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Journal of Clinical Medicine

Review Ultrasound of the Uterosacral , , and Paracervix: Disagreement in Terminology between Imaging Anatomy and Modern Gynecologic Surgery

Marco Scioscia 1,* , Arnaldo Scardapane 2 , Bruna A. Virgilio 3, Marco Libera 3, Filomenamila Lorusso 2 and Marco Noventa 4

1 Unit of Gynecological Surgery, Mater Dei Hospital, 70125 Bari, Italy 2 Section of Diagnostic Imaging, Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70100 Bari, Italy; [email protected] (A.S.); [email protected] (F.L.) 3 Department of Obstetrics and Gynecology, Policlinico Hospital, 35031 Abano Terme, Italy; [email protected] (B.A.V.); [email protected] (M.L.) 4 Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35121 Padua, Italy; [email protected] * Correspondence: [email protected]

Abstract: Ultrasound is an effective tool to detect and characterize lesions of the , parametrium, and paracervix. They may be the site of diseases such as and the later stages of cervical cancer. Endometriosis and advanced stages of cervical cancer may infiltrate the parametrium and may also involve the ureter, resulting in a more complex surgery. New functional, surgical anatomy requires the complete diagnostic description of retroperitoneal spaces and tissues   that contain vessels and . Most endometriosis lesions and cervical cancer spread involve the cervical section of the uterosacral ligament, which is close to tissues, namely the parametrium Citation: Scioscia, M.; Scardapane, and paracervix, which contain vessels and important nerves and anastomoses of the inferior A.; Virgilio, B.A.; Libera, M.; Lorusso, F.; Noventa, M. Ultrasound of the hypogastric plexus. Efferent fibers of the plexus travel to the , , rectovaginal ligament, Uterosacral Ligament, Parametrium, deep vesicouterine ligament, and bladder. These efferent fibers are essential for bladder and rectal and Paracervix: Disagreement in functionality so tailored nerve-sparing surgery became a standard approach for treating deep infiltrat- Terminology between Imaging ing endometriosis and cervical cancer. An accurate diagnosis by ultrasound has significant clinical Anatomy and Modern Gynecologic impact and is important for appropriate treatment. In this article, we try to establish a common Surgery. J. Clin. Med. 2021, 10, 437. terminology between imaging diagnostic and modern surgical anatomy. https://doi.org/10.3390/jcm10030437 Keywords: endometriosis; cervical cancer; ultrasound; anatomy; ureter; nerves; hypogastric nerve Academic Editor: Amerigo Vitagliano Received: 29 November 2020 Accepted: 19 January 2021 Published: 23 January 2021 1. Introduction

Publisher’s Note: MDPI stays neutral The uterosacral (USLs) are extraperitoneal structures that extend backward with regard to jurisdictional claims in from the posterior surface of the and upper to the second-to-fourth sacral published maps and institutional affil- vertebrae, forming the lateral boundaries of the rectouterine and rectovaginal spaces. They iations. are composed mainly of connective tissue along with vessels and splanchnic nerve fibers [1]. The USLs are surrounded by the paracervical and parametrial tissues, which are fibrous and fatty connective tissues rich with vessels and nerves. These structures can be clinically evaluated by a combined rectovaginal examination and by ultrasound, and they may be the site of diseases such as endometriosis and the later stages of cervical cancer. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Endometriosis is a common, chronic, and debilitating gynecological condition that This article is an open access article affects between 5% and 15% of women of reproductive age [2,3]. It is characterized by the distributed under the terms and growth of tissue that looks and acts like endometrial tissue, exhibiting the same response conditions of the Creative Commons to hormonal changes; however, this abnormal tissue growth occurs outside the uterus, Attribution (CC BY) license (https:// usually on other organs inside the and in the . These growths, creativecommons.org/licenses/by/ called endometriosis implants, lead to local inflammatory reactions that, in turn, promote a 4.0/). fibrotic reaction and the formation of adhesions, which prevent organs from sliding along

J. Clin. Med. 2021, 10, 437. https://doi.org/10.3390/jcm10030437 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 437 2 of 11

each other normally and can result in an altered normal pelvic anatomy [4–6]. This cascade of events often causes menstrual and/or chronic , , or malfunction of the affected abdominopelvic organs [2]. Endometriosis of the uterosacral ligament (USL) is a leading cause of deep and pelvic pain [7,8], and large endometrial nodules may also involve the parametrium and the ureter, resulting in a more complex surgery [4,9]. The posterior pelvic compartment, and the USL specifically, have been reported to be among the most common locations for endometriosis lesions [10,11]. In a study of patients with all stages of endometriosis, Chapron et al. [11] reported a prevalence of USL endometriosis of about 69%. In 83% of cases, USL endometriosis was found as an isolated lesion (study population 241, number of lesions 344) [11]. We previously studied a large cohort of patients with ASRM-stage IV endometriosis (study population 1548; number of lesions 10,466) [10,12] and reported a USL endometriosis prevalence of about 52%, with a parametrial/paracervical involvement in 25% of cases. Cervical cancer arises from the cervix and may invade adjacent structures, such as the vagina and the paracervical tissue, as it progresses. From the International Federation of Gynecology and Obstetrics (FIGO) stage IIB onwards, the cancer may spread further to the USLs and to more distant organs [13]. The estimated incidence of cervical cancer is of 15.7 per 100,000 women, although incidence varies widely among countries, with a gener- ally high prevalence of early-stage cervical cancer due to cervical screening programs [14]. Extracervical cancerous lesions require a more aggressive treatment and are associated with higher case-fatality rates [14,15]. Here, we discuss the potential for using ultrasound to detect endometrial or cancerous lesions, and we emphasize the importance of a correct diagnosis for optimizing treatment (modern functional surgery) and preventing severe surgical complications.

2. Discrepancies between the anatomical terminology used in imaging diagnostic and modern gynecological surgery was reported [16,17]. Surgeons have developed a different nomenclature from classical anatomical terminology for pelvic retroperitoneal spaces and the connective tissue bundles to describe in detail surgical procedures [16–18]. In ultrasound and magnetic resonance imaging (MRI), the pelvic connective tissue covered with the is identified in general as parametrium and cardinal and uterosacral ligaments and this hinders communication between diagnosis and treatment of pelvic pathologies. In fact, anatomical structures that are of potential clinical interest for functional- sparing surgery (i.e., the paracervical tissue) are often neglected in imaging reports. The purpose of this paragraph was to meet pelvic diagnostic images with new surgical anatomy.

2.1. The Uterosacral Ligament The uterosacral ligaments are retroperitoneal structures that extend posteriorly from the uterine cervix to , defining the lateral boundaries of the rectouterine and recto- vaginal spaces (Figure1). From an anatomical perspective, the USL can be divided into three parts: cervical, intermediate, and sacral sections [1]. The cervical section is composed of dense connective tissue containing small blood vessels and small branches of the inferior hypogastric plexus (IHP).

2.2. The Parametrium The parametrium is the fibrous and fatty connective tissue that surrounds the uterus. It is bordered laterally by the internal iliac vessels, medially by the uterus, superiorly by the peritoneum, and inferiorly by the ureter. This tissue contains the uterine artery and the superficial uterine vein [17]. J. Clin. Med. 2021, 10, x FOR PEER REVIEW 3 of 11 J. Clin. Med. 2021, 10, 437 3 of 11

Figure 1. Anatomical definitiondefinition of the uterosacraluterosacral ligament,ligament, parametrium,parametrium, paracervix, and paracolpium. ( A) shows the frontal and (B) the upper view of thethe pelvicpelvic posteriorposterior compartment.compartment. Abbreviations: C, cervix; CL, ; PC, paracervix; PCl, paracolpium; PM, parametrium; PSF, presacral ; R, rectum; U, uterus; Ur, ureter; USL, uterosacral paracervix; PCl, paracolpium; PM, parametrium; PSF, presacral fascia; R, rectum; U, uterus; Ur, ureter; USL, uterosacral ligament; UtA, uterine artery; UtV, uterine vein. ligament; UtA, uterine artery; UtV, uterine vein. 2.2. The Parametrium 2.3. TheThe Paracervix parametrium is the fibrous and fatty connective tissue that surrounds the uterus. It is borderedThe paracervix laterally is by the the fibrous internal and iliac fatty vessels, tissue medially that lies by beneath the uterus, the superiorly parametrium by the(Figure peritoneum,1 )[18]. Like and the inferiorly parametrium, by the ureter. it is bordered This tissue laterally contains by the the internal uterine iliac artery vessels, and thebut superficial its medial borderuterine isvein the [17]. upper two-thirds of the vaginal wall and the insertion of the USL. It is the upper part of the paracolpium that contains important functional nerves and 2.3.vessels. The Paracervix The upper limit of the paracervix is the ureter and the lower limit is the levator ani muscleThe paracervix and the presacralis the fibrous fascia. and The fatty paracervix tissue that contains lies beneath the inferior the parametrium vesical artery, (Figure the 1)vaginal [18]. Like artery, the the parametrium, proximal part it ofis thebordered deep uterine laterally vein, by thethe pelvicinternal splanchnic iliac vessels, nerves, but theits medialdistal part border of the is the hypogastric upper two-thirds nerve, and of thethe IHP.vaginal wall and the insertion of the USL. It is the upper part of the paracolpium that contains important functional nerves and ves- 3. What Ultrasound Should Investigate and Detect sels. The upper limit of the paracervix is the ureter and the lower limit is the levator ani muscleUltrasound and the presacral visualization fascia. of the The USL paracervix can be obtained contains using the ainferior transvaginal vesical approach artery, [the19]. vaginalThese images artery, can the beproximal used to part assess of thethe presencedeep uterine of disease vein, the and pelvic determine splanchnic if there nerves, is any theparametrial distal part involvement. of the hypogastric For this nerve, procedure, and the the IHP. ultrasound probe is placed in the pos- terior in longitudinal axis and then rotated laterally of about 45◦, showing 3.the What hyperechoic Ultrasound USL. Should Disease Investigate (either endometriosis and Detect or cancer) appears as a hypoechoic lesion that alters the regular (fibrotic) pattern of the ligament. Parametrial involvement Ultrasound visualization of the USL can be obtained using a transvaginal approach may be seen as an extension (same echogenicity) of the primary lesion more distant from [19]. These images can be used to assess the presence of disease and determine if there is the probe. any parametrial involvement. For this procedure, the ultrasound probe is placed in the The cervix should appear on one side of the image to ensure that the edge of the posterior vaginal fornix in longitudinal axis and then rotated laterally of about 45°, show- ligament that is closest to the cervix can be assessed. The first important consideration ingduring the hyperechoic ultrasound of USL. the USLDisease is to (either not push endometriosis the probe upwards or cancer) while appears it is correctlyas a hypoechoic placed. lesionThis method that alters allows the for regular clear visualization(fibrotic) pattern of not of onlythe ligament. the USL, butParametrial also the parametriuminvolvement may(distal be toseen the as probe) an extension and, most (same importantly, echogenicity) the paracervixof the primary (proximal lesion more to the distant probe). from As theshown probe. in Figure2, we placed a 5 Ti-CronTM polyester suture (a heavy braided suture for orthopedics,The cervix diameter should 0.7 appear mm) alongon one a side physiological of the image USL to during ensure surgery that the to confirmedge of the ligamentultrasound that visualization is closest to of the the cervix ligament. can Inbe thisassessed. way,we The could first simultaneouslyimportant consideration visualize duringthe vaginal ultrasound wall, the of the paracervical USL is to not tissue, push the the USL, probe and upwards the parametrium. while it is correctly All structures placed. Thiscould method be visualized allows for from clear the visualization probe to more of not distant only regionsthe USL, (Supplementary but also the parametrium Materials (distalVideo S1).to the probe) and, most importantly, the paracervix (proximal to the probe). As shown in Figure 2, we placed a 5 Ti-CronTM polyester suture (a heavy braided suture for orthopedics, diameter 0.7 mm) along a physiological USL during surgery to confirm the ultrasound visualization of the ligament. In this way, we could simultaneously visualize

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the vaginal wall, the paracervical tissue, the USL, and the parametrium. All structures J. Clin. Med. 2021, 10, 437 could be visualized from the probe to more distantdistant regionsregions (Supplementary(Supplementary MaterialsMaterials4 of 11 Video S1).

Figure 2. UltrasoundUltrasound visualization of the uterosacral li ligament,gament, paracervix, and parametrium. Figure ( A) shows the normal appearance and explanations are reported in figure figure (B). AA polyesterpolyester suturesuture waswas placedplaced onon aaa physiologicalphysiologicalphysiological USLUSL duringduring laparoscopylaparoscopy (figure(figure(figure ( (C(C)) and and identified identified via via ultrasound ultrasound (arrow) (arrow) in in figure figure (D ().D Abbreviations:). Abbreviations: C, cervix;C, cervix; MR, MR, mesorectum; mesorectum; PC, PC, paracervix; PM, parametrium; R, rectum; USL, uterosacral ligament; V, vagina wall. paracervix;PC, paracervix; PM, PM, parametrium; parametrium; R, rectum; R, rectum; USL, USL, uterosacral uterosacral ligament; ligament; V, vagina V, vagina wall. wall.

Another important consideration is that, during the ultrasound, strongly pushing the probe to make the USL closer to the vagina may result in a displacement (rotation) of the ligament,ligament, which which can can mask mask the the actual extent of the lesionlesion (Figure(Figure 33 and and Supplementary Supplementary materials Video S2).

Figure 3. Modification of the visualization of lesions of the uterosacral ligament during the ultrasound when the probe is Figure 3. ModificationModification of the visualization of lesions of the uter uterosacralosacral ligament during the ul ultrasoundtrasound when the probe is pushed. Figure 3 (D–F) represent the marked images respectively of figure (A–C). The uterosacral ligament is marked in pushed. Figure 33( (D–F) represent the marked images respectively of figure figure (A–C). The uterosacral ligament is marked in yellow and lesions in red. yellow and lesions in red.

To obtain a correct visualization of both the USL and the paracervical and parametrial tissues, we suggest not only relying on the subjective feeling of the operator (i.e., not pushing), but also visualizing the small vessels within the lowest part of the USL using J. Clin. Med. 2021, 10, x FOR PEER REVIEW 5 of 11 J. Clin. Med. 2021, 10, x FOR PEER REVIEW 5 of 11

J. Clin. Med. 2021, 10, 437 To obtain a correct visualization of both the USL and the paracervical and parametrial5 of 11 tissues,To weobtain suggest a correct not only visualization relying on of the both subjec the USLtive feelingand the of paracervical the operator and (i.e., parametrial not push- ing),tissues, but we also suggest visualizing not only the relying small vesselson the subjec withintive the feeling lowest of part the operatorof the USL (i.e., using not push-color Dopplering),color but Doppler (Figurealso visualizing (Figure 4 and4 and Supplemen the Supplementary small taryvessels Materials Materialswithin theVideo Video lowest S3). S3). partThese These of thinthe thin USLvessels vessels using may color bebe temporarilyDopplertemporarily (Figure closed 4 by and pushing pushing Supplemen the probe. probe.tary Materials Ligament Ligament Video rotation rotation S3). and These vessel vessel thin disappearance disappearance vessels may arebe particularlytemporarily evident closed by for pushing endometriosis the probe. lesions Ligament but are rotation less pronounced and vessel indisappearance cases of cervical are cancerparticularly spread, evident as the for latter endometriosis lesions are integral lesions butwith are the less cervix pronounced (Figure 5 5)in) andand cases thethe of cervixcervix cervical isis lesscancerless easy easy spread, to to rotate. as the latter lesions are integral with the cervix (Figure 5) and the cervix is less easy to rotate.

Figure 4. 4. VisualizationVisualization of ofthe the small small vessels vessels within within the lowest the lowest part partof the of uterosacral the uterosacral ligament ligament using color using Doppler. color Doppler. Figure Figure 4. Visualization of the small vessels within the lowest part of the uterosacral ligament using color Doppler. Figure Figure(C,D) are (C ,Dthe) aremarked the marked images images of figure of figure(A,B), (respectively.A,B), respectively. Endometriosis Endometriosis lesions lesions of the ofuterosacral the uterosacral ligament ligament and para- and metrium(C,D) are are the in marked red. Abbreviations: images of figure PM, parametrium;(A,B), respectively. USL, uterosacralEndometriosis ligament. lesions of the uterosacral ligament and para- parametriummetrium are in are red. in red.Abbreviations: Abbreviations: PM, PM,parametrium; parametrium; USL, USL, uterosacral uterosacral ligament. ligament.

Figure 5. Cervical carcinoma (A,D) that spreads to the uterosacral ligaments (B) as marked in figure (C). Figure (E) demon- Figurestrate the 5. Cervical uterosacralCervical carcinoma carcinoma spread (ofA,D ( Ath,)De that )cancer that spreads spreadsas marked to the to uterosacral thein figure uterosacral ( Fligaments). Abbreviations: ligaments (B) as ( markedB) C, as cervix marked in figure; PC, in (paracervix; figureC). Figure (C). ( EPM, Figure) demon- para- (E) demonstratemetrium;strate the U,uterosacral ureter; the uterosacral USL, spread uterosacral spreadof the cancer ofligament. the canceras marked as marked in figure in figure(F). Abbreviations: (F). Abbreviations: C, cervix C,; cervix; PC, paracervix; PC, paracervix; PM, para- PM, parametrium;metrium; U, ureter; U, ureter; USL, USL, uterosacral uterosacral ligament. ligament. The diagnostic accuracy for endometriosis lesions evaluated using ultrasound has been Thereported diagnosticdiagnostic as moderate accuracyaccuracy (sensitivity for for endometriosis endometriosi 0.67, specificity lesionss lesions evaluated 0.86) evaluated [20], using which using ultrasound isultrasound similar has to been hasthe accuracybeenreported reported asof moderate MRI as moderate(sensitivity (sensitivity (sensitivity 0.70, 0.67, specificity specificity 0.67, specificity 0.93) 0.86) [20[21]. 0.86)], which Alcazar [20], is which similar et al. is to [22]similar the assessed accuracy to the parametrialaccuracyof MRI (sensitivity of infiltrationMRI (sensitivity 0.70, in specificitycervical 0.70, cancer 0.93)specificity an [21d]. reported 0.93) Alcazar [21]. a etsimilar al.Alcazar [22 diagnostic] assessedet al. [22] accuracy parametrial assessed for ultrasoundparametrialinfiltration ininfiltration(sensitivity cervical cancer in0.78, cervical andspecificity reportedcancer an0.96), ad similar reported which diagnostic a wassimilar also accuracy diagnostic comparable for accuracy ultrasound to thefor ultrasound(sensitivity 0.78,(sensitivity specificity 0.78, 0.96), specificity which was 0.96), also comparablewhich was toalso the performancecomparable ofto MRI.the For many years, MRI was the diagnostic gold standard for assessing the extent of lesions palpated with a bimanual combined rectovaginal examination (Figure6).

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performance of MRI. For many years, MRI was the diagnostic gold standard for assessing J. Clin. Med. 2021, 10, 437 the extent of lesions palpated with a bimanual combined rectovaginal examination6 of 11 (Figure 6).

Figure 6. Thickened right uterosacral ligament in a woman with deepdeep infiltratinginfiltrating endometriosisendometriosis andand .adenomyosis. Axial HR T2w-Turbo SpinSpin EchoEcho (TSE)(TSE) imageimage ((A),), SagittalSagittal HRHR T2w-TSET2w-TSE imageimage ((B),), CoronalCoronal HRHR T2w-TSET2w-TSE imageimage ((C).). TheThe rightright uterosacral ligament shows a nodularnodular thickeningthickening (arrows).(arrows). Diffuse adenomyosis of posteriorposterior uterine wallwall (*).(*). AdvancedAdvanced cervical cancer infiltrating right uterosacral ligament (arrow) and parametrium (arrowhead). Axial HR T2w-Turbo Spin cervical cancer infiltrating right uterosacral ligament (arrow) and parametrium (arrowhead). Axial HR T2w-Turbo Spin Echo (TSE) image (D), Sagittal HR T2w-TSE image (E), Coronal HR T2w-TSE image (F). Echo (TSE) image (D), Sagittal HR T2w-TSE image (E), Coronal HR T2w-TSE image (F).

Recently, fusion imaging has gained interestinterest for determiningdetermining USL andand parametrialparametrial involvement inin endometriosisendometriosis and and cervical cervical cancer cancer spread spread [23 [23–25].–25]. Fusion Fusion imaging, imaging, also also re- referredferred to to as as real-time real-time virtual virtual sonography, sonography, displays displays live live ultrasound ultrasou imagerynd imagery and previously-and previ- ously-acquiredacquired MRI images MRI images side-by-side side-by-side on a single on screen.a single This screen. technique This technique requires an requires average an of 13average min to of perform 13 min [to24 ],perform but early [24], work but has early shown work that has it shown may improve that it may the detection improve ratethe detectionof parametrial rate of involvement parametrial [involvement23,24]. Larger [23,24]. studies Larger are required studies toare confirm required these to confirm pivotal thesefindings. pivotal One findings. of the main One advantages of the main of advantages fusion imaging of fusion is the imaging visualization is the ofvisualization peripheral ofnerves peripheral (i.e., the nerves hypogastric (i.e., the nerve). hypogastric Peripheral ne nervesrve). Peripheral cannot be seennerves via cannot ultrasound be seen but arevia ultrasoundvisible with but an are MRI; visible although with MRIan MRI; is multiplanar, although MRI it is is more multiplanar, expensive, it is requires more expensive, between requires20 and 30 between min to be20 completed,and 30 min and to be does comple not allowted, and a real-time does not evaluation. allow a real-time During evalua- fusion tion.imaging, During the MRIfusion image imaging, reconstruction the MRI image follows reconstruction all ultrasound follows probe movements all ultrasound (real-time probe movementsevaluation), (real-time making it evaluation), possible to obtainmaking oblique it possible sections to obtain with oblique a clear visualizationsections with ofa clearnerves visualization [25]. of nerves [25].

4. Anatomical Considerations and Surgical Implications Most endometriosis endometriosis lesions lesions of of the the USL USL involve involve the thecervical cervical section, section, which which is the isthick- the estthickest (5–20 (5–20mm) part mm) of part the ligament of the ligament [1]: We [re1]:-analyzed We re-analyzed cases reported cases reportedin Scioscia in et Scioscia al. [10] (USLet al. involvement [10] (USL involvement n = 1608) and n found = 1608) that and 96.3% found of endometriosis that 96.3% of endometriosislesions occurred lesions in the cervicaloccurred section in the cervicalof the USL, section with of a theslightly USL, higher with a prevalence slightly higher of lesions prevalence on the of left lesions USL (53.9%on the leftvs. 46.1%). USL (53.9% In cases vs. of 46.1%). cervical In cancer cases ofspread, cervical all cancerthe metastatic spread, lesions all the of metastatic the USL obligatelylesions of theinvolve USL obligatelythe proximal involve (cervical) the proximal part because (cervical) they part are becausea direct theyinvasion are a of direct the tumor.invasion Macroscopically, of the tumor. Macroscopically, the cervical section the of cervical the USL section is composed of the USL of dense is composed connective of tissuedense connectivecontaining tissuesmall blood containing vessels small and blood small vessels branches and of small the IHP branches [1]. These of the diseases IHP [1]. These diseases that involve the USL may spread to nearby tissues like parametrium and paracervix in about 35% of cases [26]. Parametrial and paracervical involvement makes surgery more complex and requires a specific surgical-anatomical preparation [9,15]. In fact, the paracervix and USL contain J. Clin. Med. 2021, 10, x FOR PEER REVIEW 7 of 11

that involve the USL may spread to nearby tissues like parametrium and paracervix in about 35% of cases [26]. Parametrial and paracervical involvement makes surgery more complex and re- quires a specific surgical-anatomical preparation [9,15]. In fact, the paracervix and USL contain the pelvic , the distal part of the hypogastric nerve, and the IHP (Figure 7). The IHP is composed of sympathetic fibers from the hypogastric nerve and parasympathetic fibers from the splanchnic nerves and nerve anastomoses (which arise from the second-to-fourth sacral roots) [27]. Efferent fibers from the IHP travel to the rec- tum, uterus, rectovaginal ligament, and deep vesicouterine ligament. These efferent fibers are essential for bladder and rectal functionality so tailored nerve-sparing surgery became a standard approach for treating deep infiltrating endometriosis and cervical cancer [15,28–30]. Diseases of the USL, such as endometriosis and cervical cancer, may also involve nearby structures such as the ureter, the hypogastric nerve, and the IHP (Figure 8). These diseases, therefore, require expert surgery to avoid major complications, such as ureter J. Clin. Med. 2021, 10, 437 fistulas, voiding dysfunction, or constipation. 7 of 11 From a surgical point of view, parametrium and paracervix, which is the upper part of the paracolpium (see above), contain structures that require different surgical ap- proachesthe pelvic [31]. splanchnic Namely, nerves, the parametrium the distal part contai of thens hypogastric the ureter and nerve, vessels and the that IHP are (Figure usually7). isolatedThe IHP in is advanced composed surgery of sympathetic (radical fibers hyster fromectomy the hypogastric and deep infiltrating nerve and parasympatheticendometriosis) whilefibers the from paracervix the splanchnic contains nerves vessels and (usually nerveanastomoses sacrificed whenever (which ariserequired) from and the second-nerves thatto-fourth should sacral be, if possible, roots) [27 preserved]. Efferent in fibersmodern from nerve-sparing the IHP travel radical to thesurgery. rectum, However, uterus, unilateralrectovaginal resection ligament, of the and HN, deep when vesicouterine the disease ligament. involves Thesedeeply efferent the nerve fibers and are perineural essential spacesfor bladder and neurolysis and rectal functionalityis not possible, so is tailored considered nerve-sparing acceptable surgery in the becamecontext aof standard nerve- sparingapproach surgery. for treating deep infiltrating endometriosis and cervical cancer [15,28–30].

FigureFigure 7. 7. TheThe hypogastric hypogastric nerve (orange)(orange) andand inferiorinferior hypogastric hypogastric plexus plexus (yellow) (yellow) in in an an anatomical anatomical table table (A); (A the); the image image was wasmodified modified from from “Innervazione “Innervazione viscerale viscerale e somatica e somatica della della pelvi pe femminile”lvi femminile” by Ceccaroni, by Ceccaroni, M,Fanfani M, Fanfani F, Ercoli F, Ercoli A, Scambia A, Scam- G; bia G; Ed. 2017, CIC Edizioni Internazionali) and surgery (B). In figure (B), the edge of the left uterosacral ligament that is Ed. 2017, CIC Edizioni Internazionali) and surgery (B). In figure (B), the edge of the left uterosacral ligament that is close to close to the vagina and cervix is exposed after resection for endometriosis. Abbreviations: HN, hypogastric nerve; IHP, the vagina and cervix is exposed after resection for endometriosis. Abbreviations: HN, hypogastric nerve; IHP, inferior inferior hypogastric plexus; PC, paracervix; PM, parametrium; R, rectum; RVS, rectovaginal septum; Ur, ureter; USL, uterosacralhypogastric ligament; plexus; PC,Ut, paracervix;uterus. PM, parametrium; R, rectum; RVS, rectovaginal septum; Ur, ureter; USL, uterosacral ligament; Ut, uterus.

Diseases of the USL, such as endometriosis and cervical cancer, may also involve nearby structures such as the ureter, the hypogastric nerve, and the IHP (Figure8). These diseases, therefore, require expert surgery to avoid major complications, such as ureter fistulas, voiding dysfunction, or constipation. From a surgical point of view, parametrium and paracervix, which is the upper

part of the paracolpium (see above), contain structures that require different surgical approaches [31]. Namely, the parametrium contains the ureter and vessels that are usually isolated in advanced surgery (radical and deep infiltrating endometriosis) while the paracervix contains vessels (usually sacrificed whenever required) and nerves that should be, if possible, preserved in modern nerve-sparing radical surgery. However, unilateral resection of the HN, when the disease involves deeply the nerve and perineural spaces and neurolysis is not possible, is considered acceptable in the context of nerve- sparing surgery. J. Clin. Med. 2021, 10, x FOR PEER REVIEW 8 of 11 J. Clin. Med. 2021, 10, 437 8 of 11

Figure 8. An isolated lesion of endometriosis of the left uterosacral ligament (A). DuringDuring the dissection,dissection, the nodulenodule was shown to extend laterally through the parametrium to the ureter (B) and inferiorly to the hypogastric nerve (C). After the complete removal of the nodule, the parametrium and the upper part of the paracervix was exposed (D). Abbreviations: complete removal of the nodule, the parametrium and the upper part of the paracervix was exposed (D). Abbreviations: HN, hypogastric nerve; N, endometriosis nodulus; PC, paracervix; PM, parametrium; U, ureter; UA, uterine artery; USL, HN, hypogastric nerve; N, endometriosis nodulus; PC, paracervix; PM, parametrium; U, ureter; UA, uterine artery; USL, uterosacral ligament. uterosacral ligament. 5. Discussion 5. DiscussionUltrasound is an accurate method for identifying the extent of pelvic endometriosis and cervicalUltrasound cancer. is an A accuratecorrect visualization method for identifying of the USL themay extent improve of pelvic the detection endometriosis of le- sionsand cervical and their cancer. possible Acorrect extension visualization to the parametrium of the USL and may the improve paracervix. the detection Evaluating of paracervicallesions and theirtissue possible is a key extension component to the of parametriumpre-operative and assessment the paracervix. as it contains Evaluating im- portantparacervical structures, tissue such is a key as ureters component and nerv of pre-operativees, which may assessment make surgery as it containsmore complex. impor- Atant multidisciplinary structures, such surgical as ureters approach and nerves, may sometimes which may be make required surgery to avoid more the complex. long-term A complicationsmultidisciplinary that surgicalcan result approach from inadvertent may sometimes damage be to required these structures. to avoid the long-term complicationsThe role of that ultrasound can result in from assessing inadvertent USLs, parametrium, damage to these and structures. paracervix has been dis- cussedThe in rolethe literature of ultrasound but in in all assessing cases the USLs, visualization parametrium, of the USL and paracervixwas suggested has to been be obtaineddiscussed by in pushing the literature the probe but in to all make cases the the li visualizationgament closer of to the the USL transducer was suggested to improve to be theobtained imagine by quality pushing [19,20,32]. the probe In to this make article, the ligamentwe suggest closer placing to the the transducer probe in the to posterior improve vaginalthe imagine fornix quality and then [19, 20rotate,32]. of In about this article, 45° without we suggest pushing placing the transducer the probe in to the also posterior visual- izevaginal structures fornix that and lie then between rotateof the about USL45 and◦ without the vagina pushing (paracervix; the transducer proximal to alsoto the visualize probe) andstructures laterally that to lie the between USL the(parametrium; USL and the distal vagina to (paracervix; the probe). proximal As we toreported the probe) above, and stronglylaterally pushing to the USL the (parametrium;probe to make distalthe USL to clos theer probe). to the Asvagina we reportedmay result above, in a displace- strongly mentpushing of the the ligament, probe to make which the can USL mask closer the to actual the vagina extent may of the result lesion, in a perhaps displacement to relevant of the structuresligament, whichlike nerves can mask and ureter. the actual We extentreported of thesome lesion, surgical perhaps and anatomical to relevant considera- structures tionslike nerves that make and clear ureter. the We relevance reported of somethis an surgicalatomical and area anatomical and the need considerations for a correct thatvis- ualizationmake clear and the diagnosis. relevance of this anatomical area and the need for a correct visualization and diagnosis.Another important consideration for ultrasound visualization is the experience level of sonographers,Another important as demonstrated consideration by high for ultrasound variability visualizationin the detection is the of USL experience endometri- level osisof sonographers, (sensitivity ranges as demonstrated from 0.10 to by 0.89) high [3 variability3]. According in the to detection recent studies of USL on endometriosis the learning curve(sensitivity for using ranges transvaginal from 0.10 ultrasound to 0.89) [33 in]. cases According of deep toinfiltrating recent studies endometriosis on the learning [34,35], curve for using transvaginal ultrasound in cases of deep infiltrating endometriosis [34,35],

J. Clin. Med. 2021, 10, 437 9 of 11

the USL appears to be the most difficult structure to explore accurately: lower sensitiv- ity/specificity values are reported for the USL than for other structures, and clinicians need to perform a higher number of scans to achieve proficiency. A systematic approach, such as the one proposed by the International Deep Endometriosis Analysis (IDEA) group [5], may improve the diagnostic accuracy and predictive value of ultrasound [36], and we therefore look forward to the findings of the ongoing multicenter IDEA study.

6. Conclusions This article highlights the importance of a correct visualization by ultrasound not only of the USL but the contemporary assessment of the paracervix and parametrium. This can be achieved during transvaginal sonographic dynamic real-time assessment of the USL without pushing the probe to assess the depth of the lesion that may extend to structures like nerves. Paracervical and parametrial infiltration represents an important aspect in preoperative assessment to optimize preoperative counselling and informed consent (for risk of postoperative bladder dysfunctions), and to involve expert surgeons during the operation. In this paper, we attempted to establish a common terminology between imaging diagnostic and modern surgical anatomy to overcome discrepancies in clinical and research settings.

Supplementary Materials: The following are available online at https://www.mdpi.com/2077-0 383/10/3/437/s1, Video S1. Ultrasound visualization during surgery of the uterosacral ligament, paracervix, and parametrium. The hyperechoic line (arrow) is the suture that was placed on the uterosacral ligament. Abbreviations: C, cervix; PC, paracervix; PM, parametrium; USL, uterosacral ligament; V, vagina wall. Video S2. Displacement of the uterosacral ligament during the ultrasound when the probe is strongly pushed. Video S3. Visualization of the small vessels within the lowest part of the uterosacral ligament using color Doppler. Author Contributions: Conceptualization: M.S.; methodology: B.A.V.; data curation: M.S., B.A.V., and A.S.; writing—original draft preparation: M.S.; writing—review and editing: M.L., F.L., and M.N.; visualization: M.S. and A.S.; supervision: M.N. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Acknowledgments: We thank our nurse instrumentalists, Daniela Bastianelli and Donata Carriero, for valuable advices and help in planning and executing research surgery. Conflicts of Interest: The authors declare no conflict of interest.

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