{"paper_id":"9994f6ed-c1fb-4a44-bb73-0a27e2eb2c91","body_text":"ABC of Endometriosis Surgery: Aqua Blue Contrast Technique \nTamer Seckin, Bahar Yuksel, Serin Seckin, Ayse Ayhan \n \n \n \n \nTamer Seckin, MD,Lenox Hill Hospital-Northwell Health Department of Obstetrics and \nGynecology, New York \nBahar Yuksel, MD,Endofoundation of America, Northwell Health Obstetrics and Gynecology \nDepartment, New York \nSerin Seckin, MD, Department of Gynecology, Mt. Sinai St. Luke's and Mt. Sinai West, New \nYork \nAyse Ayhan, MD, Department of Pathology, Seirei Mikatahara Hospital, and the Department of \nTumor Pathology, Hamamatsu University School of Medicine Hamamatsu, and the Department \nof Molecular Pathology, Hiroshima University School of Medicine, and the department of \npathology \n \n \n \n \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.\n\nAbstract \nObjective: Peritoneal endometriosis is the most prevalent yet least diagnosed type due to its \nunrecognizable nature on imaging modalities especially non- pigmented lesions would escape \nthe surgeons’ eye and experience during diagnostic laparoscopy. We used color adjuvant by the \ntechnique called Aqua Blue Contrast Technique (ABCT) to optimize the view and to improve \nresults. \nMaterial methods: Patient charts who undergone surgery from 2014 to 2015 and their 5 year \nfollow up data, along with two different control groups, have been analyzed retrospectively. As \nthe first group the patients who had conventional surgery without the use of ABCT)were \nincluded, the second group  were patients who had ABCT applied on both pelvic side walls but \nnot in cul-de-sac and as the third group the patients who had the surgery with the use of ABCT in \nall peritoneal cavity have been analyzed. Cases involving ovarian endometriomas and DIE were \nexcluded. \nResults: All patients have been followed up for up to 5 years. In group 1, the recurrence within \nthe postoperative 3 years was 11.9% , and 16.1% after 5 years of surgery. The recurrence of 3 \nyears period and 5 years period for the patients in group 2 were 8.7& and 12.1% respectively. \nThe patients in group 3 recurred 3.2% in the 3 years period and the 4.3% recurrence rate \ncalculated as  4.5% for the following 5 years after surgery. \nConclusion: Results indicate elimination of high-end spectrum of light using aqua blue contrast \ntechnique with hydrodistension of the retroperitoneum enhances the surgeon’s vision, allows \nlesions otherwise not detected with white light.   \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nIntroduction \nWhat is invisible to human eye does not mean its non-existence, and science always have its way \nto find it! This is one of the many situations where physics merges into medicine to solve \nproblems.  \nLaparoscopy offered magnified access to the cavities, including the pelvic cavity eventually \nleading to recognition peritoneal endometriosis lesions otherwise not recognized during \nlaparotomy. Late 1980’s and early 1990’s pigmented and non-pigmented occult lesions were \ndescribed(1, 2). Since then no further discussions, and descriptions concerning the non-typical \nlesions were subject of any publication for about 30 years. A narrow band imaging via the \ncouplers light source as well as color adjuvants such as ICG - fluorescent dye and indigo carmine \nwere used to detect early angiogenesis of endometriosis lesions, with no clear documented \ndiagnostic advantage(3-5). Here we offer a simple, cost effective novel technique to identify \nwide range of non-pigmented occult peritoneal lesions otherwise not recognized under the \nroutine bright laparoscopic white light.  \n \nEndometriosis is an estrogen sensitive stem cell driven chronic inflammatory condition of the \nfemale pelvis characterized by the presence of endometrium like lesions outside of the uterine \ncavity(6, 7). Subsequent to visual recognition, the definitive diagnosis is based on surgical \nexcision and histopathological examination of the resected tissue under the microscope for \nverifying endometrial glands and stroma. Based on surgically proven lesions that are excised, the \nprevalence of endometriosis in women on their reproductive ages all over the world, is at least \n10% (2, 3).  The real prevalence is still unknown because of underdiagnosis due to the lack of \nvisibility/perceptibility hence to capture endometriotic lesions during surgery. \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nEndometriosis, as described by Nisolle and Donnez, is considered to have three anatomical \nsubtypes, which are peritoneal endometriosis, ovarian endometriomas and deep infiltrative \nendometriosis (DIE)(8-10). Peritoneal endometriosis is the most prevalent yet least diagnosed \ntype due to its unrecognizable nature on imaging modalities while ovarian endometriomas and \ndeep infiltrative endometriosis lesions can be readily detected by ultrasound or MRI imaging \n(11). Furthermore, the preponderant presence of non- pigmented lesions would escape the \nsurgeons’ eye and experience during diagnostic laparoscopy.  In fact, most of the surgeries \nperformed for deep endometriosis or ovarian endometriomas usually fail and may necessitate re-\nsurgery upon insufficient excision of the peritoneal disease (12). Overall the lesions on the \nperitoneum can be scant in number, yet the presence of diffuse miliary and aggressive lesion is \nnot uncommon. Therefore, defining this condition as “superficial” endometriosis may underscore \nthe validation of multiple organ symptoms. Missing the lesions and so the disease cause \nmisleading, misdiagnosing these patients as irritable bowel syndrome or pelvic floor disfunction \nhence undertreatment. Not only the problems of recurrence, occurrence of new lesions or the \ngrowth of occult ones, but also many symptoms including infertility, all should be based on the \nabove facts (13) \nThe cardinal presentations of endometriosis are progressive pelvic pain primarily initiated with \ndysmenorrhea, gastrointestinal symptoms and infertility (14). Whether it can be thought the most \ndevastating anatomical lesion may cause more pain, the pain of endometriosis is usually \nunrelated with the characteristics of pathology or severity of the disease (15). Therefore, a small \nlesion even not visible to the naked eye may cause more pain than a large DIE nodule. This \nknowledge further strengthens the importance of appropriately treating all lesions on a \nsymptomatic patient with pain. \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nThe standard surgical technique to diagnose and treat endometriosis is laparoscopic surgery. \nUnder laparoscopic scope, endometriotic lesions can readily be identified when they are \npigmented, also known as classical typical lesions as described by Sampson back in 1920’s(16) . \nThese lesions are in black, red, blue raspberry. Occult types of white colors and as flat or \npolypoid are described later 1n 1980’s (10).  Although human eye can see wavelengths between \n400-700 nm , it is not always easy to visualize all pathologies even with the 4 to 40 times \nmagnification of usual laparoscopic scopes(17).Reflection of underlying red and yellow hues \nprevents  discrimination of different tissue types under white light (18). As certain color \ncombinations provide better contrast than others like, red and yellow against blue; to make \nobjects easy to be caught by human eye using color contrasts would be an important advantage. \nGiven the orange-red color of the intraabdominal tissues a blue dye would provide the best color \ncontrast. \nIn our novel, Aqua Blue Contrast Technique™(ABCT ) for endometriosis surgery we used \nmethylene blue (methylene blue-methylthioninium chloride, C16H18N3SCl) for its natural blue \ncolor to make endometriotic lesions more visible and to filter red, yellow and white colors \nreflecting from peritoneal surface yet endometriosis primarily of its initial stage a peritoneal \nprocess. We aimed to evaluate the advantage of the technique to detect the peritoneal occult \nlesions, to see and compare the difference in endometriosis lesions ,recurrence rates and quality \nof life changes within the same patient which ABC is used on pelvic side walls but not in cul-de- \nsac, also in patients groups that the technique is applied and not applied. \n \n \nMaterial Methods \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nAfter institutional review board (IRB) approval (17-0645-NH) has been taken, patient charts who \nundergone surgery from 2014 to 2015 and their 5 year follow up data, along with two different \ncontrol groups, have been analyzed retrospectively. As the first group the patients who had \nconventional surgery without the use of ABC technique (ABCT) were included, the second \ngroup  were patients who had ABCT applied on both pelvic side walls but not in cul-de-sac and \nas the third group the patients who had the surgery with the use of ABCT in all peritoneal cavity \nhave been analyzed. All patients who had suspicious endometriosis according to the pain \nsymptoms but has no DIE nodules or endometriomas either in transvaginal ultrasound or in \nMagnetic Resonance Imaging (MRI) techniques and histologically proven peritoneal \nendometriosis after surgical removal have been included into the study. Cases involving ovarian \nendometriomas and DIE were excluded. All patients gave informed consent that their surgical \nnotes can be used on a scientific research manner. \nIn the second and third groups a novel surgical approach has been used which includes a blue \ndye contrast usage, a unique aspect of excision surgery procedure called Aqua Blue Contrast \nTechnique™(19).  A solution made of 1 % methylene blue in 3000 cc isotonic sodium chloride \nhas been prepared for the use at the surgery. All surgeries were done by the same trained \nendoscopic surgeon (TS). Laparoscopic approach using 10 mm umbilical trocars and 2 or 3 5 \nmm sister trocars has been placed. After visual inspection of pelvic and peritoneal organs, first \nphase involve hydro floatation, and submersion. MB is flushed, filled to the pelvic peritoneal \ncavity catch vision of floating or vegetative lesions under blue liquid which we called as \nimmersion phase. And after sucking out all blue water, the second step which is called as \nretroperitoneal hydrodistension phase was initiated with a small 0.5cm excision was made on the \nperitoneum medial to IP ligament at the pelvic brim. Through the incision, laparoscopic \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nirrigation tip which is connected to the ABC dye, was advanced into retroperitoneum of the \npelvic sidewalls. Under 200 mmHg irrigation pressure  retro peritoneal connective tissue space \nwas hydro distended with diluted blue dye adjuvant Methylene Blue (20). All peritoneal cavity \nwere inspected under direct submersion, but ABC hydro distention was only performed on the \npelvic sidewalls while cul-de-sac has left for bare eye recognition in group 2 and all \nretroperitoneum was hydro distended in group 3. All suspected lesions for endometriosis have \nbeen excised by cold scissors and specimens send for histopathological investigation. No adverse \neffects related to the MB use have been reported. Hematoxylin and eosin (H&E) staining has \nbeen used for microscopic evaluation and diagnosis. And all specimens have been undergone \nhistopathological evaluation and classified according to the results. \nAfter all cases were collected their files were searched for following 5 years period and patients \nwho are re-operated because of pain recurrence have been noted. \nStatistical analyses were performed using the version 20.0 of Statistical Package for the Social \nSciences software (SPSS, Inc, Chicago, Illinois). A P value of <0.05 was considered significant. \n \n \n \n \n \n \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nResults \nThe pathology reports were analyzed, and histological diagnosis were noted as typical \nendometriosis, stromal endometriosis without glands in exhausted serial sections, inflammation, \nand fibrosis, documented in Table …In group one 371 cases have been reviewed. Out of 1452 \nsamples taken from all locations   1383(95.2%) were found to be typical endometriosis, \n13(0.95%) as stromal endometriosis, 56 (3.9%) as inflammation and/or fibrosis. In group 2 out of \n775 samples, 407 were found to be typical endometriosis, 49 stromal endometriosis, 237 \ninflammation and 82 fibrosis. Six hundred sixty-three samples were collected from pelvic side \nwalls where ABC technique have been applied but only 112 suspected lesions have been \ndetected without blue contrast from cul-de-sac (z=2.133, p<0.05) The distribution of pathology \ndiagnoses of the samples taken from cul-de-sac were; 58 (52%) typical endometriosis, 2 (2%) \nsamples for  stromal endometriosis, 52 (47%) inflammation and/or fibrosis , while  663 samples \nfrom pelvic side walls came out as 349 (53%) typical endometriosis, 47 stromal endometriosis \n(7%) ,267 (40%) inflammation and or fibrosis. The evaluation of the pathological diagnoses \nregarding typical endometriosis, fibrosis and inflammation showed similar distribution while the \nproportion of stromal endometriosis significantly greater in pelvic sidewall excisions compared \nto cul-de-sac excisions (47 sidewalls, 2 cul de sac; z=19.79, p<0.0001). And out of 7080 samples \ntaken from 684 patients in group 3, 5217 (73.7%) samples analyzed as typical endometriosis, \n476 (6.7%) as stromal endometriosis, 1387 (19.5%) as inflammation and/or fibrosis. \n \nAll patients have been followed up for up to 5 years. In group 1, the recurrence within the \npostoperative 3 years was 11.9% , and 16.1% after 5 years of surgery. The recurrence of 3 years \nperiod and 5 years period for the patients in group 2 were 8.7& and 12.1% respectively. The \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\npatients in group 3 recurred 3.2% in the 3 years period and the 4.3% recurrence rate calculated as  \n4.5% for the following 5 years after surgery. When the histopathological evaluation of surgically \nresected material from  recurrent 14 patients in group 2 ,where the ABCT partially used ,were \nanalyzed, 25 pelvic side wall [13 (52%) typical endometriosis , 9(36%) inflammation and \n3(12%) fibrosis] and 84 cul-de-sac [53 (63%) typical endometriosis, 5(6%) inflammation, \n26(31%) fibrosis]. The statistical comparison of the number and distribution of histopathology \nresults between pelvic side wall and cul-de-sac samples did not reveal any statistical  \nsignificance (p=0.60). In the recurrent operation, additionally two patients needed DIE nodule \nresection, 8 patients required endometrioma surgery, 1 patients had endometrial polyp resection, \n3 patients had appendix removal because of being affected by endometriosis. \n \n \n \n \n \n \n \n \n \n \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nDiscussion \n       MB by having minimal and benign side effects as dizziness, head ache, diarrhea \nand also very rarely excitation caused by its monoamine oxidase inhibitor (MAOI)function, \nfound its place in World Health Organization’s essential medicine medications list(21).  \n \nABC technique provides a laparoscopic surgery method allowing better inspection of peritoneal \nsurfaces under a blue colored solution, by a contrast enhancing agent, typically using near \ncontact scanning by a laparoscope. This technique easily identified normal peritoneum and its \ntexture and successfully distinguished it from abnormal peritoneal surfaces. This method assists \nthe surgeon to precisely target the lesion by distinct recognition of even most subtle lesions and \nassociated peritoneal changes in endometriosis. Eliminating the yellow and red hues by blue \nretroperitoneal  contrast, it helps to perform tedious, precise and  accurate excision surgery \nwithout indiscriminate removal of normal peritoneum(22).  \nThis study however showed that by the aid of ABC technique, it is possible to recognize and \nremove more endometriosis lesions from pelvic sidewalls which was assumed to be less effected \ncompared to cul-de-sac and also from all over the  peritoneal area that the technique has been \napplied Also long term results showed that using ABCT prevented recurrence of the disease \nsignificantly. \nChanging the color spectrum and using hydro floatation with contrast color and retroperitoneal \ndistention may help to visualize the morphological features of the peritoneum along with \nendometriosis otherwise undetectable by standard laparoscopic light inspection. Further, \nretroperitoneum hydro-distention and creation of blue color contrast in the background makes it \npossible to identify peritoneal micro defects to determine the excision boundaries and allows \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\ninspection of retroperitoneal space under blue colored solution for microinvasion and fibrosis \n(23). Under these circumstances, the blue color infused into the connective tissue of \nretroperitoneal organs and peritoneum itself acts as a blue color filter just reflecting only blue \nlight and eliminating the interfering  all reds and yellows. By absorbing and blocking red and \ngreen colors, blue reflection in addition contributes visual representation of only blue light,  \ntherefore  objects with contrast color light component would seem without a color which is black \nto human eye(24). Red is a primary color while yellow on one perception a secondary color and, \nmade of green and red light so this explains any kind of red or yellowish spot would appear as \nblack spot under blue filter(25) On the other hand, according to Isaac Newton’s almost 300 years \nold color wheel theory, primary colors are three: blue, red and yellow.  Red  and yellow represent \nthe opposite spectrum, meaning they are contrast colors of blue (26). Also, fibrotic tissues more \ndistintive features, conspicuously recognized with white, and off-white nature towards blue \neffluence. This might explain why all endometriotic lesions seem more visible to human eye \nunder Aqua Blue Contrast Technique™. \nAccording to the retrograde menstruation theory of Sampson’s, as also quoted by published \nworks of others, cul-de-sac is the most common location for peritoneal endometriosis (27). \nHowever, a trained endometriosis surgeon should be aware that the non-pigmented \nendometriosis lesions constitute the majority of the disease and are unrecognizable by human eye \nbecause of the color and light reflections under white light of the scope.  \nThe easy-to-visualize types of endometriosis, namely the pigmented lesions,  are   typically  red, \npurple or black, and easily recognized over others which are subtle and invisible, also called as \nmicroscopic endometriotic lesions (1, 28, 29). The results of our study may not be enough to say \nthat the pelvic side walls are affected more than cul-de-sac, but definitely mean to say that the \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\ncolor contrast technique efficiently helps human eye to recognize distorted areas easily. In the \npresent study, we reached at the conclusion that aided by  Aqua Blue Contrast Technique™, the \nexcision rate multiplied by at least 2.13 times compared to unaided detection under laparoscopic \nlight. \nLaparoscopic surgery is the only standard availing both diagnosis and treatment of \nendometriosis. The efficiency of the primary surgery increases patient’s quality of life whereas \nincomplete excision risks symptom relapses and recurrent surgeries (15, 26). In our study the \nfive year follow up of the patients with focal excision of endometriosis lesions using Aqua Blue \nContrast Technique™ showed a recurrence rate resulting in 13% reoperation, while studies in the \nliterature showed more than 30% recurrence after 36 months follow up of the patients who are \noperated by conventional techniques (30).   \nPelvic pain with dysmenorrhea is the cardinal symptom of endometriosis but the underlying \nmechanism is remains inconclusive(31). The studies aiming to specify a correlation between \nlesion feature and pain symptoms have been unsuccessful. It is not known whether the pain is \ncaused by endometriosis itself or due to the fibrosis or inflammation (32). However numerous \nstudies demonstrated that the angiogenesis component of endometriosis also reveal neurogenesis \nalong with the macrophage activity in the developing new lesions(33)  The resection of all \nlesions along with fibrotic distortions caused by endometriosis with the aim of restoring \nanatomy, remains critical center core of the treatment. Previous studies showing endometriosis as \na stem cell derived estrogen sensitive metaplastic inflammation with the presence of gland and/or \nstroma increases the importance of resection of all effected tissues(7). The effect of fibrosis, \ninflammation and stromal endometriosis should be investigated in further studies. \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nThe limitations of this study is its retrospective character, however, has enough power when the \npatient numbers are concerned.  The in vivo effect, the chance to compare lesions on each same \npatient and all operations being done by the same surgeon give further strength to the study. \nAlso, the low cost, simple applicability of the technique over other color adjuvants or  narrow-\nband light techniques, and the safety without any side effect, offer more opportunity along with a \nwide range utilization.  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\n \nConclusion  \n \nIdentification of the disease by the surgeons is only possible by recognizing the lesion based on \nits visual characteristics. Failing the visual recognition of different endometriosis lesions and \nmissing the non-colored lesions would lead to incomplete surgery, lead to inaccurate data \nnegatively impacting forthcoming research and scholarly reviews, and most importantly leading \nto treatment failure.   \n  Results indicate elimination of high-end spectrum of light using aqua blue contrast technique \nwith hydrodistension of the retroperitoneum enhances the surgeon’s vision, allows lesions \notherwise not detected with white light.  We have shown the evidence by increased number of \nexcision specimens and increased proportion of stroma-positive specimens with Aqua Blue \nContrast Technique™. It is notable that statically significant increase of cul-de-sac lesions in \nrepeat surgeries would imply either the persistence of the disease possibly missed due to not \nusing Aqua Blue Contrast Technique™, or de novo appearance of new lesions in favor cul-de-\nsac over previously excised pelvic sidewalls. \n \n \n \n \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nTable 1: Distribution of pathology results  \n \n Patients (n) \n samples (n) Endometriosis \nn (%) Stromal endometriosis \nn (%) Inflammation+/- fibrosis \nn (%) P value \nGroup 1 371 1452 1383 (95.2%) * 13(0.95%) 56(3.9%)  \nGroup 2, CDS 115 112 58 (52%) 2(2%) 52(47%)  \nGroup 2, PSW 115 663 349(53%) 47(7%)267(40%)  \nGroup 3 684 7080 5217(73.7%) *476(6.7%) 1387(19.5%)  \nP value   P<0.001    \n \n \n \nTale 2: Recurrence ratios of each groups for 3 and 5 years follow up periods \n Group1 \n(n=371) Group2 \n(n=115) Group3 \n(n=684) P value \nRecurrence within 3 years of postoperative period \nn (%) 44(11.9%) 10(8.7%) 22(3.2%)  \nRecurrence within 5 years of postoperative period \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\nn (%) 60 (16.1%) 14 (12.1%) 4.5%(expected)??  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\n \n \n \n1. Redwine DB. Age-related evolution in color appearance of endometriosis. Fertility and \nsterility. 1987;48(6):1062-3. \n2. Martin DC, Hubert GD, Vander Zwaag R, el-Zeky FA. Laparoscopic appearances of \nperitoneal endometriosis. Fertility and sterility. 1989;51(1):63-7. \n3. Rauh-Hain JA, Laufer MR. Increased diagnostic accuracy of laparoscopy in \nendometriosis using indigo carmine: a new technique. Fertility and sterility. 2011;95(3):1113-4. \n4. Cosentino F, Vizzielli G, Turco LC, Fagotti A, Cianci S, Vargiu V, et al. Near-infrared \nimaging with indocyanine green for detection of endometriosis lesions (Gre-Endo Trial): a pilot \nstudy. Journal of minimally invasive gynecology. 2018;25(7):1249-54. \n5. Al-Taher M, Hsien S, Schols RM, Hanegem NV, Bouvy ND, Dunselman GAJ, et al. \nIntraoperative enhanced imaging for detection of endometriosis: A systematic review of the \nliterature. European journal of obstetrics, gynecology, and reproductive biology. 2018;224:108-\n16. \n6. Alimi Y, Iwanaga J, Loukas M, Tubbs RS. The Clinical Anatomy of Endometriosis: A \nReview. Cureus. 2018. \n7. 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Color vision, cones, and color-coding in the cortex. Neuroscientist. \n2009;15(3):274-90. \n25. Gismondi E. Polychrome lighting device having primary colors and white-light sources \nwith microprocessor adjustment means and remote control. Google Patents; 1999. \n26. Newton IOp. Optics PP 114–117. 1704. \n27. Sampson JA. The development of the implantation theory for the origin of peritoneal \nendometriosis. American Journal of Obstetrics and Gynecology. 1940;40(4):549-57. \n28. Donnez J, Van Langendonckt A. Typical and subtle atypical presentations of \nendometriosis. Curr Opin Obstet Gynecol. 2004;16(5):431-7. \n29. Redwine DB. 'Invisible' microscopic endometriosis: a review. Gynecologic and obstetric \ninvestigation. 2003;55(2):63-7. \n30. Vercellini P, Aimi G, Busacca M, Apolone G, Uglietti A, Crosignani PG. Laparoscopic \nuterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a \nrandomized, controlled trial. Fertility and sterility. 2003;80(2):310-9. \n31. Tokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. \nHuman Reproduction. 2006;21(11):3001-7. \n32. Morotti M, Vincent K, Becker CM. Mechanisms of pain in endometriosis. European \njournal of obstetrics, gynecology, and reproductive biology. 2017;209:8-13. \n33. Asante A, Taylor RN. Endometriosis: the role of neuroangiogenesis. Annu Rev Physiol. \n2011;73:163-82. \n \n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\n \n \n \n Figure 3: Picture of normal healthy peritoneum under ABC technique and peritoneum effected \nby endometriosis  \n \n  \n  \n  \n  \n \n \n  \n   \n \n       \n \n  \nIsaac Newton - Optics, 4th ed., 1730. From Book I, Part II, Proposition VI, Problem 2. This \nfigure is nearly unchanged from that in the 1704 first-edition printing. \n  \nThe primary and secondary colors on light and color palette spectrum (from right to left) \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\n \n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint \n\n \nAll rights reserved. No reuse allowed without permission. \n(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. \nThe copyright holder for this preprintthis version posted February 29, 2020. ; https://doi.org/10.1101/2020.02.27.20027888doi: medRxiv preprint","source_license":"CC0","license_restricted":false}