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Diagnostics
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Diagnosis of Endometriosis: Biomarkers and Clinical Methods
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Diagnosis of Endometriosis: Biomarkers and Clinical Methods

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

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 54905

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Antonio Simone Laganà

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Guest Editor
Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, 21100 Varese, VA, Italy
Interests: women’s health; minimally invasive procedures; up-to-date management; gynecology; reproductive health; surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endometriosis is defined as the presence of endometrial-like endometrial cells, glands, and stroma outside the uterus, causing a wide range of symptoms and signs, including acute and chronic pelvic pain and infertility. Endometriosis affects approximately 10% of women in reproductive age, and up to 50% of infertile women. The etiopathogenesis of endometriosis still remains controversial: immune, hormonal, genetic, and epigenetic factors may be all involved, and several theories have been proposed to explain it.

One of the main problems for the management of endometriosis is the significant diagnostic delay: to date, several biomarkers are currently being tested in order to provide a reliable non-invasive diagnosis in case of symptoms and signs suspicious for endometriosis.

In addition, ultrasound techniques and magnetic resonance imaging are evolving rapidly, allowing for better accuracy, even with the use of artificial intelligence. Finally, new potential histological makers are helping to correlate the occurrence of endometriosis in different anatomical landmarks, supporting specific pathways to clarify the etiology of the disease.

This Special Issue will publish reviews and original research about the diagnostics of endometriosis: in particular, we welcome articles about molecular, cellular and histological biomarkers; imaging techniques, including ultrasound and magnetic resonance imaging, and new invasive (surgical) techniques.

Dr. Antonio Simone Laganà
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Endometriosis
  • Diagnosis
  • Biomarkers
  • Ultrasound
  • Magnetic resonance imaging
  • Invasive diagnosis

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Related Special Issue

Published Papers (10 papers)

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Research

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18 pages, 884 KiB  
Article
Assessment of Coagulation Parameters in Women Affected by Endometriosis: Validation Study and Systematic Review of the Literature
by Jessica Ottolina, Ludovica Bartiromo, Carolina Dolci, Noemi Salmeri, Matteo Schimberni, Roberta Villanacci, Paola Viganò and Massimo Candiani
Diagnostics 2020, 10(8), 567; https://doi.org/10.3390/diagnostics10080567 - 7 Aug 2020
Cited by 20 | Viewed by 3004
Abstract
The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database [...] Read more.
The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including n = 572 women who underwent laparoscopic surgery for endometriosis (cases, n = 324) or other benign gynecologic diseases (controls, n = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III–IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III–IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00–0.445; p = 0.024). Results from the n = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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10 pages, 888 KiB  
Article
BIRC5/Survivin Expression as a Non-Invasive Biomarker of Endometriosis
by Carolina Filipchiuk, Antonio Simone Laganà, Rubia Beteli, Tatiana Guida Ponce, Denise Maria Christofolini, Camila Martins Trevisan, Fernando Luiz Affonso Fonseca, Caio Parente Barbosa and Bianca Bianco
Diagnostics 2020, 10(8), 533; https://doi.org/10.3390/diagnostics10080533 - 30 Jul 2020
Cited by 28 | Viewed by 5406
Abstract
The etiology of endometriosis is highly complex, and although it is a benign disease, it has several biological behaviors similar to malignant lesions, including cell invasion, neo-angiogenesis, and decreased apoptosis. Survivin is a protein encoded by the BIRC5 gene that plays a role [...] Read more.
The etiology of endometriosis is highly complex, and although it is a benign disease, it has several biological behaviors similar to malignant lesions, including cell invasion, neo-angiogenesis, and decreased apoptosis. Survivin is a protein encoded by the BIRC5 gene that plays a role in cell division by inhibiting apoptosis and regulating the process of mitosis in embryonic and cancer cells. Therefore, we aimed to evaluate the expression of BIRC5 in samples of peripheral blood of women with and without endometriosis. This study comprised of 40 women with endometriosis and 10 healthy women as controls. Peripheral blood samples were collected in the three phases of the menstrual cycle (follicular, ovulatory, and luteal). The expression of the BIRC5 gene was evaluated by RT-qPCR using the TaqMan methodology. The BIRC5 expression was significantly higher in all phases of the menstrual cycle in women with endometriosis, regardless of the disease stage. The accuracy of BIRC5 expression in the peripheral blood for the diagnosis endometriosis presented AUC of 0.887 (p < 0.001), with 97.2% of sensitivity and specificity of 65.5% considering the overall endometriosis group. Regarding the minimal/mild endometriosis group, the AUC presented a value of 0.925 (p < 0.001), with 100% of sensitivity and 79.3% of specificity, whereas in the moderate/severe endometriosis group the AUC was 0.868 (p < 0.001), with a sensitivity of 95.8% and specificity of 65.5%. These findings suggest that the expression of BIRC5 may be a potential noninvasive biomarker for the diagnosis of endometriosis. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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17 pages, 3137 KiB  
Article
Uncovering Potential Roles of Differentially Expressed Genes, Upstream Regulators, and Canonical Pathways in Endometriosis Using an In Silico Genomics Approach
by Zeenat Mirza and Umama A. Abdel-dayem
Diagnostics 2020, 10(6), 416; https://doi.org/10.3390/diagnostics10060416 - 19 Jun 2020
Cited by 9 | Viewed by 4006
Abstract
Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological [...] Read more.
Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological data of endometriosis patients and controls from NCBI’s Gene Expression Omnibus, after a systematic search of multiple independent studies comprising 156 endometriosis patients and 118 controls to identify causative genes, risk factors, and potential diagnostic/therapeutic biomarkers. Comprehensive gene expression meta-analysis, pathway analysis, and gene ontology analysis was done using a bioinformatics-based approach. We identified 1590 unique differentially expressed genes (129 upregulated and 1461 downregulated) mapped by IPA as biologically relevant. The top upregulated genes were FOS, EGR1, ZFP36, JUNB, APOD, CST1, GPX3, and PER1, and the top downregulated ones were DIO2, CPM, OLFM4, PALLD, BAG5, TOP2A, PKP4, CDC20B, and SNTN. The most perturbed canonical pathways were mitotic roles of Polo-like kinase, role of Checkpoint kinase proteins in cell cycle checkpoint control, and ATM signaling. Protein–protein interaction analysis showed a strong network association among FOS, EGR1, ZFP36, and JUNB. These findings provide a thorough understanding of the molecular mechanism of endometriosis, identified biomarkers, and represent a step towards the future development of novel diagnostic and therapeutic options. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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15 pages, 3702 KiB  
Article
A Prospective Study Comparing Three-Dimensional Rectal Water Contrast Transvaginal Ultrasonography and Computed Tomographic Colonography in the Diagnosis of Rectosigmoid Endometriosis
by Fabio Barra, Ennio Biscaldi, Carolina Scala, Antonio Simone Laganà, Valerio Gaetano Vellone, Cesare Stabilini, Fabio Ghezzi and Simone Ferrero
Diagnostics 2020, 10(4), 252; https://doi.org/10.3390/diagnostics10040252 - 24 Apr 2020
Cited by 22 | Viewed by 4896
Abstract
(1) Objectives: In patients with symptoms suggestive of rectosigmoid endometriosis, imaging techniques are required to confirm the presence and establish the extent of the disease. The objective of the current study was to compare the performance of three-dimensional rectal water contrast transvaginal ultrasonography [...] Read more.
(1) Objectives: In patients with symptoms suggestive of rectosigmoid endometriosis, imaging techniques are required to confirm the presence and establish the extent of the disease. The objective of the current study was to compare the performance of three-dimensional rectal water contrast transvaginal ultrasonography (3D-RWC-TVS) and computed tomographic colonography (CTC) in predicting the presence and characteristics of rectosigmoid endometriosis. (2) Methods: This prospective study included patients with suspicion of rectosigmoid endometriosis who underwent both 3D-RWC-TVS and CTC and subsequently were surgically treated. The findings of imaging techniques were compared with surgical and histological results. (3) Results: Out of 68 women included in the study, 37 (48.9; 95% C.I. 38.2–59.7%) had rectosigmoid nodules and underwent bowel surgery. There was no significant difference in the accuracy of 3D-RWC-TVS and CTC in diagnosing the presence of rectosigmoid endometriotic nodules (p = 0.118), although CTC was more precise in diagnosing endometriosis located in the sigmoid (p = 0.016). 3D-RWC-TVS and CTC had similar precision in estimating the largest diameter of the main endometriotic nodule (p = 0.099) and, in patients undergoing segmental resection, the degree of the stenosis of the bowel lumen (p = 0.293). CTC was more accurate in estimating the distance between the lower margin of the intestinal nodule and the anal verge (p = 0.030) but was less tolerated than 3D-RWC-TVS (p < 0.001). (4) Conclusion: This was the first study comparing the performance of 3D-RWC-TVS and CTC in the diagnosis of rectosigmoid endometriosis. Both techniques allowed for the evaluation of the profile of the bowel lumen in a pseudoendoscopic fashion and had a similar performance for the diagnosis of rectosigmoid endometriosis, although CTC was more accurate in diagnosing and characterizing sigmoid nodules. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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10 pages, 268 KiB  
Article
Does Endometriosis Influence the Embryo Quality and/or Development? Insights from a Large Retrospective Matched Cohort Study
by Ana M. Sanchez, Luca Pagliardini, Greta C. Cermisoni, Laura Privitera, Sofia Makieva, Alessandra Alteri, Laura Corti, Elisa Rabellotti, Massimo Candiani and Paola Viganò
Diagnostics 2020, 10(2), 83; https://doi.org/10.3390/diagnostics10020083 - 3 Feb 2020
Cited by 34 | Viewed by 5094
Abstract
In vitro fertilization can be an effective tool to manage the endometriosis-associated infertility, which accounts for 10% of the strategy indications. Nevertheless, a negative effect of endometriosis on IVF outcomes has been suggested. The aim of this study was to evaluate the potential [...] Read more.
In vitro fertilization can be an effective tool to manage the endometriosis-associated infertility, which accounts for 10% of the strategy indications. Nevertheless, a negative effect of endometriosis on IVF outcomes has been suggested. The aim of this study was to evaluate the potential effect of endometriosis in the development of embryos at cleavege stage in assisted reproduction treatment cycles. A total of 429 cycles from women previously operated for moderate/severe endometriosis were compared with 851 cycles from non-affected women. Patients were matched by age, number of oocyte retrieved and study period. A total of 3818 embryos in cleavage stage have been analyzed retrospectively. Overall, no difference was found between women with and without endometriosis regarding the number of cleavage stage embryos obtained as well as the percentage of good/fair quality embryos. Excluding cycles in which no transfers were performed or where embryos were frozen in day three, no difference was observed for blastulation rate or the percentage of good/fair blastocysts obtained. Despite similar fertilization rate and number/quality of embryos, a reduction in ongoing pregnancy rate was observed in patients affected, possibly due to an altered endometrial receptivity or to the limited value of the conventional morphological evaluation of the embryo. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)

Review

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15 pages, 9590 KiB  
Review
Differential Diagnosis of Endometriosis by Ultrasound: A Rising Challenge
by Marco Scioscia, Bruna A. Virgilio, Antonio Simone Laganà, Tommaso Bernardini, Nicola Fattizzi, Manuela Neri and Stefano Guerriero
Diagnostics 2020, 10(10), 848; https://doi.org/10.3390/diagnostics10100848 - 20 Oct 2020
Cited by 24 | Viewed by 9895
Abstract
Ultrasound is an effective tool to detect and characterize endometriosis lesions. Variances in endometriosis lesions’ appearance and distorted anatomy secondary to adhesions and fibrosis present as major difficulties during the complete sonographic evaluation of pelvic endometriosis. Currently, differential diagnosis of endometriosis to distinguish [...] Read more.
Ultrasound is an effective tool to detect and characterize endometriosis lesions. Variances in endometriosis lesions’ appearance and distorted anatomy secondary to adhesions and fibrosis present as major difficulties during the complete sonographic evaluation of pelvic endometriosis. Currently, differential diagnosis of endometriosis to distinguish it from other diseases represents the hardest challenge and affects subsequent treatment. Several gynecological and non-gynecological conditions can mimic deep-infiltrating endometriosis. For example, abdominopelvic endometriosis may present as atypical lesions by ultrasound. Here, we present an overview of benign and malignant diseases that may resemble endometriosis of the internal genitalia, bowels, bladder, ureter, peritoneum, retroperitoneum, as well as less common locations. An accurate diagnosis of endometriosis has significant clinical impact and is important for appropriate treatment. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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12 pages, 1354 KiB  
Review
Endometriosis in Menopause—Renewed Attention on a Controversial Disease
by Cristina Secosan, Ligia Balulescu, Simona Brasoveanu, Oana Balint, Paul Pirtea, Grigoraș Dorin and Laurentiu Pirtea
Diagnostics 2020, 10(3), 134; https://doi.org/10.3390/diagnostics10030134 - 29 Feb 2020
Cited by 30 | Viewed by 11020
Abstract
Endometriosis, an estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial tissue, has been the topic of renewed research and debate in recent years. The paradigm shift from the belief that endometriosis only affects women of reproductive age has drawn attention to [...] Read more.
Endometriosis, an estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial tissue, has been the topic of renewed research and debate in recent years. The paradigm shift from the belief that endometriosis only affects women of reproductive age has drawn attention to endometriosis in both premenarchal and postmenopausal patients. There is still scarce information in literature regarding postmenopausal endometriosis, the mostly studied and reported being the prevalence in postmenopausal women. Yet, other important issues also need to be addressed concerning diagnosis, pathophysiology, and management. We aimed at summarizing the currently available data in literature in order to provide a concise and precise update regarding information available on postmenopausal endometriosis. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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Other

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3 pages, 4425 KiB  
Reply
Transvaginal Strain Elastosonography in the Differential Diagnosis of Rectal Endometriosis: Some Potentials and Limits
by Marco Scioscia, Antonio Simone Laganà, Giuseppe Caringella and Stefano Guerriero
Diagnostics 2021, 11(1), 99; https://doi.org/10.3390/diagnostics11010099 - 9 Jan 2021
Cited by 4 | Viewed by 1997
Abstract
We sincerely thank Szabó et al [...] Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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3 pages, 3335 KiB  
Comment
Transvaginal Strain Elastosonography May Help in the Differential Diagnosis of Endometriosis?
by Gábor Szabó, István Madár, Attila Bokor and János Rigó, Jr.
Diagnostics 2021, 11(1), 100; https://doi.org/10.3390/diagnostics11010100 - 9 Jan 2021
Cited by 3 | Viewed by 2276
Abstract
Dear Editor, [...] Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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11 pages, 2106 KiB  
Brief Report
Microbiome Profile of Deep Endometriosis Patients: Comparison of Vaginal Fluid, Endometrium and Lesion
by Camila Hernandes, Paola Silveira, Aline Fernanda Rodrigues Sereia, Ana Paula Christoff, Helen Mendes, Luiz Felipe Valter de Oliveira and Sergio Podgaec
Diagnostics 2020, 10(3), 163; https://doi.org/10.3390/diagnostics10030163 - 17 Mar 2020
Cited by 72 | Viewed by 6244
Abstract
This work aimed to identify and compare the bacterial patterns present in endometriotic lesions, eutopic endometrium and vaginal fluid from endometriosis patients with those found in the vaginal fluid and eutopic endometrium of control patients. Vaginal fluid, eutopic endometrium and endometriotic lesions were [...] Read more.
This work aimed to identify and compare the bacterial patterns present in endometriotic lesions, eutopic endometrium and vaginal fluid from endometriosis patients with those found in the vaginal fluid and eutopic endometrium of control patients. Vaginal fluid, eutopic endometrium and endometriotic lesions were collected. DNA was extracted and the samples were analyzed to identify microbiome by high-throughput DNA sequencing of the 16S rRNA marker gene. Amplicon sequencing from vaginal fluid, eutopic endometrium and endometriotic lesion resulted in similar profiles of microorganisms, composed most abundantly by the genus Lactobacillus, Gardnerella, Streptococcus and Prevotella. No significant differences were found in the diversity analysis of microbiome profiles between control and endometriotic patients; however deep endometriotic lesions seems to present different bacterial composition, less predominant of Lactobacillus and with more abundant Alishewanella, Enterococcus and Pseudomonas. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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