Intraoperative implantation of 125I seeds improves prognosis in refractory stage IIIB cervical cancer: a case report and literature review.

BACKGROUND: Concurrent chemoradiation is the standard treatment for advanced cervical cancer. However some patients still have a poor prognosis, and currently, there is no effective treatment for recurrence. In recent years, 125I seed implantation therapy has emerged as a treatment for advanced malignant tumors including surgically unresectable tumors, residual tumors after surgical resection, and metastatic tumors. However, the use of 125I seeds implantation in primary advanced cervical cancer has not been reported. In this study, we present a case of stage IIIB cervical cancer in a patient who had poor response to radiotherapy and chemotherapy. Subsequently, a radical hysterectomy was performed, and 125I radioactive seeds were successfully implanted during the surgery. This effectively controlled the lesions that were resistant to radiotherapy and had the potential to improve the prognosis. CASE PRESENTATION: A 56-year-old woman was diagnosed with stage IIIB (FIGO 2009) IIIC1r (FIGO 2018) squamous carcinoma of the cervix. After receiving 4 cycles of platinum-based chemotherapy and 30 rounds of radiotherapy, she underwent a radical hysterectomy. The localized cervical lesions were reduced, but there was no reduction in the size of the enlarged pelvic lymph nodes. Therefore, 125I seed implantation was performed under direct surgical vision for the right paracervical lesion and the enlarged pelvic lymph nodes on the right side. During the 18-month follow-up period, the enlarged lymph nodes subsided without any signs of recurrence or metastasis. CONCLUSION: Intraoperative implantation of 125I seeds in lesions that are difficult to control with radiotherapy or in sites at high risk of recurrence is a feasible and effective treatment option for patients with advanced squamous cervical cancer, and it may contribute to improved survival.

Comparison of two 3D reconstruction models for understanding of complicated female pelvic tumors.

OBJECTIVE: Three-dimensional (3D) reconstructed models have been shown to improve visualization in complex female pelvic tumors. Cinematic rendering (CR) is a 3D imaging technique for computed tomography (CT) images, which creates more realistic images with the ability to enhance imaging of anatomical features for diagnosis. This study was set up to compare two types of 3D models and to validate the use of 3D anatomical techniques for the diagnosis of complex female pelvic tumors. METHODS: The preclinical, randomized, two-sequence crossover investigation was performed from December 2022 to January 2023 at First Affiliated Hospital of Chongqing Medical University. Sixteen residents and 10 attending surgeons assessed the cases of 23 patients with two types of 3D model images. The surgeons were randomly assigned to two assessment sequences (CR-3D model group and CT-3D model group). For each case, participants selected one question that probed fundamental questions about the tumor's genesis throughout each assessment period. Following a 4-week washout period, case assessments were transferred to the other image modality. RESULTS: The main result assessment was the accuracy of the answers. The time to answer the questions and the case assessment questionnaire was added as a secondary outcome. The mean scores in the CR-3D models (19.35 ± 1.87) varied significantly from those in the CT-CR group (16.77 ± 1.8) (P < 0.001), and solving the questions in the CT-3D model sequence (41.96 ± 6.31 s) varied significantly from that in the CR-3D model sequence (52.88 ± 5.95 s) (P < 0.001). Subgroup analysis revealed that there were statistically significant variations in the scores of female reproductive tumors, pelvic tumors other than the reproductive system, and retroperitoneal tumors (P = 0.005). Analysis of the assessment questionnaire showed that more surgeons choose CR 3D reconstruction (8.31 ± 0.76 vs 7.15 ± 1.19, P < 0.001). CONCLUSIONS: The results suggest that each 3D reconstruction method has its own advantages. Surgeons feel that CR reconstruction models are a useful technique that can improve their comprehension of complex pelvic tumors, while traditional 3D models have an advantage in terms of speed to diagnosis.

Constructing Cu defect band within TiO2 and supporting NiOx nanoparticles for efficient CO2 photoreduction.

Effectively harnessing solar energy for the conversion of CO2 into valuable chemical energy presents a viable solution to address energy scarcity and climate change concerns. Nonetheless, the limited light absorption and sluggish charge kinetics significantly hinder the photoreduction of CO2. In this study, we employed a facile sol-gel method combined with wetness impregnation to synthesize Cu-doped TiO2 coated with NiOx nanoparticles. Various characterizations verified the successful incorporation of Cu ions into the TiO2 crystal lattice and the formation of NiOx co-catalysts within the composites. The optimal performance attained with CTN-0.5 demonstrates an output of 11.85 µmol h-1 g-1 for CO and 9.51 µmol h-1 g-1 for CH4, which represent a 4.4-fold and 15.6-fold increase, respectively, compared to those achieved with pure TiO2. The induced Cu defect band broadens the light absorption by decreasing the conduction band edge of TiO2, while NiOx upshifts the valence band of TiO2 because of the interaction of valence orbitals. Light irradiation EPR and FTIR tests suggest that the collaboration of CuOx and NiOx promotes the formation of oxygen vacancies/defects and a rapid charge transfer pathway, thereby provides numerous active sites and electrons to enhance CO2 photoreduction performance.

Human Aha1's N-terminal extension confers it holdase activity in vitro.

Molecular chaperones are key components of protein quality control system, which plays an essential role in controlling protein homeostasis. Aha1 has been identified as a co-chaperone of Hsp90 known to strongly accelerate Hsp90's ATPase activity. Meanwhile, it is reported that Aha1 could also act as an autonomous chaperone and protect stressed or disordered proteins from aggregation. Here, in this article, a series of in vitro experiments were conducted to verify whether Aha1 has a non-Hsp90-dependent holdase activity and to elucidate the associated molecular mechanism for substrate recognition. According to the results of the refolding assay, the highly conserved N-terminal extension spanning M1 to R16 in Aha1 from higher eukaryotes is responsible for the holdase activity of the protein. As revealed by the NMR data, Aha1's N-terminal extension mainly adopts a disordered conformation in solution and shows no tight contacts with the core structure of Aha1's N-terminal domain. Based on the intrinsically disordered structure feature and the primary sequence of Aha1's N-terminal extension, the fuzzy-type protein-protein interactions involving this specific region and the unfolded substrate proteins are expected. The following mutation analysis data demonstrated that the Van der Waals contacts potentially involving two tryptophans including W4 and W11 do not play a dominant role in the interaction between Aha1 and unfolded maltose binding protein (MBP). Meanwhile, since the high concentration of NaCl could abolish the holdase activity of Aha1, the electrostatic interactions mediated by those charged residues in Aha1's N-terminal extension are thus indicated to play a crucial role in the substrate recognition.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Nomogram to predict postoperative complications after cytoreductive surgery for advanced epithelial ovarian cancer: A multicenter retrospective cohort study.

Objective: To establish nomograms to predict the risk of postoperative complications following cytoreductive surgery in patients with advanced epithelial ovarian cancer (AEOC). Methods: A multicenter retrospective cohort study that included patients with FIGO stage IIIC-IV epithelial ovarian cancer who underwent cytoreductive surgery was designed. By using univariate and multivariate analyses, patient preoperative characteristics were used to predict the risk of postoperative complications. Multivariate modeling was used to develop Nomograms. Results: Overall, 585 AEOC patients were included for analysis (training cohort = 426, extrapolation cohort = 159). According to the findings, the training cohort observed an incidence of postoperative overall and severe complications of 28.87% and 6.10%, respectively. Modified frailty index (mFI) (OR 1.96 and 2.18), FIGO stage (OR 2.31 and 3.22), and Surgical Complexity Score (SCS) (OR 1.16 and 1.23) were the clinical factors that were most substantially associated to the incidence of overall and severe complications, respectively. The resulting nomograms demonstrated great internal discrimination, good consistency, and stable calibration, with C-index of 0.74 and 0.78 for overall and severe complications prediction, respectively. A satisfactory external discrimination was also indicated by the extrapolation cohort, with the C-index for predicting overall and severe complications being 0.92 and 0.91, respectively. Conclusions: The risk of considerable postoperative morbidity exists after cytoreductive surgery for AEOC. These two nomograms with good discrimination and calibration might be useful to guide clinical decision-making and help doctors assess the probability of postoperative complications for AEOC patients.

Perioperative and Survival Outcomes of Robotic-Assisted Surgery, Comparison with Laparoscopy and Laparotomy, for Ovarian Cancer: A Network Meta-Analysis.

Objective: We aimed to compare the perioperative and survival outcomes of robotic-assisted surgery, traditional laparoscopy, and laparotomy approaches in ovarian cancer. Methods: PubMed, Cochrane Library, Embase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) were searched using multiple terms for ovarian cancer surgeries, including comparative studies in Chinese and English. Literatures are published before August 31, 2021. The outcomes include operating time, estimated blood loss, length of hospital stay, postoperative/intraoperative/total complications, pelvic/para-aortic/total lymph nodes, transfusion, and five-year overall survival rate. The dichotomous data, continuous data, and OS data were pooled and reported as relative risk, standardized mean differences, and hazard ratio HRs with 95% confidence intervals, respectively. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included studies. Results: Thirty-eight studies, including 8,367 patients and three different surgical approaches (robotic-assisted laparoscopy surgery, traditional laparoscopy, or laparotomy approaches), were included in this network meta-analysis. Our analysis shows that the operating time of laparotomy was shorter than laparoscopy. The robotic-assisted laparoscopy has the least estimated blood loss during the surgery, followed by laparoscopy, and finally laparotomy. Compared with laparotomy, the incidence of blood transfusion was lower in the robotic-assisted laparoscopy and laparoscopy groups, and the length of hospital stay is shorter. Laparotomy had a significantly higher incidence of total complications than robotic-assisted laparoscopy and laparoscopy and higher postoperative complications than laparoscopy. For the number of pelvic/para-aortic/total lymph nodes removed by different surgical approaches, our analysis revealed no statistical difference. Our analysis also revealed no significant differences in intraoperative complications and 5-year OS among the three surgical approaches. Conclusion: Compared with laparotomy, robotic-assisted laparoscopy and laparoscopy had a shorter hospital stay, decreased blood loss, fewer complications, and transfusion happened. The 5-year OS of ovarian cancer patients has no difference between robotic-assisted laparoscopy, laparoscopy, and laparotomy groups.

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial.

PURPOSE: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

Endometriosis in para-aortic lymph node resembling a malignancy: a case report and literature review.

BACKGROUND: Endometriosis is a common benign gynecological disease characterized by growing-functioning endometrial tissue outside the uterus. Extra-pelvic endometriosis, which accounts for approximately 12% of endometriosis, is more challenging to diagnose because of its distance from the pelvic organs. Halban's theory of benign metastasis indicates that endometrial cells can appear in extra-pelvic organs via lymphatic and blood vessels, but endometrial lymph node metastasis cases are still rare. We report a case of endometriosis in a para-aortic lymph node whose clinical behavior mimicked a malignancy. CASE PRESENTATION: A 52-year-old perimenopausal woman underwent laparoscopic hysterectomy plus bilateral salpingectomy (the patient insisted on the preservation of her ovaries) at a local hospital 2 years earlier because of adenomyosis. The patient presented with a complaint of low back pain to the gastrointestinal outpatient department of our hospital. The carbohydrate antigen 125 (CA125) was abnormally elevated at 5280.20 U/ml, human epididymis 4 (HE4) was 86.0 pmol/L, while other tumor markers were normal. Serum female hormone results were in the postmenopausal range, and her gastroenteroscopy showed no abnormalities. Moreover, both enhanced magnetic resonance imaging and positron emission tomography-computed tomography showed a high possibility of a retroperitoneal malignant lymph node (metastasis possible, primary site unknown). One week after admission, she underwent laparoscopic exploratory surgery, during which we observed normal shape and size of both ovaries while the left ovary was cystic-solid. After opening the retroperitoneal space, an enlarged lymph node-like tissue measuring 8 × 4 × 3 cm3 was found near the abdominal aorta. When the surrounding adhesions were separated, lymph node-like tissue was poorly demarcated from the abdominal aorta and renal artery. Some lymph node samples and left ovary were sent for intraoperative frozen section, which revealed benign lesions, similar to endometrial tissue. The lymph node tissue was then excised as much as possible, and the second set of intraoperative frozen sections showed high probability of endometrial tissue. The final histopathology and immunohistochemistry staining reached a diagnosis of para-aortic lymph node endometriosis. Gonadotropin-releasing hormone antigen treatment was recommended every 28 days because of the high preoperative CA125 and imaging-based suspicion of malignancy. The serum CA125 subsequently decreased to normal levels, and no para-aortic lesions were detected on abdominal enhancement CT. She is being followed up regularly. CONCLUSION: It is known that the incidence of lymph node metastasis in pelvic endometriosis is relatively rare. Our report shows that endometriotic tissue can metastasize via the lymphatic route and suggests that endometriotic tissue has the characteristics of invasion and metastasis.

Fabrication of a ternary NiS/ZnIn2S4/g-C3N4 photocatalyst with dual charge transfer channels towards efficient H2 evolution.

As a renewable green energy, hydrogen has received widespread attention due to its huge potential in solving energy shortages and environment pollution. In this paper, a one-step solvothermal method was applied to grow ultra-thin g-C3N4 (UCN) nanosheets and NiS nanoparticles on the surface of ZnIn2S4 (ZIS). A ternary NiS/ZnIn2S4/ultra-thin-g-C3N4 composite material with dual high-speed charge transfer channels was constructed for the advancement of the photocatalytic H2 generation. The optimal ternary catalyst 1.5wt.%NiS/ZnIn2S4/ultra-thin-g-C3N4 (NiS/ZIS/UCN) achieved a H2 evolution yield reached to 5.02 mmolg-1h-1, which was 5.23 times superior than that of pristine ZnIn2S4 (0.96 mmolg-1h-1) and even outperform than that of the best precious metal modified 3.0 wt%Pt/ZnIn2S4 (4.08 mmolg-1h-1). The AQY at 420 nm could be achieved as high as 30.5%. The increased photocatalytic performance of NiS/ZIS/UCN could be ascribed to the type-I heterojunctions between intimated ZIS and UCN. In addition, NiS co-catalyst with large quantity of H2 evolution sites, could result in efficient photo-induced charges separation and migration. Furthermore, the NiS/ZIS/UCN composite exhibited excellent H2 evolution stability and recyclability. This work would also offer a reference for the design and synthesis of ternary co-catalyst with heterojunction composite for green energy conversion.

Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study.

BACKGROUND: Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods. METHODS: In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard. FINDINGS: For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886-0·936) in the internal dataset, 0·870 (95% CI 0·822-0·918) in external validation dataset 1, and 0·831 (95% CI 0·793-0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0-90·2] vs 78·3% [72·1-84·5], p<0·0001; 82·7% [78·5-86·9] vs 70·4% [59·1-81·7], p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05). INTERPRETATION: The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists' accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials. FUNDING: National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.

Application of Da Vinci robotic surgery system in cervical cancer: A single institution experience of 557 cases.

OBJECTIVE: Conflicting data have been published regarding the oncologic appropriateness of minimally invasive surgery (MIS) in the treatment of cervical cancer. The purpose of the present study was to investigate whether our experience in the treatment of early cervical cancer using a robotic surgical approach was safe and oncologically effective. METHODS: The data of 557 patients with cervical cancer treated by robotic surgery were retrospectively collected, including the perioperative and survival outcomes. Tumor stage was based on the International Federation of Gynecology and Obstetrics (FIGO 2009). The disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. RESULTS: Of the 557 patients, 196 (35.2%) patients were stage IA1 to IB1, and 304 (54.6%) patients were stage IB2 to I1A2. Also included were 57 (10.2%) patients with either recurrent or persistent disease following concurrent chemoradiotherapy. Two patients (0.4%) experienced severe intraoperative complications and 11 patients (2.0%) developed postoperative complications. A stratified analysis of survival was conducted in 91 patients who met a follow-up time of 3-year or more. The median follow-up time was 49 (range, 6-57) months. Both the 3-year DFS and OS of early-stage (stage IA1 to IB1) cervical cancer were 97.6%. For patients with locally advanced (stage IB2 to IIA2) disease, DFS and OS were 88.1% and 90.5%, respectively. The patients with recurrent or persistent disease had DFS and OS of 62.5%. CONCLUSION: Our study results demonstrated that the robotic surgical approach could achieve satisfying therapeutic outcomes in patients with early-stage cervical cancer, with a low complication rate. For advanced cervical cancer patients with recurrent or persistent disease following concurrent chemoradiotherapy, robotic surgery undertaken as supplementary therapy may improve prognosis. However, there remains a need for additional prospective data reporting long-term survival of cervical cancer patients treated with a robotic surgical approach.

Survival outcomes of minimally invasive surgery for early-staged cervical cancer: A retrospective study from a single surgeon in a single center.

OBJECTIVE: Recent studies have shown that minimally invasive surgery (MIS) is associated with a higher recurrence rate in patients with early-stage cervical cancer. In this study, we aim to report the survival outcomes of patients with early-stage cervical cancer who received MIS, performed in a single center by the same surgeon. METHODS: Eligible participants included patients with early-stage cervical cancer in stage IA1 with lymphovascular space invasion (LVSI+), IA2, and IB1. The surgeries were carried out by a single surgeon and survival outcomes of the 137 patients were evaluated retrospectively. RESULTS: The median follow-up time for the 137 patients was 53 (25-94) months, with the five-year disease-free survival (DFS) rate of 96.4% and the five-year overall survival (OS) rate of 96.8%. Among them, six (4.38%) patients relapsed and four (2.92%) of whom died. The five-year DFS rate was significantly higher in patients with tumor≤2 cm in size than in those with tumor >2 cm (P = 0.013), however, with no significant difference in the five-year OS rate (P = 0.219). CONCLUSION: According to the existing literature and the results of this study, for MIS, the proficiency levels of a surgeon may be associated with survival outcomes of cancer patients. Tumor size may also be an important factor affecting survival outcomes of cervical cancer patients.

Preoperative Conization May Have a Positive Impact on Survival in Early-Stage Cervical Cancer: A Propensity-Matched Study.

INTRODUCTION: A recent prospective randomized study demonstrated that minimally invasive surgery (MIS) was inferior to open surgery in disease survival in early-stage cervical cancer. Our aim was to investigate whether there were survival benefits of preoperative conization prior to MIS for early-stage cervical cancer. METHODS: We retrospectively analyzed patients who eventually underwent definitive MIS with stage IA2 to IB1 (no >2 cm) squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. Preoperatively, the patients were separated into 2 groups: one managed with conization and the other undergoing biopsy without conization. Propensity scoring weight and matching were used to reduce the influence of possible allocation biases. The Cox regression model was used for univariate and multivariate analyses of disease recurrence and survival. RESULTS: 227 patients were contained in this study (99 patients in the conization group and 128 patients in the nonconization group). The 5-year DFS of the conization group was statistically better than that of the nonconization group (98.4% vs. 91.8%, p = 0.011). By univariate analysis, conization (HR = 0.11, 95% CI = 0.01-0.87, p = 0.03) and histologic cell type (p = 0.01) were considered as risk factors for recurrence. Multivariate analysis further confirmed conization (HR = 0.04, 95% CI = 0.01-0.51, p = 0.01) and histologic cell type (p < 0.01) correlated with DFS. After propensity score matching (1:1), 84 patients were included in the conization and nonconization groups, respectively, with 5-year DFS still higher in the conization group (98.3% vs. 92.9%, p = 0.037). The results after univariate and multivariate analyses were consistent with those prior to propensity score matching. CONCLUSION: Preoperative conization in conjunction with MIS seemed to be a safe and feasible approach, with results that may have implications for the reduction of recurrence. Histologic cell type also impacted survival. Therefore, more future prospective studies are warranted.

Hysteroscopic treatment and reproductive outcomes in cesarean scar pregnancy: experience at a single institution.

OBJECTIVE: To study the risk factors leading to type II/III cesarean scar pregnancy and evaluate the efficacy of hysteroscopic treatment and subsequent reproductive outcomes. DESIGN: Retrospective study from 2013 to 2018. SETTING: Inpatient samples. PATIENT(S): A total of 439 patients with cesarean scar pregnancy received hysteroscopic treatment. They were grouped according to the type of surgery as hysteroscopy combined with dilation and curettage, systemic methotrexate followed by hysteroscopy combined with dilation and curettage, and uterine artery embolization or laparoscopic ligation of bilateral uterine arteries followed by hysteroscopy combined with dilation and curettage. Cesarean scar pregnancy was classified as types I, II, and III on the basis of the relationship between the gestational sac and myometrial thickness by ultrasound. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Risk factors leading to type II/III cesarean scar pregnancy. The success of hysteroscopic treatment as well as favorable reproductive outcomes. RESULT(S): The significant variables were multiple parity, prior cesarean section (CS), hysteroscopic therapy, and dilation and curettage after the last CS between type I and type II/III. There were significant differences among the three groups in symptoms, largest diameter of the gestational sac, presence of fetal heartbeat, myometrial thickness, type of cesarean scar pregnancy, blood loss, length of hospital stay, and expense. The rates of complications and success were 8.2% and 93.6%, respectively. Thirty-seven women conceived again, and 22 women completed a term pregnancy with no uterine rupture. The recurrence rate of cesarean scar pregnancy was 10.8%. CONCLUSIONS: The type of cesarean scar pregnancy is related to the rates of multiple parity, cesarean deliveries, and dilation and curettage procedures after the last CS. Hysteroscopic therapy is a safe and effective surgical approach with a low risk of subsequent ectopic pregnancy.

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis.

BACKGROUND: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment. METHODS: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo. RESULTS: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200. CONCLUSION: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.

Single-cell electroporation with high-frequency nanosecond pulse bursts: Simulation considering the irreversible electroporation effect and experimental validation.

To study the electroporation characteristics of cells under high-frequency nanosecond pulse bursts (HFnsPBs), the original electroporation mathematical model was improved. By setting a threshold value for irreversible electroporation (IRE) and considering the effect of an electric field on the surface tension of a cell membrane, a mathematical model of electroporation considering the effect of IRE is proposed for the first time. A typical two-dimensional cell system was discretized into nodes using MATLAB, and a mesh transport network method (MTNM) model was established for simulation. The dynamic processes of single-cell electroporation and molecular transport under the application of 50 unipolar HFnsPBs with field intensities of 9 kV cm-1 and different frequencies (10 kHz, 100 kHz and 500 kHz) to the target system was simulated with a 300 s simulation time. The IRE characteristics and molecular transport were evaluated. In addition, a PI fluorescent dye assay was designed to verify the correctness of the model by providing time-domain and spatial results that were compared with the simulation results. The simulation achieved IRE and demonstrated the cumulative effects of multipulse bursts and intraburst frequency on irreversible pores. The model can also reflect the cumulative effect of multipulse bursts on reversible pores by introducing an assumption of stable reversible pores. The experimental results agreed qualitatively with the simulation results. A relative calibration of the fluorescence data gave time-domain molecular transport results that were quantitatively similar to the simulation results. This article reveals the cell electroporation characteristics under HFnsPBs from a mechanism perspective and has important guidance for fields involving the IRE of cells.

Improved prognosis for recurrent epithelial ovarian cancer by early diagnosis and 125I seeds implantation during suboptimal secondary cytoreductive surgery: a case report and literature review.

BACKGROUND: Epithelial ovarian cancer (EOC) has the worst prognosis in all of gynecologic malignant tumors because of its high recurrence and eventually chemo-resistance. Early diagnosis of recurrence is crucial to avoid diffuse dissemination. Failure of traditional treatment in recurrent epithelial ovarian cancer remains a challenge for clinicians. On the other hand, 125I brachytherapy has been accepted as a useful and hopeful treatment for multiple advanced cancers in recent years. However, its success in advanced epithelial ovarian cancer is limited. Here we report a case of recurrent ovarian cancer who had been early diagnosis of isolated recurrence and successfully treated with 125I seeds implantation during suboptimal cytoreductive surgery. CASE PRESENTATION: A 59-year-old woman presented with recurrent epithelial ovarian cancer who have had a history of ovarian cancer stage IIIB and an R0 resection had been achieved nearly 2 years before presented in our hospital. She underwent suboptimal secondary cytoreductive surgery after four cycles of chemotherapy with little effectiveness and severe chemotherapy-related side effects. Approximately 70% of the cancer-bulk was resected during surgery. For residual lesion which fixed around the right ureter and right external iliac vessel, 125I seeds implantation was performed. Postoperatively, the patient was treated with two cycles of combination chemotherapy with paclitaxel and carboplatin. The patient was free of disease at 26 months' follow-up period. CONCLUSION: In recurrent EOC patients with unresectable isolated lesion, salvage 125I seeds implantation are feasible and may contribute to survival.

Targeted gold nanorods combined with low-intensity nsPEFs enhance antimelanoma efficacy in vitro.

High-intensity nanosecond pulsed electric fields (nsPEFs) are a novel treatment with promising applications for cell stimulation and tissue ablation, and many research studies have shown that gold nanorods (GNRs) are high-conductivity nanomaterials that can enhance electroporation for biomedical applications. In addition, the folic acid (FA) receptor has been demonstrated as a valuable therapeutic target that is highly expressed in a variety of cancers. To reduce the electric field strength required to treat tumors by nsPEFs, for the first time, gold nanorods with folic acid were proposed to achieve higher antimelanoma efficacy at lower electric field intensity in this study. The surface of polyethylene glycol-gold nanorods with good biocompatibility was further modified by folic acid (FA) to provide modified gold nanorods (GNR-PEG-FA) with specific targeted recognition of A375 melanoma cells. The binding of GNRs to A375 melanoma cells was observed by dark field microscopy. After combined treatment with nsPEFs and GNRs, cell viability was evaluated by a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis and the cell cycle. And active caspase 3 was also detected after treatment. The antimelanoma efficacy was enhanced in a pulsed electric field-dependent manner. More importantly, compared with the group of nsPEFs alone and gold nanorods without FA, treating cells with nsPEFs combined with GNR-PEG-FA resulted in a lower percentage of viable cells, higher percentages of necrosis and apoptosis and higher concentration of active caspase 3 and induced cell cycle arrest in S phase, effectively inhibiting the proliferation of A375 melanoma cells. nsPEFs combined with GNR-PEG-FA showed the best antimelanoma efficacy in vitro and effectively killed melanoma cells with low-intensity nsPEFs. The combined treatment of cells with nsPEFs and GNR-PEG-FA is expected to become a safer and more efficient physical treatment of melanomas.