Host Cytokine Genotype is Related to Adverse Prognosis and Systemic Inflammation in Gastro-Oesophageal Cancer

Background Systemic inflammation has been linked with reduced survival in cancer, however, the role of the host cytokine genotype versus tumour phenotype in the generation of this response is not clearly established. This study examined the relationship between cytokine polymorphisms (IL-1β 511, IL-6 174, IL-10 1082, TNFα 308 and LTα +252) and serum cytokine concentrations, serum CRP concentration and survival duration in patients with gastro-oesophageal malignancy. Methods Two hundred and three newly diagnosed patients with gastric or oesophageal cancer had serum CRP and cytokine concentrations determined by ELISA. SNP genotyping was performed by Taqman allelic discrimination genotyping and compared with the genotype observed in 266 healthy volunteers. Clinico-pathological information was collected prospectively and survival duration was recorded. Results Distribution of the cytokine genotypes was similar between patients and controls. The IL-6 174 CC and IL-10 1082 GG genotypes were associated with elevated serum CRP (P = .03, P = .01, respectively; Mann–Whitney U test) and sTNF-R (P = .015, P = .02) concentrations. These genotypes were also associated with reduced survival duration (P = .01, P = .047; log-rank test). TNFα AA genotype was also associated with reduced survival duration on univariate (P = .032) and multivariate analysis (P = .006, multivariate model), but not with inflammatory markers. No other cytokine polymorphisms were associated with systemic inflammatory markers or prognosis. Conclusions There is a pro-inflammatory cytokine haplotype (IL-6 CC, IL-10 GG, TNFα AA) that is associated with adverse prognosis that may act, at least in part, through an inflammatory mediated mechanism. Determining patients’ cytokine haplotype may improve prognostication and allow stratification for intervention studies.     

Serum Levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in Colorectal Cancer Patients

Purpose Expression of tissue inhibitor of metalloproteinases (TIMP)-1 in colorectal cancer tissue is known to be related to disease progression; however, the clinical significance of measuring the blood level of TIMP-1, which we evaluate herein, has not yet been clarified.Methods The serum level of TIMP-1 was measured by a one-step enzyme immunoassay in 123 patients who underwent resection of primary colorectal cancer.Results An elevated level of serum TIMP-1 was associated with advanced Dukes stage (P = 0.03), greater diameter of the primary tumor (P = 0.03), more lymph node metastasis (P = 0.04), and liver metastasis (P 0.001). There was a weakly positive correlation between the serum carcinoembryonic antigen (CEA) level and the serum TIMP-1 level. In patients who underwent potentially curative resection, the disease-free survival was not different between those with a high TIMP-1 level (203.5ng/ml, n = 32) and those with a low TIMP-1 level (203.5ng/ml, n = 66, P = 0.62). In patients with Dukes stage D cancer who underwent noncurative resection, the survival times were not different between those with a high TIMP-1 level (n = 13) and those with a low TIMP-1 level (n = 10, P = 0.20).Conclusions Elevated levels of serum TIMP-1 reflect the extent of colorectal cancer, without a close correlation with the serum CEA level. These findings suggest that measuring the serum TIMP-1 level would not help to predict the prognosis of patients with colorectal cancer.     

Prognostic Effect of Perioperative Change of Serum Carcinoembryonic Antigen Level: A Useful Tool for Detection of Systemic Recurrence in Rectal Cancer

Background The prognosis of patients even with the same stage of rectal cancer varies widely. We analyzed the capability of perioperative change of serum carcinoembryonic antigen (CEA) level for predicting recurrence and survival in rectal cancer patients. Methods We reviewed 631 patients who underwent potentially curative resection for stage II or III rectal cancer. Patients were categorized into three groups according to their serum CEA concentrations on the seventh day before and on the seventh day after surgery: group A, normal CEA level (≤5 ng/mL) in both periods; group B, increased preoperative and normal postoperative CEA; and group C, continuously increased CEA in both periods. The prognostic relevance of the CEA group was investigated by analyses of recurrence patterns and survival. Results Stage III patients showed higher systemic recurrence (P = .001) and worse 5-year survival rates (P < .0001) for group C than for groups A and B. On multivariate analysis, the CEA group was a significant predictor for recurrence (P < .001; relative risk, 2.740; 95% confidence interval, 1.677–4.476) and survival (P = .001; relative risk, 2.174; 95% confidence interval, 1.556–3.308). Conclusions The perioperative serum CEA change was a useful prognostic indicator to predict for systemic recurrence and survival in stage III rectal cancer patients.     

Association of Obestatin, Ghrelin, and Inflammatory Cytokines in Obese Patients with Non-alcoholic Fatty Liver Disease

Background

Three protein products of ghrelin gene (acylated ghrelin, des-acylated ghrelin, and obestatin) are involved in appetite stimulation and suppression. Additionally, there is some evidence suggesting their involvement in metabolic and inflammatory pathways which may be implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the relationships of ghrelin gene products in patients with NAFLD.

Methods

We included 75 morbidly obese patients with biopsy-proven NAFLD (41 with histologic non-alcoholic steatohepatitis (NASH)) with clinical and laboratory data as well as frozen serum samples from the time of liver biopsy. Fasting serum was assayed for obestatin as well as acylated and des-acyl-ghrelin concentrations using ELISA. Bio-Plex inflammatory cytokine assays were used to profile expression of 17 inflammatory mediators, including IL-6, IL-7, IL-8, G-CSF, CCL2, and MIP-1??.

Results

Patients with NASH had twofold higher concentration of des-acyl-ghrelin than patients with non-NASH (2.58 vs. 1.24 pg/ml, P?P?P?P?=?0.014). Obestatin levels at baseline significantly correlated with rate of weight loss after bariatric surgery at various time points.

Conclusions

This study suggests that products of the GHRL gene may be important for the pathogenesis of NASH and fibrosis. Additional confirmatory studies are needed.     

Preoperative Serum Carcinoembryonic Antigen Level as a Predictive Factor of Recurrence After Curative Resection of Colorectal Cancer

Background  We evaluated the prognostic value of the preoperative serum carcinoembryonic antigen (CEA) level in patients with colorectal cancer (CRC). Patients and Methods  The study group comprised 638 patients. The optimal cutoff value for the preoperative serum CEA level was determined. Predictive factors of recurrence were evaluated using multivariate analyses. The relapse-free time was investigated according to the CEA level. Results  All patients underwent potentially curative resection for CRC without distant metastasis, classified as stage I, II, or III. The optimal cutoff value for preoperative serum CEA level was 10 ng/ml. Elevated preoperative serum CEA level was observed in 92 patients. Multivariate analysis identified tumor–node–metastasis (TNM) stage and preoperative serum CEA level as independent predictive factors of recurrence. The relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml significantly differed in patients with stage II and III. However, there was no significant difference in relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml in patients with stage I. Conclusion  Preoperative serum CEA is a reliable predictive factor of recurrence after curative surgery in CRC patients and a useful indicator of the optimal treatment after resection, particularly for cases classified as stage II or stage III.     

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma

ABSTRACT

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Materials and Methods: Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. Results: The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002–1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002–1.015, p =.009) were independent prognostic factors for DSS. Conclusions: IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.     

Interleukin 6 and interleukin 1 receptor antagonist as early markers of complications after lung cancer surgery.

OBJECTIVE: To assess changes of interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1ra) in serum, sputum, and drained pleural fluid of patients operated on due to lung cancer. METHODS: Twenty-seven patients treated with lobectomy or pneumonectomy, including 14 with complications and 13 without complications, were analyzed. Serum IL-6 and IL-1ra concentration was measured before, at the end of surgery, and on postoperative day 1, 3, and 7, by ELISA test. Additionally, concentration of IL-6 and IL-1ra was measured in sputum at the end of surgery and in pleural fluid on postoperative day 1. RESULTS: In the entire group serum concentrations of IL-6 and IL-1ra were significantly elevated after surgery, in comparison with preoperative values. Serum IL-6 concentration was higher in patients with complications only on day 7 (median 59.0 (range: 41.25-76.65) pg/ml vs 21.5 (9.87-35.0) pg/ml; p=0.012). Patients with complications had higher concentration of IL-6 in pleural fluid (91312 (51812-94872) pg/ml vs 2006 (1926-2108) pg/ml; p=0.00008). Serum IL-1ra concentration was higher in patients with complications on day 1 (1832.4 (1144.7-2362.2) pg/ml vs 1088.4 (817.5-1312.5) pg/ml; p=0.01). Concentration of IL-1ra in drained fluid was higher in patients with complications (68128.8 (48104-108564) pg/ml vs 16470 (15930-16875) pg/ml; p=0.0003). On day 1 after surgery a significant correlation between serum and pleural fluid concentration for IL-6 as well as for IL-1ra were observed (Spearman test for IL-6: r=0.47; p=0.02; for IL-1ra: r=0.48; p=0.02). CONCLUSIONS: Elevated concentrations of IL-6 and IL-1ra in pleural fluid on postoperative day 1 are promising early markers of postoperative complications. Elevated concentrations of IL-6 and IL-1ra in serum are good early markers of severity of surgical injury and may reflect development of postoperative complications.     

Cytokine profiles in axial spondyloarthritis

Objectives

Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis.

Material and methods

Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient''s medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined.

Results

In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity.

Conclusions

We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more severe course of aSpA.     

Interleukin-10 and Interleukin-1 receptor antagonists increase during cardiac surgery

Background

It has been reported that inflammatory cytokines such as interleukin-8 and 6 (IL-8, IL-6) increase during cardiac surgery and cause postoperative cardiac dysfunction. Therefore, it is important to investigate changes of suppressive cytokines such as IL-10, interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1 ra) dunng cardiac surgery.

Method

Serum levels of cytokines and IL-1 ra were measured in 10 patients during cardiac surgery with cardiopulmonary bypass. Six blood samples were drawn after inducing anaesthesia. In each sample, serum IL-10, IL-4, IL-8, IL-6 and IL-1 ra were measured by enzyme linked immunosorbent assay.

Results

Serum IL-6 and IL-8 concentration (19.1 ±8.8 pg · ml^?1, and 13.4±5.2 pg · ml^?1, preoperatively) increased to 227.5± 191 pg · ml^?1 and 81.0±56 pg · ml^?1 at 60 min after declamping the aorta (P< 0.01, respectively). Serum IL-10 concentration increased at 60 min after dedamping the aorta compared with the preoperative value (from 1.0±0 pg · ml^?1 to 552.0± 158 pg · ml^?1 P< 0.001]). Similarly, serum IL-1 ra concentration increased from the preoperative value of 1331±896 pg · ml^?1 to 43353±12812 pg · ml^?1 at 60 min after dedamping the aorta (P< 0.00l). Positive correlations were obtained between IL-10 and IL-8. and between IL-10 and IL-6 (γ=0.7, γ=0.8, P< 0.001, respectively).

Conclusion

These findings demonstrate that pro-and anti-inflammatory cytokines increase to maintain their balance during cardiac surgery.     

Interleukin-6 and granulocytic elastase levels following laparoscopic cholecystectomy

Interleukin-6 (IL-6) levels have been shown to correlate well with the magnitude of surgical stress. Serum IL-6 and plasma granulocytic elastase levels, 24 h after surgery, were determined in 12 patients who underwent open major surgery [MS group; esophageal carcinoma (n=5), gastric carcinoma (n=3), colorectal carcinoma (n=4) 5 patients who had open cholecystectomy [OC group] and 17 patients who had laparoscopic cholecystectomy [LC group]. IL-6 levels correlated significantly with the duration of surgery (r=0.685,P < 0.01) and with intraoperative blood loss (r=0.583,P < 0.02). However, there was no significant correlation between granulocytic elastase and the duration of surgery or blood loss. Plasma IL-6 levels in the LC group (21±3 pg/ml) were significantly lower than those in the OC group (47±5 pg/ml) and the MS group (186±36pg/ml) (P<0.05;P<0.01). However, there was no significant difference in granulocytic elastase levels between the LC group (318±8g/l), the OC group (360±130 gmg/ml), and the MS group (701±344 g/l). Increased IL-6 levels correlated well with increased duration of surgery. The lower IL-6 levels following laparoscopic cholecystectomy may therefore be indicative of lower surgical stress associated with laparoscopic cholecystectomy.     

Correlation between levels of TNF-α and IL-6 and hematological involvement in SLE Egyptian Patients with lupus nephritis

Background Systemic lupus Erythematosus (SLE) is a rheumatic autoimmune disease characterized by multisystem organ involvement and by high titers of auto antibodies against several nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network have been described in patients suffering from SLE. However the role of cytokines in different organ involvement is not yet well defined. Objective To determine if levels of Interlukin-6 (IL-6) and Tumor necrosis factor (TNF-α) correlate with SLE disease activity in Egyptian SLE patients and more specifically with hematological involvement. Methods Levels of TNF-α and IL-6 in serum samples from sixty individuals (40 with Systemic lupus Erythmatosus and 20 healthy controls) were determined and renal biopsies were obtained from SLE patients. Results Levels of TNF-α and IL-6 were higher in SLE patients with active compared with inactive hematological disease. Further analysis showed that this association was dependent on inverse correlation (P=0.017, r=−0.49) for IL-6 and (P=0.76, r=−.243) for TNF-α. The mean level of TNF-α and Il-6 was (766.95±357.82 pg/ml) and (135.4±54.23 pg/ml) respectively for patients with active disease while it was (314.01±100.87 pg/ml) and (47.33±18.61 pg/ml) for those with inactive disease and (172.7±39.19 pg/ml) and (21.15±10.99 pg/ml) for the healthy control group respectively. The difference was statistically significant (P=0.002). We found significant positive correlations between TNF-α and IL-6 and the SLE Disease Activity Index (SLEDAI) score. (r=+0.743 and +0.772 respectively). Conclusion Raised level of Il-6 and TNF-α may influence the development of anemia in Egyptian patients with Lupus Nephritis.     

Inflammatory response after laparoscopic and conventional colorectal resections – results of a prospective randomized trial

Background: Short-term benefits of laparoscopic relative to conventional colorectal resections have been demonstrated in randomized controlled trials. It has been suggested that a diminished cytokine and acute-phase response may be responsible for these advantages. Methods: In a randomized controlled trial, patients underwent laparoscopic (n=30) or conventional (n=30) resection of colorectal tumors. Plasma levels of interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) were analyzed repeatedly. Postoperative peak levels and area under the curve values were calculated and compared between groups using the Mann-Whitney U-test. Results: Patient characteristics, preoperative cytokine, and CRP plasma levels were not different between each group. Postoperative peak concentrations of IL-6 (P=0.05) and CRP (P<0.001) and the overall postoperative plasma concentrations of IL-6 (P=0.03) and CRP (P=0.002) were lower in the laparoscopic than in the conventional group. Peak and overall IL-1RA (P=0.2; P=0.2) and IL-10 (P=0.4; P=0.6) plasma concentrations, respectively, were not different between groups. Conclusions: IL-6 and CRP plasma levels were lower after laparoscopic than conventional colorectal resections. The less intense inflammatory response may be an indicator of the milder surgical trauma inflicted by laparoscopic than conventional colorectal resection. Received: 31 March 1999; in revised form: 15 July 1999 Accepted: 20 August 1999     

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).     

The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer

Aim It has been suggested that colorectal neoplasms with or without microsatellite instability (MSI) can stimulate angiogenesis in different ways. The vascular endothelial growth factor (VEGF) system is essential for the angiogenetic process and the growth of malignant tumours. The aim of this study was to analyse the relationship between serum VEGF‐A and the MSI status of patients with colorectal cancer (CRC). Method In the study, 249 patients with CRC were divided into a test cohort of 83 patients and a validation cohort of 166. MSI was determined using immunohistochemistry. Tumours lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as high MSI. The rest were considered to be microsatellite stable (MSS). The serum VEGF‐A analyses were performed by ELISA. Results The tumours of 15 patients in the test cohort and 27 in the validation cohort were classified as MSI. In the test cohort, patients with an MSI tumour had a significantly higher median serum VEGF‐A concentration [617 pg/ml (95% CI 445–863)], compared with patients with an MSS tumour, [317 pg/ml (95% CI 224–386)], P = 0.01. A similar relationship was confirmed in the validation cohort, P = 0.04. Conclusion This study provides some evidence to suggest that patients with an MSI tumour have higher serum VEGF‐A levels than patients with an MSS tumour. If further validated, these findings could be of importance when considering the effects of anti‐VEGF‐A treatment.     

Th1/Th2 cytokine levels: A potential diagnostic tool for patients with necrotizing fasciitis

IntroductionNecrotizing fasciitis (NF) has emerged as rare but rapidly progressive, life-threatening severe skin and soft tissue infection. We conducted a study to investigate whether Th1/Th2 cytokines could serve as biomarkers to distinguish NF from class III skin and soft tissue infections (SSTIs).MethodsA retrospective review was performed for 155 patients suffering from serious skin and soft tissue infections from October 2020 to February 2022. Th1/Th2 cytokines were obtained from peripheral blood and wound drainage fluid samples. Data on demographic characteristics, causative microbiological organisms, Th1/Th2 cytokines, c-reactive protein, procalcitonin and white blood cell (WBC) were extracted for analysis. Factors with statistical difference(p < 0.1) were included in the multivariate logistic regression model. The clinical differential diagnostic values of interleukin-2(IL-2), IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-r (IFN-r) were analyzed by receiver operating characteristic (ROC) curve.ResultsAmong the 155 patients, 66(43%) patients were diagnosed as NF. We found no significant difference for sex, age, location of infection, coexisting condition, predisposition, duration of symptoms before admission and micro-organisms, WBC, procalcitonin and c-reactive protein in NF and class III SSTIs group. NF had higher levels of IL-6 in serum (50.46 [24.89, 108.89] vs. 11.87 [5.20, 25.32] pg/ml; p＜0.01), IL-10 in serum (3.45 [2.03, 5.12] vs. 2.51 [1.79, 3.29] pg/ml; p＜0.01), IL-2 in wound drainage fluid (0.89 [0.49, 1.33] vs. 0.63 [0.14, 1.14] pg/ml; p = 0.02), IL-6 in wound drainage fluid (5000.84 [1392.30, 13287.19] vs. 1927.82 (336.65, 6759.27) pg/ml; p＜0.01), TNF-a in wound drainage fluid (5.20 [1.49, 22.97] vs. 0.96 [0.12, 3.21] pg/ml; p＜0.01) and IFN-r in wound drainage fluid (1.32 [0.47, 4.62] vs. 0.68 [0.10, 1.88] pg/ml; p = 0.02) as compared to the class III SSTIs. Multivariate logistic regression analyses showed that IL-6 in serum, IL-10 in serum and TNF-a in wound drainage fluid exhibited independently significant associations with diagnosis of NF(p＜0.05). In ROC curve analysis of IL-2, IL-6, IL-10, TNF-a and IFN-r for diagnosis of NF, the area under the curve (AUC) of IL-6 in serum could reach to 0.80 (p＜0.001). Using 27.62 pg/ml as the cut off value, the sensitivity was 74% and the specificity was 79% in IL-6 in serum.ConclusionsTh1/Th2 cytokines, IL-6 in serum in particular, are potential biomarkers for the diagnosis of NF in the early stage. However, larger patient populations with multiple centers and prospective studies are necessary to ensure the prognostic role of Th1/Th2 cytokines.     

Interleukin 6 in bile as an indicator of liver function after hepatectomy in patients with biliary tract carcinoma

BACKGROUND: Interleukin (IL) 6 is one of the important components of the early signalling pathways leading to liver regeneration, and has been detected in the bile after liver transplantation. IL-6 concentrations in the bile were studied in an attempt to predict liver function after major hepatectomy for biliary tract carcinoma. METHODS: This study involved 24 patients without cirrhosis who underwent major hepatectomy for biliary tract carcinoma. The bile was sampled regularly through external biliary drainage tubes. IL-6 concentrations in bile and serum were measured using an enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 concentrations increased 37-fold (from mean(s.e.) 56(13) pg/ml before hepatectomy to 2071(398) pg/ml on day 1 after operation) in patients without liver failure after hepatectomy (n = 18) and increased sevenfold (from 71(24) to 530(76) pg/ml) in patients with liver failure after hepatectomy (n = 6). The values were significantly lower in patients with liver failure than in those without liver failure (P < 0.05). The bile IL-6 concentration on day 1 after operation exhibited a significant negative correlation with the maximum serum total bilirubin concentration after hepatectomy. Although serum IL-6 concentrations were also increased in both groups after hepatectomy, there was no significant correlation with postoperative liver function. CONCLUSION: Increased bile IL-6 concentrations after hepatectomy may reflect liver regenerative capacity. Measurement of bile IL-6 concentrations may be clinically useful for the early identification of liver failure after hepatectomy.     

Serum and urine interleukin-6 and transforming growth factor-beta1 in young infants with pyelonephritis

Background Cytokines are involved both in the acute response during pyelonephritis and in the progression to renal scarring. The aim of the present study was to assess the pro-inflammatory interleukin-6 (IL-6) and the anti-inflammatory pro-fibrotic transforming growth factor-beta1 (TGF-beta) in very young infants with pyelonephritis. Methods Serum and urine concentrations of IL-6 and TGF-beta1 were determined by enzyme immunoassay in infants with acute pyelonephritis before antibiotic treatment and in infants with non-renal fever. IL-6 was studied in 12 infants with pyelonephritis and in eight with non-renal fever (median ages, 2 months for both groups). TGF-beta1 was studied in 11 infants with pyelonephritis and in nine with non-renal fever (median ages, 2 and 4 months, respectively). Results No significant differences were documented in serum concentrations of IL-6 and TGF-beta1 between patients and controls. Urine IL-6 levels were significantly higher in infants with pyelonephritis than in controls (medians, 147 and 21.4 pg/ml, respectively; P = 0.0106). The urine levels of TGF-beta1 were lower in infants with pyelonephritis than in controls, although not significantly (medians, 6.12 and 11.0 ng/ml, respectively; P = 0.0705). Conclusions Our findings confirm the implication of IL-6 but not of TGF-beta1 in the pathogenesis of the early stages of pyelonephritis in young infants. Τhe role of the pro-fibrotic TGF-beta1 in the development of renal scarring deserves further investigation.     

Interleukin-6, Transforming Growth Factor-Beta 1, and Bone Markers After Kidney Transplantation

The aim of this study was to investigate the relationship between interleukin 6 (IL-6), transforming growth factor (TGF)-beta 1, IL-6 soluble receptors, and biochemical parameters of bone turnover after kidney transplantation. Of 64 patients enrolled in the study, 19 received the kidney transplant 2 to 12 months before the study, and 45 within the previous 15 to 175 months. We measured IL-6, TGF-beta 1, intact parathyroid hormone (PTH) bone alkaline phosphatase (BALP), osteocalcin (OC), and procollagen type I propeptide (P1CP) concentrations in the serum, and deoxypyridinoline crosslinks (DPD) in the urine of the patients. In 16 patients in the first posttransplantation year, the concentrations of IL-6 (P = 0.02), TGF-beta 1 (P = 0.01), BALP (P = 0.0002), OC (P = 0.001), and DPD (P = 0.01) were significantly higher than in patients with longer posttranslation period. Statistically significant negative correlation was found between posttransplantation time and IL-6 (P = 0.04), BALP (P = 0.003), OC (P = 0.0009), P1CP (P = 0.03), and DPD (P = 0.01) concentrations. Repeated measurements of the investigated parameters in the first posttransplantation year showed a significant decrease only in TGF-beta 1 level. In all patients, IL-6 correlated positively with PTH (P = 0.0009) and DPD (P = 0.03), and IL-6 soluble receptor (IL-6 sR) with DPD (P = 0.03). A decrease in IL-6 and TGF-beta 1 concentrations that paralleled the decrease in bone turnover markers in the posttransplantation period indicated that IL-6 and TGF-beta 1 were probably involved in the bone turnover after kidney transplantation.     

Low lean tissue mass can be a predictor of one-year survival in hemodialysis patients

Purpose: Nutritional status has a significant impact on the outcomes in the dialysis population. The aim of this study was to evaluate the association between body composition and a one-year survival of hemodialysis patients.

Methods: Forty-eight patients with chronic kidney disease stage V treated with hemodialysis for more than three months were included. Body composition was assessed by bioimpedance spectroscopy (Body Composition Monitor, Fresenius Medical Care). Blood samples for serum creatinine, serum albumin, serum prealbumin, high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), insulin-like growth factor 1(IGF-1) concentrations were taken before the midweek dialysis session.

Results: Over the course of a one-year observation, seven patients died. We observed a significantly lower lean tissue index (LTI) (p?=?.013) and higher IL-6 (p?=?.032) and hsCRP levels (p?=?.011) among the patients who died. The remaining biochemical markers did not differ between these two groups. Kapplan–Meier analysis revealed a worse survival rate in patients with sarcopenia (lower than the 10th percentile for their age and gender) in comparison with those with normal LTI. However, it was not of statistical significance (p?=?.055). LTI inversely correlated with age and IL-6 and positively with IGF-1.

Conclusions: Sarcopenia defined as decreased LTI, is a relatively common condition among patients undergoing maintenance hemodialysis, it can also be associated with a lower one-year survival rate. Decreased lean tissue mass can be associated with old age, lower IGF-1 levels and higher IL-6 levels. Body composition assessment may provide prognostic data for hemodialysis patients.     

Peritoneal Carcinoembryonic Antigen Level for Predicting Locoregional and Distant Spread of Gastric Cancer

Purpose Peritoneal recurrence is not an uncommon cause of death after surgery for gastric cancer, even after surgery with curative intent. This indicates that there is undetected residual disease in the peritoneal cavity. We conducted this study to determine the value of peritoneal and serum carcinoembryonic antigen (CEA) levels and peritoneal washing cytology in predicting the locoregional and distant spread of gastric cancer. Methods We prospectively evaluated 70 consecutive patients with gastric cancer by measuring peritoneal CEA (pCEA) and serum CEA (sCEA) levels and peritoneal washing cytology results, and studying their effect on the histopathologic properties. The effect of the pCEA level on disease-free survival (DFS) and overall survival (OS) was also evaluated in patients treated with curative intent. Results Twenty-one (30%) patients had sCEA levels >10 ng/ml, whereas 25 patients (35.7%) had pCEA levels >10 ng/g protein and 26 patients (37.1%) had positive cytology. The pCEA levels were significantly higher in patients with hepatic metastases (P = 0.034), or serosal (P = 0.028), and peritoneal (P = 0.026) involvement, whereas the sCEA levels were significantly higher only in patients with hepatic metastases (P = 0.04). Similarly, positive cytology was mainly detected in patients with hepatic metastases (P = 0.004). The pCEA levels significantly affected DFS (P = 0.002) and OS (P = 0.01) in 34 patients treated with curative intent. Conclusion Since pCEA levels are more useful for predicting locoregional recurrence, their measurement during surgery may help plan the most appropriate surgical strategy and adjuvant therapy.