Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

The DC-T cell axis is an effective target for the treatment of non-small cell lung cancer.

The dendritic cell (DC)-T cell axis is a bridge that connects innate and adaptive immunities. The initial immune response against tumors is mainly induced by mature antigen-presenting DCs. Enhancing the crosstalk between DCs and T cells may be an effective approach to improve the immune response to non-small cell lung cancer (NSCLC). In this article, a review was made of the interaction between DCs and T cells in the treatment of NSCLC and how this interaction affects the treatment outcome.

Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

BACKGROUND: The main types of PD-L1 in the blood include soluble PD-L1 (sPD-L1), exosomal PD-L1 (exoPD-L1), and PD-L1 in circulating tumor cells (CTCs). However, the predictive and prognostic values of these three indicators in patients with non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy are unclear, warranting a systematic meta-analysis. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) values were extracted from the included studies to investigate the correlation between the three PD-L1 indicators and overall survival (OS) or progression-free survival (PFS). The Newcastle-Ottawa Scale (NOS) was used to examine the quality of the included studies. Subgroup analyses were employed to investigate the heterogeneity. The publication bias of the included studies was assessed using Begg's and Egger's tests. P < 0.05 was regarded as significantly different. RESULTS: The pooled results revealed that high pre-treatment sPD-L1 levels were significantly associated with inferior OS (HR = 2.32, 95% CI = 1.68-3.18, P < 0.001) and PFS (HR = 2.52, 95% CI = 1.72-3.68, P < 0.001). However, dynamic changes in sPD-L1 after immunotherapy were not statistically significant for OS (HR = 1.46, 95% CI = 0.65-3.26, P > 0.05) or PFS (HR = 1.62, 95% CI = 0.92-2.86, P > 0.05). Meanwhile, the upregulated pre-treatment exoPD-L1 levels were significantly associated with poor PFS (HR = 4.44, 95% CI = 2.87-6.89, P < 0.001), whereas the post-treatment dynamic upregulation of exoPD-L1 was significantly correlated with superior PFS (HR = 0.36, 95% CI = 0.24-0.54, P < 0.001) and OS (HR = 0.20, 95% CI = 0.07-0.53, P < 0.001). For PD-L1 in CTCs, the pooled results indicated that PD-L1 expression in CTCs was not significantly correlated with OS (HR = 0.75, 95% CI = 0.49-1.13, P = 0.170) and PFS (HR = 0.79, 95% CI = 0.59-1.06, P = 0.12). CONCLUSIONS: Blood-based PD-L1 analysis is a potential strategy for predicting treatment efficacy and prognosis in patients with cancer.

Perioperative chemotherapy versus adjuvant chemotherapy treatment for resectable locally advanced gastric cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS: Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS: Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.

Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials.

BACKGROUND: The effect of early achievement of energy targets (EAETs) using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of EAETs on the incidence of nosocomial infections in patients undergoing major abdominal surgery. METHODS: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the EAET (521 EAET and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. RESULTS: Overall, 635 patients [mean (SD) age, 59.5 (11.3) years] were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 vs. 15.1±4.8 kcal/kg/d; P <0.001). The EAET group had significantly fewer nosocomial infections than the NAET group [46/521(8.8%) vs. 21/114(18.4%); risk difference, 9.6%; 95% CI, 2.1-17.1%; P =0.004]. A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups [121/521(23.2%) vs. 38/114(33.3%); risk difference, 10.1%; 95% CI, 0.7-19.5%; P =0.024]. The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group ( P <0.001), and other indicators were comparable between groups. CONCLUSION: EAETs was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).

Identification of SPRYD4 as a tumour suppressor predicts prognosis and correlates with immune infiltration in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive solid tumour with a 5-year survival rate ranging from 7% to 20%. It is, therefore, urgent to identify novel biomarkers and therapeutic targets to improve the outcomes of patients with CCA. SPRY-domain containing protein 4 (SPRYD4) contains SPRY domains that modulate protein-protein interaction in various biological processes; however, its role in cancer development is insufficiently explored. This study is the first to identify that SPRYD4 is downregulated in CCA tissues using multiple public datasets and a CCA cohort. Furthermore, the low expression of SPRYD4 was significantly associated with unfavourable clinicopathological characteristics and poor prognosis in patients with CCA, indicating that SPRYD4 could be a prognosis indicator of CCA. In vitro experiments revealed that SPRYD4 overexpression inhibited CCA cells proliferation and migration, whereas the proliferative and migratory capacity of CCA cells was enhanced after SPRYD4 deletion. Moreover, flow cytometry showed that SPRYD4 overexpression triggered the S/G2 cell phase arrest and promoted apoptosis in CCA cells. Furthermore, the tumour-inhibitory effect of SPRYD4 was validated in vivo using xenograft mouse models. SPRYD4 also showed a close association with tumour-infiltrating lymphocytes and important immune checkpoints including PD1, PD-L1 and CTLA4 in CCA. In conclusion, this study elucidated the role of SPRYD4 during CCA development and highlighted SPRYD4 as a novel biomarker and tumour suppressor in CCA.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. METHODS: Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (-) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194-0.468, p = 0.002). Multivariable Cox regression analysis identified that lymph node status after NACT was an independent prognostic factor associated with survival (OS: hazard ratio 1.756, 95% CI 1.114-3.278, p = 0.029; DFS: hazard ratio 1.901, 95% CI 1.331-3.093, p = 0.012). CONCLUSION: Lymph node status is a potential independent prognostic factor for LAGC patients treated with NACT and may be more efficient than pathological response in primary tumor.

Comparisons of nutritional status and complications between patients with and without postoperative feeding jejunostomy tube in gastric cancer: a retrospective study.

Background: Feeding jejunostomy tube (FJT) enables early postoperative nutritional supply for gastric cancer patients undergoing surgery. However, the nutritional benefit of FJT may be accompanied by potential risk of increased complications, so both the nutritional improvement and the complication rates associated with FJT should be assessed. Methods: From January 2009 to December 2014, 715 consecutive patients underwent gastric cancer resection at the Peking Union Medical College Hospital in China. The perioperative nutritional index and incidence of complications in patients with FJT placement were retrospectively compared to those in patients without FJT placement. Nutritional data including albumin, prealbumin, hemoglobin, and high sensitivity C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutrition index (OPNI) were recorded at the following 3 timepoints: preoperatively, 1-week postoperatively, and 1-month postoperatively. Postoperative complications including surgical site infection, intra-abdominal infections, anastomotic leaks and gastroparesis were assessed. Multivariate logistic regression was used to study the association between FJT and complications. Results: A total of 715 patients were included in the study. The mean age was 60.4 years and 72.2% were male. The overall characteristics between FJT and no-FJT groups were comparable. Of the 247 total gastrectomy cases, 98 (39.7%) had a FJT placed. Compared to the total gastrectomy patients without a FJT, the 98 patients with a FJT had a lower hemoglobin level (P=0.048) and NLR (P=0.030) preoperatively, and higher albumin (P=0.005), prealbumin (P<0.001), and hemoglobin (P=0.014) levels, a higher OPNI (P=0.027), and a lower NLR (P=0.005) 1-month postoperatively. Of the 468 subtotal gastrectomy cases, 87 (18.6%) had a FJT placed. Compared to the subtotal gastrectomy patients without a FJT, these 87 patients had a lower NLR (P=0.006) 1-week postoperatively, and a higher albumin level (P=0.009) 1-month postoperatively. In the multivariate analysis, FJT placement was not associated with postoperative adverse outcomes, including surgical site infection [odds ratio (OR) =1.21, P=0.79], intra-abdominal infection (OR =0.38, P=0.11), anastomotic leak (OR =0.58, P=0.53), reoperation (OR =0.22, P=0.23), gastroparesis (OR =6.35, P=0.08), or hospitalization for more than 30 days (OR =0.58, P=0.32). Conclusions: Early enteral nutritional support by FJT after gastrectomy tended to improve the nutritional status of patients, while it did not appear to increase the incidence rate of postoperative complications.

A clinical nomogram based on absolute count of lymphocyte subsets for predicting overall survival in patients with non-small cell lung cancer.

BACKGROUND: The absolute count of lymphocyte subsets (ACLS) is correlated to the prognosis of multiple malignancies. This study aimed to combine the ACLS with the clinicopathological parameters to develop a nomogram to accurately predict the prognosis of non-small cell lung cancer (NSCLC) patients. METHODS: This retrospective study included a training cohort (n = 1685) and validation cohort (n = 337) with NSCLC patients treated in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine between January 2018 and January 2021. Cox regression were conducted to identify factors associated with overall survival. The nomogram was built based on 10 significant factors, and evaluated by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULTS: In the training cohort, the multivariate cox proportional hazard regression analysis showed that the independent factors for overall survival (OS) included age, brain metastases, hepatic metastases, respiratory system diseases, clinical stages, surgery, absolute count (AC) of CD3+, CD4+, CD8+, and NK cells, which were all applied in the nomogram. The C-index of the nomogram to predict OS was 0.777 (95% CI, 0.751-0.802) in training cohort and 0.822 (95% CI, 0.798-0.846) in validation cohort. The area under the ROC showed a good discriminative ability in both cohorts. Calibration curves presented an excellent consistence between the nomogram predicted probability and actual observation. CONCLUSIONS: We established a prognostic nomogram to predict OS of the NSCLC patient. This nomogram provided a more quantitative, scientific and objective basis for accurate diagnosis and individual management of NSCLC patients.

Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway.

Urolithin A (UA) is a microbial metabolite of natural polyphenols ellagitannins and ellagic acid with well-established antitumor properties against various malignancies. However, the exact role of UA in gastric cancer (GC) progression remains largely unclear. In the present study, we investigated the effects and potential mechanisms of UA in GC in vitro and in vivo. Our results revealed that UA could suppress GC cell proliferation, inhibit migration and invasion, promote apoptosis, and induce autophagy via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway in vitro. The autophagy inhibitors 3-methyladenine and chloroquine augmented the inhibitory effect of UA on proliferation and promoted apoptosis, implying that UA mediated the cytoprotective role of autophagy. Meanwhile, the in vivo experiments showed that UA effectively suppressed tumor growth, enhanced the therapeutic effects, and alleviated chemotherapy toxicity in xenograft models. Overall, these findings offer novel insights into the role of UA in tumor therapy and suggest that UA may possess potential therapeutic applications for GC.

Intestinal Nutrition Played a Vital Important Role in an Intestinal Perforation Patient with Chronic Constipation: A Case Report.

Introduction: Nutrition treatment is important in the critically ill patient. Nutritional therapy should be instituted as soon as possible if indicated. Case presentation: A 64-year-old woman with malnutrition and intestinal obstruction with gastrointestinal bleeding came to our emergency room. She had a history of constipation. After CT scan, we found perforations in the digestive tract. Because she could not tolerate surgery and parenteral nutrition (PN), we chose to start enteral nutrition (EN). She recovered after the initiation of EN. Discussion: Chronic constipation may cause intestinal obstruction, which is rare but fatal. Providers should evaluate the nutritional status for the intensive care patient and start PN/EN at once if necessary. EN may help the closure of perforations. Conclusion: EN may play a vital important role even in the patients who have perforations in the digestive tract. Chronic constipation may cause obstruction and perforation, which are rare but fatal.

Association between Plasma FGF21 Levels and Body Composition in Patients with Gastric Cancer.

BACKGROUND: Accumulating evidence has suggested that Fibroblast growth factor 21 (FGF21) plays an important role in metabolic diseases. This study aimed to investigate the relationship between plasma FGF21 levels and body composition parameters in gastric cancer (GC) patients. METHODS: This study was cross-sectional based on a prospective cohort of GC patients in a single center. Computer tomography (CT) and bioelectrical impedance analysis (BIA) were used to estimate skeletal muscle and adipose tissue mass. Blood samples were collected and plasma concentrations of FGF21 were measured by ELISA. Spearman's rank correlation test and logistic regression analysis were performed to assess associations between plasma FGF21 levels and these body composition parameters. RESULTS: A total of 66 GC patients were enrolled in this study. Plasma FGF21 levels were significantly higher in women compared with men. The plasma FGF21 levels were positively correlated with fat mass index (FMI), fat mass percentage (FM%), and subcutaneous adipose tissue index (SATI). Furthermore, after adjustment for confounders, the lower plasma FGF21 levels were remain associated with increased odds for low SATI. CONCLUSIONS: Plasma FGF21 levels were positively associated with FMI, FM%, and SATI in GC patients, suggesting a potential mechanistic link between FGF21 and subcutaneous adipose tissue in GC.

Visceral Adipose Tissue Assessment Enhances the Prognostic Value of GLIM Criteria in Patients with Gastric Cancer Undergoing Radical Gastrectomy after Neoadjuvant Treatment.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) criteria has been recently published for diagnosing malnutrition in adults. However, the validity of the GLIM criteria has not been well-established in patients with gastric cancer (GC) treated with neoadjuvant treatment (NT) followed by radical gastrectomy. The present study aimed to explore the prognostic value of GLIM-defined malnutrition before NT and after NT in GC patients and to investigate whether additional visceral adipose tissue (VAT) assessment could improve the predictive power of the GLIM criteria for NT-related adverse events (AEs) and long-term survival. METHODS: GC patients who underwent radical surgery after NT from June 2016 to June 2020 were enrolled in this study. The cross-sectional areas of total skeletal muscle (TSM) and VAT were measured using computed tomography (CT) before NT and after NT. GLIM-defined malnutrition was diagnosed using the two-step approach, including nutritional risk screening and diagnostic assessment. Low VAT was also added to the diagnosis of malnutrition in this study. The predictive value of these malnutrition diagnoses for NT-related AEs, and long-term survival was evaluated in GC patients. RESULTS: A total of 182 GC patients were included in this study, of which 66 (36.3%) patients before NT and 55 (30.2%) patients after NT were diagnosed with GLIM-defined malnutrition, respectively. In addition to GLIM-defined malnutrition, 54 (29.7%) patients had additional low VAT before NT, and 39 (21.4%) patients had additional low VAT after NT. GLIM-defined malnutrition alone before NT was not associated with NT-related AEs in GC patients. The addition of low VAT to GLIM-defined malnutrition led to a significant predictive value for NT-related AEs. Furthermore, GLIM-defined malnutrition before NT and after NT were both identified as independent risk factors for overall survival (OS) and disease-free survival (DFS). The combination of low VAT and GLIM-defined malnutrition showed a higher hazard ratio for the prediction of OS and DFS both before NT and after NT. CONCLUSIONS: The addition of VAT assessment using CT improved the predictive value of GLIM-defined malnutrition for NT-related AEs and long-term survival in GC patients treated with NT followed by radical gastrectomy, which further supports the prognostic importance of assessing adipose tissue simultaneously during the routine nutritional assessment in patients with cancer.

Does postoperative chemotherapy improve overall survival of patients with ypT1-2N0 cancer?

BACKGROUND: Perioperative chemotherapy combined with curative gastrectomy has been increasingly represented the standard therapeutic strategy for resectable gastric cancer (GC). However, it is still unclear whether postoperative chemotherapy has a survival benefit for ypT1-2N0 gastric cancer patients who have undergone preoperative chemotherapy followed curative gastrectomy. METHODS: The data of patients who undergone neoadjuvant chemotherapy followed by gastrectomy and had pathological classification of ypT1-2N0 between March 2016 and December 2020 at Peking Union Medical College Hospital were retrospectively reviewed. Chi-square test was adopted to compare the difference between the patients with postoperative chemotherapy (pCHT) and without postoperative chemotherapy (no pCHT). Survival curves for overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 134 patients met the inclusion criteria and 56 (41.8%) of them have undergone postoperative chemotherapy. There were no statistically significant differences in demographic and clinicopathologic characteristics between pCHT group and no pCHT group (all p > 0.05). Postoperative chemotherapy was not associated with a significant improvement in overall survival (OS) (Hazard ratio [HR] 0.815, 95% confidence interval [CI] 0.403-1.650; p = 0.474). Subgroup analyses demonstrated survival was equivalent between pCHT and no CHT group in ypT1N0 patients (HR 0.832, CI 0.222-3.121; p = 0.786) and ypT2N0 patients (HR 1.284, CI 0.564-2.924; p = 0.551). Multivariable analysis identified that clinical T stage independently influenced prognosis (cT3 vs. cT2: HR 2.875, 95% CI 0.998-8.281, p = 0.050; cT4 vs. cT2: HR 7.382, 95% CI 2.569-21.211, p < 0.001). In clinical T3-4 patients, there was an overall survival benefit for postoperative chemotherapy (HR 0.270, 95% CI 0.114-0.634; p = 0.006). No survival benefit of postoperative chemotherapy was identified in clinical T2 patients (HR 0.689, 95% CI 0.200-2.372; p = 0.579). Furthermore, postoperative chemotherapy was proved to be an independently positive prognostic factor for clinical T3-4 patients (HR 0.132, 95% CI 0.051-0.345; p < 0.001). CONCLUSION: Postoperative chemotherapy might offer survival benefit to patients with ypT1-2N0 gastric cancer whose clinical T stage was T3-4 before preoperative chemotherapy.

Risk factors for cancer-specific survival in elderly gastric cancer patients after curative gastrectomy.

BACKGROUND/OBJECTIVES: This study aimed to investigate cancer-specific survival (CSS) and associated risk factors in elderly gastric cancer (EGC) patients. SUBJECTS/METHODS: EGC patients (≥ 70 yrs) who underwent curative gastrectomy between January 2013 and December 2017 at our hospital were included. Clinicopathologic characteristics and survival data were collected. Receiver operating characteristic (ROC) analysis was used to extract the best cutoff point for body mass index (BMI). A Cox proportional hazards model was used to determine the risk factors for CSS. RESULTS: In total, 290 EGC patients were included, with a median age of 74.7 yrs. The median follow-up time was 31 (1-77) mon. The postoperative 1-yr, 3-yr and 5-yr CSS rates were 93.7%, 75.9% and 65.1%, respectively. Univariate analysis revealed risk factors for CSS, including age (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.01-1.15), intensive care unit (ICU) admission (HR = 1.73; 95% CI, 1.08-2.79), nutritional risk screening (NRS 2002) score ≥ 5 (HR = 2.33; 95% CI, 1.49-3.75), and preoperative prognostic nutrition index score < 45 (HR = 2.06; 95% CI, 1.27-3.33). The ROC curve showed that the best BMI cutoff value was 20.6 kg/m2. Multivariate analysis indicated that a BMI ≤ 20.6 kg/m2 (HR = 2.30; 95% CI, 1.36-3.87), ICU admission (HR = 1.97; 95% CI, 1.17-3.30) and TNM stage (stage II: HR = 5.56; 95% CI, 1.59-19.43; stage III: HR = 16.20; 95% CI, 4.99-52.59) were significantly associated with CSS. CONCLUSIONS: Low BMI (≤ 20.6 kg/m2), ICU admission and advanced pathological TNM stages (II and III) are independent risk factors for CSS in EGC patients after curative gastrectomy. Nutrition support, better perioperative management and early diagnosis would be helpful for better survival.

The Predictive Value of Changes in the Absolute Counts of Peripheral Lymphocyte Subsets for Progression and Prognosis in Breast Cancer Patients.

Background: As the number and proportion of lymphocyte subsets are an important indicator of the immune function, an in depth understanding of the immune function of patients with malignant tumor has important clinical values for the treatment, prognosis, and evaluation of the disease. This retrospective study was to evaluate the clinical value of the absolute counts of lymphocyte subsets as potential blood biomarkers for progression and prognosis in breast cancer patients. Methods: A total of 237 BC patients and 55 age-matched female normal healthy donors were included in this study. Flow cytometry was used to determine the absolute counts and the percentages of CD3+, CD4+, CD8+, B, and NK cells. The receiver operating characteristic curve (ROC) was used to evaluate the accuracy of absolute count of lymphocyte subsets in the curative efficacy assessment. The clinicopathological parameters influencing the disease progression were determined by Cox proportional hazards regression. Progression-free survival (PFS) was estimated using the Kaplan-Meier method with the log-rank test. Results: Compared with the healthy donors, the absolute counts of lymphocyte subsets in patients decreased significantly. ROC analysis showed that the area under the curve of the CD4+ absolute count was 90% (95% confidence interval 0.859-0.940), and the sensitivity and specificity were 80.9% and 85.3%, respectively. The analysis of Cox regression showed that the cutoff value of the CD4+ absolute count ≥451 cells/µL might be a favorable prognostic factor. Multivariate analysis of prognostic factors of PFS showed that the CD4+ and CD8+ absolute count were independent factors for predicting PFS. Conclusions: The remarkably impaired absolute counts of the CD3+, CD4+, CD8+, B, and NK cells in patients with breast cancer can be used as potential susceptible biomarkers to evaluate the patient's immune status. The higher level of CD4+ and CD8+ absolute counts probably contributed to the longer PFS and favorable outcome of BC patients.

Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer.

BACKGROUND: 5-fluorouracil (5-FU)-based chemotherapy regimen has been widely used for the treatment of gastric cancer, but meanwhile the development of chemotherapeutic resistance remains a major clinical challenge. Tumor microenvironment (TME) frequently correlates with the development of chemoresistance in human cancer. As a major component of TME, the role of tumor-associated macrophages (TAMs) in the chemoresistance of gastric cancer has not been fully elucidated. METHODS: Immunohistochemistry (IHC) was applied to detect the density of TAMs in clinical samples of 103 patients with gastric cancer who had undergone 5-FU-based neoadjuvant chemotherapy. 5-FU-resistant gastric cell lines MKN45-R and HGC27-R were established, macrophages were then separately co-cultured with MKN45-R, HGC27-R cells and their parental cells. The effect of gastric cancer cells on the polarization of macrophages, the biological function of M2-polaried macrophages and the mechanism for promoting 5-FU-resistance were investigated. Then the correlation between the expression of CXC motif chemokine ligand 5 (CXCL5) and the infiltration of hemoglobin scavenger receptor (CD163) positive and mannose receptor (CD206) positive macrophages was analyzed, the prognostic value of CXCL5 expression in clinical samples was further explored. RESULTS: The high infiltration of macrophages marked by CD68 in gastric cancer samples was significantly associated with the resistance of gastric cancer to chemotherapy. Gastric cancer cells could modulate macrophages to M2-like polarization through indirect co-culture, and chemoresistant cells were more efficient in inducing macrophages polarization to M2 phenotype. Co-culturing M2-polarized macrophages in turn enhanced 5-FU-resistance of gastric cancer cells, and it was further verified that CXCL5 derived from M2-polarized macrophages promoted chemoresistance through activing the PI3K/AKT/mTOR pathway. Besides, high level of CXCL5 could recruit monocytes to form more M2-polarized macrophages. Clinically, high expression of CXCL5 in gastric cancer samples was associated with the high infiltration of CD163 positive macrophages and CD206 positive macrophages, and patients with high expression of CXCL5 presented lower overall survival (OS) rates than those with low expression of CXCL5. CONCLUSION: Interaction between TAMs and gastric cancer cells promoted chemoresistance in gastric cancer via CXCL5/PI3K/AKT/mTOR pathway. Thus, targeting TAMs and blocking the cell-cell crosstalk between TAMs and gastric cancer cells may represent prospective therapeutic strategies for patients with gastric cancer.

Clinical predictive value of naïve and memory T cells in advanced NSCLC.

Currently, there is no sensitive prognostic biomarker to screen out benefit patients from the non-benefit population in advanced non-small cell lung cancer patients (aNSCLCs). The 435 aNSCLCs and 278 normal controls (NCs) were recruited. The percentages and absolute counts (AC) of circulating naïve and memory T lymphocytes of CD4+ and CD8+ T cells (Tn/Tm) were measured by flow cytometry. The percentage of CD4+ naïve T (Tn), CD8+ Tn, CD8+ T memory stem cell (Tscm), and CD8+ terminal effector T cell decreased obviously. Still, all AC of Tn/Tm of aNSCLCs was significantly lower compared to NCs. Higher AC and percentage of CD4+ Tn, CD8+ Tn, and CD4+ Tscm showed markedly longer median PFS in aNSCLCs. Statistics demonstrated the AC of CD4+ Tn (≥ 3.7 cells/µL) was an independent protective factor for PFS. The analysis of the prognosis of immunotherapy showed the higher AC and percentage of CD4+ Tn and CD4+ Tscm and higher AC of CD8+ Tscm had significantly longer median PFS and the AC of CD4+ Tn (≥ 5.5 cells/µL) was an independent protective factor for PFS. Moreover, higher AC and percentages of Tn/Tm suggested higher disease control rate and lower progressive disease rate. The AC of Tn/Tm showed more regular patterns of impairment and was more relative with the disease progression than percentages in aNSCLCs. AC had a better predictive value than percentages in Tn/Tm for PFS. Notably, the AC of CD4+ Tn was a potential prognostic biomarker for the PFS and efficacy of immunotherapy.

Risk factors for inpatient malnutrition and length of stay assessed by 'NutritionDay' in China.

BACKGROUND AND OBJECTIVES: NutritionDay is a yearly global point-prevalence study of malnutrition or nutritional risk in hospitals. We aimed to provide a comprehensive nutritional survey of hospitalized patients and analyze the risk factors of malnutrition and prolonged hospitalization in Chinese inpatients. METHODS AND STUDY DESIGN: The international daylong cross-sectional survey was performed on November 07th, 2019. Ten hospitals were invited to participate in this NutritionDay survey. Nutritional risk was identified by nutritional risk screening 2002, and malnutrition was identified by the ESPEN criteria. We measured the incidence of malnutrition and nutritional risk. And we analysed risk factors for malnutrition and length of stay in Chinese hospitalized patients. RESULTS: 875 hospitalized patients from 6 departments were included in the analysis. The malnutrition rate was 11.6% and the incidence of nutritional risk was 17.8%. It was analyzed that tumor load, end-stage disease, motility, self-rated health, types of oral medicine, and food intake during the past week were independent risk factors for malnutrition or nutritional risk. 56.2% (118/210) of patients at nutritional risk or malnutrition received extra nutritional support, whereas 22.5% (88/391) well-nourished patients did. Moreover, nutrition status, ever stayed in ICU and self-rated health were associated with prolonged length of stay. CONCLUSIONS: In a word, the prevalence of malnutrition or nutritional risk was about 29.4%. Patients with malnutrition or nutritional risk had a higher transfer rate, lower rehabilitation rate and longer hospital stays. The attention to malnutrition patients needs to be further strengthened.