Dye diffusion during laparoscopic tubal patency tests may suggest a lymphatic contribution to dissemination in endometriosis: A prospective, observational study
Authors:
Marco Scioscia aff001; Anna Pesci aff003; Arnaldo Scardapane aff004; Marco Noventa aff002; Gloria Bonaccorsi aff005; Pantaleo Greco aff005; Giuseppe Zamboni aff003
Authors place of work:
Department of Obstetrics and Gynecology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy
aff001; Department of Obstetrics and Gynecology, Policlinico Hospital, Abano Terme, Padua, Italy
aff002; Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy
aff003; Interdisciplinary Department of Medicine, Section of Radiology, University of Bari Medical School, Bari, Italy
aff004; Department of Morphology, Surgery and Experimental Medicine, Section of Obstetrics and Gynecology, University of Ferrara, S. Anna University Hospital, Cona, Ferrara, Italy
aff005
Published in the journal:
PLoS ONE 14(12)
Category:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0226264
Summary
Aim
Women with adenomyosis are at higher risk of endometriosis recurrence after surgery. This study was to assess if the lymphatic vessel network drained from the uterus to near organs where endometriosis foci lied.
Methods
A prospective, observational study, Canadian Task Force Classification II-2, was conducted at Sacro Cuore Don Calabria Hospital, Negrar, Italy. 104 white women aged 18–43 years were enrolled consecutively for this study. All patients underwent laparoscopy for endometriosis and a tubal dye test was carried out.
Results
Evidence of dye dissemination through the uterine wall and outside the uterus was noted in 27 patients (26%) with adenomyosis as it permeated the uterine wall and a clear passage of the dye was shown in the pelvic lymphatic vessels regardless whether the tubes were unobstructed. Histological assessment of the uterine biopsies confirmed adenomyosis.
Conclusion
Adenomyosis is characterized by ectatic lymphatics that allow the drainage of intrauterine fluids (the dye and, perhaps, menstrual blood) at minimal intrauterine pressure from the uterine cavity though the lymphatic network to extrauterine organs. Certainly, this may not be the only explanation for endometriosis dissemination but the correlation between the routes of the dye drainage and location of endometriosis foci is highly suggestive.
Keywords:
Surgical and invasive medical procedures – histology – Biopsy – Ligaments – laparoscopy – Uterus – Myometrium – Gynecologic surgery
Introduction
Endometriosis is an estrogen-dependent disease characterized by endometrial tissue abnormally growing outside the uterus. It contributes significantly to pelvic pain and infertility and affects up to 10% of women of reproductive age and 30 to 50% of infertile women [1, 2]. Endometriosis and secondary adhesions in advanced stages can affect all pelvic structures leading to profound changes in pelvic anatomy that contribute heavily to symptoms (pain and infertility) and make imaging diagnosis [3–5] and surgery [2] harder. Although peritoneal superficial lesions and ovarian endometriomas represent the majority of endometriotic implants within the pelvis, deep infiltrating endometriosis and extra pelvic endometriosis are the most challenging conditions to face off. Despite medical therapy is a valid approach to reduce symptoms [6], often a surgical treatment with complete eradication [7] using a nerve- and vascular-sparing approach [8–10] is needed to improve clinical symptoms (pain unresponsive to medical treatment) and to restore the normal pelvic anatomy and its functions (when non-sexual organs are compromised or to improve fertility) [11].
The pathophysiology of endometriosis remains unclear as different theories have been proposed although peritoneal implants of endometrial tissues derived from retrograde menstruation in women with a genetic predisposition and immune dysfunction seems to be the most widely accepted hypothesis [2, 12]. Certainly, deep infiltrating endometriosis [13] without peritoneal involvement and distant localizations [14] cannot be easily explained by this model but are probably due to lymphatic/hematogenic dissemination or metaplastic transformation [15]. Lymphatic spread was hypothesized based on histological findings as endometrial cells were found in lymph nodes in women with endometriosis [16]. Angiogenesis and lymphangiogenesis in endometriosis and adenomyosis were shown to play a role in the histological and clinical presentation of the disease [17].
Adenomyosis is a specific form of endometriosis characterized by endometrial tissue within the myometrium and contributes to dysmenorrhea, pain during sexual intercourse, chronic pelvic pain, and subfertility [18]. It is characterized by endometrial glands and stroma that break through the myometrium and induce hypertrophy and hyperplasia of the surrounding myometrium associated with an abnormal distribution of uterine vessels [18, 19].
The correlation between adenomyosis and endometriosis is still debated as cases with isolated adenomyosis are reported [18, 19]. Nevertheless, it is very often found in cases of extrapelvic endometriosis [12]. Ueki [20] demonstrated ectatic lymphatic vessels in the myometrium of adenomyotic uteri after hysterectomy and proposed that the lymphatic system could carry endometrial tissue away from the uterus promoting endometriosis of ovaries and pelvic organs.
This study was to assess the diffusion of the dye during a laparoscopic tubal patency test through the uterine wall and to extrauterine structures especially where endometriosis foci lay.
Methods
This study took the cue from an observation in September 2016: During a laparoscopic procedure in an infertile woman with presurgical evidence of endometriosis, the dye test to verify tubal permeability showed a peculiar effect on the uterine wall. Some areas of the external layer of the myometrium showed a pale blue color and, notwithstanding both tubes were unobstructed, the drainage of the dye from the uterine cavity was noted along the infundibulopelvic ligament through lymphatic vessels. Subsequently, all women undergoing laparoscopy for endometriosis were enrolled and the diffusion sites of the dye during a tubal patency test were recorded.
Laparoscopic procedure
All laparoscopies were performed at the Sacro Cuore Don Calabria Hospital, Negrar, Italy, by an expert gynecologic surgeon (MS) with more than 10 years of experience in laparoscopic gynecological surgery according to our previously described surgical approach [21]. All patients undergoing laparoscopy for endometriosis were considered for this study and those with infertility problems were enrolled. According to our internal protocol [7, 21], all the patients were not on hormonal therapy at the time of surgery as we ask to suspend estroprogestin/progestin treatment one month before surgery. The evaluation of tubal patency for routine assessment of infertility during laparoscopy can be easily obtained injecting a diluted methylene blue solution (0.1%) into the uterine cavity [22]. An hysterometer was used to sound the uterus length and an appropriate manipulator tip was used (1 cm shorter than the uterus length to avoid uterine perforation/trauma). A uterine manipulator with die injection system was inserted into the cervix under direct vision at beginning of the surgical procedure and used to drive the methylene blue solution into the uterine cavity to verify tubal permeability. Laparoscopic uterine biopsy was performed where the dye reached the uterine external layer (Fig 1) to confirm the presence of adenomyosis [23] in cases where the preoperative evaluation (ultrasound and MRI) did not suggested adenomyosis.
Histological assessment
All specimens were evaluated in a blind manner by two different pathologists following the same protocol. Surgical specimens were fixed in 10% buffered formalin for 12 hours, paraffin embedded blocks were sectioned and processed with a standard technique followed by hematoxylin/eosin staining. For immunohistochemistry, deparaffinized 4-μm sections were incubated with the following monoclonal antibodies using standard reagents and techniques on Ventana Bench Marks ULTRA: CD34 (QBend 10 RTU) and podoplanin (D2-40 RTU). CD34 is a commonly used marker of hematopoietic progenitor cells and endothelial cells; podoplanin identifies lymphatic endothelium and is not expressed in vascular blood vessel endothelial cells.
Ethical approval
The clinical trial was registered on UMIN Clinical Trials Registry (https://www.umin.ac.jp/ctr/; registration number is UMIN000034585). Our internal review board considered not necessary a formal approval as the tubal dye test is routinely performed during laparoscopy in adult women suffering from endometriosis and infertility. According to our surgical approach to endometriosis, when a suspect of adenomyosis is made, a biopsy may be taken to complete the diagnosis. Furthermore, a specific preoperative written consent for the removal of all endometriosis lesions (radical approach) and the tubal dye test was obtained by all patients as well as a written clearance for imaging use for research/teaching.
Results
Between September 2016 and January 2018, 191 patients underwent laparoscopy for endometriosis (Table 1). All patients were adults (range 18 to 43 years of age). In 104 cases (55%), a tubal permeability test (dye test) was carried out as the patients were infertile. It is not unusual to observe during a laparoscopic tubal dye test a color change, at least in some areas, of the adenomyotic uterus from pale to deep blue. In fact, a change of color of the uterus was noted in 27 cases (26%) that in most cases (93%) extended to extrauterine organs. A clear perfusion through the lymphatic vessels of the methylene blue solution from the uterine cavity to extrauterine structures was seen and this was not related to tubal patency as at least unilateral unobstructed tube was confirmed in 24 out of the 27 cases. Other 7 women with suspect of adenomyosis at preoperatory assessment (ultrasound or MRI) and underwent tubal dye test did not show a macroscopic color chance of the uterus wall. Fig 2 and S1 Video show diffused blue color of the fundus and focal changes of the posterior wall of the uterus (Fig 2A) with a clear staining of the proximal part of the right uterosacral ligament (Fig 2B). Lymphatic vessels surrounding the ovarian artery and vein in the infundibulopelvic ligament were stained (Fig 2C), with a single spot close to the internal iliac vein (a lymph node) (Fig 2D). In some cases, the dye permeated the uterine fundus and flowed slowly into small subperimetrial vessels (Fig 3A and 3B) before reaching lymphatics surrounding the utero-ovarian vessels (Fig 3C) and the external layer of the right ovary (Fig 3D). In some cases, endometriosis lesions of subperitoneal lymphatic vessels and distal endometriosis (diaphragmatic endometriosis) can be found (Fig 2E and 2F). In other cases, a blue staining of the subperitoneal structures could be seen during dissection (Fig 4A and 4B). Endometriosis lesions (endometriotic tissue and/or endometriosis-related reactive fibrosis) were all confirmed at histology and by the assessment of the uterine biopsy (Fig 4C) revealed ectatic lymphatic vessels surrounding endometrial glands within the myometrium (Fig 4D) as described by other authors as a typical feature of adenomyosis. Adenomyotic tissue reached the outer layer of the myometrium without perimetrium infiltration. It is interesting to note that in two cases of symptomatic women (infertility, dysmenorrhea, and prolonged menstrual bleeding) with unremarkable pelvic ultrasound and office hysteroscopy, the whole uterus shaded into a “bizarre” blue color during a blue tubal test that toned down in a few minutes (Fig 5), notwithstanding unobstructed tubes and without any pelvic endometriosis lesion. Adenomyosis was confirmed at biopsy and a diffuse adenomyosis was confirmed by subsequent MRI.
Discussion
The correlation between lymphatics and endometriosis was hypothesized many years ago [24]. Different studies assessed biochemical (growth factors and cytokines) and histological features during menstrual changes in lymphatics in eutopic and heterotopic endometrial tissues as summarized by Jerman and Hey-Cunningham [16]. Several aspects of the pathogenesis of endometriosis have been investigated showing that immune cells, adhesion molecules, extracellular matrix metalloproteinase and pro-inflammatory cytokines activate and modify peritoneal microenvironment, prompting endometrial cells to abnormal differentiation, adhesion, proliferation, and survival in ectopic sites [25, 26]. Nevertheless, the key aspect that was always debated was if menstrual blood could flow into the lymphatic vessels as easily as through the tubes in retrograde menstruations.
To the best of our knowledge, this is the first in vivo observation of the spread of an intravital solution in women suffering from endometriosis/adenomyosis. We evaluated the dissemination of the dye (methylene blue) from the uterine cavity through the myometrium where adenomyosis was to the lymphatic system up to extrauterine endometriosis lesions. Interestingly, the lymphatic vessel network draining from the uterus lie where endometriosis foci are more commonly found. Certainly, this is a cohort of 27 cases only but the evidence of the lymphatic network involvement in the pathophysiology of endometriosis represents a key aspect that deserves a special attention.
Uterine adenomyosis is diagnosed histologically with a uterine biopsy or strongly suspected with ultrasonography and magnetic resonance imaging although diffuse adenomyosis can be undetected by ultrasound [27]. In an internal survey of a referral radiologic center for endometriosis, prevalence of adenomyosis at magnetic resonance was 35.9% and 18.6% in women with and without evidence of endometriosis, respectively (data not published of the University of Bari, Italy). These data are similar to those reported in previous surveys [28]. Recently, a meta-analysis demonstrated that ultrasound and magnetic resonance are reliable and comparable as non-invasive methods for the diagnosis of adenomyosis [29, 30]. In cases of difficult diagnosis [30], a uterine biopsy can be considered.
In our cases, a peculiar effect when adenomyotic uterine walls are permeated with methylene blue during a dye test was shown. Another important aspect is that the drainage of permeated myometrium occurred through the lymphatic system with a prevalent staining where endometriosis lesions were found. A clear transitory staining of lymphatic vessels of the uterosacral, infundibulopelvic, and round ligaments that contribute to the collecting system of the uterine lymphatics was shown. Although endometriosis of the vesical-vaginal and recto-vaginal septa was hypothesized to be a progressive deepening of superficial lesions more than an infiltration from close uterine adenomyosis [31], we found dyed connective tissue beneath the peritoneum and/or ligaments where lymphatic vessels laid.
Ueki [20] demonstrated a definite diffusion of Indian ink through lymphatic vessels of the round ligaments after subserosal injection in removed uteri (ex vivo observation). Lymphatic drainage out of the uterus involved also infundibulopelvic (that drained into the ovary and tubes) and cardinal ligaments (that appeared to flow back to the bladder). The first hypothesis of a “composite theory” involving retrograde menstruation and lymphatic/hematogenous spread dates back to 1949 when Javert [32] suggested a multifactorial origin of the disease based on ex vivo findings. Actually, a lymphatic route of dissemination was initially proposed by Sampson in 1922 [24].
At present, very little is known about the direct correlation between adenomyosis and endometriosis [33] but it is demonstrated that (i) women with endometriosis present an altered junctional zone at histology compared to women who do not suffer from endometriosis and (ii) women with adenomyosis are at increased risk of recurrence of endometriosis after complete surgical excision [34]. We can hypothesize that microscopic alterations (undetectable in vivo by magnetic resonance and ultrasound) of the junctional zone and lymphatic ectasia may promote lymphatic dissemination of menstrual endometrium to proximal organs (ovaries and tubes, ligaments, bladder, and rectum) and less frequently to distal organs [16]. Certainly, the retrograde menstruation and endometrium implants contribute to proximal and distal abdominal endometriosis (caecum, small bowel, liver, and diaphragm) [2, 12] while it cannot explain rare distal forms like endometriosis of the lungs (pleura), pericardium, nose, and the central nervous system [14, 35]. Although intraparenchymal lesions of endometriosis of splanchnic organs are very rare, several cases involving the liver, pancreas, and kidney have been reported and this certainly cannot be justified by the reflux theory. Endometriosis presenting with recurrent ascites and pleural effusion in women with otherwise “normal” deep infiltrating endometriosis and without other possible causes like liver disease, congestive cardiac failure, or nephrotic syndrome may support the hypothesis of the lymphatic involvement [36].
Knowledge of the pathophysiology of a disease allows treatments to be developed based upon mechanisms that cause and promote the progression of the disease. At present, there is neither a cure for endometriosis nor a therapy that may prevent endometriosis progression but only hormonal therapies that slow down the progression of the disease [37, 38]. It is still unclear to what extent our findings can be of some, if any, help in clinical practice although studies on progestins in adenomyosis demonstrated a reduced lymphangiogenesis [39]. Certainly, future research on the pathophysiology of endometriosis can be driven by these observations combining new with existing evidence. If our findings will be confirmed and extended by other studies, the pivotal role of lymphatics in endometriosis dissemination can prompt research on medications that reduce the lymphangiogenesis to prevent endometriosis spread and progression, like recently proposed in oncology. Furthermore, the study of lymphatic biomarkers may identify a reliable test to identify women with endometriosis and/or monitor its progression.
A well-known proverb in research says “In vivo veritas”. In fact, objections raised to ex vivo studies (carried out injecting the dye into the myometrium) were against the possibility that menstrual fluids could flow into the lymphatic vessels as easily as through the tubes. We demonstrated that the minimal pressure to allow tubal seepage of the dye that was put inside the uterine cavity showed a spread through the lymphatic vessel network.
Intravital dyes are currently applied for sentinel lymph node detection in oncological surgery. Recently, Restaino et al. [40] proposed the use of blue dye for sentinel lymph node detection in early endometrial cancer.
Conclusions
The dissemination of endometriosis is likely to be multifactorial and the lymphatic network contributes to the reflux theory. During menstruation, exfoliated menstrual cells can pour into lymphatic vessels and spread to close and distant structures and organs. These findings throw a different light on the pathogenesis of this common disease and may prompt new researches in this direction, perhaps focusing on translational models [41] to test new drugs and early molecular targets for the treatment of endometriosis [42].
Supporting information
S1 Video [mp4]
Laparoscopic video of a tubal dye test.
Zdroje
1. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591–8. doi: 10.1016/j.fertnstert.2012.05.031 22704630
2. Giudice Linda C., Kao Lee C. Endometriosis. Lancet Lond Engl. 2004;364(9447):1789–99.
3. Guerriero S, Saba L, Pascual MA, Ajossa S, Rodriguez I, Mais V, Alcazar JL. Transvaginal ultrasound vs magnetic resonance imaging for diagnosing deep infiltrating endometriosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;51(5):586–595. doi: 10.1002/uog.18961 29154402
4. Fratelli N, Scioscia M, Bassi E, Musola M, Minelli L, Trivella G. Transvaginal sonography for preoperative assessment of deep endometriosis. J Clin Ultrasound. 2013;41(2):69–75. doi: 10.1002/jcu.22018 23233390
5. Scioscia M, Orlandi S, Trivella G, Portuese A, Bettocchi S, Pontrelli G, et al. Sonographic differential diagnosis in deep infiltrating endometriosis: The bowel. Biomed Research Internat, 2019, Vol. 2019, Article ID 5958402, https://doi.org/10.1155/2019/5958402
6. Laganà AS, Vitale SG, Granese R, Palmara V, Ban Frangez H, Vrtacnik-Bokal E, et al. Clinical dynamics of Dienogest for the treatment of endometriosis: from bench to bedside. Expert Opin Drug Metab Toxicol. 2017;13(6):593–596. doi: 10.1080/17425255.2017.1297421 28537213
7. Minelli L, Ceccaroni M, Ruffo G, Bruni F, Pomini P, Pontrelli G, et al. Laparoscopic conservative surgery for stage IV symptomatic endometriosis: short-term surgical complications. Fertil Steril. 2010;94(4):1218–22. doi: 10.1016/j.fertnstert.2009.08.035 19969292
8. Raffaelli R, Garzon S, Baggio S, Genna M, Pomini P, Laganà AS, et al. Mesenteric vascular and nerve sparing surgery in laparoscopic segmental intestinal resection for deep infiltrating endometriosis. Eur J Obstet Gynecol Reprod Biol. 2018; 231:214–219. doi: 10.1016/j.ejogrb.2018.10.057 30415128
9. Laganà AS, Vitale SG, Trovato MA, Palmara VI, Rapisarda AM, Granese R, et al. Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options. Biomed Res Int. 2016;2016:3617179. doi: 10.1155/2016/3617179 27579309
10. Ceccaroni M, Clarizia R, Alboni C, Ruffo G, Bruni F, Roviglione G, et al. Laparoscopic nerve-sparing transperitoneal approach for endometriosis infiltrating the pelvic wall and somatic nerves: anatomical considerations and surgical technique. Surg Radiol Anat. 2010;32(6):601–4. doi: 10.1007/s00276-010-0624-6 20087591
11. Stepniewska A, Pomini P, Scioscia M, Mereu L, Ruffo G, Minelli L. Fertility and clinical outcome after bowel resection in infertile women with endometriosis. Reprod Biomed Online. 2010;20(5):602–9. doi: 10.1016/j.rbmo.2009.12.029 20359953
12. Scioscia M, Bruni F, Ceccaroni M, Steinkasserer M, Stepniewska A, Minelli L. Distribution of endometriotic lesions in endometriosis stage IV supports the menstrual reflux theory and requires specific preoperative assessment and therapy. Acta Obstet Gynecol Scand. 2011;90(2):136–9. doi: 10.1111/j.1600-0412.2010.01008.x 21241258
13. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Donnez J. Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012;98(3):564–71. doi: 10.1016/j.fertnstert.2012.07.1061 22938769
14. Davis A, Goldberg J. Extrapelvic Endometriosis. Semin Reprod Med. 2016;35(01):098–101.
15. Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261–75. doi: 10.1038/nrendo.2013.255 24366116
16. Jerman LF, Hey-Cunningham AJ. The Role of the Lymphatic System in Endometriosis: A Comprehensive Review of the Literature. Biol Reprod. 2015;92(3).
17. Sheveleva T, Bejenar V, Komlichenko E, Dedul A, Malushko A. Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2016;32(sup2):75–9.
18. Struble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol. 2016;23(2):164–85. doi: 10.1016/j.jmig.2015.09.018 26427702
19. García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018;109(3):371–9. doi: 10.1016/j.fertnstert.2017.12.030 29566849
20. Ueki M. Histologic study of endometriosis and examination of lymphatic drainage in and from the uterus. Am J Obstet Gynecol. 1991;165(1):201–9. doi: 10.1016/0002-9378(91)90252-m 1853897
21. Ceccaroni M, Clarizia R, Bruni F, D'Urso E, Gagliardi ML, Roviglione G, et al. Nerve-sparing laparoscopic eradication of deep endometriosis with segmental rectal and parametrial resection: the Negrar method. A single-center, prospective, clinical trial. Surg Endosc. 2012;26(7):2029–45. doi: 10.1007/s00464-012-2153-3 22278102
22. Ansari AH. Methylene blue test for assessment of tubal patency: a new and simple technique. Can Med Assoc J. 1968;99(4):182–44. 5317820
23. Jeng CJ., Huang SH., Shen J, Chou CS., Tzeng CR. Laparoscopy-guided myometrial biopsy in the definite diagnosis of diffuse adenomyosis. Hum Reprod. 2007;22(7):2016–9. doi: 10.1093/humrep/dem084 17428879
24. Sampson JA. Ovarian hematomas of endometrial type (perforating hemorrhagic cysts of the ovary) and implantation adenomas of endometrial type. Boston Med Surg J. 1922;186:445–56.
25. Laganà AS, Vitale SG, Salmeri FM, Triolo O, Ban Frangez H, Vrtacnik-Bokal E, et al. Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis. Med Hypotheses. 2017;103:10–20. doi: 10.1016/j.mehy.2017.03.032 28571791
26. Laganà AS, Salmeri FM, Vitale SG, Triolo O, Götte M. Stem Cell Trafficking During Endometriosis: May Epigenetics Play a Pivotal Role? Reprod Sci. 2018;25(7):978–979. doi: 10.1177/1933719116687661 28100109
27. Benagiano G, Brosens I, Habiba M. Adenomyosis: a life-cycle approach. Reprod Biomed Online. 2015;30(3):220–32. doi: 10.1016/j.rbmo.2014.11.005 25599903
28. Di Donato N, Montanari G, Benfenati A, Leonardi D, Bertoldo V, Monti G, et al. Prevalence of adenomyosis in women undergoing surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2014;181:289–93. doi: 10.1016/j.ejogrb.2014.08.016 25201608
29. Tellum T, Nygaard S, Lieng M. Noninvasive Diagnosis of Adenomyosis: A Structured Review and Meta-Analysis of Diagnostic Accuracy in Imaging. J Minim Invasive Gynecol. 2019, S1553-4650(19)31287-7
30. Van den Bosch T, Van Schoubroeck D. Ultrasound diagnosis of endometriosis and adenomyosis: State of the art. Best Pract Res Clin Obstet Gynaecol. 2018; 51:16–24. doi: 10.1016/j.bpobgyn.2018.01.013 29506961
31. Vercellini P, Frontino G, Pietropaolo G, Gattei U, Daguati R, Crosignani PG. Deep endometriosis: definition, pathogenesis, and clinical management. J Am Assoc Gynecol Laparosc. 2004;11(2):153–61. doi: 10.1016/s1074-3804(05)60190-9 15200766
32. Javert C. T. Pathogenesis of endometriosis based on endometrial homeoplasia, direct extension, exfoliation and implantation, lymphatic and hematogenous metastasis, including five case reports of endometrial tissue in pelvic lymph nodes. Cancer. 1949;2(3):399–410. doi: 10.1002/1097-0142(194905)2:3<399::aid-cncr2820020304>3.0.co;2-l 18131400
33. Benagiano G, Brosens I, Habiba M. Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update. 2014;20(3):386–402. doi: 10.1093/humupd/dmt052 24140719
34. Landi S, Mereu L, Pontrelli G, Stepniewska A, Romano L, Tateo S, et al. The Influence of Adenomyosis in Patients Laparoscopically Treated for Deep Endometriosis. J Minim Invasive Gynecol. 2008;15(5):566–70. doi: 10.1016/j.jmig.2008.06.009 18722969
35. Machairiotis N, Stylianaki A, Dryllis G, Zarogoulidis P, Kouroutou P, Tsiamis N, et al. Extrapelvic endometriosis: a rare entity or an under diagnosed condition? Diagn Pathol. 2013;8(1):194.
36. Gungor T, Kanat-Pektas M, Ozat M, Zayifoglu Karaca M. A systematic review: endometriosis presenting with ascites. Arch Gynecol Obstet. 2011;283(3):513–8. doi: 10.1007/s00404-010-1664-1 20821226
37. Scioscia M, Scardapane A, Ceccaroni M. Regarding “Continuous Amenorrhea May be Insufficient to Stop the Progression of Colorectal Endometriosis.” J Minim Invasive Gynecol. 2016;23(7):1203–5. doi: 10.1016/j.jmig.2016.06.010 27329546
38. Netter A, d'Avout-Fourdinier P, Agostini A, Chanavaz-Lacheray I, Lampika M, Farella M, et al. Progression of deep infiltrating rectosigmoid endometriotic nodules. Hum Reprod. 2019: dez188. doi: 10.1093/humrep/dez188 31687764
39. Cho S, Choi YS, Yun BH, Chon SJ, Jung YS, Kim H, et al. Effects of Levonorgestrel-Releasing Intrauterine System on Lymphangiogenesis of Adenomyosis. Am J Clin Pathol. 2015;143(3):352–61. doi: 10.1309/AJCPP8F4SFYFVXRN 25696793
40. Restaino S, Ronsini C, Finelli A, Perrone E, Scambia G, Fanfani F. Role of blue dye for sentinel lymph node detection in early endometrial cancer. Gynecol Surg. 2017;14(1):23. doi: 10.1186/s10397-017-1026-0 29213225
41. Laganà AS, Garzon S, Franchi M, Casarin J, Gullo G, Ghezzi F. Translational animal models for endometriosis research: a long and windy road. Ann Transl Med. 2018;6(22):431. doi: 10.21037/atm.2018.08.24 30596061
42. Barra F, Scala C, Mais V, Guerriero S, Ferrero S. Investigational drugs for the treatment of endometriosis, an update on recent developments. Expert Opin Investig Drugs. 2018;27(5):445–458. doi: 10.1080/13543784.2018.1471135 29708812
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