NPCs in video games: a reflective resource for sports coaches and participant engagement.

This perspective article explores the potential of non-player characters (NPCs) in video games as a reflective tool for coaches to enhance participant engagement in sports. While coaches traditionally focus on movement skill instruction, their role extends to fostering young people's immersion in sports contexts and potentially contribute to the possibility of lifelong participation. However, challenges persist in translating coaching theory in coach education programs into practice, including the awareness of roles and how to make young people immersion in sports. Integrating elements from video games, where NPCs play pivotal roles in shaping player experiences, presents a possible avenue for re-thinking the role of coach, especially in participation. By drawing parallels between NPCs and coaches, this article advocates for a new reflection tool for coaching roles. Future research should investigate the effectiveness of leveraging NPCs to enhance athlete engagement and motivation, ultimately creating dynamic and inclusive coaching environments that cater to the evolving needs of participants.

Design, Synthesis, and Evaluation of 8-(o-Tolyl)quinazoline Derivatives as Small-Molecule PD-1/PD-L1 Antagonists.

Small-molecule inhibitors targeting programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions can compensate for the shortcomings of antibody-based inhibitors and have attracted considerable attention, some of which have already entered clinical trials. Herein, based on our previous study on small-molecule PD-L1 inhibitors, we reported a series of 8-(o-tolyl)quinazoline derivatives by the skeleton merging strategy. Homogenous time-resolved fluorescence (HTRF) assay against PD-1/PD-L1 interaction identified compound A5, which showed the most potent inhibition with an IC50 value of 23.78 nM. Meanwhile, based on the results of HTRF assay, the structure-activity relationships (SARs) of the tail were focused on. Cell-based PD-1/PD-L1 blockade assay further revealed that A5 significantly blocked the PD-1/PD-L1 interaction at 1.1 µM in the co-culture system of Jurkat-NFAT-PD-1 cells and Hep3B-OS8-hPD-L1 cells with no significant cytotoxicity on Jurkat cells. Moreover, the proposed binding mode of A5 was investigated by a docking analysis. These results indicate that compound A5 is a promising lead compound that deserves further investigation.

Effects of shared governance and cost redistribution on air pollution control: a study of game theory-based cooperation.

This study seeks cost-effective strategies for PM2.5 reduction to generate insights into minimizing pollution abatement costs subject to different scenarios. This study theorizes that the cooperation of PM2.5 abatement has potential gains for participants and develop an empirical way to compare the costs and efficiency of PM2.5 abatement involving the variation of environmental conditions. This study revises the cooperative game model in the context of threshold effects using data obtained from the Beijing-Tianjin-Hebei metropolitan cluster in China. In general, the results support the key assertion that cooperation in the metropolitan cluster plays a vital role in optimizing the efficiency and costs of PM2.5 abatement. In addition to extending the application of the revised model, this study provides a way to estimate the costs and the mitigation benefits of meeting the pollution targets for each coparticipant and take the scenario of multiparty cooperation into account as well as the scenarios involving other types of pollutants. The empirical findings have important policy implications for regional shared governance, decentralization, and resource reallocation. Economic incentive-based shared governance and cost reallocation work better than traditional regulations.

Impact of job control on hospital workers' safety performance: A moderated mediation analysis of the influences of hospital safety climate and social support.

AIM: To improve the level of hospital workers' safety performance in response to emergencies (e.g. COVID-19), this paper examines the relationship between hospital workers' job control on safety performance, and the mediating role of hospital safety climate and the moderating role of social support. DESIGN: In this cross-sectional questionnaire survey, a convenience sampling of hospital workers from three hospitals that have COVID-19 cases from Beijing and Shandong Province in China. METHODS: These questionnaires were used to obtain self-reported data on hospital workers' job control, hospital safety climate, social support and safety performance. Mplus software was used to calculate CFA. SPSS25.0 software was used to calculate mean values, standard deviations, correlations and regression analyses. RESULTS: The participants were 241 hospital workers from three hospitals in China (male = 55.2%, female = 44.8%; age range <30 to >45; physician = 58%, nurse = 22%, other hospital worker = 20%). A moderated mediation model among job control, hospital safety climate, social support and safety performance was supported. Moderated mediation analysis indicates hospital workers' job control effectively improves the level of safety performance; hospital safety climate plays a partially mediating role in the process of job control affecting hospital workers' safety performance; social support moderates the effect of work control on medical workers' safety climate. Hence, it is important to increase job control and hospital safety climate. Further, social support for hospital workers should be encouraged, advocated and supported.

Regorafenib with or without a programmed cell death protein 1 antibody as third-line treatment for microsatellite stable metastatic colorectal cancer.

BACKGROUND: Although the use of regorafenib plus nivolumab demonstrates promising outcomes in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC), this effect has not been substantiated in other studies. Moreover, a comparison between the outcomes of regorafenib and programmed cell death protein 1 (PD-1) antibody combination therapy and regorafenib monotherapy remains unexplored. In this study, we aimed to assess whether regorafenib and PD-1 antibody combination therapy is superior to regorafenib monotherapy as a third-line treatment for MSS mCRC. METHODS: Patients with MSS mCRC who received regorafenib and PD-1 antibody or regorafenib monotherapy as third-line treatment were eligible for inclusion. RESULTS: In total, 179 patients were enrolled, of which 84 were administered regorafenib combined with a PD-1 antibody and 95 were administered regorafenib monotherapy. Patients administered regorafenib combined with a PD-1 antibody had similar progression-free survival (PFS) as those on regorafenib monotherapy (median PFS was 2.4 months and 1.9 months, respectively, p = 0.086). The administration of regorafenib combined with a PD-1 antibody resulted in significantly longer PFS than that seen with regorafenib monotherapy in both male (5.2 months vs. 2.4 months, p = 0.001) and female (3.9 months vs. 1.8 months, p = 0.037) patients without liver metastasis. Female patients with liver metastasis who were administered regorafenib combined with a PD-1 antibody had shorter PFS than those administered regorafenib monotherapy (1.8 months vs. 2.0 months, p = 0.030). CONCLUSION: Liver metastasis and sex are predictors of survival benefit following the addition of a PD-1 antibody to regorafenib in patients with MSS mCRC.

Anastomotic leakage and postoperative mortality in patients after esophageal cancer resection.

OBJECTIVE: Esophagectomy is a high-risk surgical procedure with significant postoperative morbidity and mortality. This study aimed to investigate the risk factors of cervical anastomotic leakage and postoperative mortality. METHODS: In this retrospective, observational study, we recruited 1010 patients with esophageal cancer. Cox regression analysis was performed to identify factors affecting anastomotic leakage and postoperative mortality. After propensity score matching, the Kaplan-Meier curve was used to evaluate the effect of leakage on postoperative mortality. RESULTS: The number of patients with cervical anastomotic leakage, in-hospital mortality, 30-day postoperative mortality, and 60-day postoperative mortality was 194 (19.2%), 13 (1.3%), 12 (1.2%), and 16 (1.6%), respectively. The total length of hospital stay and hospital stay postoperatively were 29.7 ± 21.1 and 21.3 ± 20.3 days, respectively. Diabetes, stage IV, and an upper thoracic tumor were significant risk factors for leakage. Leakage and diabetes were significant risk factors for postoperative mortality. After propensity score matching, leakage also significantly affected postoperative mortality. CONCLUSIONS: Patients with tumors in the upper thoracic segment of the esophagus may be more prone to developing anastomotic leakage compared with those with tumors in the middle or lower thoracic segment. Anastomotic leakage may prolong the length of hospital stay and increase postoperative mortality.

Efficacy and mechanism of combination of oxaliplatin with PKM2 knockdown in colorectal cancer.

M2 isomer of pyruvate kinase (PKM2), a key enzyme in aerobic glycolysis, is closely related to cancer development and progression. Suppression of PKM2 exhibits synergistic effects with docetaxel in lung cancer, but the therapeutic potential in colorectal cancer (CRC) is unclear. The aim of the present study was to explore the synergic effects and mechanism of knocking down PKM2 combined with oxaliplatin (a chemosensitizer) treatment in two CRC cell lines (HCT116 and DLD1). The PKM2 gene was initially knocked down using small interfering (si)RNAs (si155 and si156). Subsequently, the effects of PKM2-siRNAs and oxaliplatin, on CRC cells were determined using MTS, cell cycle analysis and apoptosis assays. The mechanism of targeting PKM2 was explored by detecting glucose uptake, lactate secretion fluxes, and the levels of glucose-6-phosphate dehydrogenase (G6PD) mRNA, glutathione (GSH) and reactive oxygen species (ROS). Cell viability in the experimental groups (PKM2-siRNAs, oxaliplatin, PKM2-siRNAs + oxaliplatin) was significantly reduced compared with the control group, and combination treatments (PKM2-siRNAs + oxaliplatin) were more effective than single treatments (PKM2-siRNAs and oxaliplatin only groups). Similar results were observed with the apoptosis assay. The combination groups showed synergistic effects compared with both single treatment groups. Furthermore, glucose uptake and lactate secretion and mRNA levels of G6PD and PKM2 were decreased after PKM2 knockdown in the PKM2-siRNAs and PKM2-siRNAs + oxaliplatin groups. The GSH levels in the PKM2-siRNAs group was significantly lower compared with the negative control group. The ROS levels in the PKM2-siRNAs groups were also significantly increased. The combination of PKM2-siRNAs and oxaliplatin had synergistic effects on CRC cells (HCT116 and DLD1). PKM2 silencing may alter energy metabolism in cancer cells and initiate ROS-induced apoptosis after downregulation of the pentose phosphate pathway by PKM2-siRNAs.

Association of body composition with survival and inflammatory responses in patients with non-metastatic nasopharyngeal cancer.

OBJECTIVES: It is unknown whether or not the body composition is correlated with the prognosis and inflammatory response in patients with nasopharyngeal cancer (NPC). MATERIALS AND METHODS: This cohort included 1767 patients with NPC. Visceral, subcutaneous and intra muscular adipose tissues (VAT, SAT and IMAT), and skeletal muscle index were quantified with computed tomography. We used the optimal stratification to select cut points for VAT, SAT and IMAT. We defined sarcopenia according to a widely used cut-point. The primary endpoint was overall survival (OS). The association between body composition and inflammatory response was also examined. RESULTS: Low VAT, SAT, IMAT and sarcopenia were observed in 260 (14.7%), 451 (25.5%), 773 (43.7%) and 683 (38.7%) patients, respectively. Low VAT (P < 0.001, hazard ratio [HR], 1.884; 95% confidence interval [CI], 1.436-2.473,) and SAT (P = 0.022, HR, 1.334, 95%CI, 1.043-1.706) were both associated worse survival. IMAT and sarcopenia were not with prognostic value. In multivariate analysis, we found the prognostic value of the VAT (HR: 1.544, 95% CI: 1.128-2.114; P = 0.007) was independent of T stage, N stage, disease stage, lactic dehydrogenase, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), the systemic immune-inflammation index (SII), EBV-DNA and body mass index. We observed higher NLR (P = 0.028) and PLR (P < 0.001) in patients with low SAT. Both low VAT (P = 0.009) and SAT (P = 0.005) were associated with decreased stromal lymphocyte infiltrating intensity. CONCLUSIONS: Among body composition parameters, VAT was an independent prognostic factor, especially in patients with locally advanced NPC.

Systemic neutrophil lymphocyte ratio and mismatch repair status in colorectal cancer patients: correlation and prognostic value.

Purpose: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated with increased local immune response as compared with mismatch repair-proficient (pMMR) CRC. We evaluated the relationship between MMR status and systemic inflammatory factors, including neutrophil lymphocyte ratio (NLR) and C-reactive protein (CRP). We also assessed the prognostic value of these parameters. Methods and materials: We analysed the relationship between MMR status (obtained by histochemical analysis), neutrophil and lymphocyte counts, NLR, and CRP level. The impact of systemic inflammatory factors on survival was also evaluated in dMMR and pMMR CRC patients. Results: A total of 1353 male and 892 female patients were eligible for analysis, of which, 253 patients (11.3%) were found to have dMMR status. Patients with dMMR status presented with increased neutrophil counts, and higher NLR and CRP levels in early stage CRC. In stage IV CRC patients, no correlation between MMR status and systemic inflammatory factors was found. Lymphocyte counts did not correlate with MMR status. High NLR was a prognostic factor for poor survival in pMMR CRC. However, NLR was not a prognostic factor in dMMR CRC. Conclusions: Our results suggest that dMMR CRC correlates with higher neutrophil count, NLR and CRP levels only in non-metastatic patients, and NLR has prognostic value only in pMMR CRC.

Association of low skeletal muscle index with increased systematic inflammatory responses and interferon γ-induced protein 10 levels in patients with colon cancer.

BACKGROUND: Skeletal muscle depletion is a prognostic factor in patients with cancer. Here, we evaluated the association between the skeletal muscle index (SMI) and local and systemic responses in patients with colon cancer. PATIENTS AND METHODS: We analyzed the relationships of the SMI with neutrophil, lymphocyte, monocyte, and platelet counts; the neutrophil-to-lymphocyte ratio; albumin levels; and C-reactive protein levels in a cohort of 561 patients, and with the circulating levels of 39 cytokines in a cohort of 125 patients. We also studied the association between the SMI and tumor local inflammatory response and the effect of SMI on survival. RESULTS: The median SMIs for male and female subjects were 44.1 and 34.2 cm2/m2, respectively. We observed positive correlations of the SMI with neutrophil (p=0.022), lymphocyte (p=0.001), and monocyte counts (p=0.003). A low SMI correlated significantly with an increased platelet count (p=0.017), decreased albumin level (p=0.006), neutrophil-to-lymphocyte ratio >3 (p=0.021), and an increased interferon γ-induced protein 10 level (IP-10, r = -0.276, p=0.002). The SMI did not correlate significantly with local inflammatory reactions or the C-reactive protein level. Finally, the SMI was a significant prognosticator in patients with stage III colon cancer (3-year disease-free survival rates: 35.1% for the low SMI arms versus 46.0% in the high SMI arms; HR =2.036; p=0.034). CONCLUSION: This study highlights the association of a low SMI with a high systematic inflammatory response and IP-10 levels. Furthermore, low SMI is a predictor of poor disease-free survival in patients with stage III colon cancer.

An increased number of negative lymph nodes is associated with a higher immune response and longer survival in colon cancer patients.

BACKGROUND: The purpose of the present study was to examine the relationship among the number of negative lymph nodes (LNs), the local and systemic immune response, and survival in patients with colon cancer. PATIENTS AND METHODS: One thousand one hundred and fifty-seven patients with colon cancer who underwent surgery at Sun Yat-sen University Cancer Center between 2009 and 2014 were included. We examined negative LNs in relation to the local and systemic immune response, including percentage carcinoma, neutrophil and lymphocyte infiltration, Crohn's-like reaction, neutrophil to lymphocyte ratio, platelets, and C-reactive protein (CRP). Disease-free survival and overall survival were also examined. We performed subgroup analysis based on the distribution of negative LNs. RESULTS: An increased number of negative LNs was associated with greater neutrophil invasion (p=0.001), more lymphocyte invasion (p=0.001), and more Crohn's-like reaction (p=0.001). No significant correlation was observed between negative LNs and the neutrophil to lymphocyte ratio. More than 12 negative LNs were associated with increased platelets and CRP levels. A higher number of negative LNs was independently associated with longer disease-free survival in stage I+II patients (p=0.004) and stage III patients (p=0.015), while negative LNs were also independent prognostic factors in stage IV patients (p=0.007). CONCLUSION: Our study suggests that negative LNs are indicators of the immune response and are associated with a better prognosis in patients with colon cancer.

Association between Mismatch-repair Genetic variation and the Risk of Multiple Primary Cancers: A Meta-Analysis.

Microsatellites instability (MSI) is a risk factor for multiple primary cancers (MPCs). However, a variety of studies focused on the risk in the hereditary non-polyposis colorectal cancer (HNPCC) not the sporadic colorectal cancer (CRC) patients. The aim of this meta-analysis was to comprehensive overview and quantitative summary the association between MSI and risk of MPCs. A comprehensive literature search in MEDLINE, EMBASE, Web of science, ScienceDirect, Weily and OVID was conducted. Up to May 2016, we identified 22 observational studies. We calculated the summary relative risk (RR) for the risk of MPCs in MSI patients compared with microsatellites stability (MSS) patients using fixed- or random-effects models. The RR of the association between mismatch-repair gene (MMR) genotype and MPCs was 2.59 (95% confidence interval [CI], 2.06 to 3.27); the RR was 2.14 (95% CI, 1.78 to 2.57) for sporadic CRC and 5.59 (95% CI, 2.69 to 11.59) for HNPCC for the MSI versus MSS category. The subgroup analyses showed different mutant gene, mutant locus, and mutant level of MMR with different influence on the patients susceptible to MPCs. In addition, MSI genotype increase the risk of MPC was not associated with an apparently specific in regard to site, timing, age and detection method. In conclusion, this meta-analysis indicates that MSI is associated with an increased risk of MPCs both in the HNPCC and sporadic CRC patients. Our findings will form the backbone of the treatment for MSI genotype may be an important valuable strategy for MPCs prevention.

Primary Tumor Location as a Predictive Factor for First-line Bevacizumab Effectiveness in Metastatic Colorectal Cancer Patients.

Background: Published papers reported contradictory results about the correlation between bevacizumab effectiveness and primary tumor location of metastatic colorectal cancer (mCRC). Methods: 740 mCRC patients treated with chemotherapy (CT group) and 244 patients treated with bevacizumab plus chemotherapy as first-line setting (CT + B group) were included. Propensity score analyses were used for patients' stratification and matching. Kaplan-Meier curves with log-rank tests were used to detect different overall survival (OS). Results: Patients in CT + B group had similar OS comparing with CT group only when the primary tumor located at right-side colon (20.2 for CT + B versus 19.7 months for CT group, p = 0.269). For left-side colon and rectal cancer patients, significantly longer OS were observed in CT + B than CT group. Conclusion: Our data suggested only patients with left-side colon or rectal cancer could get survival benefit from the addition of bevacizumab to first-line chemotherapy.

The Effects of Anti-inflammatory Drug Treatment in Gastric Cancer Prevention: an Update of a Meta-analysis.

Gastric cancer has high incidence and fatality rates, making chemoprevention agents necessary. There is an ongoing debate about aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) use can significant reduce the risk of GC. We conducted a meta-analysis of existing studies evaluating the association of anti-inflammatory drug and GC. We performed a systematic literature search of PubMed, Web of Science, Embase, OVID, Cochrane Library and Clincialtrials.gov up to August 31, 2015. Either a fixed-effects or a random-effects model using was based on the result of homogeneity analysis. Subgroup, sensitivity, meta-regression, and publication bias analyses were evaluated. Forty-seven studies were finally included in this meta-analysis. The overall GC risk reduction benefit associated with anti-inflammatory drug use represented an RR of 0.78 (95% CI 0.71 to 0.85) and an adjusted RR of 0.74 (95% CI 0.71 to 0.77). Besides, the prevention benefit of aspirin/NSAIDs ingestion appeared to be confined to those patients with regiment of short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day). Further, our data also suggest that COX-2 inhibitors use is a more effective approach in GC prevention (RR, 0.45; 95% CI, 0.29-0.70). In this meta-analysis, our finding support short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day) aspirin/NSAIDs intake is a well method for GC prevention and also confirm the inverse association between aspirin/NSAIDs use and GC risk. Additionally, selective COX-2 inhibitors use probably a more effective approach to reduce GC risk.

The Efficacy of Bevacizumab in Different Line Chemotherapy for Chinese Patients with Metastatic Colorectal Cancer.

Objective: To evaluate the effect of bevacizumab in different lines for Chinese patients with metastatic colorectal cancer (mCRC). Methods: Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2007 to 2013 were recruited as study and control group. Endpoints were overall survival (OS), progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Corresponding survival rates of first- and second-line in study and control group were compared. Results: 1. Median OS of study and control group were 44.8 (95% CI: 37.1~52.4) months, 36.1 (95% CI: 32.8~39.5) months respectively, which were significantly different (P=0.004). 2. In the first line treatment, median OS of study and control group were 49.9(95% CI: 40.1~59.8) months and 36.1 (95% CI: 32.7~39.4) months (P=0.002), respectively. And median PFS were 10.1(95% CI: 8.7~11.5) months and 6.2 (95% CI: 5.5~6.8) months (P<0.001), respectively. 3. In the second line treatment, median OS of study and control group were 34.8 (95% CI: 26.3~43.3) months and 24.6 (95% CI: 22.2~27.0) months (P=0.022), respectively. And the mPFS were 6.3 (95% CI: 4.7~7.8) months and 3.1 (95% CI: 2.5~3.6) months (P<0.001), respectively. 4. Median OS of first- and second-line treatment of the study groups were 49.9(95% CI: 40.1~59.8) months and 34.8 (95% CI: 26.3~43.3) months (P=0.189), respectively. Conclusion: The combination of bevacizumab and chemotherapy had a promising efficacy in Chinese mCRC patients. However, their OS were statistically insignificant between first- and second-line of bevacizumab groups.

Palliative primary tumor resection provides survival benefits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen.

BACKGROUND: It remains controversial whether palliative primary tumor resection (PPTR) can provide survival benefits to the patients with metastatic colorectal cancer (mCRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with mCRC. METHODS: We conducted a retrospective study on consecutive mCRC patients with unresectable metastases who were diagnosed at Sun Yat-sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival (OS) and progression-free survival (PFS) after first-line chemotherapy failure were compared between the PPTR and non-PPTR patient groups. RESULTS: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non-PPTR groups was 20.8 and 14.8 months (P < 0.001), respectively. The median PFS after first-line chemotherapy was 7.3 and 4.8 months (P < 0.001) in the PPTR and non-PPTR groups, respectively. A larger proportion of patients in the PPTR group (219 of 254, 86.2%) showed local progression compared with that of patients in the non-PPTR group (95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase (LDH) levels and with carcinoembryonic antigen (CEA) levels <70 ng/mL benefited from PPTR (median OS, 22.2 months for the PPTR group and 16.2 months for the non-PPTR group; P < 0.001). CONCLUSIONS: For mCRC patients with unresectable metastases, PPTR can improve OS and PFS after first-line chemotherapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/mL.

Elevated preoperative neutrophil-to-lymphocyte ratio is associated with poor prognosis in gastrointestinal stromal tumor patients.

PURPOSE: To investigate the prognostic relevance of preoperative peripheral neutrophil- to-lymphocyte ratio (NLR) in gastrointestinal stromal tumor (GIST) patients. MATERIALS AND METHODS: We enrolled 129 consecutive GIST patients who underwent initial curative surgical resection with or without adjuvant/palliative imatinib treatment in our study. Blood NLR was calculated as neutrophil count (number of neutrophils ×10(9)/L) divided by lymphocyte count (number of lymphocytes ×10(9)/L). Survival curves were constructed by using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variable. All tests were two-sided, and P<0.05 was considered statistically significant. RESULTS: The optimal cut-off value of NLR was 2.07 in the receiver operating characteristic curve analysis. The median overall survival (OS) of high NLR group was 113.0 months, whereas that of the low NLR group had not reached the median OS both in the general (P<0.001) and subgroup analyses. The elevated NLR suggested shorter OS in the high malignant potential groups (P=0.01) and the combined low and moderate groups (P=0.02). Increased NLR indicated poor OS in patients regardless of whether if received imatinib treatment or not (P=0.005, and P=0.032, respectively). High NLR indicated poor OS of patients in stage I and II disease (P=0.005) and a clear tendency that increased level of NLR is inimical to OS. CONCLUSION: Elevated NLR was detected as an independent adverse prognostic factor. Elevated preoperative NLR predicts poor clinical outcome in GIST patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

A high LDL-C to HDL-C ratio predicts poor prognosis for initially metastatic colorectal cancer patients with elevations in LDL-C.

Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.

Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer.

BACKGROUND: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC) is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting. METHODS: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine. RESULTS: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%), 22 stable disease responses (62.9%), and six progressive disease responses (17.1%) were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7-48.0 months), the median progression-free survival was 5.98 months (95% confidence interval: 4.76-7.2 months), and the median overall survival was 14.77 months (95% confidence interval: 11.45-18.1 months). In the univariate analysis, patients with a primary colon tumor might have had a longer overall survival than patients with a primary rectal tumor (18.8 months vs 11.1 months, respectively; P=0.037). Common chemotherapy-related toxicities were nausea/vomiting (48.6%), fatigue (34.3%), leucopenia (40%), neutropenia, (42.9%), and anemia (42.9%), with one patient with grade 3 neutropenia, and two patients with grade 3 thrombocytopenia. The common bevacizumab-associated toxicity was hypertension (31.4%). None of the patients discontinued therapy or died because of bevacizumab-associated toxicities. CONCLUSION: Our data showed that adding bevacizumab to third- or later-line therapy might lead to tumor control and improved survival in heavily pretreated mCRC patients. In addition, preliminary data suggested that primary colon cancer was more likely to benefit from bevacizumab-containing regimens. Toxicities were acceptable, and no new toxicity was identified. Further studies are needed to validate these findings.

Prognostic model built on blood-based biomarkers in patients with metastatic colorectal cancer.

BACKGROUND: We had previously showed that the neutrophil lymphocyte ratio (NLR), γ-glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. MATERIALS AND METHODS: A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). RESULTS: NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). CONCLUSIONS: We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model.