Advances in Diagnosis and Management of Endometriosis

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 May 2023) | Viewed by 7012

Special Issue Editors


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Guest Editor
Department of Obstetrics and Gynecology, Gynecologic Oncology and Minimally-Invasive Pelvic Surgery, International School of Surgical Anatomy, IRCCS "Sacro Cuore - Don Calabria" Hospital, Negrar, VR, Italy
Interests: endometriosis surgery; oncology surgery; nerve-sparing surgery

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Guest Editor
Academic Unit of Obstetrics and Gynecology, IRCCS Ospedale Policlinico San Martino, University of Genova, 16132 Genoa, Italy
Interests: endometriosis; adenomyosis; gynecological ultrasound; gynecological imaging; reproductive surgery; uterine myomas; uterine malformation; ultrasound
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Special Issue Information

Dear Colleagues,

Endometriosis is a chronic hormone-dependent condition with a large impact on social life and work activities of women of reproductive age, being responsible for pain symptoms and infertility. Endometriosis is subdivided according to the type and location of the lesions into peritoneal endometriosis, deep endometriosis and endometrioma. In 2022, the European Society of Human Reproduction and Embryology (ESHRE) has published an updated version of guidelines for the management of patients with endometriosis. Recent studies have shown that patients with endometriosis wait an average of seven years before receiving diagnosis of endometriosis, which, therefore, must be performed by skilled operators with adequate training in non-invasive diagnostic techniques, such as transvaginal ultrasound. 

Medical therapy is often employed in the long-term treatment of endometriosis. Nevertheless, current hormonal therapies used to treat endometriosis have no role in improving endometriosis-related infertility, aiming only to alleviate pain symptoms. Thus, these therapies do not “cure” definitively the disease which may persist despite the use of endocrine therapies and the improvement of pain symptoms. Therefore, pain usually recurs when patients discontinue the hormonal treatment either because of the adverse effects or because of the desire to conceive. Surgical excision of endometriosis significantly ameliorates pain symptoms; however, it may be associated with a not negligible rate of complications, if not performed by expert operators in minimally invasive procedures working in referral centers for this benign chronic disease. In general, when there is a clear indication for surgery, radical removal of disease is essential and must be balanced with a fertility- and nerve-sparing approach. This special issue aims to collect innovative and updated manuscript related to diagnosis and management of endometriosis. 

Prof. Dr. Marcello Ceccaroni
Dr. Fabio Barra
Guest Editors

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Keywords

  • endometriosis
  • deep endometriosis
  • ovarian endometrioma
  • peritoneal endometriosis
  • medical therapy
  • laparoscopy
  • nerve-sparing surgery
  • transvaginal ultrasound
  • magnetic resonance imaging

Published Papers (5 papers)

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16 pages, 1556 KiB  
Article
Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?
by Michele Paudice, Chiara Maria Biatta, Giulia Scaglione, Alessia Parodi, Serafina Mammoliti, Melita Moioli, Maria Grazia Centurioni, Fabio Barra, Simone Ferrero, Franco De Cian, Katia Mazzocco and Valerio Gaetano Vellone
Diagnostics 2023, 13(13), 2171; https://doi.org/10.3390/diagnostics13132171 - 26 Jun 2023
Cited by 1 | Viewed by 1125
Abstract
Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. Background: In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. Methods: [...] Read more.
Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. Background: In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. Methods: Each surgical specimen was routinely processed; the most significant block was selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, β-catenin, Bcl-2 and cyclin D1. For each immunomarker, the percentage of positive tumor cells was evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). Thirty-three cases were eligible: 19 resulted in FIGO I–II; 14 resulted in FIGO III–IV. Twelve patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). Results: Women with recurrent disease demonstrated a significantly higher Bcl2% (35.84 ± 30.96% vs. 8.09 ± 11.56%; p = 0.0032) while DOD patients had higher ki67% (75 ± 13.09% vs. 58.6 ± 19.97%; p = 0.033) and Bcl2% of border significance (34.37 ± 34.99% vs. 13 ± 17.97%; p = 0.078). As expected, FIGO III–IV had a worse DFS (HR = 3.34; 95% CI: 1.1–10.99; p = 0.034) and OS (HR = 5.19; 95% CI: 1.27–21.14; p = 0.0217). Bcl-2-high patients (Bcl2 > 10%) demonstrated a significantly worse DFS (HR = 9.11; 95% CI: 2.6–32.4; p = 0.0006) and OS (HR = 7.63; 95% CI: 1.7–34; p = 0.0084); moreover, PR low patients (PR ≤ 10%) had significantly worse DFS (HR = 3.74; 95% CI: 1.2–11.9; p = 0.02). Conclusions: HG-NEC represents a heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis, often at an advanced stage at presentation. Bcl-2 and PR may represent promising markers to identify a subgroup of patients having an even worse prognosis requiring a careful and close follow-up. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometriosis)
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12 pages, 873 KiB  
Article
Epigenetic Regulation Interplays with Endometriosis Pathogenesis in Low-Birth-Weight Patients via the Progesterone Receptor B–VEGF-DNMT1 Axis
by Arief Setiawan, Ruswana Anwar, Mas Rizky Anggun Adipurna Syamsunarno, Johanes Cornelius Mose, Budi Santoso, Ani Melani Maskoen, Wiryawan Permadi, Budi Setiabudiawan, Meita Dhamayanti and Yudi Mulyana Hidayat
Diagnostics 2023, 13(12), 2085; https://doi.org/10.3390/diagnostics13122085 - 16 Jun 2023
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Abstract
Background: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B [...] Read more.
Background: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. Methods: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. Results: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = −0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24–33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57–3.49, p = 0.113), although the relationship was not statistically significant. Conclusion: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometriosis)
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11 pages, 1184 KiB  
Article
Clinical Significance of a Pain Scoring System for Deep Endometriosis by Pelvic Examination: Pain Score
by Masao Ichikawa, Tatunori Shiraishi, Naofumi Okuda, Kimihiko Nakao, Yuka Shirai, Hanako Kaseki, Shigeo Akira, Masafumi Toyoshima, Yoshimitu Kuwabara and Shunji Suzuki
Diagnostics 2023, 13(10), 1774; https://doi.org/10.3390/diagnostics13101774 - 17 May 2023
Cited by 2 | Viewed by 1741
Abstract
Endometriosis-associated pain is an essential factor in deciding surgical indications of endometriosis. However, there is no quantitative method to diagnose the intensity of local pain in endometriosis (especially deep endometriosis). This study aims to examine the clinical significance of the pain score, a [...] Read more.
Endometriosis-associated pain is an essential factor in deciding surgical indications of endometriosis. However, there is no quantitative method to diagnose the intensity of local pain in endometriosis (especially deep endometriosis). This study aims to examine the clinical significance of the pain score, a preoperative diagnostic scoring system for endometriotic pain that can be performed only with pelvic examination, devised for the above purpose. The data from 131 patients from a previous study were included and evaluated using the pain score. This score measures the pain intensity in each of the seven areas of the uterus and its surroundings via a pelvic examination using a numeric rating scale (NRS) which contains 10 points. The maximum value was then defined as the max pain score. This study investigated the relationship between the pain score and clinical symptoms of endometriosis or endometriotic lesions related to deep endometriosis. The preoperative max pain score was 5.93 ± 2.6, which significantly decreased to 3.08 ± 2.0 postoperatively (p = 7.70 × 10−20). Regarding preoperative pain scores for each area, those of the uterine cervix, pouch of Douglas, and left and right uterosacral ligament areas were high (4.52, 4.04, 3.75, and 3.63, respectively). All scores decreased significantly after surgery (2.02, 1.88, 1.75, and 1.75, respectively). The correlations between the max pain score and dysmenorrhea, dyspareunia, perimenstrual dyschezia (pain with defecation), and chronic pelvic pain were 0.329, 0.453, 0.253, and 0.239, respectively, and were strongest with dyspareunia. Regarding the pain score of each area, the combination of the pain score of the pouch of Douglas area and the VAS score of dyspareunia showed the strongest correlation (0.379). The max pain score in the group with deep endometriosis (endometrial nodules) was 7.07 ± 2.4, which was significantly higher than the 4.97 ± 2.3 score obtained in the group without (p = 1.71 × 10−6). The pain score can indicate the intensity of endometriotic pain, especially dyspareunia. A local high value of this score could suggest the presence of deep endometriosis, depicted as endometriotic nodules at that site. Therefore, this method could help develop surgical strategies for deep endometriosis. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometriosis)
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12 pages, 3348 KiB  
Article
Claudin-10 Expression Is Increased in Endometriosis and Adenomyosis and Mislocalized in Ectopic Endometriosis
by Anna C. Loeffelmann, Alena Hoerscher, Muhammad A. Riaz, Felix Zeppernick, Ivo Meinhold-Heerlein and Lutz Konrad
Diagnostics 2022, 12(11), 2848; https://doi.org/10.3390/diagnostics12112848 - 17 Nov 2022
Cited by 3 | Viewed by 1188
Abstract
Claudins, as the major components of tight junctions, are crucial for epithelial cell-to-cell contacts. Recently, we showed that in endometriosis, the endometrial epithelial phenotype is highly conserved, with only minor alterations. For example, claudin-11 is strongly expressed; however, its localization in the endometriotic [...] Read more.
Claudins, as the major components of tight junctions, are crucial for epithelial cell-to-cell contacts. Recently, we showed that in endometriosis, the endometrial epithelial phenotype is highly conserved, with only minor alterations. For example, claudin-11 is strongly expressed; however, its localization in the endometriotic epithelial cells was impaired. In order to better understand the role of claudins in endometrial cell-to-cell contacts, we analyzed the tissue expression and localization of claudin-10 by immunohistochemistry analysis and two scoring systems. We used human tissue samples (n = 151) from the endometrium, endometriosis, and adenomyosis. We found a high abundance of claudin-10 in nearly all the endometrial (98%), endometriotic (98–99%), and adenomyotic (90–97%) glands, but no cycle-specific differences and no differences in the claudin-10 positive endometrial glands between cases with and without endometriosis. A significantly higher expression of claudin-10 was evident in the ectopic endometrium of deep-infiltrating (p < 0.01) and ovarian endometriosis (p < 0.001) and in adenomyosis in the cases with endometriosis (p ≤ 0.05). Interestingly, we observed a shift in claudin-10 from a predominant apical localization in the eutopic endometrium to a more pronounced basal/cytoplasmic localization in the ectopic endometria of all three endometriotic entities but not in adenomyosis. Significantly, despite the impaired endometriotic localization of claudin-10, the epithelial phenotype was retained. The significant differences in claudin-10 localization between the three endometriotic entities and adenomyosis, in conjunction with endometriosis, suggest that most of the aberrations occur after implantation and not before. The high similarity between the claudin-10 patterns in the eutopic endometrial and adenomyotic glands supports our recent conclusions that the endometrium is the main source of endometriosis and adenomyosis. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometriosis)
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16 pages, 470 KiB  
Systematic Review
Appendiceal Endometriosis: A Comprehensive Review of the Literature
by Leila Allahqoli, Afrooz Mazidimoradi, Zohre Momenimovahed, Veronika Günther, Johannes Ackermann, Hamid Salehiniya and Ibrahim Alkatout
Diagnostics 2023, 13(11), 1827; https://doi.org/10.3390/diagnostics13111827 - 23 May 2023
Cited by 3 | Viewed by 1458
Abstract
Objective: the purpose of this review was to evaluate the prevalence of appendiceal endometriosis and the safety of concomitant appendectomy in women with endometriosis or pelvic pain. Materials and Methods: We searched the electronic databases Medline (PubMed), Scopus, Embase, and Web of Science [...] Read more.
Objective: the purpose of this review was to evaluate the prevalence of appendiceal endometriosis and the safety of concomitant appendectomy in women with endometriosis or pelvic pain. Materials and Methods: We searched the electronic databases Medline (PubMed), Scopus, Embase, and Web of Science (WOS). The search was not subject to any limitation in terms of time or method. The primary research question was: what is the prevalence of appendiceal endometriosis? The secondary research question was: is it safe to perform appendectomy during surgery for endometriosis? Publications that reported data about appendiceal endometriosis or appendectomy in women with endometriosis were reviewed regarding the inclusion criteria. Results: We found 1418 records. After review and screening, we included 75 studies published between 1975 and 2021. With regard to the first question of the review, we found 65 eligible studies and divided these into the following two categories: (a) endometriosis of the appendix presenting as acute appendicitis, and (b) endometriosis of the appendix as an incidental finding in gynecological surgery. Forty-four case reports described appendiceal endometriosis in women who were admitted for the treatment of pain in the right-sided lower abdomen. Endometriosis of the appendix was observed in 2.67% (range, 0.36–23%) of women who were admitted due to acute appendicitis. In addition, appendiceal endometriosis was an incidental finding during gynecological surgery in 7.23% of cases (range, 1–44.3%). With regard to the second question of the review, which was the safety of appendectomy in women with endometriosis or pelvic pain, we found 11 eligible studies. Reviewed cases had no significant intraoperative or follow-up complications during the 12 weeks. Conclusion: Based on the reviewed studies, coincidental appendectomy appears reasonably safe and was associated with no complications in the cases reviewed for the present report. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometriosis)
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