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The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles.Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency.After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three-cycle IC regimen was correlated with better OS and PFS than the two-cycle regimen for N2-3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0-1 patients. The incidences of acute toxicities were higher in the IC = 3 group.Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three-cycle IC regimen seemed to be preferable for N2-3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0-1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.

Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed.Data of ascending type (T3-4N0-1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted.Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer-specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677-0.711) and 0.678 (95%CI, 0.659-0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715-0.765) and 0.708 (95%CI, 0.679-0.737), separately.The as-constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS.

Background The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients.

De-Song Shen,1 Chang Yan,1 Yu Liang,1 Kai-Hua Chen,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaCorrespondence: Xiao-Dong Zhu Tel +86 771 533 1466Email zhuxdonggxmu@126.comPurpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy.Patients and Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test.Results: NPC patients with high levels of CD19+ B cells (> 9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly.Conclusion: NPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body’s immune function in NPC patients.Keywords: nasopharyngeal carcinoma, lymphocyte subsets, prognosis, chemoradiotherapy, immune function

Postoperative pulmonary complications (PPCs) most commonly occur after thoracic surgery. Not only prolonged hospital stay and increased financial expenses but also morbidity and even mortality may be troublesome for those with PPCs. Herein, we aimed to conduct a comprehensive systematic review and meta-analysis of available data to examine the effectiveness of incentive spirometry (IS) to reduce PPCs and shorten hospital stay. This systematic review and meta-analysis included 5 randomized controlled trials (RCT) and 3 retrospective cohort study (10,322 patients in total) in PubMed, Embase and Cochrane Library until September 31, 2021. We assessed the clinical efficacy of IS using length of hospital stay, PPCs, postoperative pneumonia, and postoperative atelectasis with meta-analysis, meta-regression and trial sequential analysis (TSA). With this meta-analysis, the length of hospital stay in patients undergoing IS was significantly shorter (1.8 days) than that in patients not receiving IS (MD = -1.80, 95% CI = -2.95 to -0.65). Patients undergoing IS also had reduced risk of PPCs (32%) and postoperative pneumonia (17.9%) with statistical significance than patients not undergoing IS (PPC: OR = 0.68, 95% CI = 0.51-0.90) (Pneumonia: OR = 0.821, 95% CI = 0.677-0.995).In meta-regression, the benefits of undergoing IS in patients with preoperative predicted FEV

Ru-Rong Peng,1 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Song Qu,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Oncology, Affiliated Wu-Ming Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 He-di Road, Nanning, 530021, People’s Republic of ChinaTel +86 15778028340Email zhuxdonggxmu@126.comPurpose: The prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC.Patients and Methods: This was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan–Meier methods.Results: Multivariate Cox analysis resulted that age, plasma Epstein–Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706– 0.738) and 0.747 (95% CI: 0.717– 0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680– 0.713) and 0.690 (95% CI: 0.660– 0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations.Conclusion: LAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.Keywords: intensity-modulated radiotherapy, nasopharyngeal carcinoma, lactate dehydrogenase to albumin ratio, platelet-to-lymphocyte ratio, tumor–node–metastasis staging system

Yu-Ting Jiang,1 Kai-Hua Chen,1 Zhong-Guo Liang,1 Jie Yang,1 Song Qu,1,2 Ling Li,1,2 Xiao-Dong Zhu1– 3 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Guangxi, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High‐Incidence‐ Tumor, Guangxi Medical University, Ministry of Education, Guangxi, People’s Republic of China; 3Department of Oncology, Affiliated Wuming Hospital of Guangxi Medical University, Guangxi, People’s Republic of ChinaCorrespondence: Xiao-Dong Zhu, Tel/Fax +86-771-5331466, Email zhuxiaodong@gxmu.edu.cnPurpose: We aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in advanced N-stage nasopharyngeal carcinoma (NPC).Patients and Methods: A total of 624 NPC patients with N2-3 stage received CCRT with or without IC were retrospectively reviewed. We constructed a nomogram for predicting overall survival (OS) based on the result of the multivariate analysis in the training cohort (n = 468) and then tested it on the validation cohort (n = 156). Harrell’s concordance indices (C-index) and time-independent receiver operating characteristic (tdROC) analysis were applied to evaluate the discriminatory ability of the nomogram and compare it with TNM staging. IC plus CCRT was compared with CCRT in the whole cohort and two risk groups based on the nomogram with balanced baseline characteristics. In addition, acute toxicities were compared between different treatment groups.Results: The nomogram showed good prognostic accuracy with a C-index of 0.716 (95% CI 0.669– 0.763) in the validation cohort. The 5-year OS of low and high-risk groups stratified by the nomogram were significantly different. IC+CCRT was significantly associated with superior OS as compared with CCRT (75.4 vs 52.6%, p = 0.009) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed (p = 0.843) in the low-risk group. IC plus CCRT was associated with more grade 1– 4 acute toxicities.Conclusion: Our study can help clinicians select NPC patients with advanced N stage who benefit from IC.Keywords: nasopharyngeal carcinoma, advanced N-stage, induction chemotherapy, survival, nomogram

To investigate the efficacy of chemotherapy among intermediate-risk (stage II/T3N0) nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT).We identified stage II/T3N0 NPC patients who received radiotherapy with or without chemotherapy from the Surveillance, Epidemiology and End Results database (2004-2019). Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method with log-rank test and Cox proportional hazards models to evaluate the efficacy of chemotherapy. Subgroup analysis was also conducted based on the baseline characteristics. Propensity score matching (PSM) was performed to balance the intergroup covariates.A total of 1623 patients were enrolled in the study, 1444 received chemoradiotherapy (CRT) and 179 received RT alone. CRT, compared to RT alone, was independently associated with a better OS (HR 0.57, 95% CI 0.45-0.71) and CSS (HR 0.55, 95% CI 0.39-0.79). After PSM, similar results were obtained, and CRT was superior to RT alone in terms of OS (HR 0.60, 95% CI 0.39-0.92) and CSS (HR 0.60, 95% CI 0.40-0.91). Subgroup analysis revealed that OS benefits from CRT were mainly observed in T0-2N1(HR 0.51, 95% CI 0.38-0.70) and T3N0 (HR 0.64, 95% CI 0.42-0.98) rather than T2N0 (HR 1.00, 95% CI 0.51-1.94). Interestingly, after PSM, OS benefits were still seen in T0-2N1 (HR 0.44, 95% CI 0.24-0.82), while not seen in T2N0 (HR 1.83, 95% CI 0.56-5.97) and T3N0 (HR 0.56, 95% CI 0.28-1.12).For T0-2N1 NPC patients, CRT was superior to RT alone with better survival, whereas, for T2-3N0 patients, CRT was comparable to RT alone. Prospective large studies should be encouraged to verify the results.

PurposeThe role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT).MethodsWe searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3–4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy.ResultsNine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44–0.82), LRFS (HR = 0.62, 95% CI 0.50–0.78), and PFS (HR = 0.65, 95% CI 0.54–0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46–1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62–1.15), LRFS (HR = 0.85, 95% CI 0.54–1.34), DMFS (HR = 0.96, 95% CI 0.60–1.54), and PFS (HR = 0.96, 95% CI 0.66–1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37–2.96), LRFS (HR = 0.70, 95% CI 0.34–1.45), DMFS (HR = 1.03, 95% CI 0.53–2.00), and PFS (HR = 1.04, 95% CI 0.58–1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3–4 leukopenia (RR = 4.00, 95% CI 2.29–6.97), mucositis (RR = 1.43, 95% CI 1.16–1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63–29.12). No significant differences of grade 3–4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85–13.94) was found between the two groups.ConclusionFor unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.

Objective Patients with chronic hepatitis C virus (HCV) infection are at high risk of developing hepatocellular carcinoma (HCC). Previous studies suggested that menopause may increase the risk of HCC. We investigated the association between bilateral oophorectomy (BO) and the risk of HCC in women with HCV infection. Study design We used data from the National Health Insurance Research Database of Taiwan and conducted a matched cohort study. Main outcome measures The main outcome was HCC. We used a competing risk model to adjust for potential confounding factors. Results From 1997–2013, we identified 2176 patients with BO and 8704 controls. A total of 107 HCC cases (4.9 %, 107/2176) were identified in the BO group compared with 465 HCC cases (5.3 %, 465/8704) in the control group. The incidence rates were 506.3 and 538.9 cases per 100,000 person-years among the HCV-infected patients with and without BO, respectively. The competing risk model showed that BO did not increase the risk of developing HCC. Furthermore, a sub-analysis of only women under 50 years of age similarly showed that BO did not increase the risk of developing HCC after adjusting for additional covariates. The log-rank test revealed that whether or not the patients had received HRT, patients with BO did not have an increased risk of developing HCC (non-BO vs BO with HRT, p = 0.10; non-BO vs BO without HRT, p = 0.09). The use of HRT after BO did not influence the risk of developing HCC. Conclusions This study examined a large dataset with a long follow-up period to test the relationship between BO and the risk of HCC in HCV-infected women. Our findings suggest that BO did not increase the risk of HCC, regardless of HRT usage, in these women.

Background: According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. Methods. Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients’ clinical and pathological characteristics were analyzed. Results. Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). Conclusions. MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens for T3-4N1M0 nasopharyngeal carcinoma (NPC) patients. Therefore, we established a nomogram to predict clinical prognosis and guide individualized IC in T3-4N1M0 NPC. Overall, 699 T3-4N1M0 NPC patients treated with CCRT with or without IC between January 2010 and December 2018 were examined. Overall survival (OS) was the main endpoint. A nomogram was developed that included prognostic variables selected by multivariable analysis. The risk score, which was calculated according to the nomogram, was used for risk stratification. The survival difference of patients undergoing CCRT with or without IC was then compared in risk-stratified subgroups. The nomogram yielded C-indexes of 0.708 (95% confidence interval [CI]: 0.682-0.734) in the training cohort and 0.670 (95% CI: 0.625-0.715) in the validation cohort. Calibration curves for 1-, 3- and 5-year OS suggested a good association between the nomogram predicted and observed probabilities. High-risk patients stratified by nomogram benefited from IC (IC + CCRT vs CCRT: 5-year OS: 77.8% vs 58.8%; P = 0.040; 5-year disease-free survival: 75.0% vs 58.2%; P = 0.017), whereas in the low-risk group, the application of IC was associated with worse locoregional recurrence-free survival and distant metastasis-free survival. This nomogram can serve as a reliable model for prognostic prediction and can be used to guide individualized treatment of T3-4N1M0 NPC. High-risk patients are candidates for IC before CCRT, while the use of IC for low-risk patients should be considered carefully.

Objective: The chest tube drainage system (CTDS) of choice for the pleural cavity after pulmonary resection remains controversial. This systematic review and network meta-analysis (NMA) aimed to assess the length of hospital stay, chest tube placement duration, and prolonged air leak among different types of CTDS. Methods: This systemic review and NMA included 21 randomized controlled trials (3399 patients) in PubMed and Embase until 1 June 2021. We performed a frequentist random effect in our NMA, and a P-score was adopted to determine the best treatment. We assessed the clinical efficacy of different CTDSs (digital/suction/non-suction) using the length of hospital stay, chest tube placement duration, and presence of prolonged air leak. Results: Based on the NMA, digital CTDS was the most beneficial intervention for the length of hospital stay, being 1.4 days less than that of suction CTDS (mean difference (MD): −1.40; 95% confidence interval (CI): −2.20 to −0.60). Digital CTDS also had significantly reduced chest tube placement duration, being 0.68 days less than that of suction CTDSs (MD: −0.68; 95% CI: −1.32 to −0.04). Neither digital nor non-suction CTDS significantly reduced the risk of prolonged air leak. Conclusions: Digital CTDS is associated with better outcomes than suction and non-suction CTDS for patients undergoing pulmonary resections, specifically 0.68 days shorter chest tube duration and 1.4 days shorter hospital stay than suction CTDS.

Objective This study aimed to explore the effect of silencing hTERT on the CSC-like characteristics and radioresistance of CNE-2R cells. Results Silencing hTERT suppressed CNE-2R cell proliferation and increased the cell apoptosis rate and radiosensitivity in vitro. Moreover, it could also inhibit the growth of xenografts and increase the apoptosis index and radiosensitivity in vivo. Further study discovered that after silencing hTERT, telomerase activity in CNE-2R cells was markedly suppressed, along with remarkably down-regulated stem cell-related protein levels both in vitro and in vivo. Conclusion Silencing hTERT can suppress the CSC-like characteristics of CNE-2R cells to enhance their radiosensitivity, revealing that hTERT may become a potential target for treating radioresistant NPC. Methods An RNAi lentiviral vector specific to the hTERT gene was constructed to infect CNE-2R cells, the hTERT silencing effect was verified through qPCR and Western blot assays, and telomerase activity was detected by PCR-ELISA. Moreover, radiosensitivity in vitro was detected through colony formation assays, CCK-8 assays and flow cytometry. Tumor growth and radioresistance were also evaluated using xenograft models, while the apoptosis index in xenografts was measured through TUNEL assay. Levels of stem cell-related proteins were determined in vitro and in vivo.

Objective The present study aimed to investigate the predictive value of some inflammatory indexes, such as the ratio of C-reactive protein-to-albumin (CAR), high-sensitivity C-reactive protein-to-albumin (HCAR), C-reactive protein-to-lymphocyte (CLR), and high-sensitivity C-reactive protein-to-lymphocyte (HCLR) in the survival and toxicity of nasopharyngeal carcinoma and provide reference for the development of treatment. Methods A retrospective analysis was conducted on 162 patients from 2013 to 2018. The value of the indexes before the treatment was calculated. SPSS 25.0 software was used for the analysis, and the cutoff values of the indexes were determined by the receiver operating characteristic curve (ROC). The prognostic value of the indexes was evaluated according to the overall survival rate (OS), progression-free survival rate (PFS), and the incidence of toxic side effects. Results The index CLR was found to be the predictor of mortality of nasopharyngeal carcinoma but not the indicator for toxicity. Conclusion The index CLR can be used for risk-stratification. However, whether the risk-stratification treatment based on these indicators can improve the prognosis subsequently needs further prospective study.

Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. Accumulating data have indicated that VEGF is involved in tumour metastasis. However, the mechanism through which VEGF regulates nasopharyngeal carcinoma (NPC) metastasis is largely unknown. This study aimed to examine the biological function of VEGF in NPC metastasis and its underlying mechanism. Methods: We used western blotting and qPCR to examine the difference in VEGF expression between NPC cells and the immortalized nasopharyngeal epithelial cell line NP69. Wound healing assays, transwell assays and animal experiments were used to further verify the role of VEGF in the invasion and migration of NPC cells. The protein levels of the epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family were analysed by immunofluorescence (IF) and western blotting. Enzyme-linked immunosorbent assay (ELISA) and transwell assays were used to determine whether VEGF enhanced the invasion and migration of NPC cells in an autocrine manner. Western blotting was used to examine how autocrine VEGF-VEGFR2 signalling regulated EMT and MMPs. Results: We observed higher levels of VEGF in NPC cells than that in NP69 cells and identified an association between high VEGF levels and tumour invasion and migration. Mechanistically, the VEGF-mediated increase in EMT markers, MMP2 and MMP9 promoted NPC cell invasion and migration. Additionally, NPC cells secreted VEGF to promote cell invasion, migration and angiogenesis. Autocrine VEGF-VEGFR2 signalling increased ERK1/2 phosphorylation, promoted EMT process and MMPs at the indicated times. Conclusion: This study revealed that VEGF plays a role in controlling NPC cell metastasis by regulating EMT markers and MMPs in an autocrine manner.

Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. VEGF was reported to promote the occurrence of autophagy, which enhanced the radioresistance of tumors. The purpose of this study was to investigate the influence of VEGF silencing on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells and the underlying mechanisms. The radiosensitivity of NPC cells after VEGF silencing was detected by cell counting kit 8 (CCK-8) and clonogenic assay, while cell cycle and apoptosis were detected by flow cytometry. The processes of DNA damage, repair and autophagy were examined by immunofluorescence and western blotting. The interaction between VEGF and mTOR was confirmed by western blotting and co-immunoprecipitation studies. The effect of VEGF on radiosensitivity of NPC cells was investigated in vivo using a xenograft model. Furthermore, immunohistochemistry and TUNEL assays were used to verify the relationship between autophagy and radiosensitivity in NPC after VEGF depletion. Downregulation of VEGF significantly inhibited cell proliferation and induced apoptosis of NPC cells after radiotherapy in vitro and in vivo. In addition, VEGF knockdown not only decreased autophagy level, but also delayed the DNA damage repair in NPC cells after irradiation. Mechanistically, silencing VEGF suppressed autophagy through activation of the mTOR pathway. VEGF depletion increased radiosensitivity of NPC cells by suppressing autophagy via activation of the mTOR pathway.

We conducted a systematic review and meta-analysis to assess the efficacy of intragastric BTA injection in patients with obesity and morbid obesity. Five RCTs were identified. Intragastric BTA injection was no superior to saline in absolute weight loss or BMI change, but significantly lengthened the gastric emptying time (MD, 15.57; 95% CI, 8.75 to 22.38). In meta-regression analysis, the absolute weight loss was lower in the patients with high baseline BMI. In subgroup analysis, the use of BTA in absolute weight loss was significantly lower among the patients with baseline BMI more than 40 kg/m2 (MD, − 5.31; 95% CI, − 6.17 to − 4.45). The benefit of intragastric BTA injection in reduction of absolute weight was observed in patients with baseline BMI more than 40 kg/m2.

Background: Hyperglycemia in the acute phase after trauma is a stress response and a metabolic reflection in humans with injury, which could adversely affect outcome in trauma patients. In this study, we attempted to identify if hyperglycemia a reliable predictor for mortality in major trauma patients. Objectives: In order to identify if hyperglycemia a reliable predictor for mortality in major trauma, we designed and proformed a prospective observational study in a tertiary hospital. Method: We performed a prospective observational study to review the records of 601 patients with major trauma (injury severity scores >15) who visited our hospital’s emergency department from August 2012 to July 2015. Logistic regression was performed to assess the effect of hyperglycemia on mortality. Result: Major trauma patients in the hyperglycemia group had low systolic/diastolic blood pressure at triage, low initial Glasgow Coma Scale score, high incidence of hypotension episodes, coagulopathy, acidosis, and anemia. Hyperglycemia was significantly correlated with mortality in major trauma patients in this study (odds ratio: 1.97, 95% confidence interval: 1.04–3.74). Conclusion: In major trauma patients with injury severity scores >15, hyperglycemia has a positive correlation with mortality, which could be a predictor of mortality in clinical practice.

Background Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. Methods Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. Results The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting β-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or β-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. Conclusion miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

Accumulating evidence has shown that Signal Transducer and Activator of Transcription 3 (STAT3) is thought to be a promising target for cancer therapy as STAT3 is frequently overexpressed in a wide range of cancer cells as well as clinical specimens, promoting tumor progression. It is widely accepted that STAT3 regulates a variety of cellular processes, such as tumor cell growth, survival, invasion, cancer stem cell-like characteristic, angiogenesis and drug-resistance. In this review, we focus on the role of STAT3 in tumorigenesis in ovarian cancer and discuss the existing inhibitors of STAT3 signaling that can be promisingly developed as the strategies for ovarian cancer therapy.

To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis.A total of 498 patients with stage III-IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122).Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein-Barr virus DNA, lymphocyte-to-monocyte ratio, and tumor response achieved an ideal C-index of 0.703 (95% CI 0.655-0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C-index, 0.670, 95% CI: 0.622-0.718). In addition, the nomogram could successfully classified patients into different risk groups.We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients.

The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT).From 2010 to 2018, 648 patients with LA-NPC treated with IC followed by CCRT were included.A total of 172 pairs of patients with LA-NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (75 days) had a significant lower 5-year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients.A prolonged wait time (75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA-NPC receiving IC plus CCRT, particularly those with IVa stage.

There is insufficient evidence to prove the effect of the Post-acute Care (PAC) program on post-stroke recovery. This study aimed to determine the effectiveness of the PAC versus traditional inpatient rehabilitation (non-PAC) for middle- and old-aged stroke survivors. This multicenter cohort study enrolled 334 stroke patients admitted for post-stroke rehabilitation. The outcome variables included the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment-Short Form (MNA-SF), EuroQoL-5D (EQ-5D), Lawton–Brody Instrumental Activities of Daily Living (ADL) Scale, and Mini-Mental State Examination (MMSE). The inverse-probability-of-treatment-weighting method was used to analyze the differences in outcomes between the PAC and non-PAC groups. The PAC group showed better improvements in BI, MNA-SF, EQ-5D, Instrumental ADL, and MMSE compared to the non-PAC group, with differences in effect sizes of 0.54 (95% confidence interval [CI] 0.38–0.71), 0.26 (95% CI 0.10–0.42), 0.50 (95% CI 0.33–0.66), 0.44 (95% CI 0.28–0.60) and 0.34 (95% CI 0.17–0.50), respectively. The PAC project showed more improvement in basic and instrumental ADL and status of swallowing, nutrition, and cognition than those of non-PAC, which had less length of stay restricted by the National Health Insurance. More studies are warranted to investigate the influence of hospital stay and duration from stroke onset on the PAC’s effectiveness.

PurposeTo evaluate the efficacy and safety of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) versus CCRT combined with adjuvant chemotherapy (AC) in patients with stage II–IVA nasopharyngeal carcinoma (NPC), we conducted a retrospective study and a meta-analysis combining the results of our studies.Patients and MethodsWe used the propensity score matching (PSM) to balance variables. A total of 168 patients were chosen by one-to-two PSM, including 101 patients with IC + CCRT and 67 cases with CCRT + AC. We used the Kaplan–Meier curve to compare survival outcomes and also used Cox regression analysis to determine independent prognostic factors. For meta-analysis, we determined the related studies by searching the PubMed database. We used STATA v12 software to perform meta-analysis of the extracted data and calculate pooled hazard ratios, 95% confidence intervals of survival outcomes, and risk ratios for the toxicities.ResultsIn this retrospective study, there was no significant difference in 5-year overall survival (76.9% vs. 79.0%, P = 0.966), progression-free survival (71.3% vs. 68.5%, P = 0.332), distant metastasis-free survival (80.5% vs. 74.2%, P = 0.140), and locoregional relapse-free survival (91.5% vs. 91.8%, P = 0.894) among patients with NPC with IC + CCRT versus CCRT + AC after PSM. For meta-analysis, six articles (including our study) reporting 1,052 cases of IC + CCRT and 883 cases of CCRT + AC were included in the meta-analysis. There was no difference of OS (pooled HR = 0.90, 95% CI: 0.63–1.29, P = 0.561), PFS (pooled HR = 1.07, 95% CI: 0.87–1.33, P = 0.633), DMFS (pooled HR= 0.98, 95% CI: 0.76-1.25, P=0.861), and LRRFS (pooled HR = 1.06, 95% CI: 0.76–1.48, P = 0.724).ConclusionThe efficacy of IC + CCRT and CCRT + AC was comparable in patients with stage II–IVA NPC. In terms of compliance and acute adverse reactions, IC + CCRT may be a potential therapeutic strategy.

Chang Yan,1 De-Song Shen,1 Xiao-Bo Chen,2 Dan-Ke SU,3 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Xia Liang,1 Hai Liao,3 Xiao-Dong Zhu1,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2School of First Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 4Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530100, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning City, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 1466Email zhuxdonggxmu@126.comHai LiaoDepartment of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 4950Email 42442427@qq.comPurpose: We aimed to construct of a nomogram to predict progression-free survival (PFS) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with risk stratification using computed tomography (CT) radiomics features and clinical factors.Patients and Methods: A total of 311 patients diagnosed with LA-NPC (stage III–IVa) at our hospital between 2010 and 2014 were included. The region of interest (ROI) of the primary nasopharyngeal mass was manually outlined. Independent sample t-test and LASSO-logistic regression were used for selecting the most predictive radiomics features of PFS, and to generate a radiomics signature. A nomogram was built with clinical factors and radiomics features, and the risk stratification model was tested accordingly.Results: In total, 20 radiomics features most associated with prognosis were selected. The radiomics nomogram, which integrated the radiomics signature and significant clinical factors, showed excellent performance in predicting PFS, with C-index of 0.873 (95% CI: 0.803∼ 0.943), which was better than that of the clinical nomogram (C-index, 0.729, 95% CI: 0.620∼ 0.838) as well as of the TNM staging system (C-index, 0.689, 95% CI: 0.592– 0.787) in validation cohort. The calibration curves and the decision curve analysis (DCA) plot obtained suggested satisfying accuracy and clinical utility of the model. The risk stratification tool was able to predict differences in prognosis of patients in different risk categories (p< 0.001).Conclusion: CT-based radiomics features, an in particular, radiomics nomograms, have the potential to become an accurate and reliable tool for assisting with prognosis prediction of LA-NPC.Keywords: computed tomography, locoregionally advanced nasopharyngeal carcinoma, radiomics, nomogram

Objective The purpose of this study was to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and the impact of chemoradiotherapy on lymphocyte subsets. Methods 934 patients with non-metastatic nasopharyngeal carcinoma were analyzed retrospectively. The percentage of circulating lymphocyte subsets was detected by flow cytometry and analyzed retrospectively. The correlation between lymphocyte subsets and prognosis was evaluated by the log-rank test and Cox proportional hazards model, and the differences of lymphocyte subsets before and after chemoradiotherapy was comparing by the paired t-test and Wilcoxon signed rank test. Results Univariate and multivariate analyses indicated that high CD19+ B lymphocytes (HR 0.705, 95%CI 0.519–0.958, P = 0.026) and CD4+ T lymphocytes (HR 0.560, 95%CI 0.331–0.946, P = 0.030) before treatment were independent favorable prognostic factors for overall survival (OS) and distant metastasis-free survival (DMFS) in NPC patients, respectively. After chemoradiotherapy, the percentage of CD3+ T lymphocytes, CD4+ T lymphocytes, CD4/CD8 ratio and CD19+ B lymphocytes decreased significantly, while the percentage of CD8+ T lymphocytes and NK lymphocytes increased significantly. Conclusion Patients with high CD19+B lymphocytes and CD4+T lymphocytes have a better prognosis, and perhaps the immune response can be improved to make the prognosis better by increasing the number of lymphocyte subsets. Chemoradiotherapy may reduce the immune function of patients with nasopharyngeal carcinoma.

Background Radioresistance plays an important role in the failure of radiotherapy (RT) for nasopharyngeal carcinoma (NPC), leading to poor prognosis. The purpose of this study was to explore the relationship between the expression of the c-Jun oncogene and the prognosis of NPC. In addition, we investigated the potential mechanisms of c-Jun in the regulation of tumor growth and radioresistance in NPC. Methods c-Jun expression in NPC tissues and nasopharyngeal mucosa tissues was evaluated using immunochemistry. c-Jun and its downstream targets were verified by dual-luciferase reporter assays. Inhibitors or activators were used to interfere with the PI3K/AKT/mTOR pathway. Protein expression was analyzed by western blotting. NPC nude mouse xenograft models were used to investigate the potential effects of c-Jun and ionizing radiation in vivo. Results The expression of c-Jun in NPC tissues was significantly higher than that in normal nasopharyngeal mucosa (NNM) tissues, and Cox regression analysis revealed that c-Jun overexpression was an independent risk factor for poor prognosis in NPC patients. Both in vitro and in vivo experiments verified that c-Jun targeted PI3K/AKT signaling. We also performed an in vivo study showing that c-Jun knockdown effectively suppressed NPC growth in a xenograft tumor model by autophagy inhibition, and these effects were accompanied by the upregulation of p-PI3K p-AKT, p-mTOR, and P62 and downregulation of LC3-II expression. Conclusions High expression of c-Jun was correlated with poor prognosis in NPC patients. c-Jun knockdown increased cell sensitivity to radiation by inhibiting autophagy activation via the PI3K/AKT/mTOR signaling pathway. The present study provides a theoretical basis for a promising treatment for radioresistant NPC by inhibiting c-Jun expression.

The standard size of bougie for laparoscopic sleeve gastrectomy (LSG) is not yet established. Therefore, a systematic review and network meta-analysis were conducted to assess the weight loss effects and associated complications of LSG for patients with morbid obesity, based on different bougie sizes. A total of 15 studies were reviewed in this systemic review and network meta-analysis (2,848 participants), including RCTs and retrospective studies in PubMed, and Embase until September 1, 2020. The effectiveness of different bougie calibration sizes was assessed based on excess weight loss (EWL), total complications, and staple line leak. Within this network meta-analysis, S-sized (≤ 32 Fr.) and M-sized (33–36 Fr.) bougies had similar effects and were associated with the highest EWL improvement among all different bougie sizes (S-sized: standardized mean difference [SMD], 10.52; 95% confidence interval [CI] − 5.59 to − 26.63, surface under the cumulative ranking curve [SUCRA], 0.78; and M-sized: SMD, 10.16; 95% CI − 3.04–23.37; SUCRA, 0.75). M-sized bougie was associated with the lowest incidence of total complications (M-sized: odds ratio, 0.43; 95% CI, 0.16–1.11; SUCRA, 0.92). Based on our network meta-analysis, using M-sized bougie (33–36 Fr.) is an optimal choice to balance the effectiveness and perioperative safety of LSG in the clinical practice.

ObjectivesTo establish and validate an effective nomogram to predict clinical outcomes for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Materials and MethodsThe clinicopathological parameters and follow-up information of 402 locoregionally advanced NPC patients (training cohort, n = 302; validation cohort, n = 100) were retrospectively enrolled. The nomogram was built with the important prognostic variables identified by Cox regression analysis. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. The predictive power and clinical utility of the nomogram were assessed using the Harrell concordance index (C-index), calibration curve, and decision curve analysis. We compared the eighth staging system model with the nomogram to analyze whether the model could improve the accuracy of prognosisResultsEpstein–Barr virus (EBV) DNA load, the gross tumor volume (GTVnx), and cervical lymph node tumor volume (GTVnd) after induction chemotherapy were the independent predictors of OS and PFS. The calibration curves indicated superb agreement between the nomogram-predicted probabilities and observed actual probabilities of survival. The C-index and area under the receiver operator characteristic curve (AUC) of the nomogram integrating these significant factors and N stage, and TNM stage were higher than those of the eighth TNM system alone. In addition, the decision curve analyses demonstrated the clinical value and higher overall net benefit of the nomogram. High-risk groups identified by the nomogram had significantly poorer OS and PFS than the low-risk group (p < 0.05).ConclusionsThe multidimensional nomogram incorporating TNM stage, EBV DNA load, and tumor volume after induction chemotherapy led to a more precise prognostic prediction and could be helpful for stratifying risk and guiding treatment decisions in locoregionally advanced NPC patients who have undergone induction chemotherapy and concurrent chemoradiation.

Purposes To evaluate retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma (NPC). Methods NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of retropharyngeal lymph node metastasis were investigated. The included patients were divided into N1a and N1b groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method and propensity score matching (PSM) analyses. Results This retrospective cohort study examined 759 patients: 70 who were stage N1a and 689 who were stage N1b. Before PSM, N1a group was associated with similar 5-year OS (77.7% vs. 72.4%; P = 0.15) and CSS (85.6% vs. 79.9%; P = 0.09) compared to N1b group. After PSM, a similar OS (75.0% vs. 60.7%; P = 0.12) was found between the radiotherapy and chemoradiotherapy groups. However, N1a group showed a better 5-year CSS (83.8% vs. 71.1%; P = 0.04) compared to N1b group. Stage N1b was an independent risk prognostic factor for CSS (hazard ratio = 2.54, 95% confidence interval: 1.02–6.34; P = 0.04). Conclusions OS was not different between N1a and N1b groups. Retropharyngeal lymph node metastasis defined as stage N1 of the 8th edition American Joint Committee on Cancer staging system is reasonable.

Objective. Persons with stroke frequently suffer from cognitive impairment. The Montreal Cognitive Assessment (MoCA), a recently developed screening tool, is sensitive to poststroke cognitive deficits. The present study assessed its psychometric and clinimetric properties (i.e., responsiveness, minimal clinically important difference (MCID), and criterion validity) in stroke survivors receiving rehabilitative therapy. Method. The MoCA and the Stroke Impact Scale (SIS) were administered to 65 stroke survivors before and after 4 to 5 weeks of therapy. The effect size and standardized response mean (SRM) were calculated for responsiveness. Anchor- and distribution-based methods were used to estimate the MCID. Criterion validity was measured with the Spearman correlation coefficient. Results. The responsiveness of the MoCA was moderate (SRM=0.67). Participants exceeding the MCID according to the anchor- and distribution-based approaches were 33 (50.77%) and 20 (30.77%), respectively. Fair to good concurrent validity was reported between the MoCA and the SIS communication subscale. The MoCA had satisfactory predictive validity with the SIS communication and memory subscales. Conclusion. This study may support the responsiveness, MCID, and criterion validity of the MoCA in stroke populations. Future studies with larger sample sizes are needed to validate the current findings.

Fang Su*, Kaihua Chen*, Zhongguo Liang, Song Qu, Ling Li, Long Chen, Yunli Yang, Chunhua Wu, Xia Liang, Xiaodong ZhuDepartment of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workObjective: Even in early-stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult tumor location. To compare the safety and efficacy of different fractions on the survival of patients with tumors smaller than 10 cm in size, hepatocellular carcinoma (HCC) patients ineligible for curative therapies were treated with three-dimensional conformal radiotherapy (3DCRT).Methods: A total of 198 HCC patients who had tumors smaller than 10 cm and were not eligible for surgical resection or local ablation therapy received 3DCRT. Participants were separated into two groups. The treatment for Group A (n=111) was a median total dose of 53Gy with a fraction of 2.5–4.9Gy given three times a week, while treatment for Group B (n=87) was a median total dose of 52Gy with a fraction of 5.0–7.0 Gy given three times a week. Propensity score matching (PSM) was conducted, and after the PSM, 81 pairs of patients arose. The Kaplan–Meier method was adopted to analyze overall survival; multivariate analysis was applied to identify the prognostic factors of survival.Results: The median follow-up time was 19.7months (ranging from 1 to 186months). The median survival for Group A patients versus Group B patients was 14.4 versus 24.8months (P=0.003), respectively. The overall survival rates at 1, 3, and 5years were 57.7%, 30.6%, and 18.9% for Group A patients and 73.6%, 43.7%, and 33.3% for Group B patients, respectively (P=0.009). In addition, the results in the PSM model appeared to be similar between the two groups. After PSM, the association between four independent prognostic factors and worse overall survival was discovered as follows: tumor size (>5 cm), Child–Pugh class B, portal vein tumor thrombosis, and fraction of 2.5−4.9Gy/fx. The two groups also shared similar toxicities.Conclusions: Higher fraction dose radiotherapy delivered by 3DCRT was effective, as it offered a survival benefit without aggravating the toxicities in patients with small- to medium-sized HCC tumors who were ineligible for curative therapies.Keywords: three-dimensional conformal radiotherapy, higher fraction dose, hepatocellular carcinoma, curative therapy, survival

Objective: CD166 is known as a tumor stem cell specific marker, associating with tumor metastasis. The purpose of this study was to further discuss CD166 gene on cell proliferation, invasion, metastasis, and the epithelial-mesenchymal transition (EMT) in CNE-2R cell line of nasopharyngeal carcinoma (NPC). Materials and methods: CNE-2R cells were transfected with lentivirus CD166-shRNA, and quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting were used to confirm the silencing effects. The wound healing test and transwell test were carried out to assess cell invasive and migratory abilities in vitro. With the establishment of xenograft nude mouse model, Western blotting and immunohistochemistry were undertaken to detect the expression level of E-cadherin, N-cadherin, and vimentin. In vivo metastasis detection was carried out by injecting tumor cells into nude mice via the tail vein. Results: The invasive and migratory abilities of CNE-2R cells were significantly reduced after CD166 was downregulated. In addition, silencing of CD166 of CNE-2R cells increased the expression of E-cadherin, while down-regulated the expression of N-cadherin and vimentin. Immunohistochemistry of tumors showed consistent results with in-situ tumor formation experiment. Additionally, the growth of transplanted tumor was inhibited. In addition, in vivo metastasis test proved that knockdown of CD166 suppressed pulmonary metastasis and liver metastasis according to hematoxylin and eosin (H&E) staining. Expression of E-cadherin increased, while expression of N-cadherin and vimentin decreased, as revealed by Western blotting of metastatic lung tumors. Conclusion: Silencing of CD166 in CNE-2R cells evidently inhibited proliferation, invasion, metastasis, and EMT process in vivo and in vitro.

Background An abnormal sternocleidomastoid muscle in congenital muscular torticollis can be classified into one of the four types via sonography. However, this categorization lacks quantitative measurements. The purpose of the study was to determine quantitative measurements of the sonograms via image analysis. Methods Infants younger than 12 months of age suspected of having congenital muscular torticollis were included. Intraclass correlation coefficient estimates for interobserver reliability and a simple regression analysis for criterion validity were calculated. Spearman correlation analysis was then performed. The analyzed parameters included cervical passive range of motion for lateral flexion and rotation, area, brightness, max/min Feret's diameters, and muscular width/thickness. Results Of the 29 (4.0 ± 2.6 months) screened infants, 13 (1.9 ± 1.7 months) were included. Nine were male, and 4 were female. Seven infants with mass were ultrasonographically classified into type I, and the other six infants were classified into type II. The affected/unaffected side ratios of cervical passive range of motion for lateral flexion and rotation were 0.92 ± 0.13 and 0.88 ± 0.16, respectively. The parameters measured on the sonograms were reliable, and the max/min Feret's diameters were valid measurements. The affected/unaffected side ratio of cervical passive range of motion for rotation significantly correlated with the affected/unaffected side ratios of the sternocleidomastoid muscle sonogram on area (r = −0.62, p = 0.03) and min Feret's diameter (r = −0.69, p = 0.01). Conclusions The area and min Feret's diameter were efficacious parameters for image analysis on sternocleidomastoid sonograms, and the min Feret's diameter would be more suitable than thickness for measuring the thickening SCM in transverse view. A healthy control group, more data and follow-up would be needed to confirm the changes on the SCM sonograms for clinical decision.

Background: An abnormal sternocleidomastoid muscle in congenital muscular torticollis can be classified into one of the four types via sonography. However, this categorization lacks quantitative measurements. The purpose of the study was to determine quantitative measurements of the sonograms via image analysis. Methods: Infants younger than 12 months of age suspected of having congenital muscular torticollis were included. Intraclass correlation coefficient estimates for interobserver reliability and a simple regression analysis for criterion validity were calculated. Spearman correlation analysis was then performed. The analyzed parameters included cervical passive range of motion for lateral flexion and rotation, area, brightness, max/min Feret's diameters, and muscular width/thickness. Results: Of the 29 (4.0 ± 2.6 months) screened infants, 13 (1.9 ± 1.7 months) were included. Nine were male, and 4 were female. Seven infants with mass were ultrasonographically classified into type I, and the other six infants were classified into type II. The affected/unaffected side ratios of cervical passive range of motion for lateral flexion and rotation were 0.92 ± 0.13 and 0.88 ± 0.16, respectively. The parameters measured on the sonograms were reliable, and the max/min Feret's diameters were valid measurements. The affected/unaffected side ratio of cervical passive range of motion for rotation significantly correlated with the affected/unaffected side ratios of the sternocleidomastoid muscle sonogram on area (r = −0.62, p = 0.03) and min Feret's diameter (r = −0.69, p = 0.01). Conclusions: The area and min Feret's diameter were efficacious parameters for image analysis on sternocleidomastoid sonograms, and the min Feret's diameter would be more suitable than thickness for measuring the thickening SCM in transverse view. A healthy control group, more data and follow-up would be needed to confirm the changes on the SCM sonograms for clinical decision. Keywords: Congenital muscular torticollis, Sternocleidomastoid, Sonography, Cervical passive range of motion

An increasing number of studies have demonstrated the bidirectional hemostatic effect of selective serotonin reuptake inhibitors (SSRIs) on the risk of cerebrovascular and cardiovascular diseases. However, no previous study has focused on the relationship between SSRI and the risk of peripheral artery disease (PAD) in diabetes mellitus (DM). We sought to evaluate the association between SSRIs and the PAD risk in individuals with DM.We conducted a retrospective, population-based cohort study using data from the Longitudinal Health Insurance Database from 1999 to 2010 in Taiwan. A total of 5049 DM patients were included and divided into 2 groups: DM with SSRI users and DM with SSRI non-users. Propensity score matching and 1-year landmark analysis were used for our study design. Stratified Cox proportional hazard regressions were used to analyze the hazard ratio of the PAD risk in certain subgroups.DM with SSRI users did not affect the PAD risk compared to DM with SSRI non-users. These findings were consistent with all sensitivity analyses (i.e., age, sex, SSRI doses, antithrombotic medication use, and medical and psychiatric comorbidities).In this study, we found that there was no significant difference of PAD risk between DM with SSRI users and DM with SSRI non-users. DM with SSRI user did not affect PAD risk across any SSRI dose, age, sex, antithrombotic medications, and multiple comorbidities in the subgroup analysis.

Laparoscopic gastric clipping (LGC) is a relatively novel restrictive bariatric surgery wherein a horizontal metallic clip is applied to the gastric fundus. Its intraoperative complications or the difficulties associated with the applied gastric clip (GC) during revisional procedures have seldom been mentioned. Herein, the experience of revisional procedures after initial gastric clipping is reported. A retrospective cohort review of LGC based on the Taiwan Bariatric Registry of Taiwan Society Metabolic and Bariatric Surgery was performed. Six patients with severe obesity presented for revisional surgery after initial LGC by other surgeons. Patients’ characteristics, indications, and details of revisional surgery were recorded. Between 2012 and 2019, 39 patients who underwent pure LGC and six patients with previous LGC history were referred for revisional surgery. Their mean age and the mean body mass index were 34.7 ± 9.5 years and 38.4 ± 10.5 kg/m2, respectively. Three, two, and one patient underwent revisional surgery for insufficient weight loss, weight recidivism, and intractable belching, respectively. The mean interval between initial LGC and revisional surgery was 40.5 ± 22.4 months. Laparoscopic removal of the GC with concomitant revisional surgeries were collected, including a revision to sleeve gastrectomy (n = 5) and revision to Roux-en-Y gastric bypass (n = 1). Moreover, the mean operative time was 286.8 ± 78.2 min. All patients had uneventful recovery postoperatively but experienced significant adhesion around the GC and the left liver. Laparoscopic revisional surgery with concomitant GC removal for patients with severe obesity after gastric clipping could be feasibly conducted by experienced bariatric surgeons.

BackgroundThe 8th edition of AJCC/UICC TNM staging system (TNM system) and the previous nomograms have limitations, therefore we aimed to develop and validate nomograms incorporating routine hematological biomarkers with or without EBV DNA for overall survival (OS) and progression-free survival (PFS). We also evaluated the prognostic role of EBV DNA.Material and Methods1203 patients at our hospital from 2013 to 2016 were retrospectively reviewed and divided into two parts (922 patients for primary cohort and 281 for validation cohort). Nomograms (nomogram with or without EBV DNA) were developed and compared with other models (TNM system alone, TNM system with EBV DNA), via comparison the prognostic role of EBV DNA was evaluated. Internal and external validation were performed. Risk stratification were conducted with recursive partitioning analysis.ResultsThe nomograms with EBV DNA for OS and PFS included sex, age, T category, N category, EBV DNA, albumin, neutrophil to lymphocyte ratio and lactate dehydrogenase. The nomograms without EBV DNA for OS and PFS included the same variables but without EBV DNA. The C-index for nomogram with EBV DNA was 0.715 for OS and 0.705 for PFS. For nomogram without EBV DNA, it was 0.709 and 0.700, respectively. It was 0.639 and 0.636 for TNM system alone and 0.648, 0.646 respectively for TNM system with EBV DNA. The nomograms with or without EBV DNA had better performance than both the TNM system alone and TNM system with EBV DNA, while the TNM system with EBV DNA were better than TNM system alone. The validation cohort indicates great applicability of nomograms. The patients were stratified into 4 risk groups.ConclusionThe nomograms with or without EBV DNA provide better prognostication than the TNM system and also the TNM system with EBV DNA. EBV DNA is valuable in predicting survival, but it is not suggested to incorporate EBV DNA alone to TNM system.

Objective The present study aimed to investigate the predictive value of some inflammatory indexes, such as the ratio of C-reactive protein-to-albumin (CAR), high-sensitivity C-reactive protein-to-albumin (HCAR), C-reactive protein-to-lymphocyte (CLR), and high-sensitivity C-reactive protein-to-lymphocyte (HCLR) in the survival and toxicity of nasopharyngeal carcinoma and provide reference for the development of treatment. Methods A retrospective analysis was conducted on 162 patients from 2013 to 2018. The value of the indexes before the treatment was calculated. SPSS 25.0 software was used for the analysis, and the cutoff values of the indexes were determined by the receiver operating characteristic curve (ROC). The prognostic value of the indexes was evaluated according to the overall survival rate (OS), progression-free survival rate (PFS), and the incidence of toxic side effects. Results The index CLR was found to be the predictor of mortality of nasopharyngeal carcinoma but not the indicator for toxicity. Conclusion The index CLR can be used for risk-stratification. However, whether the risk-stratification treatment based on these indicators can improve the prognosis subsequently needs further prospective study.

We conducted a systematic review and meta-analysis to assess the efficacy of intragastric BTA injection in patients with obesity and morbid obesity. Five RCTs were identified. Intragastric BTA injection was no superior to saline in absolute weight loss or BMI change, but significantly lengthened the gastric emptying time (MD, 15.57; 95% CI, 8.75 to 22.38). In meta-regression analysis, the absolute weight loss was lower in the patients with high baseline BMI. In subgroup analysis, the use of BTA in absolute weight loss was significantly lower among the patients with baseline BMI more than 40 kg/m

Yu Liang,1,2 Kai-hua Chen,1 Jie Yang,1 Jing Zhang,1 Ru-rong Peng,1 Song Qu,1 Ling Li,1 Xiao-dong Zhu1– 4 1Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiao-dong ZhuAffiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaEmail zhuxdonggxmu@126.comPurpose: To explore acute toxicities and prognosis of elderly NPC patients after IMRT; to identify predictors regarding age, chemotherapy, comorbidities, nutrition status, and psychological condition; and to establish a nomogram for the prediction of prognosis.Patients and Methods: Elderly NPC patients were divided into three groups (age of 60– 65, age of 66– 70, and age over 70) and were retrospectively analyzed. The acute toxicities, prognosis, and potential predictors were analyzed. Then, a nomogram for PFS was established, and the performance of nomogram was compared with the performance of TNM system.Results: A total of 214 elderly patients (214/1981, 10.8%) were involved. Patients of Stage III and IV accounted for 73.4%. The 3-year, 5-year PFS and OS were 77.9%, 66.3%, 79.3% and 66.8%, respectively. Elder patients had a worse prognosis (P=0.002). The main cause of death remained in recurrence and metastasis; few died from comorbidities, and some died from nutrition status and psychological condition. Age (HR=1.10, 95% CI=1.05– 1.15, P< 0.001), ALB level (HR=0.93, 95% CI=0.88– 0.99, P=0.019), and T stage (HR=1.85, 95% CI=1.10– 3.13, P=0.022) were critical for PFS, but chemotherapy or comorbidities were not. Acute toxicities were mainly at or under grade II. N stage (OR=2.50, 95% CI=1.28– 4.88, P=0.007) and chemotherapy (OR=6.01, 95% CI=3.11– 11.63, P< 0.001) were risk factors for hematological toxicity; while age (OR=0.59, 95% CI=0.37– 0.92, P=0.020) and chemotherapy (OR=225.14, 95% CI=61.91– 818.64, P< 0.001) influenced emesis; ALB (OR=1.11, 95% CI=1.04– 1.19, P=0.002) affected mucositis. Comorbidities were not influential in acute toxicities. The nomogram for PFS (C-index=0.682, 95% CI=0.617– 0.747) performed better than the TNM system (C-index=0.604, 95% CI=0.532– 0.674, P< 0.001).Conclusion: Elderly NPC patients sustained poor prognosis. The easily applied nomogram is hopeful to benefit the clinical decision-making.Keywords: cancer, geriatric, survival, outcome, side effect, model

BACKGROUND: Emergency department (ED) revisits may be associated with a higher percentage of adverse events and increased costs. Our hospital is a university affiliation hospital accepted regional referral patients, and located in the region in Taiwan with the highest percentage of elderly people. In this study, we attempted to identify whether old age was a risk factor of ED revisit. METHODS: Patients who visited the ED from July 2011 to June 2016 were included. Factors associated with revisit were collected from medical information database. A total of 239,405 patients were included in our study, with 13,272 having ED revisits within 72 hours. Chi square and independent t test were applied for univariable factors, and a logistic regression model was used for multivariable analysis. RESULTS: Old age (age ≥ 65 years) was found to be a risk factor for ED revisit (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.09–1.19). Diagnosis, pulse rate, diastolic blood pressure, fever, pain management, paracentesis, triage level, registration category, male gender, discharge status, and major illness may have some effect on ED revisit. CONCLUSIONS: In our patients, old age is a risk factor for ED revisit; however, only a weak association was found.

Objective This study aimed to evaluate the safety and efficacy of three‐dimensional conformal radiotherapy (3D‐CRT) and hepatic resection for patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT). Methods We retrospectively analyzed 323 HCC patients involving PVTT. Among them, 134 patients underwent 3D‐CRT, while 189 controls treated with hepatic resection (HR). Survival rate and prognostic analysis were performed using Kaplan‐Meier method and Cox regression analyses. Results The 1‐, 2‐, and 3‐year overall survival (OS) of RT group and HR group was 54% vs 62%, 33% vs 47%, and 18% vs 43%, respectively (P = 0.003). In the subgroup of PVTT type analysis, the 1‐, 2‐, and 3‐year OS in RT group was 65%, 39%, and 19%, respectively, while that in HR group was 83%, 53%, and 42%, respectively, in type I PVTT (P

Objective To evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) for the treatment of unresectable liver metastases. Methods Twenty-five patients with unresectable liver metastases treated with IMRT were enrolled from January 2003 to September 2016. The median longest diameter of the lesions was 3.3 cm (range, 1.6–16.7 cm). The fraction dose ranged from 2 to 5.2 Gy, with a median total dose of 50 Gy (range, 30–60 Gy). Results The median follow-up was 9.2 months (range, 2.1–48.8 months). The overall survival rates at 1 and 2 years were 46.4% and 27.4%, respectively. The 1-year local control rate was 69.8%. The 1-year progression-free survival rate was 26.3%. One patient had grade 4 liver dysfunction. One case of grade 4 leukopenia and one case of grade 3 leukopenia occurred, and one case of grade 3 leukopenia and thrombocytopenia was observed. Conclusion IMRT may be a promising and safe treatment for unresectable liver metastases and can be used as a treatment option.

Background Previously, we found that c-jun was highly expressed in radiation-resistant human nasopharyngeal carcinoma cells (CNE-2R) compared with human nasopharyngeal carcinoma cells (CNE-2). Materials and methods In this study, we first used the scratch assays and transwell assays to detect the migration and invasion of CNE-2R and CNE-2 cells and tested the epithelial mesenchymal transformation (EMT)-related proteins E-cadherin and N-cadherin by Western blot analysis. Subsequently, c-jun was knocked down to establish the effect of c-jun on EMT, migration, and invasion of CNE-2R cells both in vitro and in vivo. Results A high EMT level, CNE-2R cells were more capable of migration and invasion than CNE-2 cells. Moreover, silencing of c-jun has upregulated the expression of E-cadherin and downregulated N-cadherin in CNE-2R cells, and subsequently the migration and invasion capacity of the cells was decreased. Consistent with in vitro results, in vivo studies indicated that the c-jun silencing reduced pulmonary migration of CNE-2R cells. Immunohistochemistry of lung metastatic tumor tissue showed that E-cadherin was upregulated, and N-cadherin was downregulated. Conclusion These findings suggest that silencing of c-jun in CNE-2R cells reduces cells migration, invasion, and EMT both in vitro and in vivo.

Background We undertook a meta-analysis to evaluate the clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the detection of distant metastases in patients with non-small cell lung cancer (NSCLC) at initial staging. Materials and methods All topic-related studies were comprehensively searched in the MEDLINE and Embase databases. We obtained the summary estimates and constructed the summary receiver operating characteristic curve for 18F-FDG PET/CT using the bivariate regression model. Results Across 10 studies (1333 patients), the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for 18F-FDG PET/CT were 0.81 (95% confidence interval [CI] = 0.63-0.92), 0.96 (95% CI = 0.94-0.98), 22.9 (95% CI = 13.3-39.5), and 0.20 (95% CI = 0.09-0.42), respectively. Overall weighted area under the curve was 0.97 (95% CI = 0.96-0.98). Conclusion 18F-FDG PET/CT has a good diagnostic performance for distant metastasis staging in patients with NSCLC at initial staging.