Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases

Background The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) in patients with colorectal liver metastases. Methods Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Results Patients with 2–5 elevated biomarkers were at an increased risk of relapse compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1–1.72) or postoperatively (HR 1.54, 95% CI 1.23–1.92). Patients with 2–5 elevated biomarkers were also at an increased risk of death compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39–2.24) or postoperatively (HR 1.83, 95% CI 1.44–2.33). Conclusion The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.Peer reviewe

Increasing Incidence of Hospitalization for Stroke and Transient Ischemic Attack in Young Adults:A Registry-Based Study

BACKGROUND: Studies have reported increasing incidence of ischemic stroke in adults younger than 50 to 55 years. Information on temporal trends of other stroke subtypes and transient ischemic attack (TIA) is sparse. The aim of this study was to investigate temporal trends of the incidence of hospitalizations for TIA and stroke including sex‐ and subtype‐specific trends in young adults aged 15 to 30 years. METHODS AND RESULTS: From the Danish National Patient Register, we identified all cases of first‐ever stroke and TIA (age 15–30 years) in Denmark, who were hospitalized during the study period of 1994 to 2012. Incidence rates and estimated annual percentage changes (EAPCs) were estimated by using Poisson regression. During the study period, 4156 cases of first‐ever hospitalization for stroke/TIA were identified. The age‐standardized incidence rates of hospitalizations for stroke increased significantly (EAPC 1.83% [95% CI 1.11–2.55%]) from 11.97/100 000 person‐years (PY) in 1994 to 16.77/100 000 PY in 2012. TIA hospitalizations increased from 1.93/100 000 PY in 1994 to 5.81/100 000 PY in 2012 and after 2006 more markedly in men than in women (EAPC 16.61% [95% CI 10.45–23.12%]). The incidence of hospitalizations for ischemic stroke was markedly lower among men, but increased significantly from 2006 (EAPC 14.60% [95% CI 6.22–23.63%]). The incidences of hospitalizations for intracerebral hemorrhage and subarachnoid hemorrhage remained stable during the study period. CONCLUSIONS: The incidence rates of first‐time hospitalizations for ischemic stroke and TIA in young Danish adults have increased substantially since the mid 1990s. The increase was particularly prominent in the most recent years

Lower Urinary Tract Symptoms, Erectile Dysfunction, and Quality of Life in Poststroke Men:A Controlled Cross-Sectional Study

The aim of the current study was to compare lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and quality of life (QoL) in poststroke and healthy men. Thirty poststroke men with stroke-related LUTS, and as controls, 96 healthy men participated in this controlled, cross-sectional study. Participants filled in the Danish Prostate Symptom Score (DAN-PSS-1) Questionnaire, the International Index of Erectile Function (IIEF-5), the 36-Item Short Form (SF-36), the Nocturia Quality-of-Life (N-QoL) Questionnaire. In the age group ≤55 years, comparing poststroke men with healthy controls both with LUTS, the results indicated DAN-PSS-1, total score median 13 (4-17) versus 3 (2-6), p =.05; IIEF-5 25 (14-25) versus 24 (23-25), p =.06; SF-12, total score 499 (360-679) versus 695 (644-734), p =.02; and N-QoL 98 (70-100) versus 96 (90-100), p =.65. In the age group >55 years, comparing poststroke men with healthy controls both with LUTS, the results indicated DAN-PSS-1, total score 13 (8-24) versus 5 (2-7), p <.01; IIEF-5 13 (5-20) versus 25 (24-25), p <.01; SF-36, total score 585 (456-718) versus 742 (687-772), p <.01; and N-QoL, total score 81 (66-95) versus 98 (80-100), p <.01. The results demonstrated that in age group above, but not below 55 years, poststroke men with LUTS had significantly higher frequency of severe and bothersome LUTS and ED than the healthy controls with LUTS, while QoL and N-QoL were significantly lower in comparison. It is recommended to identify and assess older poststroke men for LUTS, ED, and QoL

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer:the ACCORE study

BACKGROUND: Elderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes. PATIENTS AND METHODS: A retrospective single-centre study of 529 patients with stages II–III CRC treated with adjuvant chemotherapy (5-fluorouracil/capecitabine+/÷oxaliplatin) from 2001 to 2011 at Herlev Hospital, Denmark. Baseline characteristics, chemotherapy and outcome were analysed with respect to age after adjusting for PS and comorbidity. RESULTS: Elderly patients (>70 years) had significantly more comorbidity (p<0.001) and poorer PS (p=0.001) than younger patients. Elderly were more frequently treated with single-agent therapy (p=0.001) and at lower initial dose (p<0.001). There was no age-dependent difference in 3-year disease-free survival (DFS; HR 1.09, 95% CI 0.80 to 1.47, p=0.59), in grade 3–5 toxicity (29% vs 28%, p=0.86) or in 10-year CRC mortality (28%, HR 1.07, p=0.71). In elderly patients, a reduction in chemotherapy dose intensity compared with full dose had no impact on DFS or CRC mortality. Elderly patients receiving <50% of planned cycles had shorter DFS (HR=1.78, p=0.020) and higher CRC mortality (HR=2.17, p=0.027) than elderly receiving all cycles. Poor PS in younger and elderly patients was related to shorter DFS (HR=1.95, p=0.002; HR=1.6, p=0.035, respectively) and overall survival (OS; HR=2.28, p<0.001; HR=2.03, p=0.002). Comorbidity in younger patients was significantly related to shorter DFS (HR 2.72, p<0.001), OS (HR 3.16, p<0.001) and higher CRC mortality (HR 2.70, p=0.001). CONCLUSIONS: Choice of regimen, primary dose reduction and given dose intensity in patients treated with adjuvant chemotherapy for CRC were highly dependent on age. However, age had no impact on DFS and CRC mortality. Comorbidity in younger patients and PS in all patients were associated with shorter DFS and higher CRC mortality

Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer

Background In colorectal cancer (CRC) patients, guidelines only recommend measurement of preoperative carcinoembryonic antigen (CEA), although postoperative CEA may be more informative. However, the sensitivity of both preoperative and postoperative CEA in identifying relapse is limited. We studied whether CA19-9, YKL-40, C-reactive protein (CRP) and interleukin (IL)-6 add prognostic information combined with postoperative CEA. Material and methods This post-hoc analysis included 147 radically resected stage II (n = 38), III (n = 91) and IV (n = 18) CRC patients treated with adjuvant 5-fluorouracil (5-FU)-based therapy in the phase III LIPSYT study (ISRCTN98405441). We collected postoperative blood samples a median of 48 days after surgery. We analysed relapses, sensitivity, positive predictive value (PPV) and disease-free (DFS) and overall survival (OS) by bootstrap, Kaplan-Meier and adjusted Cox-models in the elevated vs. normal biomarker groups. Results Elevated postoperative CEA associated with impaired DFS (HR 7.23; CI(95%)3.85-13.58), impaired OS (HR 7.16; CI(95%)3.76-13.63), and more relapses (HR 7.9; CI(95%)3.4-18.2); but sensitivity for CEA in finding relapses was only 31% (CI(95%)21-48%). Normal CEA combined with an elevated YKL-40 or elevated CRP showed more relapses (HR for YKL-40 2.13 [CI(95%)1.10-4.13], HR for CRP 3.14 [CI(95%)1.21-8.16]), impaired DFS (HR 2.18 [CI(95%)1.12-4.24] or 3.23 [CI(95%)1.34-7.82]), and impaired OS (2.33 [CI(95%)1.24-4.40] or 2.68 [CI(95%)1.12-6.44]). Elevated CEA combined with a concomitantly elevated CA19-9, YKL-40, CRP or IL-6 showed a respective PPV of 100, 90, 100, and 100%. Conclusion In radically operated stage II to IV CRC patients who received adjuvant 5-FU-based chemotherapy, a postoperatively elevated CEA alone or in combination with CA19-9, YKL-40, CRP, or IL-6, or a normal CEA combined with an elevated YKL-40 or with an elevated CRP, may indicate patients at high risk of relapse.Peer reviewe