BackgroundIn 5–20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear.MethodsAmong 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up.ResultsThe age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6–43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P < 0.05). A multivariate analysis indicated that an age of 35 years or older was the only independent risk factor (OR 4.97, 95 % CI 1.14–21.62, P = 0.03).ConclusionIn patients with HSIL and HSIL-involved margins after an initial LEEP, age is a strong independent predictor of persistence/recurrence. Follow-up with screening cytology and/or biopsy may be considered in younger patients, whereas a secondary LEEP/hysterectomy may be considered in older patients.

Rapidly and accurately identifying tumor cells and blood cells is an important part of circulating tumor cell detection. Raman spectroscopy is a molecular vibrational spectroscopy technique that can provide fingerprint information about molecular vibrational and rotational energy levels. Deep learning is an advanced machine learning method that can be used to classify various data accurately. In this paper, the surface-enhanced Raman scattering spectra of blood cells and various tumor cells are measured with the silver film substrate. It is found that there are significant differences in nucleic acid-related characteristic peaks between most tumor cells and blood cells. These spectra are classified by the feature peak ratio method, principal component analysis combined with K-nearest neighbor, and residual network, which is a kind of deep learning algorithm. The results show that the ratio method and principal component analysis combined with the K-nearest neighbor method could only distinguish some tumor cells from blood cells. The residual network can quickly identify various tumor cells and blood cells with an accuracy of 100%, and there is no complex preprocessing for the surface-enhanced Raman scattering spectra. This study shows that the silver film surface-enhanced Raman scattering technology combined with deep learning algorithms can quickly and accurately identify blood cells and tumor cells, indicating an important reference value for the label-free detecting circulating tumor cells.

Supplemental digital content is available in the text.

BackgroundOur research aimed to investigate whether lymphadenectomy was required in patients with intermediate-risk endometrioid endometrial cancer (EEC).MethodsBetween 1989 and 2015, 1009 patients with intermediate-risk EEC: grade 1 or 2 tumor, <50% myometrial invasion, and a tumor diameter ≥ 2 cm and 818 low-risk patients with grade 1 or 2 tumor, <50% myometrial invasion, and a tumor diameter < 2 cm were enrolled in this study. The rate and risk factors of node metastasis were evaluated and compared between the two risk groups. Survival data were analyzed in patients with intermediate-risk EEC with or without lymphadenectomy.ResultsIn all, 624 of 1009 (61.8%) patients with intermediate-risk EEC underwent pelvic ± para-aortic lymphadenectomy with a nodal metastasis rate of 1.9% (12/624), whereas 394 of 818 (48.2%) patients with low-risk EEC underwent pelvic ± para-aortic lymphadenectomy with a nodal metastasis rate of 0.3% (1/394) (p = 0.021). Notably, intermediate-risk EEC patients with a microcystic, elongated and fragmented (MELF) pattern of invasion, lymphatic vascular space invasion (LVSI), diffuse lesions, or lesions located in the cornua were more likely to have node metastasis. The 5-year overall cancer-related survival and the recurrence-free survival rates of the 742 intermediate-risk EEC patients who were followed for more than 3 years were 99.4% and 94.7%, respectively. In intermediate-risk group, 6 patients (6/443, 1.4%) with lymphadenectomy and 9 patients (9/299, 3.0%) without lymphadenectomy recurred, with a mean recurrence time of 38.3 and 18.7 months respectively. The five-year overall and recurrence-free survival rates of intermediate-risk patients with and without lymphadenectomy were similar (100% vs 98.9%, p = 0.351; 95.2% vs 93.3%, p = 0.464).ConclusionPatients with intermediate-risk EEC have low nodal metastasis rate and a favorable outcome whether lymphadenectomy is performed or not. Omission of lymphadenectomy may be a reasonable option in the surgical management of patients with intermediate-risk EEC.

Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

ObjectiveHigh-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models.MethodsFresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors.ResultsThe total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts.ConclusionsThe combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.

Objective This study aimed to retrospectively investigate the safety of ovarian preservation of premenopausal women with stage 1a endometrial carcinoma. Methods We performed a population-based study to identify surgically treated stage Ia endometrial cancer of premenopausal women who were diagnosed between August 1989 and December 2015 in our center. Survival outcomes and recurrence rate were examined for premenopausal women who underwent ovarian preservation. Recurrence-free survival rates were calculated following generation of Kaplan–Meier curves and were compared with the log-rank test. Cox regression analysis was performed to identify the independent factors affecting the recurrence rate. Results Patients with ovarian preservation tended to be significantly younger at diagnosis, have less myometrial invasion, and were less likely to undergo lymphadenectomy compared with women treated with bilateral salpingo-oophorectomy. There was no significant difference in recurrence-free survival between the two groups. In the Cox regression model, ovarian preservation remained an independent prognostic factor for improved overall survival. Conclusion Ovarian preservation does not have a negative effect on oncological outcomes. Ovarian preservation can be applied to premenopausal women with stage Ia endometrial carcinoma.

Objective We aimed to compare the survival and perioperative outcomes of patients with stage II endometrial cancer (EC) undergoing simple hysterectomy (SH) or radical hysterectomy (RH), to validate the various guidelines. Methods A total of 155 consecutive patients diagnosed with stage II EC from 2000 to 2014 were reviewed. We identified 40 pairs of patients (40 SH and 40 RH) who were matched in terms of age, pathological type, and lymphovascular space invasion status using matched-pair analysis. Patient data were collected from medical records and outcomes were determined by telephone follow-up. Results Among the 80 patients in the two groups, seven died from tumor recurrence. However, cancer-related survival rates were not significantly different between the SH and RH groups. The 3-year cancer-related survival rates in the SH and RH groups were 94.97% and 92.53%, and the 5-year survival rates were 92.40% and 90.03%, respectively. Regarding perioperative outcomes, the SH group had significantly less intraoperative bleeding and a significantly shorter catheter-indwelling time than the RH group. Conclusions SH provides similar survival outcomes and a superior perioperative quality of life compared with RH in patients with stage II EC.