Lack of MMP-9 expression is a marker for poor prognosis in Dukes’ B colorectal cancer

Background

Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer.

Methods

We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens.

Results

Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p?<?0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p?=?0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p?=?0.034).

Conclusion

Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.

     

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil

IntroductionLiver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics.MethodsWe reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients’ clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups.ResultsAlmost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795).DiscussionThe new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.     

Ki-67, p53, ER receptors, ploidy and S phase as long-term prognostic factors in T1 node-negative breast cancer.

BACKGROUND: The aim of the present study was to evaluate a series of biomarkers with regard to long-term prognostic value in patients with T1 (< or =2 cm) node-negative breast cancer. METHOD: The prognostic value of Ki-67, p53, oestrogen receptor (ER) immunohistochemical labelling, flow-cytometric S phase fraction and ploidy was evaluated in 212 patients with pT1N0M0 breast cancer. The median follow-up time was 15.9 years (range 0.2-27.2 years). RESULTS: In an analysis of breast cancer-specific survival up to 5 years, high Ki-67 (> or =10%; p = 0.002), high p53 (> or =20%; p = 0.01), negative ER (<30%; p = 0.01) as well as aneuploidy of the tumour (p = 0.02) were significant prognostic factors. When the follow-up was extended to 10 years, only Ki-67 (p = 0.03) was significantly associated with outcome and beyond 15 years none of the studied markers provided significant prognostic information when analyzed separately. There was a weak but significant difference in long-term survival when patients with a combination of high Ki-67 (> or =10%), high SPF (>3%) and high p53 (> or =20%) were compared to patients with other combinations (p = 0.03). CONCLUSION: According to the results of our series, it seems that several prognostic markers which are associated with short-term survival (< or =5 years) in pT1N0M0 breast cancer may not be significant predictors of long-term (>15 years) breast cancer-specific survival.     

Concentrations and enantiomer fractions of organochlorine compounds in Baltic species hit by reproductive impairment

Concentrations and enantiomer fractions (EFs) of organochlorine compounds (OCs) were determined in tissues of gray seal (Halichoerus grypus) and salmon (Salmo salar) originating from the Baltic Sea. The selected seal specimens ranged from starved to unstarved animals, and some of them suffered from a disease complex, while the salmon samples originated from individuals, which were known to produce offspring with and without the M74 syndrome. Significant differences in residue levels and EFs were found between seal groups but not between M74 salmon and non-M74 salmon. The relations between chemical and biological variables of seal samples were investigated with multivariate statistics. Poor health status correlated strongly with age, while bad nutrition condition was associated mainly with high pollution loads and distinctively nonracemic chiral OC compositions. High biotransformation rate (as indicated by fraction of chlordane metabolites in relation to total level of chlordanes) was also associated with large deviations from racemic values and high contaminant levels.     

Increased arterial stiffness in young adults with end-stage renal disease since childhood

Increased arterial stiffness is a risk factor for mortality in adults over 40 yr of age with end-stage renal disease (ESRD). As no data exist on vascular changes in young adults with ESRD since childhood, a long-term outcome study was performed. All living Dutch adult patients with onset of ESRD between 1972 and 1992 at age 0 to 14 yr were invited for carotid artery and cardiac ultrasound and BP measurements. Data on clinical characteristics were collected by review of all medical charts. Carotid ultrasound data were compared with those of 48 age-matched and gender-matched healthy controls. Carotid artery and cardiac ultrasound was performed in 130 out of 187 eligible patients. Mean age was 29.0 (20.7 to 40.6) yr. Compared with controls, patients had a similar intima media thickness but a reduced mean arterial wall distensibility DC (40.0 versus 45.0 kPa(-1). 10(-3); 95% CI, -9.1 to -0.8; P < 0.001), an increased stiffness parameter beta (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P = 0.02), an increased elastic incremental modulus E(inc) (0.35 versus 0.27 kPa. 10(3); 95% CI, 0.02 to 0.12; P < 0.001). Multiple regression analyses in all subjects revealed that ESRD was associated with an increase in beta and E(inc). Arterial wall properties of patients currently on dialysis and transplanted patients were comparable. In all patients, current systolic hypertension was associated with increased E(inc) and decreased DC. In conclusion, carotid arterial wall stiffness is increased in young adult patients with pediatric ESRD. Hypertension is a main determinant and might be a target for treatment of these potentially lethal arterial wall changes.     

Alteration of the fibrinogen molecule and its phosphorylation state in myocardial infarction patients undergoing thrombolytic treatment

Fibrinogen was purified by protamine-agarose chromatography from plasma from three patients after their submission to hospital due to acute myocardial infarction. The total amount of phosphate bound to fibrinogen and the concentration of fibrinogen was determined in samples withdrawn immediately after submission and after thrombolytic treatment. Streptokinase treatment almost totally removed circulating fibrinogen while recombinant tissue plasminogen activator spared much of it. In patients treated with streptokinase, the new circulating fibrinogen was homogeneous according to the single alpha-band seen after sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis under reducing conditions, whereas fibrinogen from the recombinant tissue plasminogen activator-treated patient as well as healthy controls exhibited two alpha-bands in the 66-kDa region. The molar ratios of phosphate to fibrinogen of healthy controls and commercial fibrinogen were 0.82 (+/-0.04) and 0. 87 (+/-0.05), respectively. For two streptokinase-treated patients the degree of phosphorylation increased threefold from a normal range of 0.97 (+/-0.11) and 0.67 (+/-0.09) mol/mol fibrinogen before treatment to 3.33 (+/-0.32) and 1.86 (+/-0.17) mol/mol in newly formed fibrinogen on day 1. Recombinant tissue plasminogen activator treatment led to a smaller increase in phosphorylation, from 1.14 (+/-0.13) pretreatment to 1.65 (+/-0.11) after treatment on day 1. In conclusion we show in this report that after streptokinase treatment of patients with acute myocardial infarction, the new Aalpha-chain of fibrinogen was a homogeneous single 66-kDa band on sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and that the degree of phosphorylation of plasma fibrinogen was elevated, approaching the theoretical limit of 4 mol phosphate/mol fibrinogen.     

Asymmetry of neuronal activity during extracellular microelectrode recording from left and right human temporal lobe neocortex during rhyming and line-matching

Recordings of neuronal activity in humans have identified few correlates of the known hemispheric asymmetries of functional lateralization. Here, we examine single-unit activity recorded from both hemispheres during two delayed match-to-sample tasks that show strong hemispheric lateralization based on lesion effects; a line-matching (LM) task related to the right hemisphere, and a rhyming (RHY) task related to the left. Nineteen neuronal populations were recorded with extracellular microelectrodes from the left temporal neocortex of 11 awake patients, and 18 from the right in 9 patients during anterior temporal lobectomy for complex partial seizures under local anesthesia. All subjects were left hemisphere dominant for language. Twelve (32%) populations exhibited statistically significant changes in activity at p <.05. Although changes in firing frequency were recorded from both hemispheres during both tasks, the RHY task elicited changes in activity several hundred milliseconds earlier on the left side than on the right. The LM task, on the other hand, induced changes earlier on the right side than on the left. Both hemispheres contained units active during verbal responses regardless of which behavior elicited the response. Our results indicate that cerebral dominance is reflected in earlier neuronal activity in the anterior temporal lobe during tasks lateralized to that hemisphere.     

Cyst fluid tumor-associated trypsin inhibitor may be helpful in the differentiation of cystic pancreatic lesions

In clinical practice it is important to differentiate pseudocysts from cystic pancreatic tumors, especially potentially malignant mucinous cystic tumors. We investigated three new markers—tumor-associated trypsin inhibitor (TATI) and the free α and β subunits of human choriogonadotropin (hCGα and hCGβ, respectively)—in the cyst.uid of patients with cystic pancreatic lesions and compared the concentrations of these markers to those of carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 125, CA 15-3, alpha-fetoprotein, and tissue polypeptide antigen in order to distinguish benign cysts from malignant cysts. Between 1995 and 2001, a total of 34 patients operated on for cystic pancreatic lesions at Tampere University Hospital were included. Cyst fluid was aspirated at operation and stored at_70 C. Thehistologic diagnosis was pseudocyst in 23 patients, serous cystadenoma (SCA) in four patients, benign mucinous cystadenoma (MCA) in four patients, cystic papillary neoplasm (CPN) in one patient, glucagonoma in one patient, and malignant endocrine islet cell carcinoma (EC) in one patient. Significantly higher concentrations of TATI were found in patients with MCA and EC (2239 ± 149 μg/L [mean ± SEM]) than in patients with pseudocyst (55 ± 29 μg/L; P = 0.001) and in patients with SCA (36 ± 23 μg/L; P = 0.01). The patient with CPN and the patient with glucagonoma had relatively low levels of TATI (30.7 and 46.5 μg/L). Mean CEA was higher in patients with MCA compared to those with pseudocysts (19,993 ± 9418 vs. 53 ± 20 μg/L, P = 0.002) and SCA (0.4 ± 0.1 μg/L; P = 0.02), but in the patient with malignant EC, the patient with CPN, and the patient with glucagonoma, CEA was normal. HCGα, hCGβ, CA 19-9, CA 242, CA 125, CA 15-3, alpha fetoprotein, and tissue polypeptide antigen could not distinguish between MCA vs. pseudocyst or SCA, because both normal and elevated values were seen in all groups. To our knowledge, this is the first time that TATI has been quantitated in the cyst fluid of patients with cystic pancreatic lesions. It appears to be a potential marker in the differential diagnosis of benign from malignant cystic pancreatic lesions. Supported by the Medical Research Fund of Tampere University Hospital.     

Social differences in Swedish infant mortality by cause of death, 1983 to 1986.

OBJECTIVE. We sought to investigate social differences in Swedish infant mortality by cause of death. METHODS. All live single births in Sweden between 1983 and 1986 to mothers 15 to 44 years old with Nordic citizenship were studied. The causes of death were classified into six major groups. Mother''s education was used as a social indicator. Logistic regression analysis was used with identical models for all groups of causes of death. RESULTS. There were 355,601 births and 2012 infant deaths. Only for sudden infant death syndrome were significant social differences found, with crude odds ratios of 2.6 for mothers with less than 10 years of education and of 1.9 for mothers with 10 to 11 years, compared with 1.0 for mothers with 15 years or more. After adjusting for age, parity, and smoking habits, these ratios were no longer significant. CONCLUSIONS. The social differences obtained could be explained by the fact that mothers with less education smoke more, are younger, and have higher parity than those with more education.