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Yu W, Zhou J, Luo J, Xia J, Li S, Xie L, He Y, Li H, Jiang G, Chen X, Bai X, Mao M, Wang X. The Associations Between Gallstone Disease and Pan-Cancer Incidence Risk Based on Over 13 Million Participants. Cancer Med 2025; 14:e70857. [PMID: 40276904 PMCID: PMC12022677 DOI: 10.1002/cam4.70857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 02/05/2025] [Accepted: 03/12/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Increasing evidence connects gallstone disease (GSD) to all types of cancer incidence; however, the results were inconsistent. The present study aimed to evaluate whether and to what extent these associations exist comprehensively. METHODS We systematically searched published longitudinal studies indexed in PubMed and Embase database from dates of inception to March 31, 2020. We pooled the effect of GSD on all-cause cancer incidence. Moreover, we further employed stratified analysis concerning sex, geographic background, surgery status, and follow-up period. Trial sequential analysis (TSA) was applied to decide whether the included sample size was sufficient for evaluating these associations. RESULTS Fifty-one studies incorporating over 13 million participants were eligible for analysis in this study. GSD pose an increased risk of all-cause cancer risk (pooled RR = 1.43; 95% CI: 1.33-1.54) compared with the healthy controls, especially hematologic malignancy (pooled RR = 1.14; 95% CI: 1.05-1.25), gastrointestinal cancers (pooled RR = 1.28; 95% CI: 1.15-1.41), liver, pancreas, and biliary tract cancer (pooled RR = 1.84; 95% CI: 1.62-2.10), and kidney cancer (pooled RR = 1.19; 95% CI: 1.03-1.37). These associations are not markedly changed after stratification by different subgroups. Moreover, the TSA confirmed the sample size was sufficient to draw these conclusive conclusions. CONCLUSIONS The present meta-analysis with sufficient evidence indicates GSD increases the risk for all causes of cancer incidence. The evidence may warrant GSD patients to perform screening and prophylactic treatment for the prevention of these complications. The indication for cholecystectomy should be determined through a comprehensive evaluation of the patient's clinical presentation, with a thorough assessment of the potential therapeutic benefits and surgical risks.
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Affiliation(s)
- Wenqian Yu
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Jin Zhou
- Department of Anorectal SurgeryHospital of Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceP. R. China
| | - Jing Luo
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Jing Xia
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Shiyi Li
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Linjun Xie
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - YaZhou He
- Department of Oncology, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Hongyu Li
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Guoheng Jiang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Xin Chen
- Department of Oncology, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Xuan Bai
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
| | - Min Mao
- Department of Pediatric Pulmonology and Immunology, West China Second University HospitalSichuan UniversityChengduP. R. China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of EducationChengduP. R. China
- NHC Key Laboratory of Chronobiology (Sichuan University)ChengduP. R. China
- The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University HospitalSichuan UniversityChengduP. R. China
- Sichuan Birth Defects Clinical Research Center, West China Second University HospitalSichuan UniversityChengduP. R. China
| | - Xin Wang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
- West China‐PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduP. R. China
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Holoğlu EN, Uzunlulu M, Torun C. Extremely elevated erythrocyte sedimentation rates: Associations with patients' diagnoses and clinical characteristics. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2025; 63:70-78. [PMID: 39721052 DOI: 10.2478/rjim-2024-0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Indexed: 12/28/2024]
Abstract
INTRODUCTION The aim of the study was to assess the etiological distribution of patients with an erythrocyte sedimentation rate (ESR) over 100 mm/hour and to evaluate differences in demographic, comorbidity, laboratory characteristics, and clinical outcomes. METHODS This retrospective observational clinical study included patients aged 18 years and older who were admitted to the internal medicine inpatient clinic between May 1, 2015 and June 1, 2021 and had ESR values above 100 mm/h. Demographic data, comorbidities, laboratory parameters, imaging studies, histopathological findings, microbiological and serological data, along with in-hospital and post-discharge mortality, were collected from the hospital's electronic database. Two independent clinicians evaluated the data to identify diagnoses associated with elevated ESR. Patients were divided into six categories based on the most likely diagnosis. RESULTS The study included 441 patients, 52.6% of whom were female, and the mean age was 72.6 years. The etiological distribution was as follows: infectious diseases (34%), malignancies (31.5%), undiagnosed cases (15.9%), renal diseases (9.8%), other causes (5%), and rheumatologic diseases (3.8%). Etiological distributions did not differ by gender, age, or ESR ranges. The in-hospital mortality rate was 3.6%, and the overall mortality rate from hospitalization to the data collection date was 64.4%. Mortality was higher in patients with malignancies (81.3%) compared to other etiologies (p<0.001). Patients who died had higher mean age, ferritin levels, having diabetes mellitus, heart failure, or malignancy, and lower hemoglobin and lymphocyte levels compared to survivors (p<0.05 for all). CONCLUSION Most patients with an ESR over 100 mm/hour had significant underlying medical conditions, with infectious diseases and malignancies comprising two-thirds of the cases.
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Affiliation(s)
- Esen Nur Holoğlu
- Department of Internal Medicine Goztepe Training and Research Hospital, Istanbul Medeniyet University, Kadikoy/Istanbul, Türkiye
| | - Mehmet Uzunlulu
- Department of Internal Medicine Goztepe Training and Research Hospital, Istanbul Medeniyet University, Kadikoy/Istanbul, Türkiye
| | - Cundullah Torun
- Department of Internal Medicine Goztepe Training and Research Hospital, Istanbul Medeniyet University, Kadikoy/Istanbul, Türkiye
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Tan L, Mei J, Tang R, Huang D, Qi K, Ossowski Z, Wang X. Can exercise as a complementary technique manage inflammatory markers in women with breast cancer who are overweight and obese? A systematic review and meta-analysis. Complement Ther Med 2025; 88:103119. [PMID: 39710346 DOI: 10.1016/j.ctim.2024.103119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/05/2024] [Accepted: 12/18/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Inflammation can result in the development of breast cancer in women with overweight and obese, and also affects the outcome and prognosis of breast cancer patients, thereby decreasing the cure and survival rates of breast cancer patients. Exercise may benefit breast cancer patients as a supplement to conventional treatments. However, research on the effects of exercise on inflammatory markers in women with breast cancer who are overweight and obese remains incomplete. OBJECTIVE A systematic review and meta-analysis were used to study the effects of exercise on inflammatory markers in women with breast cancer who are overweight and obese. METHOD Literature up to May 2024 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO, and English-language randomized controlled trials (RCTs) that met the inclusion criteria were screened. The screening criteria were as follows (A) written in English; (B) RCT; (C) studied in women with overweight obese and breast cancer; (D) outcome measures: inflammatory markers; (E) the duration of the exercise intervention was unlimited. RESULTS A total of 14 articles and 1064 participants were included. Exercise significantly reduced C-reactive protein (CRP) (MD: -0.52, 95 % CI: -0.94 to -0.11; p = 0.01; heterogeneity p < 0.1), interleukin-6 (IL-6) (MD: -0.87, 95 % CI: -1.62 to -0.11; p = 0.02; heterogeneity p < 0.1), and leptin (MD: -0.92, 95 % CI: -1.71 to -0.13; p = 0.02; heterogeneity p < 0.1) levels and exercise significantly increased adiponectin levels (MD: 0.89, 95 % CI: 0.03-1.75, p = 0.04; heterogeneity p < 0.1) but had no effect on tumor necrosis factor-α (TNF-α) (MD: -0.26, 95 % CI: -0.82-0.29; p = 0.35; heterogeneity p < 0.1) and IL-10 (MD: 0.14, 95 % CI: -0.17-0.45; p = 0.37; heterogeneity p = 0.45) were not significant. In addition, subgroup analyses suggest that combination training (CE) may be the most recommended type of exercise to decrease pro-inflammatory markers, and increase anti-inflammatory markers in women with overweight obesity, and have breast cancer. CONCLUSION Exercise significantly reduced CRP, IL-6, and leptin levels and overall increased adiponectin levels in women with overweight obese, and breast cancer. However, the effects on TNF-α and IL-10 levels were not significant. CE may be the most recommended type of exercise for reducing pro-inflammatory factors and increasing anti-inflammatory factors. Therefore, this study considers exercise as an effective complementary approach to managing inflammatory markers in women with breast cancer who are overweight and obese. Future researchers may consider exploring the combined effects of exercise and dietary control, weight loss, and other factors, and formulate a comprehensive treatment plan accordingly.
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Affiliation(s)
- Liang Tan
- Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland.
| | - Jinyu Mei
- Department of Physical Education, Harbin Institute of Technology (Weihai), Weihai 264209, China.
| | - Ruihong Tang
- Education University of Hong Kong (EdUHK), Hongkong, 999077, China; Hunan First Normal University, Changsha 410002, China.
| | - Duo Huang
- Shangrao Normal University, Shangrao 334001, China.
| | - Kai Qi
- Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland.
| | - Zbigniew Ossowski
- Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland.
| | - Xiaoning Wang
- School of Physical Education, Shandong University, Jinan 250061, China.
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Liu K, Wang W, Liu Y, Li J, Ma C, Tian Y, Dong Z, Zhu L, Wei W, Ren M, Wu S, Liu S. Correlation of cumulative fasting blood glucose exposure with gastrointestinal cancers: A prospective cohort study. Medicine (Baltimore) 2025; 104:e41529. [PMID: 39960953 PMCID: PMC11835132 DOI: 10.1097/md.0000000000041529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 01/27/2025] [Indexed: 02/20/2025] Open
Abstract
At present, there is a lack of research on the correlation between cumFPG and digestive malignancies, and previous cohort studies have not considered the competitive risk between death and digestive malignancies, which may overestimate the impact of related risk factors. To explore the correlation between cumFPG and malignant tumors of the digestive system. In this study, 53,747 participants who had undergone 3 consecutive physical examinations since 2006 were collected. Finally, a total of 53,747 participants were included in this study. According to the grouping method of previous studies, cumFPG was divided into 4 groups according to the quartile. Cox regression model and competitive risk model were used to assess the risk of new digestive system malignancy. In sensitivity analyses, participants with cancer within 5 years of follow-up were excluded to eliminate the possibility of reverse causation. Subjects taking hypoglycemic drugs were excluded to eliminate the effect of the drug on blood glucose. Restricted cubic splineregresion (RCS) was then used to calculate the relationship between cumFPG and GI cancers. The mean age of participants was 49.02 ± 11.78 years. During a mean follow-up of 10.58 years, 817 new Gastrointestinal cases were identified, and the Cox proportional hazards model suggested that the risk of incidence in the Q2 to Q4 group increased sequentially compared with the lowest Q1 group, even after excluding the diagnosis of digestive malignancy within 5 years, the participants taking hypoglycemic drugs, and the death competition risk model analysis. In site-specific analysis, we observed that this risk was more pronounced in colorectal cancer, liver cancer, and pancreatic cancer, while gastric cancer, small bowel cancer, and bile duct cancer all had a similar trend to the main model but were not statistically significant, while esophageal cancer was U-shaped but not statistically significant. RCS results showed that cumFPG was associated with a similar risk of digestive system tumors, showing an inverted "√" type relationship. High levels of cumFPG are an independent factor in malignancy of the digestive system. cumFPG can provide a new idea for the prevention of Gastrointestinal cancers.
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Affiliation(s)
- Kuan Liu
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Wanchao Wang
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Ye Liu
- Affiliated Hospital of North China University of Science and Technology, Breast Disease Treatment Center, Tangshan, Hebei, China
| | - Jiaxing Li
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Chao Ma
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Yuan Tian
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Zhigang Dong
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Lichao Zhu
- Affiliated Hospital of North China University of Science and Technology, GastrointestinalOncology Treatment Center, Tangshan, Hebei, China
| | - Wenqiang Wei
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Minqiang Ren
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Shouling Wu
- Kailuan Employee Health Examination Center, Tangshan, Hebei, China
| | - Siqing Liu
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
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Lei J, Wu L. Impact of breakfast skipping on esophageal health: A mendelian randomization study. Clin Nutr ESPEN 2025; 65:86-92. [PMID: 39603344 DOI: 10.1016/j.clnesp.2024.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 10/24/2024] [Accepted: 11/19/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND & AIMS Previous studies have indicated that, in addition to the types of food consumed, eating habits are also associated with the risk of esophageal diseases. Some studies have suggested a possible link between breakfast skipping and esophageal tumors as well as gastroesophageal reflux disease. However, it remains unclear whether breakfast skipping has a causal relationship with esophageal diseases. To address this issue, this study aimed to investigate the potential causal relationship between breakfast skipping and esophageal diseases using a two-sample mendelian randomization (MR) approach. METHODS We obtained data from genome-wide association studies (GWAS) involving 193,860 individuals from the UK Biobank on breakfast skipping. The summary statistics for the esophageal diseases were derived from the IEU open GWAS project. In this two-sample MR analysis, inverse variance weighted was used, supplemented with weighted median, simple mode and weighted mode methods. RESULTS The results revealed significant causal relationships between breakfast skipping and esophageal cancer (odds ratio (OR): 5.992, 95 % confidence interval (CI): 1.606-22.350, p = 0.008), Barrett's esophagus (OR: 4.041, 95 % CI: 1.837-8.889, p < 0.001), gastroesophageal reflux disease (OR: 2.463, 95 % CI: 1.995-3.041, p < 0.001), and esophageal varices (OR: 4.454, 95 % CI: 1.785-11.112, p = 0.001). All of the supplementary methods supported the findings. CONCLUSION Our research provides evidence for the association between breakfast skipping and esophageal diseases. Breakfast skipping could be a potential risk factor for esophageal cancer, Barrett's esophagus, gastroesophageal reflux disease and esophageal varices. For high-risk groups prone to these esophageal diseases, emphasizing the importance of regular breakfast and maintaining consistent dietary habits is crucial for esophageal health.
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Affiliation(s)
- Jiaming Lei
- Department of Gastroenterology, People's Hospital of Leshan, Leshan City, Sichuan Province, China
| | - Ling Wu
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China.
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Megyesfalvi E, Ghimessy A, Bauer J, Pipek O, Saghi K, Gellert A, Fillinger J, Okumus O, Teglas V, Ganofszky E, Bogos K, Renyi-Vamos F, Megyesfalvi Z, Aigner C, Hegedus B, Dome B, Moser B. Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study. Lung Cancer 2025; 200:108111. [PMID: 39889465 DOI: 10.1016/j.lungcan.2025.108111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 01/20/2025] [Accepted: 01/22/2025] [Indexed: 02/03/2025]
Abstract
BACKGROUND Complementary prognostic markers are needed in thymic epithelial tumors (TETs) to aid patient stratification and determine the most appropriate follow-up strategies. This study aimed to assess the diagnostic and prognostic relevance of blood-based inflammatory markers in a large cohort of surgically treated TET patients. MATERIAL AND METHODS A total of 743 TET patients who underwent surgical resection between 1999-2021 were included in this multicenter study. Inflammatory markers were recorded from the most recent preoperative blood cell count prior to surgery. Measured variables were rescaled and harmonized to obtain comparable values across the participating centers. RESULTS Preoperative CRP was significantly higher in TET patients with increased tumor size (vs. those with T1 tumors, p = 0.035). Likewise, neutrophil-to-lymphocyte ratio (NLR) (p = 0.002) and platelet-to-lymphocyte ratio (PLR) (p < 0.001) were both significantly higher in thymic carcinomas than in thymomas. Notably, increased NLR and PLR were mainly attributed to significantly decreased lymphocyte levels in thymic carcinoma patients. Concerning survival outcomes, we found that elevated PLR and fibrinogen influenced overall survival (OS) (p = 0.002 and p = 0.018, respectively) and cause-specific survival (CSS) (p = 0.002 and p = 0.009, respectively) independently of other variables in our multivariate models, and they constituted negative prognosticators in TETs. Elevated CRP had an independent negative impact only on OS. Although elevated NLR was linked with impaired prognosis in our univariate model (p = 0.008), its independent prognostic significance could not be validated. CONCLUSIONS Using the so-far largest cohort of surgically treated TET patients, our study demonstrates that CRP, PLR, and NLR have diagnostic significance in TETs, while elevated PLR and fibrinogen constitute independent negative prognosticators for OS and CSS. Accordingly, the current multicenter study offers additional guidance in developing personalized surveillance protocols in thymoma and thymic carcinoma.
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Affiliation(s)
- Evelyn Megyesfalvi
- Department of Thoracic and Abdominal Tumors and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
| | - Aron Ghimessy
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
| | - Jonas Bauer
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Orsolya Pipek
- Department of Physics of Complex Systems, Eötvös Loránd University, Budapest, Hungary
| | - Kevin Saghi
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
| | - Aron Gellert
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Janos Fillinger
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Ozlem Okumus
- Department of Thoracic Surgery, Cologne-Merheim Hospital, Witten/Herdecke University, Cologne, Germany
| | - Vivien Teglas
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
| | - Erna Ganofszky
- Department of Thoracic and Abdominal Tumors and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary
| | - Krisztina Bogos
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Ferenc Renyi-Vamos
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary; National Institute of Oncology and National Tumor Biology Laboratory, Budapest, Hungary
| | - Zsolt Megyesfalvi
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Clemens Aigner
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Balazs Hegedus
- Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, University Duisburg-Essen, Essen, Germany
| | - Balazs Dome
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Translational Medicine, Lund University, Lund, Sweden.
| | - Bernhard Moser
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
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Ceylan A, Artac M, Kocak MZ, Artac H. Epidermal growth factor receptor and programmed cell death-1 expression levels in peripheral T cell subsets of patients with non-small cell lung cancer. Scand J Immunol 2024; 100:e13398. [PMID: 39072784 DOI: 10.1111/sji.13398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 07/02/2024] [Accepted: 07/12/2024] [Indexed: 07/30/2024]
Abstract
Lung cancer is the leading cause of cancer-related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non-small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min-max) = 64.03 (45-83); 20 stage I-III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD-1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD-1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC.
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Affiliation(s)
- Ayca Ceylan
- Division of Immunology and Allergy, Department of Pediatrics, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Mehmet Artac
- Department of Medical Oncology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Mehmet Zahid Kocak
- Department of Medical Oncology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Hasibe Artac
- Division of Immunology and Allergy, Department of Pediatrics, Faculty of Medicine, Selcuk University, Konya, Turkey
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Ali N, Debernardi S, Kurotova E, Tajbakhsh J, Gupta NK, Pandol SJ, Wilson P, Pereira SP, Greenhalf B, Blyuss O, Crnogorac-Jurcevic T. Evaluation of urinary C-reactive protein as an early detection biomarker for pancreatic ductal adenocarcinoma. Front Oncol 2024; 14:1450326. [PMID: 39309742 PMCID: PMC11412792 DOI: 10.3389/fonc.2024.1450326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 08/19/2024] [Indexed: 09/25/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. Up to now, no specific screening or diagnostic tests are available for early PDAC detection. As a result, most patients are diagnosed with advanced or metastatic disease, which leads to a poor prognosis. In this study, we aimed to evaluate the diagnostic value of urinary CRP (uCRP) alone and in combination with our previously established urine biomarker panel (REG1B, LYVE1 and TFF1) for early detection of PDAC. A total of 534 urine samples from multiple centres were analysed: 93 from healthy individuals, 265 from patients with benign hepatobiliary diseases and 176 from PDAC patients. The uCRP and the urinary biomarker panel were assessed using commercial ELISA assays, while plasma CA19-9 and blood CRP (bCRP) were measured using Roche Cobas platform. Multiple logistic regression and nonparametric Kruskal-Wallis test were used for statistical analysis. An internal validation approach was applied, and the validated AUC estimators were reported to ensure accuracy. A significant difference was observed in the medians of uCRP between healthy and benign controls and PDAC sample groups (p < 0.001). uCRP levels were not dependent on gender and age, as well as cancer stage. When uCRP was combined with the urinary biomarker panel, it achieved AUCs of 0.878 (95% CI: 0.802-0.931), 0.798 (95% CI: 0.738-0.859) and 0.813 (95% CI: 0.758-0.869) in healthy vs PDAC, benign vs PDAC and healthy and benign vs PDAC sample groups, respectively. However, adding plasma CA19-9 to the urinary biomarker panel yielded a better performance, with AUCs of 0.978 (95% CI: 0.959-0.996), 0.911 (95% CI: 0.873-0.949) and 0.919 (95% CI: 0.883-0.955) in the healthy vs PDAC, benign vs PDAC and healthy and benign vs PDAC comparisons, respectively. In conclusion, we show that measuring CRP in urine is a feasible analytical method, and that uCRP could potentially be a promising biomarker in various diseases including other cancer types.
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Affiliation(s)
- Nurshad Ali
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Silvana Debernardi
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Evelyn Kurotova
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Jian Tajbakhsh
- 3rd Street Diagnostics, Cedars-Sinai, Los Angeles, CA, United States
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, CA, United States
| | - Nirdesh K. Gupta
- 3rd Street Diagnostics, Cedars-Sinai, Los Angeles, CA, United States
| | - Stephen J. Pandol
- Department of Medicine, Cedars-Sinai, Los Angeles, CA, United States
| | - Patrick Wilson
- Barts Health, Royal London Hospital, London, United Kingdom
| | - Stephen P. Pereira
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Bill Greenhalf
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Oleg Blyuss
- Centre for Cancer Screening, Prevention and Early Detection, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom
- Department of Pediatrics and Pediatric Infectious Diseases, Institute of Child´s Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Tatjana Crnogorac-Jurcevic
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
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9
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Cierpiak K, Wityk P, Kosowska M, Sokołowski P, Talaśka T, Gierowski J, Markuszewski MJ, Szczerska M. C-reactive protein (CRP) evaluation in human urine using optical sensor supported by machine learning. Sci Rep 2024; 14:18854. [PMID: 39143107 PMCID: PMC11324656 DOI: 10.1038/s41598-024-67821-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 07/16/2024] [Indexed: 08/16/2024] Open
Abstract
The rapid and sensitive indicator of inflammation in the human body is C-Reactive Protein (CRP). Determination of CRP level is important in medical diagnostics because, depending on that factor, it may indicate, e.g., the occurrence of inflammation of various origins, oncological, cardiovascular, bacterial or viral events. In this study, we describe an interferometric sensor able to detect the CRP level for distinguishing between no-inflammation and inflammation states. The measurement head was made of a single mode optical fiber with a microsphere structure created at the tip. Its surface has been biofunctionalized for specific CRP bonding. Standardized CRP solutions were measured in the range of 1.9 µg/L to 333 mg/L and classified in the initial phase of the study. The real samples obtained from hospitalized patients with diagnosed Urinary Tract Infection or Urosepsis were then investigated. 27 machine learning classifiers were tested for labeling the phantom samples as normal or high CRP levels. With the use of the ExtraTreesClassifier we obtained an accuracy of 95% for the validation dataset. The results of real samples classification showed up to 100% accuracy for the validation dataset using XGB classifier.
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Affiliation(s)
- Kacper Cierpiak
- Department of Metrology and Optoelectronics, Faculty of Informatics, Telecommunications and Informatics, Gdańsk University of Technology, Narutowicza Street 11/12, 80-233, Gdańsk, Poland
| | - Paweł Wityk
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland
- Department of Molecular Biotechnology and Microbiology, Chemical Faculty, Gdańsk University of Technology, 11/12 Narutowicza Street, 80-233, Gdańsk, Poland
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Monika Kosowska
- Faculty of Telecommunications, Computer Science and Electrical Engineering, Bydgoszcz University of Science and Technology, Al. prof. S. Kaliskiego 7, 85-796, Bydgoszcz, Poland
| | - Patryk Sokołowski
- Department of Metrology and Optoelectronics, Faculty of Informatics, Telecommunications and Informatics, Gdańsk University of Technology, Narutowicza Street 11/12, 80-233, Gdańsk, Poland
| | - Tomasz Talaśka
- Faculty of Telecommunications, Computer Science and Electrical Engineering, Bydgoszcz University of Science and Technology, Al. prof. S. Kaliskiego 7, 85-796, Bydgoszcz, Poland
| | - Jakub Gierowski
- Kayon sp. z o.o., Romualda Traugutta 115c, 80-226, Gdańsk, Poland
| | - Michał J Markuszewski
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland
| | - Małgorzata Szczerska
- Department of Metrology and Optoelectronics, Faculty of Informatics, Telecommunications and Informatics, Gdańsk University of Technology, Narutowicza Street 11/12, 80-233, Gdańsk, Poland.
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10
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Jin Y, Ye X. Prognostic value of C-reactive protein in patients with glioma: a meta-analysis. Biomark Med 2024; 18:629-637. [PMID: 39082387 PMCID: PMC11370958 DOI: 10.1080/17520363.2024.2380246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 07/11/2024] [Indexed: 09/03/2024] Open
Abstract
Background: In this meta-analysis, we investigated C-reactive protein (CRP)'s role in glioma prognosis prediction.Methods: We conducted the current meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. An analysis of the prognostic effect of CRP on glioma was conducted using combined hazard ratios (HRs) and 95% confidence intervals (CIs).Results: The combined data suggested that a higher CRP level was markedly related to poor overall survival in glioma (hazard ratio: 1.73; 95% CI: 1.22-2.46; p = 0.002).Conclusion: According to results in the present meta-analysis, elevated CRP levels were significantly related to inferior overall survival in glioma.
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Affiliation(s)
- Yin Jin
- Clinical Laboratory, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China
| | - Xingchen Ye
- Clinical Laboratory, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China
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11
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Miyazaki R, Tamura M, Sakai T, Furukawa N, Yamamoto M, Okada H. Using the combined C-reactive protein and controlling nutritional status index for elderly non-small cell lung cancer. J Thorac Dis 2024; 16:4400-4408. [PMID: 39144366 PMCID: PMC11320273 DOI: 10.21037/jtd-24-435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 05/17/2024] [Indexed: 08/16/2024]
Abstract
Background We found that conventional controlling nutritional status (CONUT) score can serve as a sensitive prognostic marker. Some prognostic indicators do include C-reactive protein (CRP), such as the CRP-lymphocyte ratio (CLR), CRP-albumin-lymphocyte index (CALLY), and CRP-albumin ratio (CAR). However, CRP has not been combined with the CONUT score, which we believe could result in a more sensitive marker. This study evaluated the combined use of the CONUT score and CRP to predict prognostic outcomes in elderly non-small cell lung cancer (NSCLC) patients undergoing surgical resection. Methods This study involved the retrospective analysis of 114 NSCLC patients who were over 80 years old and underwent curative resection. The summation of the CRP score and CONUT score was defined as the combined CRP and controlling nutritional status (C-CONUT) score. The capacity of CRP, CONUT score, and C-CONUT score to predict overall survival (OS) was evaluated via receiver operating characteristics (ROC) curves. Prognostic markers for OS were then identified using the Cox proportional hazards regression model. Results The ROC curves identified the C-CONUT score as the most reliable marker of prognosis (area under the curve =0.745). Forty-seven patients were included in the high C-CONUT (≥3) group, while 67 patients were included in the low C-CONUT (0 to 2) group. Worse prognosis rates were observed in the high C-CONUT group in comparison to the low C-CONUT group in terms of OS (five-year OS: 39.8% versus 87.4%, P<0.001). Lymphatic invasion (P<0.001), histological findings (P=0.02), and C-CONUT score [hazard ratio (HR): 5.07, 95% confidence interval (CI): 2.39-10.8, P<0.001] were identified as exclusive markers for OS prognosis in the multivariate analysis. Conclusions Our current findings indicate that C-CONUT score may serve as an innovative prognostic marker in the elderly NSCLC population.
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Affiliation(s)
- Ryohei Miyazaki
- Department of Thoracic Surgery, Kochi Medical School, Nankoku, Kochi, Japan
| | - Masaya Tamura
- Department of Thoracic Surgery, Kochi Medical School, Nankoku, Kochi, Japan
| | - Takashi Sakai
- Department of Thoracic Surgery, Kochi Medical School, Nankoku, Kochi, Japan
| | - Naoki Furukawa
- Department of Thoracic Surgery, Kochi Medical School, Nankoku, Kochi, Japan
| | - Marino Yamamoto
- Department of Thoracic Surgery, Kochi Medical School, Nankoku, Kochi, Japan
| | - Hironobu Okada
- Department of Thoracic Surgery, Kochi Medical School, Nankoku, Kochi, Japan
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12
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Holm JB, Baggesen E, Cronin-Fenton D, Frystyk J, Bruun JM, Christiansen P, Borgquist S. Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups. Sci Rep 2024; 14:14486. [PMID: 38914635 PMCID: PMC11196728 DOI: 10.1038/s41598-024-64428-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/10/2024] [Indexed: 06/26/2024] Open
Abstract
Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14-2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09-2.66]; HRadj:1.75 [95% CI = 1.08-2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78-3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62-3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95-6.87]; HRadj:1.92 [95% CI = 1.06-3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64-3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.
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Affiliation(s)
- J B Holm
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - E Baggesen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - D Cronin-Fenton
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - J Frystyk
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | - J M Bruun
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - P Christiansen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - S Borgquist
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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13
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Saitta C, Afari JA, Patil D, Tanaka H, Yuen KL, Wang L, Cortes J, Liu F, Mahmood M, Matian J, Mansour M, Puri D, Cerrato C, Nguyen MV, Hakimi K, Kobayashi M, Fukuda S, Meagher MF, Fujii Y, Master V, Derweesh IH. Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry. Clin Genitourin Cancer 2024; 22:102098. [PMID: 38733897 DOI: 10.1016/j.clgc.2024.102098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 04/14/2024] [Accepted: 04/14/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). PATIENTS AND METHODS We queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression were fitted to elucidate predictors of outcomes. RESULTS Total 3902 patients (high CRP n = 1266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, P < .001), ccRCC (HR 2.69, P < .001), chRCC (HR 3.99, P < .001), pRCC (HR 1.76, P = .009) and vhRCC (HR 2.97, P =.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, P < .001), chRCC (HR 6.16, P = .003) and pRCC (HR 2.29, P = .011), while in vhRCC was not (P = .27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, P = .013), while in chRCC (P = .33), pRCC (P = .34) and vhRCC (P = .52) was not. On multivariable logistic regression CRP was a predictor of pRCC (OR 1.003, P = .002), while decreasing CRP was associated with benign tumors (OR 0.994, P = .048). CONCLUSION Elevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non-vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.
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Affiliation(s)
- Cesare Saitta
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Jonathan A Afari
- Department of Urology, UC San Diego Health System, San Diego, CA
| | | | - Hajime Tanaka
- Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kit L Yuen
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Luke Wang
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Julian Cortes
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Franklin Liu
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Mirha Mahmood
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Joshua Matian
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Mariam Mansour
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Dhruv Puri
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Clara Cerrato
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Mimi V Nguyen
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Kevin Hakimi
- Department of Urology, UC San Diego Health System, San Diego, CA
| | - Masaki Kobayashi
- Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shohei Fukuda
- Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan
| | | | - Yasuhisa Fujii
- Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Viraj Master
- Department of Urology, Emory Medical Center, Atlanta, GA
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14
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Banerjee S, Khubchandani J, Tisinger S, Batra K, Greenway M. Mortality risk among adult americans living with cancer and elevated CRP. Cancer Epidemiol 2024; 90:102569. [PMID: 38599039 DOI: 10.1016/j.canep.2024.102569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 03/26/2024] [Accepted: 03/28/2024] [Indexed: 04/12/2024]
Abstract
The role of C Reactive Protein (CRP) in predicting long-term outcomes among people living with cancer has not been well explored. We aimed to assess the role of elevated CRP in predicting all-cause mortality among a community-based sample of adult Americans living with cancer. The National Health and Nutrition Examination Survey, 1999-2010 was linked with mortality files up to December 2019 from the National Death Index. Sociodemographic and health-related variables of 30,711 participants (mean age=46.5 years) were analyzed to compute adjusted hazard ratios (HR) for all-cause mortality. The risk of mortality, in unadjusted analysis, was significantly higher among those with cancer compared to those without cancer 3.53 (95% CI= 3.13-3.98, p < 0.001). In adjusted analysis, when stratified by CRP levels (elevated=cutoff point at ≥2 mg/dL), among individuals with elevated CRP but no cancer history, the risk of mortality was significantly higher (HR=1.67, 95% CI=1.24-2.25) compared to those without cancer or elevated CRP. Among individuals with cancer but without elevated CRP as well, the risk of mortality was 20% higher compared to their counterparts. The highest risk of mortality was observed among those with both cancer and elevated CRP (HR=2.10, 95% CI=1.11-4.33). Age and income were significant predictors of these relationships. Among people living with cancer, CRP may serve as a marker for mortality and future studies should explore the pathways by which the risk of mortality may increase due to variation of CRP in cancer patients.
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Affiliation(s)
- Srikanta Banerjee
- College of Health Sciences, Walden University, Minneapolis, MN 55401, United States
| | - Jagdish Khubchandani
- College of Health, Education, and Social Transformation, New Mexico State University, Las Cruces, NM 88003, United States.
| | - Shalika Tisinger
- College of Health Sciences, Walden University, Minneapolis, MN 55401, United States
| | - Kavita Batra
- Department of Medical Education, University of Nevada, Las Vegas, Las Vegas, NV 89102, United States
| | - Maribeth Greenway
- Department of Infection Prevention and Control, Carilion Clinic, Roanoke, VA 24014, United States
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15
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Nakanishi S, Goya M, Suda T, Yonamine T, Sugawa A, Saito S. Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma. BMC Urol 2024; 24:94. [PMID: 38658967 PMCID: PMC11040933 DOI: 10.1186/s12894-024-01481-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 04/11/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Currently, no useful serum markers exist for clear cell renal cell carcinoma (ccRCC), making early detection challenging as diagnosis relies solely on imaging tests. Radiation exposure is also a concern due to multiple required CT examinations during treatment. Renal cell carcinoma (RCC) histological types include ccRCC and non-clear cell RCC (non-ccRCC); however, treatment response to medications varies which necessitates accurate differentiation between the two. Therefore, we aimed to identify a novel serum marker of RCC. Increased LRG1 expression in the serum has been demonstrated in multiple cancer types. However, the expression of LRG1 expression in the serum and cancer tissues of patients with RCC has not been reported. Since ccRCC is a hypervascular tumor and LRG1 is capable of accelerating angiogenesis, we hypothesized that the LRG1 levels may be related to ccRCC. Therefore, we examined LRG1 expression in sera from patients with RCC. METHODS Using an enzyme-linked immunosorbent assay, serum levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) were measured in 64 patients with ccRCC and 22 patients non-ccRCC who underwent radical or partial nephrectomy, as well as in 63 patients without cancer. RESULTS Median values of serum LRG1 and their inter-quartile ranges were 63.2 (42.8-94.2) µg/mL in ccRCC, 23.4 (17.7-29.6) µg/mL in non-ccRCC, and 36.0 (23.7-56.7) µg/mL in patients without cancer, respectively (ccRCC vs. non-ccRCC or patients without cancer: P < 0.001). C-reactive protein (CRP) levels (P = 0.002), anemia (P = 0.037), hypercalcemia (P = 0.023), and grade (P = 0.031) were independent predictors of serum LRG1 levels in ccRCC. To assess diagnostic performance, the area under the receiver operating characteristic curve of serum LRG1 was utilized to differentiate ccRCC from non-cancer and non-ccRCC, with values of 0.73 (95% CI, 0.64-0.82) and 0.91 (95% CI, 0.82-0.96), respectively. CONCLUSIONS LRG1 served as a serum marker associated with inflammation, indicated by CRP, anemia, hypercalcemia, and malignant potential in ccRCC. Clinically, serum LRG1 levels may assist in differentiating ccRCC from non-ccRCC with excellent diagnostic accuracy.
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Affiliation(s)
- Shotaro Nakanishi
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, 903-0215, Okinawa, Japan.
| | - Masato Goya
- Chubu Tokusyukai Hospital, Kitanakagusuku, 801 higa, 901-2392, Okinawa, Japan
| | - Tetsuji Suda
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, 903-0215, Okinawa, Japan
| | - Tomoko Yonamine
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, 903-0215, Okinawa, Japan
| | - Ai Sugawa
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, 903-0215, Okinawa, Japan
| | - Seiichi Saito
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, 903-0215, Okinawa, Japan
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16
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Kassubek R, Winter MAGR, Dreyhaupt J, Laible M, Kassubek J, Ludolph AC, Lewerenz J. Development of an algorithm for identifying paraneoplastic ischemic stroke in association with lung, pancreatic, and colorectal cancer. Ther Adv Neurol Disord 2024; 17:17562864241239123. [PMID: 38596402 PMCID: PMC11003337 DOI: 10.1177/17562864241239123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 02/19/2024] [Indexed: 04/11/2024] Open
Abstract
Background Paraneoplastic ischemic stroke has a poor prognosis. We have recently reported an algorithm based on the number of ischemic territories, C-reactive protein (CRP), lactate dehydrogenase (LDH), and granulocytosis to predict the underlying active cancer in a case-control setting. However, co-occurrence of cancer and stroke might also be merely incidental. Objective To detect cancer-associated ischemic stroke in a large, unselected cohort of consecutive stroke patients by detailed analysis of ischemic stroke associated with specific cancer subtypes and comparison to patients with bacterial endocarditis. Methods Retrospective single-center cohort study of consecutive 1612 ischemic strokes with magnetic resonance imaging, CRP, LDH, and relative granulocytosis data was performed, including identification of active cancers, history of now inactive cancers, and the diagnosis of endocarditis. The previously developed algorithm to detect paraneoplastic cancer was applied. Tumor types associated with paraneoplastic stroke were used to optimize the diagnostic algorithm. Results Ischemic strokes associated with active cancer, but also endocarditis, were associated with more ischemic territories as well as higher CRP and LDH levels. Our previous algorithm identified active cancer-associated strokes with a specificity of 83% and sensitivity of 52%. Ischemic strokes associated with lung, pancreatic, and colorectal (LPC) cancers but not with breast and prostate cancers showed more frequent and prominent characteristics of paraneoplastic stroke. A multiple logistic regression model optimized to identify LPC cancers detected active cancer with a sensitivity of 77.8% and specificity of 81.4%. The positive predictive value (PPV) for all active cancers was 13.1%. Conclusion Standard clinical examinations can be employed to identify suspect paraneoplastic stroke with an adequate sensitivity, specificity, and PPV when it is considered that the association of ischemic stroke with breast and prostate cancers in the stroke-prone elderly population might be largely incidental.
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Affiliation(s)
- Rebecca Kassubek
- Department of Neurology, University of Ulm, Oberer Eselsberg 45, Ulm 89081, Germany
| | | | - Jens Dreyhaupt
- Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Mona Laible
- Department of Neurology, University of Ulm, Ulm, Germany
| | - Jan Kassubek
- Department of Neurology, University of Ulm, Ulm, Germany
- German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany
| | - Albert C. Ludolph
- Department of Neurology, University of Ulm, Ulm, Germany
- German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany
| | - Jan Lewerenz
- Department of Neurology, University of Ulm, Ulm, Germany
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17
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Ruan GT, Deng L, Xie HL, Shi JY, Liu XY, Zheng X, Chen Y, Lin SQ, Zhang HY, Liu CA, Ge YZ, Song MM, Hu CL, Zhang XW, Yang M, Hu W, Cong MH, Zhu LC, Wang KH, Shi HP. Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia. Cancer Metab 2024; 12:3. [PMID: 38273418 PMCID: PMC10809764 DOI: 10.1186/s40170-024-00332-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 01/12/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.
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Affiliation(s)
- Guo-Tian Ruan
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Li Deng
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Hai-Lun Xie
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Jin-Yu Shi
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Xiao-Yue Liu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Xin Zheng
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Yue Chen
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Shi-Qi Lin
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - He-Yang Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Chen-An Liu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Yi-Zhong Ge
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Meng-Meng Song
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Chun-Lei Hu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Xiao-Wei Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Ming Yang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China
| | - Wen Hu
- Clinical Nutrition Department, Sichuan University West China Hospital, Chengdu, 610041, Sichuan, China
| | - Ming-Hua Cong
- Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, China
| | - Li-Chen Zhu
- Department of Immunology, School of Preclinical Medicine, Guangxi Medical University, Nanning, 530021, China
| | - Kun-Hua Wang
- Yunnan University, Kunming, 650091, China
- General Surgery Clinical Medical Center of Yunnan Province, Kunming, 650032, China
| | - Han-Ping Shi
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100053, China.
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China.
- Laboratory for Clinical Medicine, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.
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Park BS, Cho SH, Lee SH, Son GM, Kim HS. Role of C-Reactive Protein, White Blood Cell Counts, and Serum Glucose Levels as Early Predictors of Infectious Complications After Laparoscopic Colorectal Surgery for Colorectal Cancer. Am Surg 2023; 89:5821-5828. [PMID: 36270320 DOI: 10.1177/00031348221135786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND The early detection of infectious complications of colorectal surgery leads to better patient outcomes. This study aimed to assess the role of C-reactive protein (CRP), white blood cell count (WBC), and serum glucose in the early prediction of infectious complications of laparoscopic colorectal surgery. METHODS Patients who underwent laparoscopic colorectal surgery were included and stratified into two groups: infectious complication (IC) or no infectious complication (non-IC). Serum levels were measured on postoperative days (PODs) 2 and 4. RESULTS Analysis of 224 patients (IC group: 27, Non-IC group: 197) revealed higher CRP levels in IC group on POD 2 (P = .001). On POD 4, CRP levels and WBC counts were higher in IC group (P<.001, P = .011, respectively). The area under the curve (AUC) of the receiver operating characteristic (ROC) for CRP on PODs 2 and 4 were .743 and .907, respectively, and for WBC on POD 4 was .687. The cut-offs of CRP on PODs 2 and 4 were 156.2 mg/L and 91.3 mg/L, respectively; the cut-off of WBC was 7,220 cells/mm3. Sensitivity of CRP level ≥91.3 mg/L or WBC count ≥7,220 cells/mm3 was 96.3%; (cf. 88.9% for CRP alone), and specificity of CRP level ≥91.3 mg/L and WBC count ≥7,220 cells/mm3 was 93.4% (cf. 82.2% for CRP alone). DISCUSSION The CRP level on postoperative day (POD) 2 and the combined CRP and WBC on POD 4 were meaningful in predicting infectious complications after laparoscopic colorectal surgery. However, serum glucose levels had a low predictive value for infectious complications.
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Affiliation(s)
- Byung-Soo Park
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Sung Hwan Cho
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Si Hak Lee
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Gyung Mo Son
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Hyun Sung Kim
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea
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Nassar YM, Ojara FW, Pérez-Pitarch A, Geiger K, Huisinga W, Hartung N, Michelet R, Holdenrieder S, Joerger M, Kloft C. C-Reactive Protein as an Early Predictor of Efficacy in Advanced Non-Small-Cell Lung Cancer Patients: A Tumor Dynamics-Biomarker Modeling Framework. Cancers (Basel) 2023; 15:5429. [PMID: 38001689 PMCID: PMC10670607 DOI: 10.3390/cancers15225429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 11/03/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
In oncology, longitudinal biomarkers reflecting the patient's status and disease evolution can offer reliable predictions of the patient's response to treatment and prognosis. By leveraging clinical data in patients with advanced non-small-cell lung cancer receiving first-line chemotherapy, we aimed to develop a framework combining anticancer drug exposure, tumor dynamics (RECIST criteria), and C-reactive protein (CRP) concentrations, using nonlinear mixed-effects models, to evaluate and quantify by means of parametric time-to-event models the significance of early longitudinal predictors of progression-free survival (PFS) and overall survival (OS). Tumor dynamics was characterized by a tumor size (TS) model accounting for anticancer drug exposure and development of drug resistance. CRP concentrations over time were characterized by a turnover model. An x-fold change in TS from baseline linearly affected CRP production. CRP concentration at treatment cycle 3 (day 42) and the difference between CRP concentration at treatment cycles 3 and 2 were the strongest predictors of PFS and OS. Measuring longitudinal CRP allows for the monitoring of inflammatory levels and, along with its reduction across treatment cycles, presents a promising prognostic marker. This framework could be applied to other treatment modalities such as immunotherapies or targeted therapies allowing the timely identification of patients at risk of early progression and/or short survival to spare them unnecessary toxicities and provide alternative treatment decisions.
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Affiliation(s)
- Yomna M. Nassar
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, 12169 Berlin, Germany; (Y.M.N.)
- Graduate Research Training Program PharMetrX, Berlin/Potsdam, Germany
| | - Francis Williams Ojara
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, 12169 Berlin, Germany; (Y.M.N.)
- Graduate Research Training Program PharMetrX, Berlin/Potsdam, Germany
- Department of Pharmacology, Faculty of Medicine, Gulu University, Gulu P.O. Box 166, Uganda
| | - Alejandro Pérez-Pitarch
- Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 55216 Ingelheim am Rhein, Germany
| | - Kimberly Geiger
- Institute of Laboratory Medicine, German Heart Centre Munich of the Free State of Bavaria, Technical University Munich, 80636 Munich, Germany
| | - Wilhelm Huisinga
- Institute of Mathematics, University of Potsdam, 14476 Potsdam, Germany; (W.H.); (N.H.)
| | - Niklas Hartung
- Institute of Mathematics, University of Potsdam, 14476 Potsdam, Germany; (W.H.); (N.H.)
| | - Robin Michelet
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, 12169 Berlin, Germany; (Y.M.N.)
| | - Stefan Holdenrieder
- Institute of Laboratory Medicine, German Heart Centre Munich of the Free State of Bavaria, Technical University Munich, 80636 Munich, Germany
| | - Markus Joerger
- Department of Medical Oncology and Hematology, Cantonal Hospital, CH-9007 St. Gallen, Switzerland
| | - Charlotte Kloft
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, 12169 Berlin, Germany; (Y.M.N.)
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Liang Z, Zhang M, Shi F, Wang C, Wang J, Yuan Y. Comparative efficacy of four exercise types on obesity-related outcomes in breast cancer survivors: A Bayesian network meta-analysis. Eur J Oncol Nurs 2023; 66:102423. [PMID: 37742423 DOI: 10.1016/j.ejon.2023.102423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 09/12/2023] [Accepted: 09/16/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE Exercise training is associated with improving the prognosis of breast cancer survivors, but no studies have evaluated the optimal exercise intervention. We aimed to investigate the most effective exercise intervention to improve obesity-related outcomes in breast cancer survivors. METHODS A comprehensive search strategy was conducted in Medline, Embase, Web of Science, Cochrane Library, and Chinese biomedical literature databases from the time of library construction to April 2, 2023. We included randomized controlled trials reporting the effects of four types of exercise interventions (aerobic exercise; aerobic combined with resitance exercise, resitstance exercise and mind-body exercise ) on obesity-related outcomes in breast cancer survivors. A Bayesian network meta-analysis was used to analyze and rank the effectiveness of four exercise types. RESULTS A total of 76 randomized controlled trials that contained 5610 breast cancer survivors were included. The treatment effect of combined aerobic and resistance exercise (mean difference = -0.59; 95% credible interval: 1.15, -0.08) was significantly better than that of the control groups in terms of body mass index. For percentage of body fat, combined aerobic and resistance exercise (mean difference = -1.74; 95% credible interval: 0.87, -0.90) and aerobic exercise (mean difference = -1.16; 95% credible interval: 2.15, -0.16) were significantly better than controls. Subgroup analysis suggested that combined aerobic and resistance exercise significantly affected body mass index at an intervention duration >12 weeks or weekly time on exercise >150 min. CONCLUSION Our network meta-analysis found combined aerobic and resistance exercise may be the most effective intervention to improve obesity-related outcomes in breast cancer survivors. In addition, intervention duration and participant adherence are important factors that influence the effectiveness of exercise interventions.
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Affiliation(s)
- Zhide Liang
- Cancer Institute of the Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao, 266071, China.
| | - Meng Zhang
- Xi'an Physical Education University, Xi'an, 710068, China.
| | - Fang Shi
- School of Education and Physical Education, Yangtze University, Jingzhou, 434023, China.
| | - Chuanzhi Wang
- Department of Physical Education, College of Physical Education, Qingdao University, Qingdao, 266071, China.
| | - Jingtai Wang
- Department of Physical Education, College of Physical Education, Qingdao University, Qingdao, 266071, China.
| | - Yang Yuan
- Cancer Institute of the Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao, 266071, China.
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Ali S, Zehra A, Khalid MU, Hassan M, Shah SIA. Role of C-reactive protein in disease progression, diagnosis and management. Discoveries (Craiova) 2023; 11:e179. [PMID: 39554800 PMCID: PMC11569793 DOI: 10.15190/d.2023.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/27/2023] [Accepted: 12/30/2023] [Indexed: 11/19/2024] Open
Abstract
C-reactive protein (CRP) is a ring-shaped pentameric protein synthesized in the liver via CRP gene transcription. It is an inflammatory marker, whose serum levels can be measured using traditional and high-sensitivity tests. In healthy adults, the normal CRP serum concentrations vary between 0.8 mg/L and 3.0 mg/L. These can be grouped into low-, moderate-, and high-risk categories according to CRP levels of less than 1, 1-3, and greater than 3 mg/L, respectively. Elevated levels have been observed in infections, autoimmune diseases, neurodegenerative disorders, and malignancies. However, it is not specific to any disease. Serum CRP levels have also been shown to indicate the risk of cardiovascular disease, owing to their role as inflammatory markers in atherosclerosis, coronary artery disease, and peripheral arterial disease. Furthermore, its role in autoimmune diseases, such as Systemic Lupus Erythematosus and rheumatoid arthritis, and its involvement in the development of cancers, including breast, colorectal, ovarian, prostate, and lung cancers, have also been studied. The involvement of CRP in determining the course of infection and differentiating between bacterial and viral infections has also been investigated. This review summarizes the published literature on C-reactive protein and its role in disease management and progression.
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Affiliation(s)
- Sarah Ali
- MBBS, CMH Lahore Medical University, Lahore, Pakistan
| | - Aiza Zehra
- MBBS, CMH Lahore Medical University, Lahore, Pakistan
| | | | - Momina Hassan
- MBBS, CMH Lahore Medical University, Lahore, Pakistan
| | - Syed Imran Ali Shah
- Head of Department, Department of Biochemistry, CMH Lahore Medical University, Lahore, Pakistan
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Garvik OS, Póvoa P, Vinholt PJ, Nielsen SL, Jensen TG, Frederiksen H, Chen M, Dessau RB, Coia JE, Møller JK, Gradel KO. Detection of infections by computerized capture of peaks in longitudinally measured C-reactive protein levels. Biomark Med 2023; 17:635-642. [PMID: 37962480 DOI: 10.2217/bmm-2023-0419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2023] Open
Abstract
We developed four algorithms for the automatic capture of C-reactive protein (CRP) peaks in 296 adult patients with acute myeloid leukemia who had bloodstream infection (BSI) episodes, negative blood cultures (BCs) or possible infections where no BCs were performed. The algorithms detected CRP peaks for 418-446 of the 586 documented BSI episodes (71.3-76.1%) and 2714-3118 of the 4382 negative BCs (61.9-71.2%). The four algorithms captured 382-789 CRP peaks in which there were neither BSI episodes nor negative BCs. We conclude that automatic capture of CRP peaks is a tool for the monitoring of BSI episodes and possibly other infections in patients with acute myeloid leukemia.
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Affiliation(s)
- Olav Sivertsen Garvik
- Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark and Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, Ground Floor, Odense C, 5000, Denmark
| | - Pedro Póvoa
- Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark and Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, Ground Floor, Odense C, 5000, Denmark
- NOVA Medical School, Comprehensive Health Research Center, New University of Lisbon, Campo Mártires da Pátria 130, Lisbon, 1169-056, Portugal
- Department of Intensive Care, São Francisco Xavier Hospital, Centro Hospitalar de Lisboa Ocidental, Estrada do Forte do Alto do Duque, Lisbon, 1449-005, Portugal
| | - Pernille Just Vinholt
- Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, Entrance 40, Odense C, 5000, Denmark
| | - Stig Lønberg Nielsen
- Department of Infectious Diseases, Odense University Hospital and Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Kløvervænget 4, Odense C, 5000, Denmark
| | - Thøger Gorm Jensen
- Department of Clinical Microbiology, Odense University Hospital and Research Unit of Clinical Microbiology, University of Southern Denmark, JB Winsløws Vej 21, Second Floor, Odense C, 5000, Denmark
| | - Henrik Frederiksen
- Department of Hematology, Odense University Hospital and Research Unit of Hematology, Department of Clinical Research, University of Southern Denmark, Kløvervænget 10, Entrance 112, 12th Floor, Odense C, 5000, Denmark
| | - Ming Chen
- Department of Clinical Microbiology, Hospital of Southern Jutland, Kresten Philipsens Vej 15, Aabenraa, 6200, Denmark
| | - Ram Benny Dessau
- Department of Clinical Microbiology, Zealand University Hospital, Ingemannsvej 46, Slagelse, 4200, Denmark
- Department of Regional Health Research, University of Southern Denmark
| | - John Eugenio Coia
- Department of Clinical Microbiology, Hospital South West Jutland and Department of Regional Health Research, University of Southern Denmark, Finsensgade 35, Esbjerg, 6700, Denmark
| | - Jens Kjølseth Møller
- Department of Clinical Microbiology, Hospital Lillebaelt, Beriderbakken 4, Vejle, 7100, Denmark
- Department of Regional Health Research, University of Southern Denmark
| | - Kim Oren Gradel
- Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark and Center for Clinical Epidemiology, Odense University Hospital, Kløvervænget 30, Entrance 216, Ground Floor, Odense C, 5000, Denmark
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Liu T, Wang Y, Wang X, Liu C, Zhang Q, Song M, Song C, Zhang Q, Shi H. Habitually Skipping Breakfast Is Associated with the Risk of Gastrointestinal Cancers: Evidence from the Kailuan Cohort Study. J Gen Intern Med 2023; 38:2527-2536. [PMID: 36869181 PMCID: PMC10465444 DOI: 10.1007/s11606-023-08094-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 02/08/2023] [Indexed: 03/05/2023]
Abstract
BACKGROUND Habitually skipping breakfast may promote the initiation and progression of gastrointestinal (GI) cancers, which have never been systematically explored in large-scale prospective studies. METHODS We prospectively examined the effects of breakfast frequency on the occurrence of GI cancers among 62,746 participants. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of GI cancers were calculated by Cox regression. The CAUSALMED procedure was used to perform the mediation analyses. RESULTS During a median follow-up of 5.61 (5.18 ~ 6.08) years, 369 incident GI cancer cases were identified. Participants who consumed 1-2 times breakfasts per week exhibited an increased risk of stomach (HR = 3.45, 95% CI: 1.06-11.20) and liver cancer (HR = 3.42, 95% CI: 1.22-9.53). Participants who did not eat breakfast had an elevated risk of esophageal (HR = 2.72, 95% CI: 1.05-7.03), colorectal (HR = 2.32, 95% CI: 1.34-4.01), liver (HR = 2.41, 95% CI: 1.23-4.71), gallbladder, and extrahepatic bile duct cancer (HR = 5.43, 95% CI: 1.34-21.93). In the mediation effect analyses, BMI, CRP, and TyG (fasting triglyceride-glucose) index did not mediate the association between breakfast frequency and the risk of GI cancer incidence (all P for mediation effect > 0.05). CONCLUSIONS Habitually skipping breakfast was associated with a greater risk of GI cancers including esophageal, gastric, colorectal, liver, gallbladder, and extrahepatic bile duct cancer. TRIAL REGISTRATION Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August, 2011-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050.
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Affiliation(s)
- Tong Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038 China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038 China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038 China
| | - Yiming Wang
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000 China
| | - Xiaomeng Wang
- Department of Education, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038 China
- Department of Education, Peking University Ninth School of Clinical Medicine, Beijing, 100038 China
| | - Chenan Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038 China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038 China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038 China
| | - Qi Zhang
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038 China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038 China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038 China
| | - Mengmeng Song
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038 China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038 China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038 China
| | - Chunhua Song
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, ZhengzhouHenan, 450001 China
| | - Qingsong Zhang
- Department of General Surgery, Kailuan General Hospital, Tangshan, 063000 China
| | - Hanping Shi
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038 China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038 China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038 China
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Uchida Y, Nakano T, Hiyamuta H, Kitamura H, Taniguchi M, Ooboshi H, Tsuruya K, Kitazono T. Association between Serum C-Reactive Protein Concentrations and Risk of Cancer-Related Mortality in Patients Undergoing Hemodialysis: 10-Year Outcomes of the Q-Cohort Study. Blood Purif 2023; 52:694-701. [PMID: 37331339 DOI: 10.1159/000530846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/17/2023] [Indexed: 06/20/2023]
Abstract
INTRODUCTION Cancer constitutes a major source of morbidity and mortality among people undergoing hemodialysis (HD). A systemic inflammatory response is associated with the incidence and prognosis of cancer in the general population. However, the effect of systemic inflammation on cancer-related mortality in patients undergoing HD remains unclear. METHODS We analyzed 3,139 patients registered in the Q-Cohort Study, which is a multicenter, observational cohort study of patients on hemodialysis in Japan. The primary outcome was cancer-related mortality during a 10-year follow-up. The covariate of interest was serum C-reactive protein (CRP) concentrations at baseline. The patients were divided into tertiles based on their serum CRP concentrations at baseline (tertile [T] 1: ≤0.07; T2: 0.08-0.24; and T3: ≥0.25). The association between serum CRP concentrations and cancer-related mortality was calculated using the Cox proportional hazards model and the Fine-Gray subdistribution hazards model with non-cancer-related death as a competing risk. RESULTS During the 10-year follow-up, 216 patients died of cancer. In the multivariable analysis, the risk of cancer-related mortality in the highest tertile (T3) of serum CRP concentrations was significantly higher than that in the lowest tertile (T1) (multivariable-adjusted hazard ratio [95% confidence interval]: 1.68 [1.15-2.44]). This association remained consistent in the competing risk model, in which the subdistribution hazard ratio was 1.47 and the 95% confidence interval was 1.00-2.14 for T3 compared with T1. CONCLUSION Higher serum CRP concentrations are associated with an increased risk of cancer-related mortality in patients undergoing maintenance HD.
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Affiliation(s)
- Yushi Uchida
- Division of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroto Hiyamuta
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Hiromasa Kitamura
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | - Hiroaki Ooboshi
- Division of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan
| | | | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Hogea P, Tudorache E, Fira-Mladinescu O, Marc M, Manolescu D, Bratosin F, Rosca O, Mavrea A, Oancea C. The Association of IFN-γ, TNF-α, and Interleukins in Bronchoalveolar Lavage Fluid with Lung Cancer: A Prospective Analysis. J Pers Med 2023; 13:968. [PMID: 37373957 DOI: 10.3390/jpm13060968] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/04/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Lung cancer is a leading cause of cancer-related mortality worldwide. Identifying novel diagnostic and prognostic biomarkers is essential for improving patient outcomes. This study aimed to investigate the predictive role of cytokines from bronchoalveolar lavage fluid (BALF) in lung cancer diagnosis and prognosis. A prospective study was conducted on 33 patients with suspected lung cancer, divided into inflammatory and non-inflammatory BALF groups. Inflammatory markers in BALF were assessed, and their association with lung cancer risk was analyzed using receiver operating characteristic (ROC) plot analysis, sensitivity and specificity percentages, and regression analysis. Statistically significant differences were observed between the inflammatory and non-inflammatory groups for several inflammatory markers, including IFN-gamma, IL-1b, IL-2, IL-6, IL-10, and IL-12p70. In the follow-up analysis, significant differences persisted for IFN-gamma, IL-1b, IL-2, IL-4, and IL-6. ROC plot analysis revealed that IL-12p70 had the highest area under the curve (AUC) value (0.702), followed by IL-2 (0.682), IL-6 (0.620), IL-4 (0.611), TNF-alpha (0.609), IL-10 (0.604), IL-1b (0.635), and IFN-gamma (0.521). IL-6 showed the highest sensitivity (73%), and IL-1b had the highest specificity (69%). Regression analysis demonstrated that IL-6 (cut-off = 25 pg/mL) and IL-12p70 (cut-off = 30 pg/mL) had the highest odds ratios for lung cancer risk, at 5.09 (95% CI: 2.38-9.24, p < 0.001) and 4.31 (95% CI: 1.85-8.16, p < 0.001), respectively. Cytokines from BALF, particularly IL-6 and IL-12p70, show potential as diagnostic and prognostic biomarkers for lung cancer. Further studies with larger cohorts are warranted to confirm these findings and elucidate the clinical implications of these markers in lung cancer management.
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Affiliation(s)
- Patricia Hogea
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Doctoral School, Faculty of General Medicine, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Emanuela Tudorache
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- First Pulmonology Clinic, Clinical Hospital of Infectious Diseases and Pulmonology, "Victor Babes", Gheorghe Adam Street 13, 300310 Timisoara, Romania
| | - Ovidiu Fira-Mladinescu
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Second Pulmonology Clinic, Clinical Hospital of Infectious Diseases and Pulmonology, "Victor Babes", Gheorghe Adam Street 13, 300310 Timisoara, Romania
| | - Monica Marc
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Second Pulmonology Clinic, Clinical Hospital of Infectious Diseases and Pulmonology, "Victor Babes", Gheorghe Adam Street 13, 300310 Timisoara, Romania
| | - Diana Manolescu
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Discipline of Radiology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Felix Bratosin
- Discipline of Infectious Diseases, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Ovidiu Rosca
- Discipline of Infectious Diseases, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Adelina Mavrea
- Department of Internal Medicine I, Cardiology Clinic, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Cristian Oancea
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- First Pulmonology Clinic, Clinical Hospital of Infectious Diseases and Pulmonology, "Victor Babes", Gheorghe Adam Street 13, 300310 Timisoara, Romania
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Al-Shalah MI, Alabdallat S, Alzayed A, Abunaser N, Khamees A. Benign Paratesticular Fibrous Pseudotumor in a Young Male: A Case Report. Urology 2023; 176:171-174. [PMID: 36764489 DOI: 10.1016/j.urology.2023.01.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/20/2023] [Accepted: 01/29/2023] [Indexed: 02/11/2023]
Abstract
Paratesticular fibrous pseudotumor (PFPs) is an uncommon intra-scrotal mass that originated from tunica vaginalis and resulted in a reactive fibrous proliferation after a history of inflammation, infection, trauma, or hydrocele. We report here on a case of a 17-year-old man with a mass in the hemiscrotum that was found to be PFP in the orchidectomy specimen pathologic examination. The diagnosis of PFPs, before and during the operation, can be complicated despite it being a benign tumor. Radical orchidectomy is usually performed for these types of lesions. A frozen section intraoperatively is essential to avoid unnecessary radical orchidectomy and preserve testicle.
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Affiliation(s)
- Mustafa I Al-Shalah
- Division of Urology, Department of Special Surgery, Al Bashir Hospital, Ministry of Health, Amman, Jordan
| | - Sadam Alabdallat
- Division of Urology, Department of Special Surgery, Al Bashir Hospital, Ministry of Health, Amman, Jordan
| | - Ashraf Alzayed
- Department of Surgery, King Hussein Cancer Center, Amman, Jordan
| | - Neebal Abunaser
- Department of Surgery, King Hussein Cancer Center, Amman, Jordan
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Mohamadkazem M, Neshastehriz A, Amini SM, Moshiri A, Janzadeh A. Radiosensitising effect of iron oxide-gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting. IET Nanobiotechnol 2023; 17:212-223. [PMID: 37083267 DOI: 10.1049/nbt2.12129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 03/13/2023] [Accepted: 03/14/2023] [Indexed: 04/22/2023] Open
Abstract
Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is necessary to give a lower dose to the patient with targeted therapy. In this study, the radio-sensitising effect of gold-coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold-coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold-coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold-coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay blood test were also performed. Gold-coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.
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Affiliation(s)
- Mahshad Mohamadkazem
- Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran
- Radiation Science Department, Iran University of Medical Science (IUMS), Tehran, Iran
| | - Ali Neshastehriz
- Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran
- Radiation Science Department, Iran University of Medical Science (IUMS), Tehran, Iran
| | - Seyed Mohammad Amini
- Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran
| | - Ali Moshiri
- Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran
| | - Atousa Janzadeh
- Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran
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Tada T, Kumada T, Hiraoka A, Kariyama K, Tani J, Hirooka M, Takaguchi K, Atsukawa M, Fukunishi S, Itobayashi E, Tsuji K, Tajiri K, Ochi H, Ishikawa T, Yasuda S, Ogawa C, Toyoda H, Hatanaka T, Nishimura T, Kakizaki S, Kawata K, Shimada N, Tada F, Nouso K, Tsutsui A, Ohama H, Morishita A, Nagano T, Itokawa N, Okubo T, Arai T, Kosaka H, Imai M, Naganuma A, Nakamura S, Koizumi Y, Kaibori M, Iijima H, Hiasa Y, the Real‐life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group. New prognostic system based on inflammation and liver function predicts prognosis in patients with advanced unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A validation study. Cancer Med 2023; 12:6980-6993. [PMID: 36484470 PMCID: PMC10067064 DOI: 10.1002/cam4.5495] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 10/18/2022] [Accepted: 11/19/2022] [Indexed: 12/13/2022] Open
Abstract
AIM Recently, the neo-Glasgow prognostic score (GPS), a composite biomarker determined by the C-reactive protein level and albumin-bilirubin grade, was developed to predict outcomes in hepatocellular carcinoma (HCC) patients who undergo hepatic resection. The present research investigated whether the neo-GPS could predict prognosis in HCC patients treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS A total of 421 patients with HCC who were treated with Atez/Bev were investigated. RESULTS Multivariate Cox hazards analysis showed that a GPS of 1 (hazard ratio (HR), 1.711; 95% confidence interval (CI), 1.106-2.646) and a GPS of 2 (HR, 4.643; 95% CI, 2.778-7.762) were independently associated with overall survival. Conversely, multivariate Cox hazards analysis showed that a neo-GPS of 1 (HR, 3.038; 95% CI, 1.715-5.383) and a neo-GPS of 2 (HR, 5.312; 95% CI, 2.853-9.890) were also independently associated with overall survival in this cohort. Additionally, cumulative overall survival rates differed significantly by GPS and neo-GPS (p < 0.001). The neo-GPS, compared with the GPS, had a lower Akaike information criterion (1207 vs. 1,211, respectively) and a higher c-index (0.677 vs. 0.652, respectively) regarding to overall survival. In a subgroup analysis of patients considered to have a good prognosis as confirmed using a Child-Pugh score of 5 (p = 0.001), a neutrophil-to-lymphocyte ratio <3 (p = 0.001), or an α-fetoprotein level < 100 ng/mL (p < 0.001), those with a high neo-GPS (≥1) had a statistically poorer overall survival than those with a low neo-GPS. CONCLUSIONS The neo-GPS can predict prognosis in advanced unresectable HCC patients treated with Atez/Bev.
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Baichan P, Naicker P, Augustine TN, Smith M, Candy G, Devar J, Nweke EE. Proteomic analysis identifies dysregulated proteins and associated molecular pathways in a cohort of gallbladder cancer patients of African ancestry. Clin Proteomics 2023; 20:8. [PMID: 36855072 PMCID: PMC9976386 DOI: 10.1186/s12014-023-09399-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 02/23/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is a lethal cancer with a poor prognosis. The lack of specific and sensitive biomarkers results in delayed diagnosis with most patients presenting at late stages of the disease. Furthermore, there is little known about the molecular mechanisms associated with GBC, especially in patients of African ancestry. This study aimed to determine dysregulated proteins in South African GBC patients to identify potential mechanisms of the disease progression and plausible biomarkers. METHODS Tissues (27 GBC, 13 Gallstone disease, and 5 normal tissues) and blood plasma (54 GBC and 73 Benign biliary pathology) were obtained from consenting patients. Protein extraction was performed on all tissues and liquid chromatography-mass spectrometry was used for proteomic profiling. A project-specific spectral library was built using the Pulsar search algorithm. Principal component and Spearman's rank correlation analyses were performed using PAST (V4.07b). Pathway and Network analyses were conducted using REACTOME (v3.7) and stringAPP (v1.7.0), respectively. RESULTS In the tissue sample group, there were 62 and 194 dysregulated proteins in GBC compared to normal and gallstone groups, respectively. In the plasma group, there were 33 altered proteins in GBC compared to the benign biliary pathology group. We found 9 proteins (APOA1, APOA2, RET4, TTR, HEMO, HBB, HBA, PIGR, and APOE) to be commonly dysregulated in both tissue and plasma. Furthermore, a subset analysis demonstrated that 2 proteins, S100A8 and S100A9, were downregulated in GBC patients with GD history compared to those without. Pathway analysis showed that the dysregulated proteins in GBC patients were enriched in pathways involved in smooth muscle contraction, metabolism, ECM organization, and integrin cell surface interactions. CONCLUSION The identified dysregulated proteins help in understanding GBC molecular mechanisms in our patient group. Furthermore, the alteration of specific proteins in both tissue and plasma samples suggests their potential utility as biomarkers of GBC in this sample cohort.
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Affiliation(s)
- Pavan Baichan
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa
| | - Previn Naicker
- Council for Scientific and Industrial Research, Pretoria, 0001, South Africa
| | - Tanya Nadine Augustine
- School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
| | - Martin Smith
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa
- Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto, Johannesburg, South Africa
| | - Geoffrey Candy
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa
| | - John Devar
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa
- Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto, Johannesburg, South Africa
| | - Ekene Emmanuel Nweke
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa.
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The Significance of Serum C-Reactive Protein and Neutrophil-Lymphocyte Ratio in Predicting the Diagnostic Outcomes of Renal Mass Biopsy Procedure. J Kidney Cancer VHL 2023; 10:9-14. [PMID: 36793395 PMCID: PMC9902900 DOI: 10.15586/jkcvhl.v10i1.259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/20/2023] [Indexed: 02/09/2023] Open
Abstract
This study aimed to investigate the predictive role of serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) on renal mass biopsy outcomes. A total of 71 patients with suspected kidney masses who underwent renal mass biopsy procedure between January 2017 and January 2021 were retrospectively evaluated. Pathological results after the procedure were obtained and pre-procedural serum CRP and NLR levels were extracted from the patients' data. The patients were grouped into benign and malignant pathology groups according to the histopathology results. The parameters were compared between the groups. Diagnostic role of the parameters in terms of sensitivity, specificity, and positive and negative predictive values was also determined. Additionally, Pearson correlation analysis, and univariate and multivariate cox proportional hazard regression analyses were also performed to investigate the above association with tumor diameter and pathology results, respectively. At the end of the analyses, a total of 60 patients had malignant pathology on histopathological investigations of the mass biopsy specimens, whereas the remaining 11 patients had a benign pathological diagnosis. Significantly higher CRP and NLR levels were detected in the malignant pathology group. The parameters positively correlated with the malignant mass diameter, as well. Serum CRP and NLR determined the malignant masses before the biopsy with sensitivity and specificity of 76.6 and 81.8%, and 88.3 and 45.4%, respectively. Moreover, univariate and multivariate analyses showed that serum CRP level had a significant predictive value for malignant pathology (HR: 0.998, 95% CI: 0.940-0.967, P < 0.001 and HR: 0.951, 95% CI: 0.936-0.966, P < 0.001, respectively). In conclusion, serum CRP and NLR levels were significantly different in patients with malignant pathology after renal mass biopsy compared to the patients with benign pathology. Serum CRP level, in particular, diagnosed malignant pathologies with acceptable sensitivity and specificity values. Additionally, it had a substantial predictive role in determining the malign masses prior the biopsy. Therefore, pre-biopsy serum CRP and NLR levels may be used to predict the diagnostic outcomes of renal mass biopsy in clinical practice. Further studies with larger cohorts can prove our findings in the future.
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Grümme L, Schulze-Koops H. [Rheumatological side effects of checkpoint inhibitors and their treatment]. Z Rheumatol 2023; 82:187-194. [PMID: 36607420 DOI: 10.1007/s00393-022-01311-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2022] [Indexed: 01/07/2023]
Abstract
The spectrum of tumors for which checkpoint inhibitor (CI) treatment is used is constantly expanding. The European Medicines Agency has currently approved nine CIs: one anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CI, one anti-lymphocyte activation gene 3 (LAG-3) CI, four anti-programmed cell death protein 1 (PD-1) CIs and three anti-programmed death ligand 1 (PD-L1) CIs. By blocking immune checkpoints the physiological downregulation of T cell activity against autologous tissue is prevented. This results in an immunologically unregulated activation of T cells directed against malignant cells. Healthy tissue also expresses antigens and thereby continuously activates autologous T cells. Thus, the blockade of immune checkpoints can lead to T cell activity against healthy tissue (immune-related adverse events, irAE). The irAEs can occur in any organ system and approximately 10% of all patients under CI treatment develop rheumatological irAEs, mostly arthralgia and myalgia. The classification criteria of rheumatological diseases do not need to be met to initiate treatment and the primary goal of treatment of irAEs is to enable continuation of CI treatment. Rheumatological irAEs should be recognized and treated quickly. In the treatment of musculoskeletal irAEs, three stages can be defined. In the first stage, nonsteroidal anti-inflammatory drugs or intra-articular as well as systemic glucocorticoids are used. In the second stage, conventional synthetic and in the third stage, biologic disease-modifying antirheumatic drugs are used. The most severe musculoskeletal irAE is myositis with cardiac and/or respiratory involvement and/or myasthenia gravis. In addition to high-dose glucocorticoids, intravenous immunoglobulins or plasma exchange are used in treatment.
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Affiliation(s)
- Lea Grümme
- Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik und Poliklinik IV, LMU Klinikum München, Pettenkoferstr. 8a, 80336, München, Deutschland.
| | - Hendrik Schulze-Koops
- Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik und Poliklinik IV, LMU Klinikum München, Pettenkoferstr. 8a, 80336, München, Deutschland.
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Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study. Respir Res 2023; 24:7. [PMID: 36624433 PMCID: PMC9830761 DOI: 10.1186/s12931-022-02309-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 12/30/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Several observational studies have found that idiopathic pulmonary fibrosis (IPF) is often accompanied by elevated circulating C-reactive protein (CRP) levels. However, the causal relationship between them remains to be determined. Therefore, our study aimed to explore the causal effect of circulating CRP levels on IPF risk by the two-sample Mendelian randomization (MR) analysis. METHODS We analyzed the data from two genome-wide association studies (GWAS) of European ancestry, including circulating CRP levels (204,402 individuals) and IPF (1028 cases and 196,986 controls). We primarily used inverse variance weighted (IVW) to assess the causal effect of circulating CRP levels on IPF risk. MR-Egger regression and MR-PRESSO global test were used to determine pleiotropy. Heterogeneity was examined with Cochran's Q test. The leave-one-out analysis tested the robustness of the results. RESULTS We obtained 54 SNPs as instrumental variables (IVs) for circulating CRP levels, and these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR analysis revealed a causal effect between elevated circulating CRP levels and increased risk of IPF (ORIVW = 1.446, 95% CI 1.128-1.854, P = 0.004). CONCLUSIONS The present study indicated that elevated circulating CRP levels could increase the risk of developing IPF in people of European ancestry.
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Song R, Ni H, Huang J, Yang C, Qin S, Wei H, Luo J, Huang Y, Xiang B. Prognostic Value of Inflammation-Immunity-Nutrition Score and Inflammatory Burden Index for Hepatocellular Carcinoma Patients After Hepatectomy. J Inflamm Res 2022; 15:6463-6479. [PMID: 36467989 PMCID: PMC9717599 DOI: 10.2147/jir.s386407] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 11/12/2022] [Indexed: 07/26/2023] Open
Abstract
PURPOSE The study aimed to investigate the ability of inflammation-immunity-nutrition score (IINS) and inflammatory burden index (IBI), individually or in combination, to predict prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. METHODS A total of 701 patients who underwent HCC resection at Guangxi Medical University Cancer Hospital were enrolled in the study. An IINS ranging from 0 to 3 was defined based on preoperative C-reactive protein (CRP), lymphocyte count, and serum albumin level, while an IBI was based on CRP and neutrophil-to-lymphocyte ratio. The prognostic value of IINS and IBI was assessed using univariate and multivariate Cox regression and Kaplan-Meier survival curves. The concordance index and calibration curve were used for internal validation of models. Decision curve analysis, net reclassification index and integrated discrimination improvement were used to compare the predictive performance of the models with traditional staging systems. RESULTS IINS and IBI were able to predict poor prognosis in HCC patients after hepatectomy, and a nomogram based on the IINS predicted survival at 1, 3, and 5 years better than other models or traditional staging systems. CONCLUSION IINS may be accurate predictors of survival in HCC patients after hepatectomy, with potentially greater prognostic value than conventional markers.
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Affiliation(s)
- Rui Song
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China
| | - Hanghang Ni
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Juntao Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Chenglei Yang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Shangdong Qin
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China
| | - Huaning Wei
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Jiefu Luo
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Yuxiang Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
| | - Bangde Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China
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Banait T, Wanjari A, Danade V, Banait S, Jain J. Role of High-Sensitivity C-reactive Protein (Hs-CRP) in Non-communicable Diseases: A Review. Cureus 2022; 14:e30225. [PMID: 36381804 PMCID: PMC9650935 DOI: 10.7759/cureus.30225] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022] Open
Abstract
Non-communicable diseases like cardiovascular diseases, cerebrovascular diseases, diabetes mellitus, and cancer are very common causes of death worldwide. Therefore, the need to search for novel, affordable, and easily accessible biomarkers and risk factors for non-communicable diseases continues, which can predict the future risk of having these diseases with greater accuracy and precision. In this context, among available biomarkers, high-sensitivity C-reactive protein (Hs-CRP) is considered to be the best-suited marker. Various drug intervention trials demonstrated positive results in reducing Hs-CRP in individuals with raised levels. Numerous pharmacological and non-pharmacologic interventions in the form of lifestyle modifications, exercise, and cessation of smoking are being investigated to study their effect on reducing serum C-reactive protein (CRP) levels. This review article discusses the role of Hs-CRP and its isoforms in the pathogenesis of various disease conditions, factors affecting its serum concentration, its prognostic value, and its comparison with other risk factors. Further, its clinical significance in chronic inflammatory and degenerative diseases of the nervous system and other common non-communicable diseases, including recent advances in the management of various diseases, has also been discussed.
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Hamura R, Haruki K, Fujiwara Y, Tsunematsu M, Shirai Y, Furukawa K, Onda S, Gocho T, Shiba H, Uwagawa T, Usuba T, Fujioka S, Okamoto T, Ikegami T. The effectiveness of adjuvant chemotherapy for Stage I pancreatic cancer based on the UICC 8 th edition. Langenbecks Arch Surg 2022; 407:3437-3446. [PMID: 36173461 DOI: 10.1007/s00423-022-02686-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 09/13/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Adjuvant chemotherapy is recommended for patients with pancreatic cancer after curative resection. However, there is limited evidence regarding the efficacy and prognostic factors for adjuvant chemotherapy in patients with stage I pancreatic cancer. This study aimed to identify patients in whom chemotherapy was effective and to detect prognostic factors for stage I pancreatic cancer based on guidelines of the 8th edition of the Union for International Cancer Control (UICC). METHODS Between 2009 and 2017, 108 patients diagnosed with stage I pancreatic cancer were enrolled in this study. They were distributed into invasion (n = 68) and non-invasion (n = 40) groups. The relationship between clinicopathological variables, including various prognostic factors, disease-free survival (DFS), and overall survival (OS), were investigated by univariate and multivariate analyses. RESULTS Five-year survival in all patients with stage I pancreatic cancer was 38.9%. Adjuvant chemotherapy failed to improve DFS or OS in patients with stage I cancer (DFS, p = 0.26; OS, p = 0.30). In subgroup analysis, adjuvant chemotherapy significantly improved DFS (multivariate-adjusted hazard ratio (HR), 0.40; 95% confidence interval [CI], 0.21-0.78; p = 0.007) and OS (multivariate-adjusted HR, 0.32; 95% CI, 0.15-0.68; p = 0.003) in the invasion group than in non-invasion group. In contrast, in the non-invasion group, adjuvant chemotherapy failed to improve DFS and OS in univariate analysis (DFS, p = 0.992; OS, p = 0.808). CONCLUSION For stage I pancreatic cancer, based on guidelines of the UICC 8th edition, adjuvant chemotherapy may benefit patients with extrapancreatic invasion.
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Affiliation(s)
- Ryoga Hamura
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Koichiro Haruki
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Yuki Fujiwara
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masashi Tsunematsu
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yoshihiro Shirai
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Shinji Onda
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takeshi Gocho
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Hiroaki Shiba
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Tadashi Uwagawa
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Teruyuki Usuba
- Department of Surgery, The Jikei University Katsushika Medical Center, Tokyo, Japan
| | - Shuichi Fujioka
- Department of Surgery, The Jikei University Kashiwa Hospital, Chiba, Japan
| | - Tomoyoshi Okamoto
- Department of Surgery, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Toru Ikegami
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
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Avnet S, Falzetti L, Bazzocchi A, Gasperini C, Taddei F, Schileo E, Baldini N. Individual Trajectories of Bone Mineral Density Reveal Persistent Bone Loss in Bone Sarcoma Patients: A Retrospective Study. J Clin Med 2022; 11:jcm11185412. [PMID: 36143059 PMCID: PMC9506337 DOI: 10.3390/jcm11185412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/27/2022] [Accepted: 09/06/2022] [Indexed: 11/19/2022] Open
Abstract
Multiagent chemotherapy offers an undoubted therapeutic benefit to cancer patients, but is also associated with chronic complications in survivors. Osteoporosis affects the quality of life of oncologic patients, especially at the paediatric age. However, very few studies have described the extent of loss of bone mineral density (BMD) in bone sarcoma patients. We analysed a retrospective series of children and adolescents with primary malignant bone tumours (52 osteosarcoma and 31 Ewing sarcoma) and retrieved their BMD at diagnosis and follow-up as Hounsfield units (HU). We studied their individual BMD trajectories before and after chemotherapy up to 5 years, using routine chest CT scan and attenuation thresholds on T12 vertebrae ROI. At one year, bone sarcoma patients showed significant bone loss compared to diagnosis: 17.6% and 17.1% less for OS and EW, respectively. Furthermore, a bone loss of more than 49.2 HU at one-year follow-up was predictive of the persistence of a reduced bone mass over the following 4 years, especially in patients with EW. At 4 years, only 26% and 12.5% of OS and EW, respectively, had recovered or improved their BMD with respect to the onset, suggesting a risk of developing morbidities related to a low BMD in those subjects.
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Affiliation(s)
- Sofia Avnet
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40127 Bologna, Italy
| | - Luigi Falzetti
- Biomedical Science and Technologies and Nanobiotechnology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Alberto Bazzocchi
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Chiara Gasperini
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Fulvia Taddei
- BIC Bioengineering and Computing Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Enrico Schileo
- BIC Bioengineering and Computing Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Nicola Baldini
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40127 Bologna, Italy
- Biomedical Science and Technologies and Nanobiotechnology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
- Correspondence:
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Sheen HJ, Panigrahi B, Kuo TR, Hsu WC, Chung PS, Xie QZ, Lin CY, Chang YS, Lin CT, Fan YJ. Electrochemical biosensor with electrokinetics-assisted molecular trapping for enhancing C-reactive protein detection. Biosens Bioelectron 2022; 210:114338. [PMID: 35550939 DOI: 10.1016/j.bios.2022.114338] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 03/15/2022] [Accepted: 05/02/2022] [Indexed: 11/15/2022]
Abstract
C-Reactive protein (CRP) is an essential biomarker relevant to various disease prognoses. Current biosensors require a significant amount of time for detecting CRP. To address this issue, this work proposes electrokinetic flow-assisted molecule trapping integrated with an impedance biosensor, where a driving signal in terms of a gated sine wave is provided to circularly arranged electrodes which detect proteins. To verify the biosensor's efficacy, protein aggregation on the electrode surface was evaluated through a fluorescence analysis and measurement of the electrochemical impedance spectrum (EIS). The fluorescence analysis with avidin showed that target samples largely accumulated on the electrode surface upon provision of the driving signal. The EIS measurement of CRP accumulation on the electrode surface further confirmed a significant electrokinetic phenomenon at the electrode/electrolyte interface. Even at the low CRP concentration of 10 pg/ml, the proposed device's sensitivity and reliability were as high as 3.92 pg/ml with a signal-to noise ratio (SNR) of ≥3, respectively. In addition, the protein detection time (without considering the preparation time) was minimized to as low as 90 s with the proposed device. This device's advantage is its minimal time consumption, and simple drop-analysis process flow; hence, it was used for monitoring clinical serum samples.
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Affiliation(s)
- Horn-Jiunn Sheen
- Institute of Applied Mechanics, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Bivas Panigrahi
- Department of Refrigeration, Air Conditioning and Energy Engineering, National Chin-Yi University of Science and Technology, Taiping Dist., Taichung City, 41170, Taiwan.
| | - Tsung-Rong Kuo
- Graduate Institute of Nanomedicine and Medical Engineering, International Ph.D. Program in Biomedical Engineering, Taipei Medical University, 250 Wuxing St., Taipei, 11031, Taiwan
| | - Wei-Chen Hsu
- Institute of Applied Mechanics, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Pei-Shan Chung
- Department of Bioengineering, University of California at Los Angeles, 420 Westwood Plaza, Los Angeles, CA, 90095, USA
| | - Qiu-Zhe Xie
- Department of Electrical Engineering, Graduate Institute of Electronics Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Ching-Yu Lin
- PhD Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, 250 Wuxing St, Taipei, 11031, Taiwan
| | - Yu-Sheng Chang
- Division of Allergy, Immunology and Rheumatology, Shuang Ho Hospital, 291 Zhongzheng Rd, Zhonghe District, New Taipei City 23561, Taiwan, Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing St, Taipei, 11031, Taiwan
| | - Chih-Ting Lin
- Department of Electrical Engineering, Graduate Institute of Electronics Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan
| | - Yu-Jui Fan
- School of Biomedical Engineering, International PhD Program in Biomedical Engineering, International PhD Program for Cell Therapy and Regeneration Medicine, Taipei Medical University, 250 Wuxing St., Taipei, 11031, Taiwan.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Naganuma A, Aoki T, Koizumi Y, Nakamura S, Joko K, Hiasa Y, Kudo M. Glasgow prognostic score predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib: a multicenter analysis. Eur J Gastroenterol Hepatol 2022; 34:857-864. [PMID: 35802527 DOI: 10.1097/meg.0000000000002398] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The use of Glasgow prognostic score (GPS), calculated using the serum C-reactive protein and albumin levels, to predict the outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib was investigated in this study. METHODS A total of 508 patients with Child-Pugh class A HCC treated with lenvatinib were included in this study. RESULTS The median overall and progression-free survivals were 20.4 months [95% confidence interval (CI), 17.7-23.2 months] and 7.5 months (95% CI, 6.8-8.5 months), respectively. The median overall survivals of patients with a GPS of 0, 1, and 2 were 28.5, 16.0, and 9.1 months, respectively (P < 0.001). When adjusted for age, sex, performance status, etiology, α-fetoprotein, macroscopic vascular invasion, extrahepatic spread, history of sorafenib therapy, and GPS, a GPS of 1 [hazard ratio (HR), 1.664; 95% CI, 1.258-2.201; P < 0.001] and a GPS of 2 (HR, 2.664; 95% CI, 1.861-3.813; P < 0.001) were found to be independently associated with overall survival. The median progression-free survivals of patients with a GPS of 0, 1, and 2 were 8.8, 6.8, and 3.8 months, respectively (P < 0.001). When adjusted for the same factors of overall survival, a GPS of 2 (HR, 2.010; 95% CI, 1.452-2.784; P < 0.001) was found to be independently associated with progression-free survival. As the albumin-bilirubin with tumor node metastasis score increased, the proportion of patients with a GPS of 1 or 2 increased (P < 0.001). CONCLUSIONS GPS can be used to predict survival in patients with unresectable HCC who were treated with lenvatinib.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji
| | | | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi
| | | | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama
| | - Hironori Ochi
- Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa
| | - Kazuhito Kawata
- Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu
| | - Takaaki Tanaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama
| | - Hideko Ohama
- Department of Gastroenterology, Osaka Medical College, Osaka
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki
| | - Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime
| | | | - Kouji Joko
- Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
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Lee SA, Kwon SO, Park H, Shu XO, Lee JK, Kang D. Association of serum high-sensitivity C reactive protein with risk of mortality in an Asian population: the Health Examinees cohort. BMJ Open 2022; 12:e052630. [PMID: 35788076 PMCID: PMC9255402 DOI: 10.1136/bmjopen-2021-052630] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVES This study aimed to examine the association of high-sensitivity C reactive protein (hsCRP) with mortality risk and the attenuated effect of non-communicable disease history (NCD history ) on the association. DESIGN Prospective cohort study. SETTING Health Examinees cohort. PARTICIPANTS A total of 41 070 men and 81 011 women aged ≥40 years were involved (follow-up: 6.8 years). OUTCOME MEASURES Data and cause of death occurring until 31 December 2015 were confirmed by death statistics from the National Statistical Office. We conducted advanced analysis after stratification by NCD history and sensitivity analysis after excluding death before 1 or 2 years from recruitment. Cox proportional hazard and restricted cubic spline models were used to assess the association. RESULTS The association between serum hsCRP and risk of all-cause mortality was observed with strong linearity in both genders and was not influenced by NCD history . The association of serum hsCRP with risk of cancer mortality was not observed in women with NCD history , but the association with risk of cardiovascular disease (CVD) mortality was predominantly observed in men with NCD history . CONCLUSIONS This study suggests a dose-response association of hsCRP with mortality risk, including cancer and CVD mortality, in Koreans with low serum hsCRP, although the association with cancer and CVD mortality risk could be influenced by gender and NCD history .
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Affiliation(s)
- Sang-Ah Lee
- Preventive Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Sung Ok Kwon
- Preventive Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
| | - Hyerim Park
- Preventive Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
| | - Xiao-Ou Shu
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jong-Koo Lee
- JW LEE Center for Global Medicine, Seoul, Republic of Korea
| | - Daehee Kang
- Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Jotic A, Milovanovic J, Savic-Vujovic K, Radin Z, Medic B, Folic M, Pavlovic B, Vujovic A, Dundjerovic D. Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer. Dose Response 2022; 20:15593258221115537. [PMID: 35898723 PMCID: PMC9309787 DOI: 10.1177/15593258221115537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Objective The aim of this study was to evaluate cell and biochemical biomarkers and
establish their prognostic value in patients with advanced laryngeal
cancer. Material and Methods A prospective study included 52 patients with advanced laryngeal carcinoma
surgically treated at the tertiary referral center. Tumor tissue was
immunohistochemically stained for T-cell markers (CD4 and CD8), and levels
of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood
samples. Results Overall 3-year survival (OS) of patients included in the study was 69.2% and
the disease specific survival (DSS) 72.5%. Higher expression of
CD4+ and CD8+ were significant prognostic factors
with positive impact on both OS and DSS in univariate analysis, but not in
multivariate analysis. Levels of IL-8 were a significant predictor of 3-year
OS and DSS survival in patients with advanced laryngeal cancer but not
levels of IL-6 and CRP values. Conclusion Though high expression of CD4 and CD8 were demonstrated in the tumor tissue,
but their prognostic role was not established. Higher values of IL-8 proved
to be significant negative predictor of DSS. This could further collaborate
the inclusion of combination of biomarkers in assessment of favorable
treatment choice in patients with advanced laryngeal carcinoma.
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Affiliation(s)
- Ana Jotic
- Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Medical Faculty, University of Belgrade, Belgrade, Serbia
| | - Jovica Milovanovic
- Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Medical Faculty, University of Belgrade, Belgrade, Serbia
| | - Katarina Savic-Vujovic
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Zorana Radin
- Ear, Nose and Throat Clinic, Clinical Hospital Center Zvezdara, Belgrade, Serbia
| | - Branislava Medic
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Miljan Folic
- Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Medical Faculty, University of Belgrade, Belgrade, Serbia
| | - Bojan Pavlovic
- Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Medical Faculty, University of Belgrade, Belgrade, Serbia
| | - Aleksandar Vujovic
- ENT Hospital, Clinical Hospital Center ''Dr Dragisa Misovic-Dedinje'' Belgrade, Serbia
| | - Dusko Dundjerovic
- Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia
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41
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Zhang Y, Gu D. Prognostic Impact of Serum CRP Level in Head and Neck Squamous Cell Carcinoma. Front Oncol 2022; 12:889844. [PMID: 35847918 PMCID: PMC9277075 DOI: 10.3389/fonc.2022.889844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/23/2022] [Indexed: 12/02/2022] Open
Abstract
Objective This study evaluated the association of pretreatment serum C-reactive protein (CRP) level with prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Methods Within a single-center retrospective study, HNSCC patients receiving treatment between 2014 and 2016 were analyzed regarding the prognostic value of CRP serum levels. X-Tile software was used to determine the optimal cutoff value of serum CRP level. The log-rank test and Kaplan–Meier method were used to assess the effects of CRP level on prognosis in patients with HNSCC. Univariate and multivariate analyses (enter method) using a Cox proportional hazards model were utilized to identify prognostic indicators of progression-free survival (PFS) as the primary outcome and overall survival (OS) as the secondary outcome. Results A total of 221 patients with HNSCC were assessed for eligibility, and 208 cases were included in the analysis. The HNSCC patients in the low-group (CRP ≤11.3 mg/L) showed better survival than those in the high-group (CRP > 11.3 mg/L). The univariate and multivariate analyses showed that N1-3 stage and a high serum CRP level (>11.3 mg/L) were unfavorable prognostic factors for PFS and OS in patients with HNSCC. Conclusion Serum CRP level is an independent prognostic marker for patients with HNSCC. CRP level could be regarded as a novel prognostic factor for HNSCC patients.
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Ruan GT, Xie HL, Gong YZ, Ge YZ, Zhang Q, Wang ZW, Zhang X, Zhang HY, Tang M, Song MM, Zhang XW, Yang M, Chen YB, Yu KY, Deng L, Wang KH, Cong MH, Shi HP. Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study. BMC Cancer 2022; 22:700. [PMID: 35752767 PMCID: PMC9233357 DOI: 10.1186/s12885-022-09752-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 06/07/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.
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Affiliation(s)
- Guo-Tian Ruan
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Hai-Lun Xie
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Yi-Zhen Gong
- Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous, Region, 530021, P.R. China.,Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous, Region, 530021, P.R. China
| | - Yi-Zhong Ge
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Qi Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Zi-Wen Wang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Xi Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - He-Yang Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Meng Tang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Meng-Meng Song
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Xiao-Wei Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Ming Yang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Yong-Bing Chen
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Kai-Ying Yu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Li Deng
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Kun-Hua Wang
- Yunnan university, Kunming, 650091, China. .,General surgery clinical medical center of Yunnan province, Kunming, 650032, China.
| | - Ming-Hua Cong
- Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, China.
| | - Han-Ping Shi
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. .,Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China.
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Tampe D, Kopp SB, Baier E, Hakroush S, Tampe B. Compartmentalization of Intrarenal Programmed Cell Death Protein 1-Ligand 1 and Its Receptor in Kidney Injury Related to Immune Checkpoint Inhibitor Nephrotoxicity. Front Med (Lausanne) 2022; 9:902256. [PMID: 35755033 PMCID: PMC9218249 DOI: 10.3389/fmed.2022.902256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 05/20/2022] [Indexed: 11/13/2022] Open
Abstract
Background Due to advances in cancer therapy, immune checkpoint inhibitors (ICIs) are new classes of drugs targeting programmed cell death protein 1-ligand 1 (PD-L1) or its receptor (PD-1) used in many cancer therapies. Acute interstitial nephritis (AIN) is a potential and deleterious immune-related adverse events (irAE) and the most common biopsy-proven diagnosis in ICI-related nephrotoxicity. AIN in patients receiving ICIs is was only seen in cases with tubular PD-L1 positivity, while PD-1 expression is limited to inflammatory cells and also observed in injured kidneys independent of ICI therapy. We have previously described that PD-L1 positivity can also be detected in glomerular and endothelial compartments. We here aimed to describe compartmentalization of renal PD-L1 expression specifically in injured kidneys with confirmed nephrotoxicity related to ICIs, its association with presence of PD-1, and clinical findings. Methods We included human kidney samples with AIN related to ICI therapy to describe PD-L1 and PD-1 expression localized to different renal compartments in association with clinical and laboratory parameters. Results We herein report compartmentalization of PD-L1 with tubular positivity in all cases, partially overlapping with glomerular and endothelial PD-L1 positivity. Furthermore, we provide evidence that tubular PD-L1 in ICI-related nephrotoxicity correlates with levels of C-reactive protein (CRP), while glomerular and endothelial PD-L1 positivity with lower serum levels of complement component C4. Interestingly, glomerular PD-L1 correlated with kidney function, while interstitial cell PD-1 positivity specifically with severity of kidney injury. Finally, we provide evidence for signaling pathways associated with intrarenal PD-L1/PD-1 expression. Conclusion Our findings implicate that that AIN related to ICI therapy requires presence of interstitial cells positive for PD-1, and that blocking PD-L1/PD-1 signaling may contribute to nephrotoxicity specifically related to these agents.
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Affiliation(s)
- Désirée Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Sarah Birgit Kopp
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Eva Baier
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Samy Hakroush
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
| | - Björn Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Naganuma A, Aoki T, Koizumi Y, Nakamura S, Joko K, Hiasa Y, Kudo M. C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib. Sci Rep 2022; 12:8421. [PMID: 35589772 PMCID: PMC9120140 DOI: 10.1038/s41598-022-12058-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 04/18/2022] [Indexed: 11/08/2022] Open
Abstract
We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2-22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥ 0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495-2.452), Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.429), and α-fetoprotein ≥ 400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR (p < 0.001). Median progression-free survival was 7.5 (95% CI, 6.7-8.1) months. Multivariate analysis showed that age, CAR ≥ 0.108 (HR, 1.644; 95% CI, 1.324-2.043), and non-hepatitis B, non-hepatitis C etiology (HR, 0.726) were independently associated with progression-free survival. Cumulative progression-free survival differed significantly between patients with low versus high CAR (p < 0.001). CAR values were significantly higher as Japan Integrated Staging score increased (p < 0.001). In conclusion, CAR can predict outcomes in patients with unresectable HCC treated with lenvatinib.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, 1-12-1 Shimoteno, Himeji, Hyogo, 670-8540, Japan.
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Shinya Fukunishi
- Department of Gastroenterology, Osaka Medical College, Osaka, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Hironori Ochi
- Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Kazuhito Kawata
- Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takaaki Tanaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hideko Ohama
- Department of Gastroenterology, Osaka Medical College, Osaka, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, 1-12-1 Shimoteno, Himeji, Hyogo, 670-8540, Japan
| | - Kouji Joko
- Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
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Gil-Herrero L, Pollán M, Martín M, López-Tarruella S, Castellanos M, Casla-Barrio S. The importance of physical exercise in cardiovascular fitness in breast cancer survivors. A cross-sectional study: women in Motion 2.0. Support Care Cancer 2022; 30:6745-6754. [PMID: 35524144 DOI: 10.1007/s00520-022-06993-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/15/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE To compare the cardiovascular fitness of breast cancer (BC) survivors with an active lifestyle to those with a sedentary lifestyle. METHODS A cross-sectional study was conducted. Participants were classified into four groups: two groups of active women who performed more than 150 min/week of physical exercise, active with BC (Act-BCW) and active without BC (Act-HW); and two groups of sedentary women who performed less than 90 min/week of physical exercise, sedentary with BC (Sed-BCW) and sedentary without BC (Sed-HW). VO2max was estimated by the 6-min walking test (6MWT); speed, isometric strength, lower body maximum strength, explosive strength, balance, and body composition were also measured. ANOVA was used to analyze group differences and post hoc comparisons were developed with the Bonferroni test. RESULTS A total of 92 women were recruited. Significant differences were found in VO2max between the Act-BCW and Sed-BCW groups (MeanDif = 5.86, p < 0.001). No differences in VO2max were observed between the active groups (MeanDif = 0.42, p = 0.753). Related body composition and fat mass levels were significantly lower in the Act-BCW group than in the sedentary groups (Sed-BCW MeanDif = - 6.78; p = 0.012; and Sed-HW MeanDif = - 12.07; p < 0.001). CONCLUSIONS Women who are Act-BCW can achieve similar values in physical condition as women who are Act-HW and have better values than women who are sedentary. Furthermore, our results suggest than physical activity level may have a greater impact in body composition than a previous history of BC.
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Affiliation(s)
| | | | - Miguel Martín
- Hospital General Universitario Gregorio Marañon, Madrid, Spain
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Liu T, Zhang Q, Song C, Siyin ST, Chen S, Zhang Q, Song M, Cao L, Shi H. C‐Reactive
Protein Trajectories and the Risk of All Cancer Types: A Prospective Cohort Study. Int J Cancer 2022; 151:297-307. [PMID: 35368093 PMCID: PMC9325055 DOI: 10.1002/ijc.34012] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/21/2022] [Accepted: 03/28/2022] [Indexed: 11/17/2022]
Abstract
A single CRP measurement is insufficient to examine the association of long‐term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new‐onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific‐site cancer. Four CRP trajectories patterns were identified: low‐stable pattern (n = 43 258), moderate‐increasing pattern (n = 2591), increasing‐decreasing pattern (n = 2068) and elevated‐decreasing pattern (n = 4359). Relative to the low‐stable pattern, the moderate‐increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing‐decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing‐decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated‐decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia.
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Affiliation(s)
- Tong Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition Capital Medical University Affiliated Beijing Shijitan Hospital Beijing China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China
- Key Laboratory of Cancer FSMP for State Market Regulation Beijing China
| | - Qingsong Zhang
- Department of General Surgery Kailuan General Hospital Tangshan China
| | - Chunhua Song
- Department of Epidemiology and Statistics, College of Public Health Zhengzhou University Zhengzhou Henan China
| | - Sarah Tan Siyin
- Department of General Surgery, Beijing Children's Hospital National Center for Children's Health Beijing China
| | - Shuohua Chen
- Department of Cardiology Kailuan General Hospital Tangshan China
| | - Qi Zhang
- Department of Gastrointestinal Surgery/Clinical Nutrition Capital Medical University Affiliated Beijing Shijitan Hospital Beijing China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China
- Key Laboratory of Cancer FSMP for State Market Regulation Beijing China
| | - Mengmeng Song
- Department of Gastrointestinal Surgery/Clinical Nutrition Capital Medical University Affiliated Beijing Shijitan Hospital Beijing China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China
- Key Laboratory of Cancer FSMP for State Market Regulation Beijing China
| | - Liying Cao
- Department of Hepatological Surgery Kailuan General Hospital Tangshan China
| | - Hanping Shi
- Department of Gastrointestinal Surgery/Clinical Nutrition Capital Medical University Affiliated Beijing Shijitan Hospital Beijing China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China
- Key Laboratory of Cancer FSMP for State Market Regulation Beijing China
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Lee MH, Liu KH, Thomas JL, Chen CY, Chen CY, Yang CH, Lin HY. Doping of MXenes enhances the electrochemical response of peptide-imprinted conductive polymers for the recognition of C-Reactive protein. Biosens Bioelectron 2022; 200:113930. [PMID: 34979348 DOI: 10.1016/j.bios.2021.113930] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 12/15/2021] [Accepted: 12/26/2021] [Indexed: 01/08/2023]
Abstract
The level of C-reactive protein (CRP) in serum is frequently used to evaluate risk of coronary heart disease, and its concentration is related to cardiovascular disease, fibrosis and inflammation, cancer, and viral infections. In this work, three novel peptides, never previously used as imprinted templates, were selected, synthesized, and employed for epitope imprinting. Various imprinting concentrations of the template and various ratios of aniline (AN) to m-aminobenzenesulfonic acid (MSAN) were used in electropolymerization to form molecularly imprinted polymers (MIPs). The imprinting template and functional monomer concentrations were optimized to maximize the electrochemical response to target peptides. The surface morphologies of peptide- and non-imprinting poly(AN-co-MSAN) were observed using a scanning electron microscope (SEM) and an atomic force microscope (AFM). Moreover, the effect of doping of MIPs with a very small percentage of an MXene (e.g. Ti2C at 0.1 wt% in the preparation solution) on the electrochemical response was also studied. Ti2C doping dramatically increased sensing range from 0.1 to 100 fg/mL to 10000 fg/mL, and electrochemical responses were amplified by a factor of approximately 1.3 within the sensing range. Finally, commercially available serum was diluted and then measured using the MXene-doped PIP-coated electrodes to estimate the accuracy compared with ELISA results.
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Affiliation(s)
- Mei-Hwa Lee
- Department of Materials Science and Engineering, I-Shou University, Kaohsiung, 84001, Taiwan
| | - Kai-Hsi Liu
- Department of Internal Medicine, Division of Cardiology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, 81342, Taiwan; Department of Electrical Engineering, National University of Kaohsiung, Kaohsiung, 81148, Taiwan
| | - James L Thomas
- Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM, 87131, USA
| | - Chen-Yuan Chen
- Department of Chemical and Materials Engineering, National University of Kaohsiung, Kaohsiung, 81148, Taiwan
| | - Chuen-Yau Chen
- Department of Electrical Engineering, National University of Kaohsiung, Kaohsiung, 81148, Taiwan
| | - Chien-Hsin Yang
- Department of Chemical and Materials Engineering, National University of Kaohsiung, Kaohsiung, 81148, Taiwan
| | - Hung-Yin Lin
- Department of Chemical and Materials Engineering, National University of Kaohsiung, Kaohsiung, 81148, Taiwan.
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Kgokolo MCM, Anderson K, Siwele SC, Steel HC, Kwofie LLI, Sathekge MM, Meyer PWA, Rapoport BL, Anderson R. Elevated Levels of Soluble CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3 and Systemic Inflammatory Stress as Potential Contributors to Immune Suppression and Generalized Tumorigenesis in a Cohort of South African Xeroderma Pigmentosum Patients. Front Oncol 2022; 12:819790. [PMID: 35223501 PMCID: PMC8874270 DOI: 10.3389/fonc.2022.819790] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/20/2022] [Indexed: 12/03/2022] Open
Abstract
Xeroderma Pigmentosum (XP), an autosomal recessive disorder characterized by ultraviolet radiation-induced abnormalities of DNA excision and repair pathways is associated with early development of cutaneous cancers. Intracellular oxidative stress has also been proposed as a contributor to the occurrence of skin cancers. However, little is known about the possible augmentative contributions of chronic inflammation, immune suppression and oxidative stress to the pathogenesis of malignancies associated with other subtypes of XP. This has been addressed in the current study, focused on the measurement of systemic biomarkers of inflammation, immune dysfunction and oxidative damage in XP patients, consisting of XP-C, XP-D and XP-E cases, including those XP-C cases who had already developed multiple skin malignancies. The inflammatory biomarker profile measured in XP patients and healthy control subjects included the cytokines, interleukins (ILs)-2, -4, -6, -10, interferon-γ (IFN- γ) and tumor-necrosis factor-α (TNF-α), the acute phase reactant, C-reactive protein (CRP), and cotinine (as an objective indicator of smoking status). Immune suppression was detected according to the levels of five soluble inhibitory immune checkpoint proteins (CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3), as well as those of vitamin D, while oxidative stress was determined according to the circulating levels of the DNA adduct, 8-hydroxy-2-deoxyguanosine (8-OH-dG). These various biomarkers were measured in plasma using immunofluorimetric, nephelometric and ELISA procedures. Significant elevations in IL-6 (P<0.01) and TNF-α (P<0.0001), but none of the other cytokines, as well as increased levels of all five soluble inhibitory immune checkpoints (P=0.032-P=0.0001) were detected in the plasma of the XP patients. C-reactive protein and vitamin D were increased and decreased, respectively (both P<0.0001), while only one participant had an elevated level of plasma cotinine. Surprisingly, the levels of 8-OH-dG were significantly (P=0.0001) lower in the group of XP patients relative to a group of healthy control subjects. The findings of increased levels of pro-inflammatory cytokines and, in particular, those of the soluble immune checkpoints, in the setting of decreased vitamin D and moderately elevated levels of CRP in XP patients suggest a possible secondary role of ongoing, inflammatory stress and immune suppression in the pathogenesis of XP-associated malignancies.
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Affiliation(s)
- Mahlatse C M Kgokolo
- Department of Dermatology, Faculty of Health Sciences, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa
| | - Katherine Anderson
- Department of Dermatology, Faculty of Health Sciences, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa
| | - Shalate C Siwele
- Department of Dermatology, Faculty of Health Sciences, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa
| | - Helen C Steel
- Department of Immunology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Luyanda L I Kwofie
- Department of Immunology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.,Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa
| | - Mike M Sathekge
- Department of Nuclear Medicine, Faculty of Nuclear Medicine, Faculty of Health Sciences, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa
| | - Pieter W A Meyer
- Department of Immunology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.,Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa
| | - Bernardo L Rapoport
- Department of Immunology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.,The Medical Oncology Centre of Rosebank, Johannesburg, South Africa
| | - Ronald Anderson
- Department of Immunology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
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Ji M, Du L, Ma Z, Xie J, Huang Y, Wei X, Jiang X, Xu J, Yin R, Wang Y, Dai J, Jin G, Xu L, Zhu C, Hu Z, Ma H, Zhu M, Shen H. Circulating C-reactive protein increases lung cancer risk: Results from a prospective cohort of UK Biobank. Int J Cancer 2022; 150:47-55. [PMID: 34449869 DOI: 10.1002/ijc.33780] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023]
Abstract
Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; Pnonadjusted = .003, Padjusted = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers.
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Affiliation(s)
- Mengmeng Ji
- Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.,Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Lingbin Du
- Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Zhimin Ma
- Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.,Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Junxing Xie
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yanqian Huang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiaoxia Wei
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiangxiang Jiang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jing Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Rong Yin
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yuzhuo Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Juncheng Dai
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Guangfu Jin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Lin Xu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Chen Zhu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Zhibin Hu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Hongxia Ma
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Meng Zhu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Hongbing Shen
- Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.,Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, China
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50
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Jensen GL, Naziri J, Hammonds KP, Jhavar SG, Swanson G. C-Reactive Protein Is a Poor Marker of Baseline Inflammation in Prostate Cancer and Response to Radiotherapy or Androgen Ablation. Cureus 2021; 13:e19639. [PMID: 34926085 PMCID: PMC8673689 DOI: 10.7759/cureus.19639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2021] [Indexed: 11/09/2022] Open
Abstract
Introduction C-reactive protein (CRP) is an acute-phase reactant used as a general marker for inflammation. Isolated levels have been associated with prostate cancer development, prostate-specific antigen (PSA), Gleason score, and treatment response. We seek to establish whether CRP levels reflect inflammation caused by prostate cancer by comparing levels at various points of time before, during, and after therapy. Materials and methods A total of 209 patients had a complete blood count (CBC), PSA, and CRP taken at up to four different time points. Labs were performed up to one week prior to androgen ablation via leuprolide injection (pre-AA), up to one week prior to radiotherapy (RT) (pre-RT), within one week of RT completion (post-RT), and three months following RT completion (FU [follow-up]). Results Significant relationships were found between CRP and WBC pre-AA (p-value=0.0050), pre-RT (p-value=0.0170), and post-RT (p-value=0.0113), but not at FU (p=.096). CRP had no significant relationship with PSA or lymphocytes at any time points. PSA was significantly affected by androgen ablation but lymphocytes, WBCs, and CRP were not. No CRP levels were associated with risk groups or FU-PSA. Lymphatic radiation fields significantly decreased WBCs and lymphocytes but not CRP. PSA, WBC, and lymphocytes all significantly decreased from pre-RT to post-RT, followed by a significant recovery. CRP did not significantly change during any of these periods and was not significantly related to changes in PSA, WBCs, or lymphocytes. Conclusion CRP is not a sensitive marker of the acute inflammatory effects of non-metastatic prostate cancer and treatment response with androgen ablation or radiation therapy.
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Affiliation(s)
- Garrett L Jensen
- Radiation Oncology, Baylor Scott & White Medical Center - Temple, Temple, USA
| | - Jason Naziri
- Radiation Oncology, Baylor Scott & White Health, Temple, USA
| | | | - Sameer G Jhavar
- Radiation Oncology, Baylor Scott & White Medical Center - Temple, Temple, USA
| | - Gregory Swanson
- Radiation Oncology, Baylor Scott & White Health, Temple, USA
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