Effect of 5-aminolevulinic acid photodynamic therapy versus loop electrosurgical excision procedure for cervical intraepithelial neoplasia grade 2 treatment.

BACKGROUND: Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat high-grade squamous intraepithelial lesions. However, the clinical efficacy and safety of these two therapies have rarely been compared. Thus, this study aimed to compare the clinical efficacy and safety of the two treatment regimens. METHODS: One hundred and twenty patients in two groups (60 + 60) with grade 2 cervical intraepithelial neoplasia (CIN2) were voluntary treated with photodynamic therapy or LEEP between June 2020 and December 2022. Follow-up was conducted at 3, 4-6, and 7-12 months after treatment. RESULTS: Although the total effective rate of LEEP was higher during the first 6 months after treatment, both the total effective rate of lesion degradation and the double-negative rate of high-risk HPV16/18 and liquid-based cervical cytology by ALA-PDT treatment increased with time and finally exceeded those of LEEP at 7-12 months. CONCLUSIONS: ALA-PDT may be more promising than LEEP for treating patients with CIN2 because of the better CIN2 degradation and high-risk HPV negativity, less damage, and greater fertility conservation, especially after 6 months.

Incidence, prognostic factors, and a nomogram of cervical cancer with lung metastasis: A SEER-based study.

AIMS: The purpose of this study was to investigate the incidence, survival and prognostic factors of cervical cancer with lung metastasis at the initial diagnosis and to develop a visual nomogram to predict the prognosis of these patients. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2015. After strict inclusion and exclusion, the chi-square test was used to evaluate the differences in the clinical characteristics of patients with cervical cancer, and then we used Kaplan-Meier method to perform survival analysis among cervical cancer patients with lung metastasis. Next, univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors of these patients and we developed a visualized and novel nomogram to judge the prognosis. RESULTS: 476 patients with lung metastasis and 12,016 patients without lung metastasis were included in this study. The incidence of lung metastasis was higher in unmarried white cervical cancer patients between the ages of 40 and 60, and grade III cervical squamous cell carcinoma patients were more likely to have lung metastasis. In addition, grade, surgery, radiotherapy, sequence of surgery and radiotherapy and chemotherapy were significantly related to the outcomes of cervical cancer patients with lung metastasis. Furthermore, our nomogram could predict the 3-year and 5-year overall survival (OS) of these patients. Finally, the AUC of 3-year OS and 5-year OS were confirmed to be 0.969 and 0.939 respectively by ROC curves, with good consistency. CONCLUSIONS: Age at diagnosis, race, marital status, and characteristics of the tumor can influence the incidence of lung metastasis in cervical cancer patients. Besides, grade, surgery, radiotherapy, sequence of surgery and radiotherapy and chemotherapy may deeply affect the prognosis of cervical cancer patients with lung metastasis. The nomogram built in this study may help clinicians to formulate individualized treatment strategies and encourage the development of more and more comprehensive and accurate predictive models.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

Efficacy and cost-effectiveness analysis of pretreatment percutaneous endoscopic gastrostomy in unresectable locally advanced esophageal cancer patients treated with concurrent chemoradiotherapy (GASTO 1059).

BACKGROUND: We launched a single-arm phase II study to determine the efficacy and cost-effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco-regional objective response rate (ORR), loco-regional progression-free survival (LRFS), overall survival (OS), and toxicities. A 3-state Markov model was applied for cost-effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). RESULTS: Sixty-three eligible patients received pretreatment PEG-based CCRT. The mean change of weight during CCRT was -1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco-regional ORR and 1-year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco-regional ORR (p = 0.036) and longer 1-year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost-effectiveness ratio of $3457.65 per quality-adjusted life-years (QALY) compared with the ONS group with a probability of cost-effectiveness of 77.7% at the $10,000 per QALY willingness-to-pay threshold. CONCLUSION: Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost-effective because of its significant clinical benefits.

Analysis of systemic inflammatory and coagulation biomarkers in advanced cervical cancer: Prognostic and predictive significance.

OBJECTIVE: Peripheral systemic inflammatory, nutritional, and coagulation biomarkers have prognostic and predictive value in various malignancies. We evaluated the prognostic and predictive roles of systemic inflammatory, nutritional, and coagulation biomarkers in the circulating blood of patients with advanced cervical cancer. METHODS: A retrospective study of 795 patients with cervical cancer who received concurrent chemoradiation therapy was performed. Overall survival was evaluated by the Kaplan-Meier estimator. Univariate and multivariate Cox regression models were used to determine prognostic factors associated with overall survival. RESULTS: The median follow-up time was 76 months. In the univariate analysis, overall survival showed positive prognostic value in patients with a platelet-to-lymphocyte ratio (PLR) <164.29 (P = 0.010), and a plasma fibrinogen (FIB) level <4 g/L(P = 0.012). In the multivariate analysis, the PLR (P = 0.036), and FIB level (P = 0.047) maintained their significance for overall survival. Therefore, the PLR and FIB levels are independent prognostic factors in patients with advanced cervical cancer. CONCLUSIONS: Systemic inflammatory and coagulation biomarkers could help to understand survival differences in the clinical treatment of advanced cervical cancer. The PLR and FIB levels are independent prognostic factors of poor survival in patients with advanced cervical cancer.

Incidence, prognostic factors and a nomogram of cervical cancer with distant organ metastasis: a SEER-based study.

This study was to investigate the incidence, survival and prognostic factors of cervical cancer with distant organ metastasis, and to develop a nomogram to predict the prognosis of cervical cancer. We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2014. The chi-squared test was used to analyse the differences in clinical characteristics, and we used Kaplan-Meier methods to perform survival analysis. Univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors, and we developed a visual nomogram to judge the prognosis. We found that lung metastasis was the most common in cervical cancer patients with distant organ metastasis. Age, race, characteristics of the tumour, and therapy should be considered when analysing the prognosis of cervical cancer patients. The findings of this study may help clinicians to formulate individualised treatment strategies.Impact StatementWhat is already known on this subject? Distant organ metastasis of cervical cancer mainly involves lung, bone, liver and brain. Once it occurs, the survival and prognosis will be threatened seriously.What the results of this study add? 4176 patients were included, and lung metastasis was the most common in cervical cancer with distant organ metastasis (3.5%). Additionally, age, race, tumour grade, histological type, T-stage, N-stage, lung, liver and bone metastasis and the treatment mode are significantly related to the outcomes of cervical cancer patients. Furthermore, we developed a nomogram that could predict the probability of three-year and five-year OS.What the implications are of these findings for clinical practice and/or further research? The findings of this study may drive more and more studies focussing on the comprehensive prognostic assessment, diagnosis, and treatment of distant metastasis of cervical cancer. Besides, clinicians can utilise these findings to formulate individualised treatment strategies.

Apigenin induces apoptosis and counteracts cisplatin-induced chemoresistance via Mcl-1 in ovarian cancer cells.

Ovarian cancer (OC) is one of the prominent causes of mortality in female patients diagnosed with gynecologic malignancies. While it has previously been demonstrated that apigenin inhibits cell growth in colon and breast cancer cells, the effect of apigenin in OC cells is not fully understood. Therefore, the aim of the present study was to investigate the impact of apigenin on cell death and resistance to cisplatin in OC cells. It was found that apigenin inhibited proliferation, hindered cell cycle progression and promoted SKOV3 cell apoptosis. Moreover, these effects were also observed in cisplatin-resistant SKOV3/DDP cells. Furthermore, apigenin reduced the mitochondrial transmembrane potential, and elevated the ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the two cell types. Reverse transcription-quantitative PCR and western blotting results demonstrated that apigenin significantly downregulated Mcl-1 at the transcriptional and translational levels in SKOV3 and SKOV3/DDP cells, which was responsible for its cytotoxic functions and chemosensitizing effects. Collectively, the present results identified the impact of apigenin on OC cell death and resistance to cisplatin, and the potential molecular mechanisms. However, additional studies are required to further elucidate the underlying mechanisms.

Application of 5-aminolevulinic acid photodynamic therapy for vaginal intraepithelial neoplasia, a report of six cases.

BACKGROUND: Vaginal intraepithelial neoplasia (VAIN) has a high-risk for recurrence and may precede genital cancers, such as vaginal cancer and/or other invasive diseases. Human papillomavirus (HPV)-induced VAIN may occur after loop electrosurgical excision procedures (LEEPs) or panhysterectomy. 5-aminolevulinic acid (ALA) photodynamic therapy (ALA-PDT) has demonstrated utility in preventing the recurrence of cervical intraepithelial neoplasia (CIN); however, evaluation of its effect on VAIN has not been performed. METHODS: The effectiveness of ALA-PDT was evaluated in 6 women diagnosed with HPV-induced VAIN. Lesion treatment was performed 3 h after ALA using light at a wavelength of 635 nm and light density of 80 mw/cm2. Therapeutic effect was assessed using HPV-DNA tests combined with liquid-based cervical cytology (LCT). RESULTS: Six women, aged 49-54 years, who were diagnosed VAIN grade 1/2 or 2 after LEEP or panhysterectomy or no surgery underwent ALA-PDT (range, 4-8 treatments). Four of the 6 women were HPV negative on retesting 3-4 months after ALA-PDT. Most patients exhibited no signs of recurrence during the follow-up period. CONCLUSIONS: Direct use of ALA-PDT or after panhysterectomy did not necessarily lead to a negative result; however, ALA-PDT after LEEP or panhysterectomy combined with LEEP yielded a satisfactory curative effect on VAIN. Although recurrence rates need to be monitored in longer-term studies, the absence of post-treatment complications in this study supports the potential utility of the technique.

Multicenter surveillance study of surgical site infection and its risk factors in radical resection of colon or rectal carcinoma.

BACKGROUND: Colorectal surgery is associated with high rates of surgical site infection (SSI). We investigated SSI in radical resection of colon or rectal carcinoma and its epidemiological distribution in 26 hospitals in China. METHODS: We conducted prospective surveillance of patients who underwent radical resection of colon or rectal carcinoma in 26 selected hospitals from January 2015 to June 2016.An information system monitored all of the surgical inpatients. Infection control professionals observed the inpatients with suspected SSI who had been screened by the system at the bedside. The infection status of the incisions was followed up by telephone 1 month after the operation. RESULTS: In total, 5729 patients were enrolled for the two operations; SSIs occurred in 206 patients, and the infection rate was 3.60%. The incidence of SSI after radical resection of rectal carcinoma (5.12%; 119/2323) was 2.1 times higher than that after radical resection of colon carcinoma (2.55%; 87/3406) (P < 0.0001). Additionally, in the colon versus rectal groups, the rate of superficial incisional SSI was 0.94% versus 2.28% (P < 0.0001), the rate of deep incisional SSI was 0.56% versus 1.11% (P = 0.018), and the rate of organ space SSI was 1.06% versus 1.72% (P = 0.031), respectively. The most common pathogens causing SSIs after radical resection of colon carcinoma were Escherichia coli (21/38) and Pseudomonas aeruginosa (5/38). Escherichia coli (24/65) and Enterococcus spp. (14/65) were the two most common pathogens in the rectal group. The multivariate logistic regression analysis showed that only the operating time and number of hospital beds were common independent risk factors for SSIs after the two types of surgery. CONCLUSION: This multicenter study showed that there were significant differences in the incidence of SSIs, three types of SSIs, and some risk factors between radical resection of colon carcinoma and rectal carcinoma.

Novel triazole analogs of apigenin-7-methyl ether exhibit potent antitumor activity against ovarian carcinoma cells via the induction of mitochondrial-mediated apoptosis.

Ovarian cancer is one of the main causes of cancer-associated mortality across the world. Currently, ovarian cancer is mainly treated with chemotherapy. However, ovarian cancer is detected at advanced stages and chemotherapy has numerous side effects. In addition, the results of current chemotherapy on the treatment of ovarian cancer are less than satisfactory. Therefore, there is an urgent need to develop novel and more viable chemotherapeutic agents that can be used to treat ovarian cancer. The present study was designed to synthesize a series of novel triazole analogs of the bioactive apigenin-7-methyl ether to evaluate its anticancer activity against three human ovarian cancer cell lines. A total of eight novel triazole derivatives were synthesized and screened for their anticancer activity. Of all the derivatives, a derivative named 3d exhibited significant and dose-dependent anticancer activity against the SKOV3 ovarian cancer cell line. The IC50 of 3d was found to be 10 µM against the SKOV3 cancer cell line. It was also observed that 3d induced apoptosis in SKOV3 cancer cells through the accretion of reactive oxygen species and reduction in mitochondrial membrane potential. The molecule also modulated the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein. Taken together, these results showed that the apigenein-7-methyl ether novel derivative 3d may prove an important lead molecule for the treatment of ovarian cancer.

Mechanistic Study of the Inhibitory Effect of Kaempferol on Uterine Fibroids In Vitro.

BACKGROUND This study examined the effect of kaempferol on uterine fibroids in vitro and the underlying mechanism, and investigated the potential of kaempferol as a clinical drug for the treatment of uterine fibroids. MATERIAL AND METHODS Uterine fibroid tissue and surrounding smooth muscle tissue were collected for primary culture. Different concentrations of kaempferol (12 µM, 24 µM, and 48 µM) were used to treat the cells for 24, 48, and 72 hours. Ethanol was used in the control group. A CCK-8 colorimetric assay was used to detect cell proliferation. Real-time PCR and immunoblot were used to detect estrogen receptor (ER), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) levels in mRNA and protein. RESULTS The differences in proliferation at different time points and concentrations of kaempferol were statistically significant. The inhibitory effect of kaempferol on mRNA levels of ER and IGF, and protein levels of ER, VEGF, and IGF-1 were positively correlated with kaempferol concentration. Changes in kaempferol concentration showed no effect on VEGF mRNA expression. Treatment with kaempferol significantly lowered myocardin levels in uterine fibroid tissue compared to normal uterine smooth muscle (P<0.05). CONCLUSIONS Kaempferol might be used for clinical treatment of uterine fibroids due to its inhibitory effect on the proliferation of uterine fibroids cells.