Lymph-vascular Space Invasion Research Articles

High prevalence of "non-pathogenic" POLE mutation with poor prognosis in a cohort of endometrial cancer from South India.

The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra-mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients. This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes. Among 151 cases enrolled, 39 were unique POLE-mutated cases. Significant associations were high-grade tumors, myometrial invasion >50%, and Lymph-vascular space invasion (LVSI). The median follow-up was 40 months (95% confidence interval [CI], 34-46). A lower mean disease-specific survival (DSS) of 51.7 months (95% CI, 43.7-59.6) was noted in the POLE-mutated group compared with 72.11 months (95% CI, 67.60-76.62) for the POLE wild-type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE-mutated group was noted. In advanced stages (FIGO stages II-IV), a nine-fold HR for DSS and overall survival (OS) compared with POLE wild-type was identified. After controlling for treatment effects using Cox proportional HR, advanced-stage POLE-mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE-wild-type tumors of the same stage. This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.

Fully Automated Identification of Lymph Node Metastases and Lymphovascular Invasion in Endometrial Cancer From Multi-Parametric MRI by Deep Learning.

Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. Retrospective. Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. 3 TECHNICAL EFFICACY: Stage 2.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study

IntroductionThe prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. Materials and methodsWe analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. ResultsAmong 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35–5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49–3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58–2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55–3.13, P = 0.515) for non-endometrioid EC patients. ConclusionLVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.

A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer.

To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.

Assessing the survival time of women with breast cancer in Northwestern Ethiopia: using the Bayesian approach

BackgroundDespite the significant weight of difficulty, Ethiopia's survival rate and mortality predictors have not yet been identified. Finding out what influences outpatient breast cancer patients' survival time was the major goal of this study.MethodsA retrospective study was conducted on outpatients with breast cancer. In order to accomplish the goal, 382 outpatients with breast cancer were included in the study using information obtained from the medical records of patients registered at the University of Gondar referral hospital in Gondar, Ethiopia, between May 15, 2016, and May 15, 2020. In order to compare survival functions, Kaplan-Meier plots and the log-rank test were used. The Cox-PH model and Bayesian parametric survival models were then used to examine the survival time of breast cancer outpatients. The use of integrated layered Laplace approximation techniques has been made.ResultsThe study included 382 outpatients with breast cancer in total, and 148 (38.7%) patients died. 42 months was the estimated median patient survival time. The Bayesian Weibull accelerated failure time model was determined to be suitable using model selection criteria. Stage, grade 2, 3, and 4, co-morbid, histological type, FIGO stage, chemotherapy, metastatic number 1, 2, and >=3, and tumour size all have a sizable impact on the survival time of outpatients with breast cancer, according to the results of this model. The breast cancer outpatient survival time was correctly predicted by the Bayesian Weibull accelerated failure time model.ConclusionsCompared to high- and middle-income countries, the overall survival rate was lower. Notable variables influencing the length of survival following a breast cancer diagnosis were weight loss, invasive medullar histology, comorbid disease, a large tumour size, an increase in metastases, an increase in the International Federation of Gynaecologists and Obstetricians stage, an increase in grade, lymphatic vascular space invasion, positive regional nodes, and late stages of cancer. The authors advise that it is preferable to increase the number of early screening programmes and treatment centres for breast cancer and to work with the public media to raise knowledge of the disease's prevention, screening, and treatment choices.

Machine Learning-Based Models for Assessing Postoperative Risk Factors in Patients with Cervical Cancer

To investigate the value of machine learning-based radiomics, intravoxel incoherent motion (IVIM) diffusion-weighted imaging and its combined model in predicting the postoperative risk factors of parametrial infiltration (PI), lymph node metastasis (LNM), deep muscle invasion (DMI), lymph-vascular space invasion (LVSI), pathological type (PT), differentiation degree (DD), and Ki-67 expression level in patients with cervical cancer. The data of 180 patients with cervical cancer were retrospectively analyzed and randomized 2:1 into a training and validation group. The IVIM-DWI and radiomics parameters of primary lesions were measured in all patients. Seven machine learning methods were used to calculate the optimal radiomics score (Rad-score), which was combined with IVIM-DWI and clinical parameters to construct nomograms for predicting the risk factors of cervical cancer, with internal and external validation. The diagnostic efficacy of the nomograms based on clinical and imaging parameters wassignificantly better than MRI assessment alone. The area under the curve (AUC) of nomograms and MRI for the assessment of PI, LNM, and DMI were 0.981 vs 0.868, 0.848 vs 0.639, and 0.896 vs 0.780, respectively. Nomograms also performed well in the assessment of LVSI, PT, DD, and Ki-67 expression levels, with AUC of 0.796, 0.854, 0.806, 0.839 and 0.840, 0.856, 0.810, 0.832 in the training and validation groups. Machine learning-based nomograms can serve as a useful tool for assessing postoperative risk factors in patients with cervical cancer.

THU514 Atypical Presentation Of Birt-Hogg-Dubé Syndrome With Poorly Differentiated Follicular Thyroid Cancer And Paraganglioma

Abstract Disclosure: K. Lertdetkajorn: None. J. Haw: None. J.E. Paysour: None. Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare genetic disorder typically presenting with skin hamartomas, renal tumors, and lung cysts. BHD is caused by germline mutations of the folliculin (FLCN) gene. We present the case of a patient with follicular thyroid cancer and paraganglioma diagnosed with BHDS. Case: A 64-year-old female was noted to have progressive enlargement of a neck mass over six months following admission for a hypertensive emergency. CT neck demonstrated a heterogeneous mass centered within the left thyroid lobe measuring 10.4 x 8.6 x 7.6 cm with internal calcifications. TSH was normal. FNA of this mass was suspicious for follicular neoplasm, and she underwent a total thyroidectomy. The pathology reported poorly differentiated adenocarcinoma of the thyroid gland, follicular variant, pT3aN0M0 with positive margins, and lymph-vascular space invasion (LVI). FDG-PET/CT scan showed postsurgical changes of a total thyroidectomy with ill-defined FDG uptake along the left thyroid bed, 3 x 2.8 cm portacaval lymph node (SUV of 9.6) and focal soft tissue FDG avid rectal abnormality. MRI abdomen demonstrated a 4.0 x 4.1 x 3.2 cm soft tissue mass characterized by arterial hyperenhancement and washout in the portacaval region broadly interfacing with the IVC, main portal vein, and left renal vein. EGD was unremarkable, but an EUS demonstrated 3.7 x 3.5 hypoechoic, well-circumscribed, mild-vascular hypoechoic portocaval mass. FNA of this mass was consistent with paraganglioma. Laboratory results supported the diagnosis of paraganglioma with urine metanephrine 9661 mcg/24 h (224 - 832 mcg/24 h) and urine normetanephrine 9457 mcg/24 h (122 - 676 mcg/24 h). The patient was referred for genetic testing to investigate whether the co-existence of follicular thyroid cancer and paraganglioma was secondary to a genetic disorder. The germline genetic testing revealed the pathogenic variant, c.1436dup (p.Thr481Hisfs*5), identified in the FLCN gene with no detections of VHL or SDH complex variants, confirming the diagnosis of BHDS. The patient later underwent a colonoscopy and was found to have stage I colon cancer. Some early reports have shown an association between BHDS and colon tumors. The patient decided not to have any surgery at this time. She continues to follow up in the clinic and takes levothyroxine for suppressive goals. Octreotide LAR, along with blood pressure medications including phenoxybenzamine, was started to treat her paraganglioma. Conclusion: Patients with BHDS may present with atypical clinical manifestations. Genetic testing will aid in diagnosing a germline mutation in the FLCN gene. The association between thyroid cancer and BHDS has been reported previously; however, paraganglioma as a spectrum of BHDS has not been published. Further reported cases and research may provide additional data to investigate the relationship between BHDS and paraganglioma. Presentation: Thursday, June 15, 2023

Comparison of Molecular and Clinicopathologic-Based Classifications and the Transition of Adjuvant Treatment Mode for Early-Stage Endometrial Cancer

Due to the division in classification strategies based on different molecular and clinicopathologic guidelines, the current emergence of multiple molecular typing methods greatly challenges the traditional classification-guided hierarchical treatment model. The early-stage ECs who underwent a total hysterectomy and comprehensive molecular analyses were analyzed consecutively between May 2021 and December 2022. All enrolled patients were performed with immunohistochemistry for lymph-vascular space invasion (LVSI), p53, and mismatch repair (MMR) proteins, NGS-panel Sanger sequencing for POLE exonuclease domain, and TP53. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) classifier and the ESGO/ESTRO/ESP guidelines with and without molecular character were respectively employed to reclassify the enrolled patients. Categorical variables of the risk-group shift were compared by Pearson's χ2 or two-sided Fisher's exact test. A total of 81 early-stage ECs patients were enrolled. Molecular analyses identified four subgroups across the 81 ECs: 9 (11%) POLE mut, 22 (27.1%) MMRd, 38 (46.9%) NSMP, and 12 (14.8%) p53 abn. Compared with ESGO/ESTRO/ESP 2016 classifier, 26 (32.1%) and 23 (28.4%) patients in ESGO/ESTRO/ESP 2020 cohort with and without molecular classification, respectively, were risk-group downshifted (p>0.05). Ten (12.3%) patients were upshifted in ESGO/ESTRO/ESP 2020 molecular classification comparing to clinical classifier. Remarkably, two patients demonstrated discordance between the ProMisE and TCGA classifiers since the different sequences of classification strategies. On the other hand, 48 of 81 patients received adjuvant radiotherapy, and 12 patients received external beam radiation therapy (EBRT). According to the final molecular test, eight of 12 were classified into low and intermediate risk. The treatment of endometrial cancer is in a period of transition from the clinicopathologic-based model to the era of molecular precision. Discordance between different classifiers and overtreatment remain in clinical practice. Therefore, we should be cautious about using molecular typing to guide adjuvant treatment decisions until it is finally validated in prospective trials.

Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

Association between serum lactate dehydrogenase and lymph node metastasis in cervical cancer.

The aim of the present study was to evaluate the association between serum lactate dehydrogenase (LDH) and the risk of lymph node metastasis (LNM) in the International Federation of Gynecology and Obstetrics (FIGO) 2009 cervical cancer (CC) stages IB1-IIA2. All patient medical records with FIGO 2009 stage IB1-IIA2 CC between January 2012 and January 2022 were analyzed retrospectively. The association between serum LDH and LNM was assessed using uni- and multivariate logistic regression analyses, subgroup analyses and P-splines. The present study included 586 patients, 91 (15.5%) of whom had LNM. Patients with an elevated LDH level were more likely to have a deep stromal invasion, lymph-vascular space invasion, LNM and to be of an older age. Multivariate logistic regression revealed a significant association between LNM and LDH levels. After adjusting for age, FIGO stage, tumor markers and risk factors according to the Sedlis criteria, patients in the highest LDH quartile had an increased risk of LNM compared with those in the lowest LDH quartile (odds ratio, 3.5; 95% CI, 1.57-7.81). Furthermore, P-spline regression revealed a dependence of LNM on LDH. The predictive value of LDH level remained significant in the subgroup analysis. The present study suggested that a higher LDH level was independently associated with CC and LNM, and that LDH level may serve as a potential tumor marker and treatment-related indicator.

Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value.

Identification of the mismatch repair (MMR) deficiency in endometrial cancer (EC) may aid in the screening of patients who may benefit from immunotherapy. Our goal was to investigate the relationship between MMR status and 18F-FDG PET/CT metabolic parameters and clinicopathological features in patients with EC, as well as to explore their prognostic value. This retrospective study included 106 EC patients who were classified as MMR deficient (dMMR) or MMR proficient (pMMR) group based on MMR protein expression status evaluated by immunohistochemistry. Clinicopathological characteristics and PET metabolic parameters were compared between the dMMR and pMMR groups, and their relationships with MMR status and prognosis were evaluated. Of 106 EC patients, 30 patients (28.1%) had dMMR, while 76 (71.7%) had pMMR. Compared with the pMMR group, the dMMR group showed a lower prevalence of overweight (BMI ≥ 25) (17.2% vs. 43.9%, P = 0.019) and more lymph vascular space invasion (43.3% vs. 21.1%, P = 0.029). Although no relationship between glucometabolism parameters and MMR status was observed in all enrolled patients, higher SUVmax was observed in the endometrioid type of EC with MMR deficiency (P = 0.047). Additionally, SUVmax related to MMR status was found in EC patients with advanced FIGO stage (P = 0.026) or deep myometrial invasion (P = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis was independently predictive of PFS, while advanced FIGO stage was an independent predictor of OS. No significant association between MMR status and prognosis was found in EC. Higher SUVmax was associated with MMR deficiency in EC patients with endometrioid type, advanced stage, or deep myometrial invasion, which may be useful for predicting the MMR status and thus aiding in determination of immunotherapy for patients with EC.

Tumor-Infiltrating Lymphocytes and Tumor-Stroma Ratio on Early-Stage Cervix Carcinoma: Prognostic Value of Two Distinct Morphological Patterns of Microenvironment.

Background Tumor progression is influenced by the complex network of different cellular elements that make up its microenvironment. Tumor-infiltrating lymphocytes (TILs) and stroma characteristics reflect two faces of the intricate mechanisms involved in the tumor-host interaction and can be easily evaluated by routine histological examination.Their prognostic value could be demonstrated in different tumor tumor types, but they are poorly explored in cervical cancer. Methodology In this retrospective study, we analyzed the association of TILs, tumor-stroma ratio (TSR), and pattern of stromal fibroblasts with prognosis and classical clinicopathological variables. We studied 61 patients with early-stage cervical cancer. We reviewed histological type, tumor grade, Silva pattern of invasion for adenocarcinomas, tumor thickness, depth of stromal invasion, lymph vascular space invasion, and lymph node status. The median follow-up was 37.77 months (range 4.77 to 112.37 months). Results The TSR did not correlate with any clinicopathological features or disease-free and overall survival. On the other hand, the reactive pattern of stroma composed of larger fibroblasts and less collagenization was associated with the FIGO IB2 stage (p=0.04), larger tumor (p=0.03), and deeper infiltration (p=0.005). There were more recurrences in the group of reactive stroma (33.13% vs. 11.5%), although the difference did not reach statistical significance. Reactive stroma was associated with lower survival free of recurrence (p=0.05) and overall survival (p=0.009). High TILs were associated with squamous cell type (p=0.003), higher tumor grade (p=0.02), and more LVSI (p=0.02). Tumors with higher TILs presented higher free recurrence interval (p=0.06) and overall survival (p=0.03). No association was observed between stroma characteristics and TILs. Conclusions Our study suggested that although immune activation and stromal changes are important features of microenvironment remodeling during tumoral progression, they are independent, following distinct carcinogenetic pathways. Pathological assessment of stroma characteristics and TILs adds significant prognostic information and demonstrates how a simple routine laboratory assessment can generate a better understanding of biological phenomena.

Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery.

Safety of the uterine manipulator (UM) within endometrial cancer (EC) surgery is being questioned. Its use might be one of the issues for potential tumor dissemination during the procedure, especially in the case of uterine perforation (UP). No prospective data on this surgical complication, nor on the oncological consequences exist. The aim of this study was to assess the rate of UP while using UM when performing surgery for EC and the impact of UP on the choice of adjuvant treatment. We conducted a prospective single-center cohort study from November 2018 to February 2022, considering all EC cases surgically treated by a minimally invasive approach with the help of a UM. Demographic, preoperative, postoperative and adjuvant treatment corresponding to the included patients were collected and comparatively analyzed according to the absence or presence of a UP. Of the 82 patients included in the study, 9 UPs (11%) occurred during surgery. There was no significant difference in demographics and disease characteristics at diagnosis that may have induced UP. The type of UM used or the approach (laparoscopic vs. robotic) did not influence the occurrence of UP (p=0.44). No positive peritoneal cytology was found post hysterectomy. There was a statistically significantly higher rate of lymph-vascular space invasion within the perforation group, 67% vs. 25% in the no perforation group, p=0.02. Two out of nine (22%) adjuvant therapies were changed because of UP. The median follow-up time for patients was 7.6 months (range 0.5-33.1 months). No recurrence was found in the UP group. Our study found a uterine perforation rate of 11%. This information needs to be further integrated to consider the usefulness of MU for EC surgery.

Survival after sentinel node biopsy alone in early-stage cervical cancer: a systematic review

ObjectiveTo assess the oncologic outcomes of sentinel lymph node biopsy alone as part of surgical management in patients with early-stage cervical cancer.MethodsA systematic search of the literature was performed following...

Metabolic syndrome score as an indicator in a predictive nomogram for lymph node metastasis in endometrial cancer

BackgroundLymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer.MethodsThis study is based on patients diagnosed with EC in Peking University People’s Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors.ResultsThe prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81–0.90) and 0.77 (95% CI: 0.77–0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82–0.93) and 0.80 (95% CI: 0.74–0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value.ConclusionThis model may promote risk stratification and individualized treatment, thus improving the prognosis.

Unilateral ovarian recurrence 5 years after hysterectomy for microinvasive squamous cervical cancer stage IA1: a rare case report

BackgroundOvarian metastasis or recurrence of cervical microinvasive squamous cell carcinoma (SCC) is very rare. We report a case of unilateral ovarian recurrence 5 years after hysterectomy for the SCC stage IA1 without lymph vascular space invasion (LVSI).Case presentationA 49-year-old female patient suffered from a dull pain in the left lower abdomen for 3 months. And five years ago, she received a laparoscopic hysterectomy for the treatment of stage IA1 (without LVSI) SCC of the cervix. The level of squamous cell carcinoma antigen (SCC-Ag) in serum was significantly elevated (10.60 ng/mL). Pelvic magnetic resonance imaging (MRI) revealed a left ovarian solid tumor measuring 5.5 × 3.9 × 5.6 cm with heterogeneous enhancement. During laparotomy, the left ovarian tumor was measured about 5.0 × 4.5 × 3.0 cm and seemed densely adherent to the posterior peritoneal wall, including the left ureter. The tumor and pelvic lymph node were carefully removed. Postoperative anatomy revealed a solid mass with a greyish-white section. Postoperative pathology showed recurrent moderately differentiated ovarian SCC with negative pelvic lymph nodes. Immunohistochemistry showed that the tumor cells were positive for P16, P63, P40, and CK5/6 markers, and the positive rate of Ki67 was about 80%.ConclusionsOvary preservation is reasonable and appropriate in young patients with microinvasive SCC. Ovarian recurrence is rare, but gynecological oncologists should not overlook its possibility. The serum SCC-Ag is an important indicator for monitoring postoperative disease progression.

The RAINBO MMRd-GREEN trial (GCIG/DGOG/ENGOT-EN142): A phase III trial on the addition of adjuvant durvalumab to radiotherapy in patients with high-risk MMRd endometrial cancer.

TPS5633 Background: The molecular class of endometrial cancer (EC) is both prognostic and predictive in high-risk EC (HREC). The TransPORTEC research consortium showed that patients with MMRd HREC did not benefit from adjuvant chemotherapy added to radiotherapy. MMRd tumors are particularly sensitive to immunotherapy. We hypothesize that adjuvant durvalumab added to standard radiotherapy will increase recurrence-free survival (RFS) in patients with MMRd HREC. Methods: MMRd-GREEN is an international, open-label, randomized phase III trial and part of the RAINBO program (NCT05255653). Eligible patients will be allocated (1:1) to adjuvant durvalumab 1500 mg once every 4 weeks for 1 year combined with radiotherapy or standard radiotherapy alone. The primary endpoint is RFS at 3 years. Secondary endpoints are pelvic, vaginal and distant RFS, EC-specific survival, overall survival, treatment-related toxicity, health-related quality of life and exploratory translational research . Main inclusion criteria include histologically confirmed stage IB/II with (substantial) lymph-vascular space invasion (LVSI) or stage IIIA-C MMRd EC, after hysterectomy and bilateral salpingo-oophorectomy (regardless of lymphadenectomy or sentinel lymph node biopsy) without macroscopic residual disease. Molecular classification must be performed according to the WHO 2020 algorithm. The target accrual is 316 patients, accounting for a total drop-out rate of 12%. This sample size yields 80% power to detect a 13% increase in the 3-year RFS (hazard ratio 0.58) as a result of the addition of durvalumab, with an accrual duration of 48 months and follow-up period of 30 months. No interim analysis is planned; an independent data monitoring committee will routinely monitor recurrences and adverse events. Enrollment: Since August 2022, the trial is open for recruitment in the Netherlands and per February 10th 2023, the first 3 patients have been enrolled. Activation of more international centers is ongoing. Clinical trial information: NCT05255653 .

AMIGO2 expression as a predictor of recurrence in cervical cancer with intermediate risk.

Patients with recurrent cervical cancer have limited treatment options and are often considered to be incurable. Since the expression of amphoterin-induced gene and open reading frame 2 (AMIGO2) in clinical samples is a prognostic factor for colorectal cancer and gastric cancer, the present aimed to elucidate whether it is also a prognostic factor for cervical cancer. Patients with primary cervical cancer who underwent radical hysterectomy or radical trachelectomy at our institution (Faculty of Medicine, Tottori University, Yonago, Japan) between September 2005 and October 2016 were retrospectively collected. Immunohistochemical analysis using a specific antibody against AMIGO2 was performed on 101 tumor samples, and the clinical characteristics, disease-free survival (DFS) and overall survival (OS) of the patients were examined. Patients in the AMIGO2-high group had a shorter 5-year DFS and OS than those in the AMIGO2-low group (P<0.001). Furthermore, AMIGO2 was an independent prognostic factor for DFS in multivariate analysis (P=0.0012). Patients in the AMIGO2-high group exhibited obvious recurrence compared with those in the AMIGO2-low group in the high-(P=0.03) and intermediate-risk groups (P=0.003). Positive lymph node metastasis, and parametrial, stromal and lymph vascular space invasion were significantly more common in AMIGO2-high patients. Taken together, AMIGO2 expression may be a predictive marker of recurrence for cervical cancer. In particular, it may be an indicator to determine the need for postoperative adjuvant therapy in intermediate-risk group patients.

Conservative Treatment of Stage IA1 Cervical Carcinoma Without Lymphovascular Space Invasion: A 20-year Retrospective Study in Brazil.

To evaluate recurrence rates and risk factors among women with stage IA1 cervical cancer without lymph vascular space invasion managed conservatively. retrospective review of women with stage IA1 squamous cervical cancer who underwent cold knife cone or loop electrosurgical excision procedure, between 1994 and 2015, at a gynecologic oncology center in Southern Brazil. Age at diagnosis, pre-conization findings, conization method, margin status, residual disease, recurrence and survival rates were collected and analyzed. 26 women diagnosed with stage IA1 squamous cervical cancer without lymphovascular space invasion underwent conservative management and had at least 12 months follow-up. The mean follow-up was 44.6 months. The mean age at diagnosis was 40.9 years. Median first intercourse occurred at age 16 years, 11.5% were nulliparous and 30.8% were current or past tobacco smokers. There was one Human immunodeficiency virus positive patient diagnosed with cervical intraepithelial neoplasia grade 2 at 30 months after surgery. However, there were no patients diagnosed with recurrent invasive cervical cancer and there were no deaths due to cervical cancer or other causes in the cohort. Excellent outcomes were noted in women with stage IA1 cervical cancer without lymphovascular space invasion and with negative margins who were managed conservatively, even in a developing country.

Association of high expression of CD44 in clinicopathological factors of endometrial cancer.

Clinical stages, histologic type, degree of cell differentiation, myometrial invasion, and lymph-vascular space invasion (LVSI) have been identified as clinicopathological factors that are predictive for endometrial cancer, however, further prognostic indicators are still required to account for the heterogeneity of this cancer. Adhesion molecule CD44, affects the invasion, metastasis, and prognosis of many forms of cancer. The purpose of this study is to examine the expression of CD44 in endometrial cancer and its correlation with established prognostic variables. A cross-sectional study was conducted on 64 samples of endometrial cancer from Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital. Immunohistochemical analysis was used to detect CD44 expression using mouse anti-human CD44 monoclonal antibody. Differences in Histoscore were studied to determine the association between CD44 expression and clinicopathological factors of endometrial cancer. Of the overall sample, 46 samples were in the early stage, whereas 18 samples were in the advanced stage. High expression of CD44 was associated with advanced stage compare than early stage (P=0.010), poor differentiation compare than well-moderate differentiation (P=0.001), myometrial invasion ≥50% compare than myometrial invasion <50% (P=0.004), and positive LVSI compare than negative LVSI (P=0.043) in endometrial cancer, but not associated with histological type of endometrial cancer (P=0.178). High expression of CD44 may be considered as a poor prognostic marker and predictive marker for targeted therapy in endometrial cancer.