{"paper_id":"60ff4e0f-72d9-45be-926a-dbca3987a027","body_text":"1\nTitle \nSelective Removal of Endometriotic Lesions Using CUSA Clarity in Ovarian Endometriomas: \nA Case-Based Histopathological Study \n \nAuthors: \nTatsuhito Kanda, MD, PhD, Takashi Hosono, MD, PhD, Ai Sato, Yukari Maeda, Iwao \nYasoshima, MD, Yuya Sakai, MD, Haruki Kasama, MD, Kayo Kayahashi, MD, PhD, \nKyosuke Kagami, MD, PhD, Takashi Iizuka, MD, PhD, Kaoru Abiko, MD, PhD \nAffiliation: \nDepartment of Obstetrics and Gynecology, Graduate School of Medical Sciences, \nKanazawa University, Kanazawa, Ishikawa, Japan \n \nCorresponding Author: \nKaoru Abiko, MD, PhD \nDepartment of Obstetrics and Gynecology, Kanazawa University \n13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan \nEmail: kaoruvc@gmail.com\n \nAbstract \nObjective: To evaluate the feasibility of selective removal of endometriotic lesions using the \nCavitron Ultrasonic Surgical Aspirator (CUSA® Clarity) in ovarian endometriomas, with a \nfocus on histological preservation of normal ovarian tissue. \nMethods: We analyzed tissue from a woman in her early 30s who underwent laparoscopic \nsurgery for an ovarian endometrioma measuring approximately 7 cm after preoperative \ndienogest therapy. Resected cyst wall specimens were divided into five parts, each assigned to a \nTissue Select® setting (0–4). Samples were scraped with CUSA, followed by histological and \nimmunohistochemical evaluation (H&E, Sirius Red, CK7, CD10). \nResults: Endometriotic lesions (epithelial and stromal cells) were effectively removed across all \nsettings. At higher Tissue Select settings (3–4), preservation of surrounding tissue was superior, \nwith minimal vacuolization compared to lower settings (0–2). Primordial follicles were \nobserved approximately 600 \nμ m beneath the surface, highlighting the importance of limiting \ncavitation depth. \nConclusion: CUSA Clarity enabled selective removal of endometriotic lesions with relative \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.\n\n 2\npreservation of normal ovarian tissue, particularly at higher Tissue Select settings. This novel \napproach may represent a fertility-preserving alternative to cystectomy or laser ablation in the \nmanagement of ovarian endometriomas. Further studies are warranted. \nKeywords: Endometriosis; Ovarian Endometrioma; Ultrasonic Surgical Devices; Fertility \nPreservation; Histological Techniques \n \nIntroduction \nSurgical treatment is often considered for ovarian endometriomas in cases complicating \ninfertility to improve fertility (1). In ovarian endometriomas, cystectomy can inadvertently \nexcise the normal ovarian tissue, causing bleeding, local hypoxia, and thermal injury from \nhemostatic energy devices, all of which may impair ovarian function (2). Recently, laser \nablation has been reported to better preserve ovarian function than cystectomy, as indicated by \nhigher postoperative antral follicle counts and anti-Müllerian hormone (AMH) levels (3). \nAlthough its efficacy on pregnancy and recurrence rates remain inconclusive, \nfertility-preserving surgical approaches are increasingly sought. \nCavitron Ultrasonic Surgical Aspirator (CUSA®) is a surgical device that uses ultrasonic \ncavitation to selectively fragment and aspirate soft tissue. It preferentially targets water-rich \ntissues such as fat while sparing collagen-rich structures. We hypothesized that the CUSA \nsystem, particularly the Clarity model equipped with a five-step Tissue Select® mode, could \nselectively remove endometriotic lesions while minimizing damage to normal ovarian tissue. To \ndate, only one report has described its use for ovarian endometriomas, without histological \nevaluation (4). We histologically evaluated the selective effect of CUSA Clarity on \nendometriotic and ovarian tissue in surgical specimens.\n \nMethods \nThis exploratory study used tissue obtained from a single surgical case (Fig. 1). A woman in her \nearly 30s underwent laparoscopic cystectomy for an ovarian endometrioma approximately 7 cm \nin diameter, following one month of preoperative hormone therapy with dienogest. The cyst \nwall was primarily resected using forceps and scissors, with minimal energy device use. After \nconfirming the absence of solid components, part of the resected cyst wall was sampled for \nanalysis. The specimen was divided into five parts, each assigned to a Tissue Select setting \n(0–4), a mode available in the CUSA Clarity system. The central region of each sample was \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\n 3\ngently scraped using CUSA (Supplemental Video). The samples were fixed in formalin and \nparaffin embedded. H&E staining, Sirius Red staining, and immunohistochemistry (CK7, \nCD10) were performed. Histological assessment was performed to evaluate the removal of \nendometriotic lesions and the preservation of normal ovarian tissue. This study was approved by \nthe Clinical Research Ethics Committee of Kanazawa University (approval number: 114898-1), \nand a written informed consent was obtained. \n \nResults \nImmunohistochemistry confirmed epithelial (CK7), stromal cells (CD10) of endometriosis, and \na dense collagenous layer (Sirius Red) beneath the lesions (Supplemental Fig. 1). CUSA, using \nthe Tissue Select setting 4, effectively removed the epithelial and stromal cells of endometriosis \nfrom the scraped area without tissue damage (Fig. 2). In all Tissue Select settings, endometrioid \nlesions positive for CD7 and CD10 were effectively removed from the scraped areas \n(Supplemental Fig. 2). Residual lesions were observed at the scraped margins, confirming the \npresence of disease at the non-scraped side of the margin in each sample\n (Supplemental Fig. \n3).  \nDamage to normal ovarian tissue varied by Tissue Select setting (Supplemental Fig. 4). At \nsetting 0, vacuolization and tissue degeneration extended to depths of 200–400 \nμ m. Similar \neffects were observed at settings 1–2, generally within 200 μ m. At settings 3–4, effects were \nmore limited. \nIn some samples, primordial follicles were identified approximately 600 \nμ m from the surface, \nunderscoring the importance of limiting cavitation and thermal effects to superficial layers \n(Supplemental Fig. 5). \n \nDiscussion \nThis exploratory study provides preliminary histopathological evidence that the Cavitron \nUltrasonic Surgical Aspirator (CUSA® Clarity) may enable selective removal of endometriotic \nlesions in ovarian endometriomas while preserving adjacent ovarian tissue. At higher Tissue \nSelect settings (3–4), epithelial and stromal components of endometriosis were effectively \nremoved, whereas damage to surrounding collagen-rich stroma was limited. Importantly, \nprimordial follicles were identified at depths as shallow as 600 \nμ m beneath the cyst wall, \nunderscoring the clinical relevance of minimizing tissue injury during fertility-preserving \nsurgery. \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\n 4\n \nConventional cystectomy has long been considered the standard surgical approach for ovarian \nendometriomas but carries the inherent risk of excising normal ovarian tissue together with the \ncyst wall. This can lead to decreased ovarian reserve, as reflected by reductions in antral follicle \ncounts and serum AMH levels postoperatively (5, 6). Energy-based hemostasis may further \nexacerbate cortical injury through thermal effects. In contrast, ablative techniques such as CO\n/i2  \nlaser or plasma energy vaporization have been reported to better preserve ovarian function, \nthough concerns remain regarding recurrence rates and long-term fertility outcomes (3, 7). \nRec en t  st udies  eva lu ating  the  d epth of t is s u e ablat io n wi t h al t er na t iv e  en er gy \nsou rc e s  p rovi de us ef ul  b enchm ark s f o r fe rtili ty- pres er v in g  sur ger y. I n a p il o t \nstu dy  o f ar g o n pl as ma c o a gul atio n for  o va r i an  e nd ometr io m a s (A PC -E N D O),  t he m e a n  \ndep th  o f a blat io n was  r e p or ted t o  be a bo ut  0. 8 m m , sugge st ing t ha t la se r -  an d \npla sm a - bas ed m od al itie s ca n achi ev e contr ol l e d ab lati on  t o a  limi te d depth  w it h i n  \nthe  cys t w a ll  (8) . Simi larl y,  a  p rospe ct ive mu lt i ce nt er tri al  i nves ti ga t in g di o d e  \nlas er  v apo riza ti on of  o v a ri an en d ometr io ma s  (OM A l as er) d em onstr at ed a blat ion  \ndep th s  of  ar ound  5 00  μ m.  I mp o r tan t l y,  t hi s  stu dy  a l s o rep o r te d favor a ble o ut co m es  \nin  te rm s of  ovari an  r es e r ve  r eco v e ry,  f er t i li ty  p reser va t i on , an d lo w  re c ur re n c e  \nrat es ,  eve n in  p atien ts  w it h adv a nced en do m et ri o s is  (9).\n \n \nHistologic analysis has shown that the penetration of endometriosis into cyst walls is highly \nvariable, with a mean of approximately 0.6mm ±  0.4mm and 99% of cases measuring within \n1.5 mm, but occasionally reaching up to 2.0 mm (10). This variability has important surgical \nimplications. In cysts with relatively thick walls, laser vaporization may not penetrate deeply \nenough to eradicate endometriotic tissue completely, resulting in residual disease. Conversely, \nwhen the cyst wall is thin, laser ablation may extend too deeply and risk excessive thermal \ninjury to the ovarian cortex. By contrast, the mechanism of CUSA—selective disruption of \nwater-rich endometriotic tissue with preservation of collagen-rich fibrotic structures—may \nprovide an intrinsic safety advantage. Cavitation tends to halt at fibrotic boundaries, thereby \nreducing the likelihood of over-treatment and minimizing collateral damage to adjacent healthy \novarian tissue. In the current study, our pathological examination demonstrated that CUSA \ncompletely removed endometriotic lesions while preserving the ovarian \nparenchyma—composed of ovarian fibroblasts covering primordial follicles—without damage. \n \nThis study has several limitations. The analysis was based on a single surgical specimen, \nwithout correlation to postoperative ovarian reserve or fertility outcomes. The selective effect \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\n 5\nwas demonstrated only ex vivo, and the in vivo impact on hemostasis, bleeding risk, and \nrecurrence remains unknown. Moreover, optimal CUSA settings for balancing lesion removal \nwith tissue preservation require further validation. \n \nIn conclusion, this proof-of-concept study indicates that CUSA Clarity, particularly at higher \nTissue Select settings, has the potential to achieve fertility-preserving removal of endometriotic \nlesions in ovarian endometriomas. Further prospective studies with larger patient cohorts and \nclinical outcome measures are warranted to establish its safety and efficacy compared with \nestablished surgical modalities. \n \nEthics \nThis study was approved by the Clinical Ethics Committee of Kanazawa University (IRB \napproval number 114898-1). Written informed consent was obtained from the patient. \nFunding \nNo external funding was received for this study. \nConflicts of Interest \nThe authors declare no conflicts of interest relevant to this article. \nData Availability \nData are available from the corresponding author upon reasonable request. \nReferences \n1. Duffy JMN, Arambage K, Correa FJS, Olive D, Farquhar C, Garry R, et al. \n Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev 2014;CD011031. \n2. Matsuzaki S, Houlle C, Darcha C, Pouly JL, Mage G, Canis M. \n Analysis of risk factors for the removal of normal ovarian tissue during laparoscopic \ncystectomy for ovarian endometriosis. Hum Reprod 2009;24:1402–6. \n3. Adamyan L, Kasyan V, Pivazyan L, Isaeva S, Avetisyan J. \n Laser vaporization compared with other surgical techniques in women with ovarian \nendometrioma: a systematic review and meta-analysis. Arch Gynecol Obstet \n2023;308:413–25. \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\n 6\n4. Vasquez JM, Eisenberg E, Osteen KG, Hickerson D, Diamond MP. \n Laparoscopic ablation of endometriosis using the cavitational ultrasonic surgical aspirator. \nJ Am Assoc Gynecol Laparosc 1993;1:1–4. \n5. Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. \n The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle \ncount: a systematic review and meta-analysis. Hum Reprod 2014;29:2190–2198. \n6. Younis JS, Shapso N, Ben-Sira Y , Nelson SM, Izhaki I. \n Endometrioma surgery: a systematic review and meta-analysis of the effect on antral \nfollicle count and anti-Müllerian hormone. Am J Obstet Gynecol 2022;226:33–51.e7. \n7. Candiani M, Ottolina J, Posadzka E, Ferrari S, Castellano LM, Tandoi I, et al. \n Assessment of ovarian reserve after cystectomy versus ‘one-step’ laser vaporization in the \ntreatment of ovarian endometrioma: a small randomized clinical trial. Hum Reprod \n2018;33:2205–11. \n8. Ferrari SM, Dolci C, Taccagni G, Congia C, Ottolina J, Schimberni M, Bartiromo L, \nCandiani M. \n Histologic findings from ablation of ovarian endometriomas using argon plasma \ncoagulation (APC-ENDO): a pilot study. Eur J Obstet Gynecol Reprod Biol 2025;295:1–7. \n9. D’Alterio MN, Nappi L, Vitale SG, Agus M, Fanni D, Malzoni M, et al. \n Evaluation of ovarian reserve and recurrence rate after DWLS diode laser ovarian \nendometrioma vaporization (OMAlaser): a prospective, single-arm, multicenter clinical trial. \nJ Minim Invasive Gynecol 2025;32:279–87. \n10. Muzii L, Bianchi A, Bellati F, Cristi E, Pernice M, Zullo MA, et al. \n Histologic analysis of endometriomas: what the surgeon needs to know. Fertil Steril \n2007;87:362–6. \n \nFigure legends \nFigure 1. Overview of study design. \nTissue from a laparoscopically resected ovarian endometrioma was divided into five parts and \nassigned to different Tissue Select settings (0–4) of the CUSA Clarity system. The central \nregion of each specimen was gently scraped with CUSA and processed for histological analysis, \nincluding H&E, Sirius Red, and immunohistochemical staining (CK7 and CD10). \n \nFigure 2. Histological findings at Tissue Select setting 4. \n(A) Scraped margin showing residual endometriotic tissue on the unscraped side (to the left) \nwith preserved staining quality. \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\n 7\n(B) Central area of the scraped region showing minimal tissue damage and effective removal of \nthe endometriotic lesion. \nMain images were taken at ×200 magnification. Scale bar = 200\n/i2μ m.  \nThe upper right image shows CK7 immunostaining at ×10 magnification.  \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\nPathological assessment\nCUSA clarity\n・ Tissue Select 0\n・ Tissue Select 1\n・ Tissue Select 2\n・ Tissue Select 3\n・ Tissue Select 4\nTissue \nFragmentation \nEffect high\nlow\nTissue \nSelectivity\nhigh\nlow\nStudy Design A woman in her early 30s underwent \na cystectomy for an ovarian endometrioma\nCentral part of the specimen \ngently scraped with CUSA\nFormalin fixation\nSpecimen\nDissect along the red line\nFigure 1\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint \n\nTissue Select 4 \nA\nB\nA B\nH&E CK7 CD10 Sirius Red\nFigure 2\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)\nThe copyright holder for this preprint this version posted October 15, 2025. ; https://doi.org/10.1101/2025.10.12.25334539doi: medRxiv preprint","source_license":"CC0","license_restricted":false}