Pre-Treatment Imaging in the Surgical Management of Endometriosis

1 „Prof. Dr. Panait Sarbu” Clinical Hospital of Obstetrics and Gynecology, Bucharest, Romania 2 Department of Surgery, Elias University Emergency Hospital, Bucharest, Romania 3 MedicalES Imaging Clinic, Bucharest, Romania 4 Department of Radiology, Elias University Emergency Hospital, Bucharest, Romania Corresponding author: Octavian ENCIU, Elias University Emergency Hospital, 17 Marasti Boulevard, 1st District, 011461, Bucharest, Romania. E-mail: esoctavian@gmail.com Abstract


MATERIAL AND METHOD
Transvaginal ultrasound is useful and highly accurate for endometriomas and deep endometriosis diagnosis 5,7 .
Th e menstrual cycle does not infl uence ultrasound evaluation; emptying the rectum and bowel preparation with contrast medium is adjuvant but not mandatory 8 . High-resolution transvaginal scan is recommended to enhance the quality of imaging in evaluation of the rectum and sigmoid colon 9 .
Th e IDEEA Group created a protocol for ultrasound evaluation that brings multiple benefi ts for daily practice: standardization of technique, mandatory evaluation of all pelvic compartments, uniformization of terminology and defi nitions for endometriotic lesions 3 . Th is protocol is useful in current practice by increasing the rate of detection of deep endometriotic lesions and facilitates multicenter research.
Th e protocol calls for a four-step ultrasound evaluation:  Step one is routinely performed in every ultrasound examination and represents the evaluation of the uterus and adnexa searching for of signs of adenomyosis and endometriomas;  Step two checks the mobility and specifi c tenderness of the uterus and ovaries, the so-called "soft markers", using bimanual technique. An ultrasound sign that indicates the presence of

INTRODUCTION
It is essential to map the endometriosis lesions using preoperative imaging evaluation in order to off er to the surgical team details about the extension and severity of the disease. Establishing an accurate diagnosis and preoperative staging, gives the possibility for optimal therapeutic plan, to complete the surgical team with colo-rectal surgeons or urologists, to inform the patient of foreseeable intraoperative complications and to obtain informed consent for each procedure.
To avoid suboptimal treatment and multiple surgical interventions, patients with severe endometriosis (stage III-IV) must be referred to high volume specialized centers 1 .
Transvaginal ultrasound and MRI are not competing but rather complementary investigations. Ultrasound has the advantage of being readily available, routinely performed, at low cost, with minimal patient discomfort and it's a real time evaluation with the opportunity to mobilize the uterus and the adnexa. Meanwhile, MRI off ers essential details in defi ning rectal endometriosis nodules (locations, size, stenosis grade, parietal infi ltration stage) and also can diagnose endometriotic lesions located above the sigmoid colon.
According to current guidelines, transvaginal ultrasound comes fi rst as recommendation during evaluation of patients with suspected endometriosis 2,3 . Every patient with dysmenorrhea or dyspareunia that can be related with endometriosis and/or diagnosed with endometrioma should receive the ultrasound protocol of deep endometriosis.
MRI is indicated in selected cases, for example in symptomatic patients with negative ultrasound fi ndings or in suspected cases of deep endometriosis with adhesions and the absence of ovarian mobility is "kissing ovaries" sign -this fi nding indicates an advanced stage of the disease, which can be more frequently associated with Fallopian obliteration (92,6%) and bowel endometriosis. (18,5%) 10 (Figure 1).  Step three evaluates the status of the pouch of Douglas (POD) using the "sliding sign". A positive sliding sign in the retrocervical region and the level of the upper uterus indicates an unobliterated POD.  Step four aims to identify the presence of endometriotic nodules in the anterior compartment (urinary bladder, uterovesical region) and in the posterior compartment (rectovaginal septum, posterior vaginal fornix, uterosacral ligaments, rectum and sigmoid). Assessment of the mobility between uterus and posterior region of the bladder is paramount because often bladder endometriotic nodules arise from the uterus. Identifying a hypoechogenic wall thickness or nodule with low Doppler signal, involving the muscularis or submucosa of the bladder with a negative "sliding sign" in the anterior compartment are highly suggestive for the diagnosis of urinary bladder endometriotic nodule 11 ( Figure 2).
Th e normal uterosacral ligament is not visible during ultrasound examination, unless it is surrounded by fl uid. Pathological uterosacral ligament is visible in the absence of fl uid if its proximal region is thickened, nodular and hypoechogenic 8 ( Figure 3).
Transvaginal ultrasound has the great advantage of real-time bimanual examination in detecting adhesions in the posterior compartment. Furthermore, the four separate rectosigmoid wall layers have diff erent echogenicity and this allows staging of parietal infi ltration ( Figure 4).
Th e disadvantage of transvaginal ultrasound is that it can't precisely predict the grade of stenosis because the distention of the bowel cannot be estimated. Th e distance between the nodule and the anal orifi ce can be estimated at best taken into consideration that the location of POD is at 7-9 cm from the anal orifi ce. Th e gynecologist has the possibility to use a transrectal probe to estimate more precise the distance to the anal orifi ce, but this method has low compliance among patients 12 .
Previous published data sustain a high accuracy of transvaginal ultrasound in the diagnosis of endometrioma, peri-adnexal adhesions, POD obliteration and bladder nodules 13 . Regarding the uterosacral ligament, sensitivity is lower, without major impact on surgical protocol. 14 A review that included 10 studies demonstrated a sensitivity of 67-98% and a specifi city of 92-100% for bowel endometriotic lesions 15 .
To conclude, a complete imagistic report consists in describing "hard markers" -endometriomas (dimensions, number, typical/atypical aspect), "soft markers", type of surgical procedure, estimating operating time and the possibility of multidisciplinary involvement during the procedure.
Not so often, these goals are diffi cult if not impossible to achieve just by using transvaginal ultrasound, this is where MRI brings light in a dark landscape.
Th is information is extremely important for the surgeon in elaborating the therapeutic plan, choosing the  the above, patients must express an informed consent for stoma and time should be taken to explain the risks and possible complications.
Endometriosis nodules that infi ltrate the rectal muscularis should be completely resected, this implies a certain type of rectal resection 17 . For this reason, it is essential to know the grade of parietal infi ltration for choosing the correct surgical technique, and both imaging investigations, ultrasound and MRI satisfy this purpose. Th e majority of endometriotic lesions that have penetrated the muscularis and submucosa are found to aff ect at least 40 % of the circumference of the rectal wall 18 .
Predicting the stenosis grade and the dimension of the nodule is mandatory for choosing the correct type of resection -nodulectomy, discoid or segmental bowel resection. MRI and ultrasound are limited in measuring the maximum grade of bowel distention, water enema with a 24 Fr Foley rectal catheter could improve this aspect. Rectal and vaginal opacifi cation with sonographic gel is suggested as an option that could provide better evaluation of POD, the rectovaginal septum, and rectosigmoid endometriosis 4 .
In summary, MRI brings diagnosis reliability, increases the recognition of subperitoneal lesions and the ones covered by adhesions, off ers precise data of nodules characteristics and can provide a road map that MRI is an advantageous technique because it off ers multiplanar evaluation, high resolution, lack of radiation and the possibility of abdominal and pelvic complete evaluation in a single scan 16 . Compared to ultrasound, it can visualize in one slide the anatomic relation of the uterus and recto-sigmoid colon, therefore can easily identify and diff erentiate a nodule located in the inferior, medium or upper rectum or the recto-sigmoid junction. Ultrasound can only estimate the location of the nodule based on anatomical landmarks: lesions situated bellow the insertion of uterosacral ligament on the cervix are considered lower (sub-peritoneal) anterior rectal lesions, while nodules located above are considered upper anterior rectal lesions; nodules situated at the level of uterine fundus are located at the rectosigmoid junction and the ones above this limit belong to the sigmoid. Th e hyper anteverted and/or retroverted uterine position can misleading regarding the correct localization of rectal/ sigmoid nodules.
During ultrasound examination, the distance from the anal orifi ce is arbitrary evaluated while MRI can directly measure the distance taken into consideration the rectosigmoid curves. It is important for the surgeon to know the exact location of rectal nodules because low rectal resections are more diffi cult to perform, the need for a temporary stoma may occur and the risk of complications may increase manifold. In the light of uterus, T1 gradient with saturated fat in axial plane) ( Figure 6).
Given the lack of symptoms, expected menopause (FSH=60 mUI/ml) and moderate degree of rectal stenosis, a "wait and see" management was suggested with 6 months ultrasound and MRI reevaluation. Ultrasound examination demonstrated "kissing ovaries" -both ovaries were located posterior to the uterus with two endometriotic cysts of 6/5.2/4/3 cm and 4.08/3/2.35 cm; negative "sliding sign" at the retrocervical region and at the uterine fundus -completely obliterated pouch of Douglas. In the posterior compartment, at the level of the uterosacral ligaments, a 3.47/2.37 cm well defi ned hypoechoic nodule that infi ltrates all the layers of the rectal wall was visualized (this corresponds to the medium rectum) (Figure 7).
Pelvic MRI after enema and intravaginal and intrarectal gel instillation diagnosed T2 low signal intensity allows presurgical counseling and complete ablation of all possible endometriotic lesions.

RESULTS
Case 1 -A 43 years old woman with one natural labor 10 years prior describing low intensity dysmenorrhea 3-VAS, without dyspareunia, sporadic constipation without rectal bleeding was referred for routine examination.
A 3.97/3.08 cm ground glass adnexal cystic mass suggestive of endometrioma was diagnosed by ultrasound. IDEA protocol for endometriosis was applied -posterior compartment evaluation by angulating ultrasound probe towards the rectum identifi ed a hypoechoic non-homogenous, non-vascularized nodule that infi ltrates all the layers of the rectal wall. Th e mucosa of the rectal wall was intensely retracted resulting in the so-called "Indian headdress sign" (Figure 5). Th e nodule measured 4.02/1.45/3 cm.
MRI scan confi rmed the diagnosis and further evaluated a 50% degree of stenosis at the mid and upper level of the rectum, approximately 15 cm from the anal orifi ce. Th e MRI protocol lacked intrarectal gel instillation (T2 sagittal coronal and axial 3.5 mm slices, oblique axial and oblique coronal at the level of the Given the pain score, severe quality of life impairment and high degree of stenosis, the patient was referred to a specialized center where she suff ered rectosigmoid resection with termino-terminal anastomosis with no protective stoma. Th e postoperative course was uneventful and was certifi ed by good EHP-30 score 13,89 -low level of quality of life impairment -dysmenorrhea VAS-3, dyspareunia VAS-2 and chronic pelvic pain VAS-2. 3.8/2.3/1.5 cm rectal nodule at the level of the upper rectum/ rectosigmoid junction with 80% stenosiscontrast medium reaches de lower border of the nodule but not more ( Figure 8).
Th e position of the rectal nodule was estimated lower by transvaginal ultrasound because the uterus was hyper anteverted. If the uterus held its normal position, the nodule would have been located at the uterine fundus and at the level of the upper rectum/ rectosigmoid junction.  MRI scan revealed a large 5/3/1.6 cm nodule at the level of the upper rectum and rectosigmoid junction (16 cm from the anal orifi ce). Th e nodule penetrates all the layers of the rectum determining 90% rectal stenosis and also infi ltrates torus uterinus ( Figure 10).
Th e patient was referred for rectal resection. Previous suboptimal treatment permitted the deep lesions to evolve, prevented conception and had a negative psychological impact on the patient that needed constant psychological counsel.
Th e patient suff ered 2 laparoscopic interventions for endometriosis in 2016 and 2018. In 2019, she was started GnRH antagonist medication for symptom control.
A large, well bordered, rectal nodule in contact with the posterior aspect of the uterus was demonstrated by ultrasound ( Figure 9).  Pelvic MRI demonstrated several T1 high intensity signal and T2 low intensity signal cystic lesions at the level of right sciatic nerve, anterior and inferior to the piriform muscle, consistent with the presence of an endometriotic nodule ( Figure 11).
Sciatic nerve endometriosis implants are very rare extraperitoneal locations and should be taken into consideration in young women with catamenial sciatica associated with gluteal pain and motor defi cit 19 . During MRI investigation, high matrix coronal and axial T1 and T2 weighted sequences are recommended to increase the diagnostic rate for this pathology.
Case 4 -42-year-old referred for routine consultation. In depth anamnesis revealed right lumbar and vertebral pain referred to the posterior aspect of the right thigh and to the heel, pain enhanced by movement and during menstruation and chronic motor defi cit. Previous neurology examination and initial MRI examination have stated that the patient suff ered from lumbar disk disease and piriformis syndrome.
Barely in the reach of gynecology, the symptoms that worsened during menstruation drawn attention on endometriosis and the patient was referred for further imaging investigations in a specialized center.  Th e learning curve for transvaginal ultrasound is long, fact observed by Donnez in a study that involved experienced gynecologists that have performed at least 2500 general ultrasound examinations, without specialized experience in transvaginal examinations for endometriosis. After completion of training, the learning curve using the cumulative sum show that the subjects reached the level of profi ciency for diagnostic rectal endometriosis after 37-42 patients scans 23 .
Regarding the MRI learning curve, L. Saba indicated a signifi cant statistical diff erence in sensitivity regarding detection of recto-sigmoidian endometriotic nodules between fi rst and third analysis: 39,1% versus with 82% 24 .

CONCLUSION
Th e most important measures for early diagnosis of deep endometriosis are raised awareness for both patients and physicians and routine ultrasound examinations for symptomatic patients. Th eoretical and practical training at profi le conferences in order to enhance the ability of gynecologists to diagnose deep endometriosis should be encouraged.
Educational programs should be designed for both gynecologists and radiologists to improve collaboration. Feedback with operating room data or images might familiarize the radiologist with subtle surgical and pathology aspects.
Taking into consideration that deep endometriosis is a real public health problem increase eff orts are mandatory to improve diagnostic and surgical skills.
Sciatic nerve endometriosis demands multidisciplinary management and requires highly experienced gynecological surgeons both in endometriosis and neuropelveology.
Th e patient refused surgical treatment intended to remove all endometriotic lesions and was started on Dienogest. Symptoms improved only after 3 months and at 1-year follow-up, chronic pelvic pain downgraded to VAS-7 to VAS-2 and the motor defi cit was minimal. MRI at 1-year has shown 50% decrease of the nodule ( Figure 12).
Potential permanent damage to the sciatic nerve is prevented by early diagnosis and appropriate treatment.

DISCUSSION
Th e diagnosis of deep endometriosis is often challenging. Th ree main elements are required: fi rstly, we should think and raise clinical suspicion based on a complete anamnesis -questions like when, where, and how intense is the pain on a scale of 0-10; secondly, ultrasound endometriosis specifi c markers should be identifi ed, and then we must focus on each anatomical compartment in order to lower the rate of false diagnosis.
Th e delay in establishing the diagnosis is of worldwide concern: for example in Germany and Austria the average time from symptom onset to the positive diagnosis is 10.4 years 20 , in Spain and U.K 8 and 7,9 years in USA 21,22 . Th e main issues for the delay, false negative diagnosis and underestimation of severity may arise from insuffi cient awareness of endometriosis by both patients and physicians and slow development of diagnosis and therapeutic skills. sinki Declaration of 1975, as revised in 2008(5), as well as the national law. Informed consent was obtained from all the patients included in the study.
Compliance with ethics requirements: Th e authors declare no confl ict of interest regarding this article. Th e authors declare that all the procedures and experiments of this study respect the ethical standards in the Hel-