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Xiaoyan Huang,1– 3,* Yingyi Kuang,1– 3,* Qiyuan Qin,1– 3,* Miaomiao Zhu,1– 3 Yanjiong He,1– 3 Zixu Yuan,1– 3 Huaiming Wang,1– 3 Qinghua Zhong,1,2,4 Qi Guan,1– 3 Hui Wang,1– 3,* Tenghui Ma,1– 3,* Xinjuan Fan1,2,5,* 1Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 4Department of Endoscopic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 5Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinjuan FanDepartment of Pathology, Sun Yat-sen University Sixth Affiliated Hospital, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, People’s Republic of ChinaFax +86 20-38737621Email fanxjuan@mail.sysu.edu.cnTenghui MaDepartment of Colorectal Surgery, Sun Yat-sen University Sixth Affiliated Hospital, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, People’s Republic of ChinaFax +86 20-38737621Email matengh@mail.sysu.edu.cnBackground: 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.Keywords: chronic radiation intestinal injury, lower extremity deep venous thrombosis, pelvic malignancy radiation, risk factor, colostomy, hemorrhagic

Zhen Huang,* Qixing Tan,* Qinghong Qin, Qinguo Mo, Changyuan Wei Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinguo Mo; Changyuan WeiDepartment of Breast Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning 530021, People’s Republic of ChinaTel +86-771-5308593; + 86-771-5308593Fax +86-771-5312000Email qgmo135@263.net; weichangyuan@gxmu.edu.cnPurpose: The efficacy of primary site surgery in patients with de novo stage IV breast cancer remains controversial. However, few real-world studies have evaluated the benefits of local surgery on the primary site of stage IV breast cancer in China. The purpose of this study was to investigate the role of local surgery in the de novo stage IV breast cancer.Materials and Methods: Women with metastatic breast cancer at diagnosis were identified from Guangxi medical university cancer hospital (China) database from 2009 to 2017. The clinical and tumor features, surgical treatment, and survival rates were compared between surgical and non-surgical patients.Results: Two hundred forty-three patients were included, of whom 125 underwent primary site surgery. Patients who underwent surgery were more often had small primary tumors, fewer lymph node metastases, and had less visceral involvement. Patients in the surgery group had dramatically longer OS (median 35 vs 22 months, log-rank P=0.006). Stratified survival analysis showed that patients with bone metastasis alone or ≤ 3 metastasis benefit from surgery, while patients with visceral metastasis did not benefit from surgery. In multivariate analysis, surgical treatment, estrogen receptor status, progesterone receptor status and visceral metastases remained independent factors for survival.Conclusion: Surgical resection of the primary site can improve survival in selected de novo stage IV breast cancer patients.Keywords: stage IV breast cancer, surgery, survival

Zhen Huang,* Qinghong Qin,* Longjie Xia,* Bin Lian, Qixing Tan, Yinghua Yu, Qinguo Mo Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinguo MoDepartment of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, No. 71 Hedi Road, Nanning 530021 Guangxi Province, People’s Republic of ChinaTel +86-771-530859Email qgmo135@263.netObjective: To investigate the association between the recurrence score (RS) obtained by Oncotype DX 21-gene test and long non-coding RNA (lncRNA) MALAT1 expression in early and estrogen receptor-positive (ER+) breast cancer.Materials and Methods: The Oncotype DX 21-gene test and MALAT1 expression detection were performed in tumor samples from 76 ER+ and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of MALAT1 was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann–Whitney U-test or Kruskal–Wallis test were used to analyze the association between MALAT1 level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman’s rank correlation analysis.Results: The expression of MALAT1 was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641± 1.438, Z=− 2.594, p= 0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS< 18), 36.8% of patients were in medium risk (18≤RS≤ 30), and 10.5% of patients were in high risk (RS> 30). While under the new criteria, 18.4% were in low risk group (RS< 11), 63.2% were in a medium risk group (11≤RS≤ 26), and 18.4% were in a high risk group (RS> 26). The Oncotype DX 21-gene results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA MALAT1 was significantly correlated with the Oncotype DX 21-gene results under the old criteria.Conclusion: MALAT1 is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status. MALAT1 level is associated with the Oncotype DX 21-gene RS value. Therefore, combination of MALAT1 and the Oncotype DX 21-gene test may be used to predict prognosis in ER+ and early stage breast cancer.Keywords: Oncotype DX 21-gene test, MALAT1, long non-coding RNA; lncRNA, breast cancer, risk of recurrence

Purpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116)., Patients and Methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored., Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers., Competing Interests: Innovent Biologics, Inc. provided the sintilimab, but had no role in study design, or writing of the protocol. The authors report no other conflicts of interest in this work., (© 2022 Wei et al.)

Purpose: We aimed to investigate the clinicopathological characteristics and survival risk factors in small cell lung cancer (SCLC) patients with preexisting type 2 diabetes mellitus (preDM)., Patients and Methods: All patients with SCLC admitted to our hospital between January 2013 and August 2018 were followed up until August 2020 and retrospectively analyzed. Clinical characteristics of SCLC patients with and without preDM were extracted. Cox proportional hazards models were conducted to identify potential independent prognostic factors., Results: Of 628 eligible individuals, 88 individuals had preDM. preDM was independently significantly associated with distant metastasis in all SCLC patients ( p =0.016, OR=1.80, 95% CI 1.11-2.91), while preDM did not affect the outcome of SCLC patients ( p =0.803, HR=1.04, 95% CI 0.79-1.36) by multivariate analysis. In the preDM group, the median overall survival (OS) was shorter in the insulin group than in the non insulin group (13.93 months versus 21.77 months, p=0.024). Multivariate analysis identified that insulin treatment was an independent unfavorable factor associated with OS ( p =0.009, HR=2.10, 95% CI 1.19-3.64). In addition, poorer performance status (PS) and liver metastasis were also independent unfavorable prognostic factors (all p <0.01), while thoracic therapy significantly improved OS and decreased mortality risk in diabetic patients with SCLC ( p <0.05)., Conclusion: preDM may promote distant metastasis of SCLC while it is insulin therapy and not preDM which adversely affects the prognosis of SCLC patients. These findings indicate that enhancing blood glucose control and reducing insulin analog use may be essential to the improvement of the long-term survival of the diabetic population with SCLC., Competing Interests: All authors declare that they have no conflicts of interest in this work., (© 2022 Ding et al.)

Purpose: To present a nomogram to predict overall survival in patients with FIGO-2018 II to III squamous cell cervical carcinoma undergoing radical radiotherapy., Patients and Methods: Patients diagnosed with FIGO-2018 II to III squamous cell cervical cancer between December 2013 and December 2014 were analyzed retrospectively. The optimal cutoff point for tumor length and width were determined by R package. We identified prognostic factors by univariate and multivariate Cox proportional-hazard regression, then built a nomogram to visualize the prediction model. Our model was compared to the 2018 FIGO staging prediction model. Harrell's concordance index, receiver operating characteristic curve, calibration plot were used to evaluate the discriminability and accuracy of the predictive models, and decision curve analysis (DCA) was used to show the net benefits., Results: Data from 469 patients were included in the final analyses. The cutoff values of tumor length and width were 5.10 cm and 4.13 cm, respectively. Four independent prognostic variables-tumor length, tumor width, lower one-third vaginal involvement, and lymph node metastases-were used to establish the nomogram. The C-index of the nomogram was 0.71 (95%, CI = 0.66-0.77), which was better than that of the 2018 FIGO stage prediction model (C-index: 0.62, 95% CI = 0.58-0.66, p = 0.009). The calibration plot of the nomogram was a good fit for both 3-year and 5-year overall survival predictions. And DCA curves showed that net benefits for our model were higher than FIGO-2018 staging system., Conclusion: A clinically useful nomogram for calculating overall survival probability in FIGO-2018 II to III squamous cell cervical cancer patients who had received radical radiotherapy was developed. Tumor length, tumor width, lower one-third vaginal involvement, and lymph node metastases were found to be independent prognostic factors. Our model performed better than the 2018 FIGO staging model. The findings could help clinicians in China to predict the survival of these patients in clinical care and research., Competing Interests: The authors declare no conflicts of interest., (© 2021 Zang et al.)

Purpose: Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC., Materials and Methods: A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis. PD-L1 expression was evaluated in whole tissue sections of these cases by using the tumor proportion score (TPS, cut-off 1%) and combined positive score (CPS, cut-off 1) scoring methods., Results: Overall, there was a heterogeneous expression of PD-L1, focal or patchy, in ESCs. PD-L1 positivity was observed in 43.0% of ESCs by TPS and 73.4% of ESCs by CPS. Kaplan-Meier survival analysis showed that patients with PD-L1-positive tumors suffered significantly worse OS and PFS, when compared with PD-L1 negative tumors (log-rank p = 0.037 and p = 0.003, respectively). In contrast, PD-L1 positivity by CPS within the ESC cases showed no statistical significance for OS and PFS (log-rank p = 0.720 and p = 0.928, respectively). Multivariate Cox analysis showed that PD-L1 positivity by TPS was significantly associated with PFS (HR = 1.921, p = 0.039) but not OS (HR = 1.229, p = 0.631)., Conclusion: PD-L1 expression is frequently found in ESC, suggesting a potential role of the PD-1/PD-L1 pathway as a potential therapeutic target for these tumors. PD-L1 expression by TPS also serves as a negative prognostic marker in ESC and implies an unfavorable outcome., Competing Interests: The authors state they have no competing interests., (© 2021 Zhang et al.)

Background: Lung cancer has the characteristics of early metastasis, high recurrence, and high mortality rate despite emerging advances in diagnostic. Early diagnosis can significantly improve the patient's chances of cure and survival., Purpose: This study aimed to identify and assess a prognostic lncRNA/miRNA/gene signature in patients with lung cancer., Methods: Pearson correlation analysis, univariate Cox analysis and LASSO Cox analysis were used to construct a lung cancer prognostic risk model based on m6A-related lncRNA. The interaction between lncRNA-miRNA-gene was verified by luciferase reporter gene experiment., Results: The Pearson correlation analysis determined that 1655 lncRNAs significantly correlated with the expression of m6A genes. A lung cancer prognostic risk model, including 14 m6A-related lncRNAs, was constructed through univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis. ABALON was identified as the key lncRNA through cluster analysis and gene expression difference analysis., Conclusion: It was experimentally verified that ABALON acted as a competing endogenous RNA by sponging miR-139-3p and indirectly regulated the expression of NOB1. This study provided a new biological target for the early diagnosis of lung cancer and a new direction for studying the mechanism of lung cancer., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 Liu et al.)

Purpose: To evaluate the effect and immune response of transcatheter arterial embolization (TAE) combined with donafenib in rabbit VX2 liver tumor model., Materials and Methods: Thirty-six New Zealand white rabbits with VX2 liver tumor were randomly divided into three groups. The LD group was treated with the emulsion of 0.5 mL lipiodol and 4 mg donafenib via hepatic arterial administration. The LE group was treated with the emulsion of 0.5 mL lipiodol and 4 mg epirubicin. The control group was treated with the equal volume of saline. Four rabbits were euthanized in each group on day 1, 3 and 7 after treatment. The tumor growth, histological markers associated with angiogenesis and immune response were assessed by imaging and histopathology. In addition, immune modulatory cytokines included interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and biochemical hepatorenal function were measured., Results: Compared to other groups, LD group achieved lower tumor growth rate, fewer metastatic lesions, and higher tumor necrosis rate on day 7 after treatment. The percentage of CD31-positive area in the LD group was significantly lower than that in the LE group on day 3 and 7 after treatment. In addition, CD8 + lymphocytes infiltration was more pronounced in LD group than in LE group on day 7 after treatment, regardless of in the tumor or adjacent liver tissue. Serum cytokines including IL-6, TNF-α and IFN-γ were strongly upregulated in the LD group on day 1 after treatment. And there was no significant difference in the hepatorenal function between LD group and LE group after treatment., Conclusion: The combination of TAE and angiogenesis inhibitor donafenib resulted in a potentiated tumoricidal effect, anti-angiogenesis and antitumour T cell response in rabbit VX2 liver tumor model. This may provide a potential basis for exploring the immune-related mechanisms of embolization in liver cancer., Competing Interests: All authors declare that they have no potential conflict of interest in the study., (© 2021 Shi et al.)

Purpose: In clinical practice, we found some of the patients who received transarterial chemoembolization (TACE) with molecular targeted agents (MTGs) plus immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) had obvious liquefactive necrosis formation within the tumor and some even progressed to a liver abscess, which seems more frequent than patients who received other treatments. Thus, we aim to identify this condition and analyze the potential risk factors., Patients and Methods: Medical records of 72 consecutive patients with intermediate (BCLC B) and advanced (BCLC C) HCC who received TACE plus MTGs combined with (n=30) or without (n=42) ICIs were reviewed. Liquefactive necrosis formation was defined as the presence of obvious liquefactive necrosis within the tumor that required intervention., Results: The liquefactive necrosis rate was higher in the TACE+MTGs+ICIs group than in the TACE+MTGs group (30% vs 4.8%, P=0.006). Moreover, 18.2% (2/11) of the patients with liquefactive necrosis within the tumor had a bacterial infection. We then take the binary logistic regression analysis model to identify the predictors of liquefactive necrosis formation, and which showed the tumor size (P=0.006, OR=1.355, 95% CI: 1.090-1.684), alpha-fetoprotein level (P=0.036, OR=6.745, 95% CI: 1.130-40.262) and treatment modality (P=0.015, OR=11.717, 95% CI: 1.617-84.887) were the independent risk factor for liquefactive necrosis formation within the tumor., Conclusion: Patients with HCC who received TACE combined with MTGs plus ICIs have increased liquefactive necrosis formation, and the larger tumor size and higher alpha-fetoprotein level were associated with more liquefactive necrosis formation within the tumor., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Wang et al.)

Purpose: To investigate the prevalence of precancers [high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS)] and cancers [squamous cell carcinoma (SCC) and adenocarcinoma (ADC)] in various high-risk human papillomavirus (hrHPV) genotypes or age groups among women with negative for intraepithelial lesion or malignancy (NILM) and hrHPV-positive pap results., Materials and Methods: In total, 26,228 women with NILM/hrHPV+ were included in the study. Among them, 5893 had immediate follow-up biopsy results available and were selected for further prevalence analysis., Results: About 7.6% and 0.7% women with NILM/hrHPV+ had HSIL and AIS, respectively. The prevalence of HSIL+ squamous lesions is significantly higher in HPV-16+ group than that in other genotype groups ( p < 0.0001). The prevalence of AIS+ glandular lesions is significantly higher in HPV-18/45+ groups than women in other genotype groups ( p < 0.0001). In addition, the prevalence of HSIL+ lesions was significantly higher in age 25-39 years group than that in age 40-65 years group and >65 years group ( p < 0.0001). Overall, the prevalence of HSIL+ in younger women was significantly higher than that in older women when using a cutoff age of 40 years (9.3% vs 5.9%, p < 0.0001) or 50 years (8.6% vs 4.9%, p < 0.0001). No significant difference in AIS+ prevalence was found among different age groups ( p = 0.611). Interestingly, the prevalence of SCC and ADC in older women (≥40 years, 0.3% and 0.3%, respectively) was significantly higher than that in younger women (<40 years, 0% and 0.07%) ( p = 0.001 for SCC; p = 0.02 for ADC)., Conclusion: The significant risk of cervical precancers and cancers still exists in women with NILM/hrHPV+, notably the older patient group had a lower risk of cervical precancer, but higher risk of cancer. Therefore, HPV genotyping can be an effective supplemental tool to cytology, and patient age also needs to be considered in the clinical management of patient., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

Background: We aimed to explore the efficacy and tolerance of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) treatment in relapsed/refractory small cell lung cancer (SCLC) patients., Methods: Eleven relapsed/refractory SCLC patients were enrolled and treated with DEB-BACE. Then, treatment response and tumor marker levels were assessed at the first, second and sixth month post treatment. Quality of life was assessed by the EORTC QLQ-C30 scale. Progression-free survival (PFS) and overall survival (OS) were also evaluated., Results: At the first, second and sixth month post treatment, the objective response rates were 63.6%, 54.5%, and 36.4%, respectively; and the disease control rates were 90.9%, 90.9% and 54.5%, respectively. In addition, the neuron-specific enolase (NSE) and progastrin-releasing peptide levels were reduced at the second and sixth month. Quality of life assessed by EORTC QLQ-C30 scale, which included subscales of general health status, functional domains, symptom domains, and single domains except for financial difficulty, was markedly improved at second month post treatment. Median values of PFS and OS were 5.1 (95% CI: 4.1-5.9) months and 9.0 (95% CI: 6.0-12.0) months, respectively. The ECOG score and preoperative NSE level were independent predictive factors for PFS, and age as well as lesion location were independent predictive factors for OS. Adverse events were all mild and manageable with chest pain and chest stuffiness the most common ones., Conclusion: DEB-BACE could be a therapeutic option for relapsed/refractory SCLC patients regarding its favorable treatment response, quality of life, survival benefit and safety profile., Competing Interests: The abstract of this paper was presented at the European Conference on Interventional Oncology 2021 as a poster presentation with interim findings. The poster’s abstract was published in Journal Cardiovascular and Interventional Radiology volume 44, pages 1–64 (2021): [https://link.springer.com/article/10.1007/s00270-021-02819-z]. The authors declare that they have no competing interest., (© 2021 Lin et al.)

Purpose: The aim of this study was to identify the risk factors associated with delayed recovery of gastrointestinal function after ileostomy reversal for rectal cancer patients., Methods: In this retrospective study, the data of rectal cancer patients who underwent ileostomy reversal from January 2018 to December 2019 at the Sixth Affiliated Hospital of Sun Yat-sen University were assessed to investigate potential risk factors of delayed flatus after ileostomy reversal., Results: A total of 282 patients were eligible for this study. Postoperative first flatus time ranged from 1 to 9 days, of which 58.8% patients presented with delayed flatus that was longer than 3 days. Univariate analysis showed that delayed postoperative flatus was significantly associated with the length of postoperative hospital stay ( P <0.001) and postoperative complications ( P =0.037). Multivariate analysis showed that intravenous fluid infusion at postoperative day 1 (POD1) (OR=1.001, 95% CI: 1.001-1.002, P =0.001) and duration of stoma ≥6 months (OR=2.005, 95% CI:1.155-3.657, P =0.014) were independent risk factors for delayed flatus., Conclusion: Increased intravenous fluid infusion at POD1 and duration of stoma ≥6 months were related to delayed recovery of gastrointestinal function after ileostomy reversal for rectal cancer patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Chu et al.)

Background: To assess the value of radiomics based on multiphases contrast-enhanced magnetic resonance imaging (CE-MRI) for early prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with human epithelial growth factor receptor 2 (HER2) positive invasive breast cancer., Methods: A total of 127 patients with newly diagnosed primary HER2 positive invasive breast cancer underwent CE-MRI before NAT and performed surgery after NAT. Radiomic features were extracted from the 1 st postcontrast CE-MRI phase (CE 1 ) and multi-phases CE-MRI (CE m ),respectively. With selected features using a forward stepwise regression, 23 machine learning classifiers based on CE 1 and CE m were constructed respectively for differentiating pCR and non-pCR patients. The performances of classifiers were assessed and compared by their accuracy, sensitivity, specificity and AUC (area under curve). The optimal machine learning classification was used to discriminate pCR vs non-pCR in mass and non-mass groups, uni-focal and unilateral multi-focal groups, respectively., Results: For the task of pCR classification, 6 radiomic features from CE 1 and 6 from CE m were selected for the construction of machine learning models, respectively. The linear SVM based on CE m outperformed the logistic regression model using CE 1 with an AUC of 0.84 versus 0.69. In mass and non-mass enhancement groups, the accuracy of linear SVM achieved 84% and 76%. Whereas in unifocal and unilateral multifocal cases, 79% and 75% accuracy were achieved by linear SVM., Conclusion: Multiphases CE-MRI imaging may offer more heterogeneity information in the tumor and provide a non-invasive approach for early prediction of pCR to NAT in patients with HER2-positive invasive breast cancer., Competing Interests: The authors declare that they have no competing interests., (© 2021 Li et al.)

Purpose: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma., Methods: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT 1 /MRI 1 , CT 2 /MRI 2 , CT 3 /MRI 3 , and CT 4 /MRI 4 ) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan 1 , plan 2 , plan 3 and plan 4 ) were made. The dose of the initial plan (plan 1 ) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan 1-2 and plan 1-3 ) and by superimposing the doses to obtain the ART plans (plan 10+20 and plan 20+10 ), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans., Results: Compared with the projection plan, the D 2 to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D 2 /D mean to the brainstem, optic chiasm and pituitary, as well as the V 20 , V 30 , V 40 and V 50 to the normal brain decreased. The D 2 to the pituitary and optic chiasm as well as the V 20 , V 30 , V 40 and V 50 to the normal brain in plan 10+20 were lower than those in plan 20+10 , while the CI to the PTV was higher than that in plan 20+10 . The TCP of the PTV in plan 10+20 was higher than that in plan 20+10 ., Conclusion: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Cao et al.)

Background: Breast cancer (BC) is a highly heterogeneous malignant tumor that affects women's health. Circular RNAs (circRNAs) are involved in tumor growth in many cancers. However, the role of hsa&#95;circ&#95;0101187 (circYY1) in BC is still unclear., Methods: Expression of circYY1, microRNA (miR)-769-3p, and YY1 (Yin Yang 1) mRNA was tested by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, colony formation, migration, and invasion were analyzed with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, and transwell assays. Glucose uptake, lactate product, and ATP (adenosine triphosphate) content were detected with corresponding kits. Several protein levels were measured with Western blotting. The regulatory mechanisms of the circYY1, miR-769-3p, and YY1 were validated by RNA immunoprecipitation (RIP) assay, dual-luciferase reporter assay, and/or RNA pull-down assay. The role of circYY1 in BC was confirmed by xenograft assay., Results: CircYY1 and YY1 were upregulated in BC, while miR-769-3p had an opposing result. Also, BC patients with high circYY1 expression had a poor prognosis. Downregulation of circYY1 decreased xenograft tumor growth in vivo. Both circYY1 inhibition and miR-769-3p elevation constrained BC cell viability, colony formation, migration, invasion, and glycolysis in vitro. CircYY1 acted as a sponge for miR-769-3p, which targeted YY1. CircYY1 sponged miR-769-3p to modulate YY1 expression. Both miR-769-3p inhibition and YY1 upregulation antagonized circYY1 silencing-mediated influence on malignancy and glycolysis of BC cells., Conclusion: CircYY1 promoted glycolysis and tumor growth via increasing YY1 expression through sponging miR-769-3p in BC, offering a promising therapeutic target and prognostic biomarker for BC., Competing Interests: The authors declare that they have no financial or non-financial conflicts of interest for this work., (© 2021 Zhang et al.)

Background: Breast cancer is one of the most common cancer with high risk in females all over the world. It is usually complicated with depression, which can further accelerate the development and progression of breast tumors. We aim to identify a new drug and identify its functional mechanism in the regulation of hippocampal microglia (MG) in breast cancer complicated with depression (BCCD)., Methods: The activation model of MG was established by treatments from corticosterone (CORT) or lipopolysaccharides (LPS). The inhibitory effects of resatorvid on MG were investigated by CCK-8, ROS, immunofluorescence, TUNEL, scratch test, ELISA, RT-qPCR and Western blot. BCCD animal model was established using 4T1 inflammatory breast cancer cells and CORT treatment in vitro. Open field experiment (OFE), tail suspension test (TST), ELISA, RT-qPCR and Western blot experiments were utilized to examine the effects of resatorvid on the animal model in vivo., Results: The cell viability and migration ability of the BCCD model group were suppressed. The expressions of inflammatory factors, ROS, and the apoptotic rate of the BCCD model group were up-regulated, in contrast to the control group. The expressions related to the TLR4/NF-κB/NLRP3 signaling in the BCCD model group were also elevated. Resatorvid reversed the above changes, which showed good therapeutic effects in depression-related behavioral changes, tumor treatment, and blood-brain barrier function., Conclusion: In summary, resatorvid inhibited the activation of hippocampal MG in BCCD by regulating TLR4/NF-κB/NLRP3 signaling pathway., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 Luo et al.)

Introduction: Immuno-checkpoint inhibitors (ICIs) in advanced gastric cancer either as monotherapy or in combining strategies are rapidly evolving but still in early phase. Various efforts have been made to provide insights into regulating immune checkpoint molecule programmed cell death ligand-1 (PD-L1) expression to improve ICIs efficacy. The aim of this study was to investigate the effect and potential mechanism of miR-200c nanoparticles combined with radiotherapy in gastric cancer cells., Methods: We prepared miR-200c-loaded nanoparticles (miR-200c NPs) to achieve targeted delivery of miR-200c to AGS cells. The roles of miR-200c NPs and radiotherapy in regulating the viability of AGS cells were assessed by CCK-8 toxicity test and Annexin V-FITC/PI apoptosis kit. Flow cytometry was used to analyze expression of PD-L1 and CD44 on the surface of AGS cells treated by miR-200c NPs and/or ionizing radiation. Enzyme-linked immunosorbent assay (ELISA) was used to test the level of transforming growth factor-beta 1 (TGF-β1) secreted by AGS cells. The cooperation mechanism between miR-200c NPs and radiotherapy was also explored in vitro., Results: Compared with naked miR-200c mimics, miR-200c NPs significantly downregulated PD-L1 expression of gastric cancer cells. The combination of miR-200c NPs and radiotherapy showed significantly synergistic inhibitory effect on gastric cancer cells by inhibiting immune escape mediated by PD-L1, reversing EMT phenotype as well as abrogating cancer stem cells (CSCs)-associated properties of tumor cells., Conclusion: MiR-200c NPs sensitized gastric cancer cells to radiotherapy by regulating PD-L1 expression and EMT., Competing Interests: The authors declare no competing interests., (© 2020 Qian et al.)

Background: Circ&#95;0072995 is a novel identified circRNA and has been identified to involve in the metastasis of breast cancer. However, the detailed function and mechanism of circ&#95;0072995 in the biological property of breast cancer cell remain vague., Materials and Methods: The expression of circ&#95;0072995, microRNA (miR)-149-5p and serine hydroxymethyltransferase 2 ( SHMT2 ) mRNA was detected using quantitative real-time polymerase chain reaction. Western blot was used to detect the protein levels of SHMT2 , hexokinase-2 (HK-2), lactate dehydrogenase a chain (LDHA), and glucose transporter 1 (GLUT1). Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity analysis, cell adhesion assay and transwell assay, respectively. Glucose metabolism was calculated by measuring glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. The interaction between miR-149-5p and circ&#95;0072995 or SHMT2 was confirmed by dual-luciferase reporter assay. In vivo tumorigenesis was performed using the murine xenograft model., Results: Circ&#95;0072995 and SHMT2 were up-regulated in breast cancer tissues and cell lines, and knockdown of circ&#95;0072995 or SHMT2 suppressed cell malignant properties and anaerobic glycolysis; importantly, SHMT2 overexpression attenuated the anticancer action of circ&#95;0072995 knockdown in breast cancer. Besides, we also found circ&#95;0072995 directly targeted miR-149-5p, thereby regulating its downstream gene SHMT2 by competitively binding to miR-149-5p. Additionally, xenograft analysis showed circ&#95;0072995 silencing suppressed tumor growth via regulating SHMT2 and miR-149-5p in vivo., Conclusion: This study demonstrated that circ&#95;0072995 promoted cell malignant phenotypes and anaerobic glycolysis in breast cancer via up-regulating SHMT2 through sponging miR-149-5p, indicating a promising molecular target for breast cancer treatment., Competing Interests: The authors declare that they have no competing interests., (© 2020 Qi et al.)

Background: This study was to investigate the efficacy and safety of anlotinib for elderly patients with previously treated extensive-stage small cell lung cancer (ES-SCLC) and the prognostic significance of common adverse reactions., Patients and Methods: A total of 79 elderly patients (≥60 years) with ES-SCLC who failed after at least two lines of previous systemic therapy were included. Baseline characteristics of the patients were collected. Follow-up was conducted regularly. Adverse reactions were documented. Survival curves were drawn using Kaplan-Meier method. Univariate analysis was assessed using log rank test, and multivariate analysis was adjusted by Cox regression analysis. Additionally, the prognostic significance of common adverse reactions was performed., Results: All of the 79 patients were available for evaluation of efficacy. Partial response (PR) was observed in 7 patients, stable disease (SD) was noted in 48 patients and progressive disease (PD) was confirmed in 24 patients. Consequently, the objective response rate (ORR) was 8.9% and disease control rate (DCR) was 69.6%. The median progression-free survival (PFS) of the 79 elderly patients with ES-SCLC was 3.0 months [95% confidence interval (CI): 2.02-3.98]. The median overall survival (OS) was 7.1 months (95% CI: 5.07-9.13). Safety profile demonstrated that the relatively common adverse reactions of the elderly patients with ES-SCLC receiving anlotinib treatment were hypertension (40.5%), hand-foot syndrome (HFS, 31.6%), diarrhea (27.8%), decreased appetite (20.3%), fatigue (17.7%) and weight loss (17.7%). Interestingly, the prognostic significance of common adverse reactions indicated that the median PFS of patients with hypertension and without hypertension was 4.35 and 2.95 months, respectively ( P =0.01), and the median PFS of patients with HFS and without HFS was 4.20 and 2.95 months, respectively ( P =0.03)., Conclusion: The preliminary efficacy and safety of anlotinib in the treatment for elderly patients with previously treated ES-SCLC was satisfactory, and patients with hypertension and hand-foot syndrome might confer superior prognosis., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2020 Song et al.)

Purpose: To identify MRI-based radiomics signature (Rad-score) as a biomarker of risk stratification for disease-free survival (DFS) in patients with HER2-positive invasive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC) and establish a radiomics-clinicoradiologic-based nomogram that combines Rad-score, MRI findings, and clinicopathological variables for DFS estimation., Patients and Methods: A total of 127 patients were divided into a training set and testing set according to the ratio of 7:3. Radiomic features were extracted from multiphase CE-MRI (CE m ). Rad-score was calculated using the LASSO (least absolute shrinkage and selection operator) regression analysis. The cutoff point of Rad-score to divide the patients into high- and low-risk groups was determined by receiver operating characteristic curve analysis. A Kaplan-Meier survival curves and the Log rank test were used to investigate the association of the Rad-score with DFS. Univariate and multivariate Cox proportional hazards model were used to determine the association of Rad-score, MRI features, and clinicopathological variables with DFS. A radiomics-clinicoradiologic-based nomogram combining the Rad-score, MRI features, and clinicopathological findings was plotted to validate the radiomic signatures for DFS estimation., Results: The Rad-score stratified patients into high- and low-risk groups for DFS in the training set ( P <0.0001) and was validated in the testing set ( P =0.002). The radiomics-clinicoradiologic-based nomogram estimated DFS (training set: C-index=0.974, 95% confidence interval (CI)=0.954-0.994; testing set: C-index=0.917, 95% CI=0.842-0.991) better than the clinicoradiologic-based nomogram (training set: C-index=0.855, 95% CI=0.739-0.971; testing set: C-index=0.831, 95% CI=0.643-0.999)., Conclusion: The Rad-score is an independent biomarker for the estimation of DFS in invasive HER2-positive breast cancer with NAC and the radiomics-clinicoradiologic-based nomogram improved individualized DFS estimation., Competing Interests: Shaofeng Duan is an employee of GE Healthcare China. The authors of this manuscript declare no other potential conflicts of interest in this work., (© 2020 Li et al.)

Purpose: Non-curative resection (NCR) remains problematic in some cases of early gastric carcinomas (EGCs) treated by endoscopic submucosal dissection (ESD). The aim of this study was to identify predictors of NCR, especially of eCura C1 and eCura C2 resections, before ESD and study long-term outcomes of EGC patients with NCR., Patients and Methods: A retrospective review of medical records was conducted over an 8-year period for EGCs undergoing ESD. Clinicopathologic and endoscopic characteristics and patients' survival were analyzed. Risk factors for NCR and eCura C1 and C2 resections were assessed by logistic analyses. Survival of patients was estimated with the Kaplan-Meier method with a Log rank test., Results: A total of 463 patients with 472 lesions were qualified. By univariate and multivariate analyses, the predictors for NCR and eCura C2 resections were tumor size >20 mm, tumors located in cardia-fundus, uneven surface, margin elevation, and mixed and undifferentiated types, and those for eCura C1 resection were tumors located in cardia-fundus, negative lifting sign, and mixed and undifferentiated types. The 5-year cancer-specific and cancer-free survival rates were 100.0% and 94.2%, and 95.3% and 83.4% in the curative resection (CR) and NCR groups, respectively. The 5-year cancer-specific and cancer-free survival rates were significantly greater in the CR group than that in the NCR group ( P <0.0001)., Conclusion: In this cohort, we identified various endoscopic and pathologic features of EGCs to predict NCR, especially eCura C1 and eCura C2 resections before ESD. These clinically valuable factors would be very informative to endoscopists and surgeons who perform ESD to resect EGCs., Competing Interests: The authors declare no conflict of interests for this article., (© 2020 Xu et al.)

Background: Hypoxia has been shown to induce the malignant progression of cancer, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) is considered to be an important regulator of cancer progression. However, the role of a newly discovered circRNA, circ&#95;0000376, in the progression of NSCLC is unclear., Methods: The relative expression levels of circ&#95;0000376, miR-1182 and neuro-oncological ventral antigen 2 (NOVA2) were detected via quantitative real-time polymerase chain reaction (qRT-PCR). Glucose consumption and lactate production were determined using Glucose Assay Kit and Lactate Assay Kit, respectively. Moreover, the protein levels of glycolysis markers and NOVA2 were measured using Western blot (WB) analysis. Furthermore, 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess cell viability, and transwell assay was employed to evaluate cell migration and invasion. The interaction between miR-1182 and circ&#95;0000376 or NOVA2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In addition, animal experiments were conducted to assess the influence of circ&#95;0000376 silencing on NSCLC tumor growth in vivo., Results: Circ&#95;0000376 was upregulated in NSCLC, and its high expression was related to the poor overall survival of NSCLC patients. Hypoxia could enhance circ&#95;0000376 expression and promote the glycolysis, viability, migration, and invasion of NSCLC cells. However, silencing of circ&#95;0000376 could inhibit the glycolysis, viability, migration, and invasion of hypoxia-induced NSCLC cells. Additionally, circ&#95;0000376 could sponge miR-1182, and miR-1182 could target NOVA2. MiR-1182 silencing could reverse the inhibitory effect of circ&#95;0000376 knockdown on NSCLC progression, and NOVA2 overexpression also could reverse the suppressive effect of miR-1182 overexpression on NSCLC progression. Meanwhile, miR-1182 inhibitor could invert the negative regulation effect of circ&#95;0000376 silencing on NOVA2 expression. In addition, circ&#95;0000376 knockdown inhibited the NSCLC tumor growth via regulating the miR-1182 and NOVA2 expression in vivo., Conclusion: Circ&#95;0000376 promoted NSCLC progression by regulating the miR-1182/NOVA2 axis, suggesting that circ&#95;0000376 might be a potential biomarker for NSCLC treatment., (© 2020 Li et al.)

Purpose: To explore the laparoscopic technique with the retroperitoneal approach for complex adrenal tumors., Patients and Methods: The clinical data of 11 patients with complex adrenal tumors from July 2017 to July 2018 were analyzed retrospectively. Among them, there were 4 males and 7 females, 4 with adrenal myelolipomas, 3 with adrenal pheochromocytomas, 2 with adrenal cysts, 1 with adrenocortical adenoma and 1 with adrenal ganglioneuroma. The average tumor diameter was 6.5 ± 1.2 cm, and the average age of the patients was 48 ± 13 years., Results: All the operations were successfully completed. The average operation time was 95 ± 15 min, the average amount of blood loss was 50 ± 15 mL, and the average postoperative hospital stay was 2.6 ± 1.3 days. No tumor recurrence was found after 1 year of follow-up., Conclusion: Retroperitoneal laparoscopic surgery is effective for the treatment of complex adrenal tumors, but it requires good surgical skills. Surgeons skilled in laparoscopic technology can safely carry out retroperitoneal laparoscopic surgery for complex adrenal tumors., Competing Interests: The authors report no funding and no conflicts of interest for this work., (© 2020 Huang et al.)

Purpose: To evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in treating hypovascular hepatocellular carcinoma (HCC)., Materials and Methods: The medical records based on HCC patients who underwent TACE from January 2016 to June 2019 were reviewed in the study. The diagnosis of hypovascular HCC was conducted by two senior radiologists according to imaging. We evaluated the adverse events (AEs), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) in the study., Results: A total of 98 patients with hypovascular HCC were included in the study. 46 patients underwent DEB-TACE treatment, and 52 patients underwent C-TACE treatment. The PFS of DEB-TACE group and C-TACE group was 12.0 months and 7.0 months ( P < 0.001), and OS was 21.0 months and 14.0 months ( P = 0.035), respectively. In addition, DEB-TACE group had better ORR (76.1% vs 40.4%, P < 0.001) and DCR (91.3% vs 75.0%, P = 0.033) compared to C-TACE group. The occurrence rate of AEs showed no difference between the two groups (67.3% vs 57.7%, P = 0.323). Furthermore, we found that DEB-TACE can be identified as a positive independent prognostic factor for improved PFS and OS., Conclusion: DEB-TACE, as an effective treatment, can yield better objective response rate, similar safety profile and improved survival for hypovascular HCC patients compared to C-TACE., Competing Interests: All authors declare that they have no conflicts of interest in this work., (© 2020 Shi et al.)

Purpose: To investigate the potential factors to predict severe myelosuppression among low-risk gestational trophoblastic neoplasia (GTN) patients with single-agent methotrexate (MTX) chemotherapy. To analyze reproductive outcomes of patients with or without severe myelosuppression after achieving complete remission (CR)., Patients and Methods: The retrospective study included 319 low-risk GTN patients registered from January 2008 to December 2018 in our hospital. Patients were divided into two groups according to myelosuppression grading. Their clinical data and reproductive outcomes were compared and analyzed., Results: A higher proportion of patients in group A received second-line chemotherapy than group B ( P <0.001). The number of total chemotherapy courses was more in group A than group B ( P =0.001), while the number of MTX chemotherapy courses was more in group B than group A ( P =0.001). When the joint predictor of pretreatment albumin (ALB) was not more than 44.5 g/L, pretreatment serum creatinine (Scr) was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses was not less than four, there was a moderate predictive value. There was no significant difference of reproductive outcomes between the two groups after achieving CR., Conclusion: Although some patients developed severe myelosuppression, MTX was still the effective first-line treatment for low-risk GTN patients. Patient's pretreatment ALB was not more than 44.5 g/L, pretreatment Scr was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses not less than four could be used as combined predictors to recognize the risk of severe myelosuppression. Severe myelosuppression had no significant adverse influence on fertility after achieving CR., Competing Interests: The authors declare no conflict of interest in this work., (© 2020 Tu et al.)

Purpose: The long noncoding RNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) plays well-defined roles in the malignant progression of hepatocellular carcinoma. The purpose of this study was to determine whether DLGAP1-AS1 affects the aggressive behavior of gastric cancer (GC)., Methods: DLGAP1-AS1 expression in GC tissue samples and cell lines was determined by reverse-transcription quantitative PCR. GC cell proliferation, apoptosis, migration, invasion, and tumor growth in vitro as well as in vivo were examined by the Cell Counting Kit-8 assay, flow-cytometric analysis, transwell migration and invasion assays, and xenograft model experiments, respectively., Results: DLGAP1-AS1 was overexpressed in GC tissue samples and cell lines. Among patients with GC, the increased level of DLGAP1-AS1 correlated with tumor size, TNM stage, lymph node metastasis, distant metastasis, and shorter overall survival. The knockdown of DLGAP1-AS1 suppressed GC cell proliferation, migration, and invasion in vitro, as well as promoted cell apoptosis and hindered tumor growth in vivo. Mechanistically, DLGAP1-AS1 functioned as a competing endogenous RNA for microRNA-628-5p (miR-628-5p) in GC cells, thereby increasing the expression of the miR-628-5p target astrocyte elevated gene 1 (AEG-1). Functionally, the recovery of the miR-628-5p/AEG-1 axis output attenuated the effects of DLGAP1-AS1 knockdown in GC cells., Conclusion: DLGAP1-AS1 is a pleiotropic oncogenic lncRNA in GC. DLGAP1-AS1 plays a pivotal part in the oncogenicity of GC in vitro and in vivo by regulating the miR-628-5p/AEG-1 axis. DLGAP1-AS1, miR-628-5p, and AEG-1 form a regulatory pathway to facilitate GC progression, suggesting this pathway as an effective target for the treatment of GC., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Deng et al.)

Objective: The use of hepatic artery infusion (HAI) as a regional therapy against liver metastasis has rarely been reported in gastric cancer. This study aimed to evaluate the efficacy and safety of HAI oxaliplatin plus oral S-1 chemotherapy in first-line palliative therapy for gastric cancer with multiple liver metastases (GCLM)., Methods: We reviewed the records of five patients with GCLM who received HAI oxaliplatin (70-80 mg/m 2 2 hrs d1,15) administered via a port-catheter system and S-1 with oral (35-40 mg/m 2 twice daily for d1-14, 28 days for one cycle). Follow-up examination and efficacy evaluation were executed periodically., Results: Until the 4th cycle response evaluation, the local effective rate and control rate were 40% and 80%, respectively; only one patient developed progression. HAI chemotherapy had a better local control against liver metastases (median progression-free survival: hepatic, 8.8 months vs. extrahepatic, 6.2 months), accompanied by less systemic toxicity, decreased tumour markers and symptomatic relief., Conclusion: HAI oxaliplatin plus oral S-1 chemotherapy can be considered as a new choice of first-line treatment for GCLM, which is also a good approach for controlling extrahepatic lesions with less adverse events., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 Wang et al.)

Objective: Casein kinase 2 a1 (CSNK2A1) has been shown to be involved in tumorigenesis by enhancing several oncogenic signaling pathways in various cancers. However, the function and mechanism of CSNK2A1 in gastric cancer remain unclear, and this study aimed to elucidate the role of CSNK2A1 in gastric cancer., Methods: CSNK2A1 expression was assessed by Western blot and qPCR in four gastric cancer (GC) cell lines and one normal gastric epithelial cell line. Stable cancer cell lines with CSNK2A1 gene overexpression or knockdown were established to investigate the function and mechanism of CSNK2A1 in GC cells., Results: CSNK2A1 expression was higher in GC cells than in normal gastric epithelial cells. Stable overexpression of CSNK2A1 in SNU216 cells significantly increased cellular proliferation, invasion, and migration. Silencing CSNK2A1 expression in SGC-790 cells effectively inhibited its oncogenic function. We further verified that epithelial-mesenchymal transition (EMT) was affected by CSNK2A1 and that CSNK2A1 promotes GC cell invasion through the PI3K-Akt-mTOR signaling pathway., Conclusion: Our findings suggested that CSNK2A1 plays important oncogenic roles in GC invasion via EMT and the PI3K-Akt-mTOR signaling pathway and that CSNK2A1 may serve as a novel prognostic and/or therapeutic target in GC., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Jiang et al.)

Purpose: The biological functions of BHLHE41 in the proliferation of glioblastoma remained unexplored. We aimed to investigate the biological roles and underlying molecular mechanisms of BHLHE41 in glioblastoma., Materials and Methods: We used multiple methods, including Western blot analysis, soft agar colony-formation assay, CCK8 assay, and flow cytometry, to evaluate the changes in multiple cellular functions after BHLHE41 knockdown or overexpression in U87 and U251 cell lines. The TCGA database was then used to analyze the associations between BHLHE41 expression with clinicopathological factors and the overall survival (OS) of glioma patients., Results: This study determined that overexpression of BHLHE41 promoted glioma cell proliferation and colony formation. Besides, BHLHE41 upregulated cyclinD1, cyclinD3, and cyclinE1 expression and drove phase transition from G1 to S and G2 phases by upregulating these cyclins. In contrast, knockdown of BHLHE41 had an opposite effect on all of these parameters. However, BHLHE41 had no effect on apoptosis. Moreover, BHLHE41 activated MAPK/ERK signaling pathway to upregulate cyclinD1 expression. After the ERK signal pathway was blocked by a specific inhibitor, SCH772984, cyclinD1 upregulation was reversed. Furthermore, the median OS of low-grade glioma (LGG) patients with low to median level of BHLHE41 was 22.6 months, longer than that of the patients with high level of BHLHE41 (21.0 months)., Conclusion: BHLHE41 has an important role in the proliferation of glioblastoma and could serve as a novel candidate for targeted therapy of glioblastoma., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Wang et al.)

Background/Aims: The tumor-suppressive functions of interferon regulatory factor 6 (IRF6) in some tumors have been preliminarily established, but its pathogenesis and underlying molecular mechanisms in breast cancer, the most common malignancy in women, remains poorly understood. Methods: Pairs of typical breast cancer cell lines (high- and low-aggressive) in addition to 27 breast cancer tissue samples and 31 non-cancerous breast tissues were used to investigate the expression level of IRF6 and Lentivirus-mediated gain-of-function studies, short hairpin RNA-mediated loss-of-function studies in vivo and in vitro were used to validate the role of IRF6 in breast cancer. Next, we performed RNA-Seq analysis to identify the molecular mechanisms of IRF6 involved in breast cancer progression. Results: Our findings showed that IRF6 was downregulated in highly invasive breast cancer cell lines but upregulated in poorly aggressive ones. Functional assays revealed that elevated IRF6 expression could suppress cell proliferation and tumorigenicity, and enhanced cellular chemotherapeutic sensitivity. To identify the molecular mechanisms involved, we performed a genome-wide and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in breast cancer cells using RNA sequencing of gene expression profiles following the overexpression of IRF6. Genome-wide and KEGG analyses showed that IRF6 might mediate the PI3K-regulatory subunit PIK3R2, which in turn modulated the PI3K/AKT pathway to control breast cancer pathogenesis. Conclusion: We provide the first evidence of the involvement of IRF6 in breast cancer pathogenesis, which was found to modulate the PI3K/AKT pathway via mediating PIK3R2; indicating that IRF6 can be targeted as a potential therapeutic treatment of breast cancer., Competing Interests: The authors report no conflicts of interest in this work.

Background: The aim of this study was to develop and validate nomograms to predict the survival in patients with papillary thyroid cancer (PTC). Patients and methods: Adult patients who were surgically treated for PTC were selected from the Surveillance, Epidemiology and End Results (SEER) program (2004-2013). A multivariate analysis using the Cox proportional hazards regression was performed, and nomograms for predicting 10-year overall survival (OS) and cancer-specific survival (CSS) were constructed. The discrimination and calibration plots were used to measure the accuracy of the nomograms. Results: The records of 63,219 patients with PTC were retrospectively analyzed. Nine independent factors including age, race, sex, marital status, tumor size, extrathyroidal extension, radioactive iodine, T stage, and M stage were assembled into the OS nomogram. A nomogram predicting CSS was constructed based on eight factors (age, sex, marital status, tumor size, extrathyroidal extension, T stage, N stage, and M stage). With respect to the training set, the nomograms displayed improved discrimination power compared to the TNM staging system (6th edition) in both sets. The calibration curve for the probability of survival showed agreement between the predictive nomograms and the actual observation. Conclusion: We have successfully developed prognostic nomograms to predict OS and CSS for PTC with excellent discrimination and calibration., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: To evaluate a classification model of contrast-enhanced ultrasound (CEUS) and examine the characteristics of patients with false-negative diagnosis., Patients and Methods: A retrospective secondary analysis of a multicenter trial of CEUS for breast cancer diagnosis (from August 2015 to April 2017) was undertaken. Patients (n=1,023) with Breast Imaging Reporting and Data System 4-5 lesions on B-mode ultrasound underwent CEUS. Pathological diagnoses were available from surgical or biopsy specimens for correlation. Lesion maximum diameter (LMD), distance to the papilla (DtP), distance from the superficial edge of the lesion to the skin (DtS), distance from the deep edge of the lesion to the pectoralis muscle (DtPM), and body mass index (BMI) were evaluated., Results: Median age and BMI were 48.0 and 41.2 years and 23.2 and 22.4 kg/m 2 for patients with malignant and benign lesions, respectively. Overall sensitivity, specificity, and accuracy of CEUS for malignancy were 89.4%, 65.3%, and 75.8%, respectively. The patients with true-positive and false-negative diagnosis (ie, with malignant lesion) were older than those with false-positive and true-negative diagnosis (ie, with benign lesion). Patients with true-positive and false-positive diagnoses had higher BMI than patients with true-negative and false-negative diagnoses ( P =0.004). Patients with true-positive and false-negative diagnoses had larger LMD and DtP, as well as smaller DtS and DtPM., Conclusion: Older age, higher BMI, larger LMD and DtP, and smaller DtS and DtPM were associated with malignant lesions on CEUS. Patients with these characteristics should undergo further imaging., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment., Patients and Methods: A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining., Results: Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I-III accounted for 35 (49.3%) cases, while stage IVa-IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage ( P =0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein-Barr virus DNA load ( P =0.021), N stage ( P =0.009), M stage ( P =0.014), and clinical stage ( P =0.001)., Conclusion: dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: The aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression., Methods: The expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells., Results: The expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1., Conclusion: FGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The miR17-92 family is found to be aberrantly expressed and associated with clinicopathological characteristics in patients with various cancers, including digestive system cancers. However, its prognostic value is not yet established. Therefore, we performed a systematic review and meta-analysis to investigate the association between miR17-92-family expression and clinical outcomes in digestive system cancers. We searched the PubMed, Web of Science, Embase, and CNKI (Chinese) databases to retrieve eligible studies up to June 30, 2018. Prognostic data and clinicopathological features of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were extracted to evaluate correlations of the miR17-92 family with digestive system cancers. We used HRs to assess association between miR17-92-family expression and cancers prognosis. A total of 30 qualifying studies involving 4,056 subjects were included in this meta-analysis. Our results indicated that expression levels of miR17-92 can predict poor OS (HR 1.21, 95% CI 1.03-1.39; P =0). However, there was no relationship between the miR17-92 family and DFS (HR 0.86, 95% CI 0.6-1.11; P =0.170) or PFS (HR 1.37, 95% CI 0.83-1.91; P =0). Moreover, miR17-92 was related to TNM stage (III/IV vs I/II, HR 1.37, 95% CI 1.17-1.570; P =0.012), but there was no relationship between miR17-92 and metastasis (HR 1.64, 95% CI 1.34-1.95; P =0.491) or tumor size (≥5 cm vs <5 cm, HR 1.29, 95% CI 1.09-1.49; P =0.586). Subgroup analysis showed that miR17-92 expression was associated with poor OS among the Chinese subgroup (HR 1.28, 95% CI 1.08-1.48; P =0) and tissue samples (HR 1.12, 95% CI 0.93-1.31; P =0), while there was no association with other characteristics. Our results indicated that miR17-92 expression is significantly associated with poor survival in patients with digestive system cancers, suggesting that miR17-92 may be a promising prognostic marker to monitor prognosis and progression of cancers., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The survival advantage of radiotherapy for patients with extensive-disease small-cell lung cancer (ED-SCLC) has not been adequately evaluated., Methods: We analyzed stage IV SCLC patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry through January 2010 and December 2012. Propensity score analysis with 1:1 matching was performed to ensure well-balanced characteristics of all comparison groups. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and corresponding 95% CI., Results: Overall, for all metastatic ED-SCLC, receiving radiotherapy was associated with both improved OS and CSS. Radiotherapy for thoracic lesion and any metastatic sites could significantly improve the OS and CSS, except for brain metastasis. For M1a-SCLC patient, radiotherapy, most likely to the primary site, significantly improved the survival ( P <0.001). Furthermore, for those ED-SCLC patients with ≥ 2 metastatic sites, that is, polymetastatic ED-SCLC patients, radiation also significantly improved the median OS from 6.0 to 8.0 months ( P= 0.015) and the median CSS from 7.0 to 8.0 months ( P= 0.020)., Conclusion: The large SEER results support that radiotherapy in addition to chemotherapy might improve the survival of patients with metastatic ED-SCLC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Phosphatase of regenerating liver-3 (PRL-3) has been shown to be highly expressed in various types of cancers and is related to poor prognosis. Our previous study showed that silencing of PRL-3 leads to increased reactive oxygen species (ROS). However, the mechanism of PRL-3 regulating ROS is not clear., Materials and Methods: PRL-3 or Repressor activator protein 1 (RAP1) was knockdown in human colorectal cancer cell lines HCT116 and SW480. The mRNA level was measured by quantitative real-time (qRT)-PCR and the protein level was measured by western blot. ROS was detected by specific oxidationsensitive fluorescent probes. Cell cycle was analyzed through flow cytometry. Luciferase assay and chromatin immunoprecipitation (ChIP) were performed to investigate the regulation of RAP1 by PRL-3. Gene expression correlation was analyzed through an interactive web server. Statistical analysis was performed with SPSS software., Results: Knockdown of PRL-3 significantly increases mitochondrial superoxide anion, mitochondria membrane potential, and induces cell cycle arrest. Decreased PRL-3-induced mitochondrial superoxide anion accumulation is related to the downregulation of RAP1, which could also affect the level of mitochondria superoxide anion. PRL-3 regulates the expression of RAP1 through binding to the promoter of rap1 gene. PRL-3 could regulate the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) through the mediation of RAP1. Both PRL-3 and RAP1 could regulate the expression of manganese superoxide dismutase 2 (SOD2) and the uncoupling protein 2 (UCP2), which may be related to PRL-3 suppression induced mitochondria superoxide anion., Conclusion: Our study presents the first evidence that PRL-3 is involved in the regulation of mitochondria superoxide anion as a transcriptional factor., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background and Purpose: Abundant studies have shown that lncRNA PANDAR plays an oncogenic role in human solid tumors. Although abnormal expression of PANDAR has been well investigated in solid tumors, it was rarely studied in hematologic diseases. Hence, the aim of this study was to determine the PANDAR expression level and its clinical significance in patients with acute myeloid leukemia (AML)., Materials and Methods: For detecting the expression level of PANDAR in 119 AML patients and 26 controls, real-time quantitative PCR was used in this study. The prognostic values were evaluated by using Kaplan-Meier analysis, Cox regression analyses, and logistic regression analysis., Results: PANDAR was significantly overexpressed in AML and might be a promising biomarker which could distinguish AML from normal samples ( P <0.001). Patients with high expression of PANDAR ( PANDAR high ) were older and showed higher bone marrow blasts than patients in PANDAR low group ( P =0.029 and 0.032, respectively). Significant differences between these groups were also detected regarding risk group and karyotype finding ( P =0.009 and 0.041, respectively). Importantly, PANDAR high patients presented a significant lower complete remission rate compared to PANDAR low patients ( P <0.001). Furthermore, Kaplan-Meier analysis showed that PANDAR high patients had shorter overall survival compared to PANDAR low patients observing the whole AML cohort, and also in the non-M3 group of patients ( P <0.001 and P =0.005, respectively). Multivariate analysis of Cox and logistic regression analysis confirmed that high PANDAR expression was an independent unfavorable risk factor for overall survival and complete remission in both observed patient groups., Conclusion: These results revealed that PANDAR was overexpressed in AML, and that higher PANDAR expression was associated with poor clinical outcome. Our study therefore suggests that PANDAR expression is a promising biomarker for prognostic prediction for AML., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: This study aimed to investigate the value of shear wave elastography (SWE) for characterization of breast masses in a Chinese population., Patients and Methods: Two thousand two hundred seventy-three women consented to be prospectively enrolled for the characterization of breast masses with ultrasound and SWE. Breast masses were known from symptoms, palpability, and/or previous imaging screening with mammography and/or ultrasound. Correlation of SWE qualitative and quantitative features with malignancy risk and impact on diagnostic performance of combining SWE features were assessed, and the Breast Imaging Reporting and Data System (BI-RADS) scoring was calculated using histopathology as reference., Results: Data of 2,262 masses (median size: 13 mm; range: 1.3-50) from 2,262 patients (median age: 43 years; range: 18-91) were investigated, of which 752 (33.3%) were malignant. Sensitivity and specificity of BI-RADS diagnosis were 97.5% (733/752) and 54.8% (827/1,510), respectively. By logistic regression, the combination of maximum elasticity ( E max ) measurements with BI-RADS assessments increased the area under the receiver operating characteristic curve from 0.908 (95% CI: 0.896-0.920) to 0.954 (95% CI: 0.944-0.962). Using E max of 30 kPa or lower to selectively downgrade BI-RADS 4a masses to follow-up, and E max of 160 kPa or higher to selectively upgrade BI-RADS 3 lesions to biopsy, specificity significantly increased from 54.8% (827/1,510) to 66.1% (998/1,510) ( P <0.001) while sensitivity decreased nonsignificantly from 97.5% (733/752) to 96.9% (729/752) ( P =0.2891). Positive predictive value for biopsy recommendation increased from 51.7% (733/1,417) to 58.7% (729/1,241) ( P <0.001)., Conclusion: Adding SWE maximum stiffness to BI-RADS 3 and BI-RADS 4a breast masses in a Chinese population increased significantly the specificity of breast ultrasonography, without significant change in sensitivity., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Lenalidomide is effective for the treatment of low-risk myelodysplastic syndromes with deletion 5q abnormalities. However, whether lenalidomide leads to a significant improvement in treatment response and overall survival (OS) in cases of acute myeloid leukemia (AML) remains controversial. A systematic review and a meta-analysis were performed to evaluate the efficacy and safety of lenalidomide in the treatment of AML., Methods: Clinical studies were identified from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and ClinicalTrials.gov. Efficacy outcomes included overall response rate (ORR), complete remission (CR), and OS. Safety was evaluated based on the incidence of grade 3 and 4 treatment-related adverse events (AEs)., Results: Eleven studies were included in our meta-analysis; collectively these studies featured 407 AML patients. Pooled estimates for overall ORR and CR were 31% (95% CI: 26%-36%) and 21% (95% CI: 16%-27%), respectively. Thrombocytopenia, anemia, neutropenia, and infection were the most common grade 3 and 4 AEs., Conclusion: Lenalidomide may have some clinical activity in AML, but the population that would benefit from lenalidomide and incorporating lenalidomide into combination drug strategies need to be better defined., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Spy1 (SPDYA) is a new discovered cell cycle protein capable of promoting cell proliferation dependent on cyclin-dependent kinase-2 activation. However, to the best of our knowledge, the expression of Spy1 in colorectal cancer (CRC) tissues remains virtually unknown., Materials and Methods: In this retrospective study, we investigated the mRNA and protein expression levels of Spy1 in CRC tissues and corresponding non-cancerous tissues with the analyses of quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. In our research, the prognostic significances of Spy1 expression were further explored by univariate and multivariate survival analyses of 203 patients who were followed up., Results: The results demonstrated that the levels of Spy1 mRNA were significantly higher in CRC tissues compared with corresponding non-cancerous tissues ( p =0.0002). The results of immunohistochemistry demonstrated that the expressions of Spy1 were significantly associated with clinicopathological parameters, including T stage ( χ 2 =7.126, p =0.028) and TNM stage ( χ 2 =9.461, p =0.009). Kaplan-Meier analysis results indicated that high Spy1 expression (HR=2.573, p <0.001) and TNM stage (HR=1.494, p =0.011) were independent factors to predict poor prognosis for patients with CRC., Conclusion: We concluded that high Spy1 expression is significantly associated with unfavorable prognosis in CRC and could serve as a potential prognostic marker in clinical diagnosis of CRC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To compare the survival outcomes in locally advanced breast cancer (LABC) patients receiving post-mastectomy radiotherapy (PMRT) with and without immediate breast reconstruction., Methods: We used the Surveillance, Epidemiology, and End Results program to include LABC patients who were treated/not treated with immediate breast reconstruction followed by PMRT between 2003 and 2010. Statistical analysis was performed using the chi-squared test, Kaplan-Meier survival analysis, and Cox regression analysis. A 1:1 propensity score matching method was performed to decrease the selection bias., Results: We identified 1,732 patient-pairs that were completely matched. In the unmatched population, 8,198 and 1,802 patients received mastectomy only and immediate breast reconstruction, respectively. Patients who received immediate breast reconstruction had better breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.880, 95% CI 0.783-0.989, P = 0.032) and overall survival (OS) (HR 0.846, 95% CI 0.758-0.943, P = 0.003) than patients who underwent mastectomy alone. However, in the matched population, there was comparable BCSS and OS between patients who received immediate breast reconstruction and mastectomy alone. Subset analysis in the matched population found that immediate breast reconstruction was associated with better BCSS (HR 0.750, 95% CI 0.614-0.917, P = 0.005) and OS (HR 0.779, 95% CI 0.644-0.942, P = 0.010) compared to patients aged <50 years who received mastectomy alone., Conclusion: There are comparable survival outcomes in LABC patients who received immediate breast reconstruction or mastectomy alone followed by PMRT. However, patients aged <50 years had a survival advantage after immediate breast reconstruction., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To investigate the association of pretreatment Ki67 expression and the derived neutrophil-lymphocyte ratio (dNLR) with clinical outcomes in nasopharyngeal carcinoma (NPC)., Patients and Methods: For the study, 46 patients diagnosed with NPC at our hospital were recruited between April 2013 and December 2015. All patients were histologically confirmed to have non-keratinizing undifferentiated NPC. The expression of Ki67 proteins in NPC tissue was analyzed immunohistochemically, and the dNLR was assessed in the peripheral blood, both before treatment. Stage I and II disease was treated with radiotherapy with or without concurrent chemotherapy, and stage III and IV disease was treated with cisplatin-based radiochemotherapy and neoadjuvant chemotherapy regimens., Results: Forty-five of the 46 patients met the criteria, and the median follow-up period was 41 months (15-56 months). The cutoff values for Ki67 and dNLR were 77.5% and 2.01%, respectively. The 3-year overall survival (OS) and progression-free survival rates in the high versus low Ki67 expression groups were 62.5% vs. 93.1% ( P = 0.009) and 56.3% vs. 93.1% ( P = 0.003), respectively. The 3-year OS rate of patients with high dNLR vs. low dNLR was 64.3% vs. 90.3% ( P = 0.023). In the Cox risk ratio model, Ki67 expression and dNLR were independent prognostic factors for OS. Patients were then divided into three groups based on Ki67 expression and dNLR (high risk, both factors were high; intermediate risk, one factor was high; and low risk, neither factor was high). The 3-year OS rates were 20%, 85%, and 95% for the high, intermediate, and low risk groups, respectively ( P < 0.001)., Conclusion: Pretreatment Ki67 and dNLR levels can be used as independent prognostic markers in NPC, and elevated values are associated with poor prognosis. Concurrently, high Ki67 expression and dNLR predict a significantly adverse outcome., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The AURA3 clinical trial has shown that advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations in circulating tumor DNA (ctDNA) could benefit from osimertinib., Purpose: The aim of this study was to assess the usefulness of QuantStudio™ 3D Digital PCR System platform for the detection of plasma EGFR T790M mutations in NSCLC patients, and compare the performances of 3D Digital PCR and ARMS-PCR., Patients and Methods: A total of 119 Chinese patients were enrolled in this study. Mutant allele frequency of plasma EGFR T790M was detected by 3D Digital PCR, then 25 selected samples were verified by ARMS-PCR and four of them were verified by next generation sequencing (NGS)., Results: In total, 52.94% (69/119) had EGFR T790M mutations detected by 3D Digital PCR. In 69 positive samples, the median mutant allele frequency (AF) was 1.09% and three cases presented low concentration (AF <0.1%). Limited by the amount of plasma DNA, 17 samples (AF <2.5%) and eight samples (T790M-) were selected for verification by ARMS-PCR. Four of those samples were verified by NGS as a third verification method. Among the selected 17 positive cases, ten samples presented mutant allele frequency <0.5%, and seven samples presented intermediate mutant allele frequency (0.5% AF 2.5%). However, only three samples (3/17) were identified as positive by ARMS-PCR, namely, P6 (AF =1.09%), P7 (AF =2.09%), and P8 (AF =2.21%). It is worth mentioning that sample P9 (AF =2.05%, analyzed by 3D Digital PCR) was identified as T790M- by ARMS-PCR. Four samples were identified as T790M+ by both NGS and 3D Digital PCR, and typically three samples (3/4) presented at a low ratio (AF <0.5%)., Conclusion: Our study demonstrated that 3D Digital PCR is a novel method with high sensitivity and specificity to detect EGFR T790M mutation in plasma., Competing Interests: Disclosure The authors report no conflicts of interest in this work.