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Shaobo Duan,1 Ye Zhang,1 Shuang Xu,1 Pei Jiang,1 Qinghua Qi2 1Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Qinghua Qi, Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China, Email qiqinghua333@sina.comObjective: To investigate the predictive role of contrast-enhanced ultrasonography (CEUS) plus D-dimer levels in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods: CEUS was applied to assess lymph nodes in 186 patients with confirmed DLBCL. The clinical data and laboratory indicators were collected from these patients, and a retrospective analysis was conducted on the relationship between the quantitative parameters of CEUS (TTP, PI, AUC, WOT), D-dimer levels, and clinical features of the DLBCL patients. The Cox regression model was used for univariate and multivariate analyses for the risk factors associated with the prognosis.Results: There was an increase of D-dimer levels in advanced DLBCL patients, who were combined with a significant reduction in TTP and WOT and a significant increase in PI and AUC. D-dimer levels and quantitative parameters of CEUS were strongly correlated with the Ann Arbor, B symptoms, International Prognostic Index (IPI), LDH and CRP levels. The results of the Cox regression model indicated that D-dimer levels, TTP and PI, the quantitative parameters of CEUS, were important prognostic factors for DLBCL.Conclusion: CEUS results and D-dimer levels can be used as independent prognostic factors for DLBCL.Keywords: diffuse large B-cell lymphoma, contrast-enhanced ultrasonography, D-dimer, prognosis

Qingqing Qi,1 Qingxu Song,2 Yufeng Cheng,2 Nana Wang2 1Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Nana WangDepartment of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaEmail wangna03@163.comBackground: Prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are the most common factors to estimate nutritional and inflammatory status. The aim of this study is to systematically evaluate the prognostic significance of above nutritional and inflammatory indexes for overall survival (OS) and surgical complications in esophageal cancer patients.Methods: Esophageal cancer patients who underwent esophagectomy were retrospectively collected. PNI, NLR, PLR, and SII were introduced to evaluate the baseline nutritional and inflammatory status.Results: A total of 407 patients were included in the present study. Kaplan–Meier survival analysis revealed that PNI-low group, NLR-high group and PLR-high group, all showed a significantly shorter OS (34.38% vs 49.46%, P < 0.001; 36.13% vs 48.26%, P = 0.026 and 33.33% vs 48.52%, P = 0.001 respectively), while no significant difference was found in SII groups (42.33% vs 46.31%, P = 0.067). Multivariable analyses identified PNI (P = 0.002) was an independent prognostic factor for OS, but NLR (P = 0.672) and PLR (P = 0.186) were not. Postoperative complications occurred significantly more frequently in the low-PNI group (29.69% vs 13.26%, P < 0.001). However, no significant differences were found in the postoperative complication rates between different NLR (16.67% vs 22.69%, P = 0.124), PLR (18.03% vs 19.61%, P = 0.867) and SII (15.34% vs 20.49%, P = 0.326) groups. Multivariate logistic regression analysis showed only PNI (P = 0.008) was an independent prognostic factor for postoperative complications.Conclusion: Preoperative low PNI was not only an independent prognostic factor for worse survival in esophageal cancer patients but also associated with high incidence of postoperative complications.Keywords: esophageal cancer, prognostic nutritional index, prognosis, postoperative complications

Qi Qi,* Xuemeng Qian,* Xinfang Zhu, Jiajing Cai, Rong Xia, Qi Zhang Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Xia; Qi ZhangDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, People’s Republic of ChinaEmail xiarongcn@126.com; friday0451@163.comPurpose: Blood loss may be corrected with red blood cell transfusion, but may ultimately contribute to negative impacts. This study was a retrospective analysis to assess the impact of perioperative blood transfusion on hospital stay days in liver cancer patients.Methods: We retrospectively examined data from patients with primary liver cancer who underwent curative resection. Patients were divided into perioperative blood transfusion (PBT) and non-PBT groups. Data were given as means and SDs for continuous variables and as counts and percentage for categorical variables. The correlation between blood transfusion and hospital stay days was analyzed by Fisher’s exact test. Multivariable logistic regression analyses were used to identify independent predictors of length of hospital stays.Results: Totally 206/1031 patients (20.3%) were given perioperative transfusion. The mean length of hospital stay was 17.8 days in PBT and 13.9 days in non-PBT groups. Our multivariable logistic regression showed transfusion, total bilirubin, indirect bilirubin, and the ratio of albumin to bilirubin were all indicators of the length of hospital stay days. Perioperative transfusion was also associated with prolonged length of hospital stays (95% CI: 0.395– 0.811, p = 0.002). Transfusion also affected intrinsic coagulation factors (activated partial thromboplastin time, fibrinogen, platelet), inflammatory index (neutrocyte to lymphocyte ratio, monocyte), albumin and bilirubin levels.Conclusion: Perioperative transfusion of blood was associated with a significantly increased length of hospital stays probably via changing intrinsic coagulation and inflammatory factors and bilirubin levels in plasma.Keywords: primary liver cancer, transfusion, length of hospital stays, bilirubin, coagulation factor, inflammatory factor

Xi Yang,1 Miao Da,2 Wenyuan Zhang,3 Quan Qi,4 Chun Zhang,5 Shuwen Han4 1Department of Intervention and Radiotherapy, Huzhou Central Hospital, 2Medical College of Nursing, Huzhou University, 3Department of Gynaecology, 4Department of Medical Oncology, 5Department of Infectious Diseases, Huzhou Central Hospital, Huzhou, Zhejiang Province, People’s Republic of China Abstract: Cervical cancer is a common malignant cancer among women worldwide. Changes in the vaginal microecological environment lead to multiple gynecological diseases, including cervical cancer. Recent research has shown that Lactobacillus may play an important role in the occurrence and development of cervical cancer. This review explores the role of Lactobacillus in cervical cancer. A total of 29 articles were included after identification and screening. The pertinent literature on Lactobacillus in cervical cancer from two perspectives, including clinical studies and experimental studies, was analyzed. An association network for the mechanism by which Lactobacillus induces cervical cancer was constructed. In addition, we provide direction and insight for further research on the role of Lactobacillus in cervical cancer. Keywords: CIN, cervical cancer, Lactobacillus, microorganism

Introduction: Hepatocellular carcinoma (HCC), a prevalent and aggressive form of cancer, poses significant challenges due to its limited therapeutic options. This study aims to leverage multi-omics data from liver cancer to identify potential therapeutic targets for HCC., Methods: We employed an integrative approach by analyzing various omics datasets related to liver cancer. Through comprehensive data mining and analysis, we identified key genes that are significantly associated with HCC. To gain insights into their biological roles and underlying mechanisms, we constructed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway networks. Specifically, we focused on genes that exhibited high expression levels in HCC and were correlated with poor patient prognosis. Among these, CDK1 and DLGAP5 emerged as promising candidates and were further investigated for their potential involvement in tumor immune cell infiltration and HCC progression., Results: Our analysis revealed that CDK1 and DLGAP5 are highly expressed in HCC tissues compared to normal liver tissues, and their elevated expression is associated with unfavorable clinical outcomes. Furthermore, through GO and KEGG pathway analyses, we found that these genes are implicated in critical biological processes and signaling pathways relevant to HCC pathogenesis. Notably, CDK1 and DLGAP5 were shown to be associated with tumor immune cell infiltration, suggesting their potential role in modulating the tumor microenvironment and promoting HCC progression., Discussion: These findings provide valuable insights into the development of novel therapeutic approaches for HCC., Competing Interests: The authors declare no conflicts of interest., (© 2024 Li et al.)

Purpose: Treatment options for refractory metastatic colorectal cancer (CRC) are scarce. This retrospective study aimed to evaluate the efficacy and safety of raltitrexed combined with S-1 and bevacizumab in patients with heavily pretreated metastatic CRC in a clinical real-world setting., Patients and Methods: Records of patients with metastatic CRC refractory to standard therapies who initiated raltitrexed plus S-1 and bevacizumab from October 2017 to December 2021 were retrospectively reviewed at our institution. The study endpoints included median overall survival (OS), overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs)., Results: Forty-four patients with metastatic CRC, who had previously undergone standard chemotherapy received the regimen comprising raltitrexed plus S-1 and bevacizumab. As of March 2022, the median follow-up was 23.2 months (95% confidence interval 15.8-30.6). The median OS and median PFS were 13.5 (95% CI 9.9-17.1) and 4.7 months (95% CI 3.6-5.8), respectively, with a 16-week PFS rate of 60.9%. Among 43 patients with measurable lesions, the ORR and DCR were 7.0% (3/43) and 65.1% (28/43), respectively. Patients without peritoneal metastases (P = 0.003, hazard ratio 0.160, 95% CI 0.048-0.531), lower carcinoembryonic antigen level (≤42.8 ng/mL) (P = 0.039, HR 0.382, 95% CI 0.153-0.952), and no previous treatment with both vascular endothelial growth factor inhibitors (VEGF) and S-1 (P = 0.020, HR 0.215, 95% CI 0.059-0.785) had better OS. The incidence of any grade of treatment-related AEs was 88.6%, most of which were mild to moderate, and no treatment-related deaths occurred., Conclusion: Raltitrexed combined with S-1 and bevacizumab shows promising antitumor activity and safety and could be an alternative for patients with metastatic CRC who are refractory or intolerant to standard therapy., Competing Interests: All authors have no conflict of interest regarding this study., (© 2023 Liu et al.)

Introduction: Currently, there is no consensus on the specific effect of Extrathyroidal Extension (ETE) on prognosis. The purpose of our study was to study the relationship between different states of ETE and its disease-free survival rate and to determine the basic standard of Micro ETE (tumor extends through capsule only) in risk stratification., Material and Methods: We conducted a retrospective and single-center study that included the clinical data of all papillary thyroid carcinoma (PTC) patients with ETE in our hospital from 2013 to 2017 and followed them up after rigorous screening. According to ETE state, it is divided into four groups: Microscopic, Micro, Minimal, Macro. Kaplan-Meier method was used to calculate disease-free survival (DFS). Log-rank test was used to compare the differences between the groups and to polt the survival curves. P<0.05 was considered statistically significant. Micro ETE was included in different risk stratification subgroups and their DFS was compared., Results: A total of 436 patients were included: Microscopic group N=50 (11.47%), Micro group N=74 (16.97%), Minimal group N=135 (30.96%), and Macro group N=177 (40.60%). The frequency of ETE was in strap muscles N=191, trachea N=114, laryngeal recurrent nerve N=92, and capsule N=74, etc. The 5-year DFS rate in Micro group was 95.3%, higher than that in Macro group (P<0.05). The 5-year DFS rate of Micro ETE was 90.0% in the intermediate-risk group and 84.9% in the high-risk group when Micro ETE was included in different risk stratification subgroups., Conclusion: Micro ETE deserves more attention, has a batter prognosis than Macro ETE, and may have little effect on recurrence. It seems more appropriate to treat Micro ETE as the intermediate-risk group in risk stratification., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 He et al.)

Background: Cleavage stimulation factor 2 (CSTF2) encodes a nuclear protein that is implicated in the development of various cancers. However, the role of CSTF2 in hepatocellular carcinoma (HCC) has not been understood. This study aims to explore the function of CSTF2 in HCC., Methods: The expression, diagnostic capability, prognostic value, and immune cell effect of CSTF2 in HCC were explored using various databases. The expression level of CSTF2 were validated in our cell lines. The effect of CSTF2 on hepatocarcinogenesis was explored by CSTF2 silencing., Results: CSTF2 expression was significantly elevated in HCC and correlated with multiple clinicopathological characteristics. CSTF2 exhibited good diagnostic capability in discriminating HCC samples from nontumorous samples. High CSTF2 expression was significantly related to poor overall survival. Univariate and multivariate Cox regression analyses suggested that CSTF2 expression was an independent risk factor for HCC. These results were validated in ICGC cohorts. In addition, the nomogram based on CSTF2 showed better predictive performance than the AJCC staging system in TCGA and ICGC cohorts. Functional enrichment analysis revealed that CSTF2-related genes were involved in DNA/RNA processing and the cell cycle. In addition, we found that CSTF2 expression was closely related to the levels of various infiltrating immune cells, especially neutrophils. Moreover, some immune checkpoints had positive relationships with CSTF2 expression. CSTF2 silencing inhibited proliferation, invasion and migration, and promoted apoptosis in HepG2 cells. Western blotting analysis revealed that CSTF2 silencing inactivated the Wnt/β-catenin signaling pathway., Conclusion: High CSTF2 expression not only correlates with unfavorable outcomes but also affects immune cell infiltration and immune checkpoint expression in HCC. CSTF2 silencing can alleviate the malignant phenotypes of hepatic cancer cell by inactivating the Wnt/β-catenin signaling pathway. These results indicate that CSTF2 can serve as a promising prognostic marker and therapeutic target for HCC patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Zhang et al.)

Background: Macrophage receptor with collagenous structure (MARCO) reportedly plays a crucial role in the occurrence and development of several cancers. However, the association between MARCO and the prognosis of hepatocellular carcinoma (HCC) post-liver transplantation remains poorly elucidated., Methods: We examined MARCO expression at mRNA and protein level in 145 HCC samples and adjacent nontumor tissues using quantitative reverse transcription PCR, Western blot and immunohistochemistry. Furthermore, we analyzed the correlation of MARCO expression with clinicopathologic features and prognosis., Results: We assessed the association between MARCO expression and clinicopathologic features and used the Cox proportional hazards regression model to explore the association between MARCO expression and clinical prognosis of patients with HCC post-liver transplantation. We observed that the expression of MARCO at mRNA and protein level in adjacent nontumor tissues was higher than that in the HCC tissues. Low MARCO expression in HCC tissues was correlated with higher alpha-fetoprotein levels, higher incidence of microvascular invasion, and a higher number of patients beyond Milan criteria. Kaplan-Meier survival curves showed that patients with HCC with low MARCO expression exhibited poor overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analysis revealed that MARCO expression was an independent prognostic factor for OS (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.335-5.444, P=0.006) and DFS (HR 2.867, 95% CI 1.665-4.936, P<0.001) in patients with HCC post-liver transplantation. Based on immunofluorescence analysis, MARCO expression was primarily localized to macrophages and might be associated with M2-like macrophage polarization during HCC., Conclusion: MARCO expression was downregulated in HCC and associated with poor prognosis of patients with HCC post-liver transplantation. Moreover, it could be a potential prognostic marker and therapeutic target in post-liver transplantation HCC., Competing Interests: The authors declare that they have no competing interests., (© 2022 Zhang et al.)

Objective: Osimertinib is the standard targeted strategy for lung adenocarcinoma patients harboring epidermal growth factor receptor ( EGFR )-activating mutation who have achieved acquired mutation T790M beyond progression of first-line EGFR -tyrosine kinase inhibitor (TKI). In a real world setting, the efficacy for osimertinib as a subsequent treatment beyond first-generation EGFR -TKI progression under complex circumstances such as different T790M mutation status is still worth exploring., Methods: Records of 84 lung adenocarcinoma patients with an EGFR sensitive mutation who received first-generation EGFR -TKI as first-line therapy and sequenced by osimertinib after progression were retrospectively reviewed in this study. The assessment of efficacy of subsequent osimertinib treatment was evaluated by progression free survival (PFS), objective response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR) and stable disease (SD) rates. Relationship between PFS and clinicopathological characteristics was analyzed using univariate analysis., Results: Until the median follow-up time of 23.7 months (IQR 10.8-29.0 months), the median PFS (mPFS) of subsequent osimertinib was 17.0 months (HR 1.744, 95% CI, 13.547-20.382). Among 60 patients who had at least one measurable lesion, 35.0% of patients (21/60) had PR to osimertinib, and 63.3% patients (38/60) had SD during osimertinib treatment. The ORR was 35.0%, and the DCR was 98.3%. Patients with acquired T790M mutation which was detected by NGS or ddPCR assay had an mPFS of 17.0 months (HR = 1.032, 95% CI, 14.941-18.987), while the remaining 17 patients who had negative or unknown T790M mutation status had an mPFS of 23.5 months (HR = 9.404, 95% CI, 5.068-41.932). No significant difference was observed in those with and without T790M mutation (P = 0.704)., Conclusion: Osimertinib may serve as an alternative subsequent choice after progression of first-generation EGFR -TKI in EGFR -mutated lung adenocarcinoma and may represent a potential treatment option for selected T790M-negative patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Xu et al.)

Purpose: This study aimed to evaluate the role of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) and to investigate clinically relevant prognostic factors., Patients and Methods: The medical records of 350 consecutive patients who underwent LM of CRC from 2011 to 2019 were reviewed. The patients were designated into AR group (lobectomy and segmentectomy), and non-anatomical resection (NAR) group (wedge resection), respectively. Kaplan-Meier method was used to analyze disease-free survival (DFS), pulmonary-specific disease-free survival (PDFS) and overall survival (OS). Cox proportional hazards regression model was performed to analyze the factors associated with DFS, PDFS and OS., Results: A total of 92 (31.2%) patients were enrolled in AR group and 203 (68.8%) in non-anatomical resection (NAR) group. AR significantly improved the 3-year DFS (64.1% vs 46.8%, HR 0.587, 95% CI 0.397-0.867, P = 0.007) and PDFS (75.0% vs 60.1%, HR 0.565, 95% CI 0.356-0.899, P = 0.016) compared with NAR. However, the extent of resection did not significantly impact the 3-year OS (AR 92.4% vs NAR 85.7%, HR 0.511, 95% CI 0.224-1.165, P = 0.110). In multivariate analysis, AR was identified as a protective factor for DFS (HR 0.576, 95% CI 0.356-0.934, P = 0.025) and PDFS (HR 0.631, 95% CI 0.409-0.973, P = 0.037). Preoperative abnormal CA19-9 was identified as the only prognostic factor for OS., Conclusion: AR was superior to NAR for DFS and PDFS after LM from CRC., Competing Interests: There was no financial and personal relationship with other people and organizations that could inappropriately influence this work. The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

Objective: Delineation of clinical target volume (CTV) and organs at risk (OARs) is important for radiotherapy but is time-consuming. We trained and evaluated a U-ResNet model to provide fast and consistent auto-segmentation., Methods: We collected 160 patients' CT scans with breast cancer who underwent breast-conserving surgery (BCS) and were treated with radiotherapy. CTV and OARs were delineated manually and were used for model training. The dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) were used to assess the performance of our model. CTV and OARs were randomly selected as ground truth (GT) masks, and artificial intelligence (AI) masks were generated by the proposed model. Two clinicians randomly compared CTV score differences of the contour. The consistency between two clinicians was tested. Time cost for auto-delineation was evaluated., Results: The mean DSC values of the proposed method were 0.94, 0.95, 0.94, 0.96, 0.96 and 0.93 for breast CTV, contralateral breast, heart, right lung, left lung and spinal cord, respectively. The mean 95HD values were 4.31mm, 3.59mm, 4.86mm, 3.18mm, 2.79mm and 4.37mm for the above structures, respectively. The average CTV scores for AI and GT were 2.89 versus 2.92 when evaluated by oncologist A ( P =0.612), and 2.75 versus 2.83 by oncologist B ( P =0.213), with no statistically significant differences. The consistency between two clinicians was poor (kappa=0.282). The time for auto-segmentation of CTV and OARs was 10.03 s., Conclusion: Our proposed model (U-ResNet) can improve the efficiency and accuracy of delineation compared with U-Net, performing equally well with the segmentation generated by oncologists., Competing Interests: Ms Qi Chen, Mr Shaobin Wang,and Mr Yu Chen are employees of MedMind Technology Co. The authors report no other conflicts of interest in this work., (© 2021 Liu et al.)

Background: Long noncoding RNA LINC00265 or miR-4500 is involved in the pathogenesis of many cancers. However, their functions in acute lymphoblastic leukemia (ALL) remain unknown. In this study, we investigated how LINC00265 and miR-4500 regulate the malignant characteristics of ALL., Methods: Real-time PCR was used in examining the expression of LINC00265 in ALL cell lines and blood of patients with ALL. Cell proliferation, cell migration, and xenograft tumor assays were performed to verify the function of LINC00265 subjected to overexpressing and silencing experiments. The ceRNA mechanism with LINC00265/miR-4500/STAT3 was investigated through luciferase and RNA pull-down assays. Finally, the function of the LINC00265/miR-4500/STAT3 axis subjected to overexpressing and silencing assays was determined through cell proliferation, cell migration, and xenograft tumor assays., Results: LINC00265 was highly expressed in ALL cell lines and blood of patients with ALL and facilitated the proliferation, migration, invasion, and growth of xenograft tumors of ALL cells. The silencing of LINC00265 expression with LINC00265 siRNA significantly inhibited the malignancy of the ALL cells. RNA pull-down and luciferase assays demonstrated that LINC00265 competitively targeted miR-4500 and enhanced STAT3 expression. Furthermore, miR-4500 inhibitors or overexpressed LINC00265 up-regulated STAT3 expression, and miR-4500 mimics or STAT3 shRNAs eliminated the LINC00265-induced malignancy of the ALL cells., Conclusion: Mechanistically, LncRNA LINC00265 can competitively interact with miR-4500 and thereby up-regulates STAT3 signaling and enhances the malignancy of tumors., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Zhao et al.)

Objective: To explore the influence of trastuzumab (TZ) combined with docetaxel (DTX) on serum tumor markers (TMs) in the treatment of human epidermal growth factor receptor 2-positive (HER-2+) breast cancer (BC) and to analyze the factors influencing therapeutic efficacy., Methods: Ninety-six patients with HER-2+ BC treated in the First Affiliated Hospital of Anhui University Of Science and Technology from January 2019 to December 2020 were selected. According to different treatment plans, the patients were divided into two arms with 48 cases each. The control group (CG) was treated with DTX, and the research group (RG) was given TZ combined with DTX (TZ+DTX). The two arms were compared regarding the following aspects: curative effects, adverse reaction, alterations of TMs and inflammatory factors (IFs), and quality of life. Logistic regression analysis was performed to analyze the factors affecting the efficacy of patients., Results: After treatment, the TMs carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125 and CA15-3 were significantly lower in RG compared with CG. The levels of IFs C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were also lower in CG. The overall response rate and the Karnofsky performance status (KPS) score were significantly higher in RG. No evident difference was observed in the total incidence of adverse reactions between the two arms. The high expression of CEA, CA125 and CA15-3 as well as DTX monotherapy increased the risk of adverse prognosis., Conclusion: TZ+DTX can effectively improve the clinical efficacy of HER-2+ BC patients and reduce their levels of serum TMs and IFs., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Feng et al.)

Minimal deviation adenocarcinoma (MDA) of uterine cervix is a rare malignant disease with rather poorer prognosis partially due to the early misdiagnosis. Hence, better understanding of early-stage symptoms is critical. We report a case of a 39-year-old woman came to hospital with a chief complaint of "a watery vaginal discharge for 9 months". She was further diagnosed as having uterine cervical minimal deviation adenocarcinoma in cervical LEEP specimen and MDA stage IIIC1 (FIGO 2018 staging-after correction) in post-hysterectomy histopathology. Currently, the definitive treatment is hysterectomy with adjuvant therapy based on staging. This article gives concise symptoms, history, and images of MDA colposcopy finding and histopathology, through the whole process of diagnosis and treatment for future clinical reference., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Xie et al.)

Purpose: Serum albumin can indicate the onset of cancer cachexia, provide information about a patient's nutritional status, and serve as a biomarker for the prognosis of patients with cancer cachexia. However, the relationship between serum albumin levels and mortality in patients with cancer cachexia remains unclear. We aimed to examine the association of albumin and total protein with 1-year mortality in patients with cancer cachexia., Patients and Methods: We conducted a nested case-control study using data from a multicenter cancer clinical survey from 2013 to 2018. In total, 266 patients with cancer cachexia who survived for <1 year and 266 patients who survived for ≥1 year were included in this study. The participants were matched by age, sex, tumor type, tumor stage, and hospital site. The crude and adjusted risks of 1-year survival were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression, with or without adjustment for covariates., Results: Logistic regression analysis revealed a significantly negative linear association between albumin level and 1-year mortality in patients with cancer cachexia (p < 0.001). An L-shaped relationship existed between total protein and 1-year mortality, with a turning point at 70.4 g/L. When albumin was divided into quartiles, Q3 (OR: 0.40; 95% CI: 0.24, 0.68; p < 0.001) and Q4 (OR: 0.33; 95% CI: 0.19, 0.55; p < 0.001) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. When total protein was divided into quartiles, Q2 (OR: 0.38; 95% CI: 0.23, 0.64; p < 0.001), Q3 (OR: 0.57; 95% CI: 0.33, 0.96; p = 0.035), and Q4 (OR: 0.43; 95% CI: 0.25, 0.72; p = 0.002) were associated with higher 1-year survival than Q1 among patients with cancer cachexia., Conclusion: Serum albumin and total protein may predict 1-year survival. Future clinical studies should lead to a more comprehensive understanding of the effects of serum protein levels in patients with cancer cachexia., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

Purpose: This study aimed to analyze clinicopathological, survival, prognostic factors, as well as the timing of brain metastases (BM) in colorectal cancer (CRC) using data from a Chinese center., Patients and Methods: Data of 65 consecutive CRC patients with BM were collected from a single institution in China. The time from primary tumor surgery to the occurrence of BM was calculated. Kaplan-Meier analysis was used to evaluate cumulative survival of patients. Factors associated with prognosis of overall survival (OS) were explored using Cox's proportional hazard regression models., Results: The median time interval from CRC surgery to the diagnosis of BM was 24 months. After diagnosis of BM, median OS values for patients were 11 months. Extracranial metastases occurred in 45 cases (69.2%) when BM was diagnosed, and 58.5% of these patients with lung metastases Time of BMs ( P =0.018), presence of extracranial metastases ( P =0.033), treatment ( P =0.003), CA199 ( P =0.034), CA125 ( P <0.001), CA242 ( P =0.018), and CA211 ( P =0.012) were associated with OS of patients through univariate analysis. Multivariate analysis using a Cox regression model showed that only treatment was an independent predictor for OS (conservative treatment; HR=1.861, 95% CI=1.077-3.441; P =0.048)., Conclusion: Surgical treatment of metastatic lesions may be an alternative choice for CRC patients with BM. Identifying the timing of brain metastases can help to detect this disease early, leading to a better survival outcome., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 Wang et al.)

Background: Chronic radiation intestinal injury (CRII) is the most common complication after pelvic malignancy radiation. Once hemorrhagic CRII patients suffer from lower extremity deep venous thrombosis (LE-DVT), hemostasis and anticoagulation therapy will be adopted simultaneously, but the treatment strategy is a paradox, as the condition is extremely intractable and serious. The aim of this study was to investigate the prevalence of and risk factors for LE-DVT in CRII patients and explore the treatment of hemorrhagic CRII patients with LE-DVT., Methods: This was a retrospective study, and a total of 608 hospitalized CRII patients after pelvic radiotherapy were included from November 2011 to October 2018. Univariate and multivariate analyses were conducted to investigate the potential risk factors for LE-DVT in CRII patients. Furthermore, the treatment of hemorrhagic CRII patients with LE-DVT was explored., Results: Among the CRII patients, 94 (15.5%) were with suspicious symptoms of LE-DVT in the lower limbs, and 32 (5.3%) were diagnosed with LE-DVT. Among the patients with LE-DVT, 65.6% (21/32) had bleeding simultaneously, and 29 (90.6%) had anemia with 24 (75.0%) having moderate to severe anemia. Multivariate analysis showed that a recent surgical history (≤6 months) (OR = 5.761, 95% CI: 2.506~13.246, p < 0.001), tumor recurrence or metastasis (OR = 3.049, 95% CI: 1.398~6.648, p = 0.005) and the hemoglobin (Hb) level (OR = 0.960, 95% CI: 0.942~0.979, p < 0.001) were significantly associated with the development of LE-DVT. ROC curve analysis showed that the AUC of the merged risk score of the independent risk factors was 0.822 (95% CI: 0.789~0.852), and the optimal Hb cutoff was 82.5 g/L. After colostomy, obvious bleeding remission was rapidly found in 84.6% of hemorrhagic CRII patients with LE-DVT., Conclusion: The prevalence of LE-DVT in hospitalized CRII patients was 5.3%. A recent surgical history, tumor recurrence or metastasis and a lower Hb level were independently associated with LE-DVT development in CRII patients. Colostomy could be a good choice for intractable hemorrhagic CRII patients with LE-DVT., Competing Interests: All authors declare that there are no conflicts of interest for this work., (© 2021 Huang et al.)

Purpose: To investigate PD-L1 protein expression and gene amplification in lung squamous cell carcinoma (LUSC) and analyse their correlation with the clinicopathological characteristics and prognosis of LUSC patients., Patients and Methods: Tissue samples from 164 LUSC patients were collected. PD-L1 protein was detected by immunochemistry (IHC), and PD-L1 gene amplification was investigated by fluorescence in situ hybridization in LUSC patients., Results: The positive expression rate of PD-L1 in LUSC was 47.6% (78/164), and the amplification rate of PD-L1 was 6.7% (11/164); both rates were higher than those of paratumor tissue. Both PD-L1 positive expression and gene amplification were correlated with clinical stage and lymph node metastasis ( P <0.05). PD-L1 protein expression, PD-L1 gene amplification, late stage, lymph node metastasis and distant metastasis were significantly correlated with the prognosis of patients. Among these factors, late stage, lymph node metastasis, PD-L1 protein expression and PD-L1 gene amplification were independent prognostic factors for LUSC., Conclusion: Positive PD-L1 protein expression and gene amplification are involved in the malignant progression and metastasis of LUSC. Both PD-L1 protein expression and gene amplification are associated with poor prognosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Chen et al.)

Purpose: To evaluate the effects of body weight loss on reproductive outcomes in young women with early-stage endometrial cancer (EC) and atypical hyperplasia (AH) who underwent fertility-sparing therapy., Patients and Methods: Patients with well-differentiated EC (n=8, FIGO stage Ia) and AH (n=36) who achieved complete regression after fertility-sparing therapy were retrospectively reviewed. Patients were divided into a weight loss group (n=25) and a non-weight loss group (n=19). Subgroup analysis according to body mass index and relative weight loss were performed to investigate the effect of weight loss on pregnancy and live birth outcomes. Univariate and multivariate logistic regression analyses were undertaken to determine pregnancy-associated factors., Results: Mean body weight and body mass index at pre-progestin treatment and at fertility treatment initiation were 70.63±12.03 and 67.08±8.18 kg, respectively, 27.06±4.44 and 25.73±3.15 kg/m 2 , respectively. Twenty-five patients (56.82%) lost weight, the median absolute weight loss was 5.00 kg (1.00-34.50), and the median relative weight loss was 6.70% (1.00-36.00%) over a median of 12 months (5.00-97.00). A favorable pregnancy rate (65.91%) and live birth rate (50.00%) were achieved. The pregnancy and live birth rates were meaningfully higher in the weight loss group than in the non-weight loss group (88.00% vs 36.84%, P =0.000; 64.00% vs 31.58%, P =0.033); weight loss ≥5% significantly increased pregnancy and live birth rate in patients with BMI ≥25 kg/m 2 . The risk ratio of weight loss ≥5% in multivariate logistic analysis for pregnancy was 10.448 (1.102, 99.056, P =0.041)., Conclusion: Weight loss could positively affect pregnancy rate and improve live birth rate in overweight and obese women with early-stage EC and AH during/after fertility-sparing therapy. Weight loss ≥5% increased pregnancy and livebirth rates significantly in overweight and obese women., Competing Interests: All authors declare that they have no conflicts of interest., (© 2021 Zhang et al.)

Objective: Pseudocapsule (PS) of tumor-parenchyma interface (TPI) can be detected by MDCT (ctPS) in renal cell carcinoma (RCC) with exceptions. We aim to study the prognostic implications and histological reflections of no detection of ctPS in RCC., Patients and Methods: A total of 210 RCC patients who had MDCT examination and received nephrectomy in our institution were included in the analysis. Absence or presence of ctPS was recognized, and its associations with overall survival (OS) and progression-free survival (PFS), pathological PS (pPS) and vasculature were studied., Results: A total of 172 (81.9%) patients were recognized to have a ctPS and 38 (18.1%) had no detection of it. They had comparable histology, stage, grade, and necrosis. Patients without a ctPS had significantly shortened overall survival (OS, p = 0.001) and progression-free survival (PFS, p <0.001), the significance of which persisted in multivariable analysis (OS, HR 3.104, p = 0.003; PFS, HR 3.313, p = 0.001). Nearly all tumors (34/38, 89.4%) without a ctPS actually had a pPS being detected and incompleteness of pPS was also irrelevant (p = 0.739). Compared with ctPS presence, those without a ctPS had significantly thinned pPS (0.36 vs 0.43 mm, p = 0.005). In clear-cell histology, those without a ctPS also contained increased vascular density and cross-sectional area of vessels with long diameter ≥200 um in the pPS layer (p = 0.005 and 0.011) and increased vascular density in the 500 um layer outside pPS (p = 0.017)., Conclusion: Absence of ctPS on MDCT significantly increases the risk of adverse clinical outcome in RCC. It is the reflection of a thinner pPS and enriched vasculature of TPI rather than absence of pPS itself., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Xi et al.)

Purpose: To investigate risk factors for instrumentation failure (IF) in titanium (Ti) mesh reconstruction for thoracic and lumbar tumors., Patients and Methods: The clinical data of patients with thoracic or lumbar tumors who received Ti mesh reconstruction via the posterior approach in our hospital from 2013 to 2018 were analyzed retrospectively. The observation indexes included sex, age, BMI, the vertebra resection mode, the number of resected vertebral segments, application of bone cement, radiotherapy, chemotherapy, revision or primary surgery, and primary tumor metastasis. Correlations between these factors and IF were analyzed by Kaplan-Meier survival and logistics regression analyses., Results: The 178 patients included 108 males and 70 females with a mean age of 48.09±16.21 (6-78) years and a mean follow-up period of 51.18 (24-90) months. The data showed that 17 patients (9.55%) were inflicted with IF, involving the thoracic vertebra in 11 cases, thoracolumbar vertebrae (T12-L1) in 2 cases, and lumbar vertebrae in 4 cases. The mean interval between surgery to IF was 35.18±14.17 (14-59) months. Univariate analysis showed that total vertebral body resection, the number of resected vertebral segments, radiotherapy and multiple tumor resection were potential factors for IF, while multivariate analysis showed that only total vertebral body resection, the number of resected vertebral segments and radiotherapy were independent factors., Conclusion: Total vertebra resection, the number of resected vertebral segments (≥2) and radiotherapy before and after operation were significant risk factors related to IF., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2021 Bao et al.)

Background: We aimed to assess the differences in gene expression and systemic inflammatory markers in colorectal cancer (CRC) patients with different mismatch repair (MMR) statuses., Methods: Bioinformatics analysis was used to identify the different expression genes in patients with CRC at different MMR statuses. A total of 208 patients with resectable colorectal cancer, including 104 deficient mismatch repair (dMMR) patients and 104 matched proficient mismatch repair (pMMR) patients, were retrospectively analyzed., Results: Bioinformatics analysis showed that chemokine-mediated signaling pathway and inflammatory responses were the main differences in gene expression between dMMR and pMMR CRC patients. In all 208 patients with CRC, those with dMMR frequently had it located on the right side, with more mucinous adenocarcinoma and grade 3 tumors. Patients with dMMR had an earlier American Joint Committee on Cancer (AJCC) stage than pMMR patients. Meanwhile, lymph nodes (LNs) metastasis was more frequently negative in dMMR patients than pMMR patients. Interestingly, patients with CRC with dMMR had more regional lymph nodes removed during surgery, although with less metastatic cancer. Patients with resectable CRC with dMMR were more likely to have higher levels of neutrophil, monocyte, platelet, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and C-reactive protein (CRP). In patients with dMMR, those with higher levels of PLR, MLR, CAR, and co-effect present had shorter overall survival (OS) significantly. It was noteworthy that the prognosis of high levels of systemic inflammatory markers did not predict prolonged OS in patients with pMMR CRC., Conclusion: dMMR CRC has presented a comprehensively distinct systemic inflammatory microenvironment. The systemic inflammatory response can predict oncological outcomes in patients with CRC with dMMR., Competing Interests: The authors report no potential conflicts of interest., (© 2021 Li et al.)

Purpose: Red blood cell distribution width (RDW) has been considered as a potential indicator of the effects of treatment or as a prognostic indicator for various malignancies. Most chronic myeloid leukemia (CML) patients are in the chronic phase, but some have transformed to accelerated phase or blast phase (blast crisis). However, the clinical significance of RDW in CML remains limited., Patients and Methods: In the present study, detailed clinical information and the RDW of 168 healthy people and 153 CML patients (106 patients for the training cohort and 47 patients for the validation cohort) were retrospectively assessed., Results: Multivariate analysis demonstrated that patient age (OR, 1.081; 95CI% 1.039~1.125; p < 0.001), platelet counts (OR, 0.997; 95CI% 0.994~0.999; p = 0.001) and RDW at admission (OR,1.469; 95CI% 1.121~1.925; p = 0.005) were significantly associated with the patients with advanced phase. Among CML patients in the chronic phase, higher RDW was significantly associated with overall survival (OS; p = 0.0008) and the event-free survival (EFS; p = 0.0221) among CML patients with chronic phase, but not with Transformation-free survival (TFS; p = 0.0821). Furthermore, higher RDW was associated with higher mortality compared to patients with low RDW (CML-associated deaths; p < 0.0001). In addition, a decline in RDW is associated with the treatment of CML patients with tyrosine kinase inhibitors, especially at 6 and 12 months after the start of treatment., Conclusion: Higher RDW is a potential prognostic biomarker for chronic CML patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Li et al.)

Although the mortality rate of osteosarcoma (OS) patients has improved, there are still many unsolved problems concerning how to reduce recurrence and metastasis. In the tumor microenvironment, immune escape plays a more important role in tumor progression and development. Many costimulatory molecules of the B7 family have been reported to be involved in regulating immunological interactions between OS cells and immune cells. Among these molecules, B7-H1 and its receptor, programmed death-1 (PD-1), have been the focus of the fields of tumor immunology and have been recently applied in clinical trials of therapies for several solid tumors. These therapies, referred to as B7-H1/PD-1 checkpoint blockade therapies, are designed to block the interaction between the two molecules. Although the mechanism has been reported in some malignancies, the specific impact of B7-H1/PD-1 expression on OS has not been well defined. Here, we review the expression, function, and regulatory mechanism of the B7-H1/PD-1 axis in OS and introduce and compare the advantages and disadvantages of B7-H1/PD-1 immunotherapies in OS., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Fan et al.)

Introduction: Colorectal cancer (CRC) is one of the most common human cancers and a leading cause of cancer-related death. Accumulating evidence has confirmed that long non-coding RNA (lncRNA) plays crucial roles in CRC development., Methods: qRT-PCR was performed to examine the expressions of LINC01224 and miR-2467. CCK-8 assay, colony formation assay and transwell invasion assay were used to examine the progression of breast cancer cells. Luciferase and RNA-binding protein immunoprecipitation (RIP) assay were applied to verify the binding site. Correlation analysis of miR-2467 and LINC01224 expression in lung cancer tissues was shown. Pancreatic cancer cells growth in vivo was evaluated using xenograft tumor assay., Results: LINC01224 expression was observed to be up-regulated in CRC tissues and cell lines. Functional studies suggested that LINC01224 silence inhibited CRC cells proliferation and invasion of CRC cells, while co-transfection with a miR-2467 inhibitor reversed these biological effects. Luciferase reporter assays illustrated that LINC01224 regulated miR-2467 directly, and RNA-binding protein immunoprecipitation (RIP) further confirmed that the suppression of LINC01224 by miR-2467 was in an RISC-dependent manner. Finally, LINC01224 silence inhibited the growth CRC cells in vivo., Conclusion: In conclusion, our findings showed that LINC01224 promoted CRC progression through sponging miR-2467. LINC01224 may serve as a potential diagnostic biomarker and therapeutic target for CRC patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Chen et al.)

Non-coding RNAs (ncRNAs) have received significant attention over the last few years. Malat1, as one of the most extensively studied ncRNAs, is believed to be not only a potential biomarker for disease diagnosis and prognosis, but also a candidate drug target for gynecological cancers. This potential is supported by a growing body of experimental evidence demonstrating that Malat1 participates in the occurrence, progression, and metastasis of tumors. Research has also shown that Malat1 can influence patient survival by regulating a range of target genes and signaling pathways. However, previous review articles have generally failed to consider the role of Malat1 in gynecological cancer in detail. In the present review, we summarize recent progress in research relating to the clinical relevance of Malat1 and the molecular mechanisms underlying the action of this ncRNA. Besides, we put forward some action points for further research after taking into consideration the sub-location and other essential properties of Malat1, which might enable us to have a better understanding of the potential of this molecule regarding clinical diagnosis and treatment., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 Liao et al.)

Purpose: To evaluate the quality of systematic reviews/meta-analyses (SR/MAs) on alternative exercise traditions in cancer care., Methods: PubMed, Cochrane Library, Web of Science, Ovid, EBSCOhost, WanFang Database, China National Knowledge Infrastructure, and VIP Database were searched from their inception to June 30, 2020. The search used a combination of subject words and free words. The search terms included "Tai Chi," "Qigong," "Baduanjin," "Yoga," "Pilates," "Cancer," "Meta-analysis," and "Systematic review." Two researchers independently performed literature screening and data extraction and used AMSTAR scale and PRISMA statement to evaluate the methodology and the quality of the evidence., Results: A total of 26 SR/MAs were included. The AMSTAR scale score was 5-10 points, with an average of 7.46±1.33 points. Overall, the methodological quality was considered to be moderate. The PRISMA list score was 13-24 points, with an average of 19.19±2.86 points. Among the papers evaluated, eight reports were relatively complete. A total of 15 papers indicated certain defects. A total of three papers showed relatively serious information defects., Conclusion: Relative to the control group, alternative exercise traditions may be effective in improving the quality of life, anxiety, depression, distress, and fatigue of cancer patients. However, they may not necessarily improve patients' sleep outcome, body mass index, and pain. During convalescence, cancer patients can be encouraged to start engaging in physical exercise, and professionals can develop appropriate exercise alternatives to ensure the expected effect of exercise while ensuring the safety of patients. The methodological quality of the systematic evaluations of the intervention effects of alternative exercise traditions on cancer patients is not satisfactory. Hence, focus should be directed to the improvement of the preliminary design scheme, publication status, literature retrieval, conflict of interest, and other aspects., Competing Interests: The authors have declared that they have no competing interests., (© 2020 Zhang et al.)

Background: Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention., Methods: Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values <0.05 were considered statistically significant., Results: Independent factors, including preoperative postmenopausal ( P =0.034), visceral metastasIs ( P =0.021), preoperative Frankel Score ( P =0.001), estrogen receptor status ( P =0.014), platelet-to-lymphocyte ratio ( P =0.012), lymphocyte-monocyte ratio ( P <0.001) and albumin-globulin ratio ( P =0.017), were selected into the nomogram model with the C-index of 0.834 (95% CI, 0.789-0.890). TDROC curves showed that the Changzheng Hospital (CZ) Score system had the best performance and exhibited the largest IAUC value in comparison with the other scoring systems., Conclusion: We constructed a nomogram model known as CZ Score based on the significant factors to predict the prognosis for BCSM patients. The result showed that CZ Score had a better value for prognostic evaluation and surgical decision-making as compared with the other scoring systems., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2020 Zhao et al.)

Purpose: The development of esophageal squamous cell carcinoma (ESCC) is a complicated process in which cell adhesion and motility, mediated by integrins, are involved through connecting the cytoskeleton to extracellular matrix. Different mechanisms via which integrin β6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin β6 in ESCC remain unknown., Methods: To investigate the differential expression of integrin β6 in ESCC, qPCR and immunohistochemistry assays were performed in 10 paired human samples. A total of 137 ESCC samples were further enrolled to evaluate the expression levels of integrin β6 and its endocytic trafficking regulator HS1-associated protein X-1 (HAX-1), followed by the evaluation of their correlation with clinicopathological parameters. The overall survival was analyzed using the Kaplan-Meier method, with significant variables further evaluated by multivariate Cox regression analyses., Results: The expression of integrin β6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin β6 was observed in 41.6% tumors, which was associated with histological differentiation, lymph node metastasis and TNM stage. High expression of HAX-1 was detected in 47.4% tumors, and there was a positive relationship between the expression levels of integrin β6 and HAX-1. Furthermore, the expression of integrin β6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin β6 and high HAX-1 expression demonstrated worst outcomes., Conclusion: The present findings suggested the predictive value of integrin β6 and HAX-1 as independent indicators of poor prognosis for patients with ESCC, both of which may contribute to the tumor proliferation and metastasis, leading to ESCC progression. Therefore, combined targeting of integrin β6 and HAX-1 may provide a potential novel approach for the treatment of ESCC., Competing Interests: The authors declare no conflict of interest in this work., (© 2020 Li et al.)

Purpose: This study aimed to investigate the associations between the preoperative prognostic nutritional index (PNI), systemic immune-inflammation index (SII) and overall survival (OS) and cancer-specific survival (CSS) in high-risk non-muscle-invasive bladder cancer (NMIBC) patients who received intravesical instillation of Bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumour (TURBT)., Patients and Methods: We retrospectively collected data from 387 high-risk NMIBC patients between January 2004 and December 2014. PNI was calculated as total lymphocyte count (10 9 /L)×5+albumin concentration (g/L). SII was calculated as neutrophil count (10 9 /L)×platelet count (10 9 /L)/lymphocyte count (10 9 /L). The cutoff values of PNI and SII were determined through receiver operating characteristic (ROC) analysis. OS and CSS were estimated by Kaplan-Meier analysis. The Log rank test was used to compare differences between the groups. Univariate and multivariate Cox regression analyses were performed to assess the predictive values of PNI and SII for OS and CSS. Additionally, highest-risk NMIBC patients were also divided into low or high groups according to PNI and SII. The OS and CSS of highest-risk NMIBC patients were estimated using Kaplan-Meier analysis with the Log rank test., Results: The patients were divided into two groups according to the cutoff values of PNI (<50.17 vs ≥50.17) and SII (<467.76 vs ≥467.76). Kaplan-Meier analysis revealed that low PNI and high SII were associated with poorer OS and CSS in high-risk NMIBC patients. Univariate and multivariate Cox regression analyses revealed that PNI and SII were independent predictive factors for OS and CSS. Kaplan-Meier analysis also revealed that low PNI and high SII were related to poorer OS and CSS in highest-risk NMIBC patients., Conclusion: These results suggest that preoperative PNI and SII, based on standard laboratory measurements, may be useful noninvasive, inexpensive and simple tools for predicting the long-term survival of high-risk NMIBC patients who received intravesical instillation of BCG after TURBT., Competing Interests: The authors report grants from Beijing Municipal People’s Government, during the conduct of the study; and grants from Beijing Municipal People’s Government, outside the submitted work. The authors declare that there are no other conflicts of interest in this study., (© 2020 Bi et al.)

Background: The function of long non-coding RNA small nucleolar RNA host gene 14 (SNHG14) in endometrial carcinoma (EC) has not been thoroughly reported. This research is designed to research the action mechanism of SNHG14 in EC development., Methods: The expression of SNHG14 was estimated in The Cancer Genome Atlas and was verified by qRT-PCR in EC tissues. The correlation between SNHG14 expression and clinicopathological features of EC patients was analyzed. Cell viability, wound healing rate, and relative invasion rate were examined by MTT, wound healing, and transwell assay. StarBase, TargetScan, RNA pull-down, and dual luciferase reporter gene (DLR) assay were conducted to analyze the relationship among SNHG14, miR-93-5p and ZBTB7A ., Results: SNHG14 was underexpressed in EC. SNHG14 expression was significantly relevant to menstruation, FIGO stage, histological grade and lymphatic metastasis of EC patients. SNHG14 overexpression hampered viability, migration and invasion of EC cells. SNHG14 functioned as a sponge for miR-93-5p, and miR-93-5p inhibition restrained cell viability, migration and invasion in EC. In addition, miR-93-5p directly targeted to ZBTB7A , which was underexpressed in EC. The suppressive action of SNHG14 overexpression on the viability, migration and invasion of EC cells was partly rescued by miR-93-5p overexpression or ZBTB7A silencing., Conclusion: LncRNA SNHG14 hampered the viability, migration and invasion of EC cells via modulating miR-93-5p/ ZBTB7A axis., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Zhang et al.)

Purpose: Spinal metastasis from urothelial carcinoma (UC) is relatively uncommon. The aim of the present study is to explore the clinicopathological features, surgical treatments and outcomes of this rare disease., Patients and Methods: Fifteen patients with UC spinal metastasis who received surgery in our center between 2009 and 2018 were retrospectively investigated. Clinical data, treatment options, and outcomes were analyzed., Results: For the 15 patients (9 men and 6 women), the primary tumors were located in the upper urothelial tract in ten and lower urothelial tract in five. UC mainly metastasized to the lumbar spine in seven cases, followed by the thoracic spine in five. Pathologic fracture and soft tissue mass with dura mater compression were observed in 66.7% and 93.3% cases, respectively. Palliative resection was performed in nine cases and excisional resection in six. Eleven patients received postoperative chemotherapy, including three with a preoperative ECOG score >2. Bisphosphonates were administered in all patients. Pain was relieved remarkably in all patients, and both the neurological function and general status were improved significantly after surgery. The median overall survival was 14 months. Log rank test showed that patients receiving postoperative chemotherapy survived longer than those without chemotherapy ( p =0.037). WHO grade 3 was also correlated with poorer prognosis ( p =0.012)., Conclusion: Pathological fracture and soft tissue mass with dura mater compression is frequently observed on radiological images in patients with UC spinal metastasis. Surgery is useful to prevent deterioration of performance status and improve quality of life, which provide an opportunity for further systematic therapy. Multimodal treatments, including surgery, postoperative chemotherapy and bisphosphonates are recommended. WHO grade 2 and receiving postoperative chemotherapy were favorable prognostic factors for the overall survival of patients with UC spinal metastasis., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Wang et al.)

Purpose: Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported., Methods: From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared., Results: It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P<0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen., Conclusion: In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline., Competing Interests: The authors declare no conflict of interests for this work., (© 2020 Lu et al.)

Objective: Spread through air spaces (STAS) has been reported to be an invasive histological pattern with poor prognosis in lung cancer; however, little is known about its intrinsic risk factors. This work analyzed the correlation between pathological and radiological features and STAS in resected lung adenocarcinomas., Patients and Methods: We retrospectively reviewed 1821 consecutive surgically treated patients with histologically diagnosed lung adenocarcinoma (174 positive for STAS and 1647 negative for STAS) from December 2017 to November 2018 at our institution. Propensity score matching identified 170 well-balanced pairs of patients. The correlations between pathological and radiological features and the presence of STAS were analyzed., Results: Before propensity matching, the incidence rate of STAS was 9.6% in all patients. In matched cohorts, multivariate analysis showed that the presence of STAS was significantly correlated with pure solid nodules (SNs) ( p = 0.001) and solid/micropapillary patterns (SMPs) ( p = 0.002). The odds ratio for STAS in SN-positive and SMP-positive adenocarcinoma against that in SN-negative and SMP-negative adenocarcinoma was 10.922 (95% confidence interval, 5.826-20.475; p < 0.001). Tumor differentiation, visceral pleural invasion (VPI), lymphovascular invasion (LVI), invasive adenocarcinoma, and non-lepidic subtype were significantly associated with STAS in the univariate analysis ( p < 0.05); however, the differences failed to reach a significant level in the multivariate analysis., Conclusion: We found that STAS was significantly correlated with several invasive clinicopathological patterns. The presence of SNs and SMPs were revealed as independent predictors for STAS, which could offer clinicians clues to identify STAS-positive adenocarcinoma., Competing Interests: The authors declare no conflicts of interest for this work., (© 2020 Zeng et al.)

Background: This retrospective study evaluated the prognostic significance of hemoglobin (Hb) levels in patients (pts) with unresectable locally advanced or metastatic gastric cancer who have not previously received chemotherapy., Patients and Methods: We screened 249 pts with advanced gastric cancer, who were categorized into four groups, namely, non-anemia (normal Hb levels), mild (10 g/dl to normal), moderate (8-10 g/dl), and severe anemia groups (<8 g/dl), to study the prognostic significance of Hb levels. We also examined the correlation between changes in Hb levels and treatment effects via imaging during the treatment course., Results: The objective response rate (ORR) was 47.4% for pts with anemia versus 43.4% for pts without anemia ( P =0.536). Hemoglobin levels were reduced by 0.51 ± 1.86 and 1.93 ± 1.33 g/dl after chemotherapy versus before chemotherapy in the disease control group and progressive groups, respectively (P=0.002). The median progression-free survival (mPFS) of first-line chemotherapy in all pts was 6.3 months. Specifically, the mPFS was 5.7 months in pts with severe anemia, compared with 6.4 months for pts with non-severe anemia (Hb≥8g/dl). The median overall survival (mOS) of all pts was 14.0 months. In particular, the mOS was 15.0 months for pts with non-anemia and mild anemia (Hb≥10g/dl) versus 11.5 months for pts with moderate or severe anemia. In multivariate analysis, ascites and decreased Hb post-chemotherapy were identified as independent prognostic indicators for PFS and OS., Conclusion: Our findings indicate that Hb levels are associated with the prognosis in the first-line chemotherapy for pts with advanced gastric cancer. Pts with progressive disease experience a larger decrease in Hb levels, and those with baseline Hb levels ≥10 g/dl experience longer OS., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Wei et al.)

Background: Studies focused on surgical interventions of spinal metastases of nasopharyngeal carcinoma (SMNPC) are blank., Methods: Patients with SMNPC who received surgical treatment in our center between 2005 and 2017 were included. Univariate and multivariate analysis of various clinical characteristics and operation-related data were analyzed to identify the independent factors that affected prognosis. Factors with P values of 0.1 or less were subjected to multivariate Cox regression analysis. P values of 0.05 or less were considered statistically significant., Results: A total of 30 patients with SMNPC treated with surgery were included. The thoracic spine was the most frequently involved site. The patients in this series achieved good overall survival (OS, 20.26 months) with limited perioperative complications. The univariate analysis suggested that preoperative Karnofsky performance scale, number of spinal metastases, number of visceral metastases, preoperative Frankel score, surgical resection mode and Ki 67 were potential prognostic factors. In the multivariate analyses, number of visceral metastases, preoperative Frankel score and resection mode were found to be independent prognostic factors., Conclusion: This is the first study focusing on surgical outcomes in SMNPC. The thoracic spine was the most frequently involved site of SMNPC. Preoperative Frankel score, number of visceral metastasis and surgical resection mode were independent prognostic factors for SMNPC. Combined with adjuvant therapies, surgical interventions should be recommended early when necessary., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2020 Yang et al.)

Introduction: The 6-phosphogluconate dehydrogenase (6PGD) was upregulated in many solid cancers and plays an important role in tumorigenesis. In the present study, we want to discover an old drug as an inhibitor of 6PGD for suppressing tumor growth., Methods: We determined the expression of 6PGD in cancer tissues using Gene Expression Omnibus (GEO) profiles and explored the importance of 6PGD expression in cancer progression by using Kaplan-Meier Plotter. We identified Ebselen as a 6PGD inhibitor by using 6PGD in vitro enzyme activity assay. Cell viability, cell proliferation, tumor growth and cell metabolism assay were used to explore the role of 6PGD and its inhibitor in cancer cells., Results: We found that the expression of 6PGD was upregulated in different cancer tissues and it can promote tumorigenesis. Here, we analyzed our 6PGD inhibitor screening data again and found an old drug Ebselen, which blocks cancer cell proliferation and tumor growth by inhibiting 6PGD enzyme activity, while knocking down 6PGD would partially abolish the inhibition of Ebselen on cell proliferation and cell metabolism., Conclusion: Our results suggested that the conventional drug Ebselen could serve as a novel inhibitor of 6PGD for suppressing cancer growth by inhibiting 6PGD enzyme activity., Competing Interests: The authors declare that they have no competing interests in this work., (© 2020 Feng et al.)

Background: Human papillomavirus (HPV) is a high-risk etiological factor for cervical and ovarian carcinomas. p16 protein can be used as a surrogate biomarker for HPV infection in high-risk tumors. A strong correlation between HPV infection and programmed death ligand 1 (PD-L1) protein expression has consistently been reported., Objective: Given this background, this study investigates the prevalence, prognostic and clinicopathologic features of HPV-related epithelial ovarian cancer (EOC) for the last 10 years in Northeast China to elucidate the involvement of p16 in the PD-L1 protein expression, tumorigenesis, and progression of EOC., Methods: Specimens from 310 patients diagnosed with EOC collected from 2006 to 2016 were analyzed by polymerase chain reaction (PCR) for HPV DNA, and overexpression of p16 by immunohistochemistry was also evaluated. Statistical analysis was performed to estimate the significant difference between HPV positive and negative patients, the correlation among HPV state, p16 and PD-L1 expression, and clinical presentation., Results: Overexpression of p16 protein and HPV DNA were present in 100 (32.3%) of the 310 cases, and correlated with high PD-L1 expression. There was a good concordance between HPV positivity, p16 protein overexpression and PD-L1 expression. The etiological fraction of HPV in EOC is substantially higher in Northeast China than other cohorts previously reported., Conclusion: Our study demonstrates that HPV infection and p16 overexpression is significantly associated with PD-LI expression in EOC, through the cooperative roles of dendritic cells (DCs) and IFN-γ, which may represent a promising strategy for therapeutic intervention in EOC., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Yang et al.)

Purpose: Stage IIIC1 cervical cancer showed heterogeneous in oncologic outcomes with highly variable survival rates. Our objective was to determine the prognostic significance of removed and metastatic pelvic lymph node status and further perform risk stratification in patients with stage IIIC1p cervical cancer., Patients and Methods: Patients with stage IIIC1p cervical cancer and undergoing radical hysterectomy with lymphadenectomy in 2008-2018 were retrospectively analyzed. Patients' stage was classified using the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging schema. Univariate and multivariable models were used to examine the association between removed and metastatic lymph node status and recurrence-free survival/overall survival., Results: During a median follow-up of 34 months, 73 relapses and 44 deaths were observed among 273 patients with stage IIIC1p cervical cancer. Parametrial involvement and metastatic lymph node ratio (mLNR) were identified as independent predictors for recurrence-free survival. Parametrial involvement and mLNR were independent predictors for overall survival. A stratification system was then created based on parametrial involvement and mLNR. A total of 123 (45.1%), 127 (46.5%) and 23 (8.4%) patients were classified into the low-risk, intermediate-risk, and high-risk groups, with as a 5-year recurrence-free survival of 81.7%, 51.1%, 38%, respectively. Compared to the low-risk group, the intermediate- and high-risk groups had a significantly greater risk of recurrence and death., Conclusion: The prognosis of stage IIIC1p patients varied significantly. A risk stratification system based on parametrial involvement and mLNR successfully separated patients into low, intermediate, and high-risk group. Our findings could facilitate the practical use of further stratification in Stage IIIC1p cervical cancer., Competing Interests: The authors declare that they have no competing interests., (© 2020 Li et al.)

Purpose: To predict multiple prognostic factors of HCC including histopathologic grade, the expression of Ki67 as well as capsule formation with intravoxel incoherent motions imaging by extracting the histogram metrics., Patients and Methods: A total of 52 patients with HCC were recruited with the MR examinations undertaken at a 3T scanner. Histogram metrics were extracted from IVIM-derived parametric maps. Independent student t -test was performed to explore the differences in metrics across different subtypes of prognostic factors. Spearman correlation test was utilized to evaluate the correlations between the IVIM metrics and prognostic factors. ROC analysis was applied to evaluate the diagnostic performance., Results: According to the independent student t -test, there were 18, 4, and 8 IVIM-derived histogram metrics showing the capability for differentiating the subtypes of histopathologic grade, Ki67, and capsule formation, respectively, with P -values of less than 0.05. Besides, there existed a lot of significant correlations between IVIM metrics and prognostic factors. Finally, by integrating different histogram metrics showing significant differences between various subgroups together via establishing logistic regression based diagnostic models, greatest diagnostic power was obtained for grading HCC (AUC=0.917), diagnosing patients with highly expressed Ki67 (AUC=0.861) and diagnosing patients with capsule formation (AUC=0.839)., Conclusion: Multiple prognostic factors including histopathologic grade, Ki67 expression status, and capsule formation can be accurately predicted with assistance of histogram metrics sourced from a single IVIM scan., Competing Interests: Yunfei Zhang and Yongming Dai are employees of Central Research Institute, United Imaging Healthcare. The authors report no other possible conflicts of interest in this work., (© 2020 Shi et al.)

Purpose: To evaluate the colposcopic accuracy of the detection of vaginal intraepithelial neoplasia (VaIN) according to the colposcopic terminology for the vagina from the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC)., Methods: A total of 467 women who were suspected of having VaIN and underwent colposcopy at Obstetrics and Gynecology Hospital of Fudan University from January to December 2018 were included in this retrospective cohort study. The 2011 IFCPC revised terminology for the vagina was applied, and the agreement between colposcopic diagnosis and vaginal biopsy pathology was analysed., Results: Agreement between colposcopy and pathology was 69.16% (kappa=0.437, p <0.001), with 23.34% overestimated and 7.49% underestimated diagnosis for colposcopy. The agreement was the lowest (35.71%) in the high-grade VaIN group, which was significantly different from that of other lesion grade groups ( p <0.01). Among grade 1 findings, thin acetowhite epithelium was the most frequent (80.51%). Grade 2 findings and vascular patterns were rare. The positive predictive values of the micropapillary pattern were 55.98% for low-grade VaIN and 5.98% for high-grade VaIN. The specificity of iodine negativity was 10.92% for low-grade VaIN and 8.30% for high-grade VaIN. There were significant differences in the maximum size of single lesions and in the number of lesions among different grade lesion groups., Conclusion: The agreement between colposcopy findings utilizing the 2011 IFCPC terminology and vaginal pathology is moderate, and more definite findings for high-grade VaIN may be needed. The micropapillary pattern can be considered an alternative low-grade finding, while iodine staining is nonspecific for all lesions. Scattered and spotty lesions suggest low-grade VaIN, while large single lesions suggest high-grade VaIN., Competing Interests: The authors declare that they have no competing interests., (© 2020 Zhou et al.)

Background: Radiotherapy is the main treatment for localized prostate cancer. The therapeutic effects of radiotherapy are highly dependent on radiosensitivity of target tumors. Here, we investigated the impact of insulin-like growth factor-binding protein 5 (IGFBP5) on irradiation therapy in prostate cancer., Methods: IGFBP5 gene was overexpressed in human prostate cancer cell lines, PC3 and DU145, with transfection of lentivirus expression vector. Radiosensitivity of the cell lines was assessed with colony formation, cell cycle and cell proliferation assays. The expression of proteins associated with the PI3K-AKT pathway was determined by Western blotting. The effect of IGFBP5 knockdown on PI3K-AKT pathway was tested using PI3K inhibitor., Results: Higher expression of IGFBP5 improved the efficacy of radiotherapy for prostate cancer patients. The effects of IGFBP5 were linked to the PI3K-AKT signaling pathway. Overexpression of IGFBP5 enhanced radiosensitivity and induced G2/M phase arrest in prostate cancer cells. In contrast, it decreased PI3K, p-AKT expression and cell viability. These effects were reversed by IGFBP5 knockdown., Conclusion: Our results reveal that IGFBP5 regulates radiosensitivity in prostate cancer via the PI3K-AKT pathway. It is, therefore, a potential biomarker of tumors that influences the therapeutic effect of radiotherapy., Competing Interests: The authors declare no conflicts of interest., (© 2020 Chen et al.)

Background: Cisplatin (CDDP) is extensively used for esophageal adenocarcinoma (EAC) chemotherapy, while cisplatin resistance is getting worse. microRNA-181a-5p (miR-181a-5p) has been reported to play an important role in various human cancers. However, the effect and underlying mechanism of miR-181a-5p in cisplatin resistance of EAC remain unclear., Methods: Cisplatin-resistant EAC cells OE19/CDDP and parental sensitive OE19 cells were applied for experiments in vitro. The expressions of miR-181a-5p and CBLB were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. The cisplatin resistance of cells was expressed by cell viability, IC50 and apoptosis rate by using CCK-8 assay or flow cytometry. The interaction between miR-181a-5p and CBLB was evaluated by luciferase reporter assay and RIP assay. In vivo experiments were conducted via the murine xenograft model., Results: miR-181a-5p was highly expressed while CBLB was lowly expressed in OE19 cell lines compared with OE19/CDDP cells. In cisplatin-resistant OE19/CDDP cells, miR-181a-5p up-regulation or CBLB knockdown inhibited cell viability and inducted apoptosis. In cisplatin-sensitive OE19 cells, miR-181a-5p inhibition or CBLB overexpression promoted cell viability and suppressed apoptosis. CBLB was confirmed to be a target of miR-181a-5p, and rescue assay showed CBLB overexpression reversed the suppression of OE19/CDDP cell viability induced by miR-181a-5p up-regulation, and its down-regulation attenuated miR-181a-5p-inhibition-mediated enhancement of OE19 cell viability. In addition, miR-181a-5p up-regulation enhanced the cytotoxicity of cisplatin in EAC in vivo., Conclusion: miR-181a-5p enhanced the sensitivity of cells to cisplatin in EAC by targeting CBLB, indicating a promising sensitizer of cisplatin therapy in clinical esophageal cancer., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 Yang et al.)

Purpose: Metastatic spinal cord compression (SCC) secondary to small cell lung cancer (SCLC) is a disastrous oncological emergency, but it is poorly understood due to the small numbers of patients and their short survival times. Whether patients suffered from SCC caused by metastatic SCLC benefit from spinal surgery remains unknown. The aim of this study was to evaluate the role of surgical treatment and prognostic factors in patients with SCC caused by metastatic SCLC., Methods: From 2009 to 2019, 30 consecutive patients surgically treated for metastatic SCC from SCLC were enrolled in this retrospective analysis. Kaplan-Meier method and Cox regression analysis were used to estimate overall survival (OS) and identify prognostic factors. Quality of life (QoL) was assessed by the three-level EuroQol-five-Dimensions (EQ-5D-3L) instrument and compared using Student's t test., Results: The median OS time was 9 months in our series. Relief of pain, preservation of neurological function, and improvement of performance status were achieved after surgical intervention. The mean EQ-5D-3L utility score showed a significant improvement after surgery (0.3394 preoperatively vs 0.5884 postoperatively). According to Cox regression analysis, postoperative ECOG-PS and immunotherapy were identified to be independent prognostic factors for patients with SCC caused by metastatic SCLC., Conclusion: Despite the short life expectancy, prompt surgical decompression is extremely necessary for patients with SCC caused by SCLC, for surgery played a critical role in improving patients' QoL. Better performance status after surgery and receiving immunotherapy were associated with a longer OS., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2020 Gao et al.)

Purpose: To develop and validate a PI-RADS-based nomogram for predicting the probability of clinically significant prostate cancer (csPCa) at initial prostate biopsy., Patients and Methods: From February 2015 to October 2018, 573 consecutive patients made up the development cohort (DC), and another 253 patients were included as an independent validation cohort (VC). Univariate and multivariate analysis were used for determining the dependent clinical risk factors for csPCa. Prediction model1 was constructed by integrating independent clinical risk factors. Then added the PI-RADS score to model1 to develop the prediction model2 and present it in the form of a nomogram. The performance of the nomogram was assessed by receiver operating characteristic curve, net reclassification improvement analysis, calibration curve, and decision curve., Results: All clinical candidate factors were significantly different between csPCa and non-csPCa in both the DC and VC. Age, PSA density (PSAD), and free-to-total PSA ratio (f/t) were ultimately determined as dependent clinical risk factors for csPCa and integrated into prediction model1. Then, prediction model2 was developed and presented in a nomogram. In the DC, the nomogram (AUC=0.894) was superior to model1, PI-RADS score, or other clinical factors alone in detecting csPCa. Similar result (AUC=0.891) was obtained in the VC. NRI analysis showed that the nomogram improved the classification of patients significantly compared with model1. Furthermore, the nomogram showed favorable calibration and great clinical usefulness., Conclusion: This study developed and validated a nomogram that integrates PI-RADS score with other independent clinical risk factors to facilitate prebiopsy individualized prediction in high-risk patients with csPCa., Competing Interests: The authors have stated that they have no conflicts of interest., (© 2020 Zhang et al.)

Background and Aim: Hepatocellular carcinoma (HCC) is a type of cancer with high mortality rates. The overexpression of microRNA-519d (miR-519d) has been explored in different types of cancers, which could significantly help suppress cancer development. This study aimed to investigate the interaction of miR-519d with its target gene, Rab10, as well as its effects on cell proliferation and autophagy in HCC cells through modulation of the AMPK signaling pathway., Methods: Microarray analysis was used to analyze the differentially expressed genes in HCC, and the target genes of the screened-out miRNA were predicted and verified. The expression of miR-519d and Rab10, AMPK signaling pathway-related proteins, apoptosis- and autophagy-related proteins was determined by RT-qPCR and Western blot analysis in HCC tissues and cell lines. Lastly, the effects of miR-519d and Rab10 in HCC cell proliferation, apoptosis, and mouse tumour xenograft in vivo were examined through gain- and loss-of-function experiments., Results: MiR-519d was down-regulated and Rab10 was upregulated in HCC tissues and cell lines. Overexpression of miR-519d decreased the expression of Rab10, mTOR, and Bcl-2, but increased the expression of Bax, Beclin1, Atg5, and p53. Upregulated miR-519d and downregulated Rab10 expression suppressed cell proliferation and induced cell apoptosis and autophagy in HCC cells. Finally, upregulation of miR-519d inhibited tumour growth in vivo., Conclusion: The result obtained in this study indicates that up-regulation of miR-519d inhibits proliferation and promotes apoptosis and autophagy of HCC cells through activation of the AMPK signaling pathway via downregulating Rab10, which provides a potential target for the treatment of HCC., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhang et al.)

Purpose: LncRNA NR2F2-AS1 has been characterized as an oncogenic lncRNA in non-small cell lung cancer. This study aims to explore the role of NR2F2-AS1 in colorectal cancer (CRC)., Methods: All CRC patients (n=60, 35 males and 25 females, 40 to 68 years old) in this study were enrolled in Changzhou No.2 People's Hospital of Nanjing Medical University during the time period between July 2011 and December 2013. Tumor samples, CRC cells, vectors, transient transfections, RT-qPCR, western-blotting, as well as measurements of cell cycle, apoptosis and cell proliferation assay were carried out during the research., Results: Our data showed that NR2F2-AS1 was upregulated in CRC and CRC patients with high levels of NR2F2-AS1 showed a low overall survival rate. Cyclin D1 was also upregulated in CRC and a positive correlation was found between Cyclin D1 and NR2F2-AS1. In CRC cells, NR2F2-AS1 siRNA silencing mediated the downregulation of Cyclin D1 and G0/G1 arrest, while Cyclin D1 overexpression rescued G0/G1 arrest caused by NR2F2-AS1 siRNA silencing., Conclusion: Our results indicated that NR2F2-AS1 silencing mediates the downregulation of Cyclin D1 to induce G0/G1 arrest in colorectal cancer., Competing Interests: The authors report no funding and no conflicts of interest for this work., (© 2020 Liu et al.)

Objective: The study aimed to clarify clinical features and prognostic factors of thoracic oligo-postoperative recurrences that underwent local therapy of non-small-cell lung cancer (NSCLC)., Methods: From 2332 patients of resected pathological stage I-IIIA NSCLC between 2008 and 2015, a total of 542 patients in follow developed recurrence. Thoracic oligo-recurrence was defined as 1-3 loco-regional confined to lung lobe, hilar/mediastinal lymph nodes, bronchial stump, or chest wall. This study included 56 thoracic oligo-recurrences. Local therapy included secondary surgery, stereotactic radiotherapy, radiotherapy with a 45 Gy or higher dose, and proton radiation therapy, performed with radical intent. We retrospectively reviewed the postoperative data and performed the univariate and multivariate analysis by Kaplan-Meier methods and Cox regression models, respectively., Results: Thoracic Oligo-recurrence was identified in 56(542,10.3%) patients, mainly in lung lobe(n=22,39%) and regional lymph nodes(n=19,34%). Compared with distant oligo-recurrences, more of the thoracic oligo-recurrences were II-III in pathological stage at initial surgery(p=0.002) and less were adenocarcinoma(p=0.005). The 5-year postoperative survival rate and postoperative progression-free survival rate of thoracic oligo-recurrence were 10.8% and 6.7%, respectively. Median post-recurrence survival (PRS) was 31 months, and the median postoperative progression-free survival (PR-PFS) was 17 months. Multivariate analyses revealed that time to recurrence ≥ 12 months was associated with improved PRS [odds ratio (OR) 0.74, confidence interval (CI) 0.65-0.85], and regional lymph node oligo-recurrence was associated with poor PRS [OR 1.48, CI 1.38-1.60]. All the five long-term (≥5-year) progression-free survivors were with a solitary pulmonary recurrence., Conclusion: Thoracic postoperative oligo-recurrence of non-small-cell lung cancer is a limited but highly heterogeneous population, with different prognosis at different recurrence sites. Local therapy for thoracic oligo-recurrence of NSCLC achieved favourable PRS in a selected population. Pulmonary solitary oligo-recurrence may achieve a long survival time., Competing Interests: The authors declare no conflicts of interest in this work., (© 2020 Yuan et al.)

Objective: This study aims to investigate the risk factors of prelaryngeal lymph node metastasis in papillary thyroid carcinoma and its clinical application value., Methods: The clinical pathological features and metastatic risks were statistically analyzed by reviewing 254 patients with papillary thyroid carcinoma, who received their first operation and prelaryngeal lymph node dissection in our department., Results: The detection of prelaryngeal lymph nodes, tumor size and any paratracheal lymph node metastasis were correlated with the number of paratracheal lymph node metastasis ( P <0.05), but these were not correlated with age, gender, multiple foci, tumor size, any paratracheal lymph node metastasis, metastatic location, or foci location ( P >0.05)., Conclusion: Paratracheal lymph node metastasis indicates a high possibility of prelaryngeal lymph node metastasis. Paratracheal lymph node dissection combined with prelaryngeal lymph node dissection should be simultaneously considered in operations for thyroid papilla carcinoma., Competing Interests: The authors declared that there is no conflict of interest in this work., (© 2020 Gong et al.)