Predictive values of sarcopenia and systemic inflammation-based markers in advanced hepatocellular carcinoma after hepatectomy.

BACKGROUND: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC. METHODS: This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2 cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival. RESULTS: Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25 kg/m2), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325-4.820; p < 0.05); alpha-fetoprotein levels ≥25 ng/mL (HR, 1.891; 95% CI: 1.016-3.480; p = 0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009-3.776; p < 0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups. CONCLUSION: Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR.

Prognostic Significance of Sarcopenia and Systemic Inflammatory Markers in Biliary Tract Cancer: A Retrospective Cohort Study.

PURPOSE: To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC). METHODS: Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant. RESULTS: Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m2), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively). CONCLUSION: Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI.

Nomogram incorporating potent inflammatory indicators for overall survival estimation of patients with primary oral squamous cell carcinoma.

Background: Inflammation has been recognized to be a factor that substantially influences tumorigenesis and tumor prognosis. Hence, this study was aimed to investigate an inflammatory marker with the most potent prognostic ability and to evaluate the survival estimation capability of dynamic change in this marker for patients suffered from oral squamous cell carcinoma (OSCC). Methods: 469 patients' inflammatory indicators including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory response index (SIRI), were calculated. Their predictive abilities for overall survival (OS) were evaluated by Kaplan-Meier curves to screen for the one with the most potent prognostic value. The predictive ability of dynamic changes in this marker was verified and a predictive nomogram incorporating inflammatory indicators was developed. Results: A high LMR was identified to be an indicator of a satisfactory survival rate. Compared with that of other inflammatory markers, area under the receiver operating characteristics (ROC) curve (AUC) of LMR for 1-year and 3-year OS was significantly larger (P<0.001). Dynamic LMR change remained an significant parameter for predicting OS (OR: 2.492, 95% CI: 1.246-4.981, p = 0.010). The nomogram incorporating LMR exhibited a superior prognostic significance than the TNM system, as suggested by the C-index (0.776 vs 0.651 in primary cohort; 0.800 vs 0.707 in validation cohort, P<0.001) and AUC. Conclusions: LMR was demonstrated to possess a more potent survival estimation capability than the other three inflammatory parameters. Dynamic changes in LMR serves as a significant parameter for overall survival estimation of primary OSCC patients. The established nomogram incorporating inflammatory markers showed more accuracy and sensitivity for survival estimation of primary OSCC patients.

The Significance of Systemic Inflammation Markers in Intrahepatic Recurrence of Early-Stage Hepatocellular Carcinoma after Curative Treatment.

Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.

The Blood Microenvironment Influences the Molecular Phenotypes of Circulating Tumor Cells in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Circulating tumor cells (CTCs) may be affected by the environment encountered during blood circulation. We aimed to explore the association between the molecular phenotype of CTCs and systemic inflammatory markers. PATIENTS AND METHODS: CTCs isolated from patients with recurrent/metastatic head and neck squamous cell carcinoma by CD45-negative selection were analyzed for the expression of multiple genes. The correlations between gene expression levels in CTCs and systemic inflammation markers were examined. RESULTS: Thirty-five (83.3%) of the 42 patients were positive for CTCs. No significant differences in systemic inflammatory markers were observed between CTC-positive and CTC-negative patients. Notably, VIM or ZEB2 expression was strongly correlated with that of CD44 or ALDH1. PIK3CA, CD44, ALDH1A1, and PDCD1LG2 expression in CTCs was correlated with lymphocyte- and/or albumin-related systemic inflammatory markers. CONCLUSION: CTCs acquire a survival advantage through phenotypic alterations in the hostile blood environment, and evade circulatory immune surveillance.

Clinical significance of peripheral blood-derived inflammation markers in advanced gastric cancer after radical resection.

BACKGROUND: The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis. METHODS: A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly. RESULTS: The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397 ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR < 154. CONCLUSIONS: Our findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.

Diagnostic and prognostic value of preoperative systemic inflammatory markers in anaplastic thyroid cancer.

BACKGROUND: Easily accessible, generalized, and inexpensive methods are expected to differentiate anaplastic thyroid carcinoma (ATC) from advanced differentiated thyroid cancer (aDTC). We aimed to explore potential diagnostic and prognostic value of systematic inflammatory markers (SIMs) in ATC and aDTC. METHODS: About 22 ATC, 101 aDTC, and 100 matched early DTC patients were analyzed retrospectively. SIMs included the comprehensive index, neutrophil-monocyte-platelet-to-lymphocyte ratio (NMPLR) and the previously reported ones. Receiver operating characteristic, Kaplan-Meier, and COX regression analyses were mainly conducted. RESULTS: NMPLR exhibited the highest area under the curve value 0.806 (P < .0001) to diagnose ATC from aDTC. NMPLR was identified as an independent risk factor for overall survival (OS) (hazard ratio [HR]: 47.821, 95% confidence interval [CI], 2.863-798.765, P = .007) in ATC, as well as for OS (HR: 7.360, 95% CI, 1.620-33.430, P = .010) and recurrence-free survival (HR: 4.172, 95% CI, 1.139-15.286, P = .031) in aDTC. Taken both refractory types (ATC and aDTC) together, NMPLR could independently predict OS (HR: 6.470; 95% CI, 2.134-19.616; P = .001). CONCLUSION: NMPLR is a generalized index. It showed excellent potential in differential diagnosis and survival prediction in refractory thyroid cancer. However, it needs to be validated in larger cohort and clinical practice.

Prognostic value of systemic inflammatory marker in patients with head and neck squamous cell carcinoma undergoing surgical resection.

Aim: To explore the prognostic value of the systemic inflammatory marker (SIM) based on neutrophil, lymphocyte and monocyte counts in head and neck squamous cell carcinoma (HNSCC) patients. Patients & methods: We retrospectively collected the data of 367 patients with HNSCC who underwent surgery. The Kaplan-Meier survival analysis and Cox regression analysis were conducted on disease-free survival and overall survival. Results: A high SIM (>1.34) was associated with larger tumor size, advanced clinical stage and shorter survival time. The survival analysis showed that only clinical stage and SIM were independent prognostic indicators of disease-free survival and overall survival. Conclusion: The SIM positively correlated with tumor progression and might be a powerful prognostic indicator of poor outcome in patients with HNSCC.

High platelet-to-lymphocyte ratio predicts improved survival outcome for perioperative NSAID use in patients with rectal cancer.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to block tumor-associated inflammation in rectal cancer. However, the perioperative use of NSAIDs remains controversial. This study was designed to investigate whether the perioperative use of NSAIDs influences outcomes and to provide a predictive marker to identify patients who would benefit from NSAIDs. METHODS: We enrolled 515 patients with stage I to III rectal cancer in this retrospective study. Patients were classified into the NSAID and non-NSAID groups according to their perioperative use of NSAIDs. The whole cohort was stratified by platelet-to-lymphocyte ratio (PLR). The primary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: The NSAID group had a 12.6% lower risk of recurrence than the non-NSAID group (P = 0.015), while the association with survival was nonsignificant. In the high-PLR subset, the NSAID group had a 17.3% lower risk of recurrence (P = 0.003) and a better DFS (P = 0.033) outcome than the non-NSAID group. Multivariate analysis confirmed this independent significant association with DFS (P = 0.023). In the low-PLR subset, the association of NSAID use with survival was nonsignificant. CONCLUSION: Perioperative use of NSAIDs was associated with improved survival outcomes in rectal cancer patients with high PLR.

Can Systemic Inflammatory Markers Be Used to Predict the Pathological Grade of Meningioma Before Surgery?

BACKGROUND: We sought to determine whether systemic inflammatory markers (SIMs) can be used to predict the pathological grade of meningioma before surgery. METHODS: Patients with histopathologically proven intracranial meningiomas who had undergone surgery from January 2014 to April 2018 were identified. The 14 most recent SIM levels measured before surgery were retrieved. The Mann-Whitney U test was used to determine the statistically significant differences between groups. Receiver operating characteristic curves were constructed, and the areas under the curve (AUC) were calculated to assess the diagnostic value of each biomarker. Predictive models built with biomarker pairs using logistic regression or support vector machine classifiers were used to assess their combined performance. RESULTS: A total of 672 patients with 575 and 97 low-grade and high-grade meningiomas, respectively, were investigated. Of the 14 SIMS, 7 differed significantly between the 2 meningioma groups. However, receiver operating characteristic analysis showed that none of these 7 SIMs alone could predict for the meningioma grade; the highest AUC was 0.61. Two biomarkers (erythrocyte and neutrophil/lymphocyte ratio) were incorporated into the logistic regression model; the corresponding AUC was 0.64. Moreover, 21 biomarker pairs were used to train the support vector machine classifiers; the AUCs of 6 pairs were >0.55; the maximum AUC was 0.60. CONCLUSIONS: SIMs obtained from routine preoperative laboratory testing had a limited ability to differentiate low- and high-grade meningioma in our cohort of 672 patients. Further prospective, multicenter studies with larger sample sizes are warranted to confirm this finding.

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation.

Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.

Correlation Between Natural Killer Cell Activity and Systemic Inflammatory Markers for Heterogeneous Cancer Patients Treated With Wheel Balance Cancer Therapy.

BACKGROUND AND OBJECTIVE: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT). METHODS: Forty-two electronic charts of patients with gastric, breast, and pancreatic cancer treated with WBCT from February 1, 2015 to September 30, 2015, were reviewed retrospectively. These charts were statistically analyzed, looking for alterations of and correlation for NKA and the expressions of systemic inflammatory markers. RESULTS: Patients with a NKA of under 300 pg/mL at admission showed significantly higher erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio (NLR) values and decreasing NLR values due to WBCT than patients with an NKA greater than 300 pg/mL. As a result of the correlation analysis between NKA and the levels of the systemic inflammatory markers, NKA showed significant negative correlation with NLR, ESR, and fibrinogen values. CONCLUSIONS: Negative correlation was identified between NKA and NLR, NKA and ESR, and NKA and fibrinogen in patients with heterogeneous cancer patients.

Relationship between Systemic Inflammatory Marker, Oxidative Stress and Body Mass Index in Stable COPD Patient / 결핵및호흡기질환

BACKGROUND: The main factors associated with weight loss in patients with COPD are not well known. Since chronic inflammation and oxidative stress play a major pathogenic role in COPD, these factors may be responsible for the patients' weight loss. Therefore, this study measured the body mass index (BMI) in COPD patients and evaluated the variables, such as systemic inflammatory marker, oxidative stress and lung function, that correlate with the BMI. METHOD: The stable COPD patients (M:F=49:4, mean age=68.25+/-6.32) were divided into the lower (25) BMI group. The severity of the airway obstruction was evaluated by measuring the FEV1. The serum IL-6 and TNF-alpha levels were measured to determine the degree of systemic inflammation, and the carbonyl protein and 8-iso-prostaglandin F2alpha level was measured to determine the level of oxidative stress. Each value in the COPD patients and normal control was compared with the BMI. RESULTS: 1) Serum 8-iso-prostaglandin F2alpha in COPD patients was significantly higher (456.08+/-574.12 pg/ml) than that in normal control (264.74+/-143.15 pg/ml) (p<0.05). However, there were no significant differences in the serum IL-6, TNF-alpha, carbonyl protein between the COPD patients and normal controls. 2). In the COPD patients, the FEV1 of the lower BMI group was significantly lower (0.93+/-0.25L) than that of the normal BMI (1.34+/-0.52L) and higher BMI groups (1.72+/-0.41L) (p<0.05). The lower FEV1 was significantly associated with a lower BMI in COPD patients (p=0.002, r=0.42). The BMI of very severe COPD patients was significantly lower (19.8+/-2.57) than that of the patients with moderate COPD (22.6+/-3.14) (p<0.05). 3). There were no significant differences in the serum IL-6, TNF-alpha, carbonyl protein and 8-iso-prostaglandin F2alpha according to the BMI in the COPD patients. CONCLUSION: The severity of the airway obstruction, not the systemic inflammatory markers and oxidative stress, might be associated with the BMI in stable COPD patients. Further study will be needed to determine the factors associated with the decrease in the BMI of COPD patients.