Lipid metabolism reprogramming in endometrial cancer: biological functions and therapeutic implications.

BACKGROUND: Endometrial cancer is one of the major gynecological cancers, with increasing incidence and mortality in the past decades. Emerging preclinical and clinical data have indicated its close association with obesity and dyslipidemia. Metabolism reprogramming has been considered as the hallmark of cancer, to satisfy the extensive need of nutrients and energy for survival and growth. Particularly, lipid metabolism reprogramming has aroused the researchers' interest in the field of cancer, including tumorigenesis, invasiveness, metastasis, therapeutic resistance and immunity modulation, etc. But the roles of lipid metabolism reprogramming in endometrial cancer have not been fully understood. This review has summarized how lipid metabolism reprogramming induces oncogenesis and progression of endometrial cancer, including the biological functions of aberrant lipid metabolism pathway and altered transcription regulation of lipid metabolism pathway. Besides, we proposed novel therapeutic strategies of targeting lipid metabolism pathway and concentrated on its potential of sensitizing immunotherapy and hormonal therapy, to further optimize the existing treatment modalities of patients with advanced/metastatic endometrial cancer. Moreover, we expect that targeting lipid metabolism plus hormone therapy may block the endometrial malignant transformation and enrich the preventative approaches of endometrial cancer. CONCLUSION: Lipid metabolism reprogramming plays an important role in tumor initiation and cancer progression of endometrial cancer. Targeting the core enzymes and transcriptional factors of lipid metabolism pathway alone or in combination with immunotherapy/hormone treatment is expected to decrease the tumor burden and provide promising treatment opportunity for patients with advanced/metastatic endometrial cancer.

Resected lung adenocarcinoma with lymph node metastasis: is ground glass opacity component a prognostic factor?

Background: Ground glass opacity (GGO)-featured lung adenocarcinoma generally has excellent prognosis, and here is rarely the occurrence of lymph node metastasis. We conducted a retrospective cohort study to explore the prognostic impact of GGO component in node-positive lung adenocarcinomas. Methods: A total of 669 patients with pathologic N1/N2 lung adenocarcinoma receiving R0 resection and systemic lymph node dissection from 2008 to 2015 were reviewed, including 635 solid and 34 part-solid lesions. Propensity score matching (PSM) was performed to compare survival outcomes of solid and part-solid lesions, in order to determine the prognostic value of GGO component. Cox proportional hazard model was performed to identify significant prognostic factors for resected node positive lung adenocarcinoma. Results: About 5.1% (34 of 669) of resected node-positive lung adenocarcinoma presented as part-solid nodules on computed tomography (CT) images in this cohort. The median nodule size on CT of the 34 part-solid lesions was 31 mm (range, 15-68 mm), median solid component size on CT was 24 mm (range, 12-62 mm), and median consolidation/tumor ratio was 0.8 (range, 0.64-0.95). After 1:4 PSM, 136 patients and 34 patients were matched from the solid and part-solid groups. No significant difference in either recurrence-free survival (RFS) (P=0.71) or overall survival (OS) (P=0.82) was found between the solid and part-solid groups. Multivariable Cox regression showed that pN stage was the strongest prognostic factor for RFS and OS. GGO component was not an independent prognostic factor toward for RFS [P=0.75; hazard ratio (HR) =0.93; 95% confidence interval (CI): 0.59-1.46] or OS (P=0.53; HR =1.19; 95% CI: 0.69-2.05). Conclusions: A minority of resected node-positive lung adenocarcinoma presents as GGO component on CT. The presence of GGO component does not predict better prognosis in node-positive lung adenocarcinoma.

Tumor targeting peptide TMTP1 modified Antigen capture Nano-vaccine combined with chemotherapy and PD-L1 blockade effectively inhibits growth of ovarian cancer.

The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body's immune potential, providing an eutherapeutic strategy for the treatment of OC.

Molecular Biological Research on the Pathogenic Mechanism of Retinoblastoma.

Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

Clinical characteristics and treatment outcomes of patients with a septate uterus complicated by endometriosis.

OBJECTIVES: Patients with a septate uterus often have endometriosis, which can exacerbate their adverse pregnancy outcomes. We aimed to describe the clinical characteristics and treatment outcomes of patients with a septate uterus complicated by endometriosis. STUDY DESIGN: This retrospective study included patients who had a septate uterus complicated by endometriosis and were treated in Wuhan Tongji Hospital in the past 10 years. The characteristics of patients with a septate uterus and endometriosis were collected and described in terms of their preoperative and postoperative pregnancy outcomes. RESULTS: There were 24 cases with a complete septate uterus and 49 cases with an incomplete septate uterus.Combinations of other malformations are more common in patients with complete septate uterus. In patients with a septate uterus, endometriosis often affected the ovaries, most commonly the left side (P < 0.001). Non-significant difference in the staging of endometriosis between complete and incomplete septate uterus (P= 0.812). Surgical treatment greatly improved the reproductive function and increased the live birth rate of patients with a septate uterus complicated by endometriosis (P < 0.001). CONCLUSIONS: Compared to a septate uterus uncomplicated endometriosis, a septate uterus complicated by endometriosis significantly affects reproductive function. Surgical treatment can significantly improve the pregnancy outcomes of patients with a septate uterus and endometriosis. Clinicians should pay attention to timely diagnosing and treating these patients.

WEE1 Inhibitors Mediate Antitumor Effects on Endometrial Cancer through Activation of Innate Immune Responses.

Introduction: Recurrence signifies the primary mortality factor in patients suffering from endometrial cancer, with few efficacious treatments currently available for recurrent cases. This research investigates the anti-tumoral capacities of WEE1 inhibitors within the context of endometrial cancer, aiming to establish a novel therapeutic avenue for high recurrence-risk patients. Materials and methods: We evaluated WEE1 expression in endometrial cancer patients utilizing immunohistochemistry on paraffin-embedded tissue sections. The cytotoxic potential of WEE1 inhibitors on endometrial cancer cells was assessed by CCK8 assay. Assays to gauge the influence of WEE1 inhibitors on cell proliferation and migration included clonal proliferation, wound healing, and transwell assays. We determined the impacts on apoptosis and cell cycle stages by flow cytometry. Employing qRT-PCR and western blotting, we investigated the mechanistic pathways underlying the anti-tumoral activity of WEE1 inhibitors. In vivo evaluations were executed to ascertain the inhibitory effect of WEE1 inhibitors on tumor growth in mice. Results: WEE1 exhibited high-level expression in endometrial cancer tissues, particularly pronounced in recurrent compared with non-recurrent patients. WEE1 inhibitors effectively eliminated endometrial cancer cells while inhibiting their proliferation and migration. Flow cytometric analyses revealed a significant promotion of apoptosis and an increase in G2/M phase cell proportion upon WEE1 inhibitor treatment. qRT-PCR and western blotting elucidated that WEE1 inhibitors activated the innate immune signaling pathway in endometrial cancer cells. Furthermore, in vivo assessments demonstrated substantial tumor growth suppression due to WEE1 inhibitors. Conclusions: WEE1 inhibitors initiated an innate immune response in endometrial cancer, exhibiting considerable anti-tumoral effects, which was promising for postoperative treatment of endometrial cancer, especially recurrent endometrial cancer patients.

Development and validation of a nomogram for predicting recurrence-free survival in endometrial cancer: a multicenter study.

Recurrence is the main cause of death in patients with endometrial cancer (EC). This study aimed to construct and validate a nomogram to predict the recurrence-free survival of patients with EC. This was a multicenter retrospective study. A total of 812 patients from Wuhan Tongji Hospital were divided into training and validation cohorts, and 347 and 580 patients from People's Hospital of Peking University and Qilu Hospital of Shandong, respectively, were used for validation. Univariate and multivariate Cox regression analyses were used to construct a nomogram for predicting recurrence-free survival of EC. Calibration curves, receiver operating characteristic (ROC) curves, and consistency indexes (C-indexes) were used to estimate the performance of the model. Decision curve analysis (DCA) curves were used to assess the clinical utility of the model. Age (P = 0.013), cancer antigen 125 level (P = 0.014), lymphovascular space invasion (P = 0.004), International Federation of Gynecology and Obstetrics stage (P = 0.034), and P53 (P < 0.001) were independently associated with recurrence, and we constructed a nomogram based on these variables. The C-indexes of the validation cohorts were 0.880, 0.835, and 0.875, respectively. The calibration, ROC, and DCA curves revealed that this model had excellent performance and clinical utility. Combining clinical data, clinicopathological factors, serological indicators, and immunohistochemical marks, a multicenter externally verified nomogram with robust performance was constructed to predict the recurrence of patients with EC.

Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance.

Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial senescence), recapitulating different stages of squamous differentiation, showed distinct tumor immune microenvironments. Bidirectional interactions between epithelial-cytokeratin malignant cells and immunosuppressive cancer-associated fibroblasts form an immune exclusionary microenvironment through transforming growth factor ß pathway signaling mediated by FABP5. In Epi-Imm tumors, malignant cells interact with natural killer and T cells through interferon signaling. Preliminary analysis of samples from a cervical cancer clinical trial ( NCT04516616 ) demonstrated neoadjuvant chemotherapy induces a state transition to Epi-Imm, which correlates with pathological complete remission following treatment with immune-checkpoint blockade. These findings deepen the understanding of cellular state diversity in CSCC.

Hybrid deep multi-task learning radiomics approach for predicting EGFR mutation status of non-small cell lung cancer in CT images.

Objective.Epidermal growth factor receptor (EGFR) mutation genotyping plays a pivotal role in targeted therapy for non-small cell lung cancer (NSCLC). We aimed to develop a computed tomography (CT) image-based hybrid deep radiomics model to predict EGFR mutation status in NSCLC and investigate the correlations between deep image and quantitative radiomics features.Approach.First, we retrospectively enrolled 818 patients from our centre and 131 patients from The Cancer Imaging Archive database to establish a training cohort (N= 654), an independent internal validation cohort (N= 164) and an external validation cohort (N= 131). Second, to predict EGFR mutation status, we developed three CT image-based models, namely, a multi-task deep neural network (DNN), a radiomics model and a feature fusion model. Third, we proposed a hybrid loss function to train the DNN model. Finally, to evaluate the model performance, we computed the areas under the receiver operating characteristic curves (AUCs) and decision curve analysis curves of the models.Main results.For the two validation cohorts, the feature fusion model achieved AUC values of 0.86 ± 0.03 and 0.80 ± 0.05, which were significantly higher than those of the single-task DNN and radiomics models (allP< 0.05). There was no significant difference between the feature fusion and the multi-task DNN models (P> 0.8). The binary prediction scores showed excellent prognostic value in predicting disease-free survival (P= 0.02) and overall survival (P< 0.005) for validation cohort 2.Significance.The results demonstrate that (1) the feature fusion and multi-task DNN models achieve significantly higher performance than that of the conventional radiomics and single-task DNN models, (2) the feature fusion model can decode the imaging phenotypes representing NSCLC heterogeneity related to both EGFR mutation and patient NSCLC prognosis, and (3) high correlations exist between some deep image and radiomics features.

Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?

Endometrial cancer (EC) is increasingly undermining female health worldwide, with poor survival rates for advanced or recurrent/metastatic diseases. The application of immune checkpoint inhibitors (ICIs) has opened a window of opportunity for patients with first-line therapy failure. However, there is a subset of patients with endometrial cancer who remain insensitive to immunotherapy alone. Therefore, it is necessary to develop new therapeutic agents and further explore reliable combinational strategies to optimize the efficacy of immunotherapy. DNA damage repair (DDR) inhibitors as novel targeted drugs are able to generate genomic toxicity and induce cell death in solid tumors, including EC. Recently, growing evidence has demonstrated the DDR pathway modulates innate and adaptive immunity in tumors. In this review, we concentrate on the exploration of the intrinsic correlation between DDR pathways, especially the ATM-CHK2-P53 pathway and the ATR-CHK1-WEE1 pathway, and oncologic immune response, as well as the feasibility of adding DDR inhibitors to ICIs for the treatment of patients with advanced or recurrent/metastatic EC. We hope that this review will offer some beneficial references to the investigation of immunotherapy and provide a reasonable basis for "double-checkpoint inhibition" in EC.

Efficacy of Bispecific Antibody Targeting EpCAM and CD3 for Immunotherapy in Ovarian Cancer Ascites: An Experimental Study.

OBJECTIVE: This study aimed to explore the value of M701, targeting epithelial cell adhesion molecule (EpCAM) and CD3, in the immunotherapy of ovarian cancer ascites by the in vitro assay. METHODS: The expression of EpCAM in ovarian cancer tissues was analyzed by databases. The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry. The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay. The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens. Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells. RESULTS: The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue. The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites. The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells. M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites. M701 could mediate the binding of CD3+ T cells to EpCAM+ tumor cells and induce T cell activation in a dose-dependent manner. CONCLUSION: M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites, which had a promising application in immunotherapy for patients with ovarian cancer ascites.

Comparison of recurrence rate and risk factors in patients with focal adenomyosis with and without medical treatment after conservative surgery.

OBJECTIVE: To compare the recurrence rate and risk factors between conservative surgery followed by medical treatments and conservative surgery-only in patients with focal adenomyosis. METHODS: This retrospective study was conducted in a single teaching hospital from May 2011 to October 2016. All eligible patients were identified into three groups: surgery-only group, surgery combined with gonadotropin-releasing hormone agonist (GnRHa), and a levonorgestrel-releasing intrauterine system (LNG-IUS) group. The recurrence rate and risk factors were compared among groups using Kaplan-Meier and Cox proportional hazards analyses. Receiver operating characteristic (ROC) curve analysis was applied to determine a cut-off value for identifying recurrence-related risk factors. RESULTS: A total of 249 postoperative patients with adenomyosis were included in the final analysis with a mean of 41 months of follow up. The recurrence rate at the long-term follow up was significantly lower in intervention groups than in the surgery-only group (P = 0.011). The Cox proportional hazards and ROC analyses showed that a menstrual cycle longer than 26 days (P = 0.026), diameter of lesions <6 cm (P = 0.030), and combination treatment using GnRHa (P = 0.039) or LNG-IUS (P = 0.007) were protective against relapse. The risk of recurrence was lower in patients with anterior (P = 0.034) or fundus (P = 0.038) adenomyosis. CONCLUSION: Postoperative therapy using GnRHa or LNG-IUS decreases the long-term relapse rate in women undergoing conservative surgery.

Pregnancy may have little influence on ground-glass opacities suspected for lung adenocarcinoma.

PURPOSE: Owing to the popularity of low-dose computed tomography in lung cancer screening, young women spotted with ground-glass opacities (GGO) is a growing subgroup in clinical practice. We aim to investigate the influence of pregnancy on GGOs suspected for lung adenocarcinoma. METHODS: This retrospective study collected a series of female patients who were pregnant in follow-up of GGO lesions. The last CT images of GGO before pregnancy (CT1) and the first CT images after pregnancy (CT2) were reviewed to assess any radiologic change. Young female patients who were not pregnant in long-term (> 12 months) follow-up of GGO were enrolled as a comparison group. We also enrolled patients who gave birth within 2 years before surgical resection of GGOs. RESULTS: Four patients were enrolled according to the criteria. There was no significant change of the GGOs in all four patients with a median follow-up duration of 45.5 (range 17-86) months. Two patients were diagnosed pathologically to be minimally invasive adenocarcinoma, one was invasive adenocarcinoma and one did not underwent surgery. Six patients were enrolled in the comparison group and no significant change was witnessed in all the nodules. In those patients who gave birth within two years before surgical resection of GGOs, we found that the majority present as preinvasive lesions, and those with invasive adenocarcinomas were bigger in size and possess more solid component radiologically. CONCLUSION: Pregnancy seems to have little impact on GGOs suspected for lung adenocarcinoma. Therefore, pregnancy might be safely planned during the follow-up of GGOs.

Artificial Intelligence in Cervical Cancer Screening and Diagnosis.

Cervical cancer remains a leading cause of cancer death in women, seriously threatening their physical and mental health. It is an easily preventable cancer with early screening and diagnosis. Although technical advancements have significantly improved the early diagnosis of cervical cancer, accurate diagnosis remains difficult owing to various factors. In recent years, artificial intelligence (AI)-based medical diagnostic applications have been on the rise and have excellent applicability in the screening and diagnosis of cervical cancer. Their benefits include reduced time consumption, reduced need for professional and technical personnel, and no bias owing to subjective factors. We, thus, aimed to discuss how AI can be used in cervical cancer screening and diagnosis, particularly to improve the accuracy of early diagnosis. The application and challenges of using AI in the diagnosis and treatment of cervical cancer are also discussed.

Targeting regulated cell death in tumor nanomedicines.

Nanomedicines hold great potential in anticancer therapy by modulating the biodistribution of nanomaterials and initiating targeted oxidative stress damage, but they are also limited by the inherent self-protection mechanism and the evolutionary treatment resistance of cancer cells. New emerging explorations of regulated cell death (RCD), including processes related to autophagy, ferroptosis, pyroptosis, and necroptosis, substantially contribute to the augmented therapeutic efficiency of tumors by increasing the sensitivity of cancer cells to apoptosis. Herein, paradigmatic studies of RCD-mediated synergistic tumor nanotherapeutics are introduced, such as regulating autophagy-enhanced photodynamic therapy (PDT), targeting ferroptosis-sensitized sonodynamic therapy (SDT), inducing necroptosis-augmented photothermal therapy (PTT), and initiating pyroptosis-collaborative chemodynamic therapy (CDT), and the coordination mechanisms are discussed in detail. Multiangle analyses addressing the present challenges and upcoming prospects of RCD-based nanomedicines have also been highlighted and prospected for their further strengthening and the broadening of their application scope. It is believed that up-and-coming coadjutant therapeutic methodologies based on RCDs will considerably impact precision nanomedicine for cancer.

NRAS expression is associated with prognosis and tumor immune microenvironment in lung adenocarcinoma.

PURPOSE: NRAS plays a pivotal role in progression of various kinds of somatic malignancies; however, the correlation between NRAS and lung adenocarcinoma is less known. We aim to analyze the prognostic value of NRAS expression in lung adenocarcinoma, and explore the relationship between NRAS and tumor immune microenvironment. METHODS: We obtained the transcriptome profiles and clinical data of LUAD from The Cancer Genome Atlas database and three Genome Expression Omnibus datasets. Specimens from 325 patients with completely resected lung adenocarcinoma were collected for immunohistochemical assays of NRAS, PD-L1, PD-1 and TIM-3. Then, we performed gene set enrichment analysis to investigate cancer-related and immune-related signaling pathways. TIMER algorithms were performed to evaluate tumor immune infiltrating cells and immune-related biomarkers. RESULTS: Compared with adjacent non-tumor tissue, NRAS expression was significantly upregulated in LUAD tissue. NRAS expression was significantly correlated with more advanced stage and positive lymph nodes. Kaplan-Meier curves and Cox analysis suggested that high NRAS expression led to a poor prognosis, and could be an independent prognostic factor in LUAD patients. Besides, NRAS expression was positively correlated with CD8+ T cells, macrophages, and neutrophils, and negatively correlated with B cells and CD4+ T cells. The expression level of NRAS was positively correlated with PD-L1, PD-1, and TIM-3 both at RNA and protein level. CONCLUSIONS: To conclude, we found NRAS is a novel prognostic biomarker in LUAD. Besides, the expression level of NRAS may influence the prognosis of LUAD via various kinds of cancer-related pathways and remodeling TIM.

Subsolid Lesions Exceeding 3 Centimeters: The Ground-Glass Opacity Component Still Matters.

BACKGROUND: Recent studies on the favorable prognosis of ground-glass opacities (GGO) featured lung adenocarcinoma compared with solid nodules were limited to small tumors measuring 3.0 cm or less. This study investigated whether the GGO component could predict better prognosis in patients with large subsolid lesions exceeding 3 cm compared with small solid nodules within the same clinical T category. METHODS: From 2010 to 2015, 1010 patients with completely resected clinical N0 lung adenocarcinoma were enrolled, including 860 solid lesions and 150 subsolid lesions exceeding 3 cm. To analyze the prognostic significance of the GGO component, propensity score matching adjusting the solid component size was performed. RESULTS: After propensity score matching, 144 pairs of patients were analyzed. The mean size of the solid component was 23.7 mm in the GGO group and 24.4 mm in the solid group (P = .450). The GGO group had significantly better overall survival (P = .011) and recurrence-free survival (P = .003), which were also validated in patients with solid-predominant lesions. Subgroup analysis showed the GGO group was associated with better prognosis in each clinical T category. CONCLUSIONS: The prognosis of patients with GGO lesions exceeding 3 cm was better than that of patients with small solid lesions, even within the same clinical T category. Clinical T classification incorporating the GGO component may provide better prognostic prediction for patients with lung cancer exceeding 3 cm.

Surgery for pre- and minimally invasive lung adenocarcinoma.

OBJECTIVE: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are the pre- and minimally invasive forms of lung adenocarcinoma. We aimed to investigate safety results and survival outcomes following different types of surgical resection in a large sample of patients with AIS/MIA. METHODS: Medical records of patients with lung AIS/MIA who underwent surgery between 2012 and 2017 were retrospectively reviewed. Clinical characteristics, surgical types and complications, recurrence-free survival, and overall survival were investigated. RESULTS: A total of 1644 patients (422 AIS and 1222 MIA) were included. The overall surgical complication rate was significantly lower in patients receiving wedge resection (1.0%), and was comparable between patients undergoing segmentectomy (3.3%) or lobectomy (5.6%). Grade ≥ 3 complications occurred in 0.1% of patients in the wedge resection group, and in a comparable proportion of patients in the segmentectomy group (1.5%) and the lobectomy group (1.5%). There was no lymph node metastasis. The 5-year recurrence-free survival rate was 100%. The 5-year overall survival rate in the entire cohort was 98.8%, and was comparable among the wedge resection group (98.8%), the segmentectomy group (98.2%), and the lobectomy group (99.4%). CONCLUSIONS: Sublobar resection, especially wedge resection without lymph node dissection, may be the preferred surgical procedure for patients with AIS/MIA. If there are no risk factors, postoperative follow-up intervals may be extended. These implications should be validated in further studies.

Clinical, pathological and radiologic features of minute pulmonary meningothelial-like nodules.

OBJECTIVES: Reports about the radiologic features of minute pulmonary meningothelial-like nodules are sparse. This study aims to investigate the radiologic features of minute pulmonary meningothelial-like nodules. METHOD: From January 2016 to April 2019, 7589 patients underwent pulmonary resections at Fudan University Shanghai Cancer Center. Postoperative pathology records were reviewed retrospectively. Fifty-nine patients with minute pulmonary meningothelial-like nodule were included. The identification of minute pulmonary meningothelial-like nodules in pathology specimen included pathologically confirmed in resected nodules, and discovery in the peripheral tissue of other resected nodules incidentally. We went back and checked all the pre-operative scans of patients to analyze surgical decision and observe any change of visible minute pulmonary meningothelial-like nodule over time. Clinic, radiologic and pathological features were collected. RESULT: Fifty-nine patients included 10 men and 49 women, with a mean age of 57.7. Five patients had history, while 54 patients were non-smokers. 79 min pulmonary meningothelial-like nodules was found. Of them, 36 nodules were not visible on computed tomography scan. 43 nodules were visible on computed tomography scan, with an average size of 5.3 mm in 29 patients. Computed tomography appearance included pure ground-glass opacity in 36, mixed in 2, and solid nodules in 5. Nearly half of patients had a pre-operative follow-up more than 6 months (13/29, 44.8%). The median pre-operative radiologic follow-up was 4.9 months. Approximately 90% of patients underwent pulmonary surgery because of other malignant nodule on chest computed tomography scan (52/59, 88.1%). CONCLUSION: Most minute pulmonary meningothelial-like nodules tend to present as ground-glass opacity, especially pure ground-glass opacity. Continuous computed tomography monitoring revealed no radiologic change over time. Continuous computed tomography monitoring was necessary part of management of minute pulmonary meningothelial-like nodule.

Gonadotropin-releasing hormone agonist versus expectant management for treating multiple leiomyomas after myomectomy: the study protocol for a multicentre, prospective, randomised controlled clinical trial.

INTRODUCTION: Leiomyoma recurrence is a major concern for long-term myomectomy management, especially for multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is one of the most effective medications to reduce the volume of fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no randomised clinical trial determining the efficacy of GnRHa treatment for preventing multiple leiomyomas recurrence after myomectomy. METHODS AND ANALYSIS: We are conducting a phase IV randomised controlled trial in women aged 18-45 undergoing myomectomy for multiple leiomyomas. After surgery, women whose pathological result confirms multiple leiomyomas are randomised in a 1:1 ratio into an observation or GnRHa group. The primary outcome is the recurrence of either clinical symptoms or fibroids on imaging. Patients will be assessed for adverse events during the follow-up. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee of the Tongji Hospital Affiliated with the Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180311) according to the submitted study protocol (V.1.0, 10 November 2017) and informed consent (V.1.0, 10 November 2017). The results will be presented at domestic and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17012992.