Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer

BACKGROUND Preoperative risk stratification is significant for the management of endometrial cancer(EC)patients.Radiomics based on magnetic resonance imaging(MRI)in combination with clinical features may be useful to predict the risk grade of EC.AIM To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI.METHODS The study comprised 112 EC patients.The participants were randomly separated into training and validation groups with a 7:3 ratio.Logistic regression analysis was applied to uncover independent clinical predictors.These predictors were then used to create a clinical nomogram.Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images,the Mann-Whitney U test,Pearson test,and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features,which were subsequently utilized to generate a radiomic signature.Seven machine learning strategies were used to construct radiomic models that relied on the screening features.The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators.RESULTS Having an accuracy of 0.82 along with an area under the curve(AUC)of 0.915[95%confidence interval(CI):0.806-0.986],the random forest method trained on radiomics characteristics performed better than expected.The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram(AUC:0.75,95%CI:0.611-0.899)and the combined nomogram(AUC:0.869,95%CI:0.702-0.986)that integrated clinical parameters and radiomic signature.CONCLUSION The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Superiority of indocyanine green-enhanced near-infrared fluorescence-guided imaging for laparoscopic lymph node dissection in patients with early-stage endometrial cancer: A retrospective cohort study

Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complications.This study aimed to explore whether indocyanine green(ICG)-enhanced nearinfrared(NIR)fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma.Methods:In this retrospective study,we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine between January 2019 and January 2021.Depending on whether ICG-enhanced NIR fluorescence guidance was used,the patients were assigned to the ICG group or non-ICG group.Patients were followed-up for one year after surgery.Data on demographic characteristics,pathological results,operative outcomes,and complications were collected and analyzed.Results:The baseline characteristics were comparable between the ICG group and non-ICG group,including age,BMI,pregnancy history,and preoperative hemoglobin.For surgical outcomes,the patients in ICG group had significantly lower intraoperative blood loss(50 mL vs.120 mL,p<0.001),less postoperative pelvic drainage time(4.14±1.44 d vs.5.70±1.89 d,p¼0.001),shorter duration of hospital stay(5.26±1.41 d vs.7.37±1.85 d,p¼0.003),higher number of positive pelvic lymph nodes(PLNs)(1 vs.0,p¼0.003),and more PLN-positive cases(16.0%vs.3.6%,p¼0.003)than the patients in non-ICG group.However,no significant differences were noted in blood transfusion requirement,operative time,hemoglobin level decreases,number of PLNs harvested,or the presence of lymphocysts between the two groups.Conclusion:Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.

Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background:LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers.Nevertheless,the impacts of DLX6-AS1 on endometrial cancer(EC)development remained obscure.The study explored the influence of DLX6-AS1 on EC progression via the microRNA(miR)-374a-3p/zinc-finger protein(ZFX)axis.Methods:EC cell lines were collected and DLX6-AS1,miR-374a-3p,and ZFX levels in EC cell lines were detected.The EC cells were transfected with DLX6-AS1,miR-374a-3p,and ZFX constructs to examine the biological functions of EC cells.The xenograft model was established for detecting tumor growth.Rescue experiments were conducted to verify the interaction of DLX6-AS1,miR-374a-3p,and ZFX in EC cells.Results:DLX6-AS1 and ZFX levels were elevated,while miR-374a-3p exhibited a reduced level in EC cells.Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells.Reduced DLX6-AS1 repressed tumor development.MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing,while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth.Mechanically,DLX6-AS1 was found to bind to miR-374a-3p,and miR-374a-3p targeted ZFX.Conclusion:DLX6-AS1 depletion restricts the malignant phenotype of EC cells.The study might provide novel therapeutic biomarkers for EC treatment.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis

BACKGROUND Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide,and early-stage high-risk endometrial cancer has a poor prognosis.Adjuvant treatments after surgery,such as chemotherapy and radiotherapy,have been widely used in clinical practice to improve patient survival.Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer.However,its efficacy,safety,and longterm prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial.Therefore,this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with earlystage high-risk endometrial cancer and evaluate its safety.AIM To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety.METHODS We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022.The control group(100 patients)underwent conventional surgical treatment,and the study group(100 patients)was administered adjuvant medroxyprogesterone acetate tablets on top of the control group.The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients.The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer.RESULTS According to the Cox regression analysis,age[hazard ratio(HR)=4.636,95%confidence interval(95%CI):1.411-15.237],pathological type(HR=6.943,95%CI:2.299-20.977),molecular typing(HR=5.789,95%CI:3.305-10.141),and myometrial infiltration(HR=5.768,95%CI:1.898-17.520)were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer.CONCLUSION Age,pathological type,molecular typing,and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer.The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

Do peripartum and postmenopausal women with primary liver cancer have a worse prognosis? A nationwide cohort in Taiwan

BACKGROUND While primary liver cancer(PLC)is one of the most common cancers around the world,few large-scale population-based studies have been reported that evaluated the clinical survival outcomes among peripartum and postmenopausal women with PLC.AIM To investigate whether peripartum and postmenopausal women with PLC have lower overall survival rates compared with women who were not peripartum and postmenopausal.METHODS The Taiwan National Health Insurance claims data from 2000 to 2012 was used for this propensity-score-matched study.A cohort of 40 peripartum women with PLC and a reference cohort of 160 women without peripartum were enrolled.In the women with PLC with/without menopause study,a study cohort of 10752 menopausal females with PLC and a comparison cohort of 2688 women without menopause were enrolled.RESULTS Patients with peripartum PLC had a non-significant risk of death compared with the non-peripartum cohort[adjusted hazard ratios(aHR)=1.40,95%confidence intervals(CI):0.89-2.20,P=0.149].The survival rate at different follow-up durations between peripartum PLC patients and those in the non-peripartum cohort showed a non-significant difference.Patients who were diagnosed with PLC younger than 50 years old(without menopause)had a significant lower risk of death compared with patients diagnosed with PLC at or older than 50 years(postmenopausal)(aHR=0.64,95%CI:0.61-0.68,P<0.001).The survival rate of women<50 years with PLC was significantly higher than older women with PLC when followed for 0.5(72.44%vs 64.16%),1(60.57%vs 51.66%),3(42.92%vs 31.28%),and 5 year(s)(37.02%vs 21.83%),respectively(P<0.001).CONCLUSION Peripartum females with PLC have no difference in survival rates compared with those patients without peripartum.Menopausal females with PLC have worse survival rates compared with those patients without menopause.

MiR-200a and miR-200b target PTEN to regulate the endometrial cancer cell growth in vitro

Objective:To study whether miR-200a and miR-200b target PTEN gene expression to regulate the endometrial cancer cell growth in vitro. Methods:Endometrial cancer cells ECC-1 were cultured and transfected with the miR-200a and miR-200b mimics and inhibitors as well as the negative control mimics and inhibitors,and then the cell proliferation activity as well as the expression of PTEN and downstream genes in cells was determined; after transfection of miR-200a and miR-200b mimics as well as PTEN-3'UTR luciferase report gene plasmids,the fluorescence activity of luciferase reporter gene was determined. Results:12 h,24 h and 48 h after transfection,the cell proliferation activity of miR-200a mimics group and miR-200b mimics group were significantly higher than those of NC mimics group while the cell proliferation activity of mi R-200 a inhibitor group and miR-200b inhibitor group were significantly lower than those of NC inhibitor group; 48 h after transfection,PTEN expression in cells and PTEN-3'UTR luciferase reporter gene fluorescence activity of miR-200 a mimics group and miR-200b mimics group were significantly lower than those of NC mimics group while p-PI3K and p-Akt expression were significantly higher than those of NC mimics group; PTEN expression in cells and PTEN-3'UTR luciferase reporter gene fluorescence activity of miR-200 inhibitor group and miR-200b inhibitor group were significantly higher than those of NC inhibitor group while p-PI3K and p-Akt expression were significantly lower than those of NC inhibitor group. Conclusion:miR-200 a and miR-200b can promote the endometrial cancer cell growth in vitro by targeted inhibition of PTEN gene expression.

High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

Objective： To present patterns of practice and outcomes in the adjuvant treatment of intermediate- and high-risk endometrial cancer. Methods： Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed. All patients underwent surgical staging. Patterns of adjuvant treatment, consisting of pelvic radiotherapy, chemotherapy, and radiotherapy plus chemotherapy, were assessed. The 3- and 5-year disease-specific survival （DSS） rates were calculated using the Kaplan-Meier method. Results： The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group （80.65% vs. 63.80%, P=0.040）. In 110 high-risk patients who underwent adjuvant treatment, both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups （DSS rate, P=0.049; recurrent rate, P=0.047）. In 83 intermediate-risk women who underwent adjuvant treatment, there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy, radiotherapy alone and chemotherapy alone groups （DSS rate, P=0.776; recurrent rate, P=0.937）.

Leptin Activates STAT3 and ERK1/2 Pathways and Induces Endometrial Cancer Cell Proliferation

Obesity is an established risk factor for endometrial cancer.Leptin,a secreted protein of the ob gene by white adipose tissue,plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic cancer cells.However,a direct role for leptin in endometrial cancer has not been demonstrated.In the present study,the effect of leptin on the proliferation of Ishikawa endometrial cancer cells was investigated as well as the possible mechanism（s） underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors.The expression of leptin receptor（ObRb） in Ishikawa cells was detected by RT-PCR and Western blotting.The cells after serum starvation,were treated by leptin with various concentrations（0,10,50,100,150 ng/mL） for different durations（6,12,24 h）.The effect of leptin treatment on cell proliferation was examined by MTT assay.Meanwhile,inhibitory effect of Janus tyrosine kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3） inhibitor AG490 or extracellular signal-regulated kinase 1/2（ERK1/2） inhibitor PD98059 on the proliferation of Ishikawa cells induced by leptin was also studied.Ishikawa cells were treated with 100 ng/mL leptin for various periods（0,20,40,60 min）,and the levels of STAT3 phosphorylation and ERK1/2 phosphorylation were examined by Western blotting.The results showed that leptin induced the phosphorylation of STAT3 and the activation of ERK1/2 in a time-and dose-dependent manner in the Ishikawa endometrial cancer cells.Blocking STAT3 phosphorylation with the inhibitor AG490,or blocking ERK1/2 activation by the specific ERK1/2 kinase inhibitor,PD98059,abolished leptin-induced proliferation of Ishikawa cells.In addition,leptin was found to potently induce the invasion of endometrial cancer cells in a Matrigel invasion assay.Leptin-stimulated invasion was effectively blocked by pharmacological inhibitors of STAT3（AG490） and ERK1/2 kinase（PD98059）.These results suggested that leptin promotes endometrial cancer growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways and therefore blocking its action at the receptor level can be a rational therapeutic strategy.

Proteiomic patterns for endometrial cancer using SELDI-TOF-MS

Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.

Preoperative markers for the prediction of high-risk features in endometrial cancer

BACKGROUND Preoperative evaluations aiming to assess high-risk features in clinical stage 1 endometrial cancer patients are crucial to refer these patients to gynecologic oncologists.Cancer antigen 125(CA125)and human epididymis protein 4(HE4)have been reported in endometrial cancer patients with poor prognostic factors.AIM To evaluate the association between preoperative levels of CA125 and HE4 and high-risk features and establish optimal cut-off values in clinical stage 1 endometrial cancer.METHODS A retrospective study was conducted in clinical stage 1 endometrial cancer patients who underwent primary surgery between January 2013 and December 2018.A total of 128 patients had preoperative serum CA125 and HE4 measurements.High-risk features included grade 3 tumors,large tumor sizes(more than 2 cm),deep myometrial invasion(more than 50%),lymphovascular space invasion(LVSI),cervical involvement,extrauterine involvement and node metastasis.Receiver operating characteristic(ROC)curves were generated to analyze the optimal cut-off values.RESULTS The mean age of the patients was 57.4 years,and 69.5%of them were postmenopausal.Most patients presented with stage I disease(67.2%)and had the endometrioid subtype(97.7%).The median CA125 and HE4 levels in all patients were 22.1 U/mL and 104.7 pmol/L,respectively.CA125 and HE4 levels were significantly elevated in those with large tumor sizes,deep myometrial invasion,LVSI,extrauterine metastasis,and advanced stage,but node metastasis was associated with elevated CA125 only.According to the ROC curve,both serum markers had statistical significance for the prediction of high-risk features only in postmenopausal patients,with an optimal cut-off value of 20 U/mL for CA125[area under the concentration-time curve(AUC)=0.72,P=0.002]and 113 pmol/L for HE4(AUC=0.70,P=0.006).The combination of both serum markers had 80%sensitivity and 64.4%positive predictive value.Significantly worse 5-year disease-free survival was observed in patients with high levels of CA125 and HE4(78.4%and 100%,respectively;P=0.01).CONCLUSION Preoperative CA125 levels greater than 20 U/mL or HE4 levels greater than 113 pmol/L are associated with an increased risk of having high-risk features and present as prognostic factors in clinical stage 1 postmenopausal endometrial cancer patients.This information is helpful for general gynecologists to refer high-risk patients to gynecologic oncologists to perform complete surgical staging.

Red meat intake and the risk of endometrial cancer:Metaanalysis of observational studies

AIM:To evaluate whether red meat intake is related to the risk of endometrial cancer(EC) using meta-analysis.METHODS:We searched Pub Med,EMBASE,and the Cochrane Library up to June 2013,using common keywords related to red meat and EC.Case-control studies and cohort studies comparing the risk of endometrial cancer among categories by the amount of intake were included.Eleven case-control studies and five cohort studies met our criteria.We performed a conventional and a dose-response meta-analysis of case-control studies using the Der Simonian-Laird method for random-effects.For cohort studies we performed a conventional meta-analysis.Publication bias was evaluated using Egger's test.RESULTS:In the meta-analysis of 11 case-control studies including 5419 cases and 12654 controls,higher red meat consumption was associated with an increased risk of EC [summary relative risk(SRR) = 1.43,95%CI:1.15-1.79;I2 = 73.3% comparing extreme intake categories).In a dose-response analysis,for red meat intake of 100 g/d,SRR was 1.84(95%CI:1.64-2.05).In contrast,in the meta-analysis of five prospective studies including a total of 2549 cases among 247746 participants,no significant association between red meat intake and EC risk(SRR = 0.97,95%CI:0.85-1.11;I2 = 4.9% comparing extreme intake categories) was observed.CONCLUSION:Our meta-analysis found a significantlinear association between red meat intake and EC risk based on case-control studies but this was not confirmed in prospective studies.

Expressions of claudin-4 and claudin-1 in endometrial cancer and their significance

Objective:To observe the expressions of claudin-4 and claudin-1 in endometrial cancer and explore their correlations with clinicopathological parameters of endometrial cancer.Methods:Immunohistochemical methods(SP) were used to detect the expressions of claudin-4 and claudin-1 in 52 tissue samples of endometrial cancer,24 of atypical hyperplasia,20 of pericancerous endometrium,and 19 of endometrium at proliferative phase.And then the expressions were analyzed statistically to find out the correlations with clinicopathological parameters of endometrial cancer.Results:Positive rate of claudin-4 was 36.8%,70.8% and 90.4% in endometrium at proliferative phase,atypical hyperplasia and endometrial cancer,respectively,with significantly differences between them(P<0.05),and it was statistically different between pericancer endometrium and endometrial cancer(P<0.05).Positive rate of claudin-1 was 89.5%,66.7% and 63.5%,respectively showing a descending tendency and significantly differences between endometrium at proliferative phase and endometrial caner(P<0.05),and it was also statistically significantly different between pericancer endometrium and endometrial cancer(P<0.05).The high expression rate of claudin-4 was related to invasion depth,but not to histological grading,pathological staging or lymph node metastasis of endometrial cancer,and the low expression of claudin-1 in endometrial cancer was not associated with histological grading,pathological staging,invasion depth or lymph node metastasis.Conclusion:The expression levels of claudin-4 and claudin-1 are correlated with onset and development of endometrial cancer.

Adjuvant tamoxifen switched to exemestane treatment in postmenopausal women with estrogen receptor-positive early breast cancer:A pragmatic,multicenter,and prospective clinical trial in China

Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.

Recurrent postmenopausal bleeding - just endometrial disease or ovarian sex cord-stromal tumor? A case report

BACKGROUND Postmenopausal bleeding(PMB)is a common gynecologic complaint among elderly women,and endometrial hyperplasia is a common cause of this bleeding.Ovarian fibromas are the most common type of ovarian sex cord-stromal tumor(SCST).They arise from non-functioning stroma,rarely show estrogenic activity,and stimulate endometrial hyperplasia,causing abnormal vaginal bleeding.CASE SUMMARY We report herein the case of a 64-year-old Chinese woman who presented with recurrent PMB.A sex hormone test revealed that her estrogen level was significantly higher than normal,and other causes of hyperestrogenism had been excluded.The patient had undergone four curettage and hysteroscopy procedures in the past 7 years due to recurrent PMB and endometrial hyperplasia.The culprit behind the increase in estrogen level—an ovarian cellular fibroma with estrogenic activity—was eventually found during the fifth operation.CONCLUSION Ovarian cellular fibromas occur insidiously,and some may have endocrine functions.Postmenopausal patients with recurrent PMB and endometrial thickening observed on ultrasonography are recommended to undergo sex hormone testing while waiting for results regarding the pathology of the endometrium.If the estrogen level remains elevated,the clinician should consider the possibility of an ovarian SCST and follow-up the patient closely,even if the imaging results do not indicate ovarian tumors.Once the tumor is found,it should be removed as soon as possible no matter the size to avoid endometrial lesions due to long-term estrogen stimulation.More studies are needed to confirm whether preventive total hysterectomy with bilateral salpingo-oophorectomy should be recommended for women with recurrent PMB exhibiting elevated estrogen levels,despite the auxiliary examination results not indicating ovarian mass.The physical and psychological burden caused by repeated curettage could be prevented using this technique.

Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer:Clinical and pathological perspectives

Endometrial cancer is the most common gynecological cancer in developed countries,and its incidence has increased.The majority of patients with endometrial cancer have an early disease and favorable prognosis;however,a significant proportion of endometrial cancer,which mainly comprises high-grade or type II endometrial cancer such as serous,clear cell,and carcinosarcoma,shows advanced/recurrent disease and dismal prognosis.Novel therapeutic development is required for patients with aggressive endometrial cancers.Recent genomic and immunohistochemical analyses revealed human epidermal growth factor receptor 2(HER2)overexpression/gene amplification in 20%-40%of patients with type II endometrial cancer.Historically,HER2 targeted therapy has been developed for various major cancers,including breast and gastric cancer.Notably,recent advances in HER2 targeted therapy for patients with type II endometrial cancer are also expected to change.Simultaneously,an optimized HER2 test for endometrial cancer as companion diagnostics should be established.In this review,we summarize the recent findings on endometrial cancer,current treatment,optimized HER2 testing,key clinical trials on HER2 targeted therapy,and future directions in aggressive endometrial cancer,including serous carcinoma and carcinosarcoma.

The Prognostic Value of BMI, Serum Glucose, Endometrial Echo Pattern and Uterine Artery Doppler Velocimetry as a Predictor for Endometrial Pathology in Women with Postmenopausal Bleeding (Prospective Observational Study)

Background: Post-menopausal bleeding is a warning sign that accounts for about 5% of all outpatient gynaecologic visits and is a common indication for referral to rapid access clinics because of the fear of underlying malignancy. Endometrial malignancies differ from other malignancies in that early symptomization is common, allowing early cure. Patients and Methods: During the study period, 100 women with post-menopausal bleeding having inclusion criteria were evaluated in Al Hussein University Hospital. For each patient full history, general, abdominal and pelvic examination was performed. Routine pre-operative investigations were done. Patients were divided into four groups: Group 1 included 29 patients with endometrial polyp. Group 2 included 34 patients with endometrial hyperplasia. Group 3 included 21 patients with atrophic endometrium. Group 4 included 16 patients with endometrial carcinoma. Results: As regards the predictive value of BMI, in the study there was a high statistical significance in comparison between the endometrial carcinoma group and all other benign groups. When discussing the predictive value of blood glucose level, in the study there was a high statistical significance in comparison between the endometrial carcinoma group and all other benign groups. It is worth to mention that the predictive value of endometrial thickness, in the study, was with high statistical significance in comparison between the endometrial carcinoma group and all other benign groups providing the highest specificity and sensitivity. At the last the predictive value of uterine artery velocimetry, in the study, was with high statistical significance in comparison between the endometrial carcinoma group and all other benign groups. Conclusion: BMI, blood glucose level, endometrial thickness and uterine artery velocimetry indices, improve the prediction of endometrial carcinoma in women with post-menopausal bleeding.

Competing risks of death in younger and older postmenopausal breast cancer patients

AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival(P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival(P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific(Br Ca) and other cause(OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1(IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-OH vitamin D were associated with(1) all cause mortality, and if so; and(2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models.RESULTS: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447(82%) < 70 years and 120(18%) ≥ 70 years. There were 170 deaths: 106(62.3%) BrC a; 55(32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9(5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrC a and OC deaths were not significantly different by treatment arm(P = 0.40): tamoxifen patients experienced 50 BrC a and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 Br Ca and 23 OC deaths. Proportionately more deaths(P = 0.004) were from BrC a for patients< 70 years, where 70% of deaths were due to Br Ca, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index(BMI)(P = 0.02). Higher pathologic T and N were associated with more BrC a deaths(P < 0.0001 and 0.002, respectively). The cumulative hazard plot for Br Ca and OC mortality indicated the concurrent accrual of both types of death throughout followup, that is the existence of competing risks of mortality. MA.14 therapy did not impact mortality(P = 0.77). Three baseline patient and tumor characteristics were differentially associated with cause of death: older patients experienced more OC(P = 0.01) mortality; patients with T1 tumors and hormone receptor positive tumors had less BrC a mortality(respectively, P = 0.01, P = 0.06). Additionally, step-wise cause-specific models indicated that patients with node negative disease experienced less BrC a mortality(P = 0.002); there was weak evidence that, lower C-peptide(P = 0.08) was associated with less BrC a mortality, while higher BMI(P = 0.01) was associated with worse OC mortality.CONCLUSION: We demonstrate here a new paradigm of simultaneous testing of therapeutics directed at multiple diseases for which postmenopausal women are concurrently at risk. Octreotide LAR did not significantly impact breast cancer or other cause mortality, although different baseline factors influenced type of death.

Could Surgery Improve Survival in Patients with Advanced Endometrial Cancer?

Background: Patients with endometrial cancer are mostly diagnosed at an early stage. But unfortunately 10% to 15% of endometrial cancer patients will present with advanced-stage disease, and hence poorer prognosis. When disease is primarily intraperitoneal, cytoreduction to <2 cm has also been correlated with better survival, with the maximum benefit in patients who can be reduced to no visible disease remaining. Aim: Of the work is to detect the survival rate benefits of primary surgery in patients with advanced endometrial cancer at gynecologic oncology unit in El Shatby Maternity University Hospital. Methods and Materials: Retrospective study was conducted on 102 patients diagnosed to have advanced endometrial cancer FIGO (stage III/IV) in a duration of 4 years between 2016 and 2020 and had undergone cytoreductive surgery. The patients were further subdivided into two groups: group 1 who underwent optimal cytoreduction with residual disease less than or equal 1 cm visible lesion, and group 2 who had residual disease more than 1 cm visible lesion and they were followed to check the survival benefits. Results: The mean of disease free survival in group: 1) patients was 2 years which was significantly longer than those in group;2) those who had residual disease > 1 cm, p < 0.001. Also cases with type I endometrial cancer had significantly longer (DFS) than those diagnosed to have type II endometrial cancer, p = 0.046. Conclusion: Primary complete cytoreductive (upfront) surgery when possible has a favorable impact on overall survival in patients with advanced endometrial cancer.

Real-time co-registered photoacoustic and ultrasonic imaging for early endometrial cancer detection driven by cylindrical diffuser

In illuminating tissues,a cylindrical diffuser(CD)has an advantage over regular laser sources due to its ability to illuminate a larger volume of the target tissue.This paper presents a co-registered large volume photoacoustic(PA)and ultrasonic(US)imaging for early endometrial cancer(EEC)detection using CD.It has the advantage that the US imaging system is outside the body and only the PA excitation device is inside the body,which makes the system more efficient and less invasive for EEC detection.The paper reports on two sets of experiments.Thefirst set produced real-time PA images of blood vessel phantom.The second set demonstrated the imaging of pig uterus ex vivo.The results show that the system has the potential for imaging and characterizing of EEC.