Uterine Skeletonization in Modified Radical Hysterectomy for Deep Infiltrative Endometriosis: The SkeletonDIE Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Uterine Skeletonization in Modified Radical Hysterectomy for Deep Infiltrative Endometriosis: The SkeletonDIE Study Baris Kaya, Alperen Ince, Merve Sam Ozdemir, Sercan Yuksel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7098525/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Deep infiltrating endometriosis (DIE) involving the posterior compartment and parametrium often necessitates modified radical hysterectomy, and in cases of extensive rectal invasion, concomitant segmental bowel resection may be required. However, conventional approaches may endanger pelvic autonomic nerves. This study aimed to evaluate the intraoperative and early postoperative outcomes of the uterine skeletonization technique in nerve-sparing modified radical hysterectomy for stage IV DIE. Methods : This retrospective observational study included 80 patients with stage IV DIE who underwent nerve-sparing modified radical hysterectomy using the SkeletonDIE technique between 2022 and 2024 at a tertiary endometriosis center in Istanbul, Türkiye. The type of hysterectomy (Type B or C1), additional procedures (e.g., rectal resection with NOSE technique), and perioperative complications were documented. Descriptive statistics were used, and outcomes were reported as medians, ranges, and percentages. Results : The median age was 41 years and BMI 27.0 kg/m². Preoperative hormonal therapy was administered to 84.4% of patients. Adenomyosis was found in 88.7% and bilateral endometriomas in 51.2%. Mean VAS scores were 8.6 for dysmenorrhea and 7.4 for dyspareunia. Modified radical hysterectomy type B and C1 were performed in 65% and 35%, respectively. Bilateral ureterolysis was completed in 86%, dorsolateral parametrium excision in 78% (bilaterally in 19%), and rectal resection using NOSE technique in 20%. Severe postoperative complications (Clavien–Dindo ≥ III) occurred in 7.4% of cases, while intraoperative complications occurred in 3%. No conversions to laparotomy or mortalities were reported. Conclusions : The uterine skeletonization technique is a feasible and safe nerve-sparing approach to modified radical hysterectomy in patients with advanced DIE. It enables radical excision of disease while minimizing damage to pelvic autonomic nerves. Future prospective studies are needed to assess long-term functional outcomes. Trial Registration : This study was retrospectively registered at ClinicalTrials.gov (identifier: NCT06802900; registration date: January 31, 2025). Deep infiltrating endometriosis Modified radical hysterectomy Uterine skeletonization Nerve-sparing surgery Bowel resection Pelvic autonomic nerves Natural orifice specimen extraction (NOSE) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Endometriosis is a chronic, estrogen-dependent inflammatory disease, with deep infiltrating endometriosis (DIE) representing its most severe form, characterized by lesions penetrating more than 5 mm beneath the peritoneal surface [ 1 ]. DIE has since been recognized for its invasive nature and its association with fibrosis and retraction of adjacent tissues [ 2 ]. DIE most frequently affects retroperitoneal and pelvic structures including uterine ligaments such as the uterosacral ligaments, and parametrium, vagina, ureters, bladder and rectum, [ 3 , 4 ]. The involvement of these critical structures often leads to severe clinical symptoms such as severe dysmenorrhea, dyspareunia, dyschezia, and chronic pelvic pain [ 5 ]. The anatomical distortion caused by fibrosis and deep tissue invasion necessitates a high level of surgical expertise, including familiarity with pelvic neuroanatomy and vascular anatomy, to perform nerve-sparing and organ-preserving procedures effectively [ 6 – 8 ]. In women who have completed childbearing, DIE unresponsive to medical therapy is managed with nerve-sparing modified radical hysterectomy, often combined with unilateral or bilateral salpingo-oophorectomy, excision of parametrial and paravaginal nodules, and bowel surgery such as rectal shaving or segmental resection when indicated [ 9 ]. This study aimed to assess the intraoperative and early postoperative outcomes of uterine skeletonization during nerve-sparing modified radical hysterectomy for deep infiltrating endometriosis. Materials and Methods In this retrospective study, patients who underwent nerve-sparing modified radical hysterectomy for deeply infiltrating endometriosis using the uterine skeletonization technique between October 2022 and September 2024 were reviewed. The uterine skeletonization technique was developed by the principal investigator (BK) specifically for modified radical hysterectomy in cases of deeply infiltrating endometriosis and has been systematically applied at Başakşehir Çam and Sakura City Hospital in Istanbul. This study was approved by the Institutional Review Board (approval date and number: KAEK/11.09.2024.207) and was retrospectively registered at ClinicalTrials.gov (identifier: NCT06802900; registration date: January 31, 2025). Patients' age, body mass index (BMI), demographic characteristics, duration of pain symptoms, medical and surgical history, and pelvic pain intensity (assessed using the Visual Analog Scale [VAS]) were evaluated. Patients with AAGL stage IV endometriosis confirmed by transvaginal ultrasound and MRI, who suffered from severe symptoms such as dysmenorrhea, dyspareunia, dyschezia, and chronic pelvic pain, and who were either unresponsive to or had contraindications for medical therapy, and had no desire for future fertility, were considered eligible for definitive surgical management. All procedures were performed by the lead surgeon (BK), who specializes in advanced laparoscopic surgery for endometriosis. Except for rectal shaving, colorectal disease management, including bowel resection and anastomosis, was performed by the same colorectal surgeon (SY). Detailed surgical steps and intraoperative data were recorded, including operative time, surgical approach (e.g., hysterectomy with or without salpingo-oophorectomy, and excision of parametrial, rectovaginal, or vaginal nodules, as well as bowel resections). Intraoperative complications such as organ injuries, blood transfusion requirements, and conversions to open surgery were documented. Postoperative outcomes, both early and late, were systematically evaluated. All postoperative complications were categorized according to the Clavien–Dindo classification system [10], which grades complications based on the required level of intervention. Recorded complications included fever, deep vein thrombosis, sepsis, pelvic abscess, genitourinary fistulas, anastomotic leaks, reoperations, vaginal cuff bleeding or abscesses, and bladder dysfunction. Surgical Procedure of Hysterectomy with Uterine Skeletonization in DIE Surgery The nerve-sparing modified radical hysterectomy with uterine skeletonization is a structured approach designed for patients with deeply infiltrating endometriosis (DIE), especially in cases involving parametrial, rectovaginal, or uterosacral infiltration. The procedure is carried out step by step to ensure optimal clearance of deep endometriotic lesions while preserving the pelvic autonomic nerves ( see Supplementary Video 1 ). Step-by-Step Technique: 1. Mobilization of the Sigmoid Colon: o The sigmoid colon is detached from the pelvic wall to allow entry into the retroperitoneal space and to facilitate ureteral identification. 2. Ureterolysis: o The ureter is dissected from the pelvic brim down to the Wertheim tunnel, and the lateral pararectal space ( Latzko space ) is developed to ensure complete visualization and preservation of the ureter. 3. Adnexal Management: Unilateral or bilateral salpingo-oophorectomy, often including excision of endometriomas or hydrosalpinges, is performed to enhance surgical exposure and facilitate safe dissection. 4. Uterine Vascular interventions: o Vascular clips are applied to the uterine artery at their origin (and vein if necessary), prior to further dissection. 5. Parametrial Dissection: o Parametrial nodules are carefully excised, maintaining ureteral integrity up to the Wertheim tunnel . Dissection is generally limited to below the uterine vein to preserve the pelvic splanchnic nerves, unless deeper infiltration necessitates further resection (see Figure 1, 2). 6. Pararectal Space Development: o Bilateral medial ( Okabayashi ) pararectal spaces are developed to expose the lateral parametrium and pelvic nerves (see Figure 3). 7. Rectovaginal Dissection: o The rectum is detached from the posterior uterus and cul-de-sac performed using cold scissors to minimize thermal injury, and the rectovaginal space is opened with precision. 8. Transection of Uterosacral Ligaments: o Fibrotic uterosacral ligaments are transected with care to preserve the hypogastric nerves . Uterine Skeletonization: Full skeletonization of the uterus is achieved by systematically isolating the parametrial and paracervical tissues and detachment of the rectum from uterine torus facilitating safe and radical resection while sparing autonomic nerves. 9. Completion of Hysterectomy A total laparoscopic hysterectomy is completed following skeletonization. Bowel resection procedure steps (If indicated) Following hysterectomy, the specimens—including the uterus, adnexa, and parametrial nodules—are removed transvaginally. The vaginal cuff is intentionally left open to allow subsequent extraction of the resected rectal segment. In patients with colorectal involvement, rectosigmoid resection was initially performed using the laparoscopic conventional technique (mini Pfannenstiel incision with Alexis retractor), and after several cases, the procedure was refined to use the Natural Orifice Specimen Extraction (NOSE) technique as described by Malzoni et al. [11,12], with slight modifications (see Figure 4,5). Bulky pelvic lymph nodes were removed when encountered. The rectal part of surgery was always started with isolation of the inferior mesenteric artery (IMA ) using monopolar hook and bilateral hypogastric nerve dissection. Then mesorectum of the margin free segments were excised using advanced bipolar devices. For colorectal resection and anastomosis, the Covidien Endo GIA™ 60 mm Articulating Reload with Tri-Staple™ Technology ( Medtronic, Minneapolis, MN, USA ) was utilized. ( See Supplementary Video-1 ) Statistical analysis for continuous variables was based on the Student t test and the Fisher exact test for categoric variables. The relative risk (RR) was also calculated to estimate the risk of having an event with its 95% confidence interval (CI). Statistical tests with p values <.05 were considered statistically significant. Analyses were performed with R software (version 4.2.1, R foundation for Statistical Computing, Vienna, Austria) and Stata 15.1 IC software (StataCorp LLC, College Station, TX). Results During the study period, 80 patients underwent nerve-sparing modified radical hysterectomy for DIE using the SkeletonDIE technique. Table 1 presents the demographic characteristics and endometriosis-related clinical features of the study population. The median age was 41 years (range, 34–55), and the median BMI was 27.0 kg/m² (range, 18.2–41.1). A notable proportion of patients (27.5%) had a history of previous gynecologic surgery, with 14.3% having undergone prior surgery for endometriosis. Majority reported severe pelvic pain symptoms, with mean VAS scores of 8.6 for dysmenorrhea and 7.4 for dyspareunia. Preoperative hormonal therapy had been administered in 84.4% of cases. Adenomyosis was identified in 88.7% of patients, and bilateral endometriomas were present in 51.2%. Intraoperative details and surgical complexity are presented in Table 2. The mean operative time was 287 minutes (range, 123–670). Bilateral ureterolysis was performed in nearly 90% of cases. Dorsolateral parametrium excision was performed in 78.7% of patients. Rectal resection, mostly using the laparoscopic NOSE technique, was required in 20% of cases. Protective ileostomy and colostomy were performed in 3.7% (n=3) and 1.2% (n=1) of patients, respectively. According to the Querleu–Morrow classification of radical hysterectomy [13], Type B procedures were performed in 65% of cases and Type C1 in 35%. Surgical complexity was reflected by a mean AAGL score of 55, stage IV endometriosis, and extensive involvement across ENZIAN compartments (Table 2). Intraoperative complications were observed in 3.7% of patients (n=3), including two bladder injuries and one internal iliac artery bleeding. All intraoperative complications were addressed intraoperatively. Bladder injuries were repaired primarily, and internal iliac artery bleeding was controlled using vascular clamping, ensuring preservation of the posterior branches. All procedures were completed laparoscopically without conversion to open surgery. Intraoperative and postoperative transfusion requirements were observed in 10% and 11.2% of patients, respectively. No malignant pathology was detected on frozen section analysis. The mean hospital stay was 6 days (3–21). A total of 3.7% of patients (n=3) required admission to the intensive care unit (ICU). The patients were followed up for 6 to 24 months after surgery. No patients in this case series required postoperative bladder catheterization. However, two individuals reported symptoms of bladder dysfunction—specifically urgency and features consistent with neurogenic bladder. Postoperative neuropathic symptoms were observed following surgery in two patients: one experienced severe burning pain in the entire leg, while the other reported paresthesia and numbness in the medial thigh. These neuropathic symptoms were managed conservatively with pregabalin, and both patients remain under follow-up in the neurology department. Postoperative complications are presented in Table 3, with 7.4% classified as Clavien–Dindo grade III or higher (see Table 4). A vesicorectal fistula developed on postoperative day eight in a 41-year-old patient (Case 1), necessitating relaparotomy with colostomy and nephrostomy placement. A 40-year-old patient (Case 2) experienced rectal anastomotic leakage on postoperative day 18, which was successfully managed with colonoscopic clip application. In Case 3, a submassive pulmonary embolism was diagnosed on the first postoperative day; the patient underwent interventional thrombolytic therapy targeting the pulmonary artery, followed by intensive care unit (ICU) monitoring. In Case 4, a rectovaginal fistula developed after colostomy closure in a patient who had initially received a prophylactic colostomy during rectal resection. This was managed with robot-assisted low anterior resection. Case 5 involved a 44-year-old patient who developed both a bowel thermal injury and ureteral stricture on postoperative day six, requiring relaparotomy, colostomy, and nephrostomy. On postoperative day seven, one patient (Case 6) developed sepsis secondary to a pelvic abscess caused by Prevotella bivia , which was successfully treated with laparoscopic drainage and intravenous antibiotic therapy [14]. Finally, in Case 7, an umbilical hernia was detected six months postoperatively; surgical repair was recommended, but the patient declined further intervention. All complications were managed with appropriate surgical or interventional procedures, and no postoperative mortality was observed. Discussion In this retrospective cohort of 80 patients with stage IV DIE who underwent nerve-sparing modified radical hysterectomy using the uterine skeletonization technique, we observed high rates of complete resection and a low rate of major complications, consistent with prior findings from established centers. According to the literature, serious postoperative complication rates for DIE surgery range from 1.2–10.5%, depending on the degree of surgical radicality (including the extent of parametrial resection), whether hysterectomy was performed, and the type of bowel procedure applied—such as rectal shaving, bowel resection, or stoma creation [ 15 – 18 ]. Therefore, complication rates vary based on these parameters, making direct comparisons challenging. In our series, where most patients underwent nerve-sparing modified radical hysterectomy, Clavien–Dindo grade ≥ III complications were observed in 7.4% of cases, which is comparable to the 10.5% rate reported by Bafort et al. [ 17 ]. Intraoperative complications No intraoperative bowel or ureteral injuries were encountered among the 80 cases. Bladder injury due to dense adhesions (n = 2) was successfully repaired intraoperatively by the primary surgeon. A vascular complication occurred in one case (1.2%), where a parametrial nodule was densely adherent to the internal iliac artery, leading to significant bleeding during dissection. The hemorrhage was promptly controlled laparoscopically using a Hem-o-Lok vascular clamp, and the patient received an intraoperative blood transfusion. Darlet et al. [ 16 ] reported one intraoperative complication (1.9%) in a 52-patient series—specifically, a hypogastric vein injury requiring conversion to laparotomy and transfusion. Intraoperative pelvic organ injuries—including bowel, ureter, and bladder—have been reported in 1.2–5% of cases in the literature [ 15 , 19 , 20 ], with Uccella et al. [ 20 ] noting a 1.7% conversion rate to laparotomy. Postoperative Complications Postoperative bowel complications remain among the most serious and feared adverse events following DIE surgery, often necessitating relaparotomy or colostomy and resulting in significant morbidity for both patients and surgeons. However, in advanced-stage DIE—particularly when the rectum is infiltrated—such complications may be difficult to avoid. In our series, four bowel complications (5%) were observed. Two patients (2.5%) developed rectovesical and rectovaginal fistulas requiring relaparotomy and colostomy. One patient experienced an anastomotic leak, which was successfully treated with colonoscopic clip application, thereby avoiding the need for relaparotomy. Another patient developed a thermal bowel injury and concurrent ureteral stricture on postoperative day seven, managed with relaparotomy, colostomy, and nephrostomy. These outcomes are comparable with those in the literature. While Darlet et al. reported no rectovaginal fistulas in their 52-patient series [ 16 ], Bafort et al. noted a 1.8% rectovaginal fistula rate and a 2.9% bowel leakage rate in patients undergoing segmental bowel resection [ 17 ]. Roman et al. [ 21 ] and Minelli et al. [ 22 ] reported bowel fistula rates of 3.4% and 3.7%, respectively, consistent with our 3.8% rate. Uccella et al. [ 20 ] also reported a case of bowel perforation requiring open rectal resection. Malzoni et al. reported an anastomotic leakage rate of 1.6% and a rectovaginal fistula rate of 2.4% in their large series of patients undergoing segmental bowel resection for DIE [ 12 ]. Voiding Dysfunction and Self-Catheterization Bladder dysfunction requiring self-catheterization is one of the most distressing complications after DIE surgery, significantly impacting postoperative quality of life. In our series, two patients (2.5%) experienced postoperative bladder dysfunction (urgency and atonic bladder), yet none required temporary or permanent self-catheterization. In contrast, Darlet et al. [ 16 ] and Rosati et al. [ 18 ] reported postoperative voiding dysfunction requiring catheterization in approximately 13% of cases. Darlet et al. [ 16 ] further detailed that 11.6% of patients required catheterization for less than 30 days, while 1.9% experienced persistent dysfunction beyond one month. Thanks to nerve-sparing techniques, we speculate that our low rate of voiding dysfunction may be attributed to the structured nature of the uterine skeletonization technique, which facilitates targeted parametrial dissection while preserving pelvic autonomic nerves. Additionally, unlike the en-bloc resection approach described by Rosati [ 18 ] and Darlet [ 16 ], the individual excision of each parametrial nodule may contribute to minimizing the risk of nerve injury. Operating Time Although the uterine skeletonization technique improves surgical exposure, it did not result in shorter operative times in our series (mean: 287 minutes) compared to previously published data (Khazali et al. [ 15 ]: 223 minutes; Darlet et al. [ 16 ]: 265 minutes). This discrepancy may be attributed to the limited endometriosis experience of assisting residents, the technical challenges associated with using a 30-degree laparoscopic camera, and the advanced disease stage, which necessitated bilateral ureterolysis (86%) and frequent bowel or vaginal resections. Nevertheless, all procedures were successfully completed laparoscopically without conversion. Strengths and Limitations This study was conducted at a single, high-volume tertiary endometriosis center, with all surgeries and follow-up evaluations performed by the same experienced surgeon. Although not a novel technique per se, uterine skeletonization represents a strategic refinement of previously established surgical steps [ 16 , 18 , 20 , 23 ]. The primary limitation of this study is its retrospective design. Future prospective, multicenter randomized trials are warranted to further validate the outcomes and long-term benefits of the uterine skeletonization approach in DIE surgery. Conclusion Our findings support the feasibility and safety of nerve-sparing radical surgery using the uterine skeletonization technique in advanced DIE cases without fertility desire. This approach enables systematic exposure of critical pelvic structures while minimizing nerve injury, as reflected by the absence of catheter-dependent bladder or rectal dysfunction. Each DIE case presents unique intraoperative challenges, and surgical success relies not only on anatomical expertise but also on the surgeon’s capacity for creativity and refined intraoperative problem-solving. Abbreviations DIE: Deep Infiltrating Endometriosis; MRI: Magnetic Resonance Imaging; VAS: Visual Analog Scale; BMI: Body Mass Index; NOSE: Natural Orifice Specimen Extraction; ICU: Intensive Care Unit; AAGL: American Association of Gynecologic Laparoscopists; Clavien–Dindo: Clavien–Dindo Classification of Surgical Complications. Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board of Başakşehir Çam and Sakura City Hospital (approval number: KAEK/11.09.2024.207) and was retrospectively registered at ClinicalTrials.gov (identifier: NCT06802900). Written informed consent was obtained from all participants before surgery. This study was carried out in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to institutional data protection policies but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions BK designed the study, performed all surgeries, and supervised manuscript preparation. AI contributed to data collection and assisted in surgical procedures. MSÖ reviewed all preoperative MRI studies and contributed to data interpretation. SY performed all bowel resections and contributed to the surgical protocol. All authors read and approved the final manuscript. Acknowledgements The authors thank the operating room staff and anesthesiology team at Başakşehir Çam and Sakura City Hospital for their consistent support in complex surgical procedures. Authors' information BK is a dedicated surgeon specializing in advanced deep infiltrating endometriosis (DIE) surgery. He serves as the head of the Endometriosis Clinic at Başakşehir Çam and Sakura City Hospital, one of Istanbul’s largest tertiary referral centers, which accepts patients from across Istanbul as well as various provinces throughout Türkiye. SY is a colorectal surgeon experienced in performing rectal resections and complex bowel surgeries in collaboration with gynecologic teams. MSÖ is a radiologist who specializes in detailed interpretation of MRI scans for deep endometriosis and contributes to preoperative surgical planning. AI is a skilled gynecologic surgeon who actively assists in deep endometriosis surgeries and contributes to intraoperative management References Koninckx PR, Ussia A, Adamyan L, et al. Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012;98(3):564–71. 10.1016/j.fertnstert.2012.07.1061 . Cornillie FJ, Oosterlynck D, Lauweryns JM, Koninckx PR. Deeply infiltrating pelvic endometriosis: histology and clinical significance. Fertil Steril. 1990;53(6):978–83. 10.1016/s0015-0282(16)53570-5 . Keckstein J, Saridogan E, Ulrich UA, et al. The #Enzian classification: A comprehensive non-invasive and surgical description system for endometriosis. Acta Obstet Gynecol Scand. 2021;100(7):1165–75. 10.1111/aogs.14099 . Bazot M, Daraï E. Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis. Fertil Steril. 2018;109(3):389–97. 10.1016/j.fertnstert.2018.01.024 . Ceccaroni M, Clarizia R, Bruni F, et al. Nerve-sparing laparoscopic eradication of deep endometriosis with segmental rectal and parametrial resection: the Negrar method. A single-center, prospective, clinical trial. Surg Endosc. 2012;26(7):2029–45. 10.1007/s00464-012-2153-3 . Yabuki Y, Asamoto A, Hoshiba T, et al. Radical hysterectomy: An anatomic evaluation of parametrial dissection. Gynecol Oncol. 2000;77(1):155–63. 10.1006/gyno.1999.5723 . Fujii S, Takakura K, Matsumura N et al. Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. Gynecol Oncol. 2007;107(1):4–13. doi: 10.1016/j.ygyno.2007.08.076. PMID: 17905140. Ceccaroni M, Clarizia R, Roviglione G. Nerve-sparing Surgery for Deep Infiltrating Endometriosis: Laparoscopic Eradication of Deep Infiltrating Endometriosis with Rectal and Parametrial Resection According to the Negrar Method. J Minim Invasive Gynecol. 2020;27(2):263–4. 10.1016/j.jmig.2019.09.002 . Working group of ESGE, ESHRE, and, Keckstein WES, Becker J, Canis CM. Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis. Hum Reprod Open. 2020;12(1):hoaa002. 10.1093/hropen/hoaa002 . Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96. Malzoni M, Rasile M, Coppola M, et al. Totally Laparoscopic Resection with Transanal Natural Orifice Specimen Extraction for Deep Endometriosis Infiltrating the Rectum. J Minim Invasive Gynecol. 2022;29(1):19. 10.1016/j.jmig.2021.07.015 . Malzoni M, Di Giovanni A, Coppola M, et al. Total Laparoscopic Segmental Resection with Transanal Natural Orifice Specimen Extraction for Treatment of Colorectal Endometriosis: Descriptive Analysis From the TrEnd Study Database. J Minim Invasive Gynecol. 2025;32(3):240–7. 10.1016/j.jmig.2024.10.007 . Querleu D, Cibula D, Abu-Rustum NR. 2017 Update on the Querleu-Morrow Classification of Radical Hysterectomy. Ann Surg Oncol. 2017;24(11):3406–12. 10.1245/s10434-017-6031-z . Kaya B, Ince A, Sam Ozdemir M, Yuksel S. Laparoscopic Management of an Early Postoperative Pelvic Abscess Caused by Prevotella bivia Following a Deep Infiltrating Endometriosis Surgery. Cureus. 2024; 6;16(8):e66315. 10.7759/cureus.66315 Khazali S, Gorgin A, Mohazzab A, et al. Laparoscopic excision of deeply infiltrating endometriosis: a prospective observational study assessing perioperative complications in 244 patients. Arch Gynecol Obstet. 2019;299(6):1619–26. 10.1007/s00404-019-05144-6 . Darlet G, Margueritte F, Drioueche H, Fauconnier A. Laparoscopic Modified Radical Hysterectomy for Severe Endometriosis: A Single-Center Case Series. J Minim Invasive Gynecol. 2024;31(5):423–31. 10.1016/j.jmig.2024.01.022 . Bafort C, van Elst B, Neutens S, et al. Outcome after surgery for deep endometriosis infiltrating the rectum. Fertil Steril. 2020;113(6):1319–e13273. 10.1016/j.fertnstert.2020.02.108 . Rosati A, Pavone M, Campolo F, et al. Surgical and functional impact of nerve-sparing radical hysterectomy for parametrial deep endometriosis: a single centre experience. Facts Views Vis Obgyn. 2022;14(2):121–7. 10.52054/FVVO.14.2.016 . Casarin J, Ghezzi F, Mueller M, et al. Surgical Outcomes and Complications of Laparoscopic Hysterectomy for Endometriosis: A Multicentric Cohort Study. J Minim Invasive Gynecol. 2023;30(7):587–92. 10.1016/j.jmig.2023.03.018 . Uccella S, Marconi N, Casarin J, et al. Impact of endometriosis on surgical outcomes and complications of total laparoscopic hysterectomy. Arch Gynecol Obstet. 2016;294(4):771–8. 10.1007/s00404-016-4115-9 . Roman H, Bridoux V, Merlot B, et al. Risk of bowel fistula following surgical management of deep endometriosis of the rectosigmoid: a series of 1102 cases. Hum Reprod. 2020;1(7):1601–11. 10.1093/humrep/deaa131 . Minelli L, Ceccaroni M, Ruffo G, et al. Laparoscopic conservative surgery for stage IV symptomatic endometriosis: short-term surgical complications. Fertil Steril. 2010;94(4):1218–22. Epub 2009 Dec 6. PMID: 19969292. Tanaka Y, Kuratsune K, Otsuka A, et al. Total laparoscopic hysterectomy with posterior cul-de-sac obliteration: step-by-step procedures based on precise anatomical landmarks. Arch Gynecol Obstet. 2024;310(3):1795–9. 10.1007/s00404-024-07614-y . Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1preopretaivedie.docx table2.surgicaloutcomes.docx table3complications.docx Table4seriouscomplication.docx pernuhwithvoice.mp4621.mp4 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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01:32:53","extension":"mp4","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":208453335,"visible":true,"origin":"","legend":"","description":"","filename":"pernuhwithvoice.mp4621.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7098525/v1/13d9f639e7579ef7976d1c3d.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Uterine Skeletonization in Modified Radical Hysterectomy for Deep Infiltrative Endometriosis: The SkeletonDIE Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometriosis is a chronic, estrogen-dependent inflammatory disease, with deep infiltrating endometriosis (DIE) representing its most severe form, characterized by lesions penetrating more than 5 mm beneath the peritoneal surface [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. DIE has since been recognized for its invasive nature and its association with fibrosis and retraction of adjacent tissues [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDIE most frequently affects retroperitoneal and pelvic structures including uterine ligaments such as the uterosacral ligaments, and parametrium, vagina, ureters, bladder and rectum, [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The involvement of these critical structures often leads to severe clinical symptoms such as severe dysmenorrhea, dyspareunia, dyschezia, and chronic pelvic pain [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The anatomical distortion caused by fibrosis and deep tissue invasion necessitates a high level of surgical expertise, including familiarity with pelvic neuroanatomy and vascular anatomy, to perform nerve-sparing and organ-preserving procedures effectively [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In women who have completed childbearing, DIE unresponsive to medical therapy is managed with nerve-sparing modified radical hysterectomy, often combined with unilateral or bilateral salpingo-oophorectomy, excision of parametrial and paravaginal nodules, and bowel surgery such as rectal shaving or segmental resection when indicated [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study aimed to assess the intraoperative and early postoperative outcomes of uterine skeletonization during nerve-sparing modified radical hysterectomy for deep infiltrating endometriosis.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eIn this retrospective study, patients who underwent nerve-sparing modified radical hysterectomy for deeply infiltrating endometriosis using the uterine skeletonization technique between October 2022 and September 2024 were reviewed. The uterine skeletonization technique was developed by the principal investigator (BK) specifically for modified radical hysterectomy in cases of deeply infiltrating endometriosis and has been systematically applied at Başakşehir Çam and Sakura City Hospital in Istanbul. This study was approved by the Institutional Review Board (approval date and number: KAEK/11.09.2024.207) and was retrospectively registered at ClinicalTrials.gov (identifier: NCT06802900; registration date: January 31, 2025).\u003c/p\u003e\n\u003cp\u003ePatients' age, body mass index (BMI), demographic characteristics, duration of pain symptoms, medical and surgical history, and pelvic pain intensity (assessed using the Visual Analog Scale [VAS]) were evaluated. Patients with AAGL stage IV endometriosis confirmed by transvaginal ultrasound and MRI, who suffered from severe symptoms such as dysmenorrhea, dyspareunia, dyschezia, and chronic pelvic pain, and who were either unresponsive to or had contraindications for medical therapy, and had no desire for future fertility, were considered eligible for definitive surgical management.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All procedures were performed by the lead surgeon (BK), who specializes in advanced laparoscopic surgery for endometriosis. Except for rectal shaving, colorectal disease management, including bowel resection and anastomosis, was performed by the same colorectal surgeon (SY).\u003c/p\u003e\n\u003cp\u003eDetailed surgical steps and intraoperative data were recorded, including operative time, surgical approach (e.g., hysterectomy with or without salpingo-oophorectomy, and excision of parametrial, rectovaginal, or vaginal nodules, as well as bowel resections).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIntraoperative complications such as organ injuries, blood transfusion requirements, and conversions to open surgery were documented.\u003c/p\u003e\n\u003cp\u003ePostoperative outcomes, both early and late, were systematically evaluated. All postoperative complications were categorized according to the Clavien–Dindo classification system [10], which grades complications based on the required level of intervention. Recorded complications included fever, deep vein thrombosis, sepsis, pelvic abscess, genitourinary fistulas, anastomotic leaks, reoperations, vaginal cuff bleeding or abscesses, and bladder dysfunction.\u003c/p\u003e\n\u003cp\u003eSurgical Procedure of Hysterectomy with Uterine Skeletonization in DIE Surgery\u003c/p\u003e\n\u003cp\u003eThe nerve-sparing modified radical hysterectomy with uterine skeletonization is a structured approach designed for patients with deeply infiltrating endometriosis (DIE), especially in cases involving parametrial, rectovaginal, or uterosacral infiltration. The procedure is carried out step by step to ensure optimal clearance of deep endometriotic lesions while preserving the pelvic autonomic nerves (\u003cem\u003esee Supplementary Video 1\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eStep-by-Step Technique:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e1.\u0026nbsp; \u0026nbsp;Mobilization of the Sigmoid Colon:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo The sigmoid colon is detached from the pelvic wall to allow entry into the retroperitoneal space and to facilitate ureteral identification.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e2.\u0026nbsp; \u0026nbsp;Ureterolysis:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo The ureter is dissected from the pelvic brim down to the Wertheim tunnel, and the lateral pararectal space (\u003cem\u003eLatzko space\u003c/em\u003e) is developed to ensure complete visualization and preservation of the ureter.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.\u0026nbsp; \u0026nbsp;Adnexal Management:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUnilateral or bilateral salpingo-oophorectomy, often including excision of endometriomas or hydrosalpinges, is performed to enhance surgical exposure and facilitate safe dissection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e4.\u0026nbsp; \u0026nbsp;Uterine Vascular interventions:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo Vascular clips are applied to the uterine artery at their origin (and vein if necessary), prior to further dissection.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e5.\u0026nbsp; \u0026nbsp;Parametrial Dissection:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo Parametrial nodules are carefully excised, maintaining ureteral integrity up to the \u003cem\u003eWertheim tunnel\u003c/em\u003e. Dissection is generally limited to below the uterine vein to preserve the pelvic splanchnic nerves, unless deeper infiltration necessitates further resection (see Figure 1, 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e6.\u0026nbsp; \u0026nbsp;Pararectal Space Development:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo Bilateral medial (\u003cem\u003eOkabayashi\u003c/em\u003e) pararectal spaces are developed to expose the lateral parametrium and pelvic nerves (see Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.\u0026nbsp; \u0026nbsp;Rectovaginal Dissection:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo The rectum is detached from the posterior uterus and \u003cem\u003ecul-de-sac\u003c/em\u003e performed using cold scissors to minimize thermal injury, and the rectovaginal space is opened with precision.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e8.\u0026nbsp; \u0026nbsp;Transection of Uterosacral Ligaments:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eo Fibrotic uterosacral ligaments are transected with care to preserve the \u003cem\u003ehypogastric nerves\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eUterine Skeletonization:\u003c/p\u003e\n\u003cp\u003eFull skeletonization of the uterus is achieved by systematically isolating the parametrial and paracervical tissues and detachment of the rectum from uterine torus facilitating safe and radical resection while sparing autonomic nerves.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e9.\u0026nbsp; \u0026nbsp;Completion of Hysterectomy\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total laparoscopic hysterectomy is completed following skeletonization.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBowel resection procedure steps (If indicated)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFollowing hysterectomy, the specimens—including the uterus, adnexa, and parametrial nodules—are removed transvaginally. The vaginal cuff is intentionally left open to allow subsequent extraction of the resected rectal segment. In patients with colorectal involvement, rectosigmoid resection was initially performed using the laparoscopic conventional technique (mini Pfannenstiel incision with Alexis retractor), and after several cases, the procedure was refined to use the Natural Orifice Specimen Extraction (NOSE) technique as described by Malzoni et al. [11,12], with slight modifications (see Figure 4,5). Bulky pelvic lymph nodes were removed when encountered.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe rectal part of surgery was always started with isolation of the \u003cem\u003einferior\u003c/em\u003e\u003cem\u003emesenteric artery (IMA\u003c/em\u003e\u003cstrong\u003e)\u003c/strong\u003e using monopolar hook and bilateral \u003cem\u003ehypogastric nerve\u003c/em\u003e dissection. Then mesorectum of the margin free segments were excised using advanced bipolar devices. For colorectal resection and anastomosis, the Covidien Endo GIA™ 60 mm Articulating Reload with Tri-Staple™ Technology (\u003cem\u003eMedtronic, Minneapolis, MN, USA\u003c/em\u003e) was utilized. (\u003cem\u003eSee Supplementary Video-1\u003c/em\u003e)\u003c/p\u003e\n\u003cp\u003eStatistical analysis for continuous variables was based on the Student t test and the Fisher exact test for categoric variables. The relative risk (RR) was also calculated to estimate the risk of having an event with its 95% confidence interval (CI). Statistical tests with p values \u0026lt;.05 were considered statistically significant. Analyses were performed with R software (version 4.2.1, R foundation for Statistical Computing, Vienna, Austria) and Stata 15.1 IC software (StataCorp LLC, College Station, TX).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 80 patients underwent nerve-sparing modified radical hysterectomy for DIE using the SkeletonDIE technique. Table 1 presents the demographic characteristics and endometriosis-related clinical features of the study population. The median age was 41 years (range, 34–55), and the median BMI was 27.0 kg/m² (range, 18.2–41.1). A notable proportion of patients (27.5%) had a history of previous gynecologic surgery, with 14.3% having undergone prior surgery for endometriosis. Majority reported severe pelvic pain symptoms, with mean VAS scores of 8.6 for dysmenorrhea and 7.4 for dyspareunia. Preoperative hormonal therapy had been administered in 84.4% of cases. Adenomyosis was identified in 88.7% of patients, and bilateral endometriomas were present in 51.2%.\u003c/p\u003e\n\u003cp\u003eIntraoperative details and surgical complexity are presented in Table 2. The mean operative time was 287 minutes (range, 123–670). Bilateral ureterolysis was performed in nearly 90% of cases. Dorsolateral parametrium excision was performed in 78.7% of patients. Rectal resection, mostly using the laparoscopic NOSE technique, was required in 20% of cases. Protective ileostomy and colostomy were performed in 3.7% (n=3) and 1.2% (n=1) of patients, respectively. According to the Querleu–Morrow classification of radical hysterectomy [13], Type B procedures were performed in 65% of cases and Type C1 in 35%. Surgical complexity was reflected by a mean AAGL score of 55, stage IV endometriosis, and extensive involvement across ENZIAN compartments (Table 2).\u003c/p\u003e\n\u003cp\u003eIntraoperative complications were observed in 3.7% of patients (n=3), including two bladder injuries and one internal iliac artery bleeding. All intraoperative complications were addressed intraoperatively. Bladder injuries were repaired primarily, and internal iliac artery bleeding was controlled using vascular clamping, ensuring preservation of the posterior branches. All procedures were completed laparoscopically without conversion to open surgery. Intraoperative and postoperative transfusion requirements were observed in 10% and 11.2% of patients, respectively.\u0026nbsp;No malignant pathology was detected on frozen section analysis.\u003c/p\u003e\n\u003cp\u003eThe mean hospital stay was 6 days\u0026nbsp;(3–21).\u0026nbsp;A total of 3.7% of patients (n=3) required admission to the intensive care unit (ICU).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patients were followed up for 6 to 24 months after surgery.\u0026nbsp;No patients in this case series required postoperative bladder catheterization. However, two individuals reported symptoms of bladder dysfunction—specifically urgency and features consistent with neurogenic bladder. Postoperative neuropathic symptoms were observed following surgery in two patients: one experienced severe burning pain in the entire leg, while the other reported paresthesia and numbness in the medial thigh. These neuropathic symptoms were managed conservatively with pregabalin, and both patients remain under follow-up in the neurology department.\u003c/p\u003e\n\u003cp\u003ePostoperative complications are presented in Table 3, with 7.4% classified as Clavien–Dindo grade III or higher\u0026nbsp;(see Table 4). A vesicorectal fistula developed on postoperative day eight in a 41-year-old patient (Case 1), necessitating relaparotomy with colostomy and nephrostomy placement. A 40-year-old patient (Case 2) experienced rectal anastomotic leakage on postoperative day 18, which was successfully managed with colonoscopic clip application. In Case 3, a submassive pulmonary embolism was diagnosed on the first postoperative day; the patient underwent interventional thrombolytic therapy targeting the pulmonary artery, followed by intensive care unit (ICU) monitoring. In Case 4, a rectovaginal fistula developed after colostomy closure in a patient who had initially received a prophylactic colostomy during rectal resection. This was managed with robot-assisted low anterior resection. Case 5 involved a 44-year-old patient who developed both a bowel thermal injury and ureteral stricture on postoperative day six, requiring relaparotomy, colostomy, and nephrostomy. \u0026nbsp;On postoperative day seven, one patient (Case 6) developed sepsis secondary to a pelvic abscess caused by \u003cem\u003ePrevotella bivia\u003c/em\u003e, which was successfully treated with laparoscopic drainage and intravenous antibiotic therapy [14]. Finally, in Case 7, an umbilical hernia was detected six months postoperatively; surgical repair was recommended, but the patient declined further intervention.\u003c/p\u003e\n\u003cp\u003eAll complications were managed with appropriate surgical or interventional procedures, and no postoperative mortality was observed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort of 80 patients with stage IV DIE who underwent nerve-sparing modified radical hysterectomy using the uterine skeletonization technique, we observed high rates of complete resection and a low rate of major complications, consistent with prior findings from established centers. According to the literature, serious postoperative complication rates for DIE surgery range from 1.2\u0026ndash;10.5%, depending on the degree of surgical radicality (including the extent of parametrial resection), whether hysterectomy was performed, and the type of bowel procedure applied\u0026mdash;such as rectal shaving, bowel resection, or stoma creation [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Therefore, complication rates vary based on these parameters, making direct comparisons challenging. In our series, where most patients underwent nerve-sparing modified radical hysterectomy, Clavien\u0026ndash;Dindo grade\u0026thinsp;\u0026ge;\u0026thinsp;III complications were observed in 7.4% of cases, which is comparable to the 10.5% rate reported by Bafort et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eIntraoperative complications\u003c/em\u003e\u003c/p\u003e\u003cp\u003eNo intraoperative bowel or ureteral injuries were encountered among the 80 cases. Bladder injury due to dense adhesions (n\u0026thinsp;=\u0026thinsp;2) was successfully repaired intraoperatively by the primary surgeon. A vascular complication occurred in one case (1.2%), where a parametrial nodule was densely adherent to the internal iliac artery, leading to significant bleeding during dissection. The hemorrhage was promptly controlled laparoscopically using a Hem-o-Lok vascular clamp, and the patient received an intraoperative blood transfusion.\u003c/p\u003e\u003cp\u003eDarlet et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] reported one intraoperative complication (1.9%) in a 52-patient series\u0026mdash;specifically, a hypogastric vein injury requiring conversion to laparotomy and transfusion. Intraoperative pelvic organ injuries\u0026mdash;including bowel, ureter, and bladder\u0026mdash;have been reported in 1.2\u0026ndash;5% of cases in the literature [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], with Uccella et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] noting a 1.7% conversion rate to laparotomy.\u003c/p\u003e\u003cp\u003e\u003cem\u003ePostoperative Complications\u003c/em\u003e\u003c/p\u003e\u003cp\u003ePostoperative bowel complications remain among the most serious and feared adverse events following DIE surgery, often necessitating relaparotomy or colostomy and resulting in significant morbidity for both patients and surgeons. However, in advanced-stage DIE\u0026mdash;particularly when the rectum is infiltrated\u0026mdash;such complications may be difficult to avoid.\u003c/p\u003e\u003cp\u003eIn our series, four bowel complications (5%) were observed. Two patients (2.5%) developed rectovesical and rectovaginal fistulas requiring relaparotomy and colostomy. One patient experienced an anastomotic leak, which was successfully treated with colonoscopic clip application, thereby avoiding the need for relaparotomy. Another patient developed a thermal bowel injury and concurrent ureteral stricture on postoperative day seven, managed with relaparotomy, colostomy, and nephrostomy.\u003c/p\u003e\u003cp\u003eThese outcomes are comparable with those in the literature. While Darlet et al. reported no rectovaginal fistulas in their 52-patient series [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], Bafort et al. noted a 1.8% rectovaginal fistula rate and a 2.9% bowel leakage rate in patients undergoing segmental bowel resection [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Roman et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and Minelli et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported bowel fistula rates of 3.4% and 3.7%, respectively, consistent with our 3.8% rate. Uccella et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] also reported a case of bowel perforation requiring open rectal resection. Malzoni et al. reported an anastomotic leakage rate of 1.6% and a rectovaginal fistula rate of 2.4% in their large series of patients undergoing segmental bowel resection for DIE [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eVoiding Dysfunction and Self-Catheterization\u003c/em\u003e\u003c/p\u003e\u003cp\u003eBladder dysfunction requiring self-catheterization is one of the most distressing complications after DIE surgery, significantly impacting postoperative quality of life. In our series, two patients (2.5%) experienced postoperative bladder dysfunction (urgency and atonic bladder), yet none required temporary or permanent self-catheterization.\u003c/p\u003e\u003cp\u003eIn contrast, Darlet et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and Rosati et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] reported postoperative voiding dysfunction requiring catheterization in approximately 13% of cases. Darlet et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] further detailed that 11.6% of patients required catheterization for less than 30 days, while 1.9% experienced persistent dysfunction beyond one month.\u003c/p\u003e\u003cp\u003eThanks to nerve-sparing techniques, we speculate that our low rate of voiding dysfunction may be attributed to the structured nature of the uterine skeletonization technique, which facilitates targeted parametrial dissection while preserving pelvic autonomic nerves. Additionally, unlike the en-bloc resection approach described by Rosati [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and Darlet [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], the individual excision of each parametrial nodule may contribute to minimizing the risk of nerve injury.\u003c/p\u003e\u003cp\u003e\u003cem\u003eOperating Time\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAlthough the uterine skeletonization technique improves surgical exposure, it did not result in shorter operative times in our series (mean: 287 minutes) compared to previously published data (Khazali et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]: 223 minutes; Darlet et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]: 265 minutes). This discrepancy may be attributed to the limited endometriosis experience of assisting residents, the technical challenges associated with using a 30-degree laparoscopic camera, and the advanced disease stage, which necessitated bilateral ureterolysis (86%) and frequent bowel or vaginal resections. Nevertheless, all procedures were successfully completed laparoscopically without conversion.\u003c/p\u003e\u003cp\u003e\u003cem\u003eStrengths and Limitations\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThis study was conducted at a single, high-volume tertiary endometriosis center, with all surgeries and follow-up evaluations performed by the same experienced surgeon. Although not a novel technique per se, uterine skeletonization represents a strategic refinement of previously established surgical steps [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The primary limitation of this study is its retrospective design. Future prospective, multicenter randomized trials are warranted to further validate the outcomes and long-term benefits of the uterine skeletonization approach in DIE surgery.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings support the feasibility and safety of nerve-sparing radical surgery using the uterine skeletonization technique in advanced DIE cases without fertility desire. This approach enables systematic exposure of critical pelvic structures while minimizing nerve injury, as reflected by the absence of catheter-dependent bladder or rectal dysfunction.\u003c/p\u003e\u003cp\u003eEach DIE case presents unique intraoperative challenges, and surgical success relies not only on anatomical expertise but also on the surgeon\u0026rsquo;s capacity for creativity and refined intraoperative problem-solving.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDIE: Deep Infiltrating Endometriosis; MRI: Magnetic Resonance Imaging; VAS: Visual Analog Scale; BMI: Body Mass Index; NOSE: Natural Orifice Specimen Extraction; ICU: Intensive Care Unit; AAGL: American Association of Gynecologic Laparoscopists; Clavien\u0026ndash;Dindo: Clavien\u0026ndash;Dindo Classification of Surgical Complications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Başakşehir Çam and Sakura City Hospital (approval number: KAEK/11.09.2024.207) and was retrospectively registered at ClinicalTrials.gov (identifier: NCT06802900). Written informed consent was obtained from all participants before surgery. This study was carried out in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to institutional data protection policies but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBK designed the study, performed all surgeries, and supervised manuscript preparation. AI contributed to data collection and assisted in surgical procedures. MSÖ reviewed all preoperative MRI studies and contributed to data interpretation. SY performed all bowel resections and contributed to the surgical protocol. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the operating room staff and anesthesiology team at Başakşehir Çam and Sakura City Hospital for their consistent support in complex surgical procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBK is a dedicated surgeon specializing in advanced deep infiltrating endometriosis (DIE) surgery. He serves as the head of the Endometriosis Clinic at Başakşehir Çam and Sakura City Hospital, one of Istanbul’s largest tertiary referral centers, which accepts patients from across Istanbul as well as various provinces throughout Türkiye. SY is a colorectal surgeon experienced in performing rectal resections and complex bowel surgeries in collaboration with gynecologic teams. MSÖ is a radiologist who specializes in detailed interpretation of MRI scans for deep endometriosis and contributes to preoperative surgical planning. AI is a skilled gynecologic surgeon who actively assists in deep endometriosis surgeries and contributes to intraoperative management\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKoninckx PR, Ussia A, Adamyan L, et al. Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012;98(3):564\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.fertnstert.2012.07.1061\u003c/span\u003e\u003cspan address=\"10.1016/j.fertnstert.2012.07.1061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCornillie FJ, Oosterlynck D, Lauweryns JM, Koninckx PR. Deeply infiltrating pelvic endometriosis: histology and clinical significance. Fertil Steril. 1990;53(6):978\u0026ndash;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0015-0282(16)53570-5\u003c/span\u003e\u003cspan address=\"10.1016/s0015-0282(16)53570-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKeckstein J, Saridogan E, Ulrich UA, et al. The #Enzian classification: A comprehensive non-invasive and surgical description system for endometriosis. Acta Obstet Gynecol Scand. 2021;100(7):1165\u0026ndash;75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/aogs.14099\u003c/span\u003e\u003cspan address=\"10.1111/aogs.14099\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBazot M, Dara\u0026iuml; E. Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis. Fertil Steril. 2018;109(3):389\u0026ndash;97. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.fertnstert.2018.01.024\u003c/span\u003e\u003cspan address=\"10.1016/j.fertnstert.2018.01.024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCeccaroni M, Clarizia R, Bruni F, et al. Nerve-sparing laparoscopic eradication of deep endometriosis with segmental rectal and parametrial resection: the Negrar method. A single-center, prospective, clinical trial. Surg Endosc. 2012;26(7):2029\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00464-012-2153-3\u003c/span\u003e\u003cspan address=\"10.1007/s00464-012-2153-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYabuki Y, Asamoto A, Hoshiba T, et al. Radical hysterectomy: An anatomic evaluation of parametrial dissection. Gynecol Oncol. 2000;77(1):155\u0026ndash;63. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1006/gyno.1999.5723\u003c/span\u003e\u003cspan address=\"10.1006/gyno.1999.5723\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFujii S, Takakura K, Matsumura N et al. Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. Gynecol Oncol. 2007;107(1):4\u0026ndash;13. doi: 10.1016/j.ygyno.2007.08.076. PMID: 17905140.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCeccaroni M, Clarizia R, Roviglione G. Nerve-sparing Surgery for Deep Infiltrating Endometriosis: Laparoscopic Eradication of Deep Infiltrating Endometriosis with Rectal and Parametrial Resection According to the Negrar Method. J Minim Invasive Gynecol. 2020;27(2):263\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jmig.2019.09.002\u003c/span\u003e\u003cspan address=\"10.1016/j.jmig.2019.09.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWorking group of ESGE, ESHRE, and, Keckstein WES, Becker J, Canis CM. Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis. Hum Reprod Open. 2020;12(1):hoaa002. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/hropen/hoaa002\u003c/span\u003e\u003cspan address=\"10.1093/hropen/hoaa002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMalzoni M, Rasile M, Coppola M, et al. Totally Laparoscopic Resection with Transanal Natural Orifice Specimen Extraction for Deep Endometriosis Infiltrating the Rectum. J Minim Invasive Gynecol. 2022;29(1):19. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jmig.2021.07.015\u003c/span\u003e\u003cspan address=\"10.1016/j.jmig.2021.07.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMalzoni M, Di Giovanni A, Coppola M, et al. Total Laparoscopic Segmental Resection with Transanal Natural Orifice Specimen Extraction for Treatment of Colorectal Endometriosis: Descriptive Analysis From the TrEnd Study Database. J Minim Invasive Gynecol. 2025;32(3):240\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jmig.2024.10.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jmig.2024.10.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQuerleu D, Cibula D, Abu-Rustum NR. 2017 Update on the Querleu-Morrow Classification of Radical Hysterectomy. Ann Surg Oncol. 2017;24(11):3406\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1245/s10434-017-6031-z\u003c/span\u003e\u003cspan address=\"10.1245/s10434-017-6031-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaya B, Ince A, Sam Ozdemir M, Yuksel S. Laparoscopic Management of an Early Postoperative Pelvic Abscess Caused by Prevotella bivia Following a Deep Infiltrating Endometriosis Surgery. Cureus. 2024; 6;16(8):e66315. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.66315\u003c/span\u003e\u003cspan address=\"10.7759/cureus.66315\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhazali S, Gorgin A, Mohazzab A, et al. Laparoscopic excision of deeply infiltrating endometriosis: a prospective observational study assessing perioperative complications in 244 patients. Arch Gynecol Obstet. 2019;299(6):1619\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-019-05144-6\u003c/span\u003e\u003cspan address=\"10.1007/s00404-019-05144-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDarlet G, Margueritte F, Drioueche H, Fauconnier A. Laparoscopic Modified Radical Hysterectomy for Severe Endometriosis: A Single-Center Case Series. J Minim Invasive Gynecol. 2024;31(5):423\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jmig.2024.01.022\u003c/span\u003e\u003cspan address=\"10.1016/j.jmig.2024.01.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBafort C, van Elst B, Neutens S, et al. Outcome after surgery for deep endometriosis infiltrating the rectum. Fertil Steril. 2020;113(6):1319\u0026ndash;e13273. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.fertnstert.2020.02.108\u003c/span\u003e\u003cspan address=\"10.1016/j.fertnstert.2020.02.108\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRosati A, Pavone M, Campolo F, et al. Surgical and functional impact of nerve-sparing radical hysterectomy for parametrial deep endometriosis: a single centre experience. Facts Views Vis Obgyn. 2022;14(2):121\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.52054/FVVO.14.2.016\u003c/span\u003e\u003cspan address=\"10.52054/FVVO.14.2.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCasarin J, Ghezzi F, Mueller M, et al. Surgical Outcomes and Complications of Laparoscopic Hysterectomy for Endometriosis: A Multicentric Cohort Study. J Minim Invasive Gynecol. 2023;30(7):587\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jmig.2023.03.018\u003c/span\u003e\u003cspan address=\"10.1016/j.jmig.2023.03.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUccella S, Marconi N, Casarin J, et al. Impact of endometriosis on surgical outcomes and complications of total laparoscopic hysterectomy. Arch Gynecol Obstet. 2016;294(4):771\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-016-4115-9\u003c/span\u003e\u003cspan address=\"10.1007/s00404-016-4115-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoman H, Bridoux V, Merlot B, et al. Risk of bowel fistula following surgical management of deep endometriosis of the rectosigmoid: a series of 1102 cases. Hum Reprod. 2020;1(7):1601\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/humrep/deaa131\u003c/span\u003e\u003cspan address=\"10.1093/humrep/deaa131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMinelli L, Ceccaroni M, Ruffo G, et al. Laparoscopic conservative surgery for stage IV symptomatic endometriosis: short-term surgical complications. Fertil Steril. 2010;94(4):1218\u0026ndash;22. Epub 2009 Dec 6. PMID: 19969292.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTanaka Y, Kuratsune K, Otsuka A, et al. Total laparoscopic hysterectomy with posterior cul-de-sac obliteration: step-by-step procedures based on precise anatomical landmarks. Arch Gynecol Obstet. 2024;310(3):1795\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-024-07614-y\u003c/span\u003e\u003cspan address=\"10.1007/s00404-024-07614-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Deep infiltrating endometriosis, Modified radical hysterectomy, Uterine skeletonization, Nerve-sparing surgery, Bowel resection, Pelvic autonomic nerves, Natural orifice specimen extraction (NOSE)","lastPublishedDoi":"10.21203/rs.3.rs-7098525/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7098525/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eDeep infiltrating endometriosis (DIE) involving the posterior compartment and parametrium often necessitates modified radical hysterectomy, and in cases of extensive rectal invasion, concomitant segmental bowel resection may be required. However, conventional approaches may endanger pelvic autonomic nerves. This study aimed to evaluate the intraoperative and early postoperative outcomes of the uterine skeletonization technique in nerve-sparing modified radical hysterectomy for stage IV DIE.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThis retrospective observational study included 80 patients with stage IV DIE who underwent nerve-sparing modified radical hysterectomy using the SkeletonDIE technique between 2022 and 2024 at a tertiary endometriosis center in Istanbul, T\u0026uuml;rkiye. The type of hysterectomy (Type B or C1), additional procedures (e.g., rectal resection with NOSE technique), and perioperative complications were documented. Descriptive statistics were used, and outcomes were reported as medians, ranges, and percentages.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe median age was 41 years and BMI 27.0 kg/m\u0026sup2;. Preoperative hormonal therapy was administered to 84.4% of patients. Adenomyosis was found in 88.7% and bilateral endometriomas in 51.2%. Mean VAS scores were 8.6 for dysmenorrhea and 7.4 for dyspareunia. Modified radical hysterectomy type B and C1 were performed in 65% and 35%, respectively. Bilateral ureterolysis was completed in 86%, dorsolateral parametrium excision in 78% (bilaterally in 19%), and rectal resection using NOSE technique in 20%. Severe postoperative complications (Clavien\u0026ndash;Dindo\u0026thinsp;\u0026ge;\u0026thinsp;III) occurred in 7.4% of cases, while intraoperative complications occurred in 3%. No conversions to laparotomy or mortalities were reported.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe uterine skeletonization technique is a feasible and safe nerve-sparing approach to modified radical hysterectomy in patients with advanced DIE. It enables radical excision of disease while minimizing damage to pelvic autonomic nerves. Future prospective studies are needed to assess long-term functional outcomes.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrial Registration\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThis study was retrospectively registered at ClinicalTrials.gov (identifier: NCT06802900; registration date: January 31, 2025).\u003c/p\u003e","manuscriptTitle":"Uterine Skeletonization in Modified Radical Hysterectomy for Deep Infiltrative Endometriosis: The SkeletonDIE Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-25 01:32:38","doi":"10.21203/rs.3.rs-7098525/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cf847830-e12f-4ef7-9885-392bf36c6817","owner":[],"postedDate":"September 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-08T08:26:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-25 01:32:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7098525","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7098525","identity":"rs-7098525","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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