The Performance of Artificial Intelligence in Cervical Colposcopy: A Retrospective Data Analysis.

OBJECTIVE: We aimed to evaluate the performance of artificial intelligence (AI) system in detecting high-grade precancerous lesions. METHODS: A retrospective and diagnostic study was conducted in Chongqing Cancer Hospital. Anonymized medical records with cytology, HPV testing, colposcopy findings with images, and the histopathological results were selected. The sensitivity, specificity, and areas under the curve (AUC) in detecting CIN2+ and CIN3+ were evaluated for the AI system, the AI-assisted colposcopy, and the human colposcopists, respectively. RESULTS: Anonymized medical records from 346 women were obtained. The images captured under colposcopy of 194 women were found positive by the AI system; 245 women were found positive either by human colposcopists or the AI system. In detecting CIN2+, the AI-assisted colposcopy significantly increased the sensitivity (96.6% vs. 88.8%, p=0.016). The specificity was significantly lower for AI-assisted colposcopy (38.1%), compared with human colposcopists (59.5%, p < 0.001) or the AI system (57.6%, p < 0.001). The AUCs for the human colposcopists, AI system, and AI-assisted colposcopy were 0.741, 0.765, and 0.674, respectively. In detecting CIN3+, the sensitivities of the AI system and AI-assisted colposcopy were not significantly higher than human colposcopists (97.5% vs. 92.6%, p=0.13). The specificity was significantly lower for AI-assisted colposcopy (37.4%) compared with human colposcopists (59.2%, p < 0.001) or compared with the AI system (56.6%, p < 0.001). The AUCs for the human colposcopists, AI system, and AI-assisted colposcopy were 0.759, 0.674, and 0.771, respectively. CONCLUSIONS: The AI system provided equally matched sensitivity to human colposcopists in detecting CIN2+ and CIN3+. The AI-assisted colposcopy significantly improved the sensitivity in detecting CIN2+.

Baicalin Attenuates YAP Activity to Suppress Ovarian Cancer Stemness.

PURPOSE: This study aims to reveal the mechanism underlying baicalin-suppressing ovarian cancer stemness. METHODS: OVCAR-3 and the primary ovarian cancer cells were used for cell model. The ovarian cancer stem cells were isolated by suspension culture. Cell viability and clonogenicity were examined by CCK-8 assay and colony formation assay. The self-renewal of the cells was evaluated by the determination of sphere-forming capacity and the frequency of in vitro sphere-forming and in vivo tumor-initiating cells. The mRNA and protein levels were relatively quantified by qRT-PCR and Western blot. The transcription regulation of target genes was tested by luciferase reporter assay and a modified nuclear rn-on qRT-PCR assay. RESULTS: Treatment with a non-toxic dose of baicalin significantly inhibited the spherogenicity of ovarian cancer cells. Moreover, a non-toxic dose of baicalin treatment suppressed the frequency of sphere-forming and tumor-initiating ovarian cancer cells. Furthermore, the expression of ovarian cancer stem cell markers (CD133 and ALDH1A1) was inhibited by a non-toxic dose of baicalin treatment. Baicalin inhibits YAP activity and suppresses RASSF6, a positive regulator of YAP, at the transcriptional level. Overexpression of both YAP and RASSF6 abolished the inhibitory effect of baicalin on the proliferation and stemness of ovarian cancer cells. CONCLUSION: The results in this study demonstrated that baicalin suppresses the stemness of ovarian cancer cells by attenuating YAP activity via inhibiting RASSF6 at the transcriptional level. This finding revealed baicalin as a novel YAP inhibitor that could serve as an anti-cancer drug for eradicating ovarian cancer stem cells.

Laparoscopic hepatectomy versus radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis.

Aim: To compare the effectiveness of laparoscopic hepatectomy (LH) with that of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: We conducted a literature search without a language restriction to identify relevant available articles that had been published with the EMBASE and PubMed databases and the Cochrane Library. Studies comparing the outcomes of LH versus RFA for HCC were eligible for inclusion. Results: A total of 10 studies with 1570 patients was included in this meta-analysis. The pooled results revealed that LH was superior to RFA in terms of the 5-year overall survival rate (OR=0.53, 95% CI=0.40, 0.69, p<0.001). In the subgroup analysis of small HCCs, there was still a significantly better 5-year overall survival rate in the LH group compared with the RFA group (OR=0.47, 95% CI=0.33, 0.66, p<0.001). Additionally, the LH group had better 1- and 3-year disease-free survival rate and a lower local recurrence rate, compared with the RFA group. However, the complication rate was higher in the LH group than the RFA group (OR=0.64, 95% CI=0.46, 0.89, p=0.008). Conclusion: Patients who underwent LH had a better long-term prognosis and a lower recurrence rate than those who received RFA. However, we did not obtain conclusive evidence for the superiority of LH over RFA for the treatment of HCCs due to the inclusion of retrospective studies in the present meta-analysis, and well-designed RCTs are needed.

Increasing negative lymph node count is independently associated with improved long-term survival in resectable perihilar cholangiocarcinomas.

To evaluate the prognostic value of numbers of negative lymph nodes (NLNs) for patients with perihilar cholangiocarcinomas.The surveillance, epidemiology, and end results database was used to screen for patients with perihilar cholangiocarcinomas. Kaplan-Meier and Cox regression analyses were used for statistical evaluations. Subsequently, propensity score matching (PSM) was performed to confirm the results.A total of 938 patients with perihilar cholangiocarcinomas met the inclusion criteria. The cut-off number for the grouping of patients with different numbers of NLNs was 17. Both the univariate and multivariate survival analyses demonstrated that there was a significant improvement in terms of cancer-specific survival for patients with >17 NLNs, compared with patients with ≤17 NLNs. Then, the above results were confirmed via a PSM procedure. Additionally, the independent prognostic value of NLNs was evaluated in subgroup univariate and multivariate analyses of patients with stage I or stage II tumors.The numbers of NLNs were evaluated and determined to be important independent prognostic factors for the cancer-specific survival of patients with perihilar cholangiocarcinomas.

A four-miRNA signature as a novel biomarker for predicting survival in endometrial cancer.

BACKGROUND: The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. The aim of this study was to identify new miRNA prognostic biomarkers in endometrial cancer (EC) and to develop an expression-based miRNA signature to provide survival risk prediction for EC patients. METHODS: From TCGA database, the miRNA datasets of EC and clinical information were downloaded in April 2018. Using univariate and multivariate Cox regression analyses identify prognostic factors. Using area under the curve (AUC) of receiver operating characteristic (ROC) curve assess the sensitivity and specificity of prognostic model. RESULTS: 530 patients were randomly divided into training set and testing set. Among 561 differentially expressed miRNAs, 4 miRNAs (miR-4758, miR-876, miR-142, miR-190b) were demonstrated to be predictive biomarkers of overall survival (OS) for EC patients in training set. Based on the risk score of 4-miRNA model, patients in the training set were divided into high-risk and low-risk groups with significantly different OS. This 4-miRNA model was validated in testing and entire set. The AUC for the ROC curves in the entire set was 0.704. Meanwhile, multivariate Cox regression combined with other traditional clinical parameters indicated that the 4-miRNA model can be used as an independent OS prognostic factor. Functional enrichment analysis revealed that these miRNAs are involved in biological processes and pathways that are closely related to cancer. CONCLUSION: A robust 4-miRNA signature as an independent prognostic factor for OS in EC patients was established.

Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta-analysis.

BACKGROUND: TAS-102 has been applied to metastatic colorectal cancer (mCRC) patients who had received at least two prior regimens of standard chemotherapy. This meta-analysis is designed to assess the efficacy and safety of TAS-102 in patients with mCRC. METHODS: We searched randomized controlled trials (RCTs) through PubMed, Embase, Web of Science and Cochrane clinical trial databases and clinicaltrial.gov from database initiation to March 2018. The overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and incidence of adverse events were summarized with the use of hazard ratio (HR) or risk ratio (RR). RESULTS: Three RCTs with 1318 patients were included. Results showed that TAS-102 significantly improved OS (HR 0.70, 95% confidence interval [CI] 0.62-0.79) and PFS (HR 0.46, 95% CI 0.40-0.52) in patients who were intolerant or refractory to fluoropyrimidine, irinotecan and oxaliplatin. The pooled odds ratio of DCR was 4.15 (95% CI 3.18-5.43). Notably, there were significant OS benefits both in patients with KRAS mutation (HR 0.76, 95% CI 0.63-0.92) and those with wild-type KRAS (HR 0.66, 95% CI 0.55-0.79). These benefits were also observed in patients with different numbers of metastatic sites. However, patients with >18 months since the diagnosis of first metastases seemed to have better OS (HR 0.65, 95% CI 0.55-0.77). The most common toxicities associated with TAS-102 were neutropenia (RR 116.51, 95% CI 23.51-577.33), leucopenia (RR 67.70, 95% CI 13.63-336.29), anemia (RR 4.28, 95% CI 2.70-6.79) and diarrhea (RR 5.10, 95% CI 1.40-18.61). CONCLUSION: TAS-102 significantly improves OS, PFS and DCR in refractory mCRC patients with tolerable toxicity. Meanwhile, the OS benefits have nothing to do with KRAS status and the number of metastatic sites.

Early developmental alterations in GABAergic protein expression in fragile X knockout mice.

Fragile X syndrome is the most common heritable form of mental retardation. It is caused by silencing of the Fmr1 gene and the absence of the encoded protein. The purpose of this study was to examine global protein expression levels of GABA(A) and GABA(B) receptors, and GABAergic enzymes and trafficking proteins in fragile X knockout mice during brain maturation. Quantitative western blotting of homogenates of forebrain revealed that the levels of GABA(A) beta1 and beta3, GABA(B)-R1, NKCC1, KCC2, gephyrin and ubiquilin were not significantly different from wild-type mice at any of the postnatal time points examined. In contrast, the GABA(A) receptor alpha1, beta2, and delta subunits, and the GABA enzymes GABA transaminase and succinic semialdehyde dehydrogenase were down-regulated during postnatal development, while GAD65 was up-regulated in the adult knockout mouse brain. The GABA(A) receptor alpha1 and beta2 subunits displayed a divergent pattern of developmental expression whereby alpha1 was reduced in the immature brain but regained a level of expression similar to wild-type mice by adulthood, while the expression of beta2 was similar to wild-types at postnatal day 5 but reduced at day 12 and in the adult brain. The GABA(A) receptor delta subunit and the GABA catabolic enzymes GABA transaminase and succinic semialdehyde dehydrogenase were simultaneously but transiently decreased only at postnatal day 12. Our results demonstrate that GABA(A) receptor subunits and GABA enzymes display complex patterns of changes during brain development suggesting that dynamic interactions may occur between GABA transmitter levels and GABA receptors in fragile X syndrome.