitudinal questionnaire in the Lucy app collects real-world, self-reported information on symptoms of endometriosis, socio-demographics, mental and physical health, economic factors, nutritional, and other lifestyle factors. 5,000 women with confirmed endometriosis and 5,000 women without diagnosed endometriosis in a control group will be enrolled and followed up for one year. With this information, any connections between recorded symptoms and endometriosis will be analyzed using machine learning. CONCLUSIONS: We aim to develop a phenotypic description of women with endometriosis by linking the collected data with existing registry-based information on endometriosis diagnosis, healthcare utilization, and big data approach. This may help to achieve earlier detection of endometriosis with pelvic pain and significantly reduce the current diagnostic delay. Additionally, we may identify dietary components that worsen the quality of life and pain in women with endometriosis, upon which we can create real-world data-based nutritional recommendations.

Diagnostic accuracy of the IDEA protocol for non invasive diagnosis of rectosigmoid DE - a prospective cohort study.

OBJECTIVES: To test the accuracy of TVS applying the IDEA approach for suspected rectosigmoid DE and to determine the frequency of other pelvic diseases mimicking DE in patients undergoing surgery. MATERIALS UND METHODS: Prospective single center observational study including consecutive women undergoing TVS for clinically suspected rectosigmoid DE followed by conservative or surgical therapy. TVS findings were compared with those obtained by laparoscopy and confirmed histologically. RESULTS: Of the 671 included patients, 128 women opted for medical therapy, and 6 patients decided for surgery but did not give consent to participate in the study. 537 women were enrolled in the final analysis. 279 (52 %) exhibited surgically confirmed rectosigmoid DE. The sensitivity and specificity, positive and negative predictive value (PPV, NPV), positive and negative likelihood ratio (LR+/-) and accuracy of TVS for diagnosing DE in the rectosigmoid were 93.5 %, 94.6 %, 94.9 %, 93.1 %, 17.24, 0.07, 94.04 %. 12 women who were clinically suspected for DE and mimicked sonographic signs fulfilling the IDEA criteria did exhibit other pathologies. Diagnoses were as follows: vaginal Gartner duct cyst (3/291;1.0 %), anorectal abscess (3/291; 1.0 %), rectal cancer (2/291;0.7 %), hydrosalpinx (2/291;0.7 %), metastatic endometrial cancer (1/291;0.35 %) and Crohn's disease (1/291;0.35 %). CONCLUSION: TVS for diagnosing colorectal DE applying the IDEA criteria is highly accurate for presurgical diagnosis. However, additional pelvic pathologies are encountered in 4-5 % of women attending for suspected rectosigmoid DE. These need to be taken into account when investigating patients for suspected DE.

Pain, gastrointestinal function and fertility outcomes of modified nerve-vessel sparing segmental and full thickness discoid resection for deep colorectal endometriosis - A prospective cohort study.

INTRODUCTION: There is an ongoing debate on surgical techniques for colorectal deep endometriosis (DE) and their effects on gastrointestinal (GI) function. The aim of this study was to prospectively investigate the differences in pre- and postsurgical GI function, health profiles and pain symptoms in women undergoing colorectal surgery for symptomatic DE either with a modified segmental resection technique, so-called nerve-vessel sparing segmental resection (NVSSR), or full thickness discoid resection (FTDR). Complication rates and fertility outcomes were also evaluated. MATERIAL AND METHODS: A total of 162 consecutive patients, 125 (77.2%) of whom underwent NVSSR and 37 (22.8%) FTDR, were evaluated regarding complication rates. Furthermore a lower anterior resection syndrome (LARS) scores, gastrointestinal function-related quality of life index (GIQLI), pain symptoms, endometriosis health profile (EHP-30) parameters were analyzed pre- and post-surgery in a final cohort of 121 patients. RESULTS: There was no difference between postsurgical prevalence of LARS in either surgery group (14/98, 14.1% NVSSR; 2/23, 8.6% FTDR), with significantly decreased LARS scores and increased GIQLI values before vs after surgery in both groups (P < 0.001). The overall grade III complication rate was 7/162 (4.3%) with no significant differences between NVSSR and FTDR groups. Overall, EHP-30 and pain scores significantly decreased after a median follow-up of 41 (± 17.6) months (EHP-30 51.1, SD 21.5 vs 12.7, SD 19.3, P < 0.001; dysmenorrhea, dyspareunia, dyschezia all P < 0.001 both cohorts, respectively). The overall life birth rate and postsurgical pregnancy in infertile patients undergoing NVSSR and FTDR was respectively 58.1% in 25/43 patients; 55.6% in 5/9 patients; 56.0% in 14/25 patients and 100% in 5/5 patients. CONCLUSIONS: NVSSR and FTDR for symptomatic colorectal DE confer a significant amelioration of GI function reflected by decreased LARS symptoms and increased GIQLI scores with no differences in postsurgical function in between the two techniques. Both techniques confer similar complication rates and effects on pain reduction and health profiles.

Laparoscopic natural orifice specimen extraction colectomy versus conventional laparoscopic colorectal resection in patients with rectal endometriosis: a randomized, controlled trial.

BACKGROUND: The conventional laparoscopic approach for the surgical management of deep endometriosis (DE) infiltrating the rectum appears to ensure improved digestive functional outcomes. The natural orifice specimen extraction (NOSE) technique for the treatment of colorectal DE can significantly accelerate postoperative recovery; however, data on gastrointestinal function following conventional laparoscopic segmental bowel resection (CLR) compared with NOSE colectomy (NC) for DE are sparse. MATERIALS AND METHODS: Between 30 September 2019 and 31 December 2020, a randomized, open-label, two-arm, parallel-group controlled trial with women aged 18-45 years was conducted at University Hospital.Ninety-nine patients were randomized to CLR or NC, with DE infiltrating at least the muscular layer, at least 50% of the circumference of the bowel, up to 15 cm from the anal verge, exhibiting pain and bowel symptoms and/or infertility. The primary endpoint was bowel function, represented by low anterior resection syndrome (LARS). Secondary parameters included the Endometriosis Health Profile 30 (EHP30), Gastrointestinal Quality of Life Index (GIQLI), Visual Analog Scale (VAS) scores preoperatively and at set times (1 and 6 months, 1 year) following surgery. RESULTS: No significant differences were observed in the postoperative LARS scores, VAS, EHP30, and GIQLI between the NC and CLR groups. LARS scores did not reveal significant differences 12 months postoperatively compared to the preoperative values in both groups (CLR group P =0.93 versus NC group, P =0.87). GIQLI scores were significantly improved 12 months after the operation compared with baseline values in the CLR group ( P =0.002) and NC group ( P =0.001). Pain symptoms and quality of life scores significantly improved 12 months postoperatively in both groups. CONCLUSIONS: NC is a feasible surgical approach for treating patients with rectal DE. Our study did not show a statistically significant difference between CLR and NC techniques in mid-term digestive and pain outcomes.

[Laparoscopic treatment of deeply infiltrating colorectal endometriosis - ten years of single center experience]. / Mélyen infiltráló colorectalis endometriosis laparoszkópos kezelésével szerzett tízéves tapasztalataink.

INTRODUCTION: Deep infiltrating endometriosis penetrates the peritoneal surface beneath 5 mm. The bowel is affected in 3-37% of the cases. OBJECTIVE: The aim of the authors was to analyze the results of the surgical procedures performed for bowel endometriosis. METHOD: Between 2009 and 2020, 675 patients underwent bowel endometriosis surgery at the Department of Obstetrics and Gyanecology of Semmelweis University. Four surgical approaches were performed: shaving, discoid, segmental and NOSE resection. RESULTS: 182 shaving, 93 discoid, 130 NOSE and 270 segmental bowel resections were performed. Ultra-deep anastomosis was performed in 40 cases. The median operative time was 85 minutes, the shortest intervention lasted 25 minutes, the longest 585 minutes. The average operating time was 260 (± 161.3) minutes for the first, and 114 (± 47.0) minutes for the last ten operations. The average blood loss was 10 (± 20.3) mL. The average hospital stay was 6 (± 2.3) days. Serious surgical complication (Clavien-Dindo III or more severe) developed in 18 cases. In a total of 17 cases sigmoideo- or ileostomy were used. Conversion to laparotomy was necessary in 6 cases. DISCUSSION: The same team performed all the interventions, which can show the effectiveness of the surgical techniques instead of the technique of individual surgeons. The complication rate is low in the case of an experienced surgical team, and the operating time decreases significantly in proportion to the number of operations performed. CONCLUSION: Bowel endometriosis can be treated safely and effectively with both conservative (shaving or discoid) and radical (segmental or NOSE resection) approach. Orv Hetil. 2023; 164(9): 348-354.

Comparison of #Enzian classification and revised American Society for Reproductive Medicine stages for the description of disease extent in women with deep endometriosis.

STUDY QUESTION: How is endometriosis extent described by the #Enzian classification compared to the revised American Society for Reproductive Medicine (rASRM) stages in women undergoing radical surgery for deep endometriosis (DE)? SUMMARY ANSWER: The prevalence and severity grade of endometriotic lesions and adhesions as well as the total number of #Enzian compartments affected by DE increase on average with increasing rASRM stage; however, DE lesions are also present in rASRM stages 1 and 2, leading to an underestimation of disease severity when using the rASRM classification. WHAT IS KNOWN ALREADY: Endometriotic lesions can be accurately described regarding their localization and severity by sonography as well as during surgery using the recently updated #Enzian classification for endometriosis. STUDY DESIGN, SIZE, DURATION: This was a prospective multicenter study including a total of 735 women between January 2020 and May 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Disease extent in women undergoing radical surgery for DE at tertiary referral centers for endometriosis was intraoperatively described using the #Enzian and the rASRM classification. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 735 women were included in the study. Out of 31 women with rASRM stage 1, which is defined as only minimal disease, 65% (i.e. 20 women) exhibited DE in #Enzian compartment B (uterosacral ligaments/parametria), 45% (14 women) exhibited DE in #Enzian compartment A (vagina/rectovaginal septum) and 26% (8 women) exhibited DE in #Enzian compartment C (rectum). On average, there was a progressive increase from rASRM stages 1-4 in the prevalence and severity grade of DE lesions (i.e. lesions in #Enzian compartments A, B, C, FB (urinary bladder), FU (ureters), FI (other intestinal locations), FO (other extragenital locations)), as well as of endometriotic lesions and adhesions in #Enzian compartments P (peritoneum), O (ovaries) and T (tubo-ovarian unit). In addition, the total number of #Enzian compartments affected by DE lesions on average progressively increased from rASRM stages 1-4, with a maximum of six affected compartments in rASRM stage 4 patients. LIMITATIONS, REASONS FOR CAUTION: Interobserver variability may represent a possible limitation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The #Enzian classification includes the evaluation of DE in addition to the assessment of endometriotic lesions and adhesions of the ovaries and tubes and may therefore provide a comprehensive description of disease localization and extent in women with DE. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. All authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Different segmental resection techniques and postoperative complications in patients with colorectal endometriosis: A systematic review.

INTRODUCTION: The aim of this study was to analyze the available literature by conducting a systematic review to assess the possible effects of nerve-sparing segmental resection and conventional bowel resection on postoperative complications for the treatment of colorectal endometriosis. MATERIAL AND METHODS: Pubmed, Clinical Trials.gov, Cochrane Library, and Web of Science were comprehensively searched from 1997 to 2021 in order to perform a systematic review. Studies including patients undergoing segmental resection for colorectal endometriosis including adequate follow-up, data on postoperative complications and postoperative sequelae were enrolled in this review. Selected articles were evaluated and divided in two groups: Nerve-sparing resection (NSR), and conventional segmental resection not otherwise specified (SRNOS). Within the NSRs, studies mentioning preservation of the rectal artery supply (artery and nerve-sparing SR - ANSR) and not reporting preservation of the artery supply (NSR not otherwise specified - NSRNOS) were further analyzed. PROSPERO ID: CRD42021250974. RESULTS: A total of 7549 patients from 63 studies were included in the data analysis. Forty-three of these publications did not mention the preservation or the removal of the hypogastric nerve plexus, or main rectal artery supply and were summarized as SRNOS. The remaining 22 studies were listed under the NSR group. The mean size of the resected deep endometriosis lesions and patients' body mass index were comparable between SRNOS and NSR. A mean of 3.6% (0-16.6) and 2.3% (0-10.5%) of rectovaginal fistula development was reported in patients who underwent SRNOS and NSR, respectively. Anastomotic leakage rates varied from 0% to 8.6% (mean 1.7 ± 2%) in SRNOS compared with 0% to 8% (mean 1.7 ± 2%) in patients undergoing NSR. Urinary retention (4.5% and 4.9%) and long-term bladder catheterization (4.9% and 5.6%) were frequently reported in SRNOS and NSR. There was insufficient information about pain or the recurrence rates for women undergoing SRNOS and NSR. CONCLUSIONS: Current data describe the outcomes of different segmental resection techniques. However, the data are inhomogeneous and not sufficient to reach a conclusion regarding a possible advantage of one technique over the other.

ESHRE guideline: endometriosis.

STUDY QUESTION: How should endometriosis be diagnosed and managed based on the best available evidence from published literature? SUMMARY ANSWER: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. WHAT IS KNOWN ALREADY: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. LIMITATIONS REASONS FOR CAUTION: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).

Low anterior resection syndrome following different surgical approaches for low rectal endometriosis: A retrospective multicenter study.

INTRODUCTION: There is increasing evidence that intermediate and long-term bowel dysfunction may occur as a consequence of radical surgery for rectal deep endometriosis (DE). Typical symptoms include constipation, feeling of incomplete evacuation, clustering of stools, and urgency. This is described in the colorectal surgical literature as low anterior resection syndrome (LARS). Within this, several studies suggested that differences regarding functional outcomes could be favorable to more conservative surgical approaches, that is, excision of endometriotic tissue with preservation of the luminal structure of the rectal wall when compared with classical segmental resection techniques for DE, especially when performed for low DE. MATERIAL AND METHODS: A total of 211 patients undergoing rectal surgery for low DE (≤7 cm from the anal verge) in three different tertiary referral centers between October 2009 and December 2018 were retrospectively reviewed regarding major complications and LARS. From the 211 eligible patients, six women were excluded because of loss to follow-up. Finally, a total number of 205 patients were enrolled for the statistical analysis; 139 with nerve- and vessel-sparing segmental resection (NVSSR) and 66 operated for laparoscopic-transanal disk excision (LTADE) were included. Gastrointestinal functional outcomes of the two procedures were compared using the validated LARS questionnaire. The median follow-up time was 46 ± 11 months. As a secondary outcome, the surgical sequelae were examined. RESULTS: We found no statistically significant difference between the incidence of LARS (31.7% and 37.9%, respectively) among patients operated by LTADE when compared with NVSSR (P = .4). The occurrence of LARS was positively associated with the use of protective ileostomy or colostomy (P = .02). A higher rate of severe complications was observed in women undergoing LTADE (19.7%) when compared with patients with NVSSR (9.0%, P = .029). CONCLUSIONS: LARS is not more frequent after NVSSR when compared with a more conservative approach such as LTADE in patients undergoing rectal surgery for low DE. To confirm our findings prospective studies are required.

Gamma-Synuclein Levels Are Elevated in Peritoneal Fluid of Patients with Endometriosis.

BACKGROUND The role of gamma-synuclein (SNCG) has been widely examined in malignant conditions due to its possible role in disease progression, but very little information is available on its theoretical function on endometriosis formation. MATERIAL AND METHODS Between January 2016 and December 2016, we collected peritoneal fluid and plasma samples from 45 consecutive female patients, of which 15 were without endometriosis, 15 had minimal to mild endometriosis, and 15 had moderate to severe endometriosis. The statistical power was 0.98. We evaluated SNCG levels in the peritoneal fluid and plasma of patients diagnosed with endometriosis, and we compared them with the levels obtained from disease-free control subjects by using enzyme-linked immunosorbent assay. RESULTS SNCG levels were statistically significantly (1.2-fold) higher in the peritoneal fluid of patients with endometriosis compared to controls (p=0.04). We did not find a significant difference between SNCG levels in the plasma of our endometriosis patients and the control group (p=0.086). However, despite previous data showing very limited expression of SNCG in healthy tissues, we found SNCG in the peritoneal fluid of all of the patients in our healthy control group. CONCLUSIONS Levels of SNCG were statistically significantly higher in the peritoneal fluid of patients with endometriosis compared to disease-free controls, which may indicate its possible role the formation and progression of the disease. Moreover, its biological function should be further investigated due to the conflicting results concerning its expression in healthy tissues.

[The effect of surgical treatment of bowel endometriosis on fertility]. / A bélendometriosis miatt végzett mutétek hatása a fertilitásra.

Introduction: Bowel endometriosis is when endometrial-like tissue penetrates the bowel serosa, or it reaches the subserous neurovascular plexus. The effect of surgery for colorectal endometriosis on infertility and pregnancy is not fully proven. Aim: The aim of the present study was to analyse the pregnancy outcome and mode of delivery of patients who underwent 'nerve sparing' anterior resection of the colon. Method: Between 2009 and 2017, we operated 121 patients with bowel endometriosis, and built up a prospective database where we assessed their wish of pregnancy, the way of the conception, pathologies during pregnancy and mode of delivery. Statistical analysis: The relationship between endometriosis and pregnancy pathologies was tested by a χ2 probe and Fisher's exact test, additionally the odds ratio (OR) and 95% confidence interval (CI) were determined. For p<0.05, the result was considered significant. Results: Out of 121 bowel endometriosis patients, 48 (39.6%) women got pregnant, 37 (30.5%) of them with in vitro fertilisation. The control group was built from patients who underwent in vitro fertilisation because of andrological factors. We found that women with endometriosis have a significantly higher risk for praeeclampsia (p = 0.023) and placenta praevia (p = 0.045) during pregnancy. Conclusions: Our study is a unique description of pregnancy outcome and mode of delivery after surgery for bowel endometriosis, which, despite the small number of cases, has yielded similar results to the previous multicentric studies. Orv Hetil. 2019; 160(41): 1633-1638.

Natural Orifice Specimen Extraction during Laparoscopic Bowel Resection for Colorectal Endometriosis: Technique and Outcome.

STUDY OBJECTIVE: To present a detailed description of a modified natural orifice specimen extraction (NOSE) colectomy technique. We also report the postoperative outcomes of our prospective case series when compared with conventional laparoscopic bowel resection in a relatively large series of patients. DESIGN: Canadian Task Force classification II-1. SETTING: A university tertiary referral center. PATIENTS: The last 90 consecutive patients in our care with deep infiltrating endometriosis of the bowel are presented in this study. Patients were diagnosed at the 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary. INTERVENTIONS: We performed laparoscopic bowel resection using the transrectal NOSE technique and compared the results of the new operative method (n = 30) with traditional laparoscopic bowel resection (n = 60). MEASUREMENTS AND MAIN RESULTS: The median duration of surgery was 121 minutes in the control group and 96 minutes in the NOSE group (p = .005). According to the Clavien-Dindo classification, we observed a severe, grade IIIb or higher, overall complication rate of 3.3% among all 90 patients. In the control group, anastomosis insufficiency occurred in 3.3% of patients (2/60 cases), and in 1 patient with anastomotic leakage a rectovaginal fistula was observed (1.7%). There was no significant difference in the rates of severe postoperative complications (p = .55). The length of hospital stay in the control group was a median of 7 days (range, 5-13 days), whereas in the NOSE group it was 6 days (range, 3-11 days) (p < .001). CONCLUSION: According to our findings, the use of NOSE colectomy offers a shorter recovery time and can eventually lead to a shorter surgery duration compared with traditional laparoscopic bowel resection.

[Prospective study to determine the diagnostic sensitivity of sigmoidoscopy in bowel endometriosis]. / Prospektív vizsgálat a sigmoideoscopia diagnosztikai érzékenységének meghatározására vastagbelet infiltráló endometriosisban.

INTRODUCTION AND AIM: In the treatment of colorectal endometriosis a multidisciplinary laparoscopic resection is suggested, for this reason the correct selection of bowel infiltration is essential before surgery. PATIENTS AND METHOD: Between 2009 and 2015, 383 sigmoidoscopies were performed in patients with endometriosis. Where mucosal invasion was absent secondary signs (wall rigidity, impression, kinking, pain during the examination, suffusion) were analysed. In endoscopically confirmed cases multidisciplinary surgery was performed, the remaining patients were operated by a gynecologic team only. RESULTS: Endometriosis was endoscopically confirmed in 224 patients (58.49%), 108 of them underwent multidisciplinary operation, the negative 135 cases received gynaecological surgery. Bowel endometriosis was confirmed in 103 out of 108 cases intraoperatively, while in 8 cases of the sigmoidoscopically negative patients bowel infiltration was diagnosed intraoperatively by the gynaecological team. Complete sigmoidoscopy was performed in 43.47% of the cases. Intraluminal endometriosis was found in 4.91%, secondary signs as rigidity in 38.39%, impression in 45.54%, kinking in 57.14%, pain (in cases of examination without narcosis) in 26.06% and suffusion in 3.82% of the cases was found during sigmoidoscopy. Sigmoidoscopic examination has a 92.8% specificity and 96.2% sensitivity in cases of bowel endometriosis. CONCLUSION: Sigmoidoscopy performed by an experienced gastroenterologist is a highly sensitive examination for the diagnosis of bowel endometriosis. Orv. Hetil., 2017, 158(7), 264-269.

[First attempts in the introduction of cryopreservation of ovarian tissues]. / Kezdeti tapasztalataink a petefészekszövet-fagyasztás bevezetésével.

INTRODUCTION: The oncological treatment may damage ovarian function. To prevent this, it is possible to cryopreserve the ovarian tissue, and to keep the samples for long-term storage. The frozen-thawed tissue could be retransplanted after chemo- or radiotherapy. AIM: The aim of our study was to examine the effect of cryopreservation on the viability of ovarian tissue. METHOD: We analyzed the survival of frozen-thawed donated ovarian tissues. The quality of the follicles and hormone production in fresh and frozen-thawed samples were compared. RESULTS: Histological analysis showed that the number of viable follicles was reduced by 23% in the frozen-thawed samples. However, viable follicles still presented in post thawing ovarian tissues. Maximal estradiol production in frozen-thawed tissues was 908 pg/ml and hormone production was similar to the control tissues. The maximal progesterone production was 1.95 ng/ml post thawing, but these values were lower than the progesterone production of fresh tissues. CONCLUSIONS: The method of ovarian cryopreservation used in our laboratory was able preserve the viability of follicles in frozen-thawed ovarian tissues. Orv. Hetil., 2016, 157(49), 1947-1954.

[Bowel endometriosis: new challenge for gastroenterology and surgery? Three cases of endometriosis caused large bowel ileus and review of the literature]. / Belet infiltráló endometriosis: a gasztroenterológia és a sebészet új kihívása? Vastagbélileust okozó endometriosis három esete és irodalmi áttekintés.

INTRODUCTION: A number of the patients suffer from endometriosis increased in the past decades and the cases have became more serious. The most critical complication of bowel endometriosis is the large bowel obstruction. Up to recently, 16 similar case reports of large bowel endomteriosis causing obstruction, with detailed medical history have been published in the literature in English language. PATIENTS: Since 2007 535 female have been treated in the 1st Gynaecological Department with endometriosis, out of them three patients from emergency surgery in the history because of large bowel obstruction. RESULTS: Symptoms suggesting endometriosis or previous intervention due to endometriosis were detected in 59% (13/21) of the cases. Preoperative ultrasound, computertomography, magnetic resonance imaging did not give correct diagnosis. Colonoscopy was carried out before the primary operation in 61% (13/21) and after the surgery in 24% (5/21) of the cases, but none of them confirmed endometriosis. Although all the patients developed obstruction, only in 5% (1/19) of the patients was the mucosa infiltrated by the endometriosis. CONCLUSIONS: In a young female patient, intestinal obstruction can be caused by bowel endometriosis. Identification of colonoscopic signs (rigidity, impression, kinking) of endometriosis may help to avoid unnecessary extension of intestinal resection. Gynaecologists should take part in the operations. Orv. Hetil., 2016, 157(49), 1960-1966.

[Technical questions of the transrectal specimen extraction]. / A transrectalis specimeneltávolítás sebésztechnikai kérdései.

INTRODUCTION: During laparoscopic partial colectomy the specimen can be extracted transrectally. This technique decreases the invasiveness of the surgery, because the abdominal wall incision is avoided. Premises of a new surgical technique are precise technical description as well as a favourable balance of advantages and disadvantages. In this paper the authors review the technique they apply and analyse their first results. PATIENTS AND METHOD: 45 laparoscopic bowel resections were performed by a multidisciplinary team between 16th April 2014 and 1st November 2015. Indication of surgery was endometriosis, and the specimen was extracted transrectally in 11 patients. Having ligated both bowel ends proximal and distal to the section infiltrated with endometriosis, and the proximal bowel secured with a laparoscopic bulldog. Then the bowel was resected and the specimen was extracted in a camera bag transrectally. A purse-string suture was placed into the proximal bowel end, and the anvil of the circular stapler--which was introduced transrectally--was inserted into the bowel. After closing the rectal stump, the anastomosis was performed with a circular stapler. We used this technique when the upper third of the rectum or sigmoid colon was infiltrated with endometriosis. RESULTS: The difference between the operation time of the two techniques (transabdominal vs. transrectal specimen extraction: 108 min vs. 118 min) was not significant. There was not difference in the WBC count between the first and second postoperative day, and there was not any anastomosis leakage detected either. CONCLUSION: By using the above technique, postoperative infections could have been reduced to minimum. Transrectal specimen extraction did not increase postoperative complication The authors believe this is a safe way of specimen extraction after partial colectomy.

Vascular endothelial growth factor pathway in endometriosis: genetic variants and plasma biomarkers.

OBJECTIVE: To study single nucleotide polymorphisms (SNPs) involved in angiogenesis (VEGF, PLGF, VEGFR1, VEGFR2, HIF-1α) and plasma levels of the corresponding proteins (VEGF, PLGF, sVEGFR1, sVEGFR2) in women with and without endometriosis. DESIGN: Allele frequencies of vascular endothelial growth factor (VEGF) pathway SNPs and plasma levels of the corresponding proteins were investigated in patients with endometriosis and in controls. SETTING: University hospital. PATIENT(S): Samples of DNA from 1,931 Caucasian patients were included (1,109 patients with endometriosis and 822 controls). An additional study group included 973 DNA samples from volunteers, self-reported to be healthy without laparoscopic evaluation. INTERVENTION(S): Women who underwent a laparoscopy for subfertility and/or pain and healthy volunteers without laparoscopic evaluation. MAIN OUTCOME MEASURE(S): Functional SNPs of the VEGF, VEGFR1, VEGFR2, HIF-1α genes and Hap Map tagging SNPs of the PLGF gene were genotyped by using iPLEX technology on a Sequenom MassArray and TaqMan SNP Genotyping Assay. The VEGF levels were determined in ethylenediaminetetraacetic acid plasma samples by using Bio-Plex Protein Array System. PLGF, sVEGFR1, and sVEGFR2 levels were measured in ethylenediaminetetraacetic acid plasma samples by using ELISA Quantikine kits. RESULT(S): A significant association was found between the rs2268613 polymorphism in the PLGF gene and PLGF plasma levels. In all study subjects, women with the AA variant of the rs2268613 PLGF gene had significantly lower PLGF plasma levels (median [interquartile range] 9.36 [8.19-10.43] pg/mL) than those with the AG variant (12.1 [11.81-20.84] pg/mL; P(a)=.0085, P(b)=.04), both before and after multiple testing. Plasma levels of VEGF were elevated in endometriosis patients (especially in minimal-mild endometriosis during the menstrual cycle phase) compared with laparoscopic controls but had a moderate diagnostic performance (area under the curve, 0.73) in this discovery dataset. At a cut-off plasma level of VEGF >3.88 pg/mL, minimal-mild stages of endometriosis were diagnosed with a sensitivity of 74% and a specificity of 80% during the menstrual phase of cycle. The associations between the presence of endometriosis and SNPs in PLGF (rs2268614), HIF-1α (rs11549465), and VEGFR1 (rs9582036) genes lost statistical significance after multiple testing. CONCLUSION(S): Genetic variants in the PLGF rs2268613 gene may influence plasma levels of the corresponding protein. Plasma levels of VEGF were elevated in endometriosis patients compared with controls. The associations between the presence of endometriosis and SNPs in PLGF (rs2268614), HIF-1α (rs11549465), and VEGFR1 (rs9582036) genes lost statistical significance after multiple testing.

[Importance of nerve-sparing surgical technique in the treatment of deep infiltrating endometriosis]. / Az idegkímélo mutéti technika jelentosége a mélyen infiltráló endometriosis sebészetében.

INTRODUCTION: Traditional surgeries performed in cases of deep infiltrating endometriosis lead to impaired quality of life. AIM: To summarize the postoperative outcome and to compare the rate of postoperative complications after different therapeutic approaches applied in deep infiltrating endometriosis. METHOD: The authors analized the articles published between March 31, 2004 and March 31, 2015, in the database http://www.pubmed.org using the following keywords: endometriosis, deep infiltrating, nerve sparing, surgery. RESULTS: Non-nerve sparing surgery resulted in temporary urinary dysfunction in 19.1-38.5% of patients, while it occurred in 0.61-33.3% of patients after nerve-sparing surgery. Non-nerve sparing surgical technique resulted in an average of 121 days of need for self-catheretisation. When nerve-sparing surgeries were performed the duration of self-catheterisation varied between 7 to 39.8 days. After nerve sparing surgeries, permanent bladder dysfunction was not detected in any case. CONCLUSIONS: Because of the successful treatment of the patients symptoms and the lower postoperative complication rate, nerve-sparing surgical technique leads to a significant improvement of the quality of life.

Belet infiltráló endometriosis ellátásának sebészi szempontjai 120 eset kapcsán.

INTRODUCTION: The number of patients operated on with endometriosis increases, the urological organ and the bowels are involved in 10-40% of the cases in addition to the gynaecological organs. PATIENTS AND METHODS: Sigmoideoscopy detected bowel endometriosis in 224 patients from 383 patients with endometriosis, and 127 patients were operated on from 14.07.2009 to 13.01.2014 at the 1st Gynaecological Department of Semmelweis University, Budapest, Hungary. All the operation was made by the same gynaecologist and surgeon team. RESULTS: Segment resection of the bowel was performed in 120 patients, local resection in two patients and shaving in another two cases. The involved part of the bowels were the rectum at 46 patients, rectosigmoid in 68, sigmoid bowel in 30, coecum in 4, appendix in 2 and the small intestine in 2 patients. Bladder resection was carried out in 9 patients, ureter resection in two patients and ureterolysis in 26 cases were done due to infiltration of the urological organs. The laparoscopic operation needed to be converted on one single occasion due to bleeding from the epigastric artery, and a laparoscopic suture of the anastomosis was applied for bleeding in another patient. The specimen was extracted transvaginally in 16 patients and transanally in 13 patients. Anastomotic leakage was detected in two patients and rectovaginal fistula in four patients. All reoperations (creation and closing of the stoma) were done laparoscopically. CONCLUSIONS: The treatment of the bowel endometriosis is suggested with segment resection by multidisciplinary team, where the invasivity can be decreased by transanal specimen extraction.

[Reducing invasiveness of laparoscopic surgery using natural orifices and abdominal wall defects for extraction of the specimen]. / A laparoszkópos sebészet invazivitásának csökkentése természetes szájadékok és hasfali defektusok felhasználásával a mutéti specimen eltávolítására.

INTRODUCTION: Due to significant technical evolution complex surgeries can be performed laparoscopically nowadays. However, laparotomy is needed frequently for the extraction of the specimen, which decreases the advantages of laparoscopy. AIM: The aim of the authors was to analyse and present their experience on the use of natural orifices and abdominal wall defects for extraction of the surgical specimen. METHOD: From 2009 the authors used natural orifices (stomach, vagina, rectum) when viscerotomy was an obligate part of laparoscopic surgery and, in a special gastrointestinal laparoscopic operation, the gate of the inguinal hernia for specimen extraction. RESULTS: In 3 patients benign lesions of the stomach were extracted using gastroscope. In 6 patients with bowel endometriosis, in whom the wall of the vagina was completely infiltrated, the resected bowel was extracted transvaginally, and in 5 patients transrectal extraction of the specimen was performed. In 2 patients the inguinal hernia was used for the surgical specimen extraction after laparoscopic sigmoid resection, and in one patient a single-port was inserted into the gate of the hernia during laparoscopic cholecystectomy. Complications occurred only after transvaginal specimen extraction (rectovaginal fistula in 2 patients). CONCLUSIONS: Use of natural orifices and abdominal wall defects for surgical specimen extraction further decreases the invasiveness of laparoscopic surgery, if indications made appropriately.