A novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer.

BACKGROUND: Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM. MATERIALS AND METHODS: We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy. RESULTS: The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR (P = 0.009) and PLR (P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR (P = 0.025) was an independent risk factor in multivariate analyses, together with age (P = 0.009), differentiation (P = 0.017), invasive depth (P < 0.001), and tumor size (P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively. CONCLUSIONS: Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients.

Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.

BACKGROUND: Sarcopenia is characterized by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was performed to determine the association of sarcopenia with short-term postoperative outcomes after gastrectomy for gastric cancer. METHODS: We conducted a prospective study of 255 consecutive patients with gastric cancer who underwent curative gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis. RESULTS: Sarcopenia was present in 32 of 255 patients (12.5 %), and was significantly correlated with advance age, lower body mass index, higher nutritional risk screening (NRS) 2002 score, and lower preoperative serum albumin and hemoglobin. Compared with non-sarcopenic patients, sarcopenic patients had a higher risk of postoperative complications, longer postoperative hospital stay, and more hospital costs. In univariate analysis, sarcopenia (p < 0.001), nutritional risk (NRS 2002 score ≥3; p = 0.003), advanced age (≥75 years; p = 0.014), anemia (p = 0.012), hypoalbuminemia (p = 0.029), and diabetes (p = 0.014) were associated with postoperative complications. Multivariable analysis revealed that sarcopenia (p < 0.001) and diabetes (p = 0.006) were independent predictors of postoperative complications. CONCLUSIONS: Sarcopenia is an independent predictor of postoperative complications in patients with gastric cancer after gastrectomy.

Long noncoding RNA GAS5 inhibits proliferation and metastasis in papillary thyroid carcinoma through the IFN/STAT1 signaling pathway.

Dysregulation of the long noncoding RNA GAS5 in human cancer has been identified in recent studies. In this study, we confirmed a negative correlation between the GAS5 expression level and papillary thyroid carcinoma clinicopathologic characteristics, such as the tumor size, lymph node metastasis, the TNM stage and BRAFV600E mutation. The viability and metastasis of papillary thyroid carcinoma cells were detected by CCK-8 and transwell assays, respectively. The results showed that upregulation of GAS5 significantly inhibited papillary thyroid cancer cell growth, migration and invasion in vitro. RNA transcriptome sequencing was performed to explore the underlying targets of GAS5. Through qRT-PCR and Western blot analysis, we found that ectopic expression of GAS5 significantly increased IFI44 and STAT1 levels. Taken together, these findings suggest that GAS5 is a tumor suppressor in papillary thyroid carcinoma, and the action of GAS5 may be mediated through the IFNγ/STAT1 signaling pathway.

LncRNA RP11-138J23.1 Contributes to Gastric Cancer Progression by Interacting With RNA-Binding Protein HuR.

In spite of improvements in diagnostics and treatment of gastric cancer (GC), it remains the most common malignancy of human digestive system. It is now widely appreciated that long noncoding RNAs (lncRNAs) exert extensive regulatory effects on a spectrum of fundamental biological processes through diverse mechanisms. In this study, we explored the expression level and functional role of lncRNA RP11-138J23.1 in GC. Through bioinformatics analyses and in situ hybridization (ISH), we identified that RP11-138J23.1 was upregulated in GC tissue. Further study showed that RP11-138J23.1 knockdown significantly inhibited cell proliferation and metastatic ability. Whereas, RP11-138J23.1 overexpression could promote tumor cell growth and metastasis in vitro. Additionally, loss-of-function assays were used to confirm the role of RP11-138J23.1 in vivo. Mechanistically, RP11-138J23.1 exerted its oncogenic functions by binding to HuR protein and increasing stability of VAV3 mRNA. Overall, our study highlights the essential role of RP11-138J23.1 in GC, suggesting that RP11-138J23.1 might be a potent therapeutic target for patients with GC.

Interferon gamma inhibits CXCL8-CXCR2 axis mediated tumor-associated macrophages tumor trafficking and enhances anti-PD1 efficacy in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to achieve significant clinical effects so far. Interferon gamma (IFN-γ) is a soluble dimeric cytokine that is closely associated with tumor immune surveillance and cytotoxicity. IFN-γ suppresses a variety of tumor-derived cytokines in PC, such as CXCL8. In the present study, we investigated the therapeutic efficacy of combined anti-PD1 and IFN-γ treatment in PC. METHODS: BxPC-3 and Panc-1 human PC cell lines were used to construct a murine PC model. Blood samples (n=44) and surgical resection specimens (n=36) from human patients with PC were also collected. χ2 test, two-tailed unpaired t-test or Kaplan-Meier survival analysis was used to calculate p values. RESULTS: PD1/PD-L1 signaling was overexpressed in PC tumor-bearing mice. Anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 treatment showed limited benefit. Murine PC model had a preferential expansion of CXCR2+CD68+ macrophages, and these cells showed an immunosuppressive nature (M2 polarization). PC tumors overexpressed CXCL8 and tumor-derived CXCL8 deficiency prohibited the trafficking of CXCR2+CD68+ macrophages. IFN-γ suppressed the expression of tumor-derived CXCL8, and combined with IFN-γ treatment, delayed anti-PD1 treatment showed significant antitumor effects. Thus, we conclude that murine CXCR2+CD68+ macrophages traffic to PC tumors by tumor-derived CXCL8 and mediate local immunosuppression, which limits the efficacy of PD1 blockade therapy. IFN-γ suppresses tumor-derived CXCL8 and inhibits the tumor trafficking of CXCR2+CD68+ macrophages by blocking the CXCL8-CXCR2 axis to enhance anti-PD1 efficacy. Human PC also produces high levels of CXCL8. Patients with PC present elevated CXCR2 expression on peripheral and tumor-infiltrating CD68+ macrophages, which are associated with advanced tumor stage and poor prognosis. CONCLUSION: Our findings suggest that IFN-γ is a translatable, therapeutic option to improve the efficacy of PD1 blockade therapy by preventing trafficking of CXCR2+CD68+ macrophages via blocking the CXCL8-CXCR2 axis.

Sarcopenia is associated with the neutrophil/lymphocyte and platelet/lymphocyte ratios in operable gastric cancer patients: a prospective study.

PURPOSE: Sarcopenia is distinguished by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was designed to demonstrate the relationship between sarcopenia and systemic inflammatory response (neutrophil/lymphocyte ratio [NLR], platelet/lymphocyte ratio [PLR], and large platelet/lymphocyte ratio [LPLR]) prior to radical gastrectomy for gastric cancer. PATIENTS AND METHODS: We conducted a prospective study of gastric cancer patients who underwent radical gastrectomy. The clinical utility of the NLR, PLR, and LPLR was evaluated by receiver operating characteristic curves. Sarcopenia components including skeletal muscle index, handgrip strength, and 6 m usual gait speed were measured. Logistic analysis was used to identify the independent indices associated with sarcopenia. RESULTS: A total of 670 patients were included, representing 504 men and 166 women. Of these, 104 patients (15.5%) were diagnosed with sarcopenia and 567 (84.5%) were non-sarcopenia. PLR has a diagnostic sensitivity of 91.3% for sarcopenia. In addition to the indicators of preoperative age, nutritional risk screening, body mass index, preoperative albumin, and diabetes, the NLR and PLR were independent predictors for sarcopenia (P<0.05). CONCLUSION: The present study showed that at-diagnosis sarcopenia was associated with inflammation in patients with operable gastric cancer. Due to the complex assessment of muscle condition, PLR may be used as a primary screening test for sarcopenia. How systemic inflammatory response influences changes in sarcopenia may provide new therapeutic perception toward improving outcomes.

Sarcopenic Obesity Is Associated with Severe Postoperative Complications in Gastric Cancer Patients Undergoing Gastrectomy: a Prospective Study.

OBJECTIVE: This study aimed to determine the risk of severe postoperative complications (SPCs) in patients with gastric cancer and to construct a nomogram based on independently related factors to identify high-risk patients. METHODS: We conducted a prospective study of 636 consecutive patients with gastric cancer who underwent radical gastrectomy. Degrees of sarcopenia and obesity were calculated before surgery. Factors contributing to SPCs were determined using univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of SPCs. RESULTS: Logistic analysis revealed that sarcopenic obesity, age, open surgery, and combined resection were independent prognostic factors for SPCs. Sarcopenic obese patients have the highest risk in all patients (sarcopenic obesity vs normal, OR = 6.575 p = 0.001; sarcopenic obesity vs obesity, OR = 5.833 p = 0.001; sarcopenic obesity vs sarcopenia, OR = 2.571 p = 0.032), while obese patients share the similar rate of SPCs with normal people (obesity vs normal, OR = 1.056 p = 0.723). The nomogram we constructed was able to quantify the risk of SPCs reliably (c-index, 0.737). CONCLUSIONS: Sarcopenic obesity, together with age, open surgery, and combined resection are independent predictors of SPCs. Obesity will significantly increase the risk of SPCs in sarcopenic patient with gastric cancer, but it will not bring higher risk to normal patients. Our nomogram is a simple and practical instrument to identify patients at high risk of surgical complications.

A Novel Nomogram for Predicting Postsurgical Intra-abdominal Infection in Gastric Cancer Patients: a Prospective Study.

BACKGROUND: This study aimed to determine the relationship between intra-abdominal infection (IAI) and sarcopenia prospectively and to construct a nomogram to identify patients at a high risk of IAI. METHODS: We conducted a prospective study of 682 consecutive patients with gastric cancer who underwent radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Factors contributing to IAI were determined through univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of IAI. RESULTS: Of the 682 patients enrolled in this study, 132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI. Logistic analysis revealed that sarcopenia, tumor size, pathological type, and multivisceral resection were independent prognostic factors for IAI. The nomogram model for IAI was able to reliably quantify the risk of IAI with a strong optimism-adjusted discrimination (concordance index, 0.736). CONCLUSIONS: Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and practical instrument to quantify the individual risk of IAI and could be used to identify patients at a high risk.

Urinary Microvesicle-Bound Uromodulin: A Potential Molecular Biomarker in Diabetic Kidney Disease.

This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD.

Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.

BACKGROUND: The association between sarcopenia and postoperative outcomes has been well reported. However, the impact of different sarcopenia stages on postoperative outcomes has never been investigated. METHODS: We conducted a large, prospective study of patients who underwent radical gastrectomy for gastric cancer from August 2014 to December 2015. Sarcopenia was staged as "presarcopenia," "sarcopenia," and "severe sarcopenia" according to the definition of the European Working Group on Sarcopenia in Older People. Univariate and multivariate analyses evaluating the risk factors for total, surgical, and medical complications were performed. RESULTS: A total of 470 patients were included, in which 20.6%, 10%, and 6.8% of the patients were identified as having "presarcopenia," "sarcopenia," and "severe sarcopenia," respectively. Postoperative complications, duration of hospital stays, and costs increased with advancing sarcopenia stages. Severe sarcopenia, visceral fat area to total abdominal muscle area ratio, American Society of Anesthesiologists grade III, and tumor located at the cardia were independent risk factors for total complications. Visceral fat area to total abdominal muscle area ratio and tumor located at the cardia were independent risk factors for operative complications. Presarcopenia, sarcopenia, and severe sarcopenia were all identified as independent risk factors for medical complications, as well as age ≥75 years and Charlson Comorbidity Index. CONCLUSION: Patients had worse postoperative outcomes after gastric cancer operation with advancing sarcopenia stages. Severe sarcopenia, but not presarcopenia or sarcopenia, was an independent risk factor for total postoperative complications. The 3 sarcopenia stages independently influence medical but not surgical complications. Recognizing sarcopenia stages is important for preoperative risk stratification.

Use of the combination of the preoperative platelet-to-lymphocyte ratio and tumor characteristics to predict peritoneal metastasis in patients with gastric cancer.

The aims of the present study were to evaluate the predictive value of the platelet-to-lymphocyte ratio for peritoneal metastasis in patients with gastric cancer and to construct an available preoperative prediction system for peritoneal metastasis. A total of 1080 patients with gastric cancer were enrolled in our study. The preoperative platelet-to-lymphocyte ratio and other serum markers and objective clinical tumor characteristics were evaluated by receiver operating characteristic curves. A logistic analysis was performed to determine the independent predictive indicators of peritoneal metastasis. A prediction system that included the independent predictive indicators was constructed and evaluated by receiver operating characteristic curves. Based on the receiver operating characteristic curves, the ideal platelet-to-lymphocyte ratio cutoff value to predict peritoneal metastasis was 131.00. The logistic analysis showed that the platelet-to-lymphocyte ratio was an independent indicator to predict peritoneal metastasis. The area under the receiver operating characteristic curve was 0.599. When integrating all independent indicators (i.e., platelet-to-lymphocyte ratio, invasion depth, lymphatic invasion, pathological type), the prediction system more reliably predicted peritoneal metastasis with a higher area under the receiver operating characteristic curve (0.769). The preoperative platelet-to-lymphocyte ratio was an indicator that could be used to predict peritoneal metastasis. Our prediction system could be a reliable instrument to discriminate between patients with gastric cancer with and those without peritoneal metastasis.

Combination of preoperative platelet/lymphocyte and neutrophil/lymphocyte rates and tumor-related factors to predict lymph node metastasis in patients with gastric cancer.

OBJECTIVE: Lymph node (LN) metastasis is widely accepted as a poor prognosis indicator in patients with gastric cancer. An accurate preoperative prediction of LN status is of crucial importance for the planning treatment. The aim of the present study was to assess the predictive value of the preoperative platelet/lymphocyte (PLR) and neutrophil/lymphocyte rates (NLR) on the LN metastasis in gastric cancer patients and to develop a new preoperative score system to predict LN metastasis. PATIENTS AND METHODS: A total of 492 operable patients with gastric cancer were enrolled in our study. The clinical utility of the PLR and NLR was evaluated by receiver operating characteristic (ROC) curves. The logistic analysis was used to identify the independent parameters associated with LN metastasis. Then, a score system including those independent parameters that can be detected preoperatively was established, which was also tested by an ROC curve. RESULTS: The ideal cutoff values for predicting LN metastasis were 1.59 for NLR and 155.67 for PLR according to the ROC curve. Multivariate analyses showed that both PLR and NLR are significantly associated with LN metastasis independent of depth of invasion, lymphatic invasion, macroscopic type, and tumor size. The area under the ROC curve of the score system was 0.830 (95% confidence interval 0.782-0.878), showing a reliable ability to evaluate the status of nodal involvement. CONCLUSION: Preoperative PLR and NLR are useful biomarkers to predict LN metastasis and the score system in our study may serve as a reliable instrument to predict LN metastasis in gastric cancer patients.

Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a Large-Scale Cohort.

Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm²/m² for women and 40.8 cm²/m² for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I.

Prediction of Prolonged Postoperative Ileus After Radical Gastrectomy for Gastric Cancer: A Scoring System Obtained From a Prospective Study.

Currently, there is a paucity of study investigating postoperative ileus in gastric cancer surgery. This prospective study aims to identify the risk factors for prolonged postoperative ileus (PPOI) and to use these risk factors to generate a risk stratification scoring system for the occurrence of PPOI.Patients who underwent radical gastrectomy for gastric cancer were included in this study. A multivariate logistic analysis was applied to identify independent risk factors for PPOI and to generate the scoring system. A receiver operating characteristic curve was generated and the area under the curve was calculated to demonstrate the predictive power of the scoring system.Finally, 296 patients were included and analyzed, of whom 96 (32.4%) developed PPOI. The multivariate analysis showed that age ≥65 years, operative duration ≥4 hours, tumor-node-metastasis (TNM) stage = III, open/converted operative technique, and total postoperative opiates dose (TOD) ≥0.3 mg/kg were independent risk factors for PPOI. Based on these factors, a risk stratification scoring system was generated, classified by low-risk (score 0-2), moderate-risk (score 3-4), and high-risk (score 5-6) groups. The incidence of PPOI increased by 7.5-fold from low-risk to high-risk group. The area under the curve of the scoring system was 0.841 (95% CI, 0.793-0.890), indicating a good predictive capability for the occurrence of PPOI.We have identified independent risk factors for the occurrence of PPOI and used these factors to construct a risk stratification scoring system.

Risk factors for hospital readmission after radical gastrectomy for gastric cancer: a prospective study.

BACKGROUND: Hospital readmission is gathering increasing attention as a measure of health care quality and a potential cost-saving target. The purpose of this prospective study was to determine risk factors for readmission within 30 days of discharge after gastrectomy for patients with gastric cancer. METHODS: We conducted a prospective study of patients undergoing radical gastrectomy for gastric cancer from October 2013 to November 2014 in our institution. The incidence, cause and risk factors for 30-day readmission were determined. RESULTS: A total of 376 patients were included in our analysis without loss in follow-up. The 30-day readmission rate after radical gastrectomy for gastric cancer was 7.2% (27of 376). The most common cause for readmission included gastrointestinal complications and postoperative infections. On the basis of multivariate logistic regression analysis, preoperative nutritional risk screening 2002 score ≥ 3 was an independent risk factor for 30-day readmission. Factors not associated with a higher readmission rate included a history of a major postoperative complication during the index hospitalization, prolonged primary length of hospital stay after surgery, a history of previous abdominal surgery, advanced age, body mass index, pre-existing cardiopulmonary comorbidities, American Society of Anesthesiology grade, type of resection, extent of node dissection and discharge disposition. CONCLUSIONS: Readmission within 30 days of discharge after radical gastrectomy for gastric cancer is common. Patients with nutritional risk preoperatively are at high risk for 30-day readmission. Preoperative optimization of nutritional status of patients at nutritional risk may effectively decrease readmission rates.

Evaluation of a risk factor scoring model in screening for undiagnosed diabetes in China population.

OBJECTIVE: To develop a risk scoring model for screening for undiagnosed type 2 diabetes in Chinese population. METHODS: A total of 5348 subjects from two districts of Jinan City, Shandong Province, China were enrolled. Group A (2985) included individuals from east of the city and Group B (2363) from west of the city. Screening questionnaires and a standard oral glucose tolerance test (OGTT) were completed by all subjects. Based on the stepwise logistic regression analysis of Group A, variables were selected to establish the risk scoring model. The validity and effectiveness of this model were evaluated in Group B. RESULTS: Based on stepwise logistic regression analysis performed with data of Group A, variables including age, body mass index (BMI), waist-to-hip ratio (WHR), systolic pressure, diastolic pressure, heart rate, family history of diabetes, and history of high glucose were accepted into the risk scoring model. The risk for having diabetes increased along with aggregate scores. When Youden index was closest to 1, the optimal cutoff value was set up at 51. At this point, the diabetes risk scoring model could identify diabetes patients with a sensitivity of 83.3% and a specificity of 66.5%, making the positive predictive value 12.83% and negative predictive value 98.53%. We compared our model with the Finnish and Danish model and concluded that our model has superior validity in Chinese population. CONCLUSIONS: Our diabetes risk scoring model has satisfactory sensitivity and specificity for identifying undiagnosed diabetes in our population, which might be a simple and practical tool suitable for massive diabetes screening.