Fertility-sparing treatment in MSI-H/MMRd endometrial carcinoma or atypical endometrial hyperplasia: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to describe the oncological and reproductive outcomes of patients with MSI-H/MMRd endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. METHODS: The study protocol was registered with the PROSPERO database (No: CRD42024530406). A systematic literature search in major electronic databases (PubMed, Embase, and Cochrane Library) was conducted from January 1, 2013 to August 10, 2024. The primary outcomes were complete remission (CR) rate and recurrence rate. Other outcomes included oncological outcomes in patients with Lynch syndrome and overall patient fertility status. RESULTS: The study included ten retrospective studies summarizing 66 patients with MSI-H/MMRd undergoing fertility-sparing treatment. The publication bias analysis was low. The length of follow-up varied from 3 to 164 months according to the different studies analyzed. After fertility-sparing treatment, 61.8 % of patients achieved CR, and 41.2 % of patients relapsed. Twelve patients were identified with germline mutations in Lynch syndrome, nine (75 %) achieved CR, and seven (77.8 %) relapsed. Only one study with active use of assisted reproductive technology reported a 1-year cumulative pregnancy rate of more than 60 % and more than half live births, while the remaining five studies assessed fertility outcomes and reported only one live birth. CONCLUSION: EC and AEH patients with the MSI-H/MMRd subtype had a low remission rate and high recurrence rate compared to conservative treatment. Caution is recommended when evaluating fertility-sparing therapy for patients with the MSI-H/MMRd subtype.

Multi-omic analyses identified SFRP4 as a novel biomarker in abnormal uterine bleeding with ovulatory dysfunction.

The goal of the study was to explore the mechanism underlying the progression from abnormal uterine bleeding with ovulatory dysfunction (AUB-O) to AUB with atypical hyperplasia/malignancy (AUB-M). AUB-O, AUB-M and control endometrial tissues were subjected to multi-omic analyses to identify biomarkers. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs), including SFRP4, between the AUB-O and AUB-M groups were identified. The expression of SFRP4 was upregulated in endometrial tissues from AUB-O groups compared to that from AUB-M groups. SFRP4 knockdown in human endometrial epithelial cells (hEECs) promoted cell migration, invasion, proliferation and colony formation but inhibited apoptosis. Furthermore, the levels of key Wnt pathway proteins were altered by SFRP4 knockdown: Wnt-5A was downregulated and Wnt-7A was upregulated. In conclusion, we identified SFRP4 as an AUB-O-related molecule. SFRP4 might play a key role in hEECs apoptosis, migration, invasion, proliferation and colony formation via the Wnt pathway. SFRP4 may serve as a repressive factor regarding the progression of AUB-O to AUB-M. However, further studies are warranted to elucidate the exact mechanism.

When is it necessary to perform biopsy in asymptomatic postmenopausal women with incidental finding of thickened endometrium?

OBJECTIVE: To determine the cutoff value for endometrial thickness (ET) that prompts a biopsy in asymptomatic postmenopausal women with an incidental finding of thickened endometrium, and to develop a risk prediction model. METHODS: This is a retrospective cohort analysis of the clinical records of the Hysteroscopic Center of Fu Xing Hospital, Capital Medical University, Beijing, China. We collected asymptomatic postmenopausal women who presented with an ET of ≥4 mm (double-layer) as an incidental finding. We stratified the participants into non-malignant and malignant groups based on pathology results and assessed differences between the two groups. A receiver operating characteristic curve (ROC) was used to identify the cutoff value of ET for predicting endometrial malignancy. Logistic regression models were also constructed to predict the risk of malignancy. RESULTS: A total of 581 consecutive eligible cases were included. The optimal cutoff value for ET was 8 mm, with a maximum area under the curve (AUC) of 0.755 (95 % CI: 0.645-0.865). In addition to ET, the regression model incorporated diabetes, blood flow signal, BMI, and hypertension to predict the risk of malignancy. A ROC curve constructed for the model yielded an AUC of 0.834 (95 % CI: 0.744-0.924). CONCLUSION: It is reasonable to offer hysteroscopy and visually-directed endometrial biopsy for asymptomatic postmenopausal women when ET is 8 mm or above. For those with an ET between 4 and 8 mm, further decision to perform biopsy should be determined on an individual basis, considering risk factors and blood flow signals of the endometrium.

Nomogram using human epididymis protein 4 predicted concurrent endometrial cancer from endometrial atypical hyperplasia before surgery.

Objective: To establish a nomogram based on presurgical predictors of concurrent endometrial cancer (EC) for patients diagnosed with endometrial atypical hyperplasia before definitive surgery (preoperative-EAH) to improve the risk stratification and clinical application. Methods: Preoperative-EAH patients who underwent hysterectomy in a tertiary hospital from January 2020 to December 2022 were retrospectively analyzed. Independent predictors from the multivariate logistic regression model were used to establish a nomogram, and bootstrap resampling was used for internal validation. Results: Of 370 preoperative-EAH patients, 23.4% were diagnosed with EC after definitive surgery (final-EC). Multivariate analyses found three independent predictors of final EC: human epididymis protein 4 (HE4) ≥43.50 pmol/L [odds ratio (OR) = 3.70; 95% confidence intervals (CI) = 2.06-6.67], body mass index (BMI) ≥ 28 kg/m2 (OR = 2.05; 95% CI = 1.14-3.69), and postmenopausal status, particularly at postmenopausal time ≥5 years (OR = 5.84, 95% CI = 2.51-13.55), which were used to establish a nomogram model. The bootstrap-corrected C-index of the nomogram was 0.733 (95% CI = 0.68-0.79), which was significantly higher than that of each individual factor. The calibration curve and decision curve showed good consistency and clinical net benefit of the model. At the maximum Youden index, 49.4% (43/87) of women in the high-risk group defined by nomogram had concurrent EC, versus 16.6% in the low-risk group (P< 0.001). Conclusion: The nomogram based on HE4, menopausal status, and BMI was found with an improved predictive value to stratify preoperative-EAH patients at high risk of concurrent EC for better clinical management.

Risk factors for atypical hyperplasia or endometrial cancer in premenopausal women aged ≤ 45 years with abnormal uterine bleeding.

OBJECTIVES: To assess the prevalence and risk factors for atypical hyperplasia (AH) or endometrial cancer (EC) in premenopausal women aged ≤ 45 years with abnormal uterine bleeding (AUB). METHODS: This was a retrospective study of premenopausal patients aged 18 to 45 years who underwent hysteroscopy, dilation and curettage, or pipelle sampling at Inha University Hospital, South Korea, from 2014 to 2023. We used multivariable logistic regression analysis to identify risk factors and calculate the predicted probabilities of AH or EC with various combinations of these factors. RESULTS: Of 821 patients included in the study, 6.0 % were diagnosed with AH or EC. The significant risk factors identified were nulliparity (odds ratio (OR): 4.75, 95 % confidence interval (CI): 2.11-10.70), PCOS (OR: 2.72, 95 % CI: 1.34-5.52), and multiple polyps (OR: 2.33, 95 % CI: 1.23-4.41). The predicted probabilities of developing AH or EC increased with the number of risk factors present, ranging from 1 % to 33.6 %. CONCLUSIONS: The predicted probabilities within combinations of risk factors may be considered helpful in making better clinical decisions regarding endometrial sampling for patients ≤ 45 years with AUB.

Endometrial carcinoma with cervical stromal invasion: Three case reports.

BACKGROUND: Endometrial cancer is a kind of well-known tumors of female genitourinary system. Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer. There is still controversy regarding the use of magnetic resonance imaging (MRI) in the diagnosis of cervical stromal invasion of endometrial cancer. The diagnosis of cervical stromal invasion varies significantly between different observers and institutions. We present a limited case series of the particular pattern of endometrial cancer, which infiltrates the cervical stroma and is often overlooked. CASE SUMMARY: We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity. One patient, a reproductive-aged woman, exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage. A MRI scan revealed polypoid nodules within the internal cervical orifice. The other two cases were postmenopausal women who presented with abnormal vaginal bleeding. Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium. MRI scans did not detect any malignant signs in the endometrium. In one case, a non-thickened endometrium was observed, while in another, hyperplasia of the endometrium was seen. Notably, none of these patients had malignant tumors identified in the uterine cavity via MRI scans. However, postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion. CONCLUSION: Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI. Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Risks and benefits of sentinel lymph node evaluation in the management of endometrial intraepithelial neoplasia.

INTRODUCTION: Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer. Increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) evaluation during hysterectomy for EIN to ensure complete staging if there is cancer on the final specimen. However, there are no clear guidelines and the benefits and risks to performing SLN evaluation for EIN patients are unclear. AREAS COVERED: This narrative review examines the advantages and disadvantages of SLN evaluation for EIN patients and provides an algorithm to assist clinicians in selectively applying the procedure for maximal patient benefit. Relevant articles up to March 2024 were obtained from a PubMed search on SLN use with endometrial pathology. EXPERT OPINION: Sentinel lymph node evaluation for patients with EIN is safe, feasible, and particularly important for the approximately 10% of patients with high-risk endometrial carcinoma on final pathology. However, as most diagnosed carcinomas are low-risk, SLN evaluation would have limited oncologic benefit. While SLN assessment may overtreat most patients with EIN, a significant minority of patients will be improperly staged. We propose an algorithm highlighting the importance of maximal preoperative endometrial sampling and stratifying patients via risk factors to selectively identify those who would benefit most from SLN evaluation.

Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer, the most common gynecologic cancer in the United States. The definitive treatment for EIN is hysterectomy. An increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) assessment during surgery for EIN since 30­40% of patients with EIN will have underlying carcinoma. For those patients, lymph node evaluation is important for cancer staging, especially if high-risk or advanced stage disease is found on the pathologic specimen. The SLN procedure cannot be performed post-hysterectomy, so an improperly staged patient may require a second operation for lymphadenectomy; this has a greater chance of morbidity compared to an SLN biopsy. However, an SLN evaluation still confers perioperative risk and comes at an additional monetary cost, especially when most patients diagnosed with endometrial cancer after EIN will ultimately have low-risk, stage IA disease. We propose an algorithm for clinicians to help determine which patients with EIN would best benefit from the SLN procedure; this includes maximizing preoperative endometrial sampling and considering selective criterion with risk factors for concurrent endometrial carcinoma including age, endometrial thickness, obesity, and molecular classification.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Objective: Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. Methods: This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. Results: The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Conclusion: Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

Mismatch repair deficiency and abnormal p53 expression has significant predictive value for progesterone resistance and endometrial tumorigenesis in patients with endometrial atypical hyperplasia receiving fertility-preserving treatment.

OBJECTIVE: This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment. METHODS: This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status. RESULTS: Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively). CONCLUSIONS: EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.

Pregnancy and obstetric outcomes after fertility-sparing management of endometrial cancer and atypical hyperplasia: a multicentre cohort study.

STUDY QUESTION: What are the pregnancy and obstetric outcomes in women with atypical hyperplasia (AH) or early-stage endometrial cancer (EC) managed conservatively for fertility preservation? SUMMARY ANSWER: The study found a live birth rate of 62% in patients with AH or EC after conservative treatment, with higher level of labour induction, caesarean section, and post-partum haemorrhage. WHAT IS KNOWN ALREADY: Fertility-sparing treatment is a viable option for women with AH or EC during childbearing years, but the outcomes of such treatments, especially regarding pregnancy and obstetrics, need further exploration. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analysed data from January 2010 to October 2022, involving 269 patients from the French national register of patients with fertility-sparing management of AH/EC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women above 18 years of age, previously diagnosed with AH/EC, and approved for fertility preservation were included. Patients were excluded if they were registered before 2010, if their treatment began <6 months before the study, or if no medical record on the pregnancy was available. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 95 pregnancies in 67 women were observed. Pregnancy was achieved using ART in 63 cases (66%) and the live birth rate was 62%, with early and late pregnancy loss at 26% and 5%, respectively. In the 59 cases resulting in a live birth, a full-term delivery occurred in 90% of cases; 36% of cases required labour induction and 39% of cases required a caesarean section. The most common maternal complications included gestational diabetes (17%) and post-partum haemorrhaging (20%). The average (±SD) birthweight was 3110 ± 736 g; there were no significant foetal malformations in the sample. No significant difference was found in pregnancy or obstetric outcomes between ART-obtained and spontaneous pregnancies. However, the incidence of induction of labour, caesarean section, and post-partum haemorrhage appears higher than in the general population. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study may introduce bias, and the sample size might be insufficient for assessing rare obstetric complications. WIDER IMPLICATIONS OF THE FINDINGS: This study offers valuable insights for healthcare providers to guide patients who received fertility-sparing treatments for AH/EC. These pregnancies can be successful and with an acceptable live birth rate, but they seem to be managed with caution, leading to possible tendency for more caesarean sections and labour inductions. No increase in adverse obstetric outcomes was observed, with the exception of suspicion of a higher risk of post-partum haemorrhaging, to be confirmed. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Effect of vinegar supplementation on patients with esophageal lesions lightly stained with Lugol's iodine solution: Prospective single-centre trial.

BACKGROUND: Esophageal chromoendoscopy with iodine solution is important for detecting early esophageal cancer. The effect of routine treatment for lesions lightly stained with Lugol's iodine solution is limited, and the addition of natural substances to a regular diet is becoming increasingly common. Vinegar has antitumor effects as reported in previous studies. AIM: To evaluate whether vinegar supplementation could improve the prognosis of patients with lightly stained esophageal lesions. METHODS: This prospective single-centre trial included consecutive patients with lightly stained lesions between June 2020 and April 2022. Patients in the experimental group received increased amounts of vinegar for 6 months. The primary outcome of the study was the clinical therapeutic effect. Complications related to vinegar ingestion and adverse events were also recorded in detail. RESULTS: A total of 166 patients were included in the final analysis. There was no significant difference in the baseline data between the two groups. Intention-to-treat (ITT) analysis demonstrated that the rates at which endoscopic characteristics improved were 33.72% in the experimental group and 20.00% in the conventional group (P = 0.007); and the rates at which biopsy pathology improved were 19.77% and 8.75%, respectively (P = 0.011). Additional vinegar consumption had a statistically protective effect on the rate at which endoscopic characteristics improved [hazard ratio (HR) ITT = 2.183, 95%CI: 1.183-4.028; HRper-protocol (PP) = 2.307, 95%CI: 1.202-4.426] and biopsy pathology improved (HRITT = 2.931, 95%CI: 1.212-7.089; HRPP = 3.320, 95%CI: 1.295-8.507). No statistically significant effect of increased vinegar consumption on preventing high-grade intraepithelial neoplasia or early cancer was observed (HRITT = 0.382, 95%CI: 0.079-1.846; HRPP = 0.382, 95%CI: 0.079-1.846). The subgroup analyses indicated that the overall therapeutic improvement of endoscopic characteristics and biopsy pathology seemed more obvious in older (age > 60) male patients with small lesions (lesion size ≤ 0.5 cm). Three patients in the experimental group reported acid regurgitation and heartburn. No adverse event during gastroscopy were recorded during follow-up. CONCLUSION: A moderately increased ingestion of vinegar could not directly reduce the risk of esophageal cancer in the mucosa dysplasia population, but it improved the endoscopic characteristics and ameliorated the biopsy pathology to a certain extent. Further research is needed to verify the effect of nutritional intervention on precancerous esophageal lesions.

Serum proteomic profiling of precancerous gastric lesions and early gastric cancer reveals signatures associated with systemic inflammatory response and metaplastic differentiation.

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.

Unique immunohistochemical profiles of MUC5AC, MUC6, P53, and Ki67 in gastric atypical hyperplasia and dysplasia.

OBJECTIVES: Differentiating gastric atypical hyperplasia (AH) from dysplasia, including low-grade dysplasia (LGD) and high-grade dysplasia (HGD), poses significant challenges in small biopsies and specimens with technical artifacts. This study aims to establish objective diagnostic criteria for these conditions through combined morphologic and immunohistochemical (IHC) analyses. METHODS: Between January 2018 and September 2020, a total of 123 gastric mucosa biopsy specimens were collected at Anyang Tumor Hospital. According to the WHO Classification of Digestive System Tumors (5th edition), specimens were categorized into three groups: AH (n=48), LGD (n=30), and HGD (n=45). Morphologic characteristics were assessed, and IHC staining for MUC5AC, MUC6, MUC2, CD10, P53, and Ki67 was performed, followed by statistical analysis. RESULTS: Histologically, AH was predominantly marked by a pronounced inflammatory background (60.42%), intestinal metaplasia (64.58%), indistinct boundaries (83.33%), and a distinct maturation gradient (97.72%). AH nuclei were typically circular (97.92%), with a high nucleus-to-cytoplasm ratio (64.58%), prominent nucleoli (47.92%), and preserved polarity (89.58%). In contrast, LGD and HGD typically exhibited well-defined boundaries with an absent maturation gradient. LGD nuclei were rod-shaped (96.67%), with a low nucleus-to-cytoplasm ratio (96.67%) and preserved polarity (100%), whereas HGD demonstrated a loss of cellular polarity (77.78%). IHC findings revealed a consistent maturation gradient in AH, with polarized MUC5AC and MUC6 expression, significantly reduced in LGD (86.67%), and absent in HGD. P53 expression in HGD showed a predominant 'mutation-type pattern' (66.67%), contrasting with 'wild-type pattern' expression in AH and LGD (100%, 93.33%). Ki67 expression patterns varied from a 'pit neck pattern' in AH (95.83%) to a 'polarity pattern' in LGD (76.67%) and a 'diffuse pattern' in HGD (57.78%). The expression patterns of MUC5AC, MUC6, CD10, P53, and Ki67 varied significantly across the three groups (P<0.001). CONCLUSIONS: The integration of histomorphological features and expression profiles of MUC5AC, MUC6, P53, and Ki67 is instrumental in diagnosing gastric atypical hyperplasia and dysplasia.

Accuracy of Frozen Section Biopsy in the Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis.

The early and accurate diagnosis of endometrial cancer is of paramount importance for the survival of these patients. The aim of this study was to systematically appraise the available data regarding the accuracy of frozen section biopsy in diagnosing endometrial cancer. A thorough literature search was performed in PubMed/Medline, Scopus and the Cochrane Central Register of Controlled Trials databases from inception up to January 2023, with the use of specific, relevant key terms. A quality evaluation for each study was performed with the QUADAS-2 tool, whereas a bivariate random-effect model was performed to generate a summary receiver-operated curve. Heterogeneity was evaluated with Cochrane Q and Higgins' I2 statistics. Subgroup analyses were performed for studies focused on atypical hyperplasia and those focused on endometrial cancer. The search yielded 47 studies, involving 7790 patients with endometrial cancer. Among them, only 11 could be included in the quantitative analysis. QUADAS-2 evaluation resulted in rather high quality among the included studies. Quantitative synthesis resulted in a pooled sensitivity of 0.863 and pooled specificity of 0.916. The AUC was 0.948, the Q statistic was 10.488 (10 df, p = 0.399) and Higgins' I2 (4.655%) reported no significant heterogeneity. Subgroup analyses based on the diagnosis revealed a pooled sensitivity 0.886, specificity 0.862 and AUC 0.934 for endometrial cancer versus a sensitivity of 0.816, specificity of 0.962 and AUC 0.939 for atypical hyperplasia. Frozen section appears as a valid and reliable diagnostic tool for endometrial cancer. Its reliability seems to be even higher for the diagnosis of atypical hyperplasia. Therefore, this method may be considered in clinical practice and in settings with appropriate resources.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

The risk factors for premalignant and malignant endometrial polyps in premenopausal and postmenopausal women and trends over the past decade: A retrospective study in a single center, South Korea.

OBJECTIVES: To assess the prevalence and risk factors for premalignancy and malignancy in endometrial polyps and to evaluate trends over the past decade. STUDY DESIGN: This was a retrospective study of patients who underwent hysteroscopic polypectomy at Inha University Hospital, South Korea between January 2013 and June 2023. The demographic and clinical characteristics of the patients reviewed to identify risk factors for premalignancy and malignancy in endometrial polyps included the following: age, parity, body mass index, menopausal status, abnormal uterine bleeding symptoms, diabetes mellitus, hypertension, polycystic ovarian syndrome, use of menopausal hormonal therapy or oral contraceptives, tamoxifen treatment in patients with breast cancer, and the number of polyps. RESULTS: In total, 725 patients were enrolled, among whom 52 (7.2 %) had premalignant and malignant lesions. In logistic regression analysis, menopause (OR: 8.37, 95 % CI [3.33-21.04]), abnormal uterine bleeding (OR: 7.42, 95 % CI [2.13-25.86]), obesity (OR: 3.22, 95 % CI [1.53-6.77]), multiple polyps (OR: 2.86, 95 % CI [1.39-5.88]) and nulliparity (OR: 2.64, 95 % CI [1.13-6.19]) were significantly associated with premalignancy and malignancy in polyps. Annual trends during the study period showed an increase in the number of patients with three of the five risk factors (obesity, multiple polyps, and nulliparity) and an increase in the prevalence of premalignancy and malignancy in polyps. CONCLUSIONS: Menopause, abnormal uterine bleeding, obesity, multiple polyps, and nulliparity increase the risk of premalignancy and malignancy in endometrial polyps. The prevalence of premalignant and malignant polyps has been increasing over the past decade. The risk factors that have contributed to this trend were obesity, nulliparity, and multiple polyps.

Updates in the Surgical Management of Benign and High-Risk Breast Lesions.

Benign breast disease (BBD) is a heterogenous group of lesions often classified as nonproliferative or proliferative, with the latter group further categorized based on the presence of atypia. Although nonproliferative lesions are more common, the risk of breast cancer is elevated in women with proliferative lesions. Historically, the majority of proliferative lesions were excised due to concern for future and/or concomitant breast cancer at the site of the index lesion. However, contemporary data suggest that the risk of cancer associated with various proliferative lesions may be lower than previously thought, and management of BBD has become more nuanced. In this review, we will focus on recent updates in the management of a select group of benign and high-risk lesions.

Quality of information and decision regrets during fertility-sparing management for atypical hyperplasia and endometrial cancer in a prospective cohort study.

OBJECTIVE: To evaluate satisfaction with information, treatment, and decision regret during management to preserve fertility for atypical hyperplasia (AH) or endometrial cancer (EC). METHODS: A cohort study with standardized management using chlormadinone acetate was established through a national referral centre between January 2013 and November 2019. During this period, a questionnaire was given to 136 patients aged 19 to 43 years who were followed for fertility preservation for AH or EC. The questionnaire included the validated EORTC-QLQ-INFO25, as well as questions from the validated EVAPIL questionnaire, the Treatment Satisfaction with Medicines Questionnaire, and the Decision Regret Scales concerning treatment tolerability and general satisfaction. The main outcomes measured were the quality and satisfaction with the information and treatment received and the decision regret. RESULTS: 75 patients (55.1 %) responded to the questionnaire. Overall, patients were satisfied with the information received (median 75.0, range: 25-100) and thought it was helpful (median 100.0, range: 25-100). However, 54.7 % wished for more information. Most women (52.0 %) indicated that psychological support should be available. Patients who were less satisfied with the information received or wished to receive more information thought about stopping treatment more frequently. Decision regret was not related to treatment outcome (remission, hysterectomy, live birth), and 47 of the 56 patients who did not obtain a live birth did not regret fertility preservation. None of the nine patients who regretted fertility preservation obtained a live birth. Almost all the patients reported side effects. CONCLUSIONS: Dedicated information tools that detail conservative treatment for AH and EC as well as its secondary effects should be provided to improve adherence to treatment and follow-up. Furthermore, psychological support should be systematically proposed.

Triglyceride-glucose index (TyG index) and endometrial carcinoma risk: A retrospective cohort study.

OBJECTIVE: We analyzed the association between the triglyceride-glucose index (TyG index) and incident endometrial carcinogenesis, aiming to determine whether the TyG index is a promising predictive biomarker for endometrial carcinoma (EC). METHODS: In this retrospective cohort study, multiple logistic regression analysis was performed to evaluate the relationship between TyG index and EC incidence and progression. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC), as well as the cut-off value of the TyG index for EC incidence. RESULTS: The TyG index was significantly higher in patients with EC or endometrial atypical hyperplasia (EAH) than in those with normal endometrium (P < 0.001). A continuous rise was observed in the incidence of EC and EAH among the tertiles of the TyG index (P < 0.001). The multiple logistic regression analysis revealed that the TyG index was associated with EC and EAH risk after adjusting for potential confounding factors (EAH: odds ratio [OR] 2.54, 95% confidence interval [CI] 1.33-4.85, P = 0.005; EC: OR 2.65, 95% CI 1.60-4.41, P < 0.001). Moreover, high TyG index was positively associated with advanced pathological stage (OR 2.14, 95% CI 1.32-3.47, P = 0.002) and poorer differentiation (OR 2.53, 95% CI 1.36-4.72, P = 0.004). CONCLUSION: The TyG index might be a promising biomarker for endometrial carcinogenesis. Subjects with a higher TyG index should be aware of the risk of EC incidence and progression.

Role of clinical characteristics in preoperative diagnosis of adenomyosis with endometrial cancer / 安徽医科大学学报

Objective @#To analyze the clinical characteristics of patients with adenomyosis (AM) and endometrial cancer (EC) and their role in preoperative diagnosis.@*Methods @#A total of 142 patients with AM complicated with EC or endometrial atypical hyperplasia (EAH) and AM with abnormal uterine bleeding ( AUB) during the same period were collected from this hospital. They were divided into AM with EC or EAH group (71 cases) and control group (71 cases) according to whether they were complicated with EC or EAH. The clinical data of the patients were retrospectively analyzed , and the clinical characteristics and treatment strategies of the patients with adenomyosis complicated with endometrial cancer were discussed. @*Results @#Univariate analysis showed that age , increased proportion of CA125 and CA125 , uterine volume , proportion of hypertension and abnormal endometrial ultrasonography in patients with AM with EC or EAH were significantly higher than those in the control group , and the proportion of dysmenorrhea was significantly lower than that in the control group , and the difference was statistically significant (P < 0. 05) . Multivariate Logistic regression analysis showed that endometrial thickening , endometrial echogenicity , and endometrial thickening combined with echogenicity were independent risk factors for AM with EC or EAH.@*Conclusion @#In clinical practice , the patients with AM with endometrial thickening or uneven echo - echo of ultrasound should be treated by hysteroscopy and curettage before further operation plan is formulated , so as to achieve the purpose of early diagnosis and treatment of EC.