Nerve-Sparing Systematic Lymph Node Dissection in Gynaecological Oncology: an Innovative Neuro-Anatomical and Surgical Protocol for Enhanced Functional Outcomes
Article Nerve-Sparing Systematic Lymph Node Dissection in Gynaecological Oncology: An Innovative Neuro-Anatomical and Surgical Protocol for Enhanced Functional Outcomes
Mustafa Zelal Muallem 1,*, Yasser Diab 2, Thomas Jöns 3, Jalid Sehouli 1 and Jumana Muallem 1
1 Department of Gynecology with Center for Oncological Surgery, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Virchow Campus Clinic, Charité Medical University, 13353 Berlin, Germany; [email protected] (J.S.); [email protected] (J.M.) 2 Department of Gynecology, Portland Hospital, Portland, VIC 3305, Australia; [email protected] 3 Department of Anatomy, Mitte Campus Clinic, Charité Medical University, 10117 Berlin, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-30-450-664373; Fax: +49-30-450-564900
Received: 19 October 2020; Accepted: 20 November 2020; Published: 22 November 2020
Simple Summary: One of the most frequent complications of the systematic lymph node dissection (SLND) is the injury of autonomic nervous system in the para-aortal region during the procedure. These injuries are supposed to be responsible for some of the postoperative bladder, bowel, and sexual dysfunctions. The poor anatomical understanding of the sympathetic nerves within the boundaries of an infra-renal bilateral template has limited the promulgation of a precise nerve-sparing surgery during such SLND. Therefore, the principal goal of the present study was to provide the first ever-comprehensive exposition of the anatomy of the female aortic plexus and superior hypogastric plexus and their variations. This exposition was achieved by strategic dissection of 19 human female cadavers and extrapolating the findings to develop a precise surgical technique for more accurate navigation into these structures during nerve-sparing SLND in 15 cervical cancer patients and 48 ovarian cancer patients.
Abstract: Whilst systematic lymph node dissection has been less prevalent in gynaecological cancer cases in the last few years, there is still a good number of cases that mandate a systematic lymph node dissection for diagnostic and therapeutic purposes. In all of these cases, it is crucial to perform the procedure as a nerve-sparing technique with utmost exactitude, which can be achieved optimally only by isolating and sparing all components of the aortic plexus and superior hypogastric plexus. To meet this purpose, it is essential to provide a comprehensive characterization of the specific anatomy of the human female aortic plexus and its variations. The anatomic dissections of two fresh and 17 formalin-fixed female cadavers were utilized to study, understand, and decipher the hitherto ambiguously annotated anatomy of the autonomic nervous system in the retroperitoneal para-aortic region. This study describes the precise anatomy of aortic and superior hypogastric plexus and provides the surgical maneuvers to dissect, highlight, and spare them during systematic lymph node dissection for gynaecological malignancies. The study also confirms the utility and feasibility of this surgery in gynaecological oncology.
Keywords: nerve-sparing lymphadenectomy; pelvic and para-aortic lymph nodes; lymph node dissection; infra-renal bilateral template; aortic plexus
Cancers 2020, 12, 3473; doi:10.3390/cancers12113473 www.mdpi.com/journal/cancers Cancers 2020, 12, 3473 2 of 10
1. Introduction Dissection evaluation of pelvic and para-aortic lymph nodes has been an integral component of the surgical staging protocol for several gynaecologic malignancies for over a century [1,2]. However, in the recent years, this systematic dissection evaluation of lymph nodes has become less relevant because of the extensive deployment of sentinel lymph node mapping technology with a corroborated efficacy in the detection of several endometrial and cervical cancers [3]. Further, the recently published results of the randomized trial on lymphadenectomy in patients with advanced ovarian neoplasms (LION trial) [4] have narrowed down the scope for systematic lymph node dissection and, in fact, restricted the procedure only to apparent early stage ovarian cancer patients [5]. Nevertheless, the significance of the prognostic value of the para-aortic lymph node status in locally advanced cervical cancer has been accentuated again in the new International Federation of Gynaecology and Obstetrics (FIGO) staging system for cervical cancer that classifies patients with a para-aortic lymph node involvement in stage FIGO IIIC2 [6]. These developments in surgical management of gynaecological malignancies have given rise to austere diagnostic restrictions for a systematic lymph node dissection in such cases. Taking these facts and the potential additional treatment burden of a systematic lymph node dissection into account, all contentions are in place to avoid the complications of a lymph node dissection. One of the most frequent and vital complications of the para-aortic lymph node dissection that has perhaps never descended into the cognitive focus of many gynaecologic oncologists is the injury of autonomic nervous system in the para-aortal region during the procedure. The present study supposes that these nerve injuries are responsible for some of the postoperative bladder, bowel, and sexual dysfunctions. The present study also contends that a poor anatomical understanding of the sympathetic nerves within the boundaries of an infra-renal bilateral template has limited the promulgation of a precise nerve-sparing surgery during such systematic lymph node dissections. Since we already described the precise anatomy of pelvic autonomic nervous system (inferior hypogastric plexus) in our previous studies [7–9], the principal goal of the present study was to provide the first ever-comprehensive exposition of the anatomy of the female aortic plexus and superior hypogastric plexus and their variations, to elucidate and improve the surgical outcomes of a systematic nerve-sparing lymph node dissection. This exposition was achieved by strategic dissection of human female cadavers and extrapolating the findings to develop a precise surgical technique for more accurate navigation into these structures during nerve-sparing systematic lymph node dissections, especially in the para-aortic region.
2. Results
2.1. The Anatomy of Aortic Plexus The abdominal aortic plexus is the sympathetic network of autonomic nerves overlying in the front and sides of the abdominal aorta in the infra-renal bilateral template and going along with the superior hypogastric plexus at the sacral promontory [10,11]. The superior hypogastric plexus, often called the presacral nerve, terminates by dividing into right and left hypogastric nerves and consists primarily of sympathetic and visceral afferent fibers [12]. These fibers merge with the pelvic splanchnic nerves (parasympathetic) in the deep extraperitoneal spaces at the lateral sidewall of the vagina and rectum, to form the inferior hypogastric plexus bilaterally from which nerve fibers spread out to the pelvic organs [7,13–15]. The aortic plexus receives sympathetic supply from the lumbar sympathetic trunk and suprarenal pre-aortic plexuses via lumbar splanchnic nerves and intermesenteric nerves, respectively [16]. The new technique in this study effectively comprises a precise description of these nerve courses for an accurate dissection that incorporates precise nerve-sparing practices during such bilateral para-aortic lymph node dissections and efficaciously distinguishes them from the most caudal parts, to their origin, from the sympathetic trunks bilaterally. Cancers 2020, 12, 3473 3 of 10 Cancers 2020, 12, x 3 of 10
2.2. Dissection of the Right Cord of the Aortic Plexus 2.2. Dissection of the Right Cord of the Aortic Plexus The cadaver study has primarily shown that the easiest way to identify the lumbar splanchnic The cadaver study has primarily shown that the easiest way to identify the lumbar splanchnic nerves is to prepare and dissect them from their caudal most part at the superior hypogastric plexus in nerves is to prepare and dissect them from their caudal most part at the superior hypogastric plexus thein the presacral presacral area area (the (the point point of bifurcationof bifurcation of the of the common common iliac iliac arteries) arteries) and and then then to track to track carefully carefully the deepestthe deepest lumbar lumbar splanchnic splanchnic nerve nerve (which (which was, in was, all of in our all cases, of our the cases, inferior the right inferior lumbar right splanchnic lumbar nerve),splanchnic to its nerve), point ofto originits point at of the origin second at the lumbar seco ganglionnd lumbar of ganglion the right of sympathetic the right sympathetic trunk. trunk. The studystudy hashas alsoalso elucidatedelucidated thatthat it it wouldwould be be easy, easy in, in most most cases cases (81.7%, (81.7%, 67 67/82/82 cases), cases), to to identify identify a gangliona ganglion at at the the right right side side of theof the aorta aorta around around the inferiorthe inferior mesenteric mesenteric artery artery or maximal or maximal 1 cm caudal1 cm caudal from itfrom (the it inferior (the inferior mesenteric mesenteric ganglion). ganglion). Successful Successful identification identification of this ganglion of this allowsganglion the allows dissection the todissection go laterocranial to go laterocranial and dorsal and to the dorsal vertebral to the column vertebral in thecolumn interaortocaval in the interaortocaval space above space the middle above lumbarthe middle vein lumbar and then vein behind and then the venabehind cava, the at vena the levelcava, ofat thethe rightlevel lumbarof the right artery lumbar (Figure artery1 shows (Figure the right1 shows cord the of right aortic cord plexus of aortic and its plexus components). and its components).
Figure 1.1. TheThe right right cord cord of of aortic aortic plexus. plexus. SRLSN, SRLSN, superior superior right right lumbar lumbar splanchnic splanchnic nerve; nerve; MLV, middle MLV, lumbarmiddle vein;lumbar IRLSN, vein; inferiorIRLSN, inferior right lumbar right splanchniclumbar splanchnic nerve; ILV, nerve; inferior ILV, lumbarinferior vein;lumbar IMG, vein; inferior IMG, mesentericinferior mesenteric ganglion; ganglion; SHP, superior SHP, superior hypogastric hypogastric plexus. plexus.
Dissecting alongalong this this nerve nerve behind behind the cava the and cava then and laterally then gives laterally the surgeon gives athe comprehensive surgeon a prospectcomprehensive to identify prospect the right to identify sympathetic the right chain sympat and thehetic origin chain of and the inferiorthe origin lumbar of the splanchnic inferior lumbar nerve fromsplanchnic the second nerve lumbar from the ganglion second of lumbar the right ganglion sympathetic of the chain. right An sympathetic accessory inferiorchain. An right accessory lumbar splanchnicinferior right nerve lumbar was splanchnic identified innerve 72% was of the identified maneuvers in 72% (59 /of82) the in themaneuvers study. This (59/82) accessory in the study. nerve originatesThis accessory in our nerve cases originates from the in third our lumbarcases from ganglion the third of thelumbar right ganglion sympathetic of the chain right and sympathetic joins the inferiorchain and right joins lumbar the inferior splanchnic right nerve lumbar before splanchnic reaching nerve the inferior before mesenteric reaching the ganglion. inferior mesenteric ganglion.The superior right splanchnic nerve will be easy to identify when dissecting along to its origin fromThe the firstsuperior lumbar right ganglion splanchnic of the nerve right sympathetic will be easy chain to identify behind when and lateral dissecting of vena along cava to at its the origin level from the first lumbar ganglion of the right sympathetic chain behind and lateral of vena cava at the level where the left renal vein inserts into vena cava crossing over the right superior lumbar vein.
Cancers 2020, 12, 3473 4 of 10
Cancers 2020, 12, x 4 of 10 where the left renal vein inserts into vena cava crossing over the right superior lumbar vein. (Figure2 shows(Figure the 2 shows emergence the emergence of superior of and superior inferior and lumbar inferior splanchnic lumbar nerves splanchnic in the firstnerves and in second the first lumbar and ganglionssecond lumbar directly ganglions at the level directly of superior at the andlevel middle of superior lumbar and veins middle in one lumbar of the cadaver veins in preparations one of the incadaver this study.) preparations in this study.)
Figure 2.2. TheThe emergingemerging of of superior superior and and inferior inferior lumbar lumbar splanchnic splanchnic nerves nerves in the in first the and first second and lumbarsecond ganglionslumbar ganglions directly directly at the level at the of level superior of superior and middle and middle lumbar lumbar veins in veins one cadaver in one cadaver preparation preparation for this study.for this SRLSN, study. SRLSN, superior superior right lumbar right splanchniclumbar splanchnic nerve; SLV, nerve; superior SLV, lumbarsuperior vein; lumbar 1st RLG, vein; first1st RLG, right lumbarfirst right ganglion lumbar of ganglion sympathetic of sympathetic trunk; IRLSN, trunk; inferior IRLSN, right inferior lumbar right splanchnic lumbar nerve; splanchnic MLV, middlenerve; lumbarMLV, middle vein; 2ndlumbar RLG, vein; second 2nd right RLG, lumbar second ganglion right lumbar of sympathetic ganglion of trunk. sympathetic trunk.
In 18.3% of the cases in the the study, study, two ganglions at the right and ventral side of the aorta, instead of the one big inferior mesenteric ganglion, were identified.identified. Further, a ganglion at the level of inferior mesenteric arteryartery butbut lateral lateral at at the the right right side, side, where where only only the inferior the inferior lumbar lumbar splanchnic splanchnic nerve crosses, nerve couldcrosses, also could be further also be highlighted. further highlighted. (The authors (The term authors it the term prehypogastric it the prehypogastric ganglion, asganglion, referred as to inreferred the case to in of the most case anatomical of most anatomical studies of studies male cadavers). of male cadavers). In all of theseIn all cases,of these the cases, superior the superior lumbar splanchniclumbar splanchnic nerve is nerve identified is identified as crossing as crossing another even another smaller even ganglion smaller directlyganglion caudal directly from caudal the origin from ofthe right origin ovarian of right artery ovarian from artery the aorta.from the (The aorta. authors (The term authors it the term ovarian it the orovarian gonadal or gonadal ganglion). ganglion). By resecting thethe lymphlymph node node in in the the paracaval paracaval region, region there, there is trulyis truly little little or noor no chance chance toinjure to injure the rightthe right lumbar lumbar splanchnic splanchnic nerves nerves or the or rightthe right sympathetic sympathetic chain chain during during the surgery.the surgery. The The dissection dissection and resectionand resection of lymph of lymph nodes nodes in the in intra-aortocaval the intra-aortocaval region, region, on the on other the hand,other hand, always always leads toleads an injuryto an toinjury the rightto the lumbar right lumbar splanchnic splanchnic nerves, thenerves, inferior the mesentericinferior mesenteric ganglion, ganglion, the prehypogastric the prehypogastric ganglion, andganglion, the ovarian and the (gonadal) ovarian (gonadal) ganglion, ifganglion, the surgeon if the does surgeon not paydoes su notfficient pay attentionsufficient toattention recognize, to highlight,recognize,and highlight, carefully and isolate carefu theselly isolate nervous these components nervous (Figurecomponents3 shows (Figure a medial 3 shows and lateral a medial view and of thelateral dissected view of right the dissected cord of the righ aortict cord plexus). of the aortic plexus).
Cancers 2020, 12, 3473 5 of 10 Cancers 2020, 12, x 5 of 10
Cancers 2020, 12, x 5 of 10
(a) (b)
FigureFigure 3. Medial 3. Medial and and lateral (laterala) views views of of the the dissected dissected right cord cord of of the the aortic aortic plexus plexus(b) in a in patient a patient during during the primarythe primary cytoreductive cytoreductive surgery surgery for for ovarian ovarian cancer. cancer. ( (aa)) Medial Medial view view (interaortocaval (interaortocaval space): space): SRLSN, SRLSN, superiorsuperiorFigure right 3. rightMedial lumbar lumbar and splanchnic lateral splanchni views nerve;c nerve; of IRLSN,the IRLSN,dissected inferior inferior right right cord righ lumbar tof lumbar the aortic splanchnic splanchnic plexus nerve.in nerve. a patient ( b(b)) Lateral Lateralduring view the primary cytoreductive surgery for ovarian cancer. (a) Medial view (interaortocaval space): SRLSN, (para-view and (para- retrocaval and retrocaval space): SRLSN,space): SRLSN, superior superior right right lumbar lumbar splanchnic splanchnic nerve; nerve; IRLSN, IRLSN, inferior inferior right superior right lumbar splanchnic nerve; IRLSN, inferior right lumbar splanchnic nerve. (b) Lateral lumbarright splanchnic lumbar splanchnic nerve; 2nd nerve; RLG, 2nd second RLG, rightsecond lumbar right lumbar ganglion ganglion of sympathetic of sympathetic trunk; trunk; IMG, IMG, inferior view (para- and retrocaval space): SRLSN, superior right lumbar splanchnic nerve; IRLSN, inferior mesentericinferior ganglion; mesenteric SHP, ganglion; superior SHP, hypogastric superior hypogastric plexus. plexus. right lumbar splanchnic nerve; 2nd RLG, second right lumbar ganglion of sympathetic trunk; IMG, 2.3. Dissection2.3. Dissectioninferior of mesenteric the of Leftthe Left Cord ganglion; Cord of of the theSHP, Aortic Aortic superior Plexus Plexus hypogastric plexus. On2.3. theDissectionOn leftthe side,left of side, the the Left the inferior Cord inferior of leftthe left Aortic lumbar lumbar Plexus splanchnicsplanchnic nerve nerve can can be be easily easily identified identified when when dissected dissected in its short course between the superior hypogastric plexus and the left inferior mesenteric ganglion in its short course between the superior hypogastric plexus and the left inferior mesenteric ganglion at at theOn lateral the left left side, sidewall the inferior of the aorta left lumbar around splanchnic the origin nerveof inferior can be mesenteric easily identified artery. Thewhen inferior dissected left the lateral left sidewall of the aorta around the origin of inferior mesenteric artery. The inferior left lumbarin its short splanchnic course between nerve could the superiorthen be followed hypogastric in a plexus dorsocranial and the short left inferiorcourse tomesenteric its origin ganglionfrom the lumbarsecondat the splanchnic lateral lumbar left ganglion nerve sidewall could of of the the then left aorta sympathetic be around followed the trunk, inorigin a dorsocranialat of a levelinferior where mesenteric short the left course lumbarartery. to Theartery its origininferior and vein from left the seconddisappearlumbar lumbar splanchnic deep ganglion into nerve psoas of the could major. left then sympatheticThis be level followed is plac trunk, edin amore dorsocranial at a superiorly level where short than thecourse its leftright-sided to lumbar its origin counterpart, artery from and the vein disappearthesecond inferior deep lumbar intoright ganglion psoaslumbar major. ofsplanchnic the left This sympathetic nerve level is(Figure placed trunk, 4 shows more at a level superiorlya lateral where view the than ofleft the its lumbar dissected right-sided artery left and counterpart,cord vein of the inferiorthedisappear aortic right plexus). deep lumbar into psoas splanchnic major. This nerve level (Figure is placed4 shows more superiorly a lateral than view its of right-sided the dissected counterpart, left cord of the inferior right lumbar splanchnic nerve (Figure 4 shows a lateral view of the dissected left cord of the aortic plexus). the aortic plexus).
(a) (b)
Figure 4. (a) Ventral view and(a) (b) lateral view of the dissected left cord of the(b aortic) plexus in a patient during the primary cytoreductive surgery for ovarian cancer. IMN, intermesenteric nerve; SLLSN, Figure 4. (a) Ventral view and (b) lateral view of the dissected left cord of the aortic plexus in a superiorFigure 4. left(a) Ventrallumbar view splanchnic and (b )nerve; lateral ILLSN,view of infethe riordissected left lumbar left cord splanchni of the aorticc nerve; plexus 2nd in LLG, a patient left patientduring during the theprimary primary cytoreductive cytoreductive surgery surgery for ovar forian ovariancancer. IMN, cancer. intermesenteric IMN, intermesenteric nerve; SLLSN, nerve; SLLSN, superior superior left leftlumbar lumbar splanchnic splanchnic nerve; nerve; ILLSN, ILLSN, inferior inferior left lumbar leftlumbar splanchni splanchnicc nerve; 2nd nerve; LLG, 2nd left LLG, left lumbar ganglion; LST, left sympathetic trunk; RALSN, retroaortic lumbar splanchnic nerve;
IMG, inferior mesenteric ganglion; SHP, superior hypogastric plexus. Cancers 2020, 12, x 6 of 10
Cancerslumbar2020, 12 ganglion;, 3473 LST, left sympathetic trunk; RALSN, retroaortic lumbar splanchnic nerve; IMG,6 of 10 inferior mesenteric ganglion; SHP, superior hypogastric plexus.
The superior left lumbar splanchnic nerve can be identifiedidentified when dissected following its course from the upper part part of of left left inferior inferior mesenteric mesenteric ganglion ganglion to to its its origin origin from from the the first first lumbar lumbar ganglion ganglion of ofthe the left left sympathetic sympathetic chain chain directly directly dorsal dorsal to the tothe inferior inferior border border of the of theleft leftrenal renal vein vein at the at thelevel level of the of therenal–lumbar renal–lumbar vein. vein. This This vein vein could could be beemphatical emphaticallyly identified identified in in 59.7% 59.7% of of the the maneuvers maneuvers in in thethe present study (49(49/82),/82), andand it obviously complicated the clear exposure of the firstfirst lumbar ganglion of the left sympathetic chain (Figure5 5 shows shows aa laterallateral viewview ofof thethe dissecteddissected leftleft cordcord ofof thethe aorticaortic plexus,plexus, with aa focusfocus onon thethe complexcomplex anatomyanatomy atat thethe originorigin ofof thethe superiorsuperior leftleft lumbarlumbar splanchnicsplanchnic nerve).nerve).
Figure 5. A Alateral lateral view view of the of thedissected dissected left cord left of cord the ofaortic the plexus aortic plexuswith focusing with focusing on the complex on the complexanatomy at anatomy the origin at of the superior origin ofleft superior lumbar sp leftlanchnic lumbar nerve. splanchnic IMN, interm nerve.esenteric IMN, intermesenteric nerve; SLLSN, nerve;superior SLLSN, left lumbar superior splanchnic left lumbar nerve; splanchnic LRV, left nerve;renal vein; LRV, RLV, left renal renal–lumbar vein; RLV, vein; renal–lumbar ILLSN, inferior vein; ILLSN,left lumbar inferior splanchnic left lumbar nerve; splanchnic 2nd LLG, nerve; left lumbar 2nd LLG, ganglion; left lumbar IMG, ganglion;inferior mesenteric IMG, inferior ganglion; mesenteric SHP, ganglion;superior hypogastric SHP, superior plexus. hypogastric plexus.
3. Discussion Whilst the systematic lymph node dissection is lessless prevalent in the gynaecological cancer cases in thethe lastlast fewfew yearsyears forfor thethe reasonsreasons statedstated andand expoundedexpounded in the introduction, there is still a good number of cases that mandate a sy systematicstematic lymph lymph node node dissection dissection fo forr diagnostic diagnostic purposes purposes especially, especially, for thosethose in in the the early early stages stages of ovarianof ovarian cancer. cancer. In such In cases,such thecases, status the ofstatus the node of the is vital node for is numerous vital for reasons.numerous A systematicreasons. A lymphsystematic node lymph dissection node primarily dissection allows primarily for an allows accurate for assessment an accurate of assessment the clinical stage,of the clinical which oftenstage, influences which often the influences medical decision the medical for andecision adjuvant for therapyan adjuvant that therapy might bring that might about abring complete about cytoreductiona complete cytoreduction of the cancer of [ 17the]. cancer This is [17]. diagnostically This is diagnostically germane even germane in the even absence in the of publishedabsence of randomizedpublished randomized controlled trialscontrolled to substantiate trials to substantiate the efficacy the oflymphadenectomy. efficacy of lymphadenectomy. Moreover, thethe presencepresence ofof aaffectedffected para-aorticpara-aortic lymphlymph nodesnodes atat thethe timetime of the primary diagnosis of a locallylocally advancedadvanced cervical cancer correlates closelyclosely with a shorter disease-free survival [[18]18] and worsened overall survival [[19].19]. It is likewise impera imperativetive to note that, in spite of thethe availabilityavailability of advanced imagingimaging and and mapping mapping techniques, techniques, several several studies studies have have confirmed confirmed the presencethe presence of para-aortic of para- lymphaortic lymph node metastases node metastases in 8–12% in 8–12% of the casesof the after cases surgical after surgical staging staging in the para-aortic in the para-aortic region despite region negativedespite negative results withresults diagnostic with diagnostic imaging imaging techniques techniques [18,20 [18,20–22].–22]. For theseFor these reasons, reasons, it is it crucial is crucial to acknowledgeto acknowledge the the diagnostic diagnostic value value of of systematic systematic lymph lymph node node dissection dissection in inlocally locally advancedadvanced cervical cancers. Furthermore, thethe randomized randomized Uterus-11 Uterus-11 Trial Trial has has revealed revealed an an improved improved scope scope for disease-freefor disease- andfree overalland overall survival survival after surgical after surgical staging staging as compared as compared to CT-guided to CT-guided staging, which staging, could which be interpreted could be asinterpreted corroboration as corroboration of a minor therapeutic of a minor advantage therapeutic with advantage the systematic with lymph the systematic node dissection lymph in node this cancerdissection cohort in this [23 ].cancer cohort [23].
Cancers 2020, 12, 3473 7 of 10
In all of these cases and others where the systematic lymph node dissection will be rather strongly indicated, it is crucial to perform the procedure as a nerve-sparing technique with utmost exactitude, which can be achieved optimally only by isolating and sparing the all components of the aortic plexus. Failure in the isolation and sparing of all the components of aortic plexus has been established to lead to numerous postoperative urinary, bowel, and sexual functional disorders. In such a context, the clinical legitimacy of a nerve-sparing para-aortal lymph node dissection protocol is severely limited by the lack of published studies that efficaciously integrate the aforementioned anatomy and corroborate the relationships with one another by pertinent examination and explication. One of the most noticeable complications after a surgical injury of the aortic plexus and/or superior hypogastric plexus (sympathetic nervous system) during systematic lymph node dissection is the postoperative impairment of the sexual function. Impairment of the sexual function is, in fact, the most enduringly compromised quality-of-life (QOL) issue encountered after treatment for gynaecologic cancers, affecting up to 50% of the patients [24–26]. The most persistent and negative repercussions have been the loss of patients’ libido and a diminished vaginal lubrication [27]. This is primarily due to the fact that the vaginal blood-flow response to a sexual stimulus and subsequent vaginal lubrication are obvious neural reflex responses innervated by the hypogastric nerve (sympathetic innervation) [28–32]. There is growing evidence to show that the sympathetic nervous system activation plays a facilitatory role in women’s physiological sexual arousal [33] and diminishing its activity state hinders the subjective sexual arousal in sexually functional women [34]. In the recently published data of a sub-protocol of the prospectively randomized LION trial, comparing two cohorts that differed only in the performance of a lymphadenectomy, the role of radical surgery in the retroperitoneal space has been prospectively substantially evaluated with reference to the sexual function (sub-study LION-PAW). It is imperative to mention that, in the LION trial, there have been no requirements for nerve-sparing surgical techniques [35]. The sub-study LION-PAW study has confirmed that lymphadenectomy (unsparing technique) is associated with a higher incidence of post-operative complications, including a significant change of the orgasm score from baseline to 12 months in sexually active patients. This result falls in tandem with the still unpublished findings by the authors on sexual function assessment of advanced ovarian cancer patients [36], who were operated by conventional surgical technique compared with the patients operated with total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP) technique [37] and abovementioned nerve-sparing lymph node dissection. The data have shown a worsened score of discomfort during sexual intercourse and a reduced orgasm score with conventional surgical technique as compared to nerve-sparing lymph node dissection. However, the clinical expediency of such a nerve-sparing approach is still limited due to a lack of published studies, integrating the aforementioned anatomy in control randomized trials to compare the functional outcomes after nerve-sparing lymph node dissection with the conventional systematic nerve-insulting lymphadenectomy procedure.
4. Materials and Methods The anatomic dissections of two fresh and 17 formalin-fixed female cadavers were utilized to study, understand, and decipher the hitherto ambiguously annotated anatomy of the autonomic nervous system in the retroperitoneal para-aortic region. Rigorous dissection protocol was in place to interpret the retroperitoneal para-aortic nervous connections to and from the contiguous anatomical structures, with specific reference to lymph node dissection in gynae-oncology. The new anatomical know-how from this cadaver study was utilized to enhance and develop a superior technique for para-aortic lymph node dissection and was efficaciously employed in locally advanced cervical cancer (a cohort of 15) [9] and in advanced ovarian cancer as a part of total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation) for advanced ovarian cancer (a cohort of 48) [37,38] and the evidence appositely reported in multiple journals. Approval from the Charité Local Ethics Committee was provided for the clinical parts of this study (EA1/174/14 for cervical cancer patients and EK207/2003 Amendment 15/2012 for ovarian cancer patients) as per the recommendations of the Cancers 2020, 12, 3473 8 of 10
Ethics Commission of the parent institution. The data from anatomic dissections on cadavers were obtained in accordance with Charité guidelines for cadaveric use in research. We aimed in this study to describe the whole components of abdominal aortic plexus anatomically and to develop a surgical technique to help us to spare them during systematic lymph node dissection (The video presents the technique of laparoscopic nerve-sparing lymph node dissection [39]). The following papers will focus on the functional outcomes of sparing the abdominal aortic plexus during systematic lymph node dissection for gynecological cancers.
5. Conclusions The nerve-sparing systematic lymph node dissection is feasible in gynaecological malignancies by following the aforementioned anatomical depended surgical technique for dissection the aortic and superior hypogastric plexus. This might enhance the postoperative functional outcomes, especially the sexual complications after such surgeries.
Author Contributions: Conceptualization, M.Z.M.; methodology, M.Z.M. and T.J.; investigation, M.Z.M. and J.M.; resources, M.Z.M. and J.S.; data curation, Y.D. and J.M.; writing—original draft preparation, M.Z.M.; writing—review and editing, Y.D.; visualization, supervision and project administration, M.Z.M. and J.S. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations SMA, superior mesenteric artery; IMN, intermesenteric nerve; 1st RLG, first right lumbar ganglion of sympathetic trunk; SRLSN, superior right lumbar splanchnic nerve; 2nd RLG, second right lumbar ganglion of sympathetic trunk; MLV, middle lumbar vessels; IRLSN, inferior right lumbar splanchnic nerve; 3rd RLG, third right lumbar ganglion of sympathetic trunk; ILV, inferior lumbar vessels; SHP, superior hypogastric plexus; LRV, left renal vein; 1st LLG, first left lumbar ganglion; RLV, renal–lumbar vein; SLLSN, superior left lumbar splanchnic nerve; 2nd LLG, second left lumbar ganglion; ILLSN, inferior left lumbar splanchnic nerve; IMA, inferior mesenteric artery; IMG, inferior mesenteric ganglion; 3rd LLG, third left lumbar ganglion.
References
1. Emons, G. Significance of Lymph Node Dissection in Gynecological Oncology. Oncol. Res. Treat. 2014, 37, 500–504. [CrossRef][PubMed] 2. Papadia, A.; Remorgida, V.; Salom, E.M.; Ragni, N. Laparoscopic pelvic and paraaortic lymphadenectomy in gynecologic oncology. J. Am. Assoc. Gynecol. Laparosc. 2004, 11, 297–306. [CrossRef] 3. Abu-Rustum, N.R.; Angioli, R.; Bailey, A.E.; Broach, V.; Buda, A.; Coriddi, M.R.; Dayan, J.H.; Frumovitz, M.; Kim, Y.M.; Kimmig, R.; et al. IGCS Intraoperative Technology Taskforce. Update on near infrared imaging technology: Beyond white light and the naked eye, indocyanine green and near infrared technology in the treatment of gynecologic cancers. Int. J. Gynecol. Cancer 2020.[CrossRef][PubMed] 4. Harter, P.; Sehouli, J.; Lorusso, D.; Reuss, A.; Vergote, I.; Marth, C.; Kim, J.-W.; Raspagliesi, F.; Lampe, B.; Aletti, G.; et al. A randomized trial of lymphadenectomy in patients with advanced ovarian neoplasms. N. Engl. J. Med. 2019, 380, 822–832. [CrossRef][PubMed] 5. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren, Kurzversion 4.0, 2020, AWMF-Registernummer: 032/035OL. Available online: https://www.leitlinienprogramm-onkologie.de/leitlinien/ovarialkarzinom/ (accessed on 20 October 2020). 6. Bhatla, N.; Aoki, D.; Sharma, D.N.; Sankaranarayanan, R. Cancer of the cervix uteri. Int. J. Gynecol. Obstet. 2018, 143, 22–36. [CrossRef][PubMed] 7. Muallem, M.Z.; Jöns, T.; Seidel, N.; Sehouli, J.; Diab, Y.; Querleu, D. A Concise Paradigm on Radical Hysterectomy: The Comprehensive Anatomy of Parametrium, Paracolpium and the Pelvic Autonomic Nerve System and Its Surgical Implication. Cancers 2020, 12, 1839. [CrossRef] 8. Muallem, M.Z.; Miranda, A.; Muallem, J. Nerve-sparing radical hysterectomy—Muallem technique with explanation of parametrium and paracolpium precise anatomy. Int. J. Gynecol. Cancer 2020.[CrossRef] Cancers 2020, 12, 3473 9 of 10
9. Muallem, M.Z.; Armbrust, R.; Neymeyer, J.; Miranda, A.; Muallem, J. Nerve Sparing Radical Hysterectomy: Short-Term Oncologic, Surgical, and Functional Outcomes. Cancers 2020, 12, 483. [CrossRef] 10. Beveridge, T.S.; Johnson, M.; Power, A.; Power, N.E.; Allman, B.L. Anatomy of the nerves and ganglia of the aortic plexus in males. J. Anat. 2015, 226, 93–103. [CrossRef] 11. Beveridge, T.S.; Johnson, M.; Power, N.E.; Allman, B.L. Histological verification of the prehypogastric and ovarian ganglia confirms a bilaterally symmetrical organization of the ganglia comprising the aortic plexus in female human cadavers. J. Anat. 2016, 228, 805–811. [CrossRef] 12. Clemente, C.D. Gray’s Anatomy of the Human Body, 30th ed.; Lea & Febiger: Philadelphia, PA, USA, 1985. 13. Shiozawa, T.; Huebner, M.; Hirt, B.; Wallwiener, D.; Reisenauer, C. Nerve-preserving sacrocolpopexy: Anatomical study and surgical approach. Eur. J. Obstet. Gynecol. Reprod. Biol. 2010, 152, 103–107. [CrossRef] [PubMed] 14. Ripperda, C.M.; Jackson, L.A.; Phelan, J.N.; Carrick, K.S.; Corton, M.M. Anatomic relationships of the pelvic autonomic nervous system in female cadavers: Clinical applications to pelvic surgery. Am. J. Obstet. Gynecol. 2017, 216, 388.e1–388.e7. [CrossRef][PubMed] 15. Muallem, M.Z.; Diab, Y.; Sehouli, J.; Fujii, S. Nerve-sparing radical hysterectomy: Steps to standardize surgical technique. Int. J. Gynecol. Cancer 2019, 29, 1203–1208. [CrossRef][PubMed] 16. Haroun, H.S.W. Clinical anatomy of the splanchnic nerves. MOJ Anat. Physiol. 2018, 5, 87–90. [CrossRef] 17. Nagar, H. The role of lymphadenectomy in ovarian epithelial cancer. In Ovarian Cancer—From Pathogenesis to Treatment; InTechopen: Londeon, UK, 2018. [CrossRef] 18. Fastrez, M.; Goffin, F.; Vergote, I.; Vandromme, J.; Petit, P.; Leunen, K.; Degueldre, M. Multi-center experience of robot- assisted laparoscopic para-aortic lymphadenectomy for staging of locally advanced cervical carcinoma. Acta Obstet. Gynecol. Scand. 2013, 92, 895–901. [CrossRef] 19. Vandeperre, A.; Van Limbergen, E.; Leunen, K.; Moerman, P.; Amant, F.; Vergote, I. Para-aortic lymph node metastases in locally advanced cervical cancer: Comparison between surgical staging and imaging. Gynecol. Oncol. 2015, 138, 299–303. [CrossRef] 20. Gouy, S.; Morice, P.; Narducci, F.; Uzan, C.; Gilmore, J.; Kolesnikov-Gauthier, H.; Querleu, D.; Haie-Meder, C.; Leblanc, E. Nodal-staging surgery for locally advanced cervical cancer in the era of PET. Lancet Oncol. 2012, 13, e212–e220. [CrossRef] 21. Uzan, C.; Souadka, A.; Gouy, S.; Debaere, T.; Duclos, J.; Lumbroso, J.; Haie-Meder, C.; Morice, P. Analysis of morbidity and clinical implications of laparoscopic para-aortic lymphadenectomy in a continuous series of 98 patients with advanced-stage cervical cancer and negative PET-CT imaging in the para-aortic area. Oncologist 2011, 16, 1021–1027. [CrossRef] 22. Loverix, L.; Salihi, R.R.; Van Nieuwenhuysen, E.; Concin, N.; Han, S.; van Gorp, T.; Vergote, I. Para-aortic lymph node surgical staging in locally-advanced cervical cancer: Comparison between robotic versus conventional laparoscopy. Int. J. Gynecol. Cancer 2020, 30, 466–472. [CrossRef] 23. Marnitz-Schulze, S.; Tsunoda, A.; Martus, P.; Vieira, M.V.; Affonso, R.; Nunes, J.S.; Budach, V.; Schneider, A.; Hertel, H.; Mustea, A.; et al. Uterus-11 study: A randomized clinical trial on surgical staging versus CT-staging prior to primary chemoradiation in patients with FIGO 2009 stages IIb-IVa cervical cancer. Int. J. Gynecol. Cancer 2019, 29.[CrossRef] 24. Andersen, B.L. Quality of life for women with gynecologic cancer. Curr. Opin. Obstet. Gynecol. 1995, 7, 69–76. [CrossRef][PubMed] 25. Andersen, B.L.; Woods, X.A.; Copeland, L.J. Sexual self-schema and sexual morbidity among gynecologic cancer survivors. J. Consult. Clin. Psychol. 1997, 65, 221–229. [CrossRef][PubMed] 26. Carmack Taylor, C.L.; Basen-Engquist, K.; Shinn, E.H.; Bodurka, D.C. Predictors of sexual functioning in ovarian cancer patients. J. Clin. Oncol. 2004, 22, 881–889. [CrossRef][PubMed] 27. Jensen, P.T.; Groenvold, M.; Klee, M.C.; Thranov, I.; Petersen, M.A.; Machin, D. Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A longitudinal study. Cancer 2004, 100, 97–106. [CrossRef] [PubMed] 28. Bakker, R.M.; Pieterse, Q.D.; van Lonkhuijzen, L.R.C.W.; Trimbos, B.J.B.M.Z.; Creutzberg, C.L.; Kenter, G.G.; de Kroon, C.D.; Ter Kuile, M.M. A Controlled Study on Vaginal Blood Flow during Sexual Arousal among Early-Stage Cervical Cancer Survivors Treated with Conventional Radical or Nerve-Sparing Surgery with or without Radiotherapy. Int. J. Gynecol. Cancer 2017, 27, 1051–1057. [CrossRef][PubMed] Cancers 2020, 12, 3473 10 of 10
29. Maas, K.; Moriya, Y.; Kenter, G.; Trimbos, B.; van de Velde, C. A plea for preservation of the pelvic autonomic nerves. Lancet 1999, 354, 772–773. [CrossRef] 30. Meston, C.M.; Frohlich, P.F. The neurobiology of sexual function. Arch. Gen. Psychiatry 2000, 57, 1012–1030. [CrossRef] 31. Basson, R. A model of women’s sexual arousal. J. Sex Marital Ther. 2002, 28, 1–10. [CrossRef] 32. Laan, E.; Everaerd, W.; van der Velde, J.; Geer, J.H. Determinants of subjective experience of sexual arousal in women: Feedback from genital arousal and erotic stimulus content. Psychophysiology 1995, 32, 444–451. [CrossRef] 33. Lorenz, T.A.; Harte, C.B.; Hamilton, L.D.; Meston, C.M. Evidence for a curvilinear relationship between sympathetic nervous system activation and women’s physiological sexual arousal. Psychophysiology 2012, 49, 111–117. [CrossRef] 34. Meston, C.M. Sympathetic nervous system activity and female sexual arousal. Am. J. Cardiol. 2000, 86, 30F–34F. [CrossRef] 35. Hasenburg, A.; Sehouli, J.; Lampe, B.; Reuss, A.; Schmalfeld, B.; Belau, A.K.; Bossart, M.; Mahner, S.; Hillemanns, P.; Petry, U.; et al. LION-PAW (lymphadenectomy in ovarian neoplasm) sexual function assessment: A prospective sub-study of the LION trial. Int. J. Gynecol. Cancer 2020, 30, 1548–1553. [CrossRef] [PubMed] 36. Muallem, M.Z.; Department of Gynecology with Center for Oncological Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Virchow Campus Clinic, Charité Medical University, 13353 Berlin, Germany. Personal communication, 2020. 37. Muallem, M.Z.; Sehouli, J.; Miranda, A.; Richter, R.; Almuheimid, J. Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation): A novel surgical technique for advanced ovarian cancerInternational. J. Gynecol. Cancer 2020.[CrossRef][PubMed] 38. Muallem, M.Z. Nerve Sparing Aortic Lymph Node Dissection. Available online: https://www.youtube.com/ watch?v=qGqJ6NcdWz4 (accessed on 20 October 2020). 39. Muallem, M.Z. Available online: https://www.youtube.com/watch?v=jI5jEivNJuc (accessed on 20 October 2020).
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).