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.

The pathological risk score: A new deep learning-based signature for predicting survival in cervical cancer.

PURPOSE: To develop and validate a deep learning-based pathological risk score (RS) with an aim of predicting patients' prognosis to investigate the potential association between the information within the whole slide image (WSI) and cervical cancer prognosis. METHODS: A total of 251 patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IA1-IIA2 cervical cancer who underwent surgery without any preoperative treatment were enrolled in this study. Both the clinical characteristics and WSI of each patient were collected. To construct a prognosis-associate RS, high-dimensional pathological features were extracted using a convolutional neural network with an autoencoder. With the score threshold selected by X-tile, Kaplan-Meier survival analysis was applied to verify the prediction performance of RS in overall survival (OS) and disease-free survival (DFS) in both the training and testing datasets, as well as different clinical subgroups. RESULTS: For the OS and DFS prediction in the testing cohort, RS showed a Harrell's concordance index of higher than 0.700, while the areas under the curve (AUC) achieved up to 0.800 in the same cohort. Furthermore, Kaplan-Meier survival analysis demonstrated that RS was a potential prognostic factor, even in different datasets or subgroups. It could further distinguish the survival differences after clinicopathological risk stratification. CONCLUSION: In the present study, we developed an effective signature in cervical cancer for prognosis prediction and patients' stratification in OS and DFS.

Risk factors and long-term impact of urologic complications during radical hysterectomy for cervical cancer in China, 2004-2016.

OBJECTIVE: The primary objective was to describe the incidence and risk factors of urologic complications during radical hysterectomy for cervical cancer. The secondary objective was to investigate the impact of urologic complications on long-term survival. METHODS: Patients who underwent radical hysterectomy for cervical cancer from 2004 to 2016 were identified in the MSCCCC (Major Surgical Complications of Cervical Cancer in China) database. Data on demographic characteristics, clinical characteristics, hospital characteristics and urologic complications were collected. Multivariable logistic regression was used to assess the risk factors of urologic complications and Cox proportional hazards models were performed to identify prognostic factors. RESULTS: A total of 21,026 patients undergoing radical hysterectomy for cervical cancer were identified. The incidence of any urologic complications was 1.54%: 83 (0.39%) ureteral injuries, 17 (0.08%) bladder injuries, 1 (0.005%) ureteral injury combined with bladder injury, and 223 (1.05%) genitourinary fistulas. In a multivariable analysis, surgery at a women and children's hospital (OR = 2.26, 95% CI 1.47-3.48), surgery at a facility in a first-tier city (OR = 2.08, 95% CI 1.24-3.48), and laparoscopic surgery (OR = 4.68, 95% CI 3.44-6.36) were associated with a higher risk of urologic complications. Cox proportional hazards models revealed that the occurrence of urologic complications was a significant predictor of 2-year overall survival (OR = 1.78, 95% CI = 1.09-2.92), but was not a predictor of 5-year overall survival (OR = 1.27, 95% CI = 0.83-1.94). CONCLUSION: The incidence of urologic complications during radical hysterectomy is low. The risk of urologic complications may be higher for patients who are treated at a women and children's hospital, are treated in first-tier city hospitals, and receive laparoscopic surgery. Urologic complications have an impact on short-term survival, but not on long-term survival.

Influence of graphene oxide and reduced graphene oxide on the activity and conformation of lysozyme.

The dramatically different bio-effects of graphene and graphene oxide (GO) have been widely observed in diverse biological systems, which determine the applications and toxicity of graphene materials. To elucidate the mechanism at molecular level, it is urgent to investigate the enzyme-graphene interaction and its consequences. In this study, we comparatively studied the influence of GO and reduced GO (RGO) on the activity and conformation of lysozyme to provide better understandings of their different bio-effects. Both GO and RGO adsorbed large quantities of lysozyme after incubation. GO inhibited lysozyme activity seriously, while RGO nearly had no influence on the enzyme activity. The different inhibitions of enzyme activity could be explained by the lysozyme conformational changes, where GO induced more changes to the protein conformation according to UV-vis absorbance, far-UV circular dichroism spectra, intrinsic fluorescence quenching, and infrared spectra. Based on the spectroscopic changes of lysozyme, GO induced the loss of secondary structure and exposed the active site of lysozyme more to the aqueous environment. In addition, neither GO nor RGO induced the fibrillation of lysozyme after 12d incubation. The results collectively indicated that the oxidation degree significantly impacted the enzyme-graphene interaction. The implications to the designs of enzyme-graphene system for bio-related applications and the toxicological effects of graphene materials are discussed.