{"paper_id":"ab446391-a24d-455f-80b2-c29560d4582a","body_text":"Submit Manuscript | http://medcraveonline.com\nIntroduction\nEndometriosis is a benign, complex, chronic and progressive \ngynecologic disorder defined as the presence of viable, estrogen-\ndependent endometrial-like gland and stroma associated with \ninflammatory response outside the uterine cavity.1 It is estimated that \nendometriosis is present in 6 to 10% of reproductive age women 2 \nand has been reported as high as up to 40% in subfertile women. 3 \nDespite great effort to elucidate the etiology of endometriosis, its \npathogenesis remains unclear. Different theories had been proposed to \nexplain the origin of this enigmatic disease, from the initial retrograde \nmenstruation theory proposed by Sampson in 1927 to coelomic \npluripotential metaplasia, hematogeneous or lymphatic embolization.4 \nIn a recent comprehensive manuscript, Laganà et al., 5 described an \ninteresting hypothesis in which deregulation of genes could lead to \naberrations and deregulation within the mesoderm which may cause \naberrant implantation of stem cells in addition to alteration in the \nperitoneal microenvironment creating the conditions for proliferation \nectopic endometrial cells. There is three main clinically subtype forms \nof endometriosis consisting of\ni. Superficial endometriotic implants located on the surface of the \npelvic peritoneum and ovaries (peritoneal endometriosis),\nii. Ovarian cysts lined by endometrioid mucosa (endometriomas), \nand\niii. Complex solid masses of endometriosis implants mixed with \nadipose and fibromuscular tissue infiltrating the rectovaginal \nseptum (Deep infiltrating endometriosis. DIE).1\nPatients affected by endometriosis often present with a variety of \nsymptoms including dysmenorrhea, dyspareunia, chronic pelvic pain, \npresence of a pelvic mass and/or subfertility. Comorbid conditions \nfrequently present in patients with endometriosis are fibromyalgia, \ninterstitial cystitis/painful bladder syndrome, irritable bowel \nsyndrome, migraine headache and temporomandibular disorders. 6 \nLaparoscopy with tissue pathologic biopsy is well accepted as \nthe “gold standard” for the diagnosis of endometriosis and is the \ntherapeutic approach of choice when medical treatment produce \nunsatisfactory results. Accuracy of visual diagnosis at the time of \nlaparoscopy increases with disease severity. 7 However, as supported \nby the European Society of Human Reproduction and Embryology \n(ESHRE), histologic confirmation with biopsy is recommended \nbecause visual identification is associated with a high false positive \nrate.8,9 Moreover, endometriosis implants are usually found in multiple \ndifferent location such as the ovaries, fallopian tubes, utero-sacral \nligaments, broad ligaments, round ligaments, culd-de-sac, ovarian \nfossa, bladder serosa, ureters and rectovaginal septum. A thorough \ninspection of the peritoneal cavity during laparoscopy is mandatory to \nidentify all possible endometriosis implants.\nAlthough infrequent, extrapelvic endometriosis can also be found in \nthe upper abdomen, the appendix, bowel, diaphragm, abdominal wall \nas well as abdominal scars and umbilicus, pancreas, spleen, pleura and \npericardium, respiratory system, and on brain tissue. 10–12 Superficial \nperitoneal endometriosis can be clinically suspected but unfortunately, \ncannot be diagnosed by any non-invasive imaging modality. Accurate \nlaparoscopic identification of superficial endometriosis implants is \npoor. Using conventional laparoscopy with white light the positive \npredictive value of suspected endometriosis lesions confirmed with \npathology was only 66%.13 Accurate identification and excision of all \nendometriosis lesions is associated with better surgical outcomes and \ncould possible decrease the recurrence of the disease. 14,15 Enhanced \nlaparoscopic imaging techniques has been used to improve the \ndetection and diagnostic accuracy of endometriosis implants. In this \nreview, we evaluate current available enhance laparoscopic imaging \nmodalities with emphasis in detection of endometriosis implants.\nEnhanced imaging techniques in \nendometriosis\nLaparoscopic identification of superficial endometriosis implants \nrepresents a challenge for the gynecologic surgeon. Endometriosis \nlesions may present in a wide spectrum of appearance according to a \nMOJ Womens Health. 2018;7(1):14‒17. 14\n©2018 Jose et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nLaparoscopic enhanced imaging modalities for the \nidentification of endometriosis implants a review of \nthe current status\nVolume 7 Issue 1 - 2018\nCarugno Jose, Andrade Fausto, Laganà \nAntonio\nMinimally Invasive Gynecology/Robotic Unit, University of \nMiami, USA\nCorrespondence: Jose Carugno, MD FACOG, Department of \nObstetrics and Gynecology, University of Miami, Miller School \nof Medicine, Miami, USA, T el 9144739587, \nEmail jac209@med.miami.edu\nReceived: October 22, 2017 | Published: January 11, 2018\nAbstract\nEndometriosis is a benign, complex, chronic and progressive gynecologic disorder \ndefined as the presence of viable, estrogen-dependent endometrial-like gland and \nstroma associated with inflammatory response outside the uterine cavity. Laparoscopy \nwith tissue pathologic biopsy is well accepted as the “gold standard” for the diagnosis \nof endometriosis and constitute the therapeutic approach of choice when medical \ntreatment produce unsatisfactory results. Accuracy of visual diagnosis at the time of \nlaparoscopy increases with disease severity. Enhanced laparoscopic imaging techniques \nhas been used to improve the detection and diagnostic accuracy of endometriosis \nimplants. In this review, we evaluate current available enhance laparoscopic imaging \nmodalities with emphasis in detection of endometriosis implants.\nKeywords: endometriosis, laparoscopy, robotics, imaging\nMOJ W omen’s Health\nResearch Article\n Open Access\n\n\nLaparoscopic enhanced imaging modalities for the identification of endometriosis implants a review of \nthe current status\n15\nCopyright:\n©2018 Jose et al.\nCitation: Jose C, Fausto A, Antonio L. Laparoscopic enhanced imaging modalities for the identification of endometriosis implants a review of the current \nstatus. MOJ Womens Health. 2018;7(1):14‒17. DOI: 10.15406/mojwh.2018.07.00160\n“lifecycle” of the implants. The lesions can be flat or vesicular. They \ncan have any combination of color typically red, back/brown and \nwhite. Active “red” lesions, large endometriomas, deep infiltrating \nnodules, and typical “powder-burn” lesions are easier to identify \nthan “white” old fibrotic lesions. The endometriotic implants are \nhypervascular. The diagnostic accuracy at laparoscopy is also affected \nby the experience of the surgeon and the laparoscopic equipment. 16 \nBecause of the difficulty in diagnosing endometriosis based on visual \nappearance, there has been great interest in facilitating laparoscopic \nrecognition of the implants. Surgeons have always depended on white \nlight to illuminate their surgical field. Under white light, tissue color \nvaries in a limited shade of colors mostly red, yellow, white and gray \nmaking it difficult to differentiate normal from pathologic tissue.\nEnhanced laparoscopic imaging techniques that allow \ndifferentiation of normal from pathologically infiltrated tissue is \nbeen utilized in different surgical specialties especially in surgical \noncology.17,18 Like malignant process, neovascularization is present \nin most endometriosis implants and could be used to differentiate \nendometriosis lesions from normal peritoneum. Due to the diverse \nvisual appearance of the endometriosis implants and the low \npositive predictive value of performing peritoneal biopsies based on \nappearance, there is great interest in improving accuracy of the visual \ndiagnosis. Enhanced imaging modalities are used to help the surgeon \nto identify peritoneal endometriosis lesions.\nFluorescent Laparoscopy techniques: \nAutofluorescence imaging (AFI)\nAutofluorecence imaging is an advanced technology that exploits \nthe autofluorent nature of tissue and allows the detection of small \nendometriosis superficial lesions. Although the precise mechanism of \nautofluorescence of tissue has not been determined, it is accepted that \nit can change if the epithelial layer thickens or if the concentration \nof chromophores change second to hypervascularization. 19 This \ntechnique relies on blue light excitation and differences in epithelial \nthickness and neovascularization. It produces different color tones \nthat differentiate endometriosis lesions from normal peritoneum. 20,21 \nEndogenous fluorophores such as tryotophan, collagen, elastin, \nFlavin, and co-enzimes of the respiratory chain lead to tissue \ndifferentiated autofluorescence. Demco L. described the use of \nblue light at a frequency of 440Hz to facilitate the visualization of \nendometriosis implants in 25 patients with suspected endometriosis. \nHe concluded that the use of blue light facilitates the visualization of \nendometriosis lesions and allow detection of endometriosis implants \nnot visible with the use of white light. 22 Buchweitz et al., 20 reported \na prospective analysis of 83 patients undergoing laparoscopy for \nsuspected endometriosis under white light and autofluorescence for \nthe detection of non-pigmented peritoneal endometriotic lesions. \nThey reported a sensitivity of 65% with the use of white light and 92% \nwith the aid of autofluorescence (1.42 fold increase) concluding that \nthe use of white light and autofluorescence is significantly superior \nto white light illumination alone for the detection of non-pigmented \nendometriotic lesions.\n5-aminolevulinic acid induced fluorescence (5-ALA)\nThe principle of fluorescent imaging is the use of a special \nendoscope that releases light at different wavelength which \nstimulates a signal released by the biomarker that is captured by the \nendoscope and is then mapped digitally onto a screen. Fluorescence \nafter administration of 5-ALA is a diagnostic tool used in the early \ndiagnosis of cancerous disorders in urology and pulmonology. 23,24 \n5-ALA is a administered as an oral prodrug that increases the level \nof protoporphyrin IX in epithelial tissue that is then fluorescently \nilluminated. When blue light is then applied following 5-ALA \nadministration, non-pigmented endometriosis lesions are accentuated. \nPatients should avoid exposition to direct sunlight for 24hours \nafter administration due to photosensitization. A common reported \nside effect is nausea and vomiting which occur in up to 10% of \nthe cases. 20 Malik E et al.,+published a series of 37patients with \nsuspected endometriosis who underwent diagnostic laparoscopy after \nthe administration of 30mg of 5-ALA/Kg body weight PO the night \nbefore surgery. They reported a sensitivity of fluorescence diagnosis \nof 100% with a specificity of 75%. The likelihood ratio for a positive \ntest indicating endometriosis was 4.\nIn contrast, the sensitivity of the visual diagnosis of endometriosis \nunder white illumination is only 69%, with a specificity of 70%. The \nlikelihood ratio is 2.3. This represent a diagnostic increase of 46% \ncompared with white light illumination (sensitivity: 48%, specificity: \n60%) The authors concluded that the diagnosis of non-pigmented \noccult endometriotic implants is feasible and could help the surgeon \nto differentiate endometriotic lesions from other peritoneal unspecific \nchanges. Buchweitz et al., 26 found similar sensitivity of fluorescence \ndiagnosis with 20mg/Kg body weight, with the added benefit of \nreduced cost and decreased incidence of adverse effects. Fluorescence \ndiagnosis should be considered as an additional diagnostic tool \nthat complements the conventional use of white light illumination. \nHowever, it has some limitations that should be considered. \nFluorescence diagnosis cannot replace the use of white light because \nthe depth of penetration of the blue light is too shallow to detect deep \ninfiltrating endometriosis. Also, the fluorescence fades with increased \nduration of the laparoscopy which prevent its use for the entire case. \nNarrow Band Imaging T echniques (NBI)\nNarrow Band Imaging (NBI) is a modality that uses a narrow \nwavelength of light to change the color contrast of the endoscopic \nimage improving the detection of neovascularization which allows \nvisualization of endometriotic implants. In NBI only the green and \nblue light of the spectrum are excited. Barrueto et al., 27 reported \nthe sensitivity and specificity for their clinical impression for the \ndetection of endometriotic peritoneal implants using NBI and white \nlight and found that using NBI the sensitivity was 84% and specificity \n24% compare to using WL with a sensitivity of 71% and specificity \n36%. It is important to note the low specificity which can result in \nunnecessary resection of healthy peritoneum, increasing the chance of \nsurgical complications, with potential increase of postoperative pain \nand adhesion formation.\nNear-infrared (NIR) imaging with Indocyanine green (ICG) \n(FireFly®). Near infrared wavelength is often used in endoscopy as \nit results in greater depth of penetration. It is used with indygocianine \ngreen (ICG) as a non-specific biomarker. ICG is a water-soluble tracer \ndye that binds to plasma proteins with a peak spectral absorption at \n800nm. It is administered intravenously (IV), has a half-life of 3 to \n4minutes and is cleared by the liver. This is used with the infrared \nfluorescence imaging system integrated with the robotic platform. \nThere are 2 conventional laparoscopy endoscopes available to use this \ntechnology (Pinpoint, Nvadaq, Canada and D-Light, Storz, Germany) \nand one for the Da Vinci robotic platform (FireFly Intuitive Surgical, \n\nLaparoscopic enhanced imaging modalities for the identification of endometriosis implants a review of \nthe current status\n16\nCopyright:\n©2018 Jose et al.\nCitation: Jose C, Fausto A, Antonio L. Laparoscopic enhanced imaging modalities for the identification of endometriosis implants a review of the current \nstatus. MOJ Womens Health. 2018;7(1):14‒17. DOI: 10.15406/mojwh.2018.07.00160\nInc, Sunnyvale, CA) The FireFLy® mode on the da-Vinci Si platform \nhas been available since 2001 and approved by the Food and Drug \nAdministration (FDA) for imaging use in August 2014. It facilitates \nidentifying endometriosis lesions using infrared technology to identify \nvascular structures surrounded of fibro-vascular tissue.\nIt requires the injection of 5mg of ICG into the IV . The \nendometriotic lesion will fluoresce as a dark green area surrounded \nby a lighter area of fibrosis. In 2015, Guan et al., 28 reported that the \nuse of FireFly® technology and ICG facilitated the identification of \nendometriosis allowing to perform single site laparoscopic excision \nof endometriosis nodules with complete resolution of symptoms and \nexcellent cosmetic results. The use of Firefly technology has also \nproven helpful for excision of extragenital endometriosis, in particular \nfor the excision of implants nodules overlying the ureter and rectum.28 \nThese lesions are often subtle and are not visualized with the use of \nwhite light, but when illuminated using Firefly technology, complete \nresection of the targeted affected area is possible. Precaution should \nbe taken with patients with known iodine allergy, hyperthyroidism or \nkidney failure are at increased risk of anaphylaxis.\nConclusion\nLaparoscopy is the gold standard for diagnosis and treatment of \nendometriosis. The current clinical approach of endometriosis favors \nvisual inspection and tissue pathologic biopsy diagnosis. Advances \nis surgical technology specially enhanced imaging techniques show \nencouraging results to improve the identification of endometriosis \nimplants. Further studies are needed to confirm the clinical benefit of \nadopting this promising technological modality.\nCompliance of ethical standards\nThis study received no funding.\nConflicts of interest\ni. Jose Carugno declare that he has no financial conflicts to disclose.\nii. Fausto Andrade declare that he has no financial conflicts to \ndisclose.\niii. Antonio Laganà declare that he has no financial conflicts to \ndisclose.\nEthical approval\nThis article does not contain any studies with human participants \nor animals performed by any of the authors.\nAuthors contribution\ni. J Carugno: Project development and Manuscript writing.\nii. F Andrade: Project development and Manuscript writing.\niii. AS Laganà: Project development and Manuscript writing.\nReferences\n1. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.\n2. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.\n3. Brown J, Farquhar C. An overview of treatments for endometriosis. JAMA. \n2015;313(3):296–297.\n4. Burney RO, Giudice LC. Pathogenesis and pathophysiology of \nendometriosis. Fertil Steril. 2012;98(3):511–519.\n5. Laganà AS, Vitale SG, Salmeri FM, et al. Unus pro omnibus, omnes pro \nuno: A novel, evidence-based, unifying theory for the pathogenesis of \nendometriosis. Medical Hypotheses. 2017;103:10–20.\n6. 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Laparoscopic enhanced imaging modalities for the identification of endometriosis implants a review of the current \nstatus. MOJ Womens Health. 2018;7(1):14‒17. DOI: 10.15406/mojwh.2018.07.00160\n24. Kriegmair M, Waidelich R, Lumper W, et al. Integral photodynamic \ntreatment of refractory superficial bladder cancer. J Urol . \n1995;154(4):1339–1341.\n25. Malik E, Berg C, Meyhofer-Malik A, et al. Fluorescence diagnosis of \nendometriosis using 5-aminolevulinic acid. Surg Endosc. 2000;14(5):452–\n455.\n26. Buchweitz O, Wulfing P, Staebler A, et al. Detection of nonpigmented \nendometriotic lesions with 5-aminolevulinic acid-induced fluorescence. J \nAm Assoc Gynecol Laparosc. 2004;11(4):505–510.\n27. Barrueto FF, Audlin KM, Gallicchio L, et al. Sensitivity of Narrow \nBand Imaging Compared With White Light Imaging for the Detection of \nEndometriosis. J Minim Invasive Gynecol. 2015;22(5):846–852.\n28. Guan X, Walsh T, Osial P, et al. Robotic single-site endometriosis resection \nusing firefly technology. J Minim Invasive Gynecol. 2015;22(6S):S118.","source_license":"CC0","license_restricted":false}