Serum betatrophin and irisin levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 µg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 µg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 µg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.

The assessment of serum and diagnostic peritoneal lavage concentration of matrix metalloproteinase-2, matrix metalloproteinase-9, carbohydrate antigen 19-9, and carcinoembryonic antigen in patients with pancreatic cancer and chronic pancreatitis.

Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. A tumor marker that would eliminate the imperfection of preoperative serum carbohydrate antigen 19-9 (CA19-9) concentration is still being sought. This study aimed to conduct a comparative analysis of the concentrations in serum and peritoneal cavity of matrix metalloproteinases: metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9), CA19-9, and carcinoembryonic antigen (CEA) in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and a control group (CG). The study was performed in a group of 90 patients. Group 1 consisted of 30 patients with PC, group 2 consisted of 30 patients with CP. There was no case of pancreatic cancer in the CP group. Group 3 (CG) consisted of 30 individuals, who were recruited among patients operated for non-inflammatory cholelithiasis. The serum samples and intraperitoneal fluid, when present or samples of peritoneal lavage were taken from patients and the concentration of MMP-2, MMP-9, and CA19-9 were evaluated. The revealed intraperitoneal fluid concentrations of the MMP-2, MMP-9, and CA19-9 were significantly higher in both PC and CP groups in comparison to CG. There were no statistically significant differences between intraperitoneal fluid concentrations of the MMP2, MMP9, and CA19-9 in PC and CP groups. The revealed serum concentration of the MMP-2 and MMP-9 in the PC, CP, and CG were significantly higher compared to the intraperitoneal fluid. There was no significant correlation between serum and intraperitoneal fluid concentration of the MMP-2, MMP-9, and CA19-9 and the presence of cancer cells in the intraperitoneal fluid conventional cytological examination. The elevated preoperative intraperitoneal fluid concentration of MMP-2 and MMP-9 and serum concentration of CA19-9 and CEA showed significant sensitivity and specificity in PC prediction. The preoperative serum concentrations of MMP-2 and MMP-9, serum, and intraperitoneal fluid concentrations of CA19-9 and CEA have been shown to have a statistically significant effect on predicting cancer progression and the presence of distant metastases. Presented findings suggest the usefulness of MMP-2 and MMP-9 as a potential predictor of PC and marker of dissemination but its usefulness in the differential diagnosis between PC and CP is limited, however more studies on a large population are needed to support our result. To our knowledge, this was the first study evaluating not only MMP-2 and MMP-9 concentrations in serum but also the concentration of these metalloproteinases in peritoneal fluid in patients with PC and CP.

Omentin, vaspin and irisin in chronic liver diseases.

Omentin and vaspin are adipokines potentially considered in the development of liver pathology. Irisin is new myokin potentially participating in energy processes in the organisms. The aim of this study was to evaluate the plasma concentration of these cytokines and the relationships of them with selected parameters of laboratory tests and of histopathological changes in selected chronic liver diseases: non-alcoholic fatty liver diseases (NAFLD), primary biliary cholangitis (PBC) and alcoholic cirrhosis (AC). The plasma concentration of omentin was the highest in AC group and the lowest in control group (CG). Irisin plasma concentration was the highest in CG and the lowest in AC. Mean vaspin concentrations did not differ significantly between groups. Among many laboratory parameters, only in the AC group positive relationships were found between omentin concentration and bilirubin, as well as glucose, and negative between omentin level and the number of platelets and erythrocytes; there was a positive relationship between the concentration of vaspin and bilirubin, as well as negative between vaspin level and the number of erythrocytes or hematocrit value in this group. INR value had positive correlation with vaspin concentration and negative with irisin level in NAFLD group. No significant dependences between the concentrations of explored cytokines and laboratory tests were found in PBC group. It was found the positive correlation between the plasma concentration of irisin and fibrosis as well as inflammation in PBC group. The negative correlation between irisin level and inflammation in NAFLD was also showed. Omentin can be considered as an indicator for predicting inflammation, steatosis and balloon degeneration in NAFLD and PBC. Summarizing, it is unclear but possible that explored cytokines have some relationships with certain features of liver damage and development of chronic diseases of this organ.

Assessment of the Learning Process After Introducing a New Liver Transplantation Procedure in a Center With Extensive Experience in Kidney Transplantation.

BACKGROUND: Liver transplantation (LTx) is one of the most complex transplant procedures. The aim of the present study was to determine whether the learning process can be observed after the introduction of LTx in a center with extensive previous experience in renal transplantation. METHODS: This retrospective analysis included 264 primary LTx procedures performed with the piggyback technique (2005-2016). The procedures were divided into 4 equal groups. The characteristics of the recipients, data related to the surgery, and the postoperative course and complications were analyzed. RESULTS: We observed a significant reduction in surgical time and in the anhepatic phase duration between Group 1 and the other groups (median surgical time was 455 minutes vs 415 minutes, 410 minutes and 387 minutes, respectively, P < .05; median anhepatic phase duration was 75 min vs 60 min, 62 min, 60 min, respectively, P < .05). There was a decrease in the number of transfused blood units (median in Group 1 of 6 packs vs 3 packs in Group 4, P < .05) and a decrease in blood recovered from the operating field using the Cell Saver system (median in Group 1 of 1570 mL vs 1057 mL, 1123 mL, and 1045 mL, respectively, P < .05). A significant reduction in the number of hemorrhages was found (1.5% in Group 4 vs 13.6%, 10.6%, and 7.6% in the other groups P < .05). The remaining studied parameters were not statistically significant. CONCLUSIONS: Extensive previous transplantation experience affected the lack of typical features of the learning process.

Influence of Experience Acquired by a Liver Transplantation Center on Extension of Donor Acceptance Criteria.

BACKGROUND: Liver transplantation (LTx) is the only effective treatment for end-stage liver failure. Due to the ongoing lack of organs available for transplantation, there is a tendency to extend liver donor selection criteria. The aim of the study was to determine whether extension of donor acceptance criteria with increasing experience in LTx occurred at our transplant center. METHODS: This retrospective analysis included 288 donors harvested between 2005 and 2016. The donors were divided chronologically into 4 equally sized groups. They were assessed in subsequent groups according to sex, age, height, body mass index (BMI), cause of death, amount of days spent in the intensive care unit, number of episodes of cardiac arrest before organ removal, and results of laboratory and virologic tests. RESULTS: A statistically significant increase in the age of accepted donors was observed between group 2 and group 4 (median 40 vs 45 years, P < .05). There was a significant increase in the acceptance of anti-HBc-positive donors (0% in group 1 vs 7% in group 4). The remaining parameters did not show statistically significant differences. CONCLUSION: Experience acquired by our transplant center during the period of analysis did not lead to extension of liver donor acceptance criteria. Statistically significant differences for liver donor age and virologic profile (anti-HBc) between groups were observed; however, overall analysis did not confirm a clear tendency to extend liver donor acceptance criteria at this center.

Donation and Transplantation of Kidneys Harvested From Deceased Donors Over the Age of 60 Years in the Upper Silesia Region.

BACKGROUND: Population aging and shortage of organs for transplantation result in increasing numbers of kidneys retrieved from elderly donors. The aim of this study was to analyze donation of kidneys from donors after brain death (DBD) over the age of 60 years (≥60), comorbidities that affect decisions on retrieval, and early results of kidney transplantation. METHODS: Ninety-six potential DBD ≥60 and 309 aged 40-59 years (40-59) reported in Upper Silesia, Poland, from 2004 to 2013 were enrolled in the study. RESULTS: DBD >60 presented a higher rate of coexisting hypertension (53% vs 34%), limb ischemia (10% vs 1%), and past stroke (6% vs 1%) compared with DBD 40-59 (P < .05), but no differences were observed in serum creatinine concentration (85 vs 84 µmol/L), coexisting coronary disease (14% vs 6%), or diabetes (10% vs 4%). The decision of withdrawal from retrieval was more frequent in DBD ≥60 (16% vs 7%; P < .05). Twelve months after kidney transplantation, serum creatinine concentration was higher in recipients of kidneys from DBD ≥60 compared with DBD 40-59 (169 vs 138 µmol/L; P < .001). The survivals of recipients (93% vs 95%) and kidney grafts (90% vs 93%) as well as rates of proteinuria >1.0 g/24 h (6% vs 2%) did not differ between the groups. CONCLUSIONS: A higher rate of comorbidities in potential kidney DBD ≥60 results in a lower retrieval rate in these donors. The function of kidneys harvested from DBD ≥60 12 months after transplantation is worse than those from DBD 40-59, but still acceptable.

The role of the tissue plasminogen activator as a prognostic and differentiation factor in patients with pancreatic cancer and chronic pancreatitis.

Unsatisfactory pancreatic cancer treatment outcomes have prompted multiple avenues of research focused on identifying not only biomarkers of pancreatic adenocarcinoma progression but also potential prognostic survival factors in patients with pancreatic adenocarcinoma. Study consisted of 75 patients who underwent pancreatic resections between 2006 and 2011: 35 patients with pancreatic ductal adenocarcinoma (PC), 30 patients with chronic pancreatitis (CP), and a non-malignant control group (NMCG) of 10 patients who underwent surgery due to benign tumors. Tissue plasminogen activator (t-PA) concentrations in tissue homogenates and sera were evaluated. The mean t-PA concentration in PC tissue homogenates was 12.3 ± 2 (7.5, 15) ng/mg. Compared with the t-PA concentration in the PC group, lower concentrations of t-PA (3.3 ± 0.7 (2.2, 4.7) ng/mg and 5.9 ± 0.8 (4.6, 7.3) ng/mg (P < 0.01)) were observed in tissue homogenates of the CP and the NMCG patients, respectively. Although serum concentrations of t-PA did not differ between patient groups, in PC patients, the t-PA concentrations were higher in sera than in tissue homogenates. In contrast, the CP and NMCG patient groups had lower t-PA concentrations in sera compared with tissue homogenates. Increasing tissue homogenate t-PA concentrations were associated with blood vessels infiltration. Tissue homogenate and serum t-PA concentrations were not related to the survival rate of patients with PC. The t-PA concentration above 7.45 ng/ml in tissue homogenates was indicative of PC. We concluded that higher concentrations of t-PA were observed in pancreatic cancer tissue compared to chronic pancreatitis, suggesting its potential role in the development and progression of pancreatic cancer. In contrast, the lack of significant differences in the serum t-PA concentrations between treatment groups suggests that serum t-PA concentrations may not be suitable as a biomarker for the diagnosis of pancreatic cancer.

The assessment of serum concentration of adiponectin, leptin and serum carbohydrate antigen-19.9 in patients with pancreatic cancer and chronic pancreatitis.

UNLABELLED: Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. The clinical impact of preoperative serum carbohydrate antygen 19-9 (CA 19-9) levels have been disscussed. The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. Group 1 consisted of 30 patients with PC, group 2 consisted of 30 patients with CP. There was no coincidence of pancreatic cancer in CP group. Group 3 (CG) consisted of 30 persons and were recruited among patients operated for cholelithiasis. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. CONCLUSIONS: significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP, but this statement needs further investigation. To our knowledge, this was the first study evaluating not only body mass index but also the content and distribution of body fat in patients with PC and CP.

Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

UNLABELLED: Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. RESULTS: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. CONCLUSIONS: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.

Vascular endothelial growth factor (VEGF) genotype and serum concentration in patients with pancreatic adenocarcinoma and chronic pancreatitis.

Vascular endothelial growth factor (VEGF) is necessary for microvasculature development and important for growth and spread of pancreatic tumors. Functional polymorphism of VEGF gene at position C-460T and G+405C may influence VEGF serum level. VEGF gene polymorphisms at position C-460T and G+405C were evaluated in 85 patients with pancreatic adenocarcinoma (PA), 72 - with chronic pancreatitis (CP) and 50 healthy volunteers. VEGF genotypes were studied in DNA isolated from blood samples and serum VEGF concentrations were measured. We found an increased frequency of the homozygous +405C/C VEGF genotype in patients with PA (55.3%) compared with CP (25%) and control group (16%; p<0.01). In contrast, the distribution of genotype and allele frequencies of the -460C/T polymorphism in the PA patients did not differ from those in CP and control groups. Serum levels of VEGF were significantly higher in PA patients (mean level: 441 ± 37.2 pg/ml) compared with CP patients (217 ± 13.6 pg/ml; p<0.001) and control group (137 ± 7.7 pg/ml; p<0.001). No relationship between VEGF serum levels and VEGF gene polymorphisms have been found. Our findings suggest that +405C/C VEGF genotype may contribute to pancreatic carcinogenesis. VEGF serum levels, although elevated in PA patients, are not associated with analysed VEGF polymorphisms.

Management of necrotizing pancreatitis: flexible approach depending on intra-operative assessment of necrosis.

INTRODUCTION: The surgical management of necrotizing pancreatitis (NP) has changed over the years. MATERIAL AND METHODS: Among 144 patients, 12.5% (n = 18) were treated conservatively and 87.5% (n = 126) underwent surgery. The choice of operative method depended on the intra-operative assessment of consistency and on the extent of necrosis. A group of 126 patients underwent necrosectomy, followed by laparostomy with open packing in 80% (n = 101) cases, drainage in 14% (n = 18) and continuous closed lavage in 6% (n = 7). RESULTS: Postoperative complications occurred in 42.8% (n = 54) of the patients who underwent the surgery. Hospital mortality rate over all patients was 18% and 20.6% (n = 26) in the group of patients who underwent the surgery. Mean hospital stay was 61 +/- 36 days. Patients managed conservatively (n = 18) were discharged without surgical intervention. In this group no complications or deaths were observed. CONCLUSION: Using the three different surgical techniques in the management of NP, depending on intra-operative assessment of necrosis, showed promising results. A flexible approach targeted at a single patient and tailored to the clinical course and intra-operative situation should be considered in the treatment of NP.

Necrosectomy with an ultrasonic dissector in the treatment of necrotizing pancreatitis.

BACKGROUND: The surgical techniques for the treatment of necrotizing pancreatitis (NP) are varied and the ideal method is still debated. METHODS: Necrosectomy with an ultrasound dissector was performed. After the necrotic tissue was removed the bed was filled with a gentamicin-containing sponge. In the upper part of the abdominal wound a laparostomy was formed. The laparostomic cavity was packed with Mikulicz pads with physiological saline. Packs were changed every 24-48 h. RESULTS: There were 43 patients in the study with a mean age of 54 years (range 33-77). Reasons for surgical treatment were sterile necrosis- 53.5% (n = 23), infected necrosis- 39.5% (n = 17), abscess- 7% (n = 3). The mean number of packing changes under sedation was 5 (range 1-19). Postoperative complications occurred in 25.6% of patients (n = 11). There were five deaths (11.6%) after surgery. CONCLUSION: Necrosectomy with an ultrasonic dissector and gentamicin-containing sponge inserted into the post-necrotic bed are effective and well tolerated in the open packing treatment of NP.