Fragmentomics features of ovarian cancer.

Ovarian cancer (OC) is a major cause of cancer mortality in women worldwide. Due to the occult onset of OC, its nonspecific clinical symptoms in the early phase, and a lack of effective early diagnostic tools, most OC patients are diagnosed at an advanced stage. In this study, shallow whole-genome sequencing was utilized to characterize fragmentomics features of circulating tumor DNA (ctDNA) in OC patients. By applying a machine learning model, multiclass fragmentomics data achieved a mean area under the curve (AUC) of 0.97 (95% CI 0.962-0.976) for diagnosing OC. OC scores derived from this model strongly correlated with the disease stage. Further comparative analysis of OC scores illustrated that the fragmentomics-based technology provided additional clinical benefits over the traditional serum biomarkers cancer antigen 125 (CA125) and the Risk of Ovarian Malignancy Algorithm (ROMA) index. In conclusion, fragmentomics features in ctDNA are potential biomarkers for the accurate diagnosis of OC.

Predictive value of number of metastatic lymph nodes and lymph node ratio for prognosis of patients with FIGO 2018 stage IIICp cervical cancer: a multi-center retrospective study.

BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Analysis of risk factors for post-operative recurrence or progression of intravenous leiomyomatosis.

OBJECTIVE: To analyse the risk factors for post-operative recurrence or progression of intravenous leiomyomatosis and explore the impact of different treatment strategies on patient prognosis. METHODS: Patients with intravenous leiomyomatosis who underwent surgery from January 2011 to December 2020 and who were followed for ≥3 months were included. The primary endpoint was recurrence (for patients with complete resection) or progression (for patients with incomplete resection). Kaplan-Meier survival analysis was used to analyse the factors affecting recurrence. RESULTS: A total of 114 patients were included. The median age was 45 years old (range 24-58). The tumors were confined to the uterus and para-uterine vessels in 48 cases (42.1%), while in 66 cases (57.9%) it involved large vessels (iliac vein or genital vein and/or proximal large veins). The median follow-up time was 24 months (range 3-132). Twenty-nine patients (25.4%) had recurrence or progression. The median recurrence or progression time was 16 months (range 3-60). Incomplete tumor resection (p=0.019), involvement of the iliac vein or genital vein (p=0.042), involvement of the inferior vena cava (p=0.025), and size of the pelvic tumor ≥15 cm (p=0.034) were risk factors for recurrence and progression. For intravenous leiomyomatosis confined to the uterus or para-uterine vessels, no post-operative recurrence after hysterectomy and bilateral oophorectomy occurred in this cohort. Compared with hysterectomy and bilateral oophorectomy, the risk of recurrence after tumorectomy (with the uterus and ovaries retained) was significantly greater (p=0.009), while the risk of recurrence after hysterectomy was not significantly increased (p=0.058). For intravenous leiomyomatosis involving the iliac vein/genital vein and the proximal veins, post-operative aromatase inhibitor treatment (p=0.89) and two-stage surgery (p=0.86) were not related to recurrence in patients with complete tumor resection. CONCLUSION: Incomplete tumor resection, extent of tumor lesions and size of the pelvic tumor were risk factors for post-operative recurrence and progression of intravenous leiomyomatosis.

Modification of transvaginal polypropylene mesh with co-axis electrospun nanofibrous membrane to alleviate complications following surgical implantation.

BACKGROUND: Surgeries for treating pelvic organ prolapse involving the utilization of synthetic mesh have been associated with complications such as mesh erosion, postoperative pain, and dyspareunia. This work aimed to reduce the surgical implantation-associated complications by nanofibrous membranes on the surface of the polypropylene mesh. The nanofiber of the nanofibrous membrane, which was fabricated by co-axial electrospinning, was composed of polyurethane as fiber core and gelatin as the fiber out layer. The biocompatibility of the modified mesh was evaluated in vitro by cell proliferation assay, immunofluorescence stain, hematoxylin-eosin (HE) staining, and mRNA sequencing. Polypropylene mesh and modified mesh were implanted in a rat pelvic organ prolapse model. Mesh-associated complications were documented. HE and Picro-Sirius red staining, immunohistochemistry, and western blotting were conducted to assess the interactions between the modified mesh and vaginal tissues. RESULTS: The modified mesh significantly enhanced the proliferation of fibroblasts and exerted a positive regulatory effect on the extracellular matrix anabolism in vitro. When evaluated in vivo, no instances of mesh exposure were observed in the modified mesh group. The modified mesh maintained a relatively stable histological position without penetrating the muscle layer or breaching the epidermis. The collagen content in the vaginal wall of rats with modified mesh was significantly higher, and the collagen I/III ratio was lower, indicating better tissue elasticity. The expression of metalloproteinase was decreased while the expression levels of tissue inhibitor of metalloproteinase were increased in the modified mesh group, suggesting an inhibition of collagen catabolism. The expression of TGF-ß1 and the phosphorylation levels of Smad3, p38 and ERK1/2 were significantly increased in the modified mesh group. NM significantly improved the biocompatibility of PP mesh, as evidenced by a reduction in macrophage count, decreased expression levels of TNF-α, and an increase in microvascular density. CONCLUSIONS: The nanofibrous membrane-coated PP mesh effectively reduced the surgical implantation complications by inhibiting the catabolism of collagen in tissues and improving the biocampibility of PP mesh. The incorporation of co-axial fibers composed of polyurethane and gelatin with polypropylene mesh holds promise for the development of enhanced surgical materials for pelvic organ prolapse in clinical applications.

Impact of the COVID-19 pandemic on teaching and research activities in obstetrics and gynecology: a national two-stage, stratified, cluster sampling survey in China.

BACKGROUND: Few studies quantified the influence of the coronavirus disease 2019 (COVID-19) pandemic on medical teaching and scientific research activities in China. This is the first national study to investigate such topics from the viewpoint of physicians practicing obstetrics and gynecology in China. METHODS: This is a national questionnaire survey with online interviews for respondents. This two-stage, stratified, cluster sampling method was applied based on city categories (categories 1 to 3 correspond to < 10,000, 10,000 to 30,000, and > 30,000 beds, respectively), hospital levels (primary, secondary, and tertiary), and hospital types (general and specialized) in China among physicians practicing obstetrics and gynecology. Physicians documented notable alterations in both overall and specialized teaching and research engagements. Comparative analyses were conducted across diverse municipal and hospital attributes. RESULTS: Data were collected from a representative sample of 11,806 physicians from 779 hospitals across 157 cities and 31 provinces. Notably, except for online seminars, a minimum reduction of 20% in both overall and specialized teaching and research activities was observed among physicians. Up to 61.7% (95% confidence interval 59.3-64.0) of physicians reported either a complete termination or a > 50% decline in resident training. Compared with category 1 cities and primary hospitals, category 3 cities and tertiary hospitals experienced greater reductions in items of resident or graduate education, visiting scholar, clinical trials, and laboratory studies (adjusted p values < 0.05), coupled with notable increases in online seminar participation (adjusted p values of 0.002 and < 0.001, respectively). CONCLUSIONS: Amidst the COVID-19 pandemic in China, activities requiring direct, face-to-face communication were more affected in resource-rich cities and general hospitals compared to resource-limited areas and specialized hospitals. Residency training experienced the most significant decline. Conversely, participation in online seminars increased, providing additional opportunities for continuing medical education.

Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors.

BACKGROUND: To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). METHODS: Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan-Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. RESULTS: We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150-2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255-2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057-2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185-1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347-2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761). CONCLUSION: R-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Ovariectomy with simulated vaginal delivery to establish a rat model for pelvic organ prolapse.

The widespread prevalence of Pelvic Organ Prolapse (POP) and the paucity of ongoing treatments prompted us to develop a unique rat model combining ovariectomy and simulated vaginal delivery. We hypothesized that the tissue changes caused by low hormone levels and mechanical stretch could complement each other. Thus, the combined model can potentially mimic the collagen metabolism of vaginal wall tissue as well as mechanical stretch properties to complement disease progression in POP. Ovariectomy with sequential simulated vaginal delivery was performed on rats in the modeling group. Sham surgeries were performed as control. At 2, 4, and 12 weeks after modeling, the vaginal tissues of rats were evaluated by Masson's trichrome staining, Picro-Sirius red staining, immunohistochemistry, western blotting, and uniaxial tensile tests. Compared to the control group, the vaginal tissues of the model rats showed an atrophic epithelial layer and loose collagen fibers. The smooth muscle fibers were ruptured, smaller in diameter, and disorganized. The ratio of collagen type I/III significantly increased, but the contents of both Collagen I and III decreased. The expression of metalloproteinases 2 and 9 in the tissues increased, and the expression of tissue inhibitors of metalloproteinases 1 and 2 decreased. The tangent modulus of the tissues was significantly increased in the model rats. We verified a novel method to establish a pelvic organ prolapse model in rats. This approach combined the advantages of low hormone levels and mechanical stretch effects.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study.

INTRODUCTION: FIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size. MATERIAL AND METHODS: We retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I-IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC-T1, IIIC-T2a, IIIC-T2b, and IIIC-(T3a+T3b). Oncologcial outcomes of all stages were compared. RESULTS: A total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan-Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC-(T1-T2b) was significantly better than of IIIA+IIIB and IIIC-(T3a+T3b); no significant difference was noted between IIB and IIIC-(T1-T2b), or IIIC-(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC-T1, Stages T2a, T2b, IIIA+IIIB and IIIC-(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC-(T1-T2b) and IIB. Also, compared with IIB, IIIC-(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC-(T3a+T3b) and IIIA+IIIB. CONCLUSIONS: In terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC-T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.

Effect of annualized surgeon volume on major surgical complications for abdominal and laparoscopic radical hysterectomy for cervical cancer in China, 2004-2016: a retrospective cohort study.

BACKGROUND: Previous studies have suggested that higher surgeon volume leads to improved perioperative outcomes for oncologic surgery; however, the effect of surgeon volumes on surgical outcomes might differ according to the surgical approach used. This paper attempts to evaluate the effect of surgeon volume on complications or cervical cancer in an abdominal radical hysterectomy (ARH) cohort and laparoscopic radical hysterectomy (LRH) cohort. METHODS: We conducted a population-based retrospective study using the Major Surgical Complications of Cervical Cancer in China (MSCCCC) database to analyse patients who underwent radical hysterectomy (RH) from 2004 to 2016 at 42 hospitals. We estimated the annualized surgeon volumes in the ARH cohort and in the LRH cohort separately. The effect of the surgeon volume of ARH or LRH on surgical complications was examined using multivariable logistic regression models. RESULTS: In total, 22,684 patients who underwent RH for cervical cancer were identified. In the abdominal surgery cohort, the mean surgeon case volume increased from 2004 to 2013 (3.5 to 8.7 cases) and then decreased from 2013 to 2016 (8.7 to 4.9 cases). The mean surgeon case volume number of surgeons performing LRH increased from 1 to 12.1 cases between 2004 and 2016 (P < 0.01). In the abdominal surgery cohort, patients treated by intermediate-volume surgeons were more likely to experience postoperative complications (OR = 1.55, 95% CI = 1.11-2.15) than those treated by high-volume surgeons. In the laparoscopic surgery cohort, surgeon volume did not appear to influence the incidence of intraoperative or postoperative complications (P = 0.46; P = 0.13). CONCLUSIONS: The performance of ARH by intermediate-volume surgeons is associated with an increased risk of postoperative complications. However, surgeon volume may have no effect on intraoperative or postoperative complications after LRH.

Impact of different postoperative adjuvant therapies on the survival of early-stage cervical cancer patients with one intermediate-risk factor: A multicenter study of 14 years.

OBJECTIVE: To compare survival outcomes of different postoperative adjuvant therapies (PATs) for early-stage cervical cancer (ECC) patients with one intermediate-risk pathological factor (IPF). METHODS: A total of 2889 patients with stage IA1 to IIA2 cervical cancer were included in this study. Three PAT groups were identified, namely a no adjuvant therapy (NAT) group (n = 773), an adjuvant radiotherapy/chemoradiotherapy (ART) group (n = 1648) and an adjuvant chemotherapy (ACT) group (n = 468). Kaplan-Meier analysis and COX regression analysis were used to compare the overall survival (OS) and disease-free survival (DFS) among the three groups, before and after propensity score matching (PSM). RESULTS: The recurrence and mortality rate rates in the NAT, ART and ACT groups were 9.2%, 8.6%, and 7.9%, respectively (p = 0.737). Kaplan-Meier analysis demonstrated no significant differences in the NAT, ART, and ACT groups in 5-year OS rates (92.8% vs. 93.6% vs. 94.7%, p = 0.594) and DFS rates (88.7% vs. 89.6% vs. 90.5%, p = 0.772). Post-hoc tests yielded similar results, with no differences in 5-year OS and DFS (NAT vs. ART, before and after matching, p > 0.05); (NAT vs. ACT, before and after matching, p > 0.05); and (ACT vs. ART, before and after matching, p > 0.05). CONCLUSION: Postoperative adjuvant radiotherapy, chemoradiotherapy, and chemotherapy are not associated with survival outcomes of ECC patients with one IPF. Considering the side effects and impact on patients' quality of life, the PATs should be carefully considered.

Comparison between laparoscopic and abdominal radical hysterectomy for cervical adenosquamous carcinoma at stage IA2 to IIA2: A multicenter retrospective study.

OBJECTIVE: We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria. METHODS: Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4 cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study. RESULTS: Based on FIGO 2009 staging criteria (n = 474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4 cm subgroup. Based on FIGO2018 staging criteria (n = 322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma.

Abdominal pregnancy: a case report and review of 17 cases.

PURPOSE: To analyze the clinical characteristics of abdominal pregnancy, and to explore the diagnosis and prognosis of different treatment methods. METHODS: The cases of patients with abdominal pregnancy admitted to Peking Union Medical College Hospital between January 1, 1989 and January 1, 2021, were analyzed retrospectively. RESULTS: The median age of 17 patients was 34 years (22-42 years); the median gestational duration was 57 days (from 41 days to 32 weeks). Among all 17 patients, 15 (88.24%) presented with abdominal pain. The implantation sites of the gestational sac included the bladder peritoneal reflection, anterior wall of the rectum, omentum, serous membrane of the uterus, and inside or on the surface of uterosacral ligament. In all, only 29.41% cases (5/17) were diagnosed before surgery. All 17 patients were treated via surgery. Further, 58.82% (10/17) patients recovered without complications, 29.41% (5/17) developed fever, 5.88% (1/17) underwent reoperation because of intra-abdominal bleeding, and 5.88% (1/17) developed double lower limb venous thrombosis. All 17 patients survived. CONCLUSION: The preoperative diagnosis rate of abdominal pregnancy is low. Planting sites in the pelvic peritoneum and pelvic organs are more common than the others. Laparoscopic surgery in the first trimester of pregnancy can achieve better therapeutic effects. However, the blood supply of the placenta should be fully evaluated before surgery. When it is expected that attempts to remove the placenta will cause fatal bleeding, the placenta can be left in place, but long-term close follow-up should be paid attention to.

Diagnostic value of circN4BP2L2 in type I and type II epithelial ovarian cancer.

BACKGROUND: CircN4BP2L2 was previously identified to be significantly decreased in epithelial ovarian cancer (EOC) and was associated with disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 using the unifying model of type I and type II EOC. METHODS: A total of 540 plasma samples were obtained from 180 EOC patients, 180 benign ovarian cyst patients, and 180 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: Low level of circN4BP2L2 was associated with advanced tumor stage (p < 0.01) in type I EOC. Decreased circN4BP2L2 was associated with lymph node metastasis (LNM) (p = 0.04) in type II EOC. The expression level of circN4BP2L2 in type I was similar to that in type II. CircN4BP2L2 could significantly separate type I or type II from benign or normal cohort (p < 0.01). Early-stage type I or type II EOC vs. benign or normal cohort could also be distinguished by circN4BP2L2 (p < 0.01). CONCLUSION: CircN4BP2L2 might serve as a promising diagnostic biomarker for both type I and type II EOC. The diagnostic safety for circN4BP2L2 in early-stage type I or type II EOC is also acceptable. Further large-scale well-designed studies are warranted to investigate whether circN4BP2L2 is specific for all histologic subgroups.

Plasma circN4BP2L2 is a promising novel diagnostic biomarker for epithelial ovarian cancer.

BACKGROUND: Circular RNAs (circRNAs) are more stable than linear RNA molecules, which makes them promising diagnostic biomarkers for diseases. By circRNA-sequencing analysis, we previously found that circN4BP2L2 was significantly decreased in epithelial ovarian cancer (EOC) tissues, and was predictive of disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 in EOC. METHODS: Three hundred seventy-eight plasma samples were acquired prior to surgery. Samples were obtained from 126 EOC patients, 126 benign ovarian cyst patients, and 126 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). EOC cells were transfected with small interference RNAs (siRNAs) and cell proliferation, migration, invasion, cell cycle and cell apoptosis were performed to assess the effect of circN4BP2L2 in EOC. Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: Plasma circN4BP2L2 was significantly downregulated in EOC patients. Decreased circN4BP2L2 was significantly associated with advanced tumor stage, worse histological grade, lymph node metastasis and distant metastasis in EOC. CircN4BP2L2 inhibited tumor cell migration and invasion in vitro. CircN4BP2L2 could significantly separate EOC from benign (AUC = 0.82, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort. Early stage EOC vs benign (AUC = 0.81, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort could also be distinguished by circN4BP2L2. In discrimination between EOC cohort and benign or normal cohort, circN4BP2L2 performed equally well in both pre- and post-menopausal women. The combination of circN4BP2L2, CA125 and HE4 showed high sensitivity and specificity in detecting EOC cases. CONCLUSIONS: Plasma circN4BP2L2 is significantly downregulated in EOC and might serve as a promising novel diagnostic biomarker for EOC patients, especially in early stage EOC cases. CircN4BP2L2 might act as an adjunct to CA125 and HE4 in detecting EOC. Further large-scale studies are warranted to verify our results.

Comparison of survival outcomes between squamous cell carcinoma and adenocarcinoma/adenosquamous carcinoma of the cervix after radical radiotherapy and chemotherapy.

BACKGROUND: This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy. METHODS: Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China. RESULTS: Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001). CONCLUSIONS: For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC.

The application of risk models based on machine learning to predict endometriosis-associated ovarian cancer in patients with endometriosis.

INTRODUCTION: There is currently no satisfactory model for predicting malignant transformation of endometriosis. The aim of this study was to construct and evaluate a risk model incorporating noninvasive clinical parameters to predict endometriosis-associated ovarian cancer (EAOC) in patients with endometriosis. MATERIAL AND METHODS: We enrolled 6809 patients with endometriosis confirmed by pathology, and randomly allocated them to training (n = 4766) and testing cohorts (n = 2043). The proportion of patients with EAOC in each cohort was similar. We extracted a total of 94 demographic and clinicopathologic features from the medical records using natural language processing. We used a machine learning method - gradient-boosting decision tree - to construct a predictive model for EAOC and to evaluate the accuracy of the model. We also constructed a multivariate logistic regression model inclusive of the EAOC-associated risk factors using a back stepwise procedure. Then we compared the performance of the two risk-predicting models using DeLong's test. RESULTS: The occurrence of EAOC was 1.84% in this study. The logistic regression model comprised 10 selected features and demonstrated good discrimination in the testing cohort, with an area under the curve (AUC) of 0.891 (95% confidence interval [CI] 0.821-0.960), sensitivity of 88.9%, and specificity of 76.7%. The risk model based on machine learning had an AUC of 0.942 (95% CI 0.914-0.969), sensitivity of 86.8%, and specificity of 86.7%. The machine learning-based risk model performed better than the logistic regression model in DeLong's test (p = 0.036). Furthermore, in a prospective dataset, the machine learning-based risk model had an AUC of 0.8758, a sensitivity of 94.4%, and a specificity of 73.8%. CONCLUSIONS: The machine learning-based risk model was constructed to predict EAOC and had high sensitivity and specificity. This model could be of considerable use in helping reduce medical costs and designing follow-up schedules.

Comparison of survival outcomes of abdominal radical hysterectomy and radiochemotherapy IIA2 (FIGO2018) cervical cancer: a retrospective study from a large database of 63,926 cases of cervical cancer in China.

AIM: This study aimed to compare the 5-year overall survival (OS) and 5-year DFS disease-free survival (DFS) of abdominal radical hysterectomy (ARH) and radiochemotherapy (R-CT) for stage IIA2 (FIGO 2018) cervical cancer patients. METHODS: Based on this multicenter, retrospective cohort study based on data from the clinical diagnosis and treatment of cervical cancer in China (Four C) database, 609 cases with 2018 FIGO stage IIA2 cervical cancer from 2004 to 2018 were reviewed. The 5-year OS and 5-year DFS of patients with either of the two treatment methods were compared by means of a multivariate Cox regression model and the log-rank method in the total study population and after propensity score matching (PSM). RESULTS: We selected 609 of 63,926 patients and found that R-CT was associated with a significantly worse 5-year OS (71.8% vs. 95.3%, P < 0.001; hazard ratio (HR) = 6.596, 95% CI 3.524-12.346) and 5-year DFS (69.4% vs. 91.4%, P < 0.001; HR = 4.132, 95% CI 2.570-6.642, P < 0.001) than ARH in the total study population. After matching (n = 230/230), among FIGO 2018 IIA2 patients, the 5-year OS and DFS were lower in the R-CT group than in the ARH group (OS: 73.9% vs. 94.7%, P < 0.001; HR = 5.633, 95% CI 2.826-11.231, P < 0.001; DFS: 69.2% vs. 91.1%, P < 0.001; HR = 3.978, 95% CI 2.336-6.773, P < 0.001, respectively). CONCLUSIONS: In patients with stage FIGO 2018 IIA2 cervical cancer, ARH offers better 5-year OS and DFS outcomes than R-CT; however, due to the inherent biases of retrospective studies, this needs to be confirmed by randomized trials.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study.

PURPOSE: To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. METHOD: We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2 cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. RESULTS: In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). CONCLUSION: Among patients with low-risk cervical cancers < 2 cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

Modern Medicine: Ideas and Advances.

Considering the limitations of medical science and the risks associated with medical treatments, we need to re-examine the connotation of medical science from the perspective of philosophy. Medical science is the natural expression of human kindness and human nature of rescuing the dying and healing the wounded. It is a combination of the natural sciences, social sciences, and humanities. From the perspectives of medical philosophy and humanistic care, this article expounds the concepts and ideas of evidence-based, translational, and precision medicine in modern medicine and emphasizes the importance of avoiding new technical bureaucracy, paying attention to achieving a holistic view and systematic understanding, and avoiding biases in development because of the loss of the humanistic spirit in modern medical practice.