Treatment for locally resectable stage IIIC1r cervical cancer: surgery or chemoradiotherapy?

OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.

Kynureninase knockdown inhibits cisplatin resistance in vivo and in vitro and impacts the prognosis of cervical adenocarcinoma.

BACKGROUND: Chemotherapy resistance is a leading cause of treatment failure in cases of cervical adenocarcinoma (ADC), and no effective treatment approach has yet been found. We previously identified the differentially expressed kynureninase (KYNU) mRNA in cervical adenocarcinoma cells (HeLa) and cervical adenocarcinoma cisplatin resistance cells (HeLa/DDP) using gene chips. However, the role and potential mechanism of KYNU in the cisplatin resistance of cervical adenocarcinoma remain unclear. METHODS: We verified the expression of KYNU in the cells and tissues of ADC patients and analyzed its correlation with patient prognosis. A stable HeLa/DDP cell line with KYNU mRNA knockdown was constructed. We then used a CCK8 assay to detect cell survival, a transwell assay to evaluate cell migration and proliferation and flow cytometry to measure apoptosis. The effect of KYNU silence on cisplatin sensitivity was evaluated in an orthotopic model of metastatic ADC. Immunohistochemistry was performed to determine the changes in relevant drug resistance-associated protein expression, aiming to explore the underlying mechanism of KYNU-mediated drug resistance. RESULTS: KYNU is overexpressed in HeLa/DDP cells and tissues and is associated with the poor prognoses of patients with ADC. After KYNU mRNA knockdown, the invasion, migration, and proliferation of HeLa/DDP cells in the cisplatin environment significantly reduced, while the apoptosis rate of HeLa/DDP cells significantly increased. Meanwhile, KYNU knockdown improved the DDP sensitivity of ADC in vivo. Furthermore, silencing KYNU decreased the expressions of CD34 and the drug-resistance related proteins P-gp, MRP1, and GST-π and increased the level of the proapoptotic regulatory protein Bax. CONCLUSION: KYNU deficiency enhanced DDP sensitivity by suppressing cell proliferation, migration, and invasion and promoting apoptosis in DDP-resistant ADC cells in vitro. Furthermore, KYNU knockdown improved the drug sensitivity of ADC in vivo. The results showed that KYNU is involved in the chemotherapy resistance of cervical adenocarcinoma.

The Therapeutic Value of Adjuvant Chemotherapy after Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to evaluate the therapeutic value and treatment-related complications of adjuvant chemotherapy after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). DESIGN: The medical records of LACC patients who underwent CCRT were reviewed retrospectively. METHODS: A total of 1,138 patients with LACC who had been treated at our hospital between January 2013 and December 2017 were included in the study and classified into two groups: the CCRT group, comprising 726 patients who had received only CCRT, and the CCRT + adjuvant chemotherapy (ACT) group, comprising 412 patients who had received three cycles of adjuvant chemotherapy after CCRT. 39 patients in the CCRT group and 50 patients in the CCRT + ACT group had undergone lymphadenectomy, which revealed pathology-positive lymph nodes in 22 patients and 35 patients, respectively. Progression-free survival (PFS), overall survival (OS), and adverse events were compared. RESULTS: The median follow-up time was 61 months (range: 2-96 months). No significant differences in PFS and OS were found between the two groups (p > 0.05), but more grade 3-4 acute hematologic toxicities were observed in the CCRT + ACT group than in the CCRT group (24.8% vs. 31.8%, p = 0.01). A subgroup analysis of patients with pathology-positive lymph nodes showed that the 5-year PFS and OS rates were 76.5% and 74.9%, respectively, for the CCRT + ACT group and 45.0% and 49.2%, respectively, for the CCRT group; the differences were statistically significant (p = 0.015 and 0.042, respectively). LIMITATIONS: First, the sample size of the subgroup of patients with pathology-positive lymph nodes was too small for a confirmative conclusion. The heterogeneous population and the selection bias resulting from the retrospective design were the other flaws of our study. CONCLUSION: The application of adjuvant chemotherapy after CCRT may be worth investigating further for women with LACC and pathology-positive lymph nodes, but this approach is associated with an increase in acute hematology toxicities.

Consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy.

OBJECTIVE: Post-operative concurrent chemoradiotherapy has become the standard treatment for patients with positive lymph nodes after radical surgery. The aim of this study was to explore the efficiency and safety of consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy. METHOD: We reviewed the medical records of patients with early-stage cervical cancer with lymph node metastasis after radical hysterectomy from January 2010 to January 2017. All patients underwent adjuvant concurrent chemoradiotherapy (n=49) or three cycles of platinum-based consolidation chemotherapy following concurrent chemoradiotherapy (n=89). The primary end points of the study were disease-free survival and overall survival. RESULTS: The median follow-up time was 51 months (range 10-109). No significant difference was noted in disease-free survival, overall survival, or grade 3/4 gastrointestinal disorder between the consolidation chemotherapy group (78.1% vs 83.1% vs 6.7%) and the concurrent chemoradiotherapy alone group (75.4% vs 75.3% vs 4.1%), (p=0.42, 0.26, 0.80, respectively). However, the grade 3/4 myelosuppression rate in the consolidation group was higher than in the concurrent chemoradiotherapy alone group (40.4% vs 22.4%, p=0.03). For patients with >3 positive lymph nodes or patients with >2 positive lymph nodes+lymphovascular space invasion/≥1/3 stromal invasion, disease-free survival and overall survival were superior in the consolidation chemotherapy group compared with the concurrent chemoradiotherapy alone group (p<0.05). CONCLUSION: In patients with >3 positive lymph nodes or patients with >2 positive lymph nodes, lymphovascular space invasion, and greater than 1/3 stromal invasion, disease-free survival and overall survival were superior with consolidation chemotherapy. However, consolidation chemotherapy was also associated with an increased grade 3/4 myelosuppression rate.

Effects of Different Lengths of Ti Nanorods Topography on Mesenchymal Stem Cell Growth and Proliferation.

Total hip and knee arthroplasty have being successfully performed in world-wide in recent years. However, poor osseointegration between implant (polish surface) and host bone tissue is one of the main causes for aseptic loosening in Ti-based materials and result in failure. Fabricating nanotopography is a promising method to improve cell behaviors and promote osseointegration. Ti nanorods array of vary lengths have been produced via selective corrosion of Ti substrate using electrochemical anodization technique on titanium surface. In this study, we investigated the murine bone mesenchymal stem cell (MSC) behaviors in response to these different lengths of nanorods. The result showed that the nanorod of 100 nm length increased MSCs adhesion and proliferation. Increased elongation of cytoskeleton actin was also observed on 100 nm height, which resulted in substantially up-regulation of alkaline phosphatase (ALP) activity, suggesting greater bone-forming ability than control Ti. The Ti nanorods of 100 nm length may be a promising implant surface to improve the osseointegration.

[Study on the clinicopathologic features of 88 cases with mucinous cervical adenocarcinoma].

OBJECTIVE: To analyze the clinicopathologic features of mucinous cervical adenocarcinoma (ADC) and supply some reference for its diagnosis, treatment and prognosis. METHODS: Totally 88 cases with primary mucinous ADC diagnosed between January 2003 and December 2007 in Jiangxi Maternal and Child Health Hospital were retrieved. Their clinical and pathological data were reviewed and analyzed. RESULTS: Among 88 patients, 70 cases of them were endocervical ADC, 11 cases were minimal deviation adenocarcinoma (MDA), 2 cases were intestinal subtype and 5 cases were villoglandular ADC. The positive rate of cervical Pap smear cytology was only 28% (10/36). There were 10 cases were performed several times of cervical Pap smear cytology test and biopsies, while still no abnormality was found. Finally, 7 cases of them were diagnosed by cervical excisional biopsy and endocervical curettage, including 5 cases with endocervical ADC and 2 cases with MDA; 2 cases (1 case with stage Ib1 endocervical ADC and 1 case with Ib1 MDA) were diagnosed by cold knife conization, and 1 case with stageIb1 endocervical were diagnosed by uteroscopically directed biopsy. The overall 5-year survival rate was 60.0%. Using univariate analysis results showed that age (P = 0.046), stage (P = 0.007), tumor size (P = 0.007) and therapeutic methods (P = 0.009) were significant prognostic factors. Multivariate analysis showed that therapeutic methods was an independent predictor for survival (P = 0.013). Stage IIb-IIIb MDA patients occupied 7/11 of all MDA patient, while there was only one such patient of 5 cases with villoglandular ADC. The overall HPV infection rate was 65% (57/88), and there was no obvious differences about the HPV infection rates among different types of mucinous ADC. CONCLUSIONS: Cervical smear cytology is of little significance to the diagnosis of mucinous cervical adenocarcinoma. Early stage mucinous ADC is difficult to be detected, especially for MDA. Cervical excisional biopsy, endocervical curettage, cold knife conization, uteroscope are beneficial to its diagnosis. Therapeutic methods is an important prognostic factor for mucinous ADC and comprehensive treatment should be given to those patients with risky postsurgical factors.

[Application of transvaginal external fascia trachelectomy in the treatment of CIN and micro-invasive cervical cancer].

OBJECTIVE: To explore the feasibility and safety of transvaginal external fascia trachelectomy to conservatively treat patients with stage Ia1 squamous carcinoma of the uterine cervix (SCC) and cervical intraepithelial neoplasia (CIN) III, who are not suitable to take cold knife conization (CKC). METHODS: From July 2002 to September 2010, those patients who had a strong desire to preserve the uterus or fertility but also are confronted with following situations received transvaginal external fascia trachelectomy: CIN III with large area lesion (colposcopically observed lesion area was larger than 3/4 of the cervix), or patients with CIN II-III suffered recurrence or had persistent lesion or positive margin after CKC or LEEP, or patients with CIN II-III upgraded into stage Ia1 SCC through LEEP and pathological confirmation (except for those with lymphovascular space invasion), or CIN III patients complicated with upper vaginal intraepithelial neoplasia (VAIN). Their clinical information and data were reviewed and analyzed. RESULTS: Among the 79 cases, who underwent transvaginal external fascia trachelectomy, six were stage Ia1 SCC, 61 were CIN III with a large area lesion (23 cases had glandular involvement), three were CIN III complicated with VAIN, six were CIN III with persistent lesion after LEEP, two were CIN III with positive margins after LEEP, and one case had recurrence after conization. The median age of these patients was 33 years old, ranging from 23 to 40 years old. The mean operation time was 39 min (rang 20-60 min), the average amount of bleeding was 40 ml (rang 1-300 ml) and the mean hospital stay was 10 d ( rang 6-17 d). The CIN III patients complicated with VAIN received this surgery with resection of the adjacent vaginal mucosa more than 2 cm in 3.8% (3/79). The median follow-up time was 49 months (8-85 months) and none of these patients had ureteral injury or large amount of intraoperative or postoperative bleeding or post-operative recurrence. No patient complained any effect on their sexual life. Among the five patients with reproductive desire, one was at her 22 w gestation after one induced abortion and one spontaneous abortion, four patients experienced term birth in which three were cesarean section and one was natural labour. CONCLUSIONS: Transvaginal external fascia trachelectomy is a safe and effective conservative treatment for stage Ia1 SCC, CIN III with large area lesion, CIN III complicated with VAIN and CIN II-III suffering recurrence, persistent lesion or positive margins after CKC and others that are not suitable to take CKC.

[A randomized controlled trial of two chemotherapy regimens (paclitaxel liposome combined with platinum and paclitaxel combined with platinum) in concurrent chemoradiotherapy for cervical carcinoma].

OBJECTIVE: To compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on the survival rate in patients with cervical carcinoma receiving concurrent chemoradiotherapy. METHODS: One hundred and sixty two cases with primary cervical carcinoma diagnosed and treated in the Jiangxi Maternal and Children Hospital between January 2008 and November 2009 were enrolled in this randomized controlled trial. Seventy one cases were included in the paclitaxel group and 91 in the paclitaxel liposome group. The chemotherapy doses were as followings: paclitaxel liposome and paclitaxel 135 mg/m(2); cisplatin 80 mg/m(2) or carboplatin AUC 4 - 6, repeated every 21 days for two or three times. Radical radiotherapy was given to both groups at the same time. The efficacy was evaluated by the tumor regression and the patients were followed-up for six months. RESULTS: The overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89.0%, respectively (P > 0.05). The 1-year cumulative survival rate was 91.4% for the paclitaxel group and 89.2% for the paclitaxel liposom group (P > 0.05). The incidence rate of adverse effects such as rash, gastrointestinal toxicity, bone marrow suppression and muscle/joint pain in the paclitaxel liposome group was significantly lower than that in the paclitaxel group (P < 0.05), while there was no significant difference regarding the hair loss, liver damage, and peripheral neuritis (P > 0.05). CONCLUSIONS: Paclitaxel liposome plus platinum is a safe and effective therapeutic regimen for stage IIa-IV cervical carcinoma. However, the long-term efficacy of this regimen should be further observed.