The role of serum ck-18, mmp-9 and tipm-1 levels in predicting r0 resection in patients with gastric cancer / O papel dos níveis séricos de ck-18, mmp-9 e tipm-1 na predição da ressecção r0 em pacientes com câncer gástrico

ABSTRACT Background: Gastric cancer is the 3rd most common cause of death in men and the 5th common in women worldwide. Today, surgery is the only curative therapy. Currently available advanced imaging modalities can predict R0 resection in most patients, but it can only be detected with certainty in the perioperative period. Aim: To determine the role of serum CK18, MMP9, TIMP1 levels in predicting R0 resection in patients with gastric cancer. Methods: Fifty consecutive patients scheduled for curative surgery with gastric adenocarcinoma diagnosed between 2013-2015 were included. One ml of blood was taken from the patients to analyze CK18, MMP9 and TIMP1. Results: CK18, MMP9 and TIMP1 levels were positively correlated with pathological N and the stage (p<0,05). CK-18, MMP-9 and TIMP-1 averages in positive clinical lymph nodes and in clinical stage 3, were found to be higher than the averages of those with negative clinical lymph nodes and in clinical stage 2 (p<0,05). Conclusion: Although serum CK-18, MMP-9 and TIMP-1 preoperatively measured in patients scheduled for curative surgery did not help to evaluate gastric tumor resectability, they were usefull in predicting N3-stage.

RESUMO Racional: Câncer gástrico é a terceira causa mais comum de morte em homens e a quinta em mulheres em todo o mundo. Atualmente a cirurgia é a única terapia curativa. As modalidades de imagem avançadas atualmente disponíveis podem prever a ressecção R0 na maioria dos pacientes, mas ela só pode ser detectada durante o perioperatório. Objetivo: Determinar o papel dos níveis séricos de CK18, MMP9 e TIMP1 na predição da ressecção R0 em pacientes com câncer gástrico. Métodos: Foram incluídos no estudo pacientes consecutivos agendados para operação curativa entre 2013-2015. Foi retirado 1 ml de sangue dos pacientes incluídos para estudar CK18, MMP9 e TIMP1. Resultados: Os níveis de CK18, MMP9 e TIMP1 foram positivamente correlacionados com o N patológico e o estadiamento (p<0,05). As médias CK-18, MMP-9 e TIMP-1 das pessoas com linfonodos positivos e aqueles em estágio clínico 3 foram superiores às médias das pessoas com linfonodos negativos e estágio clínico 2 (p<0,05). Conclusão: Embora as dosagens séricas de CK-18, MMP-9 e TIMP-1 em pacientes agendados para operação curativa por adenocarcinoma gástrico não ajudem a ter ideia de ressecabilidade tumoral, ela foi útil na predição de estadiamento N3.

Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection

Background and study aims: Apoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 [CK18], M30, in asymptomatic hepatitis B virus [HBV] carriers and patients with chronic hepatitis B [CHB] and to evaluate the relationship between serum M30 levels and the severity of hepatic injury

Patients and methods: Asymptomatic HBV carriers [n = 169], patients with CHB [n = 100], and healthy control subjects [n = 43] were enrolled in the study. Serum CK18 [M30] levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection

Results: Serum CK18 [M30] levels were significantly higher in asymptomatic HBV carriers [198.77 +/- 77.62 U/L] than in healthy control subjects [146.92 +/- 40.18 U/L]. Patients with CHB [283.02 +/- 147.45 U/L] had significantly higher CK18 [M30] levels than asymptomatic HBV carriers [p = 0.001]. The diagnostic efficacy of CK18 [M30] levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate [c-statistics: 0.695], and the diagnostic cut-off value of CK18 [M30] was 262 U/L [specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60]. There was a positive correlation between serum CK18 [M30] levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB

Conclusions: Serum CK18 [M30] levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels

Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed by the M30 & M65 cell death markers & liver enzymes.

Background & objectives: General anaesthetics may induce apoptosis. The pro-apoptotic/necrotic markers M30 (caspase-cleaved cytokeratin-18) and M65 (intact cytokeratin-18) have been used to identify early apoptosis in liver disease. The aim of this study was to detect the effect of propofol and sevoflurane anaesthesia on these markers and blood transaminase levels in female patients undergoing elective surgery. Methods: Sixty-seven women undergoing mastectomy or thyroidectomy under general anaesthesia were randomly allocated to the propofol or sevoflurane groups. Venous blood samples for measuring the apoptotic and necrotic markers M30 and M65 as well as for measuring the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST) liver enzymes were collected before induction of anaesthesia, immediately after completion of surgery, and 24 and 48 h postoperatively. Results. The M30 values preoperatively and 0, 24 and 48 h postoperatively were 280±229, 300±244, 267±198 and 254±189 U/l in the propofol group and 237±95, 242±109, 231±94 and 234±127 U/l in the sevoflurane group, respectively. The M30 values did not differ within or between the groups. The M65 levels at the same time intervals were 470±262, 478±271, 456±339 and 485±273 in the propofol group and 427±226, 481±227, 389±158 and 404±144 U/l in the sevoflurane group, respectively. No significant changes were found in the M65 either within or between the propofol and the sevoflurane groups. The ALT and AST levels did not change at these time intervals. Interpretation & conclusions: Under the present study design propofol or sevoflurane anaesthesia did not induce apoptosis or affected the liver function as assessed by the M30, M65 markers and liver enzymes in patients undergoing mastectomy or thyroidectomy under general anaesthesia.

Evaluation of the diagnostic value of serum and tissue apoptotoic cytokeratin- 18 in patients with chronic hepatitis C

Hepatitis C virus [HCV] is considered the most common aetiology of chronic liver disease [CLD] in Egypt. The disease severity ranges from mild illness to cirrhosis and hepatocellular carcinoma. A role for apoptosis in liver damage caused by HCV chronic infection has been suggested. Cytokeratin 18 [CK-18] is the major intermediate filament protein in the liver and is a known caspase substrate in hepatocyte apoptosis. Therefore, we analysed the serum and tissue levels of CK-18 in patients with chronic HCV infection to evaluate its role in hepatocyte apoptosis. We also correlated CK-18 expression with the severity of hepatic pathology. This study examined 80 Egyptian patients with liver disease. There were 69 patients with chronic hepatitis C and 11 patients with hepatitis C-induced cirrhotic changes. Fifteen healthy controls were also included in the study. The levels of CK-18 fragment were quantified in paired serum and liver biopsy samples. The serum and tissue CK-18 levels were reduced in chronic HCV patients compared to early cirrhosis patients. This result indicates that serum levels of CK-18 and the hepatic expression of CK-18 might play an important role in disease progression. The serum and tissue levels of CK-18 were significantly increased and directly correlated with inflammation severity, stage of fibrosis, and ALT levels in the chronic HCV group and the cirrhotic liver group. There was no significant difference in viral load between patient cohorts. The serum level and the hepatic expression of CK-18 are related to disease activity and are directly correlated with METAVIR scoring. This result suggests that serum CK-18 levels may be useful for monitoring disease activity in chronic HCV and liver cirrhosis patients

[Diagnostic Value of serum cytokeratin-18 in dianosis of urothelial carcinoma]

To compare serum levels of cytokeratin-18 of patients with urinary bladder carcinoma with those of healthy controls and also to investigate if there would be any relationship between cytokeratin-18 levels and tumor stage, this study was performed. Serum cytokeratin-18 levels of 76 patients with bladder cancer and of 58 healthy people were determined. Tumor stage was T[1] in 24 patients, T[2] in 18 patients, T[3] in 20 patients and T[4] in 14 patients. The serum cytokeratin 18 levels in these cases were analyzed considering the tumor stage. Cytokeratin-18 level in the patient group was found to be significantly higher than that of control group [p<0.010]. However, when the levels of patients with different tumor stages were compared with control group, solely, the differences between those levels revealed to be not significant in patients with stage 1 and 2 tumors [p>0.05]. Regarding the cut off valueas 4.0 ng/mL, sensitivity and specificity for serum cutokeratin-18 were found to be 53% and 72%, respectively. Concerning the tumor stages, when sensitivity was calculated it was 8% for T[1], 33% for T[2], 90% for T[3] and 100% for T[4]. On the other hand, considering higher stage tumors [T[3] and T[4]] only, the sensitivity was calculated as 94%, whereas it was 19% for lower stage tumors [T[1] and T[2]]. It is obvious that serum cytokeratin-18 level increases in patients with urinary bladder carcinoma. However, as a tumor marker, it can be only useful in diagnosing the T[3] or higher staged tumors. This study indicated that cytokeratin-18 does not have any diagnostic value in lower stage bladder cancers