Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma

Ohira, Masafumi; Yoshizumi, Tomoharu; Yugawa, Kyohei; Kosai‐Fujimoto, Yukiko; Inokuchi, Shoichi; Mizutani, Takashi; Mano, Yohei; Toshima, Takeo; Itoh, Shinji; Harada, Noboru; Ikegami, Toru; Soejima, Yuji; Taketomi, Akinobu; Mori, Masaki

doi:10.1007/s00595-019-01905-7

Cited by 24 publications

(23 citation statements)

References 32 publications

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“…17 Elevated NLR might be related to an increase in circulating neutrophil count and/or the decrease in the lymphocytes count. This imbalance can promote tumor cells' metastasis through the release of various proteases, including VEGF when neutrophils are increased 18 and the circulating lymphocytes, which are ought to induce cytotoxic tumor-cell death, are decreased. This would eventually lead to a diminished immune response, thus a poor outcome.…”

Section: Introductionmentioning

confidence: 99%

<p>Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers</p>

Mansour¹,

Abu-Shawer²,

Lattouf³

et al. 2020

CMAR

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The predictive value of inflammatory parameters as indicators of poor overall survival (OS) has been well studied in various tumors. This study aimed to explore the association of neutrophil-lymphocyte ratio (NLR), among other parameters in upper gastrointestinal tract tumors with distant metastases and OS. Patients and Methods: Retrospective analysis was done for 945 patients (males n= 539, 57.0%) with a median of 57 years (range 19-90 years) treated at King Hussein Cancer Center (KHCC) for gastric (n=501), pancreatic (n=355), and biliary (n=89) carcinoma. NLR, and other parameters were calculated at primary presentation, and the association between the parameters with baseline distant metastases and OS was studied. The optimal cutoff value of NLR was based on receiver operating characteristic curve (ROC) analysis. A prognostic nomogram was then constructed to explore how accurately the OS can be predicted. Results: Patients with high baseline NLR (>3.2) had more distant metastases on presentation than patients with low NLR (≤3.2), (p-value <0.001). Age older than 57 years was associated with poor median OS (8.7 versus 10.6 months, p-value= 0.04). In addition, the location of the tumor as stomach versus biliary tract (Odds Ratio 0.443 95% CI 0.281-0.699), and pancreas versus biliary tract (Odds Ratio 1.193, 95% CI 0.749-1.902, p-value <0.001) proved to be significant. In multivariate analysis, age older than 57 years (p-value =0.0033, HR 0.792, 95% CI 0.678-0.925), location of the tumor (p-value <0.0001), presence of distant metastasis (p-value <0.0001, HR 2.063, 95% CI 1.760-2.419), and NLR (p-value <0.0001, HR 1.045, 95% CI 1.028-1.062) remained significant. Nomogram confirmed the significance of NLR as an independent prognostic factor for OS (HR = 1.62, 95% CI: 1.31-2.01, p-value <0.0001). Conclusion: Our results suggested that high baseline inflammatory markers are associated with distant metastases and poor OS. The utilization of this association in management of cancer patients still warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

<p>Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers</p>

Mansour¹,

Abu-Shawer²,

Lattouf³

et al. 2020

CMAR

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“…NLR was recently reported to be associated with tumor progression in several human malignancies [14][15][16][17][18]. In addition, NLR could serve as a predictive marker in patients with not only PanNEN but also gastrointestinal NEN [27].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, systemic immune-in ammatory markers have been reported as factors that in uence the outcomes of treatments, such as surgery, and the e cacy of chemotherapy in patients with various types of malignancies [13][14][15][16][17][18]. However, the ability of systemic immune-in ammatory markers to predict prognosis in patients with sole, well-differentiated PanNEN, based on the 2017 WHO classi cation [11], other than NEC or synchronous distant metastasis, has remained unknown.…”

Section: Introductionmentioning

confidence: 99%

Increased Circulating/Systemic Neutrophil-Lymphocyte Ratio Predicts Recurrence After Curative Resection in Patients With Well-Differentiated Pancreatic Neuroendocrine Neoplasm Based on the 2017 World Health Organization Classification: A Single-Center Retrospective Study

Miura

Ohtsuka

Aoki

et al. 2020

Preprint

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Background The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the recurrence predictive ability of such markers after curative resection in patients with these neoplasms.Methods Circulating/systemic neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet-white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan–Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals.Results Univariate analysis demonstrated that preoperative neutrophil-lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil-lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil-lymphocyte ratio (HR=3.49 95% CI 1.05-11.7; P=0.042) and 2017 World Health Organization classification (HR=8.81, 95% CI 1.46-168.2; P=0.015) were independent recurrence predictors.Conclusions The circulating/systemic neutrophil-lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

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“…We further investigated the underlying mechanism that makes most CCA cell lines sensitive to adenosine; a few CCA cell lines and imCho cell lines were resistant. The levels of proinflammatory molecules were investigated because inflammation was shown to be involved in CCA progression and aggressiveness [38][39][40]. Levels of nuclear factor-κB (NF-κB), cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS) and Notch1 were examined in five CCA cell lines and one imCho cell lines (Figure 5a,b).…”

Section: Correlation Between Level Of Inflammatory Proteins and Adenomentioning

confidence: 99%

Adenosine Suppresses Cholangiocarcinoma Cell Growth and Invasion in Equilibrative Nucleoside Transporters-Dependent Pathway

Lertsuwan

Phoaubon

Tasnawijitwong

et al. 2020

IJMS

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Cholangiocarcinoma (CCA) is a lethal disease with increasing incidence worldwide. Previous study showed that CCA was sensitive to adenosine. Thereby, molecular mechanisms of CCA inhibition by adenosine were examined in this study. Our results showed that adenosine inhibited CCA cells via an uptake of adenosine through equilibrative nucleoside transporters (ENTs), instead of activation of adenosine receptors. The inhibition of ENTs by NBTI caused the inhibitory effect of adenosine to subside, while adenosine receptor antagonists, caffeine and CGS-15943, failed to do so. Intracellular adenosine level was increased after adenosine treatment. Also, a conversion of adenosine to AMP by adenosine kinase is required in this inhibition. On the other hand, inosine, which is a metabolic product of adenosine has very little inhibitory effect on CCA cells. This indicates that a conversion of adenosine to inosine may reduce adenosine inhibitory effect. Furthermore, there was no specific correlation between level of proinflammatory proteins and CCA responses to adenosine. A metabolic stable analog of adenosine, 2Cl-adenosine, exerted higher inhibition on CCA cell growth. The disturbance in intracellular AMP level also led to an activation of 5′ AMP-activated protein kinase (AMPK). Accordingly, we proposed a novel adenosine-mediated cancer cell growth and invasion suppression via a receptor-independent mechanism in CCA.

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Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma

Cited by 24 publications

References 32 publications

<p>Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers</p>

<p>Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers</p>

Increased Circulating/Systemic Neutrophil-Lymphocyte Ratio Predicts Recurrence After Curative Resection in Patients With Well-Differentiated Pancreatic Neuroendocrine Neoplasm Based on the 2017 World Health Organization Classification: A Single-Center Retrospective Study

Adenosine Suppresses Cholangiocarcinoma Cell Growth and Invasion in Equilibrative Nucleoside Transporters-Dependent Pathway

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