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International Journal of Gynaecology... Aug 2023Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009....
INTRODUCTION
Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies.
METHODS
The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system.
RESULTS
Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (POLEmut, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICm or IAm ).
SUMMARY
The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.
Topics: Female; Humans; Peritoneal Neoplasms; Neoplasm Staging; Endometrial Neoplasms; Prognosis; Carcinoma, Endometrioid; Retrospective Studies
PubMed: 37337978
DOI: 10.1002/ijgo.14923 -
Journal of Gynecologic Oncology Sep 2023Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009....
INTRODUCTION
Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies.
METHODS
The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system.
RESULTS
Based on the existing evidence, the substages were defined as follows: non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or status in Stages I and II, this results in upstaging or downstaging of the disease (IICm or IAm).
SUMMARY
The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.
Topics: Female; Humans; Peritoneal Neoplasms; Endometrial Neoplasms; Endometrium; Uterus; Carcinoma, Endometrioid
PubMed: 37593813
DOI: 10.3802/jgo.2023.34.e85 -
Maturitas Jun 2024Abnormal uterine bleeding is a frequent symptom in the perimenopause. Causes are numerous, ranging from physiological reactions due to decreasing/unstable ovarian... (Review)
Review
Abnormal uterine bleeding is a frequent symptom in the perimenopause. Causes are numerous, ranging from physiological reactions due to decreasing/unstable ovarian function to premalignant and malignant conditions. Benign findings such as endometrial polyps and myomas increase with age, leading to more abnormal uterine bleeding in the perimenopause. Cervical and vaginal causes of abnormal uterine bleeding should be excluded by speculum examination. Sexually transmitted diseases or pregnancy should be ruled out. Measurement of haemoglobin and iron levels, human chorion gonadotropin and thyroid hormones are relevant in selected cases. Transvaginal ultrasound is an ideal first step for the evaluation of perimenopausal abnormal uterine bleeding. Saline or gel contrast sonohysterography improves the diagnostic accuracy. Based on the ultrasound findings, invasive procedures such as endometrial biopsy or hysteroscopy can be planned. Once premalignant and malignant causes are excluded, the necessity for treatment can be evaluated in collaboration with the patient. Heavy menstrual bleeding causing anaemia will need immediate treatment. In less severe cases and in intermenstrual bleeding, expectant management can be considered. Hormonal treatment, such as oral progestogens, combined oral contraceptives or insertion of the levonorgestrel intrauterine system, may be a possibility if anovulatory bleeding is interfering with quality of life. The amount of bleeding can be reduced both by antifibrinolytic and non-steroidal anti-inflammatory drugs, progestogens and the levonorgestrel intrauterine system. Focal intrauterine lesions such as endometrial polyps or submucous myomas may require operative hysteroscopic procedures. Endometrial ablation or endometrial resection are good choices in selected cases, but some women will need a hysterectomy to treat their abnormal uterine bleeding in perimenopause.
Topics: Humans; Female; Perimenopause; Uterine Hemorrhage
PubMed: 38412750
DOI: 10.1016/j.maturitas.2024.107944 -
Seminars in Ultrasound, CT, and MR Dec 2023Post-menopausal bleeding (PMB) accounts for 5% of gynecologic office visits and is the presenting symptom in 90% of women with endometrial cancer, which requires prompt... (Review)
Review
Post-menopausal bleeding (PMB) accounts for 5% of gynecologic office visits and is the presenting symptom in 90% of women with endometrial cancer, which requires prompt evaluation. The most common etiology of PMB is vaginal or endometrial atrophy and endometrial polyps, while endometrial hyperplasia and carcinoma account for less than 10% of PMB. Transvaginal ultrasonography measurement of an endometrial thickness (EMT) less than or equal to 4 mm has a 99% negative predictive value for endometrial carcinoma. Endometrial sampling is required if EMT >4 mm or persistent bleeding occurs. Further evaluation can be accomplished with saline infusion sonography, magnetic resonance imaging, and hysteroscopy.
Topics: Female; Humans; Postmenopause; Endometrial Neoplasms; Endometrium; Uterine Hemorrhage; Uterine Neoplasms; Ultrasonography
PubMed: 37832697
DOI: 10.1053/j.sult.2023.10.003 -
Maturitas Dec 2023To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and...
OBJECTIVE
To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium.
DESIGN
Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities.
MAIN FINDINGS
Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5 years, p = 0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3 % vs 9.7 % p = 0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1 % vs 50.3 % 3 = 0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95 % CI 1.28-3.07, p = 0.002), repeat endometrial biopsy (34.9 % vs. 16.8%p < 0.001) and future hysterectomy or hysteroscopy (26.6 % vs 16.2 % p < 0.001).
CONCLUSIONS
In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases.
Topics: Pregnancy; Female; Humans; Postmenopause; Retrospective Studies; Uterine Neoplasms; Endometrium; Uterine Diseases; Uterine Hemorrhage; Hysteroscopy; Leiomyoma; Polyps; Endometrial Neoplasms
PubMed: 37717294
DOI: 10.1016/j.maturitas.2023.107847 -
Cureus Aug 2023Deciduosis is an ectopic transformation of connective tissue into decidual-like cells. This is the first systematic review describing the clinical course, associated... (Review)
Review
Cervical and Vaginal Deciduosis: Insights on Management and a Systematic Review of Observational Studies on Pregnancy Complications and Management Outcomes (Including Vaginal Birth).
INTRODUCTION
Deciduosis is an ectopic transformation of connective tissue into decidual-like cells. This is the first systematic review describing the clinical course, associated pregnancy complications, and management outcomes of cervical and vaginal deciduosis.
METHODS
Our search covered worldwide observational studies published in English in five databases (PubMed, PubMed Central (PMC), Europe PMC, ScienceDirect, and Google Scholar) from inception to February 24, 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and critically appraised studies using CAse REport (CARE) and Joanna Briggs Institute (JBI) tools. Then, we extracted patient characteristics, clinical features, management-related information, and outcomes.
RESULTS
The selection process identified 15 studies describing 30 pregnancies. Macroscopic cervical and vaginal deciduosis presented as recurrent vaginal bleeding in over 16 of 24 women (57%). Differential diagnoses included miscarriages, cervical pregnancy, placenta previa, and malignancy. Significant antenatal hemorrhages, preterm rupture of membranes, and preterm birth were the most frequent pregnancy complications. Only one of 27 electively performed procedures resulted in biopsy-induced uncontrolled vaginal bleeding (0.04%), suggesting the relative safety of the interventions. Lesion resection led to the cessation of recurrent symptoms in eight of eight patients (100%) compared to eight of 15 women (53%) under observation management. All women with polypoid deciduosis over 1.5 cm entered labor and delivered without complications.
CONCLUSIONS
We described the clinical course, pregnancy complications, diagnostic-related challenges, management, and associated outcomes in women with macroscopic cervical and vaginal deciduosis. We supported the analysis with the current state of the problem and discovered gaps for prospective studies.
PubMed: 37791171
DOI: 10.7759/cureus.44479 -
The British Journal of Radiology Feb 2024Pathologies of the vagina are important causes of symptoms related to the genital tract in women. They can be missed on transabdominal ultrasonography (USG), which is...
Pathologies of the vagina are important causes of symptoms related to the genital tract in women. They can be missed on transabdominal ultrasonography (USG), which is the baseline modality used for evaluation of gynaecological complaints. Transperineal USG and MRI are the imaging modalities of choice for evaluation of the vagina. Diseases of the vagina can be grouped depending upon the age group in which they occur. In children and young adults, congenital anomalies like longitudinal or transverse vaginal septum, imperforate hymen, vaginal aplasia or atresia, and rectovaginal fistula can be seen. Malignant tumours can rarely occur in children, rhabdomyosarcoma being the most common one. Common diseases affecting adults include benign lesions like epidermoid, Gartner duct, and Bartholin cysts, and urogenital fistulas involving the vagina. Endometriosis and other benign tumours of vagina including leiomyoma, fibroepithelial polyp, and angiomyxoma are occasionally seen. Malignant tumours can be primary, the most common one being squamous cell carcinoma, or secondary, due to direct extension from cancers involving the adjacent organs. Characteristic morphological changes occur in the vagina after radiotherapy, which can be identified on imaging. Knowledge about the imaging appearances of these diseases is crucial in guiding appropriate management.
Topics: Child; Female; Humans; Vagina; Hymen; Vaginal Diseases; Genitalia, Female; Carcinoma, Squamous Cell
PubMed: 38419147
DOI: 10.1093/bjr/tqad052 -
Systems Biology in Reproductive Medicine Aug 2023For decades, the endometrium was considered to be a sterile environment. However, now this concept is disputed, and there is growing evidence that microbiota composition...
For decades, the endometrium was considered to be a sterile environment. However, now this concept is disputed, and there is growing evidence that microbiota composition might affect endometrial receptivity. Routine clinical management of infertility is still limited to a microbiological assessment of the lower reproductive tract. The purpose of this study was to compare the abundance of various bacterial, fungal, and viral species, qualitatively and quantitatively, in vaginal, cervical, and endometrial biomaterial of infertile patients. A total of 300 samples from 100 infertile patients of a private assisted reproduction clinic were analyzed. A broad real-time polymerase chain reaction panel was used to identify 28 relevant microbial taxa as well as three members of the Herpesviridae family. All patients underwent endometrial biopsy for further histopathological evaluation. Analysis of the microbial diversity (within the boundaries of the detection panel) revealed that Shannon indexes in the cervix and vagina were similar (1.4 × 10 (1.6 × 10 - 6.5 × 10) vs 1.9 × 10 (2.3 × 10 - 5.3 × 10), respectively, = 0.502), whereas endometrial indexes differed significantly from both regions (0 (0 - 1.4 × 10), < 0.0001). Surprisingly, 17 microbial and viral taxa were detected in at least one sample. Endometrium exhibited a quite distinct microbiological profile, being different at the detection rates of 14 taxa ( < 0.05). Remarkably, 4% and 2% of endometrial samples were positive for Cytomegalovirus and , respectively, while these were undetectable in corresponding cervical and vaginal samples. Prevalence of the + + group in endometrium was associated with a low abundance of . ( = 0.039). No noteworthy associations were identified between various microbiota characteristics and clinical parameters, such as chronic endometritis, uterine polyps and adhesions, endometriosis, and a history of sexually transmitted infections. These findings indicate that the microbiological profile of the endometrium is unique, and the analysis of the lower reproductive tract should supplement, rather than be a substitute for it.
Topics: Female; Humans; Cervix Uteri; Endometrium; Infertility; Vagina; Gardnerella vaginalis
PubMed: 37105537
DOI: 10.1080/19396368.2023.2195040 -
Bioscience Trends Jan 2024Microorganisms are ubiquitous in the human body; they are present in various areas including the gut, mouth, skin, respiratory tract, and reproductive tract. The... (Review)
Review
Microorganisms are ubiquitous in the human body; they are present in various areas including the gut, mouth, skin, respiratory tract, and reproductive tract. The interaction between the microbiome and reproductive health has become an increasingly compelling area of study. Disruption of the female genital tract microbiome can significantly impact the metabolism of amino acids, carbohydrates, and lipids, increasing susceptibility to reproductive tract diseases such as vaginitis, chronic endometritis, endometrial polyps, endometriosis, and polycystic ovary syndrome. The gut microbiome, considered an endocrine organ, plays a crucial role in the reproductive endocrine system by interacting with hormones like estrogen and androgens. Imbalances in the gut microbiome composition can lead to various diseases and conditions, including polycystic ovary syndrome, endometriosis, and cancer, although research on their mechanisms remains limited. This review highlights the latest advancements in understanding the female genital tract and gut microbiomes in gynecological diseases. It also explores the potential of microbial communities in the treatment of reproductive diseases. Future research should focus on identifying the molecular mechanisms underlying the association between the microbiome and reproductive diseases to develop new and effective strategies for disease prevention, diagnosis, and treatment related to female reproductive organs.
Topics: Female; Humans; Gastrointestinal Microbiome; Polycystic Ovary Syndrome; Endometriosis; Genitalia, Female; Reproduction
PubMed: 38104979
DOI: 10.5582/bst.2023.01133