Importance of Normalization of Carbohydrate Antigen 19-9 in Patients With Intrahepatic Cholangiocarcinoma

BackgroundAlthough carbohydrate antigen 19-9 (CA19-9) is an established prognostic marker for intrahepatic cholangiocarcinoma (ICC) patients, the significance of elevated preoperative CA19-9 that normalized after resection remains unknown. This study aimed to investigate whether elevated preoperative CA19-9 that normalized after curative resection had an impact on prognosis among patients with ICC.MethodsPatients who underwent curative resection for stage I to III ICC between 2009 and 2018 were identified. Patients were categorized into three cohorts: normal preoperative CA19-9, elevated preoperative CA19-9 but normalized postoperative CA19-9, and persistently elevated postoperative CA19-9. Overall survival (OS), recurrence-free survival (RFS), and hazard function curves over time were analyzed.ResultsA total of 511 patients (247 [48.3%] male; median age, 58 years) were included. Patients with elevated preoperative CA19-9 (n = 378) were associated with worse RFS and OS than those with normal preoperative CA19-9 (n = 152) (both p < 0.001). Patients with persistently elevated postoperative CA19-9 (n = 254) were correlated with lower RFS and OS than the combined cohorts with normal postoperative CA19-9 (n = 257) (both p < 0.001). The hazard function curves revealed that the risk of recurrence and mortality peaked earlier and higher in the elevated postoperative CA19-9 group than the other 2 groups. Multivariate analyses identified persistently elevated, rather than normalized, postoperative CA19-9 as an independent risk factor for shorter RFS and OS in ICC.ConclusionsElevated preoperative serum CA19-9 that normalizes after curative resection is not an indicator of poor prognosis in ICC. Patients with persistently elevated postoperative CA19-9 are at increased risk of recurrence and death.

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Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

Cancer Cell International ◽

10.1186/s12935-020-01676-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Zhi-Qiang Hu ◽

Zheng-Jun Zhou ◽

Chu-Bin Luo ◽

Hao-Yang Xin ◽

Jia Li ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Curative Resection ◽

Carbohydrate Antigen ◽

Plasmacytoid Dendritic Cells ◽

Gamma Glutamyl Transferase ◽

Advanced Tumor ◽

Glutamyl Transferase

Abstract Background Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

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Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

10.21203/rs.3.rs-60882/v2 ◽

2020 ◽

Author(s):

Zhi-Qiang Hu ◽

Zheng-Jun Zhou ◽

Chu-Bin Luo ◽

Hao-Yang Xin ◽

Jia Li ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Curative Resection ◽

Carbohydrate Antigen ◽

Plasmacytoid Dendritic Cells ◽

Gamma Glutamyl Transferase ◽

Advanced Tumor ◽

Glutamyl Transferase

Abstract Background: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods: To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

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Peritumoral Plasmacytoid Dendritic Cells Predict a Poor Prognosis for Intrahepatic Cholangiocarcinoma After Curative Resection

10.21203/rs.3.rs-60882/v1 ◽

2020 ◽

Author(s):

Zhi-Qiang Hu ◽

Zheng-Jun Zhou ◽

Chu-Bin Luo ◽

Hao-Yang Xin ◽

Jia Li ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Curative Resection ◽

Carbohydrate Antigen ◽

Plasmacytoid Dendritic Cells ◽

Gamma Glutamyl Transferase ◽

Advanced Tumor ◽

Glutamyl Transferase

Abstract Background Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19 − 9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

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Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

10.21203/rs.3.rs-60882/v3 ◽

2020 ◽

Author(s):

Zhi-Qiang Hu ◽

Zheng-Jun Zhou ◽

Chu-Bin Luo ◽

Hao-Yang Xin ◽

Jia Li ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Curative Resection ◽

Carbohydrate Antigen ◽

Plasmacytoid Dendritic Cells ◽

Gamma Glutamyl Transferase ◽

Advanced Tumor ◽

Glutamyl Transferase

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Effect of Diagnosis (Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, or Acute Myeloid Leukemia [AML]) on Outcome of AML-Type Chemotherapy

Blood ◽

10.1182/blood.v90.8.2969 ◽

1997 ◽

Vol 90 (8) ◽

pp. 2969-2977 ◽

Cited By ~ 171

Author(s):

Elihu Estey ◽

Peter Thall ◽

Miloslav Beran ◽

Hagop Kantarjian ◽

Sherry Pierce ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Multivariate Analyses ◽

Patient Characteristics ◽

Refractory Anemia ◽

Event Free Survival ◽

Free Survival ◽

Current Medical Practice ◽

Acute Myeloid

Abstract In current medical practice, patients with refractory anemia with excess blasts in transformation (RAEB-t), and especially patients with RAEB, receive chemotherapy regimens (AML Rx) administered to patients with acute myeloid leukemia (AML) less often than do patients with AML. These entities are distinguished primarily by marrow blast percentage (5% to 19% RAEB, 20% to 29% RAEB-t, and ≥30% AML). The poor prognosis of many RAEB or RAEB-t patients, if untreated, led us to give them AML Rx using the same plan as for AML. The purpose of this analysis was to see if diagnosis (RAEB, RAEB-t, or AML) affected outcome. We treated 372 patients with AML (acute promyelocytic leukemia [APL] excluded), 106 with RAEB-t, and 52 with RAEB. AML Rx produced a 62% complete remission (CR) rate in RAEB, essentially identical to the rates in RAEB-t and AML, but event-free survival (EFS) from CR and from start of treatment (start of Rx), as well as overall survival, were poorer in RAEB than in AML or RAEB-t, with AML and RAEB-t being identical. However, patients with RAEB or RAEB-t were more likely to have poor prognostic characteristics, in particular complex abnormalities involving chromosomes 5 and/or 7. Multivariate analyses indicated that, when considered together with cytogenetics and other patient characteristics, a diagnosis of RAEB rather than AML or RAEB-t had no effect on EFS from start of Rx, EFS from CR, survival, or achievement of CR. These analyses suggested a trend for patients with RAEB-t to have better EFS from start of Rx than patients with AML or RAEB (P = .08; relative risk, 0.80; 95% confidence interval, 0.62 to 1.03), but there were no differences with respect to the other outcomes. Our data suggest that the propriety of administering AML Rx to patients with RAEB or RAEB-t who have poor prognosis without treatment is identical to the propriety of treating AML in this fashion. Deterrents to standard AML Rx in these patients could justifiably include cytogenetics, age, etc, but not a diagnosis of RAEB or RAEB-t per se.

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Preoperatively elevated RDW-SD and RDW-CV predict favorable survival in intrahepatic cholangiocarcinoma patients after curative resection

10.21203/rs.3.rs-37317/v1 ◽

2020 ◽

Author(s):

Xingchen Li ◽

Qichen Chen ◽

Xinyu Bi ◽

Jianjun Zhao ◽

Zhiyu Li ◽

...

Keyword(s):

Multivariate Analysis ◽

Intrahepatic Cholangiocarcinoma ◽

Curative Resection ◽

Radical Resection ◽

Distribution Width ◽

Cox Proportional Hazard ◽

Intervention Measures ◽

Kaplan Meier ◽

Preoperative Serum ◽

Cox Proportional Hazard Models

Abstract Background Recent studies suggest red blood cell distribution width (RDW) was a prognostic factor in various types of cancer patients, although the results are controversial. The objective of this study was to investigate the significance of RDW in patients with Intrahepatic cholangiocarcinoma (ICC) after radical resection. Method: The relationship between the preoperative serum RDW value and clinic pathological characteristics was analyzed in 157 ICC patients between January 2012 and June 2018 who underwent curative resection. X-tile software was used to determine 40.2 fl, 12.6% as the optimal cut-off value for RDW-SD and RDW-CV respectively. 153 patients were classified into the low RDW-SD (≤ 40.2, n = 53) group and the high RDW-SD (> 40.2, n = 104) group, low RDW-CV (≤ 12.6, n = 94) group and the high RDW-CV (> 12.6, n = 63). Based on the RDW-SD combined with RDW-CV(SCC), classified into SCC = 0, 1 and 2 group. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. Results Kaplan-Meier curve analysis showed that Patients with RDW-SD > 40.2 were significantly associated with better OS (P = 0.004, median OS: 68.0 months versus 17.0 months). Patients with RDW-CV > 12.6 were significantly associated with better OS (P = 0.030, median OS: not reach versus 22.0 months). Compared with a SCC = 0 or SCC = 1, SCC = 2 was significantly associated with better OS (P < 0.001, median OS: not reach versus 33.0 months versus 16, respectively). In the multivariate analysis, RDW-SD > 40.2 fl (HR = 0.446, 95% CI: 0.262–0.760, P = 0.003), RDW-CV > 12.6% (HR = 0.425, 95%CI: 0.230–0.783, P = 0.006), SCC = 2 (HR = 0.270, 95%CI: 0.133–0.549, P < 0.001) were associated with favorable OS. The multivariate analysis showed RDW-SD, RDW-CV and SCC level were not independent prognostic factors for PFS. Conclusions Preoperative low levels of RDW are associated with poor survival in ICC after curative resection. This provides a new way for predicting the prognosis of ICC patients and more targeted intervention measures.

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Telomere length and recurrence risk after curative resection in women with adenocarcinoma of the lung: A prospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1532 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1532-1532

Author(s):

Eric S. Kim ◽

Yuanqing Ye ◽

Ara A. Vaporciyan ◽

Jinliang Xing ◽

Maosheng Huang ◽

...

Keyword(s):

Prospective Study ◽

Telomere Length ◽

Curative Resection ◽

Early Stage ◽

Recurrence Risk ◽

Cancer Center ◽

Risk Of Recurrence ◽

Early Stage Nsclc ◽

Increased Risk ◽

Telomere Biology

1532 Background: We hypothesized that telomere length in peripheral blood would have significant predictive value for risk of recurrence after curative resection in non-small cell lung cancer (NSCLC). Methods: This prospective study included 473 patients with histologically confirmed early stage NSCLC who underwent curative resection at MD Anderson Cancer Center between 1995 and 2008. Relative telomere length (RTL) of peripheral leukocytes was measured by real-time PCR. The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariable Cox proportional hazard regression model. Results: Median duration of follow-up was 61 months and 151 patients (32%) had developed recurrence at time of analysis. Patients who developed recurrence had significantly longer mean RTL compared to those without recurrence (1.13 vs 1.07, P=0.046). A subgroup analysis indicates that women had longer RTL compared to males (1.12 vs 1.06, P=0.025), and the patients with adenocarcinoma demonstrated longer RTL compared to those with other histologic types (1.11 vs 1.05, P=0.042). To determine if longer RTL in women and adenocarcinoma subgroup would predict risk of recurrence, multivariate Cox analysis adjusting for age, gender, stage, pack year and treatment regimens was performed. Longer telomeres were significantly associated with higher risk of developing recurrence in female (HR=2.25; 95% CI, 1.02-4.96, P=0.044) and adenocarcinoma subgroups (HR=2.19; 95% CI, 1.05-4.55, P=0.036). The increased risk of recurrence due to long RTL was more apparent in females with adenocarcinoma (HR=2.67; 95% CI, 1.19-6.03, P=0.018). Conclusions: This is the first prospective study to suggest that long RTL is associated with recurrence in early stage NSCLC after curative resection. Women and adenocarcinoma appear to be special subgroups in which telomere biology may play an important role. (Supported by NCI CA 111646, CA 55769, and CA 70907.)

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Risk and Secondary Prevention of Stroke Recurrence

Stroke ◽

10.1161/strokeaha.120.028992 ◽

2020 ◽

Vol 51 (8) ◽

pp. 2435-2444 ◽

Cited By ~ 1

Author(s):

Clare Flach ◽

Walter Muruet ◽

Charles D.A. Wolfe ◽

Ajay Bhalla ◽

Abdel Douiri

Keyword(s):

Secondary Prevention ◽

Recurrent Stroke ◽

Stroke Recurrence ◽

Recurrence Free Survival ◽

Vessel Occlusion ◽

Free Survival ◽

Stroke Treatment ◽

Risk Of Recurrence ◽

Increased Risk ◽

Index Stroke

Background and Purpose: With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence over the past 2 decades in a population-based cohort of patients with stroke. Methods: Patients with a first-ever stroke between 1995 and 2018 in South London, United Kingdom (n=6052) were collected and analyzed. Rates of recurrent stroke with 95% CIs were stratified by 5-year period of index stroke and etiologic TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype. Cumulative incidences were estimated and multivariate Cox models applied to examine associations of recurrence and recurrence-free survival. Results: The rate of stroke recurrence at 5 years reduced from 18% (95% CI, 15%–21%) in those who had their stroke in 1995 to 1999 to 12% (10%–15%) in 2000 to 2005, and no improvement since. Recurrence-free survival has improved (35%, 1995–1999; 67%, 2010–2015). Risk of recurrence or death is lowest for small-vessel occlusion strokes and other ischemic causes (36% and 27% at 5 years, respectively). For cardioembolic and hemorrhagic index strokes around half of first recurrences are of the same type (54% and 51%, respectively). Over the whole study period a 54% increased risk of recurrence was observed among those who had atrial fibrillation before the index stroke (hazard ratio, 1.54 [1.09–2.17]). Conclusions: The rate of recurrence reduced until mid-2000s but has not changed over the last decade. The majority of cardioembolic or hemorrhagic strokes that have a recurrence are stroke of the same type indicating that the implementation of effective preventive strategies is still suboptimal in these stroke subtypes.

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Comparison of Serum Tumor Markers for Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma

The American Surgeon ◽

10.1177/000313481007601119 ◽

2010 ◽

Vol 76 (11) ◽

pp. 1210-1213 ◽

Cited By ~ 21

Author(s):

Lian-Yuan Tao ◽

Lei Cai ◽

Xiao-Dong He ◽

Wei Liu ◽

Qiang Qu

Keyword(s):

Hepatocellular Carcinoma ◽

Carcinoembryonic Antigen ◽

Tumor Markers ◽

Intrahepatic Cholangiocarcinoma ◽

High Specificity ◽

Serum Levels ◽

Diagnostic Value ◽

Carbohydrate Antigen ◽

Serum Tumor Markers ◽

Preoperative Serum

Serum tumor markers such as alpha-fetoprotein (AFP), carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, CA242, and CA50 were analyzed to evaluate their diagnostic values in single and combined tests for distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). Preoperative serum levels of AFP, carcinoembryonic antigen, CA19-9, CA242, and CA50 were measured in 45 ICC and 76 HCC patients. The serum levels and the positive rate of AFP, CA19-9, and CA242 were significantly different between the ICC patients and HCC patients. Although AFP (—) was the most sensitive assay for distinguishing ICC from HCC (91.1%), its specificity was significantly lower than that of CA242 (+) and CA19-9 (+). The combination of AFP (-) and CA242 (+) afforded a high specificity of 94.3 per cent and showed highest accuracy (78.5%). Evaluation of patients without liver cirrhosis also showed similar results. The diagnostic value of CA242 (+) is better than that of CA19-9 (+) and AFP (-) in distinguishing ICC from HCC. Combined detection of AFP (—) and CA242 (+) can improve the specificity and accuracy of diagnosing ICC.

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