Predictive value of number of metastatic lymph nodes and lymph node ratio for prognosis of patients with FIGO 2018 stage IIICp cervical cancer: a multi-center retrospective study.

BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Comparative analysis of serum and saliva samples using Raman spectroscopy: a high-throughput investigation in patients with polycystic ovary syndrome and periodontitis.

BACKGROUND: Polycystic ovary syndrome (PCOS) and periodontitis significantly affect women's oral and systemic health worldwide, and yet increase the risk of cardiovascular-metabolic diseases like diabetes and coronary heart disease. Regarding the PCOS-periodontitis connection, whether sex hormones, metabolic and inflammatory mediators could account for the underlying linking mechanism needs to be further investigated. This case-control study evaluated the hormonal, metabolic and inflammatory profiles in PCOS and non-PCOS subjects with various periodontal conditions, via assessing serum and saliva samples by Raman spectroscopy. METHODS: A total of 66 females with PCOS and 22 systemically healthy female volunteers were recruited in a single hospital. Full-mouth periodontal examination was undertaken for identifying the subjects with periodontal health, gingivitis or periodontitis. The datasets of sex hormones and metabolic indicators were retrieved from the hospital information system. Both serum and saliva samples were collected for detecting inflammatory mediators and Raman spectroscopic assessment. The subjects were categorized into four groups according to their conditions of PCOS and periodontitis for Raman spectroscopic analysis. Partial least squares discriminant analysis was performed to examine the inter-group differences in Raman spectra. RESULTS: PCOS patients exhibited greater mean probing depth (P < 0.05) and higher serum levels of triglycerides (P < 0.05) and matrix metalloproteinase-8 (P < 0.05) than those in non-PCOS participants. Both probing depth and triglyceride level were positively correlated with PCOS (P < 0.05). There was a significant difference in mean Raman spectra of saliva samples among the four groups with different conditions of PCOS and periodontitis (P < 0.05), while no significant inter-group difference existed in serum samples. CONCLUSIONS: The present study shows that periodontal condition may affect the biomolecular profiles of Raman spectra in serum and saliva of PCOS patients. It underscores the importance of the collaborative teamwork of dentists and gynecologists for enhancing women's oral health, general wellbeing and quality of life.

Initial treatment for FIGO 2018 stage IIIC cervical cancer based on histological type: A 14-year multicenter study.

BACKGROUND: To compare the oncological outcomes of radical chemotherapy (R-CT), abdominal radical hysterectomy (ARH), and neoadjuvant chemotherapy and radical surgery (NACT) for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC cervical cancer, according to histological types: squamous cell carcinoma (SCC) and adenocarcinoma (AC)/adenosquamous cell carcinoma (ASC). METHODS: A comparison of 5-year overall survival (OS) and disease-free survival (DFS) was performed for the SCC and AC/ASC subgroups for the three initial treatments, assessed using Kaplan-Meier and Cox proportional hazards regression analysis and validated using propensity score matching (PSM). RESULTS: The study included 4086 patients: R-CT, n = 1913; ARH, n = 1529; and NACT, n = 644. AC/ASC had a lower survival rate (63.7%) than SCC (73.6%) and a higher recurrence and mortality rate (36.3% and 26.4%, respectively). The 5-year OS and DFS rates were different in the SCC group for R-CT, ARH, and NACT (OS: 69.8% vs. 80.8% vs. 73.0%, p < 0.001; DFS: 66.7% vs. 70.7% vs. 56.4%, p < 0.001), also in the AC/ASC group (OS: 46.1% vs. 70.6% vs. 55.6%, p < 0.001; DFS: 42.7% vs. 64.6% vs. 40.8%, p < 0.001). As for initial treatment, survival outcomes were worse for AC/ASC treated with R-CT and ARH than for SCC (both p < 0.05), with no group differences between the two treated with NACT. CONCLUSION: Initial treatment influences oncological prognosis for patients with FIGO 2018 stage IIIC cervical cancer. ARH is an alternative treatment for stage IIIC cervical SCC and AC/ASC, and NACT needs to be chosen with caution, moreover, R-CT for AC/ASC requires careful selection.

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.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study.

PURPOSE: To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. METHOD: We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2 cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. RESULTS: In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). CONCLUSION: Among patients with low-risk cervical cancers < 2 cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

The Effect of Laparoscopic Radical Hysterectomy Surgical Volume on Oncology Outcomes in Early-Stage Cervical Cancer.

Purpose: To examine the association between surgical volume and surgical and oncological outcomes of women with stage IB1 cervical cancer who underwent laparoscopic radical hysterectomy (LRH). Methods: We retrospectively analyzed the oncological outcomes of 1,137 patients with stage IB1 cervical cancer receiving LRH from 2004 to 2016. The surgical volume for each surgeon was defined as low [fewer than 50 surgeries, n = 392(34.5%)], mid [51-100 surgeries, n = 315(27.7%)], and high [100 surgeries or more, n = 430(37.8%)]. Surgical volume-specific survival was examined with Kaplan-Meier analysis, multivariable analysis, and propensity score matching. Results: The operative times of the high-volume group (227.35 ± 7.796 min) were significantly shorter than that of the low- (272.77 ± 4.887 min, p < 0.001) and mid-volume (255.86 ± 4.981 min, p < 0.001) groups. Blood loss in the high-volume group (169.42 ± 8.714 ml) was significantly less than that in the low-volume group (219.24 ± 11.299 ml, p = 0.003). The 5-year disease-free survival (DFS) and overall survival (OS) in the low-volume, mid-volume, and high-volume groups were similar (DFS: 91.9, 86.7, and 89.2%, p = 0.102; OS: 96.4, 93.5, and 94.2%, p = 0.192). Multivariable analysis revealed surgical volume was not an independent risk factor for OS or DFS. The rate of intraoperative and postoperative complications was similar among the three groups (p = 0.210). Conclusions: Surgical volume of LRH may not be a prognostic factor for patients with stage IB1 cervical cancer. Surgery at high-volume surgeon is associated with decreased operative time and blood loss.

Association between premature ovarian insufficiency and gut microbiota.

BACKGROUND: Premature ovarian insufficiency (POI) is characterized by impairment of ovarian function on a continuum before the age of 40 years. POI is affected by multiple factors. Considering new insights from recent gut microbiome studies, this study aimed to investigate the relationship between gut microbial community structure and POI. METHODS: Subjects were recruited at the Shenzhen Maternity & Child Healthcare Hospital. Fecal microbial community profiles of healthy women (n = 18), women with POI (n = 35) were analyzed using 16S rRNA gene sequencing based on Illumina NovaSeq platform. RESULTS: Compared to the controls, the serum levels of FSH, LH, T and FSH/LH ratio significantly increased in women with POI, whereas E2 and AMH decreased significantly. Higher weighted UniFrac value was observed in POI women compared with healthy women. Phylum Firmicutes, genera Bulleidia and Faecalibacterium were more abundant in healthy women, while phylum Bacteroidetes, genera Butyricimonas, Dorea, Lachnobacterium and Sutterella enriched significantly in women with POI. Moreover, these alterations of the gut microbiome in women with POI were closely related to FSH, LH, E2, AMH level and FSH/LH ratio. CONCLUSIONS: Women with POI had altered microbial profiles in their gut microbiome, which were associated with serum hormones levels. These results will shed a new light on the pathogenesis and treatment for POI.

There is a Strong Association between Early Preeclampsia and Congenital Heart Defects: A Large Population-Based, Retrospective Study.

OBJECTIVE: The aim of this study was to determine the prevalence of congenital heart defects and examine their association with preeclampsia (PE). METHODS: A clinical-based, retrospective study was conducted in Shenzhen between 2004 and 2017. Data were collected from Shenzhen Maternal and Child Health Hospital Medical Record Database. This study included all infants who were born at the hospital with or without heart defects and their mothers (N = 177,434 newborns). Data processing and analysis were performed by SPSS23.0 (Chicago, IL, USA). RESULTS: 6,852 women (3.9%) were diagnosed as PE and 1,289 newborns (7.30 per 1,000) have congenital heart disease (CHD). Prevalence of CHD in newborns of women with PE is 15.8 per 1,000 significantly higher than the overall prevalence (7.30 per 1,000). CHD in newborns has strong association with PE, especially early-onset PE (adjusted OR 3.29 and 95% CI 2.15-5.03) and severe PE (adjusted OR 2.75 and 95% CI 2.13-3.56). Among those with CHD, infants of preeclamptic women had higher prevalence of tetralogy of Fallot (43.78 vs. 28.14 per 100,000), atrial septal defect (335.67 vs. 53.93 per 100,000), ventricular dysplasia (102.16 vs. 89.69 per 100,000), and ventricular septal defect (525.39 vs. 212.22 per 100,000) than pregnant women with non-PE. CONCLUSION: PE, especially early-onset PE and severe PE, is strongly associated with offspring CHD. Our results help advance the current understanding of the association between PE and offspring CHD. So preventing PE and reducing PE may have a beneficial effect on the offspring CHD.

Development of a lateral flow recombinase polymerase amplification assay for rapid and visual detection of Cryptococcus neoformans/C. gattii in cerebral spinal fluid.

BACKGROUND: For definitive diagnosis of cryptococcal meningitis, Cryptococcus neoformans and/or C. gattii must be identified within cerebral spinal fluid from the patients. The traditional methods for detecting Cryptococcus spp. such as India ink staining and culture are not ideal. Although sensitive and specific enough, detection of cryptococcal antigen polysaccharide has a high dose hook effect. Therefore, the aim of this study was to introduce a new rapid and simple detection method of Cryptococcus neoformans and C. gattii in cerebral spinal fluid. METHODS: The lateral flow strips combined with recombinase polymerase amplification (LF-RPA) assay was constructed to detect the specific DNA sequences of C. neoformans and C. gattii. The detection limit was evaluated using serial dilutions of C. neoformans and C. gattii genomic DNA. The specificity was assessed by excessive amount of other pathogens genomic DNA. The optimal detection time and amplification temperature were also analyzed. The diagnostic parameters were first calculated using 114 clinical specimens and then compared with that of other diagnostic method. A brief analysis and comparison of different DNA extraction methods was discussed, too. RESULTS: The LF-RPA assay could detect 0.64 pg of genomic DNA of C. neoformans per reaction within 10 min and was highly specific for Cryptococcus spp.. The system could work well at a wide range of temperature from 25 to 45 °C. The overall sensitivity and specificity were 95.2 and 95.8% respectively. As amplification template for LF-RPA assay, both cell lysates and genomic DNA produce similar experimental results. CONCLUSIONS: The LF-RPA system described here is shown to be a sensitive and specific method for the visible, rapid, and accurate detection of Cryptococcus spp. in cerebral spinal fluid and might be useful for clinical preliminary screening of cryptococcal meningitis.

The significance of polymorphism and expression of oestrogen metabolism-related genes in Chinese women with premature ovarian insufficiency.

The aim of this study was to investigate whether polymorphism and expression of CYP17, CYP1A1, COMT and SULT1A1 affected the risk of idiopathic primary ovarian insufficiency (POI) in Chinese women. DNA sequencing and real-time PCR were used to detect these genes in 132 cases of idiopathic POI and 132 normal women. A significant increase in the C allele of CYP17 (rs743572) polymorphism was observed in women with POI compared with controls (PFDR = 0.046). A significant decrease was observed in the C allele of CYP1A1 (rs4646903) in women with POI compared with controls (PFDR = 0.004). The A allele of COMT (rs4680) polymorphism was more frequent in women with POI compared with controls (PFDR = 0.029). The genotypic frequency of SULT1A1 (rs9282861) was not significantly different between the two groups. For the relative expression of CYP17 and COMT were statistically significant (both PFDR = 0.066), with false discovery rate controlled at 0.1. No significant difference was observed in the RNA levels of CYP1A1 and SULT1A1 between the two groups. The frequency of expression of the CYP17 T/C variant tended to be higher and the A allele of COMT polymorphism together with down-regulation of its mRNA expression may be more frequent in Chinese women with idiopathic POI.

[Association of FOXE1 gene polymorphism with idiopathic premature ovarian failure].

OBJECTIVE: To assess the influence of length of the alanine tract of forkhead box E1 (FOXE1) gene on genetic susceptibility to idiopathic premature ovarian failure (POF). METHODS: Totally 110 patients with idiopathic POF were recruited between February 2009 and December 2012 at the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University. Controls (n = 110) were individuals with normal menstrual cycles, normal FSH concentrations. The polyalanine tract and flanking sequence of FOXE1 were screened using the multiplex ligation-dependent probe amplification (MLPA) technique and direct sequence technique. RESULTS: The most frequent of FOXE1 polyalanine stretch length was 14 residues in both groups. The length of FOXE1 polyalanine reported in this study varied from 12 to 16 alanines, and three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. The most common genotypes were 14/14 homozygote, occurring with the frequency of 81.8% (90/110) in the POF group, while 96.4% (106/110) in control subjects, respectively. The incidence of 14/14 genotypes of FOXE1-polyalanine was significantly lower in patients with POF (χ² = 119.730, P = 0.001) in comparison to the controls. There were significantly higher frequencies of the 16/16 genotypes in cases with POF [10.0% (11/110) versus 0; χ² = 3.403, P = 0.001], as compared with the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group than the controls [84.5% (186/220) versus 98.2% (216/220); χ² = 25.923, P = 0.001]. The FOXE1 16 alanine allele was significantly more common in the POF patient group than the controls [12.7% (28/220) versus 1.8% (4/220); χ² = 19.412, P = 0.001]. CONCLUSIONS: The polymorphism of the polyalanine tract of FOXE1 gene have a certain relevance for the genetic aetiology of idiopathic POF.

[Application of video endoscopic inguinal lymphadenectomy in radical vulvectomy for carcinoma].

OBJECTIVE: To evaluate the feasibility and safety of applying video endoscopic inguinal lymphadenectomy via hypogastric subcutaneous approach (VEIL-H) in the treatment of vulvar carcinoma. METHODS: From September 2009 to December 2012, 15 patients with vulvar carcinoma underwent VEIL-H plus radical vulvectomy at many participating hospitals. RESULTS: All were treated surgically. Two of them underwent laparoscopic pelvic lymphadenectomy (LPL) upon the positive results of parotid operations with frozen section. The mean operative duration of VEIL-H (bilateral groin) were (80.8 ± 2.9) minutes. The mean total volume of blood loss in VEIL was (5.5 ± 0.4) ml, the mean drainage duration (6 ± 2) days and the average postoperative hospitalization (11 ± 4) days. The mean follow-up period was 13.0 months. One patient suffered local recurrence at Month 2 postoperation. CONCLUSION: VEIL-H is both feasible and safe in inguinal lymphadenectomy.

FOXE1 polyalanine tract length screening by MLPA in idiopathic premature ovarian failure.

BACKGROUND: FOXE1 is one of the candidate genes for genetic predisposition to premature ovarian failure (POF) and it contains an alanine tract. Our purpose is to assess the influence of length of the alanine tract of FOXE1 on genetic susceptibility to POF. METHODS: The group studied consisted of 110 Chinese patients with idiopathic POF and 110 women from normal controls. The polyalanine tract and flanking sequence of FOXE1 was screened using the Multiple Ligation-dependent Probe Amplification (MLPA) technique and directly sequenced. RESULTS: Three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. There were significantly lower frequencies of the 14/14 genotypes in cases with POF (X2 = 119.73, P = 0.001), as compared with the controls. The incidence of 16/16 genotypes of FOXE1-polyalanine was significantly higher in patients with POF (X2 = 3.403, P = 0.001) in comparison to the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group (186/220) than the controls (216/220) (X2 = 25.923, P = 0.0001). The FOXE1 16 alanine allele was significantly more common in the POF patient group (28/220) than the controls (4/220) (X2 = 19.412, P = 0.0001). CONCLUSION: This finding provides evidence that polyalanine repeat expansions in FOXE1 may be responsible for the genetic aetiology of POF in Chinese women.

Identification of novel missense mutations of the TGFBR3 gene in Chinese women with premature ovarian failure.

The aim of this study was to assess the association between human transforming growth factor ß receptor, type III (TGFBR3) and idiopathic premature ovarian failure (POF) in a Chinese population. A total of 112 Chinese women with idiopathic POF and 110 normal controls were examined. DNA samples prepared from blood leukocytes were used as templates for polymerase-chain reaction amplification of DNA fragments from TGFBR3. The gene fragments were sequenced. Web-based programs, including PolyPhen, Sorting Intolerant from Tolerant (SIFT), Prediction of Pathological Mutations (PMUT), ScanProsite and ClustalW2, were used to predict the potential functional and structural impacts of the missense variants of TGFBR3. A total of 11 novel variants were identified. Among them, six were found only in the POF patients. Two missense variants, p.E459G and p.P825L, which are conserved in primates, were predicted to have functional and structural impacts on the TGFBR3 protein. The other four variants (c.381+12A>C, c.2431-7A>G, p.S172S and p.C220C) were considered benign. However, further functional studies are necessary to confirm these findings.