Benign Disease Group Research Articles

Abnormal Expression of Golgi Protein 73 in Clinical Values and Their Role in HBV-Related Hepatocellular Carcinoma Diagnosis and Prognosis.

Background:The up-regulation of hepatic Golgi protein 73 (GP73) is associated with the progression of hepatocellular carcinoma (HCC). However, the exact mechanism and clinical values of its diagnosis and prognosis still need to be clarified.Objectives:To investigate the clinical values of abnormal liver or circulating GP73 expression and their effect on HCC diagnosis and prognosis.Materials and Methods:The expression of GP73 was investigated in 88 cancerous and self-control non-cancerous tissues using tissue microarrays with immunohisto- chemistry and was confirmed by Western blotting. Circulating GP73 levels were detected in the sera of 281 patients with liver diseases using enzyme-linked immunosorbent assay.Results:The levels of circulating GP73 expression in the HCC group were higher than those in any group of benign liver diseases or controls. No significant difference was found between GP73 expression and patients’ sex or age, tumor size, or AFP level except for those with hepatitis B virus (HBV) infection or distal metastasis (P < 0.05). The area under the receiver operating characteristic curve, sensitivity, and specificity for HCC diagnosis were 0.881, 78.34%, and 77.59% for GP73 levels over 70 μg/L or 0.754, 71.97%, and 84.48% for alpha-fetoprotein levels over 50 μg/L, respectively. The total incidence of GP73 plus alpha-fetoprotein was up to 87.26% for HCC. A positive GP73 result with brown particles was mainly located in the cytosol, with a few in the nucleus and none in the cell membrane, with abnormal expression in HCC tissues (480.7 ± 148.7) that was significantly higher (t = 10.730, P < 0.001) than those in their non-cancerous tissues (208.0 ± 66.1). The high GP73 expression in HCC was related to lymph node metastasis (χ2 = 6.940, P = 0.008), gross classification (χ2 = 6.311, P = 0.012), HBV (χ2 = 4.803, P = 0.028), tumor node metastasis staging (χ2 = 4.887, P = 0.027), and five-year survival (χ2 = 5.206, P = 0.023).Conclusions:Abnormality of hepatic or circulating GP73 expression should be regarded as an emerging biomarker for HCC diagnosis and prognosis.

Clinical features of mesenteric lymphatic malformation in children

BackgroundMesenteric lymphatic malformations (MLs) are a heterogeneous group of benign diseases of the lymphatic system that present with cystic dilated lymphatics of the mesentery. MLs are rare and represent less than 5% of all lymphatic malformations. The aims of this study were to analyze the characteristics of MLs in children and to suggest a modified classification. Patients and methodsWe investigated 25 patients who underwent ML surgery. The clinical data and pathological findings were reviewed retrospectively. We divided the patients into 4 groups according to the operative findings. Group 1 included patients with MLs involving the intestinal walls. Group 2 included patients with pedicle-type MLs with no relationship to the mesenteric vessels. Group 3 patients presented with MLs located in the mesenteric boundaries near the mesenteric vessels. Group 4 patients had multicentric and diffusely infiltrated MLs. ResultThe male-to-female ratio was 11:14, and the median age at diagnosis was 5years of age. The most common symptom was abdominal pain. The jejunal mesentery was the most frequently involved site in this study. Five patients showed the macrocystic type and 20 patients showed the mixed cystic type. With the exception of one patient with a large mixed cystic-type ML who underwent incomplete mass excision, 24 patients underwent complete mass excision. The group 1 patients (n=14) underwent mass excision performed with segmental resection of the bowel. The group 2 patients (n=3) only underwent mass excision surgery. The patients in group 3 (n=7) underwent mass excision with segmental resection of the intestine because ML excision altered the blood supply of the adjacent intestines. The group 4 patients (n=1) presented with MLs involving the entire mesentery and underwent incomplete excision. ConclusionThe relationships between MLs and the neighboring organs determine the surgical strategy, and the size and location of MLs affect the operative methods. The modified classification based on these findings can facilitate effective treatment planning.

Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience.

Objective:Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey.Materials and Methods:Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated.Results:The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction.Conclusion:Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

Association of expressions and gene polymorphisms of leptin receptor with breast cancer

Objective To evaluate the association of expressions and gene polymorphism of leptin receptor (LEPR) in breast cancer with tumorigenesis, development and clinicopathologic factors. Methods The immunohistochemical method and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to evaluate LEPR expressions and LEPR Gln223Arg polymorphism in 150 cases with breast cancer, 80 cases with benign breast lesions, 50 cases with corresponding normal breast tissue and 128 healthy controls. Results The expression rate of LEPR genes in breast cancer tissues was significantly higher than that in benign breast lesions and that in corresponding normal breast tissues [70.67 % (106/150) vs 56.25 % (45/80) vs 44.00 % (22/50), P 0.05). The frequencies of alleles genes in breast cancer patients (G and A) were 78.33 % (235 cases) and 21.67 % (65 cases), and the differences were statistically significant compared with those in the benign disease group or in healthy control group (χ2 = 12.52, P= 0.001). The positive expression rate of LEPR gene in patients with lymph node metastasis was 87.8 %, which was higher than that in patients with no lymph node metastasis (60.2 %) (P= 0.02). According to the results of multivariable analyses, high expression of LEPR gene, LEPR Gin223Arg gene polymorphisms and increased waist-hip ratio (WHR) were risk factors for breast cancer (all OR > 1). Conclusion High expression of LEPR, LEPR Gln233Arg polymorphism and the elevated WHR may be correlated with breast cancer. Key words: Breast neoplasms; Leptin receptor; Genes; Polymorphism, single nucleotide

Combined use of epithelial membrane antigen and nuclear matrix protein 52 as sensitive biomarkers for detection of bladder cancer.

The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC). A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC). Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p&lt;0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p&lt;0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity. EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.

The diagnostic value of tumor markers in bronchoalveolar lavage fluid for the peripheral pulmonary carcinoma.

To investigate the value of Ubiquitin specific peptidase 8 (USP8), Chitinase 3-like 1 (YKL40), Heat shock protein 90a (HSP90α), glutathione S-transferase P1 (GSTP1), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and cytokeratin fragment antiogen 21-1 (CYFRA21-1) in bronchoalveolar lavage fluid (BALF) and serum for diagnosis in patients with peripheral lung cancer. The concentration of these markers were measured in 50 patients with peripheral lung cancer and 50 patients with benign lung diseases by using enzyme-linked immuno sorbent assay methods. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the BALF of USP8, YKL40, HSP90α, CEA, NSE and CYFRA21-1. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the serum of HSP90α and CEA. There were no differences in others. There were no correlation between the concentration of all markers and age, histological type, TNM stage (I-IV). There was a weak correlation between the primary foci diameters and the concentration of YKL40 in BALF. (Pearson's correlation: 0.203, P = 0.048) The diagnostic efficiencies of USP8, YKL40, HSP90α were superior to CYFRA21-1 and NSE, being lower CEA. Detection of tumor markers in BALF was superior to serum specimens. The measurement of USP8, HSP90α and YKL40 in BALF had more clinical value for the diagnosis of peripheral pulmonary carcinoma.

Clinical value of combined detection of serum CA724, CEA and TNF-α for advanced gastric cancer

Objective To explore the clinical value of combined detection of serum carbohydrate antigen 724 (CA724), carcinoembryonic antigen (CEA), and tumor necrosis factor-α (TNF-α) for the diagnosis, assessment of curative effect, and illness monitoring for advanced gastric cancer (AGC). Methods Serum levels of CA724, CEA and TNF-α were measured by the methods of chemiluminescence and compared in 20 patients with AGC (Group A ), 20 patients with benign gastric disease (Group B), and 20 healthy adults (Group C). Also, serum levels of CA724, CEA and TNF-α in peripheral blood as well as in portal vein were measured and compared before and after surgical treatment in patients of group A. Results The serum levels of CA724, CEA and TNF-α in patients of group A were significantly higher than groups B and C (P<0.05). In addition, the serum levels of CA724, CEA and TNF-α in patients of group A were decreased after surgical treatment and increased slightly after one month (P<0.05). Conclusions The serum levels of CA724, CEA and TNF-α in most patients of AGC are significantly elevated and the combined detection of serum CA724, CEA and TNF-α contributes to the diagnosis, assessment of curative effect, and illness monitoring for AGC. Key words: Stomach neoplasms/DI/TH/ME; Antigens, tumor-associated, carbohydrate/ME; Carcinoembryonic antigen/ME; Tumor necrosis factor-alpha/ME

Annexin A3 is a mammary marker and a potential neoplastic breast cell therapeutic target.

Breast cancers are the most common cancer-affecting women; critically the identification of novel biomarkers for improving early detection, stratification and differentiation from benign tumours is important for the reduction of morbidity and mortality.To identify and functionally characterise potential biomarkers, we used mass spectrometry (MS) to analyse serum samples representing control, benign breast disease (BBD) and invasive breast cancer (IDC) patients. Complementary and multidimensional proteomic approaches were used to identify and validate novel serum markers.Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was subsequently validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P < 0.0005).In addition, paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro.This study confirms the novel role of ANX A3 as a mammary biomarker, regulator and therapeutic target.

Calponin-h2 is upregulated in the tissues and plasma of patients with breast cancer.

Increasing evidence has demonstrated that changes in plasma nuclear matrix proteins are specific markers of cancer. Furthermore, proteomic analysis has revealed that calponin-h2 is upregulated in human breast cancer tissue, but is absent in healthy and benign controls. However, the roles of levels of plasma calponin-h2 in the diagnosis of breast cancer and its association with clinicopathological parameters remain to be elucidated. In the present study, the plasma levels of calponin-h2 in patients with breast cancer, benign breast disease and in healthy controls were examined using an enzyme-linked immunosorbent assay. The expression levels of calponin-h2 in invasive breast cancer and normal breast tissues were measured using immunohistochemistry. Statistical analyses examined the association between the levels of plasma calponin-h2 and clinicopathological parameters. The results demonstrated that the plasma level of calponin-h2 in breast cancer was significantly higher than those in the healthy control and benign breast disease groups (P<0.05). The combination of calponin-h2, carcinoembryonic antigen, carbohydrate antigen 15-3 improved the diagnosis of breast cancer. The plasma levels of calponin-h2 PR-breast cancers was significantly higher, compared with PR+ breast cancers (P=0.033), and the plasma levels of calponin-h2 in patients with breast cancer aged >50 years was significantly higher than in patients ≤ 50 years of age (P=0.001). No association was found between the level of plasma calponin-h2 and other clinicopathological parameters of breast cancer. Taken together, these results indicated that calponin-h2 may be a useful marker of breast cancer.

Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression

BackgroundScreening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups.MethodsThe expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples. Three miRNAs (miR-34a, miR-150, and miR-923) were further examined in a validation cohort of 97 subjects divided into the same five groups, and in an independent public dataset of 40 CRC samples and paired normal tissues.ResultsHigh levels of circulating miR-34a and low miR-150 levels distinguished groups of patients with polyps from those with advanced cancer (AUC = 0.904), and low circulating miR-150 levels separated patients with adenomas from those with advanced cancer (AUC = 0.875). In addition, the altered expression of miR-34a and miR-150 in an independent public dataset of forty CRC samples and paired normal tissues was confirmed.ConclusionWe identified two circulating miRNAs capable of distinguishing patient groups with different diseases of the colon from each other, and patients with advanced cancer from benign disease groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1327-5) contains supplementary material, which is available to authorized users.

Mo1376 Biliary Endoprosthesis: a Retrospective Analysis of Biliary Stent Related Late Complications

Mo1376 Biliary Endoprosthesis: a Retrospective Analysis of Biliary Stent Related Late Complications Marie Ooi*, Santosh Sanagapalli, Ken Liu, Gavin Barr, James L. Cowlishaw, Rupert W. Leong, Peter Katelaris Gastroenterology, Concord Hospital, Sydney, NSW, Australia Biliary endoprosthesis: Biliary endoprosthesis: A retrospective analysis of biliary stent related late complications. Background: Biliary sepsis may occur following placement of biliary stents either due to stent dysfunction or delay in scheduled interval stent exchange. Causes of stent dysfunction include stent occlusion by debris or tumour ingrowth, stentmigration and stent fracture. Thechoice of stent typedependson the life expectancy of the patient. According to the European Society of Gastroenterology guidelines, plastic stents are cost effective if estimated life expectancy is!4 months while self-expandable metallic stents (SEMS) are preferred if life expectancy exceeds 4 months.Aims: Toassess the frequency and causesof late (after 30days) complications of biliary stenting. Methods: We retrospectively analysed patients presenting with complications related to biliary stents over a 4-year period (Jan 2010-Dec 2013). Data collected included demographics, co-morbidities, indication for stent insertion and stent type(s). Primary outcome was stent related complications. Results: Of 699 patients who had ERCP (58% female, median age 73 yr ; interquartile age range 67-78 yr), 269 had biliary stents inserted, 141 for malignant biliary strictures (Group 1) and 128 for benign biliary disease (Group 2). In Group 1, 118 (84%) had initial palliation of biliary obstruction with a plastic stent while 23 (16%) had a SEMS. In Group 2, a majority (nZ118, 92%) had plastic stents and 10 (8%) had a SEMS. A total of 68 patients (25%) had stent related complications, of which 58 (22%) presented with obstructive jaundice or cholangitis due to occluded stents (13.5 2.9 stents/ yr). Other complications included cholecystitis (nZ3), liver abscess (nZ1), stent migration (nZ5), and stent fracture (nZ1). In Group 1, plastic stents had an OR 4.3 (95% CI 1.85-10.02; p!0.01) for stent occlusion compared to SEMS. In malignant biliary strictures, the time to stent occlusion for plastic, bare metal stents and covered metal stents were 2.1, 6.6 and 11.9 months, respectively. For Group 2, all 23 occluded stents occurred with plastic stents in patients lost to follow up with a mean stent patency of 24.9 months, whilst no stent occlusion occurred with covered SEMS. Conclusion: For malignant strictures, plastic stents had a significantly higher rate of occlusion and a lower duration of stent patency compared to SEMS. For benign biliary disease, all occluded stents were due to stents inadvertently left in situ for longer than recommended. A stent registry database is recommended to record all patients with biliary stents to ensure prophylactic stent exchange occurs at a timely interval to reduce the risk of biliary sepsis related to stent occlusion. For malignant strictures, earlier stent revision (! 2 months) should be considered if a plastic stent was inserted.

Diagnostic value of 18F-FDG PET/CT in patients with pancreatic neoplasm

Objective To evaluate the diagnostic value of 18F-FDG PET/CT in patients with pancreatic neoplasm. Methods Fifty-three patients (36 males, 17 females; age:(60.3±8.9) years) who underwent 18F-FDG PET/CT examination for suspected pancreatic tumor were retrospectively analyzed. Thirty-two of them underwent dual-time point imaging. The characteristics of PET/CT images and serum CA19-9 were reviewed. Pathological results were used as a gold standard for evaluating the diagnostic value of PET/CT. Two-sample t test, paired t test and ROC curve analysis were used for data analysis. Results Thirty-nine patients were finally diagnosed with pancreatic cancer and the other fourteen patients with benign disease. With SUVmax cutoff value of 3.13, the sensitivity and specificity of single-time point 18F-FDG PET/CT for diagnosis of pancreatic cancer were 92.3%(36/39) and 9/14, respectively. The SUVmax was significant different between pancreatic cancer group and benign disease group (6.16±2.89 vs 3.37±1.58; t=4.46, P 0.05). With the SUVmax cutoff value of 3.3, the sensitivity, specificity and accuracy in the early scan were 87.0%(20/23), 6/9 and 81.2%(26/32), respectively. While with the SUVmax cutoff value of 3.0, the sensitivity, specificity and accuracy in the delayed scan were 95.7%(22/23), 5/9 and 84.4%(27/32), respectively. Conclusion 18F-FDG PET/CT is a useful tool in the differential diagnosis of benign from malignant pancreatic diseases. Key words: Pancreatic neoplasms; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer ⁎

Abstract Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor (VEGF) and CD105-microvessel density (MVD) in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods Immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expression. Positively stained microvessels were counted in dense vascular foci under 400× magnification. MVD in the peripheral area adjacent to the lesion and in the central area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue (22.0%, P &lt; 0.05). There was a positive correlation between VEGF overexpression and histological grade, lymph node metastasis, and distant metastasis of invasive breast cancer. VEGF expression was not related to age or size of the tumor (P &gt; 0.05). MVD of the peripheral area adjacent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benign breast disease groups (P &lt; 0.01 for each group). There were significant differences in the mean CD105-MVD, between invasive breast tumors with a histological grade of I or II and grade III; between tumors with lymph node or distant metastasis; and between patients with or without recurrence (P &lt; 0.05). However, there was no difference in the mean MVD between the two age groups (≤ 50 years vs. &gt; 50 years) or the two tumor diameter groups (≤ 2 cm vs. &gt; 2 cm), P &gt; 0.05. Conclusion Overexpression of VEGF and MVD may be important biological markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor markers could provide better prognostic monitoring for disease recurrence and metastasis, as well as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as well as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better follow-up regimens and appropriate treatment strategies for breast cancer patients.

Quantification of serum MET in non-small-cell lung cancer and its clinical significance

ObjectivesMesenchymal–epithelial transition factor (MET) plays a critical role in the development and progression of lung cancer. We aimed to quantify the level of serum MET DNA, analyze its diagnostic value, and provide a novel biomarker for lung cancer. MethodsSerum MET DNA was extracted from 95 patients with lung cancer, 10 with benign lung diseases, and 34 healthy volunteers. MET DNA was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Data were analyzed using statistical software SPSS 17.0. ResultsSerum MET DNA level in the lung cancer group was higher than in the healthy group and benign lung diseases group. Serum MET DNA level was higher in lung cancers patients with smoking, squamous cell carcinoma, advanced TNM stage, and increased tumor size. The difference in serum MET DNA level was not related to sex, age, and lymph node metastasis among the lung cancer patients. The receiver operating characteristic curve showed a sensitivity of 72.6% and specificity of 90.9% for the ability of serum MET DNA to detect lung cancer at the cutoff value of 1.30×104 copies/μL. The association of serum MET DNA level with existing clinical lung tumor markers was analyzed, including neuron-specific enolase, squamous cell carcinoma antigen, and cytokeratin fragment 21-1. With the combination of serum MET DNA, the sensitivity was raised from 39.1%, 24.9%, 66.1% to 83.3%, 79.4% and 90.7%, respectively. ConclusionsQuantification of serum MET DNA by FQ-PCR may serve as a novel accessible diagnostic tool for the clinical screening and detection of lung cancer.

Effect of circulating tumor cells combined with negative enrichment and CD45-FISH identification in diagnosis, therapy monitoring and prognosis of primary lung cancer.

Circulating tumor cells (CTCs) are valuable for diagnosis, monitoring therapy and prognosis in primary lung cancer. Herein, we evaluated the clinical significance of lung cancer CTCs in this study. Detection of CTCs was performed using epithelial cell adhesion molecule-independent enrichment and CD45 fluorescence in situ hybridization detection. CTCs ≥ 2/3.2 mL were considered as positive. The positive rates in primary lung cancer, benign lung disease and healthy control groups were 84, 0 and 4.2 %. CTCs count was significantly higher in lung cancer patients than healthy controls and benign lung disease, with an area under ROC curve of 0.917 (95 % confidence interval 0.855-0.979; p = 0.000) between lung cancer and nonmalignant diseases. CTCs count significantly increased with an increase in pathological stage with mean count of 2.3 ± 2.6 (stage I-II), 3.5 ± 3.3 (stage III) and 4.5 ± 4.3 (stage IV), respectively. The positive detection rate of CTCs for primary lung cancer diagnosis was higher than serum tumor markers. In total, 25 metastasis lung cancer patients participated in the follow-up. Changes in CTCs count after two cycles of chemotherapy were consistent with radiographic appearance. Moreover, CTCs count was better than serum tumor markers for monitoring chemotherapy response. Median progression-free survival (PFS) was 2.05, 3.25 and 8.348 months (p < 0.05) in group in which post-treatment CTCs count was increased, unchanged and decreased, respectively. Furthermore, PFS in patients whose post-treatment CTCs count increased or were unchanged accompanied by a baseline CTCs count ≥3 was significantly shorter than those whose post-treatment CTCs count decreased or was unchanged accompanied with baseline value C < 3 (1.85 vs. 8.22 months, p = 0.000) [Corrected]. Therefore, CTCs are a reproducible indicator of disease status that may be superior to imaging.

733P - Expression Analyses of the Key Members of Rdgn in the Tissues of Benign Hepatic Diseases and Human Liver Cancers

ABSTRACT Aim: To analyze the differences of the expression of DACH1 in different groups of liver diseases (liver cirrhosis, fatty liver and chronic hepatitis), study the relationship between clinical pathological features (stage, pathologic grade and type, age and gender) of liver cancer and the expression of DACH1 and SIX1 which are the main members of The Retinal Determination Gene Network (RDGN) and explore the correlation among DACH1, SIX1 and cyclinD1 in the tissues of liver cancers. Methods: The expression of DACH1 in one tissue microarray including 120 cases of different hepatic diseases and the expression of DACH1, SIX1 and cyclinD1 in another tissue microarray including 120 cases of liver cancers and normal liver were detected by immunohistochemical methods. One-way ANOVA, Chi-square test, orderly logistic regression were used for data analysis. Results: In the liver cirrhosis, fatty liver and chronic hepatitis groups, DACH1 expression was lower than in the normal liver group. The amount of DACH1 in liver cancer tissues was lower than the three liver benign disease groups and normal group (P Conclusions: Several hepatic diseases were related to the low expression of DACH1 which has a negative correlation with pathologic grade and shows it may participate in regulating the occurrence and development of these diseases, especially in liver cancer tissues, and may play a protective role in these liver diseases. The high expression of SIX1 is associated with the low differentiation and advanced stage of the liver cancer, therefore, it may participate in relevant mechanisms of the progression of liver cancers. Disclosure: All authors have declared no conflicts of interest.

Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography.

BackgroundAlkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases.MethodsBile samples were obtained at endoscopic retrograde cholangiopancreatography (ERCP) in 59 patients with gallstone, other benign disease, tumour, and primary sclerosing cholangitis (PSC). The NPP7 activity was determined. The appearance of the 1.4 and 1.2 kb products in the bile was examined by Western blot. The results were correlated to the diseases and also plasma bilirubin and alkaline phosphatase.ResultsNPP7 activity in the tumour group was significantly lower than in the gallstone group (p < 0.05). The activity in the tumour plus PSC group was also lower than in gallstone plus other benign disease group (p < 0.05). Within the tumour group NPP7 activity was lowest in cholangiocarcinoma patients, being only 19% of that in gallstone patients. Bilirubin correlated inversely to NPP7 and was higher in the tumour than in the gallstone group. Western blot identified both the 1.4 kb and the 1.2 kb products in most bile samples. The density ratio for the 1.4/1.2 kb products correlated to NPP7 activity significantly. Two patients (one PSC and one cholangiocarcinoma) lacking NPP7 activity had only the 1.2 kb form in bile.ConclusionNPP7 activity and the ratio of 1.4/1.2 kb products in bile are significantly decreased in malignancy, particularly in cholangiocarcinoma. The implications of the finding in diagnosis of cholangiocarcinoma and 1.2 kb product in hepatobiliary diseases require further investigation.

CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer

Background/aimsTo determine whether the combination of tumor markers (CA72-4, CA125, CA19-9 and CEA) could increase the sensitivity and accuracy for in the diagnosis of gastric cancer (GC). MethodsThis study is a retrospective analysis. A total of 426 patients, including 106 patients with GC, 149 patients with benign gastric diseases and 171 healthy people, who visited Zhejiang Xiaoshan Hospital from January 2011 to December 2013, were measured by serum markers, including CA72-4, CA125, CA19-9 and CEA. Statistical analyses including area under curve (AUC) of receiver operating characteristic (ROC) curve, and logistic regression analysis, were performed to evaluate the diagnostic value of these markers on GC. ResultsSerum levels of CA72-4, CEA, CA125 and CA19-9 were higher in the GC group than those in the benign gastric disease group and the healthy control group (P<0.005). The sensitivities of CA72-4, CEA, CA125 and CA19-9 at the recommended cut-off level for all patients were 33.0%, 25.5%, 31.1% and 38.7%, respectively. However, when all four markers were used in combination the sensitivity increased to 66.0%. But by using an optimal cut-off value, the sensitivities of all four markers for the diagnosis of GC were improved. Especially the sensitivity of CEA increased to 73.6% and the sensitivity of the combination of the tumor markers increased to 75.5%. The age and gender had no effects on the diagnostic value of these markers. ConclusionsWith the help of optimal cut-off values based on ROC curve and logistic regression analysis, the combination of these markers could improve the sensitivity for the diagnosis of GC based on common serum tumor markers.

Clinical value of risk of ovarian malignancy algorithm in risk stratification of ovarian cancer

The serum specimens were collected from ovarian cancer (n=100), benign ovarian disease (n=69) and healthy women (n=95). The serum levels of HE4 and CA125 were detected. Risk of ovarian maliqnancy algorithm (ROMA) was calculated. Accuracy of prediction was evaluated by the area under receiver operating characteristic curve (ROC-AUC). And validity of prediction was evaluated by sensitivity and specificity. The results showed that the median level of ROMA algorithm was 83.0%, 8.9% and 8.7% in ovarian cancer, benign ovarian disease and healthy women groups respectively. The difference were statistically significant (all P<0.01). Compared with benign ovarian disease group, the ROC-AUC of ROMA algorithm was 0.900 in ovarian cancer group. The sensitivity and specificity were 81.0% and 92.8% in ovarian cancer group respectively. Thus ROMA algorithm is a useful parameter in risk stratification for ovarian cancer. The diagnostic accuracy of ROMA algorithm is better than that of HE4 and CA125 in ovarian cancer. Key words: Ovarian neoplasms; Epididymal secretory proteins

FRI0538 Juvenile Idiopathic Arthritis: from Childhood to Adult Life

BackgroundJuvenile Idiopathic Arthritis (JIA) is not a single disease but a term used to classify a group of inflammatory rheumatic diseases (Arthritis) of unknown etiology (Idiopathic) diagnosed before the patient...