OBJECTIVE: To assess the prevalence of endometriosis of the appendix and the association with other pelvic localizations of the disease and to provide pathogenesis hypotheses.
METHODS: Monocentric, observational, retrospective, cohort study. Patients undergoing laparoscopic endometriosis surgery in our tertiary referral center were consecutively enrolled. The prevalence of the different localizations of pelvic endometriosis including appendix involvement detected during surgery was collected. Included patients were divided into two groups based on the presence of appendiceal endometriosis. Women with a history of appendectomy were excluded.
RESULTS: Four hundred-sixty patients were included for data analysis. The prevalence of appendiceal endometriosis was 2.8%. In patients affected by endometriosis of the appendix, concomitant ovarian and/or bladder endometriosis were more frequently encountered, with prevalence of 53.9% (vs 21.0% in non-appendiceal endometriosis group, p = 0.005) and 38.4% (vs 11.4%, p = 0.003), respectively. Isolated ovarian endometriosis was significantly associated to appendiceal disease compared to isolated uterosacral ligament (USL) endometriosis or USL and ovarian endometriosis combined (46.2% vs 15.4% vs 7.7%, p < 0.001). Poisson regression analysis revealed a 4.1-fold and 4.4-fold higher risk of ovarian and bladder endometriosis, respectively, and a 0.1-fold risk of concomitant USL endometriosis in patients with appendiceal involvement.
CONCLUSIONS: Involvement of the appendix is not uncommon among patients undergoing endometriosis surgery. Significant association was detected between appendiceal, ovarian, and bladder endometriosis that may be explained by disease dissemination coming from endometrioma fluid shedding. Given the prevalence of appendiceal involvement, counseling regarding the potential need for appendectomy during endometriosis surgery should be considered.

Endometriosis and adenomyosis are complex gynecological conditions characterized by diverse clinical presentations, including superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The hallmark features of these pathologies involve the manifestation of pain symptoms and infertility, and approximately 30% of patients are asymptomatic. Despite ongoing research, definitive treatments for these conditions remain elusive, and clinical management primarily revolves around medical or surgical interventions. Recent advancements in our understanding of the efficacy of various treatment modalities, including medical therapy and surgical interventions, have provided clinicians with valuable insights into pain relief and fertility preservation. This review aims to provide an updated overview of the latest literature on clinical outcomes, treatment options, and management strategies for different types of endometriosis. By synthesizing the newest available data, this review seeks to inform clinicians and guide decision making based on factors such as patients\' symptom severity, childbearing desire, and overall health.

UNASSIGNED: Clear cell carcinoma of the ovary (CCCO) is a relatively rare type of epithelial ovarian cancer (EOC) that has unique biological characteristics and clinical features. Researchers have paid less attention to this disease than to other types of EOCs. However, in recent years, research in this area has still progressed. In this paper, a bibliometric analysis is used to integrate and analyse the literature in the field of CCCO in the past 20 years to determine research development, better understand the current status of research, and provide a reference for future study directions in this field.
UNASSIGNED: With CCCO as the research subject, relevant publications indexed in the Web of Science (WOS) core dataset from September 2003 to September 2023 were retrieved. After screening the publications, we used EXCEL, VOSviewer, CiteSpace, Charticulator, Gephi, OriginPro and other tools to perform in-depth analyses of and to visualize the data.
UNASSIGNED: Through a comprehensive analysis of the literature in this field, we found that research on CCCO experienced a relatively rapid increase in 2006 and is now in a period of relatively high fluctuation. The quality of the literature in this field is generally high. In this field, countries in East Asia and North America play core roles, with Japan accounting for the most studies. A stable research group has been formed in this field, and extensive collaboration has occurred among the various research groups. In the past 20 years, basic research and clinical research in the field of CCCO have developed together, and a healthy development model in which basic and clinical research promote each other has formed. Research in this field has been continuously developed from a preliminary understanding of clinical features to in-depth explorations of the pathogenesis and the continuous optimization of treatment methods. The key molecular events in the pathogenesis and development of this disease and the application of novel antitumour drugs for this disease are the current research focuses and the future development direction in this field.
UNASSIGNED: Research on CCCO has progressed significantly in the past 20 years, but there are still many important issues regarding its pathogenesis and treatment that need to be addressed, and therefore, more research in this area should be conducted in the future. The study of key molecular events and the use of novel antitumour drugs are future development directions in this field.

BACKGROUND: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate.
METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases.
RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues.
CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.

BACKGROUND: Patients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions.
OBJECTIVE: This study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis.
METHODS: In this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic.
RESULTS: Seven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment.
CONCLUSIONS: The decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.

Uncommon in nature, retroperitoneal ganglioneuroma represents a neuroblastic benign tumor, predominantly manifesting in young adults, with a notable predilection for females. Often asymptomatic, the condition is frequently diagnosed incidentally due to delayed growth. Clinical manifestations arise primarily from the compression exerted on neighboring organs and vessels. The exclusive curative recourse lies in surgical intervention, underscoring the challenging task of achieving complete tumor excision, particularly when the ganglioneuroma attains considerable development and encapsulates significant retroperitoneal vessels. In this instance, we elucidate a case involving a 33-year-old woman, who had previously undergone a triple valve replacement due to rheumatic valvular disease, presenting persistent pelvic pain, unearthing a substantial asymptomatic retroperitoneal ganglioneuroma concomitant with an ovarian endometrioma. A laparotomy procedure was conducted, and to achieve a comprehensive excision of the mass, a meticulous intratumoral circular dissection of the prominent vessels, notably the superior mesenteric artery and celiac trunk, was undertaken. No local recurrence has been reported, 6 months after surgery. The significance of an experienced and well-trained surgical staff is underscored in addressing the complexities associated with this condition.

This narrative review aims to summarize available evidence on the IVF-associated outcomes after surgery for endometriosis. Only one retrospective study investigated if surgical treatment of superficial/peritoneal endometriosis may modify the outcomes of IVF; therefore, more data are needed to confirm the benefit of surgery for this type of disease for improving ART outcomes, and to be able to support it in routine practice. Solid evidence from several meta-analyses demonstrates that surgical treatment of endometriomas does not enhance the outcomes of IVF. In contrast, surgical treatment of ovarian endometriosis may lead to a reduction in ovarian reserve, especially in cases involving bilateral endometriomas or repeated surgical procedures. Some non-randomized studies have examined if surgical treatment on deep endometriosis may influence IVF outcomes. A systematic review with meta-analysis revealed that patients who underwent surgery before IVF exhibited significantly higher pregnancy rates per patient, pregnancy rates per cycle, and live birth rates per patient compared to those without prior surgery. However, the available data are insufficient to recommend surgical excision of deep endometriosis as the first-line treatment for asymptomatic patients to enhance IVF outcomes.

Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.

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OBJECTIVE: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma?
CONCLUSIONS: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable.
BACKGROUND: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs).
METHODS: The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis.
METHODS: Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively.
RESULTS: The median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7-30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman\'s rho 0.853, P < 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases.
METHODS: Datasets are available in the supplementary tables.
CONCLUSIONS: Even though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association.
CONCLUSIONS: The observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events.
BACKGROUND: The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE-A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad\'s Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden\'s Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.