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This study aims to demonstrate the advantages of NGS molecular classification in EC diagnosis and to assess whether molecular classification could be performed on curettage specimens and its concordance with subsequent hysterectomy specimens.80 patients with hysterectomy specimens and 35/80 patients with paired curettage specimens were stratified as POLE mut, MSI-H, TP53 wt, or TP53 abn group by NGS panel. Histotype, tumor grade, IHC results, and other pathological details were taken from original pathological reports.The correlation analysis of 80 patients with hysterectomy specimens between NGS molecular classification and clinicopathological characters displayed that the POLE mut group was associated with EEC (87.5%) and TP53 abn subtype was correlated to a later stage (Stage II-IV, 47.6%), G3 (76.2%), serous histology (61.9%) and myometrial invasion ≥50% (47.6%). A favorable concordance (31/32, 96.9%) was shown in MSI analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 81.5% (53/65). Compared with the p53 IHC abnormal group, the TP53 mutation group had a higher correlation with high-risk factors. A high level of concordance (31/35, 88.0%) of NGS molecular classification was achieved between curettage specimens and hysterectomy specimens while grade and histotype (including unclassified group) from curettage specimens and hysterectomy specimens showed only moderate levels of agreement, 54.3% (19/35) and 68.6% (24/35), respectively.NGS molecular classification achieved on curettage samples showed high concordance with the final hysterectomy specimens, demonstrating superior to the conventional pathological assessment of grade and histotype and potential utilization in clinical practice.

Purpose The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined. Methods We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored. Results Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025–0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells. Conclusion HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.

e17556 Background: Homologous recombination and DNA repair are important for genome maintenance. Genetic variations in essential homologous recombination genes, including BRCA1 and BRCA2, results in homologous recombination deficiency (HRD) can be a target for therapeutic strategies of ovarian cancer (OC) including poly (ADP-ribose) polymerase inhibitors (PARPi). Here, we proposed an emerging method based on ADx-GSS algorithm to predict HRD status and explore the correlation between HRD status and first-line maintenance therapy of Olaparib in OC patients or Olaparib maintenance therapy in platinum-sensitive relapsed (PSR) OC patients. Methods: Formalin-fixed, paraffin-embedded tissues of 38 consented OC patients between January 2016 and March 2021 were retrospectively collected. Genomic DNA was extracted and subjected to AmoyDx HRD Focus Panel (Amoy Diagnostics Co., Ltd) covering HRD score and BRCA1/2. The HRD score was calculated as the weighted sum of different types of copy number variation (CNV) trained through BRCAness events. Tumors were defined as genomic instability with an HRD score of ≥ 50 (i.e. HRD-positive). The primary endpoint was progression-free survival (PFS), and was assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: Histology of collected samples were mostly serous OC (84.2%). All samples were at stage III-IV (80.84%). The fractions of HRD-positive (n = 26) and HRD-negative (n = 12) group were 68.4%, and 31.6%, respectively. 65.8% (n = 25) of the OC patients had received Olaparib first-line maintenance therapy and 34.2% (n = 13) of PSR patients had received Olaparib maintenance therapy. In December 2021, 34.2% (n = 13) of the whole patients had relapsed. A significant PFS benefit was seen in HRD-positive patients compared with HRD-negative ones (P = 0.0017) or in the first-line maintenance treated population (P = 0.0068). In patients with HRD-positive tumors that did not have BRCA mutations, the PFS benefit was improved versus HRD-negative patients without BRCA mutations. However, Olaparib showed no efficacy difference between HRD-positive and HRD-negative tumor in PSR OC patients. Conclusions: HRD status tested by AmoyDx HRD Focus Panel is significantly correlated with the efficacy of Olaparib, and our results demonstrated a significant PFS benefit for HRD-positive patients compared with HRD-negative patients, especially for patients received Olaparib first-line maintenance therapy.

e17509 Background: Postoperative adjuvant therapy decisions for early-stage cervical cancer (ESCC) without high risk factor, including parametrial extension, positive nodes and positive margins, now depend on Sedlis criteria, which do not mention the degree of differentiation. In this study, we aimed to explore the benefit of adjuvant chemotherapy for patients of ESCC with poor differentiation but without positive Sedlis criteria after radical hysterectomy, and develop a score to predict the recurrence risk in these patients, so as to further improve the indications of postoperative adjuvant therapy for patients of ESCC. Methods: Patients of ESCC with pathologically proven poor differentiation after radical hysterectomy were prospectively included in a multicenter study. Univariate Cox proportional hazards regression were developed to evaluate the independent risk factors for recurrence. The log-rank test was performed to compare the progression-free survival (PFS) and overall survival (OS) of adjuvant chemotherapy (ACT) and no further treatment (NFT) groups. Selected variables were analyzed in a Multivariate Cox Regression Model and used to build a nomogram for ESCC to predict the survival probabilities. Results: In total, 352 patients were randomly assigned to two groups, a training group and a validation group, at a ratio of 1:1 (176 patients: 176 patients). In both of training and validation cohort, the ACT groups had longer PFS than the NFT groups ( P= 0.007 and 0.016, respectively), while the differences of OS were not statistically significant ( P= 0.922 and 0.107, respectively). In the multivariate analysis, ACT was proved an independent prognostic factor for the PFS (P = 0.048), and the strongest predictor of PFS even analyzing with other potential independent prognostic factors (HR 0.116, 95%CI 0.014-0.981). Five factors, including postoperative treatment, histologic type, isthmus uteri involvement, FIGO stage, SCCA level, were included in the nomogram to predict survival probabilities in the training cohort and performed well in the validation cohorts. Conclusions: For the patients of ESCC who don't meet to Sedlis criteria but with poor differentiation, ACT after radical hysterectomy can reduce the recurrence rate.

Study Objective Nonepithelial malignant ovarian tumors are rare in the pediatric and adolescent population. The aim of this study was to observe the spectrum of pathology, presentation, outcome, and risk factors for survival of pediatric nonepithelial malignant ovarian tumors in a Chinese pediatric population. Design, Setting, Participants, Interventions, and Main Outcome Measures This was a retrospective study of 171 girls (median age at presentation of 14 years) diagnosed with primary malignant ovarian tumors between 1990 and 2014 at the Yat-Sen Memorial Hospital and Cancer Center of Sun Yat-sen University. Symptoms, pathological data, treatments, and outcomes were obtained retrospectively from the medical records. Results Most (85.96%, 147/171) tumors occurred in patients aged 10-18 years and most cases were International Federation of Gynecology and Obstetrics stage I (68.42%, 117/171). The predominant pathological type was germ cell tumors (87.13%, 149/171). All patients underwent surgery, and 87 (50.88%, 87/171) underwent conservative incomplete staging surgery (unilateral salpingo-oophorectomy or tumor excision). The 5-year progression-free survival (PFS) was 59.2%. The 5-year overall survival (OS) was 88.7%. Surgical hospital (hazard ratio, 0.388; 95% confidence interval, 0.213-0.706; P = .002) was independently associated with PFS. Recurrence state (hazard ratio, 163.26; 95% confidence interval, 1.321-20,181.875; P = .038) was independently associated with OS. Conclusion Ovarian cancers in children and adolescents have features of good prognosis. Girls who received their first surgery in a tertiary hospital had better PFS. Patients who did not suffer recurrence had better OS.

BACKGROUND The aim of this study was to investigate the advantages and disadvantages of using laparoscopic slip knot with purse-string suture technique in the surgical management of unruptured heterotopic interstitial pregnancies compared with other surgical strategies. MATERIAL AND METHODS We retrospectively analyzed data on 13 patients with unruptured heterotopic interstitial pregnancies who underwent laparoscopy in our hospital between May 2012 and August 2018. The control group consisted of 10 patients who underwent cornual resection or cornuostomy with conventional sutures and knots. The study group consisted of 3 patients whose surgical plans involved use of the slip knot with purse-string suture technique followed by cornuostomy. We evaluated the surgical records and video to comparatively analyze their operation duration, intraoperative blood loss, and pregnancy outcomes. RESULTS The average volume of intraoperative blood loss was 76.67±25 ml in the study group and 215.00±110 ml in the control group. On average, the intraoperative blood loss volume in the study group was 138 ml less than in the control group and the difference was statistically significant (P0.05). There was no statistically significant difference in the live birth rate and operation time between the 2 groups (P0.05). The duration of hemostasis in the study group was 11 min shorter than in the control group, while the duration of cornual electrocoagulation in the study group was 18.5 s shorter. Both groups achieved thorough hemostasis without the help of vasopressin and avoided use of embryo-killing drugs such as methotrexate. Neither group required second surgery or developed postoperative complications such as uterus rupture or persistent ectopic pregnancy. CONCLUSIONS This strategy is safe and reliable for gestational sac clearance while simultaneously preventing any potential harm to the intrauterine embryo. It is particularly suitable for unruptured HIP patients who have a strong desire to preserve their intrauterine embryos.

In a refining complex, an absorption-stabilization process used in the production of end-use petro-products (i.e. stable gasoline and liquefied petroleum gas) is energy-intensive and costly. A new absorption-stabilization process with a two-stage condensation section is introduced in this work to further improve energy-use performance. In the new process, a condenser, a condensed oil tank, and a side-reboiler are integrated into the original process and then a heat integration scheme is performed. Compared with the existing process, the proposed process can reduce the cold utility and hot utility by 17.98% and 25.65%, respectively, as well as decrease the total annual operating costs of the heat exchanger network by 17.48%. Additionally, the process retrofit reduces the annual operating costs of cooling water and steam by about $346,617 at the expense of capital costs around $487,006, and the corresponding payback period is approximately 17 months.

A chemical or petrochemical site is generally made up of several plants that are linked together through process streams. The linking process streams are often cooled down in their source plants, then transferred into storage tanks, and reheated in destination plants. This repeatedly cooling and heating results in low energy-use efficiency and more area installed in heat exchanger network. In this study, we introduce a heat exchanger network superstructure based on stage-wise model for heat integration using hot direct discharges/feeds between plants, and develop a new mixed-integer nonlinear optimization model to simultaneously design heat exchanger network. Unlike conventional HEN design, the model can simultaneously synthesize heat exchanger networks for multiple plants, and be able to address variable supply or target temperatures of process streams. The objective is to minimize total annual cost of heat exchanger networks in source and destination plants. Three examples are used to demonstrate the performance of the proposed model and solution approach. The computational results indicate that the simultaneous design of heat exchanger network for heat integration using hot direct discharges/feeds between plants achieves a significant decrease in total annual cost when compared to the separate design of heat exchanger networks for source and destination plants.

BACKGROUND The aim of this study was to compare magnetic resonance imaging (MRI) and hysteroscopy (HS) for assessing cervical involvement in early-stage endometrial adenocarcinoma in order to establish a more reliable screening method to aid in clinical decision-making. MATERIAL AND METHODS A retrospective analysis was performed on the clinicopathological data from 88 patients with stage I or II endometrial adenocarcinoma who underwent MRI and HS prior to surgery in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Chi-square and Fisher's exact tests were performed to compare the accuracy, sensitivity, specificity, and positive and negative predictive values in the diagnosis of cervical involvement by MRI and HS. The relationship between clinicopathological factors and the deviation of diagnosis by MRI and HS from that by pathology was also analyzed. RESULTS The accuracy of assessing cervical conditions was 93.2% by MRI and 55.7% by HS. Among these variables, the accuracy, specificity, and positive predictive values of MRI were significantly different from those of HS, while the sensitivity and negative predictive values of MRI and HS were not significantly different from each other. Age, tumor size, tumor differentiation, and depth of myometrial invasion were not associated with the differences in cervical assessment between MRI and HS. However, the tumor location may affect assessment by HS. CONCLUSIONS MRI is better than HS for cervical assessment. The negative predictive values of both MRI and HS are high and unsatisfactory.

Cervical cancer is one of the most common types of malignant gynecological tumors worldwide. Let-7g and collagen I have been reported to be involved in the occurrence and development of various cancers, but the clinical significance and biological function of these proteins in cervical squamous cell carcinoma (CSCC) have not been reported. Therefore, this study aimed to determine the underlying roles of let-7g and collagen I in CSCC. Tissue chip, qRT-PCR and western blot assays were used to examine the expression of collagen I in CSCC patients. A dual-luciferase reporter system was used to demonstrate the interaction between let-7g and collagen I. CCK8 and Transwell assays were applied to examine the effects of let-7g and collagen I on cell proliferation, migration and invasion. The results showed that collagen I was obviously increased in CSCC patients. Moreover, it was confirmed that collagen I is the direct target of let-7g. Gain- and loss-of-function experiments, for let-7g and collagen I indicated that let-7g obviously inhibited the proliferation, migration and invasion abilities of CSCC by regulating collagen I. Collectively, these data suggest that let-7g suppresses tumor growth and metastasis by targeting collagen I; therefore, let-7g and collagen I can be considered novel potential therapeutic targets for CSCC.

BTXs (benzene, toluene and xylenes), used widely as basic chemical intermediates, are separated generally from petroleum naphtha, coking naphtha, and pyrolysis gasoline. These oil fractions contain aromatic and non-aromatic hydrocarbons between C5 to C8 in which certain components have approximate boiling points and form azeotropes. Extractive distillation (ED) is one of the most attractive approaches for separating azeotropic mixtures with approximate boiling points. The aromatic ED technique aided by sulfolane used widely in recent years because of its simple process flowsheet, small equipment investment and high energy efficiency. The solvent and operating parameters are the cores of ED process in the economical design. Some results were published to rapidly screen the solvents as well as process parameter optimization for ED separating process, but few contributions have been reported to optimize an extractive distillation from the view of simultaneous optimization of the solvent composition and operation parameters for process economics. In this work, we propose a systematic optimization approach for energy saving of sulfolane aromatic ED processes based on process simulation and genetic algorithm (GA) optimization. The NRTL property method and rigorous unit models in Aspen Plus are used to simulate the ED processes. In particular, considering multi-variable and their interaction, a coordinating strategy is proposed to optimize the solvent composition and significant operating parameters for the ED processes by combining Aspen Plus with MATLAB. Under given separation specifications, the energy consumption and separation efficiency are investigated and optimized by GA optimization. The results show that the through the above optimization, the minimum heating utility of the ED process is significantly reduced by 29.2%.

Cervical cancer (including carcinoma in situ) is the most common malignancy during pregnancy. Neoadjuvant chemotherapy (NACT) with paclitaxel plus cisplatin has been used in patients with cervical cancer successfully, but experience of its prenatal treatment is limited.We report two pregnant women with locally advanced cervical cancer. They were treated with cisplatin plus paclitaxel NACT until fetal pulmonary maturity was achieved, and then accepted cesarean section followed by radical hysterectomy. To minimize the chemo-resistant/radio-resistant tumor cell clones and increase the potencies of NACT, we modified the dose of the chemotherapeutic agents and the treatment interval using cisplatin (50 mg/m(2)) and paclitaxel (75 mg/m(2)) every 2 weeks. Evaluation for clinical response to chemotherapy displayed a partial and complete response, respectively. Both patients had not had any evidence of recurrence for 21 and 13 months. Their children did not have any evidence of malformations and showed normal development at 21 and 13 months of follow-up, respectively.Neoadjuvant chemotherapy with paclitaxel plus cisplatin appears to be feasible and safe for pregnant patients with invasive cervical cancer and infants.

Background The impact of hyperglycemia on survival of patients undergoing neoadjuvant chemotherapy (NACT) for bulky early stage cervical cancer (BESCC) has not been explored. Method Records of patients who received NACT and radical hysterectomy in our institution between January 2005 and June 2010 were reviewed. Results In total, 347 patients were included. The median follow-up time was 37 months (range: 4–65). Patients with hyperglycemia (fasting blood glucose ≥ 100 mg/dl) had shorter recurrence-free survival (RFS) (univariate hazard ratio [HR] = 1.95, 95% confidence interval [CI] [1.16, 3.28], P = 0.010) and cancer-specific survival (CSS) (univariate HR = 2.24, 95% CI [1.33, 3.78], P = 0.002) compared with those with euglycemia (fasting blood glucose

Crude oil distillation unit (CDU) is significant in refinery, and retrofitting a crude oil distillation unit is more common than building a new one as consideration of the enormous investment cost. The process simulation system PRO/II is used to build a rigorous model for the crude oil distillation unit based on the conventional two-furnace and three-column process flow in refinery that addresses both the distillation columns and the heat exchanger network (HEN) simultaneously. The effect of the differences of crude oil properties on the product yield, pumparounds for heat removals, the design of heat exchanger networks and CO2 emissions in crude distillation units is focused. Furthermore, energy use improvement for crude oil distillation units with consideration of light and heavy crude oil is proposed. Based on the investigation carried out on the existing CDU, the optimum operating conditions and retrofitting solutions have been obtained by two actual crude oil distillation units with three columns and corresponding HEN, effectiveness of the retrofits is finally evaluated by means of thermodynamics and economic analysis. The results show that the retrofits required a fixed capital cost of $102925 and $177215 and saving operation cost is about 355226$/year and 656181$/year. The payback time is approximately0.29 and 0.27 year for the retrofits and optimization of light crude oil distillation process and heavy crude oil distillation process.

Miao-fang Wu,1,* Jing Li,1,2,* Huai-wu Lu,1 Li-juan Wang,1 Bing-zhong Zhang,1 Zhong-qiu Lin1 1Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, 2Team-based Learning Group of Clinical Study, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally tothis work Abstract: For many malignant diseases, specialized care has been reported to be associated with better outcomes. The purpose of this study is to investigate the influence of gynecologic oncologists on treatment outcomes for cervical cancer patients treated by radical hysterectomy. Records of patients who received radical hysterectomy between January 2005 and June 2010 were reviewed. Perioperative morbidity, recurrence-free survival, and cancer-specific survival were assessed. Cox regression model was used to evaluate gynecologic oncologists as an independent predictor of survival. A total of 839 patients were included. Of these patients, 553 were treated by gynecologic oncologists, while 286 were treated by other subspecialties. With regard to operative outcomes, significant differences in favor of operation by gynecologic oncologists were found in number of patients receiving para-aortic node sampling and dissection (P=0.038), compliance with surgical guidelines (P=0.003), operative time (P

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.

BACKGROUND AND OBJECTIVE Pelvic lymphocysts are the most common postoperative complications of pelvic lymphadenectomy. Prevention of this disease is more important than treatment. This randomized study was to evaluate the preventive effect of lymph vessel ligation during pelvic lymphadenectomy on pelvic lymphocyst formation. METHODS A total of 39 patients with gynecologic malignancy, who had pelvic lymphadenectomy in the Second Affiliated Hospital of Sun Yat-sen University from July 2006 to January 2007, were randomized into the ligation group (19 patients) and the non-ligation group (20 patients). All patients had no heart disease, hepatopathy, nephronia, pneumonopathy, hypoproteinemia and no history of radiotherapy. All the patients were followed-up with sonographic evaluation and physical examination for lymphocysts and other postoperative complications at 1, 4, 12, and 24 weeks after operation. RESULTS No significant differences were observed between the two groups in pathlogic type, age, height, weight, body surface area, body mass index (BMI), operation duration, estimated blood loss, time to the passage of flatus, total drainage volume, duration of drainage, and duration of hospital stay (P>0.05). The occurrence rate of lymphocysts was significantly lower in the ligation group than in the non-ligation group at one week after operation (26.3% vs. 60.0%, P