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Yin X, Deng N, Ding XY, Chen JL, Sun W. CRAFITY score and nomogram predict the clinical efficacy of lenvatinib combined with immune checkpoint inhibitors in hepatocellular carcinoma. World J Gastroenterol 2025; 31:101672. [PMID: 39991685 PMCID: PMC11755258 DOI: 10.3748/wjg.v31.i7.101672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/03/2024] [Accepted: 12/30/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab, with little investigation in its predictive capacity for alternative regimens, such as lenvatinib and programmed cell death protein 1 (PD-1) inhibitors, which are widely utilized in Chinese clinical practice. AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors. METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022. Patients were stratified according to CRAFITY score (based on baseline alpha-fetoprotein and C-reactive protein levels) into CRAFITY-low, CRAFITY-intermediate, and CRAFITY-high groups. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis, and independent prognostic factors were identified through Cox regression analysis. Nomograms were created to forecast survival for a year. RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group, followed by those in the CRAFITY-intermediate and CRAFITY-high groups (median PFS: 8.4 months, 6.0 months, and 3.1 months, P < 0.0001; median OS: 33.4 months, 19.2 months, and 6.6 months, P < 0.0001). Both the objective response rate (5%, 19.6%, and 22%, P = 0.0669) and the disease control rate (50%, 76.5%, and 80%, P = 0.0023) were considerably lower in the CRAFITY-high group. The findings from the multivariate analysis showed that a nomogram which included the tumor number, prior transarterial chemoembolization history, and CRAFITY score predicted 12-month survival with an area under the curve of 0.788 (95% confidence interval: 0.718-0.859), which was in good agreement with actual data. CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.
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Affiliation(s)
- Xue Yin
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Na Deng
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Yan Ding
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Jing-Long Chen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Wei Sun
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Zhang Q, Xu Z, Long L, Luo X, Wang R, Zhu K. Predictive value of neutrophil-to-lymphocyte ratio for long-term adverse outcomes in cirrhosis patients post-transjugular intrahepatic portosystemic shunt. Sci Rep 2025; 15:797. [PMID: 39755906 PMCID: PMC11700169 DOI: 10.1038/s41598-024-84630-7] [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: 08/19/2024] [Accepted: 12/25/2024] [Indexed: 01/06/2025] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) may predict outcomes in end-stage liver disease, but its value after transjugular intrahepatic portosystemic shunt (TIPS) is unclear. This study explored the link between NLR and long-term outcomes in decompensated cirrhosis patients post-TIPS. We retrospectively analyzed 184 patients treated between January 2016 and December 2021, noting demographic data, lab results, and follow-up outcomes, including liver transplantation or death. Cox regression, adjusted for various factors, showed that NLR is an independent predictor of post-TIPS progression (HR 1.665; 95% CI 1.149-2.414; P = 0.007). Patients were divided into tertiles based on NLR. The medium tertile had a 3.51-fold increased risk of progression compared to the lowest (HR 3.510; 95% CI 1.104-11.153, P = 0.033), and the highest tertile had a 5.112-fold increase (HR 5.112; 95% CI 1.653-15.806, P = 0.005). This suggests that NLR is a valuable prognostic marker for long-term progression in these patients, highlighting the role of systemic inflammation.
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Affiliation(s)
- Qian Zhang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, China
- Department of Radiology, Guizhou Provincial People' s Hospital, Guiyang, 550002, Guizhou, China
| | - Zi Xu
- Department of Radiology, Guizhou Provincial People' s Hospital, Guiyang, 550002, Guizhou, China
| | - Li Long
- Department of Infectious Diseases, Guizhou Provincial People' s Hospital, Guiyang, 550002, Guizhou, China
| | - Xinhua Luo
- Department of Infectious Diseases, Guizhou Provincial People' s Hospital, Guiyang, 550002, Guizhou, China
| | - Rongpin Wang
- Department of Radiology, Guizhou Provincial People' s Hospital, Guiyang, 550002, Guizhou, China.
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, China.
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Silva C, Abrantes AC, Fontes AC, Dias I, Domingues R, Peixoto F, Viegas C. Evaluation of Haematological Ratios at: Different Stages of Canine Periodontal Disease. Vet Sci 2024; 11:581. [PMID: 39591355 PMCID: PMC11599070 DOI: 10.3390/vetsci11110581] [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: 10/15/2024] [Revised: 11/10/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
This is a retrospective study about haematological ratios in different stages of canine periodontal disease in one single breed, more specifically the Portuguese Podengo. The aim of the study was to assess the clinical significance of five haematological ratios, namely neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-platelet count ratio (MPV/PLT), monocyte-to-lymphocyte ratio (MLR), and platelet-to-neutrophil ratio (PNR), easily obtained through the parameters provided by the complete blood count, in the stages of gingivitis and periodontitis, compared to clinical healthy individuals. Receiver operating characteristic curves were generated to identify ideal sensitivity and specificity cut-offs for cases of gingivitis or periodontitis. Our study included 80 dogs, which comprised 24 healthy dogs, 26 diagnosed with gingivitis, and 30 with periodontitis. The median NLR was significantly lower in periodontitis than in clinical healthy dogs (p = 0.040) and in dogs with gingivitis (p = 0.037). The median PLR was significantly lower in cases of gingivitis (p = 0.020) and periodontitis (p = 0.024) than in healthy dogs. MPV/PLT and MLR did not demonstrate significant differences between any of the three groups. The median PNR was significantly lower in gingivitis than in control dogs (p = 0.019). PNR had the highest accurate results, in distinguishing between healthy individuals and those with gingivitis, with an area under the curve of 0.692 (95% CI [0.539-0.845], p = 0.020). However, even this index had weak discriminatory power between the groups in the analysis. The impact of systemic inflammation generated by canine periodontal disease can thus be seen through some of these indices. However, the results obtained here demonstrate the need for complementarity with other methods to diagnose canine periodontal disease and reinforce the need for additional studies with more markers of systemic inflammatory response.
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Affiliation(s)
- Carolina Silva
- Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal; (C.S.); (A.C.A.); (A.C.F.); (I.D.)
- Animal and Veterinary Research Center (CECAV)—AL4AnimalS, University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Ana Carolina Abrantes
- Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal; (C.S.); (A.C.A.); (A.C.F.); (I.D.)
- Animal and Veterinary Research Center (CECAV)—AL4AnimalS, University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Ana Carolina Fontes
- Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal; (C.S.); (A.C.A.); (A.C.F.); (I.D.)
- Animal and Veterinary Research Center (CECAV)—AL4AnimalS, University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Isabel Dias
- Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal; (C.S.); (A.C.A.); (A.C.F.); (I.D.)
- Animal and Veterinary Research Center (CECAV)—AL4AnimalS, University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- CITAB-Centre for the Research and Technology of Agro-Environmental and Biological Sciences—Inov4Agro, University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Rosário Domingues
- Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;
- CESAM, Departament of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
| | - Francisco Peixoto
- Chemistry Center of Vila Real, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal;
- RISE-Health: Health Research Network, Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
| | - Carlos Viegas
- Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal; (C.S.); (A.C.A.); (A.C.F.); (I.D.)
- Animal and Veterinary Research Center (CECAV)—AL4AnimalS, University of Trás-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- CIVG—Vasco da Gama Research Center, University School Vasco da Gama (EUVG), Campus Universitário, Avenida José Rodrigues Sousa Fernandes, Lordemão, 3020-210 Coimbra, Portugal
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Arshad RG, Toori KU. Correlation between neutrophil to lymphocyte ratio and C-reactive protein in diverse disease states in hospitalized patients. Pak J Med Sci 2024; 40:1989-1993. [PMID: 39416637 PMCID: PMC11476157 DOI: 10.12669/pjms.40.9.8933] [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: 10/12/2023] [Revised: 05/27/2024] [Accepted: 05/31/2024] [Indexed: 10/19/2024] Open
Abstract
Objectives This study aims to find if any significant correlation exists between C-reactive protein and Neutrophil to Lymphocyte Ratio as an indirect measure of inflammation. Methods We selected 983 patients with any inflammatory condition who presented to a tertiary care hospital and were admitted in medical wards or Intensive Care Units (ICUs) of KRL Hospital Islamabad from December 2021 to December 2022. The study was a cross sectional study and convenience sampling was done. The patients were categorized into five groups depending upon their pathophysiology. Kolmogorov Smirnov test was used to assess the normality of the data, and Spearman's coefficient was used to calculate the correlation between NLR and CRP. Results A total of 983 patients were included. Mean CRP and NLR levels were 89.9±3.2 and 7.06±0.24, respectively. There was a significant positive correlation between CRP-NLR in the infectious, non-infectious non-inflammatory, and malignancy groups (0.420, 0.381, 0.642, p <0.01), and inflammatory group (0.322, p <0.05), and no correlation with chronic diseases. Conclusion A significant correlation was shown to exist between CRP and NLR in patients with malignancies, non-infective non-inflammatory, inflammatory, and infective conditions and can therefore be used interchangeably to detect the presence of inflammation. Further exploration of these associations may contribute to a more nuanced understanding of the intricate relationships between different markers of inflammation and response to treatment.
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Affiliation(s)
- Ramsha Ghazal Arshad
- Ramsha Ghazal Arshad, MBBS. Post Graduate Trainee Medicine, KRL Hospital, Islamabad, Pakistan
| | - Kaleem Ullah Toori
- Kaleem Ullah Toori. MBBS, FRCP. Head of Department Medicine, KRL Hospital, Islamabad, Pakistan
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Walther K, Gröger S, Vogler JAH, Wöstmann B, Meyle J. Inflammation indices in association with periodontitis and cancer. Periodontol 2000 2024; 96:281-315. [PMID: 39317462 PMCID: PMC11579835 DOI: 10.1111/prd.12612] [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: 05/16/2024] [Revised: 08/18/2024] [Accepted: 08/20/2024] [Indexed: 09/26/2024]
Abstract
Inflammation is a complex physiological process that plays a pivotal role in many if not all pathological conditions, including infectious as well as inflammatory diseases, like periodontitis and autoimmune disorders. Inflammatory response to periodontal biofilms and tissue destruction in periodontitis is associated with the release of inflammatory mediators. Chronic inflammation can promote the development of cancer. Persistence of inflammatory mediators plays a crucial role in this process. Quantification and monitoring of the severity of inflammation in relation to cancer is essential. Periodontitis is mainly quantified based on the severity and extent of attachment loss and/or pocket probing depth, in addition with bleeding on probing. In recent years, studies started to investigate inflammation indices in association with periodontal diseases. To date, only few reviews have been published focusing on the relationship between blood cell count, inflammation indices, and periodontitis. This review presents a comprehensive overview of different systemic inflammation indices, their methods of measurement, and the clinical applications in relation to periodontitis and cancer. This review outlines the physiological basis of inflammation and the underlying cellular and molecular mechanisms of the parameters described. Key inflammation indices are commonly utilized in periodontology such as the neutrophil to lymphocyte ratio. Inflammation indices like the platelet to lymphocyte ratio, platelet distribution width, plateletcrit, red blood cell distribution width, lymphocyte to monocyte ratio, delta neutrophil index, and the systemic immune inflammation index are also used in hospital settings and will be discussed. The clinical roles and limitations, relationship to systemic diseases as well as their association to periodontitis and treatment response are described.
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Affiliation(s)
- Kay‐Arne Walther
- Department of Periodontology, Dental ClinicJustus Liebig University of GiessenGiessenGermany
- Department of Prosthodontics, Dental ClinicJustus Liebig University of GiessenGiessenGermany
| | - Sabine Gröger
- Department of Periodontology, Dental ClinicJustus Liebig University of GiessenGiessenGermany
- Department of Orthodontics, Dental ClinicJustus Liebig University of GiessenGiessenGermany
| | | | - Bernd Wöstmann
- Department of Periodontology, Dental ClinicJustus Liebig University of GiessenGiessenGermany
- Department of Prosthodontics, Dental ClinicJustus Liebig University of GiessenGiessenGermany
| | - Jörg Meyle
- Department of Periodontology, Dental ClinicJustus Liebig University of GiessenGiessenGermany
- Department of Periodontology, Dental ClinicUniversity of BernBernSwitzerland
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Consalvo S, Hinterwimmer F, Stephan M, Breden S, Lenze U, Peeken J, von Eisenhart-Rothe R, Knebel C. C-Reactive Protein Pretreatment-Level Evaluation with Histopathological Correlation for Chondrosarcoma Prognosis Assessment-A 15-Year Retrospective Single-Center Study. Diagnostics (Basel) 2024; 14:1428. [PMID: 39001318 PMCID: PMC11241698 DOI: 10.3390/diagnostics14131428] [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: 06/03/2024] [Revised: 06/22/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND An aberrant cellular microenvironment characterized by pathological cells or inflammation represents an added risk factor across various cancer types. While the significance of chronic inflammation in the development of most diffuse tumors has been extensively studied, an exception to this analysis exists in the context of chondrosarcomas. Chondrosarcomas account for 20-30% of all bone sarcomas, with an estimated global incidence of 1 in 100,000. The average age at diagnosis is 50, and over 70% of patients are over 40. This retrospective study aimed to examine the role of C-reactive protein (CRP) as a prognostic factor in relation to the histopathological findings in chondrosarcoma. METHODS In this retrospective study, 70 patients diagnosed with chondrosarcoma and treated between 2004 and 2019 were included. Preoperative CRP levels were measured in mg/dL, with non-pathological values defined as below 0.5 mg/dL. Disease-free survival time was calculated from the initial diagnosis to events such as local recurrence or metastasis. Follow-up status was categorized as death from disease, no evidence of disease, or alive with disease. Patients were excluded if they had insufficient laboratory values, missing follow-up information, or incomplete histopathological reports. RESULTS The calculated risk estimation of a reduced follow-up time was 2.25 timed higher in the patients with a CRP level >0.5 mg/dL (HR 2.25 and 95% CI 1.13-4.45) and 3 times higher in patients with a tumor size > pT2 (HR 3 and 95% CI 1.59-5.92). We can easily confirm that risk factors for reduced prognosis lie in chondrosarcoma high grading, preoperative pathological CRP- level, and a size > 8 cm. CONCLUSIONS A pretreatment CRP value greater than 0.5 mg/dL can be considered a sensitive prognostic and risk factor for distant metastasis for chondrosarcoma patients.
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Affiliation(s)
- Sarah Consalvo
- Department of Orthopaedics and Sport Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (M.S.); (S.B.); (U.L.); (R.v.E.-R.); (C.K.)
| | - Florian Hinterwimmer
- Institute for AI and Informatics in Medicine, Technical University of Munich, 81675 Munich, Germany;
| | - Maximilian Stephan
- Department of Orthopaedics and Sport Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (M.S.); (S.B.); (U.L.); (R.v.E.-R.); (C.K.)
| | - Sebastian Breden
- Department of Orthopaedics and Sport Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (M.S.); (S.B.); (U.L.); (R.v.E.-R.); (C.K.)
| | - Ulrich Lenze
- Department of Orthopaedics and Sport Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (M.S.); (S.B.); (U.L.); (R.v.E.-R.); (C.K.)
| | - Jan Peeken
- Department of Radiooncology and Radiotherapy, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany;
| | - Rüdiger von Eisenhart-Rothe
- Department of Orthopaedics and Sport Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (M.S.); (S.B.); (U.L.); (R.v.E.-R.); (C.K.)
| | - Carolin Knebel
- Department of Orthopaedics and Sport Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (M.S.); (S.B.); (U.L.); (R.v.E.-R.); (C.K.)
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Imaoka K, Ohira M, Hattori M, Chogahara I, Sato S, Nakamura M, Bekki T, Sato K, Imaoka Y, Nakano R, Yano T, Sakai H, Kuroda S, Tahara H, Ide K, Kobayashi T, Tanaka Y, Ohdan H. Immunotherapy Using Activated Natural Killer Cells Improves Postoperative Neutrophil-to-Lymphocyte Ratio and Long-Term Prognosis of Living Donor Liver Transplant Recipients With Hepatocellular Carcinoma. Transplant Proc 2024; 56:634-639. [PMID: 38443302 DOI: 10.1016/j.transproceed.2024.02.002] [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: 10/14/2023] [Revised: 02/02/2024] [Accepted: 02/13/2024] [Indexed: 03/07/2024]
Abstract
OBJECTIVE Preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic indicator in various malignancies; however, the impact of postoperative NLR on living donor liver transplant (LDLT) recipients is unknown. Immunotherapy with donor liver-derived activated natural killer (NK) cells may improve postoperative NLR by coactivating immune cells or suppressing activated neutrophils. This study aims to clarify the clinical significance of postoperative NLR in recipients after LDLT with HCC and assess whether immunotherapy improves postoperative NLR. METHODS We conducted a retrospective study of LDLT recipients between 2001 and 2022 to evaluate the clinical significance of postoperative NLR. Furthermore, the correlation between postoperative NLR and the activation marker of infused NK cells was also evaluated. The postoperative NLR was examined 4 weeks after LDLT. RESULTS The postoperative high NLR group (N = 78) had preoperative lower NLR and higher model for end-stage liver disease and a higher rate of postoperative infection within 30 days after LDLT than the postoperative low NLR group (N = 41). Postoperative high NLR (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.01-6.79; P = .047) and nontreatment of immunotherapy (HR, 3.10; 95% CI, 1.33-7.22; P < .01) were independent risk factors for poor overall survival in multivariate analysis. Furthermore, the activation marker of infused NK cells is inversely correlated with decreased postoperative NLR. CONCLUSIONS The higher level of postoperative NLR was independently associated with poor prognosis in patients after LDLT with HCC. Immunotherapy using activated NK cells may improve postoperative NLR and long-term prognosis.
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Affiliation(s)
- Kouki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
| | - Minoru Hattori
- Advanced Medical Skills Training Center, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ichiya Chogahara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Saki Sato
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mayuna Nakamura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomoaki Bekki
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Koki Sato
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryosuke Nakano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Sakai
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Zhong J, Zong S, Wang J, Feng M, Wang J, Zhang H, Xiong L. Role of neutrophils on cancer cells and other immune cells in the tumor microenvironment. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119493. [PMID: 37201766 DOI: 10.1016/j.bbamcr.2023.119493] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/25/2023] [Accepted: 05/09/2023] [Indexed: 05/20/2023]
Abstract
The notion that neutrophils only perform a specific set of single functions in the body has changed with the advancement of research methods. As the most abundant myeloid cells in human blood, neutrophils are currently emerging as important regulators of cancer. Given the duality of neutrophils, neutrophil-based tumor therapy has been clinically carried out in recent years and has made some progress. But due to the complexity of the tumor microenvironment, the therapeutic effect is still not satisfactory. Therefore, in this review, we discuss the direct interaction of neutrophils with the five most common cancer cells and other immune cells in the tumor microenvironment. Also, this review covered current limitations, potential future possibilities, and therapeutic approaches targeting neutrophil function in cancer therapy.
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Affiliation(s)
- Junpei Zhong
- Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China
| | - Siwen Zong
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Jiayang Wang
- First Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Mingrui Feng
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Jie Wang
- Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Medical College, Fujian province university, Xiamen 361023, China
| | - Hongyan Zhang
- Department of Burn, The First Affiliated Hospital, Nanchang University, Nanchang 330066, China.
| | - Lixia Xiong
- Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China; Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Medical College, Fujian province university, Xiamen 361023, China.
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Hashemi SJ, Shokrian Tosi M, Hajiani E, Parsi A, Alavinejad P. The Association Between Peripheral Blood Neutrophil-to-Lymphocyte Ratio and Cirrhosis Complications in Adults with Compensated Liver Cirrhosis in Ahvaz, Iran. SHIRAZ E-MEDICAL JOURNAL 2023; 24. [DOI: 10.5812/semj-138859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background: The neutrophil-to-lymphocyte ratio (NLR) is an inflammation biomarker in patients with liver cirrhosis. While increased NLR is linked to poor clinical outcomes and mortality in diseases like cancers, its association with cirrhosis complications has been sparsely examined. Objectives: This study aimed to evaluate the association between NLR and cirrhosis complications in patients with compensated liver cirrhosis. Methods: This retrospective cohort study was conducted on 256 patients with compensated liver cirrhosis visiting the Gastroenterology Clinic of Imam Khomeini Hospital, Ahvaz, Iran, in 2020. The peripheral blood lymphocyte and neutrophil counts were evaluated, and the NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Cirrhosis complications were assessed based on clinical and laboratory evaluation during 1 year of follow-up. Results: During the retrospective follow-up period, 59 patients (23.05%) experienced cirrhosis complications such as spontaneous bacterial peritonitis (n = 23), gastrointestinal bleeding (n = 22), and hepatic encephalopathy (n = 14). The baseline NLR, Model for End-Stage Liver Disease (MELD) score and Child-Pugh score were significantly higher in patients who later developed complications than in those who did not (P < 0.0001). The NLR with an optimal cut-off of > 1.95 had a sensitivity of 84.75% and specificity of 93.91% in predicting complications during the 1-year follow-up (AUC = 0.905, P < 0.0001). Conclusions: Our results indicated that the NLR is a simple, non-invasive, and cost-effective marker for predicting short-term complications in patients with compensated liver cirrhosis.
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10
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Xu C, Wu F, Du L, Dong Y, Lin S. Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis. Front Immunol 2023; 14:1211399. [PMID: 37809083 PMCID: PMC10551132 DOI: 10.3389/fimmu.2023.1211399] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 09/05/2023] [Indexed: 10/10/2023] Open
Abstract
Objective Whether neutrophil-lymphocyte ratio (NLR) is an applicative predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) remains controversial. In response to the current conflicting data, this meta-analysis was conducted to gain a comprehensive and systematic understanding of prognostic value of NLR in HCC. Methods Several English databases, including PubMed, EMBASE, and the Cochrane Library, with an update date of February 25, 2023, were systematically searched. We set the inclusion criteria to include randomized controlled trial (RCT) studies that reported the prognostic value of serum NLR levels in patients with HCC receiving treatment. Both the combined ratio (OR) and the diagnosis ratio (DOR) were used to assess the prognostic performance of NLR. Additionally, we completed the risk of bias assessment by Cochrane Risk of Bias Assessment Tool. Results This meta-analysis ultimately included 16 studies with a total of 4654 patients with HCC. The results showed that high baseline NLR was significantly associated with poor prognosis or recurrence of HCC. The sensitivity of 0.67 (95% confidence interval [CI]. 0.59-0.73); specificity of 0.723 (95% CI: 0.64-0.78) and DOR of 5.0 (95% CI: 4.0-7.0) were pooled estimated from patient-based analyses. Subsequently, the combined positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were calculated with the results of 2.4 (95% CI: 1.9-3.0) and 0.46 (95% CI: 0.39-0.56), respectively. In addition, area under the curve (AUC) of the summary receiver operating characteristic (SROC) reflecting prognostic accuracy was calculated to be 0.75 (95% CI: 0.71-0.78). The results of subgroup analysis suggested that high NLR was an effective predictive factor of poor prognosis in HCC in mainland China as well as in the northern region. Conclusion Our findings suggest that high baseline NLR is an excellent predictor of poor prognosis or relapse in patients with HCC, especially those from high-incidence East Asian populations. Systematic review registration https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023440640.
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Affiliation(s)
- Chunhua Xu
- Shulan International Medical School, Zhejiang Shuren University, Hangzhou, China
| | - Fenfang Wu
- Department of Central Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Lailing Du
- Shulan International Medical School, Zhejiang Shuren University, Hangzhou, China
| | - Yeping Dong
- Shulan International Medical School, Zhejiang Shuren University, Hangzhou, China
| | - Shan Lin
- Department of Central Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong, China
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11
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Llorca-Bofí V, Bioque M, Font M, Gich I, Mur M. Correlation between C-reactive protein and the inflammatory ratios in acute schizophrenia inpatients: are they associated? J Psychiatr Res 2023; 165:191-196. [PMID: 37515951 DOI: 10.1016/j.jpsychires.2023.07.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/13/2023] [Accepted: 07/18/2023] [Indexed: 07/31/2023]
Abstract
C-reactive protein (CRP) and inflammatory ratios have been proposed to study immune dysregulation in schizophrenia. Nevertheless, links between CRP and inflammatory ratios in acute SCZ inpatients have been understudied. This study investigated the relationship between CRP and inflammatory ratios (Neutrophil-Lymphocyte Ratio [NRL], Platelet-Lymphocyte Ratio [PLR], Monocyte-Lymphocyte ratio [MLR] and Basophil-Lymphocyte Ratio [BLR]) in a total of 698 acute SCZ inpatients; and analysed how this relationship is affected by sex and type of episode. CRP correlated with NLR (rs = 0.338, p < 0.001), PLR (rs = 0.271, p < 0.001) and MLR (rs = 0.148, p < 0.001) but not with BLR (rs = 0.059, p = 0.121). Multiple lineal regression analysis showed that high levels of NLR, MLR and PLR but not BLR were independently associated with high CRP levels. No sex-related variations were found. Significant associations were maintained for NLR and MLR in first-episode and multiepisode SCZ, although the strength of the association was stronger in multiepisode SCZ. Again, no sex-related differences were found in these associations. In conclusion, inflammatory ratios were low to moderately associated with CRP in acute SCZ inpatients. NLR and multiepisode SCZ showed the highest associations with CRP. Future studies should consider inflammatory ratios not as a substitute for CRP but as a complementary biomarker.
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Affiliation(s)
- Vicent Llorca-Bofí
- Department of Medicine, University of Barcelona, Barcelona, Spain; Department of Psychiatry, Santa Maria University Hospital Lleida, Lleida, Spain; Institut de Recerca Biomèdica de Lleida (IRBLleida), Spain
| | - Miquel Bioque
- Department of Medicine, University of Barcelona, Barcelona, Spain; Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, CIBERSAM, IDIBAPS, Barcelona, Spain
| | - Maria Font
- Laboratory Department, Arnau de Vilanova University Hospital, Lleida, Spain
| | - Ignasi Gich
- CIBER Epidemiología y Salud Pública (CIBERESP), Department of Clinical Epidemiology and Public Health, HSCSP, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
| | - Maria Mur
- Department of Medicine and Surgery, Universitat de Lleida, Spain; Department of Psychiatry, Santa Maria University Hospital Lleida, Lleida, Spain; Institut de Recerca Biomèdica de Lleida (IRBLleida), Spain.
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12
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Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma. J Gastrointest Surg 2023:10.1007/s11605-023-05592-1. [PMID: 36857014 DOI: 10.1007/s11605-023-05592-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/07/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.
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Serum C-NLR score, a new inflammatory marker, predicts tumor histopathology and oncological outcomes of localized clear cell renal carcinoma after nephrectomy: A single center retrospective analysis. JOURNAL OF SURGERY AND MEDICINE 2023. [DOI: 10.28982/josam.7663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Background/Aim: Several blood and serum-based parameters have been described as prognostic markers of clear cell renal cell carcinoma (ccRCC). But most of these markers have inconsistent results and are not used in routine clinical practice. Therefore, novel potential predictor biomarkers are needed for the management of ccRCC patients in clinical practice. Here, we investigate the predictive value of a novel marker, serum C-NLR score, for pathological characteristics and oncological outcomes of ccRCC.
Methods: A total of 162 RCC patients who underwent radical or partial nephrectomy between January 2015 and January 2021 were evaluated in a retrospective cohort study setting. The serum C-NLR score was compared according to the tumor histopathology-associated parameters. The predictive role of those parameters and C-NLR score on the oncological outcomes of ccRCC was also investigated.
Results: The median serum C-NLR scores exhibited statistically significant increases in ccRCC patients with pathological necrosis, lymphovascular invasion, and variant differentiation. Among histopathological characteristics, only tumor necrosis and variant differentiation were associated with overall survival (OS) and tumor grade with metastasis-free survival (MFS) (no metastasis detected in grade 1–2 tumors) in Kaplan Meier analyses. Serum C-NLR score was also associated with OS but not MFS. In the univariate analyses, tumor necrosis, variant differentiation, and C-NLR score were associated with OS of localized RCC patients who underwent nephrectomy (HR: 0.29; 95% CI: 0.08–1.01; P=0.04, HR: 6.01; 95% CI: 1.66–21.82; P=0.006 and, HR: 1.21; 95% CI: 0.20–5.16; P=0.04). However, in the multivariate analysis, only variant differentiation and C-NLR score were associated with OS (HR: 1.43; 95% CI: 0.82–2.98; P=0.03 and HR: 1.21; 95% CI: 0.20–5.16; P=0.04). Tumor grade was directly associated with MFS because grade 1–2 tumors did not exhibit any metastasis.
Conclusion: Serum C-NLR score was higher in worse histopathological entities. Moreover, it predicts the OS for patients with ccRCC as an independent factor.
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Sung PS, Lee IK, Roh PR, Kang MW, Ahn J, Yoon SK. Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go. Front Oncol 2022; 12:1028728. [PMID: 36387149 PMCID: PMC9659956 DOI: 10.3389/fonc.2022.1028728] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/17/2022] [Indexed: 09/08/2024] Open
Abstract
The introduction of immune checkpoint inhibitors (ICIs) represents a key shift in the management strategy for patients with hepatocellular carcinoma (HCC). However, there is a paucity of predictive biomarkers that facilitate the identification of patients that would respond to ICI therapy. Although several researchers have attempted to resolve the issue, the data is insufficient to alter daily clinical practice. The use of minimally invasive procedures to obtain patient-derived specimen, such as using blood-based samples, is increasingly preferred. Circulating tumor DNA (ctDNA) can be isolated from the blood of cancer patients, and liquid biopsies can provide sufficient material to enable ongoing monitoring of HCC. This is particularly significant for patients for whom surgery is not indicated, including those with advanced HCC. In this review, we summarize the current state of understanding of blood-based biomarkers for ICI-based therapy in advanced HCC, which is promising despite there is still a long way to go.
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Affiliation(s)
- Pil Soo Sung
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Isaac Kise Lee
- Department of Computer Science and Engineering, Incheon National University, Incheon, South Korea
| | - Pu Reun Roh
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
| | - Min Woo Kang
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
| | - Jaegyoon Ahn
- Department of Computer Science and Engineering, Incheon National University, Incheon, South Korea
| | - Seung Kew Yoon
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea
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Hashimoto K, Nishimura S, Shinyashiki Y, Ito T, Akagi M. Characterizing inflammatory markers in highly aggressive soft tissue sarcomas. Medicine (Baltimore) 2022; 101:e30688. [PMID: 36181081 PMCID: PMC9524936 DOI: 10.1097/md.0000000000030688] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The prognosis for soft tissue sarcomas (STSs) is poor, especially for highly aggressive STSs, and the details of prognostic factors are unknown. This study aimed to investigate the prognostic factors for STSs in hematologic inflammatory markers. We included 22 patients with STSs treated at our institution. The STSs were histologically classified as follows: undifferentiated pleomorphic sarcoma, 7 cases; myxofibrosarcoma, 6 cases; and malignant peripheral nerve sheath tumor, 2 cases. The average patient age was 72.06 years. The numbers of patients who underwent each procedure were as follows: wide resection, 7; wide resection and flap, 2; marginal resection, 2; wide resection and radiation, 1; additional wide resection with flap, 1; wide resection and skin graft, 1; and radiotherapy only, 1. The median follow-up period was 26 months (3-92 months). The outcomes were as follows: continuous disease free, 6 cases; no evidence of disease, 6 cases; alive with disease, 1 case; and died of disease, 2 cases. Pretreatment blood examinations for C-reactive protein (CRP) and albumin levels; neutrophil, lymphocyte, and white blood cell (WBC) counts; and neutrophil/lymphocyte (N/L) ratio were investigated and correlated with tumor size, tissue grade, and maximum standardized uptake value (SUVmax). CRP level and neutrophil and WBC counts were positively correlated with tissue grade and SUVmax. N/L ratio was positively correlated with tumor size and SUVmax. CRP level, WBC and neutrophil counts, and N/L ratio may be poor prognostic factors for highly aggressive STSs.
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Affiliation(s)
- Kazuhiko Hashimoto
- Department of Orthopedic Surgery, Kushimoto Municipal Hospital, Higashimuro-Gun, Wakayama, Japan
- Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan
- *Correspondence: Kazuhiko Hashimoto, Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka 589-8511, Japan (e-mail: )
| | - Shunji Nishimura
- Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan
| | - Yu Shinyashiki
- Department of Orthopedic Surgery, Kushimoto Municipal Hospital, Higashimuro-Gun, Wakayama, Japan
- Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan
| | - Tomohiko Ito
- Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan
| | - Masao Akagi
- Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan
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16
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Seyedi SA, Nabipoorashrafi SA, Hernandez J, Nguyen A, Lucke-Wold B, Nourigheimasi S, Khanzadeh S. Neutrophil to Lymphocyte Ratio and Spontaneous Bacterial Peritonitis among Cirrhotic Patients: A Systematic Review and Meta-analysis. Can J Gastroenterol Hepatol 2022; 2022:8604060. [PMID: 36204262 PMCID: PMC9532151 DOI: 10.1155/2022/8604060] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The goal of this systematic review and meta-analysis was analyzing published studies on the role of neutrophil to lymphocyte ratio (NLR) in infection and spatially spontaneous bacterial peritonitis (SBP) among cirrhotic patients. METHODS PubMed, Web of Science, and Scopus were searched until May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment. RESULTS Of 14 studies included in our study, six studies were on infection with 2786 hospitalized cirrhotic patients, of whom 934 developed an infection. Other studies were on SBP with 1573 cirrhotic patients with ascites, of whom 557 developed SBP. The pooled results showed that there was no difference in NLR levels between hospitalized cirrhotic patients who developed infection compared to those who did not (random-effects model: SMD = 0.63, 95% CI = -0.01-1.27, p=0.054). However, cirrhotic patients with ascites who developed SBP had elevated levels of NLR compared to those who did not (random-effects model: SMD = 1.05, 95% CI = 0.52-1.57,p < 0.001). This difference remained significant in prospective studies (SMD = 0.94, 95% CI = 0.51-1.38,p < 0.001) but not in retrospective studies (SMD = 1.37, 95% CI = -0.56-3.29,p=0.165), in the subgroup analysis according to the study design. The pooled sensitivity of NLR was 92.07% (95% CI = 74.85%-97.84%) and the pooled specificity was 72.58% (95% CI = 57.72%-83.69%). The pooled positive likelihood ratio, negative likelihood ratio, DOR of NLR were 3.35(95%CI = 2.06-5.46), 0.10 (95%CI = 0.03-0.38), and 30.78 (95%CI = 7.01-135.04), respectively. CONCLUSION Our results support NLR to be a valid biomarker that can be readily integrated into clinical settings to help in the prevention and prediction of SBP among cirrhotic patients.
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Affiliation(s)
- Seyed Arsalan Seyedi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran, Iran
| | - Seyed Ali Nabipoorashrafi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran, Iran
| | - Jairo Hernandez
- Department of Neurosurgery, University of Florida, Gainesville, USA
| | - Andrew Nguyen
- Department of Neurosurgery, University of Florida, Gainesville, USA
| | | | | | - Shokoufeh Khanzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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17
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Deng PZ, Zhao BG, Huang XH, Xu TF, Chen ZJ, Wei QF, Liu XY, Guo YQ, Yuan SG, Liao WJ. Preoperative contrast-enhanced computed tomography-based radiomics model for overall survival prediction in hepatocellular carcinoma. World J Gastroenterol 2022; 28:4376-4389. [PMID: 36159012 PMCID: PMC9453776 DOI: 10.3748/wjg.v28.i31.4376] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/14/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with a rising incidence worldwide. The prognosis of HCC patients after radical resection remains poor. Radiomics is a novel machine learning method that extracts quantitative features from medical images and provides predictive information of cancer, which can assist with cancer diagnosis, therapeutic decision-making and prognosis improvement.
AIM To develop and validate a contrast-enhanced computed tomography-based radiomics model for predicting the overall survival (OS) of HCC patients after radical hepatectomy.
METHODS A total of 150 HCC patients were randomly divided into a training cohort (n = 107) and a validation cohort (n = 43). Radiomics features were extracted from the entire tumour lesion. The least absolute shrinkage and selection operator algorithm was applied for the selection of radiomics features and the construction of the radiomics signature. Univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors and develop the predictive nomogram, incorporating clinicopathological characteristics and the radiomics signature. The accuracy of the nomogram was assessed with the concordance index, receiver operating characteristic (ROC) curve and calibration curve. The clinical utility was evaluated by decision curve analysis (DCA). Kaplan–Meier methodology was used to compare the survival between the low- and high-risk subgroups.
RESULTS In total, seven radiomics features were selected to construct the radiomics signature. According to the results of univariate and multivariate Cox regression analyses, alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR) and radiomics signature were included to build the nomogram. The C-indices of the nomogram in the training and validation cohorts were 0.736 and 0.774, respectively. ROC curve analysis for predicting 1-, 3-, and 5-year OS confirmed satisfactory accuracy [training cohort, area under the curve (AUC) = 0.850, 0.791 and 0.823, respectively; validation cohort, AUC = 0.905, 0.884 and 0.911, respectively]. The calibration curve analysis indicated a good agreement between the nomogram-prediction and actual survival. DCA curves suggested that the nomogram had more benefit than traditional staging system models. Kaplan–Meier survival analysis indicated that patients in the low-risk group had longer OS and disease-free survival (all P < 0.0001).
CONCLUSION The nomogram containing the radiomics signature, NLR and AFP is a reliable tool for predicting the OS of HCC patients.
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Affiliation(s)
- Peng-Zhan Deng
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Bi-Geng Zhao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Xian-Hui Huang
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Ting-Feng Xu
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Zi-Jun Chen
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Qiu-Feng Wei
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Yi Liu
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Yu-Qi Guo
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Sheng-Guang Yuan
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Wei-Jia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
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Rich NE, Parvathaneni A, Sen A, Odewole M, Arroyo A, Mufti AR, Kerr TA, Grant L, Tujios SR, Mayo MJ, Lee WM, Yang JD, Yokoo T, Gopal P, Hoshida Y, Zhu H, Yopp AC, Marrero JA, Singal AG. High Neutrophil-Lymphocyte Ratio and Delta Neutrophil-Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer. Dig Dis Sci 2022; 67:2666-2676. [PMID: 33939138 DOI: 10.1007/s10620-021-07001-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 04/14/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The neutrophil-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC). METHODS We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR. RESULTS Among 1019 HCC patients, baseline NLR was < 5 in 815 (80.0%) and ≥ 5 in 204 (20.0%). Patients with NLR ≥ 5 had a higher proportion of infiltrative tumors (36.2% vs 22.3%), macrovascular invasion (39.6% vs 25.5%), metastatic disease (20.6% vs 11.4%), and AFP > 200 ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1 months; adjusted HR 1.70, 95%CI 1.41-2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14-1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32-0.95). CONCLUSIONS In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality. IMPACT NLR is an inexpensive test that may be a useful component of future HCC prognostic models.
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Affiliation(s)
- Nicole E Rich
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA.
| | - Aarthi Parvathaneni
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Ahana Sen
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Mobolaji Odewole
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Ana Arroyo
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Arjmand R Mufti
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Thomas A Kerr
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Lafaine Grant
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Shannan R Tujios
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - William M Lee
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Ju Dong Yang
- Division of Digestive and Liver Diseases, Comprehensive Transplant Center and Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Takeshi Yokoo
- Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Purva Gopal
- Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Yujin Hoshida
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Hao Zhu
- Children's Research Institute, UT Southwestern Medical Center, Dallas, TX, USA
| | - Adam C Yopp
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Jorge A Marrero
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
- Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, USA
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Yang XG, Huang YC, Wang CH, Sun YY, Huang Z, Xu GH. Predictive Value of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization Combined with Radiofrequency Ablation. Cancer Invest 2022; 40:494-504. [PMID: 35404178 DOI: 10.1080/07357907.2022.2065508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
PURPOSE To determine the predictive value of preoperative inflammatory markers in hepatocellular carcinoma (HCC) prognosis after transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA). MATERIALS AND METHODS A total of 161 patients with HCC who underwent TACE combined with RFA were enrolled in this retrospective study. Receiver operating characteristic (ROC) curve analysis was used to decide the cutoff value of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI). The relationship between preoperative NLR, LMR, PLR, PNI, and survival outcomes was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS The cutoff value of NLR for the best discrimination of HCC prognosis was 2.95. The median recurrence-free survival (RFS) of the low NLR (≤ 2.95) group was longer than that of the high NLR (>2.95) group (29 months vs. 20 months, P = 0.013). The median overall survival (OS) of the low NLR group was longer than that of the high NLR group (60 months vs. 38 months, P = 0.006). Multivariate analysis showed that the tumor size (≤ 3cm vs. >3cm), tumor number (single vs. multiple), and NLR (≤2.95 vs. >2.95) were independent predictors of the PFS and OS. LMR, PLR, and PNI did not have any prognostic significance. CONCLUSION NLR was confirmed as an independent predictive biomarker for hepatocellular carcinoma prognosis after TACE combined with RFA.
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Affiliation(s)
- Xue-Gang Yang
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No.55, Lane 4, RenMin Road (South),Chengdu, Sichuan 610041, China
| | - Ye-Cai Huang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, No.55, Lane 4, RenMin Road (South),Chengdu, Sichuan 610041, China
| | - Chun-Hua Wang
- Department of Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No.55, Lane 4, RenMin Road (South), Chengdu, Sichuan 610041, China
| | - Yan-Yuan Sun
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No.55, Lane 4, RenMin Road (South),Chengdu, Sichuan 610041, China
| | - Zhi Huang
- School of Basic Medicine, Guizhou Medical University, Department of Interventional Radiology, the Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550002, P.R. China
| | - Guo-Hui Xu
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No.55, Lane 4, RenMin Road (South),Chengdu, Sichuan 610041, China
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20
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Ratnasari N, Lestari P, Renovaldi D, Raditya Ningsih J, Qoriansas N, Wardana T, Hakim S, Signa Aini Gumilas N, Indrarti F, Triwikatmani C, Bayupurnama P, Setyo Heriyanto D, Astuti I, Mubarika Harjana S. Potential plasma biomarkers: miRNA-29c, miRNA-21, and miRNA-155 in clinical progression of Hepatocellular Carcinoma patients. PLoS One 2022; 17:e0263298. [PMID: 35157721 PMCID: PMC8843218 DOI: 10.1371/journal.pone.0263298] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 01/17/2022] [Indexed: 02/07/2023] Open
Abstract
This study evaluated differences in the clinical appearance of patients with hepatocellular carcinoma (HCC) based on plasma level and regulation of microRNAs (miRNA-29c, miRNA-21, and miRNA-155). The observational-analytical study with a cross-sectional design was conducted on 36 HCC patients and 36 healthy controls. The blood samples were collected from 2 Province Hospitals (Dr. Sardjito Hospital and Prof. Dr. Margono Soekarjo Hospital) for HCC and the Blood Bank Donor of the Indonesian Red Cross for 36 healthy controls. These blood samples were treated as follows: plasma isolation, RNA isolation, cDNA synthesis, quantification by qRT-PCR using a sequence-specific forward primer, and normalization of miRNA using housekeeping-stably miRNA-16. There were only 27 HCC patients with complete clinical variables (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet count, albumin, C-reactive protein (CRP), and cholinesterase (ChE)) that were able to analyses for regulation miRNAs based on its fold change expression miRNA target. All 27 HCC subjects were follow-up until 3-years of monitoring for their overall survival. The miRNA plasma expression was analyzed by Bio-Rad CFX 96 Manager software to determine the cycle of quantification, followed by the calculation of expression levels using Livak's methods. Data were analyzed using STATA 11.0, with a significant value of p<0.05. The miRNAs expression of HCC subjects were lower than that healthy control subjects in miRNA-29c (down-regulation 1.83-fold), higher than that healthy control subjects in miRNA 21 and miRNA-155 (up-regulation, 1.74-fold; 1.55-fold) respectively. NLR, CRP, ChE, and platelet count showed a significant difference in miRNA-29c regulation, though neutrophil count showed a significant difference in miRNA-21 and miRNA-155 regulation (p<0.05). Conclusion: Plasma biomarkers: miRNA-21 and miRNA-155 might be potential biomarkers as onco-miR in HCC subjects, while miRNA-29c might act as a tumor suppressor. Significant evidence was identified with clinical progression based on the regulation of miRNAs, which was consistent with miRNA -29c.
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Affiliation(s)
- Neneng Ratnasari
- Gastroenterology-Hepatology Division of Internal Medicine, Department Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/ Dr. Sardjito General Hospital, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
| | - Puji Lestari
- Graduate School of Biotechnology Universitas Gadjah Mada, Daerah Istimewa Yogyakarta, Indonesia
| | - Dede Renovaldi
- Graduate School of Biotechnology Universitas Gadjah Mada, Daerah Istimewa Yogyakarta, Indonesia
| | - Juwita Raditya Ningsih
- Graduate School of Biotechnology Universitas Gadjah Mada, Daerah Istimewa Yogyakarta, Indonesia
| | - Nanda Qoriansas
- Graduate School of Biotechnology Universitas Gadjah Mada, Daerah Istimewa Yogyakarta, Indonesia
| | - Tirta Wardana
- Department Biomedicine, School of Dentistry, Faculty of Medicine Jenderal Soedirman University, Jawa Tengah, Indonesia
| | - Suharno Hakim
- Internal Medicine Department Dr. Margono Soekarjo Hospital/Faculty of Medicine Universitas Jendral Soedirman, Jawa Tengah, Indonesia
| | - Nur Signa Aini Gumilas
- Histology Department Faculty of Medicine Universitas Jendral Soedirman, Jawa Tengah, Indonesia
| | - Fahmi Indrarti
- Gastroenterology-Hepatology Division of Internal Medicine, Department Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/ Dr. Sardjito General Hospital, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
| | - Catharina Triwikatmani
- Gastroenterology-Hepatology Division of Internal Medicine, Department Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/ Dr. Sardjito General Hospital, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
| | - Putut Bayupurnama
- Gastroenterology-Hepatology Division of Internal Medicine, Department Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/ Dr. Sardjito General Hospital, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
| | - Didik Setyo Heriyanto
- Anatomic Pathology Department, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
| | - Indwiani Astuti
- Pharmacology and Therapy Department, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
| | - Sofia Mubarika Harjana
- Histology and Cell Biology Department, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia
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Mouchli M, Reddy S, Gerrard M, Boardman L, Rubio M. Usefulness of neutrophil-to-lymphocyte ratio (NLR) as a prognostic predictor after treatment of hepatocellular carcinoma." Review article. Ann Hepatol 2021; 22:100249. [PMID: 32896610 DOI: 10.1016/j.aohep.2020.08.067] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/07/2020] [Accepted: 08/08/2020] [Indexed: 02/06/2023]
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker which has been investigated as a prognostic indicator in post-therapeutic recurrence and survival of patients with HCC. Our aim was to review all studies that assessed the prognostic value of pre-treatment NLR in predicting patient survival, cancer recurrence, and graft survival in patients undergoing various therapies for HCC. We searched the database of PubMed and Google Scholar to review all studies that have the word "NLR" and the word "HCC." We included all studies that assessed pre-treatment NLR as a prognostic factor in predicting outcomes in HCC patients. We excluded studies that assessed the correlation between post-treatment NLR or dynamic changes in NLR after treatment and HCC outcomes in an effort to minimize the confounding effect of each treatment on NLR. We reviewed 123 studies that studied the correlation between pre-treatment NLR and patient survival, 72 studies that evaluated the correlation between pre-treatment NLR and tumor recurrence, 21 studies that evaluated the correlation between NLR and tumor behavior, and 4 studies that assessed the correlation between NLR and graft survival. We found a remarkable heterogeneity between the methods of the studies, which is likely responsible for the differences in outcomes. The majority of the studies suggested a correlation between higher levels of pre-treatment NLR and poor outcomes. We concluded that NLR is a reliable and inexpensive biomarker and should be incorporated into other prognostic models to help determine outcomes following HCC treatment.
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Affiliation(s)
- Mohamad Mouchli
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States; Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States; Cleveland Clinic Foundation, Division of Gastroenterology & Hepatology, Cleveland, OH, United States.
| | - Shravani Reddy
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
| | - Miranda Gerrard
- Virginia Tech Carilion School of Medicine, Roanoke, VA, United States
| | - Lisa Boardman
- Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States
| | - Marrieth Rubio
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
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22
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Park JH. Are Peri-operative Inflammatory Markers Useful in Predicting Post-operative Ileus? J Neurogastroenterol Motil 2021; 27:451-452. [PMID: 34642266 PMCID: PMC8521474 DOI: 10.5056/jnm21174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 09/17/2021] [Indexed: 12/05/2022] Open
Affiliation(s)
- Jung Ho Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Korea
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23
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Magalhães RDS, Magalhães J, Sousa-Pinto B, Cúrdia Gonçalves T, Rosa B, Cotter J. Neutrophil-to-lymphocyte ratio: an accurate method for diagnosing infection in cirrhosis. Postgrad Med 2021; 133:613-618. [PMID: 33843439 DOI: 10.1080/00325481.2021.1916258] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 04/09/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Early diagnosing bacterial infection in cirrhotic patients is critical but challenging. Neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and is an emerging biomarker that replicates cirrhosis' imbalanced immune response. AIM Assess whether NLR levels associate with higher risk of infection in patients admitted with first cirrhosis decompensation. METHODS Retrospective, unicenter study, including patients with cirrhosis, admitted to the hospital at first decompensation. NLR was calculated at admission. Applying logistic regression models and testing for discriminative power, we correlated NLR with the outcome infection. RESULTS We included 139 patients. Forty-four infections to report (31.7%), 18 (12.9%) community infections and 26 (18.7%) hospital-acquired infections.Higher NLR values at admission were associated with increased infection risk in univariable and multivariable models - for each unit increase of NLR, infection odds increased 1.29 times (95%CI = 1.09-1.53; p = 0.003), after adjusting for covariates. We performed a classification tree based only on NLR to evaluate the risk of infection. A high-risk group (proportion of patients with infection = 87%) was identified, corresponding to NLR>14; patients with NLR <3.6 presented lower infection risk (17%).Regarding hospital-acquired infection, we were not able to discriminate groups of patients based on classification trees. CONCLUSION NLR is a straightforward approach to attest the individual infection risk on cirrhotic patients. We report NLR cutoffs 3.6 and 14 as optimal for overall infection diagnosing, mainly due to community infection.
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Affiliation(s)
- Rui De Sousa Magalhães
- Gastroenterology Department, Hospital Senhora Da Oliveira - Guimarães, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Joana Magalhães
- Gastroenterology Department, Hospital Senhora Da Oliveira - Guimarães, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Bernardo Sousa-Pinto
- MEDCIDS - Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal
- CINTESIS - Center for Health Technology and Services Research, University of Porto, Porto, Portugal
| | - Tiago Cúrdia Gonçalves
- Gastroenterology Department, Hospital Senhora Da Oliveira - Guimarães, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Bruno Rosa
- Gastroenterology Department, Hospital Senhora Da Oliveira - Guimarães, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - José Cotter
- Gastroenterology Department, Hospital Senhora Da Oliveira - Guimarães, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Portugal
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24
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Rapposelli IG, Shimose S, Kumada T, Okamura S, Hiraoka A, Di Costanzo GG, Marra F, Tamburini E, Forgione A, Foschi FG, Silletta M, Lonardi S, Masi G, Scartozzi M, Nakano M, Shibata H, Kawata K, Pellino A, Vivaldi C, Lai E, Takata A, Tajiri K, Toyoda H, Tortora R, Campani C, Viola MG, Piscaglia F, Conti F, Fulgenzi CAM, Frassineti GL, Rizzato MD, Salani F, Astara G, Torimura T, Atsukawa M, Tada T, Burgio V, Rimini M, Cascinu S, Casadei-Gardini A. Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma. ESMO Open 2021; 6:100190. [PMID: 34144271 PMCID: PMC8219999 DOI: 10.1016/j.esmoop.2021.100190] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/25/2021] [Accepted: 05/26/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.
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Affiliation(s)
- I G Rapposelli
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori'-IRST, Meldola, Italy
| | - S Shimose
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - T Kumada
- Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - S Okamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - A Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - G G Di Costanzo
- Liver Unit, Department of Transplantation, Cardarelli Hospital, Naples, Italy
| | - F Marra
- Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy
| | - E Tamburini
- Department of Medical Oncology, Card. G. Panico Hospital of Tricase, Tricase, Italy
| | - A Forgione
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - F G Foschi
- Department of Internal Medicine, Faenza Hospital, AUSL Romagna, Faenza, Italy
| | - M Silletta
- Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy
| | - S Lonardi
- Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - G Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - M Scartozzi
- Medical Oncology, University and University Hospital of Cagliari, Italy
| | - M Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - H Shibata
- Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan
| | - K Kawata
- Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - A Pellino
- Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - C Vivaldi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - E Lai
- Medical Oncology, University and University Hospital of Cagliari, Italy
| | - A Takata
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - K Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - H Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - R Tortora
- Liver Unit, Department of Transplantation, Cardarelli Hospital, Naples, Italy
| | - C Campani
- Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy
| | - M G Viola
- Department of Surgery, Card. G. Panico Hospital of Tricase, Tricase, Italy
| | - F Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - F Conti
- Department of Internal Medicine, Faenza Hospital, AUSL Romagna, Faenza, Italy
| | - C A M Fulgenzi
- Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy
| | - G L Frassineti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori'-IRST, Meldola, Italy
| | - M D Rizzato
- Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - F Salani
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - G Astara
- Medical Oncology, University and University Hospital of Cagliari, Italy
| | - T Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - M Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - T Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - V Burgio
- Unit of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - M Rimini
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy
| | - S Cascinu
- Unit of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - A Casadei-Gardini
- Unit of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
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Wainberg M, Kloiber S, Diniz B, McIntyre RS, Felsky D, Tripathy SJ. Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank. Transl Psychiatry 2021; 11:380. [PMID: 34234104 PMCID: PMC8263616 DOI: 10.1038/s41398-021-01505-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 06/16/2021] [Accepted: 06/24/2021] [Indexed: 11/23/2022] Open
Abstract
Prevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.
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Affiliation(s)
- Michael Wainberg
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Stefan Kloiber
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Breno Diniz
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Roger S McIntyre
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
| | - Daniel Felsky
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Shreejoy J Tripathy
- Centre for Addiction and Mental Health, Toronto, ON, Canada.
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada.
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
- Department of Physiology, University of Toronto, Toronto, ON, Canada.
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Zhang Z, Yu Y, Zheng J, Zhang M, Niu H. Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in papillary renal cell carcinoma patients after receiving curative surgery based on a retrospective cohort. BMC Urol 2021; 21:43. [PMID: 33752642 PMCID: PMC7983378 DOI: 10.1186/s12894-021-00805-8] [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: 05/22/2020] [Accepted: 03/02/2021] [Indexed: 12/24/2022] Open
Abstract
Background Inflammatory response biomarkers have been studied as promising prognostic factors in renal cell carcinoma, but few studies have focused on papillary renal cell carcinoma (PRCC). This study was performed to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in PRCC patients. Methods In total, 122 postoperative PRCC patients selected from 366 non-clear cell renal cell carcinoma patients were enrolled from our institution between 2012 and 2020. The optimal cutoff value of the NLR was assessed by receiver operating characteristic (ROC) curve analysis, and the Kaplan–Meier method and Cox's proportional hazards regression models were performed to analyze the association of the NLR with overall survival (OS). In addition, the potential of tumor-node-metastasis (TNM) stage, the NLR and an NLR-TNM system to predict survival were compared with ROC curves, and clinical usefulness of the predicting models were assessed by decision curve analysis. Results A threshold value of 2.39 for the NLR for OS analysis was determined by ROC curve analysis. An NLR ≥ 2.39 was associated with a more advanced TNM stage (P < 0.01) and larger tumors (P < 0.05) than a low NLR, as well as pathological subtype II (P < 0.05), and the patients with a high NLR also exhibited significantly worse overall survival outcomes (P < 0.05). The NLR was determined to be a significant independent prognostic indicator by univariable and multivariable analyses (HR = 5.56, P < 0.05). Furthermore, TNM stage and the NLR were integrated, and the area under the curve (AUC) of for the NLR-TNM system was larger than that of for the TNM system when predicting overall survival (0.84 vs 0.73, P = 0.04). Decision curve analysis also demonstrated a better clinical value for the NLR-TNM model to predict the prognosis. Conclusion A high preoperative NLR was associated with poor clinical and pathologic parameters in patients with PRCC; moreover, the NLR was also an independent prognostic factor for the OS of patients with PRCC. The NLR-TNM system, which was a model that integrated the NLR with TNM staging, could improve the ability to predict overall survival.
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Affiliation(s)
- Zhilei Zhang
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Department of Clinical Medicine, Qingdao University, Qingdao, China
| | - Yongbo Yu
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Department of Clinical Medicine, Qingdao University, Qingdao, China
| | - Jilu Zheng
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Department of Clinical Medicine, Qingdao University, Qingdao, China
| | - Mingxin Zhang
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Haitao Niu
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
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27
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Clinical biomarkers to predict preoperative lymph node metastasis in endometrial cancer. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.882342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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28
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Yamamoto M, Kurokawa Y, Kobayashi N, Takahashi T, Miyazaki Y, Tanaka K, Makino T, Yamasaki M, Nakajima K, Mori M, Doki Y. Prognostic Value of the Combined Index of Plasma Fibrinogen and the Neutrophil-Lymphocyte Ratio in Gastric Cancer. World J Surg 2020; 44:207-212. [PMID: 31559484 DOI: 10.1007/s00268-019-05193-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It has been reported that both fibrinogen and the neutrophil-lymphocyte ratio (NLR) are related to the degree of malignancy in various types of cancer. This study compared the combined index of fibrinogen and NLR (F-NLR) with NLR alone for predicting the prognosis of patients with resectable gastric cancer. METHODS We collected data on 666 patients with resectable gastric cancer. Patients were divided into three F-NLR score groups based on the following criteria: score 2, both hyperfibrinogenemia (≥350 mg/dl) and high NLR (≥2.5); score 1, either hyperfibrinogenemia or high NLR; and score 0, neither abnormality. The association between prognosis and NLR alone or F-NLR was evaluated using the Kaplan-Meier method and Cox multivariate analysis. RESULTS The high-NLR group had significantly worse overall survival (OS) than the low-NLR group (hazard ratio 1.62; 95% confidence interval [CI] 1.07-2.45; log-rank P = 0.022), but there was no significant difference between the high- and low-NLR groups after adjusting for the fibrinogen level. F-NLR groups showed significantly different OS (log-rank P < 0.001) and recurrence-free survival (log-rank P < 0.001). The 5-year OS rate for the groups with F-NLR scores of 2, 1, and 0 was 72.6%, 81.4%, and 90.4%, respectively. A Cox multivariate analysis of OS revealed that a high F-NLR score (1 or 2) was an independent prognostic factor (P = 0.007). CONCLUSIONS F-NLR was an independent prognostic factor in patients with gastric cancer and a more useful prognostic indicator than NLR alone.
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Affiliation(s)
- Masaaki Yamamoto
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan.,Department of Surgery, JCHO Hoshigaoka Medical Center, Osaka, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan.
| | - Noboru Kobayashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Yasuhiro Miyazaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
| | - Masaki Mori
- Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, 565-0871, Osaka, Japan
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Wu M, Yang S, Feng X, Yu F, Liu X, Dong J. Preoperative plus postoperative neutrophil-lymphocyte ratio for predicting overall survival following partial hepatectomy for hepatocellular carcinoma. Oncol Lett 2020; 20:375. [PMID: 33154773 PMCID: PMC7608046 DOI: 10.3892/ol.2020.12238] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023] Open
Abstract
The preoperative neutrophil-lymphocyte ratio (NLR) and the postoperative NLR have been reported to be prognostic factors for malignant tumors. However, the prognostic value of combining the preoperative NLR and postoperative NLR for hepatocellular carcinoma (HCC) remains unclear. In the present study, a cohort of 70 patients with primary HCC were retrospectively reviewed. The optimal cut-offs for continuous variables were determined by the maximally selected rank statistics. The prognostic factors included preoperative NLR, postoperative NLR, preoperative NLR plus postoperative NLR, change in postoperative NLR, and postoperative NLR minus preoperative NLR. The predictive powers of the aforementioned prognostic factors were analyzed by the area under the time-dependent receiver operating characteristic (td-AUC) curve. Prognostic values were assessed by univariate and multivariate analyses. An increased preoperative NLR was found to be associated with higher preoperative neutrophil levels, lower preoperative lymphocyte levels and larger tumor sizes (all P<0.05). An increased postoperative NLR was associated with higher postoperative neutrophil levels and lower postoperative lymphocyte levels (all P<0.05). Multivariate analysis identified the preoperative NLR plus postoperative NLR as an independent prognostic risk factor (HR, 2.985; 95% CI, 1.648-5.407; P<0.001). The preoperative NLR plus postoperative NLR had higher td-AUC values than the preoperative NLR, postoperative NLR, postoperative NLR change, and postoperative NLR minus the preoperative NLR in the first to fourth years after surgery. The preoperative NLR plus postoperative NLR, considering both the preoperative and postoperative treatment phases, is a novel and promising prognostic factor for patients with HCC and requires further investigation in the future.
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Affiliation(s)
- Meilong Wu
- School of Clinical Medicine, Tsinghua University, Haidian, Beijing 100084, P.R. China.,Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing 102218, P.R. China
| | - Shizhong Yang
- School of Clinical Medicine, Tsinghua University, Haidian, Beijing 100084, P.R. China.,Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing 102218, P.R. China
| | - Xiaobin Feng
- School of Clinical Medicine, Tsinghua University, Haidian, Beijing 100084, P.R. China.,Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing 102218, P.R. China
| | - Fei Yu
- School of Clinical Medicine, Tsinghua University, Haidian, Beijing 100084, P.R. China.,Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing 102218, P.R. China
| | - Xiangchen Liu
- School of Clinical Medicine, Tsinghua University, Haidian, Beijing 100084, P.R. China.,Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing 102218, P.R. China
| | - Jiahong Dong
- School of Clinical Medicine, Tsinghua University, Haidian, Beijing 100084, P.R. China.,Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing 102218, P.R. China
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Lu R, Li W, Wang X, Shi D, Meng H. Elevated neutrophil-to-lymphocyte ratio but not platelet-to-lymphocyte ratio is associated with generalized aggressive periodontitis in a Chinese population. J Periodontol 2020; 92:507-513. [PMID: 32909291 DOI: 10.1002/jper.20-0282] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 08/29/2020] [Accepted: 09/02/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Host inflammatory mediators are associated with tissue destruction in patients suffering from generalized aggressive periodontitis (GAgP). However, the correlations between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with GAgP remain unknown. METHODS Periodontal clinical parameters, including probing depth (PD), bleeding index (BI) and attachment loss (AL) were collected from patients with GAgP and healthy controls. Complete blood cells analyses were obtained; further, NLR and PLR were calculated using neutrophil, platelet, and lymphocyte counts. Smooth curve fitting and segmented regression models were used to analyze the roles and predictive value of NLR with GAgP. RESULTS In total, 505 participants from a Chinese population were recruited, including 133 healthy controls and 372 patients with GAgP. Periodontal clinical parameters, NLR, and neutrophil counts were significantly higher in patients with GAgP than the control group. Moreover, NLR was positively correlated with the risk and clinical parameters of GAgP. When NLR < 3, the risk of GAgP increased by 20.6% for each 0.1 increase in NLR, reaching saturation when NLR > 3. An increase in NLR equivalent to 1 was associated with an increase in PD, BI, and AL by 0.41 mm, 0.26, and 0.57 mm, respectively. Notably, PLR did not show obvious correlations with GAgP. CONCLUSIONS NLR but not PLR may be a potential marker to identify GAgP in healthy individuals, particularly in a Chinese population.
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Affiliation(s)
- Ruifang Lu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China
| | - Wenjing Li
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China
| | - Xiane Wang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China
| | - Dong Shi
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China
| | - Huanxin Meng
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China
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Park W, Bang JH, Nam AR, Jin MH, Seo H, Kim JM, Oh KS, Kim TY, Oh DY. Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients. Cancer Res Treat 2020; 53:199-206. [PMID: 33070562 PMCID: PMC7812012 DOI: 10.4143/crt.2020.497] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 10/05/2020] [Indexed: 12/16/2022] Open
Abstract
Purpose The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). Materials and Methods We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progression-free survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. Results The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. Conclusion sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.
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Affiliation(s)
- Woochan Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Ju-Hee Bang
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ah-Rong Nam
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Mei Hua Jin
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyerim Seo
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Min Kim
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoung Seok Oh
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Tae-Yong Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Do-Youn Oh
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Li SC, Xu Z, Deng YL, Wang YN, Jia YM. Higher neutrophil-lymphocyte ratio is associated with better prognosis of hepatocellular carcinoma. Medicine (Baltimore) 2020; 99:e20919. [PMID: 32629689 PMCID: PMC7337484 DOI: 10.1097/md.0000000000020919] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide; its morbidity and mortality have both recently increased. Lately, the role played by the neutrophil-lymphocyte ratio (NLR) in the development of HCC has attracted attention. However, the exact relationship is not fully understood.A total of 538 participants diagnosed with HCC were recruited between 2010 and 2018. Their relevant routine blood parameters were measured, including NLR. Pearson Chi-Squared test, Spearman Rho test, and logistic regression analysis were performed to explore any correlations between NLR and HCC. A receiver operating characteristic (ROC) curve analysis was performed to determine the usefulness of NLR for predicting HCC. Univariate and multivariate Cox regression analysis for relevant routine blood parameters and any relationships with overall survival (OS) were performed. The Kaplan-Meier method was used to explore any further relationships with OS.NLR was significantly correlated with HCC tumor size by Pearson Chi-Squared test (P = .008). Furthermore, Spearman correlation coefficient showed that HCC tumor size was significantly correlated with NLR (P = .115, P = .008). NLR could sensitively and specifically predict HCC tumor size (area under the curve [AUC], 0.605; 95% confidence interval [CI], 0.429-0.743; P = .000). Higher NLR in patients with HCC was correlated with better OS (hazard ratio [HR] = 0.584; P = .000).A close correlation existed between increased NLR and HCC; NLR could sensitively and specifically predict HCC. High NLR might be an independent protective factor in the prognosis of patients with HCC.
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Affiliation(s)
| | - Zhuo Xu
- Department of Hepatobiliary Surgery
| | - Yan-li Deng
- Clinical Laboratory, Fourth Hospital of Hebei Medical University
| | - Ya-ni Wang
- School of Basic Medical Sciences, Hebei Medical University, Shijiazhuang, Hebei , PR China
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Assessment of Inflammatory Status Based on Total Blood Count and Its Relationship to Cardiovascular Diseases. JOURNAL OF INTERDISCIPLINARY MEDICINE 2020. [DOI: 10.2478/jim-2019-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Background: Inflammation seems to be the most important trigger for atherosclerosis. Lower extremity artery disease (LEAD) and hypertension (HTN) are the most important atherosclerotic diseases. Total blood count-derived neutrophil-lymphocyte ratio (NLR) and red cell distribution width (RDW) have been proposed as inflammatory biomarkers in cardiovascular diseases. The aim of this study was to assess the correlation with LEAD and HTN.
Material and methods: In total, 134 subjects were included in the study, divided into 2 groups as follows: group 1 – patients with LEAD and HTN; group 2 – subjects with HTN, without LEAD. Complete blood count (CBC) and lipid profile were determined. To assess peripheral artery disease, the ankle-brachial index (ABI) was measured with a handheld Doppler device (BiDop ES100V3 Hadeco®). We compared the inflammatory status between the groups with the use of white blood cell count (WBC), red cell distribution (RDW), and neutrophil-lymphocyte ratio (NLR).
Results: In group 1, there was a significant negative correlation between the ABI and RDW (p = 0.04, r2 = –0.24, 95% CI: 0.4647–0.0013), as well as between the ABI and NLR (p = 0.001, r2 = –0.38, 95% CI: 0.5801–0.1592). In group 2, there was a positive correlation between NLR and total serum cholesterol levels (p = 0.003, 95% CI: 0.1274–0.5472, r2 = 0.12), as well as between NLR and triglyceride levels (p = 0.002, 95% CI: 0.1387–0.5552, r2 = 0.13).
Conclusion: NLR and RDW could represent first-line investigations in patients with cardiovascular disease due their cost efficiency. They can also play a role in triaging patients with atherosclerotic disease, monitoring treatment response and prognosis of the disease.
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Li Y, Guo D, Ren M, Zhao Y, Wang X, Chen Y, Liu Y, Lu G, He S. Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway. J Cell Mol Med 2019; 23:6271-6282. [PMID: 31264769 PMCID: PMC6714236 DOI: 10.1111/jcmm.14513] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 06/09/2019] [Accepted: 06/11/2019] [Indexed: 01/04/2023] Open
Abstract
Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression of human cancers, including hepatocellular carcinoma (HCC). However, the role and exact mechanism of most lncRNAs in tumours remains largely unknown. In the current study, we found a novel long non-coding RNA termed SNAI3-AS1 which was generally up-regulated in HCC tissues compared with normal control. Higher expression of SNAI3-AS1 was significantly correlated with shorter overall survival of HCC patients. Knockdown of SNAI3-AS1 inhibited the proliferation and metastasis of HCC cells in vitro, whereas overexpression of SNAI3-AS1 promoted the proliferation and metastasis of HCC cells. Further investigations showed that SNAI3-AS1 could affect HCC tumorigenesis by binding up-frameshift protein 1 (UPF1), regulating Smad7 expression and activating TGF-β/Smad pathway. Functionally, SNAI3-AS1 promoted HCC growth and metastasis by inducing tumour epithelial to mesenchymal transition (EMT). Taken together, these findings showed that SNAI3-AS1 promotes the progression of HCC by regulating the UPF1 and activating TGF-β/Smad pathway.
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Affiliation(s)
- Yarui Li
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Dan Guo
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Mudan Ren
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Yan Zhao
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Xin Wang
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Yifei Chen
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Yaping Liu
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Guifang Lu
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Shuixiang He
- Department of GastroenterologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
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Wu MT, He SY, Chen SL, Li LF, He ZQ, Zhu YY, He X, Chen H. Clinical and prognostic implications of pretreatment albumin to C-reactive protein ratio in patients with hepatocellular carcinoma. BMC Cancer 2019; 19:538. [PMID: 31164099 PMCID: PMC6549313 DOI: 10.1186/s12885-019-5747-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 05/23/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Despite recent advances in the treatments of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains controversial. The purpose of this study was to investigate the prognostic performance of pretreatment albumin to C-reactive protein ratio (ACR) in patients with HCC. METHODS This study included 409 initially diagnosed HCC patients retrospectively. The optimal cut-off points for distinguishing high and low ACR value was determined by the X-tile software. The chi-squared test was used for comparing the baseline clinicopathologic parameters in different groups and subgroups. The Cox regression with log-rank tests was used to analyze OS and DFS, and Kaplan-Meier curves was used to estimate the prognosis of HCC patients. RESULTS Patients with lower ACR were significantly correlated with advanced clinical parameters, using a cut-off points of 5.4 (high ACR, n = 236 vs. low ACR, n = 173). Multivariate analysis demonstrated that ACR was associated with OS (HR = 0.544, 95% CI: 0.385-0.769, p = 0.001), with DFS (HR = 0.550, 95% CI: 0.392-0.772, p = 0.001). Treatment exposure (HR = 2.191; 95% CI: 1.533-3.132; p < 0.001), tumor size (HR = 1.973; 95% CI: 1.230-3.164; p = 0.005), serum AFP level (HR = 1.752; 95% CI: 1.277-2.403; p = 0.001), and TNM stage (HR = 0.470; 95% CI: 0.319-2.504; p < 0.001), were independent factors for OS in HCC patients. Treatment exposure (HR = 2.244; 95% CI: 1.590-3.166; p < 0.001), TNM stage (HR = 2.075; 95% CI: 1.436-3.000; p < 0.001), serum AFP level (HR = 1.819; 95% CI: 1.340-2.469; p = 0.001), tumor size (HR = 1.730; 95% CI: 1.113-2.689; p = 0.015), and ACR (HR = 0.550; 95% CI: 0.392-0.772; p = 0.001) were independent factors for DFS in HCC patients. CONCLUSIONS Pretreatment ACR is a convenient and useful parameter for HCC patients predicting OS and DFS. Lower ACR was associated with advanced TNM stage, larger tumor size, and a high concentration of AFP. These results may help to design strategies to personalize management approaches among HCC patients.
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Affiliation(s)
- Mian-Tao Wu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Su-Yin He
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Shu-Lin Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lin-Fang Li
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zheng-Qiang He
- Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuan-Ying Zhu
- Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xia He
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Hao Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
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Abstract
BACKGROUND To perform a meta-analysis of retrospective studies exploring the association of C-reactive protein to albumin (CAR) with overall survival (OS) in patients with lung cancer. METHODS Relevant studies were enrolled by searching databases of PubMed, Cochrane Library, Web of Science, and Embase were searched until July 16, 2017. We combined the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the correlation between CAR and OS in patients with lung cancer RESULTS:: Four studies involving 1257 participants from several countries were involved in the meta-analysis. In a pooled analysis of all studies, elevated CAR predicted poor OS (HR: 2.13; 95% CI: 1.52-2.97; P < .05). Subgroup analysis showed that high level of CAR predicted poor OS in patients with lung cancer though multivariate analyses on 1092 participants (HR: 1.63; 95% CI: 1.24-2.51; P < .001) and the heterogeneity decreased to 45.4%. Moreover, a similar trend was observed in patients receiving surgery (HR: 2.64; 95% CI: 2.08-3.35; P < .001) and chemotherapy (HR: 1.75; 95% CI: 1.93-2.57; P = .004). And the HRs for patients receiving surgery was moderately higher than that for patients receiving chemotherapy. CONCLUSION Our findings indicate that CAR may have a prognostic value in lung cancer as we detected a significant association between elevated CAR and poorer OS. However, further studies are warranted to draw firm conclusions.
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Affiliation(s)
- Tai-Bing Deng
- Department of Pulmonary & Critical Care, West China Hospital, Sichuan University, Chengdu
- Department of Respiratory Medicine, West China-Guangan Hospital, Sichuan University, Guangan
| | - Jing Zhang
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yong-Zhao Zhou
- Department of Pulmonary & Critical Care, West China Hospital, Sichuan University, Chengdu
| | - Wei-Min Li
- Department of Pulmonary & Critical Care, West China Hospital, Sichuan University, Chengdu
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Elalfy H, Besheer T, El-Maksoud MA, Farid K, Elegezy M, El Nakib AM, El-Aziz MA, El-Khalek AA, El-Morsy A, Elmokadem A, Elsamanoudy AZ, El-Bendary M. Monocyte/granulocyte to lymphocyte ratio and the MELD score as predictors for early recurrence of hepatocellular carcinoma after trans-arterial chemoembolization. Br J Biomed Sci 2018; 75:187-191. [PMID: 29991324 DOI: 10.1080/09674845.2018.1494769] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Accepted: 06/20/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The first-line treatment option for intermediate-stage hepatocellular carcinoma is trans-arterial chemoembolization (TACE). Blood indices, such as lymphocyte/monocyte ratio (LMR), lymphocyte count, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-granulocyte/lymphocyte ratio (MGLR) and red blood cell distribution width (RDW), are prognostic biomarkers in certain diseases. The model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores have been designed for patients with cirrhosis waiting for liver transplantation and in patients with hepatocellular carcinoma. We hypothesized possible roles for these blood indices, and the MELD and CTP scores as predictors for early recurrence of hepatocellular carcinoma after TACE. METHODS Routine laboratory indices determined the NLR, LMR, MGLR, RDW, PLR, as well as MELD and CTP scores in 147 patients. Sensitivity and specificity of the indices for hepatocellular carcinoma recurrence 36 months after TACE were estimated by receiver operator characteristic curve. RESULTS In multivariate regression analysis, only male sex, the lymphocyte count, CTP, the MGLR and the MELD score significantly (P < 0.01) predicted recurrence. The area under curve (AUC) for detection of recurrence for MGLR at a cut-off value 2.75 was 0.63 (95% CI 0.54-0.72) with sensitivity 70.7%, specificity 59.2% and accuracy 63%. The MELD score at cut-off value 9.5 had diagnostic performance with AUC 0.71 (0.63-0.79), sensitivity 80% and specificity 55.8% and accuracy 71.3%. CONCLUSIONS High MGLR and MELD scores are linked to increasing frequency of hepatocellular carcinoma recurrence after TACE and could be used as novel, simple, non-invasive prognostic tests.
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Affiliation(s)
| | | | | | - K Farid
- a Tropical Medicine Department
| | | | | | | | - A A El-Khalek
- b Diagnostic and Intervention Radiology Department, Mansoura Faculty of Medicine , Mansoura , Egypt
| | - A El-Morsy
- b Diagnostic and Intervention Radiology Department, Mansoura Faculty of Medicine , Mansoura , Egypt
| | - A Elmokadem
- b Diagnostic and Intervention Radiology Department, Mansoura Faculty of Medicine , Mansoura , Egypt
| | - A Z Elsamanoudy
- c Department of Medical Biochemistry and Molecular biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. & Department of Clinical Biochemistry, Faculty of Medicine , King Abdulaziz University , Saudi Arabia
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Mazmishvili K, Jayant K, Janikashvili N, Kikodze N, Mizandari M, Pantsulaia I, Paksashvili N, Sodergren MH, Reccia I, Pai M, Habib N, Chikovani T. Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer. J Cancer 2018; 9:3187-3195. [PMID: 30210642 PMCID: PMC6134816 DOI: 10.7150/jca.25084] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 04/05/2018] [Indexed: 12/13/2022] Open
Abstract
Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes. Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate. Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38). Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings.
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Affiliation(s)
- Ketevan Mazmishvili
- Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia
| | - Kumar Jayant
- Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, DuCane Road, W120HS, UK
| | - Nona Janikashvili
- Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia
| | - Nino Kikodze
- Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia
| | - Malkhaz Mizandari
- Department of Interventional Radiology, Tbilisi State Medical University, High Technology University Clinic, 0144 Tbilisi, Georgia
| | - Ia Pantsulaia
- Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia
| | - Natela Paksashvili
- Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia
- Department of Interventional Radiology, Tbilisi State Medical University, High Technology University Clinic, 0144 Tbilisi, Georgia
| | - Mikael H Sodergren
- Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, DuCane Road, W120HS, UK
| | - Isabella Reccia
- Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, DuCane Road, W120HS, UK
| | - Madhava Pai
- Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, DuCane Road, W120HS, UK
| | - Nagy Habib
- Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, DuCane Road, W120HS, UK
| | - Tinatin Chikovani
- Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia
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Wang Y, Peng C, Cheng Z, Wang X, Wu L, Li J, Huang C, Guo Q, Cai H. The prognostic significance of preoperative neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma receiving hepatectomy: A systematic review and meta-analysis. Int J Surg 2018; 55:73-80. [PMID: 29787804 DOI: 10.1016/j.ijsu.2018.05.022] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 05/18/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Numerous reports have indicated that preoperative Neutrophil-Lymphocyte ratio (NLR) was correlated with the prognosis of hepatocellular carcinoma who underwent hepatectomy. However, the results still remained controversial. Therefore, the present meta-analysis of 17 studies was performed to evaluate the prognostic value of preoperative NLR in HCC patients. METHOD Databases of PubMed, Embase, Cochrane Library and Web of Science were retrieved. Hazard Ratio (HR) or Odds Ratio (OR) with its 95% confidence intervals (CI) was used to evaluate the association between preoperative NLR and the prognosis or clinical features of HCC patients. RESULT A total of 17 studies eventually were included in this meta-analysis. Elevated preoperative NLR had a close relationship with the overall survival (OS) (HR 1.52; 95% CI 1.37-1.69), recurrence-free survival (RFS) (HR 1.64; 95% CI 1.44-1.87) and disease-free survival (DFS) (HR 1.50; 95% CI 1.35-1.67) of hepatocellular carcinoma. Additionally, preoperative NLR was also associated with tumor vascular invasion (OR 2.08; 95% CI 1.60-2.70), HBV (OR 0.68; 95% CI 0.51-0.90) and large tumor size (OR: 4.07; 95% CI 2.60-6.37). CONCLUSION The present meta-analysis indicated that preoperative NLR had significant association with the prognosis of hepatocellular carcinoma patients and may be an effectively prognostic indicator.
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Affiliation(s)
- Yunjiao Wang
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Chuchu Peng
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Zhigang Cheng
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China.
| | - Ximei Wang
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Lei Wu
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Jingyi Li
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Changsheng Huang
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Qulian Guo
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
| | - Hongwei Cai
- Department of Anesthesiology, Xiang Ya Hospital, Central South University, China
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Prognostic value of C-reactive protein levels in patients with bone neoplasms: A meta-analysis. PLoS One 2018; 13:e0195769. [PMID: 29668751 PMCID: PMC5906001 DOI: 10.1371/journal.pone.0195769] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 03/29/2018] [Indexed: 12/19/2022] Open
Abstract
Objective The aim of this study was to conduct a meta-analysis of retrospective studies that investigated the association of preoperative C-reactive protein (CRP) levels with the overall survival (OS) of patients with bone neoplasms. Methods A detailed literature search was performed in the Cochrane Library, Web of Science, Embase and PubMed databases up to August 28, 2017, for related research publications written in English. We extracted the data from these studies and combined the hazard ratios (HR) and 95% confidence intervals (CIs) to assess the correlation between CRP levels and OS in patients with bone neoplasms. Results Five studies with a total of 816 participants from several countries were enrolled in this current meta-analysis. In a pooled analysis of all the publications, increased serum CRP levels had an adverse prognostic effect on the overall survival of patients with bone neoplasms. However, the combined data showed no significant relationship between the level of CRP and OS in Asian patients (HR = 1.73; 95% CI: 0.86–3.49; P = 0.125). Similar trends were observed in patients with bone neoplasms when stratified by ethnicity, histology, metastasis and study sample size. Conclusions The results of this meta-analysis suggest that increased CRP expression indicates a poorer prognosis in patients with bone neoplasms. More prospective studies are needed to confirm the prognostic significance of CRP levels in patients with bone neoplasms.
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He C, Mao Y, Lao X, Li S, Lin X. Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma. Oncol Lett 2018; 15:4262-4268. [PMID: 29541193 PMCID: PMC5835899 DOI: 10.3892/ol.2018.7882] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 07/20/2017] [Indexed: 12/13/2022] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) has been regarded as a prognostic factor in various types of cancer. The present study aimed to identify the association between NLR and combined hepatocellular cholangiocarcinoma (cHCC-CC) in patients who underwent surgical resection. The present study retrospectively reviewed 59 patients who were diagnosed with cHCC-CC and treated with surgical resection between January 2000 and October 2014 at the Department of Hepatobiliary and Pancreatic Surgery at Sun Yat-sen University Cancer Center (Guangzhou, China). The patients were divided into two groups: NLR≤2.75 and NLR>2.75. Patients with stage I and II or stage III and IV disease were classified into early- and advanced-stage groups, respectively, according to the Tumor-Node-Metastasis (TNM) staging system. Overall survival time (OS) was estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to evaluate the prognostic value of NLR. The NLR value was significantly higher in the HCC advanced-stage group compared with that in the HCC early-stage group according to the TNM staging system (3.19 vs. 2.00; P=0.001). The median survival time was 83.6 months in the NLR≤2.75 group and 15 months in the NLR>2.75 group (P=0.004). Upon multivariate analysis, NLR>2.75 was an independent prognostic factor for poor cHCC-CC outcomes. Overall, the easily evaluated pre-treatment NLR may be an independent prognostic factor for patients with cHCC-CC treated by surgical resection.
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Affiliation(s)
- Chaobin He
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Yize Mao
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Xiangming Lao
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Shengping Li
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
| | - Xiaojun Lin
- Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China
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Liao R, Peng C, Li M, Li D, Jiang N, Li P, Ding X, Wu Q, Du C, Gong J. Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy. Cancer Med 2018; 7:1170-1182. [PMID: 29533004 PMCID: PMC5911633 DOI: 10.1002/cam4.1424] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 02/09/2018] [Accepted: 02/09/2018] [Indexed: 12/19/2022] Open
Abstract
In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including α-fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C-indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram-predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.
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Affiliation(s)
- Rui Liao
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China
| | - Cong Peng
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China
| | - Ming Li
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China
| | - De‐Wei Li
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China
| | - Ning Jiang
- Department of PathologyChongqing Medical UniversityChongqing400016China
| | - Pei‐Zhi Li
- Department of Hepatobiliary SurgeryThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010China
| | - Xiong Ding
- Department of Hepatobiliary SurgeryThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010China
| | - Qiao Wu
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China
| | - Cheng‐You Du
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China
| | - Jian‐Ping Gong
- Department of Hepatobiliary SurgeryThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010China
- Chongqing Key Laboratory of Hepatobiliary SurgeryThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010China
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Sylman JL, Mitrugno A, Atallah M, Tormoen GW, Shatzel JJ, Tassi Yunga S, Wagner TH, Leppert JT, Mallick P, McCarty OJT. The Predictive Value of Inflammation-Related Peripheral Blood Measurements in Cancer Staging and Prognosis. Front Oncol 2018; 8:78. [PMID: 29619344 PMCID: PMC5871812 DOI: 10.3389/fonc.2018.00078] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 03/07/2018] [Indexed: 12/23/2022] Open
Abstract
In this review, we discuss the interaction between cancer and markers of inflammation (such as levels of inflammatory cells and proteins) in the circulation, and the potential benefits of routinely monitoring these markers in peripheral blood measurement assays. Next, we discuss the prognostic value and limitations of using inflammatory markers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and C-reactive protein measurements. Furthermore, the review discusses the benefits of combining multiple types of measurements and longitudinal tracking to improve staging and prognosis prediction of patients with cancer, and the ability of novel in silico frameworks to leverage this high-dimensional data.
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Affiliation(s)
- Joanna L Sylman
- VA Palo Alto Health Care System, Palo Alto, CA, United States.,Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, United States.,Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, United States
| | - Annachiara Mitrugno
- Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, United States
| | - Michelle Atallah
- Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, United States
| | - Garth W Tormoen
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, United States
| | - Joseph J Shatzel
- Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States.,Cancer Early Detection & Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
| | - Samuel Tassi Yunga
- Cancer Early Detection & Advanced Research Center, Oregon Health & Science University, Portland, OR, United States.,Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States
| | - Todd H Wagner
- VA Palo Alto Health Care System, Palo Alto, CA, United States.,Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States
| | - John T Leppert
- VA Palo Alto Health Care System, Palo Alto, CA, United States.,Department of Urology, Stanford University School of Medicine, Stanford, CA, United States
| | - Parag Mallick
- Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, United States
| | - Owen J T McCarty
- Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, United States
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Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget 2018; 8:32171-32189. [PMID: 28418870 PMCID: PMC5458276 DOI: 10.18632/oncotarget.16291] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 02/20/2017] [Indexed: 12/12/2022] Open
Abstract
An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS). We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively. Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR.
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Carr BI, Akkiz H, Guerra V, Üsküdar O, Kuran S, Karaoğullarından Ü, Tokmak S, Ballı T, Ülkü A, Akçam T, Delik A, Arslan B, Doran F, Yalçın K, Altntaş E, Özakyol A, Yücesoy M, Bahçeci Hİ, Polat KY, Ekinci N, Şimşek H, Örmeci N, Sonsuz A, Demir M, Kılıç M, Uygun A, Demir A, Yilmaz S, Tokat Y. C-reactive protein and hepatocellular carcinoma: analysis of its relationships to tumor factors. ACTA ACUST UNITED AC 2018; 15:625-634. [PMID: 29951199 DOI: 10.4172/clinical-practice.1000409] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
C-reactive protein (CRP) is a blood marker for inflammation and is an independent prognostic factor for many human cancers. Combined with albumin levels, it forms the basis of the Glasgow Index for cancer prognosis. We reviewed the literature on CRP and HCC and also evaluated blood CRP levels and combination CRP plus albumin levels in a large HCC cohort. In order to understand the prognostic significance of CRP, we retrospectively examined a large HCC cohort and examined the relationship of CRP levels to tumor parameters. We report, that CRP alone and CRP plus albumin combined as well, significantly correlated with parameters of HCC aggressiveness, such as maximum tumor dimension (MTD), portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels, both as individual parameters and all parameters together (Aggressiveness Index). This extends current thinking, to suggest a possible explanation for the usefulness of blood CRP levels in HCC prognostication.
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Affiliation(s)
- Brian I Carr
- Izmir Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey, and Liver
Transplant Institute, Inonu University, Malatya, Turkey
| | - Hikmet Akkiz
- Çukurova University Gastroenterology Department, Adana, Turkey
| | - Vito Guerra
- Trials Centre, National Institute for Digestive Diseases, IRCCS "Saverio de Bellis", Castellana, Bari, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Ahmet Uygun
- Haydarpaşa sultan Abdülhamid Eğitm Araştrma Hastanesi, Turkey
| | - Ali Demir
- Konya Necmetn Erbakan Üniversitesi, Turkey
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Min GT, Li YM, Yao N, Wang J, Wang HP, Chen W. The pretreatment neutrophil-lymphocyte ratio may predict prognosis of patients with liver cancer: A systematic review and meta-analysis. Clin Transplant 2017; 32. [PMID: 29112283 DOI: 10.1111/ctr.13151] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND At present, several studies have reported that the pretreatment neutrophil-lymphocyte ratio (NLR) may be associated with the prognosis of liver cancer. Nevertheless, their conclusions remain controversial. Thus, we performed a meta-analysis of 54 studies to evaluate the prognostic value of NLR. METHOD Databases including PubMed, Embase, Cochrane Library, and Web of Science were searched to July 2017. RESULT A total of 54 studies including 12 979 patients were included in this meta-analysis. Elevated NLR had a close relationship with the overall survival (OS) (HR 1.52; 95% CI 1.39-1.67), recurrence-free survival (RFS) (HR 1.84; 95% CI 1.48-2.30), and disease-free survival (DFS) (HR 1.71; 95% CI 1.39-2.11) of liver cancer, respectively. In addition, elevated NLR was associated with the presence of tumor vascular invasion (OR 2.35; 95% CI 1.93-2.86), multiple tumors (OR 1.38; 95% CI 1.15-1.66), alpha-fetoprotein ≥ 400 ng/mL (OR 1.51; 95% CI 1.15-1.98), presence of HbsAg (+) (OR 0.68; 95% CI 0.51-0.90), and cirrhosis (OR: 0.59; 95% CI 0.44-0.80). CONCLUSION This meta-analysis indicated that elevated NLR may be an effective and noninvasive indicator for prognosis of patients with liver cancer.
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Affiliation(s)
- Guang-Tao Min
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.,The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Yu-Min Li
- Department of general Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Nan Yao
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Jun Wang
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Hong-Peng Wang
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Wei Chen
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
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Prognostic value of the Glasgow prognostic score in lung cancer: evidence from 10 studies. Int J Biol Markers 2017; 33:201-207. [PMID: 29076522 DOI: 10.5301/ijbm.5000308] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Objective: To conduct a meta-analysis of prospective and retrospective studies to reveal the relationship between the Glasgow prognostic score (GPS) and overall survival (OS) or progression-free survival (PFS) in patients with lung cancer. Methods: Correlative studies were included by searching the databases of PubMed, Web of Science, Embase, and PubMed Cochrane Library until April 16, 2017. We combined the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the correlation between GPS and OS or PFS in patients with lung cancer. Results: Ten studies involving 5,369 participants from several regions were identified through searching databases. In a pooled analysis of all studies, elevated GPS was associated with poorer OS (HR = 2.058; 95% CI, 1.51-2.80; p<0.05). However, the combined data showed no significant relationship between the GPS of 1 or 2, and PFS, respectively. Subgroup analysis showed that the patients with GPS ≥1 had poorer OS compared with those with GPS = 0 (HR = 2.01; 95% CI, 1.75-2.32; p<0.001). A similar trend was observed in patients receiving chemotherapy (HR = 1.66; 95% CI, 1.17-2.36; p<0.05) and surgery (HR = 2.88; 95% CI, 1.59-5.22; p<0.001) when stratified by treatment. Conclusions: Increased level of GPS may have a prognostic value in lung cancer. We detected a statistical difference in the association of elevated GPS and poorer OS, though the association was not significant in PFS settings. However, further studies are warranted to draw firm conclusions.
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Lué A, Serrano MT, Bustamante FJ, Iñarrairaegui M, Arenas JI, Testillano M, Lorente S, Gil C, de la Torre M, Gomez A, Sangro B. Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib. Oncotarget 2017; 8:103077-103086. [PMID: 29262546 PMCID: PMC5732712 DOI: 10.18632/oncotarget.21528] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 09/21/2017] [Indexed: 12/14/2022] Open
Abstract
Neutrophil-to-lymphocyte ratio (NLR) is considered a prognostic factor in patients with hepatocellular carcinoma (HCC). Our aim is to investigate the prognostic significance of NLR in patients with HCC treated with sorafenib. Results Median follow-up time was 7 months. Patients were mostly in the intermediate (27.3%) or advanced (72.7%) BCLC stages, 38.6% had vascular invasion and 27.5% extrahepatic disease. A large proportion (38.9%) had been previously treated with TACE. Liver function was preserved: 65.8% were classed as Child A. Median overall survival was 7.7 months (95% CI: 5.8-9.6). In univariate analysis, vascular invasion (P = 0.004), ECOG-PS ≥ 1 (P < 0.001), high bilirubin (P < 0.001), clinical ascites (P = 0.036), BCLC stage (P = 0.004), no previous TACE (P = 0.041) and NRL ≥ 2.3 (P = 0.005) were predictors of poor survival. Skin toxicity (P = 0.039) or hypertension (P = 0.033) during treatment were related to better survival. In multivariate analysis NLR ≥ 2.3 [HR 1.72 (95% CI: 1.03-2.71)], hyperbilirubinemia [HR 3.42 (95% CI: 1.87-6.25)] and ECOG-PS ≥ 1 [HR 1.97 (95% CI: 1.19-3.26)] were found as independent indicators of poor overall survival. Dermatologic adverse effects were an indicator of good overall survival [HR 0.59 (95% CI: 0.38-0.92)]. Material and Methods One hundred and fifty-four consecutive HCC patients treated with sorafenib in four different Spanish hospitals between August 2005 and October 2013 were analysed. Clinical, laboratory, and tumour features were obtained. Survival was calculated from the moment sorafenib treatment was initiated. Log-rank and Cox regression were used to analyse the ability of NLR to predict survival. Conclusions NLR is an independent prognostic indicator for overall survival in HCC patients treated with sorafenib.
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Affiliation(s)
- Alberto Lué
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, 50009, Zaragoza, Spain.,Instituto de Investigación Sanitaria (IIS) Aragón, 50009, Zaragoza, Spain
| | - Maria Trinidad Serrano
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, 50009, Zaragoza, Spain.,Instituto de Investigación Sanitaria (IIS) Aragón, 50009, Zaragoza, Spain
| | | | - Mercedes Iñarrairaegui
- Liver Unit, Clinica Universidad de Navarra-IDISNA, 31008, Pamplona, Spain.,Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), 31008, Pamplona, Spain
| | - Juan Ignacio Arenas
- Department of Gastroenterology, Hospital Universitario Donostia, Begiristain Doktorea Pasealekua, 20014, San Sebastian, Spain
| | - Milagros Testillano
- Department of Gastroenterology, Hospital Universitario Cruces, Plaza de Cruces, 48903, Barakaldo, Spain
| | - Sara Lorente
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, 50009, Zaragoza, Spain.,Instituto de Investigación Sanitaria (IIS) Aragón, 50009, Zaragoza, Spain
| | - Cristina Gil
- Department of Gastroenterology, Hospital Universitario Cruces, Plaza de Cruces, 48903, Barakaldo, Spain
| | - Manuel de la Torre
- Liver Unit, Clinica Universidad de Navarra-IDISNA, 31008, Pamplona, Spain
| | - Alexandra Gomez
- Department of Gastroenterology, Hospital Universitario Donostia, Begiristain Doktorea Pasealekua, 20014, San Sebastian, Spain
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA, 31008, Pamplona, Spain.,Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), 31008, Pamplona, Spain
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Clinical utility of the modified Glasgow prognostic score in lung cancer: A meta-analysis. PLoS One 2017; 12:e0184412. [PMID: 28886134 PMCID: PMC5590927 DOI: 10.1371/journal.pone.0184412] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 08/23/2017] [Indexed: 02/05/2023] Open
Abstract
Objective To perform a meta-analysis of prospective and retrospective studies exploring the association of the modified Glasgow prognostic score (mGPS) with overall survival (OS) in patients with lung cancer. Methods Relevant studies were identified by searching the Cochrane Library, Web of Science, Embase and PubMed until April 16, 2017. We combined hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the correlation between mGPS and OS in patients with lung cancer. Results Eleven studies involving 5817 participants from several countries were included in the meta-analysis. In a pooled analysis of all studies, elevated mGPS predicted poorer OS (HR = 1.77; 95% CI: 1.35–2.31; P<0.05). Subgroup analyses stratified by mGPS showed that mGPS of 1 or 2 and mGPS≥1 were predictive of poorer OS and that the HR for mGPS of 2 (HR = 5.82; 95% CI: 1.85–18.22; P = 0.003) was significantly greater than that for mGPS of 1 (HR = 1.74; 95% CI: 1.24–2.45; P = 0.001) and mGPS≥1 (HR = 1.42; 95% CI: 1.14–1.76; P = 0.002). Among patients undergoing surgery, elevated mGPS had a non-significant correlation with reduced OS (HR = 2.48; 95% CI: 0.90–6.85; P = 0.079), whereas the correlation was significant for patients receiving chemotherapy or other palliative treatment (HR = 1.74; 95% CI: 1.31–2.30; P<0.05). Conclusions Our findings indicate that mGPS may have prognostic value in lung cancer, as we detected a significant association between elevated mGPS and poorer OS. The association between mGPS and poorer OS was non-significant among patients undergoing surgery, which may be attributable to lower tumor load. However, further studies are warranted to draw firm conclusions.
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50
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Melichar B, Vitásková D, Bartoušková M, Javorská L, Kujovská Krčmová L, Pešková E, Hyšpler R, Solichová D, Hrůzová K, Študentová H. Comparison of performance of composite biomarkers of inflammatory response in determining the prognosis of breast cancer patients. Pteridines 2017. [DOI: 10.1515/pterid-2017-0005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Abstract
In the present study, we determined complex indices of inflammatory activity and compared the performance of these indices as prognostic biomarkers in a cohort of breast cancer patients. All proposed composite biomarkers could be evaluated in 418 out of 474 patients in the cohort with complete data on peripheral blood cell count, urinary neopterin, albumin and C-reactive protein. Neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, Glasgow prognostic index, modified Glasgow prognostic index, prognostic nutritional index and C-reactive protein/albumin ratio were calculated and further complex indices were proposed. Although a number of the investigated indices were significantly associated with survival in the univariate analysis, only age and stage, but none of the laboratory biomarkers or composite biomarkers, were significant predictors of survival in the whole group in the multivariate analysis. In patients evaluated before the start of the treatment, age, stage and urinary neopterin were significant predictors of survival. These results underscore the importance of neopterin as a prognostic biomarker in breast cancer.
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Affiliation(s)
- Bohuslav Melichar
- Department of Oncology , Palacký University Medical School and Teaching Hospital , Olomouc , Czech Republic
- Institute of Molecular and Translational Medicine , Palacký University Medical School and Teaching Hospital , Olomouc , Czech Republic
- Fourth Department of Medicine and Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Denisa Vitásková
- Department of Oncology , Palacký University Medical School and Teaching Hospital , Olomouc , Czech Republic
| | - Marie Bartoušková
- Department of Oncology , Palacký University Medical School and Teaching Hospital , Olomouc , Czech Republic
| | - Lenka Javorská
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
- Department of Analytical Chemistry , Charles University School of Pharmacy , Hradec Králové , Czech Republic
| | - Lenka Kujovská Krčmová
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
- Department of Analytical Chemistry , Charles University School of Pharmacy , Hradec Králové , Czech Republic
| | - Eliška Pešková
- Fourth Department of Medicine and Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Radomír Hyšpler
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Dagmar Solichová
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Klára Hrůzová
- Department of Oncology , Palacký University Medical School and Teaching Hospital , Olomouc , Czech Republic
| | - Hana Študentová
- Department of Oncology , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 775 20 Olomouc , Czech Republic
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