The preoperative plasma suPAR level independently predicted survival of patients with colorectal cancer. Further studies of plasma suPAR in patients with cancer are needed to evaluate the utility of plasma suPAR measurements and cut points in identifying high-risk patients among those with early stage disease.

In a previous study we demonstrated that the kidney content of somatomedin C was maximal one to two days after uninephrectomy or induction of diabetes, and that insulin treatment prevented an increase in kidney somatomedin C as well as kidney growth in diabetic animals. In the present study we have examined the effect of a somatostatin analogue on kidney somatomedin C and initial renal growth in the two experimental situations. The kidney hypertrophy in untreated diabetic animals amounted to 23% four days after streptozotocin injection and followed an increase in kidney somatomedin C content of 60% reaching the maximum after 48 h. In young and old uninephrectomized rats kidney growth was 19% and 16% after four days. In young animals a prompt increase of 50% in kidney somatomedin C was seen as reaching the maximum after 24 h, while the somatomedin C content in kidneys from old animals was maximal after 48 h (increase of 58%) in good accordance with the slightly slower kidney growth. The new findings of the present study are that administration of a long-acting somatostatin analogue (Sandostatin) effectively prevented the obligatory increase in kidney somatomedin C content as well as kidney growth both in experimental diabetes and after uninephrectomy. It is noteworthy that Sandostatin administration did not alter the metabolic state in diabetic animals indicating that the inhibition of kidney hypertrophy could not be attributed to improved metabolic control. The results thus support the concept that somatomedin C is involved in initial diabetic and post-nephrectomy renal growth.

Compromised immune function may increase the risk of anal squamous cell carcinoma (SCC). We examined the risk of anal SCC in patients with HIV infection and other chronic disorders associated with immunosuppression. A population‐based cohort study was conducted using the Danish National Patient Registry and the Danish Cancer Registry (DCR). We identified all patients with a first‐time hospital contact or procedure for HIV infection, solid organ transplantation or autoimmune disease or a first‐time record of haematologic malignancy in the DCR, 1978–2005, and followed these for a subsequent anal SCC, starting follow‐up 1 year after diagnosis of the index disease. Standardised incidence ratios (SIRs) were computed as the ratio of observed to expected numbers of anal SCCs, based on national age‐, sex‐ and period‐specific rates. Among 4,488 patients with HIV, we observed 21 anal SCCs with 0.3 expected (SIR: 81.1 (95% confidence interval (CI): 51.6–121.9)). Risk of anal SCC was markedly increased among 5,113 solid organ recipients (SIR: 14.4 (CI: 7.0–26.4)) and 30,165 patients with haematologic malignancies (SIR: 2.3 (CI: 1.1–4.2)) but only moderately increased among 242,114 patients with autoimmune diseases (SIR: 1.3 (CI: 1.0–1.6)). SIRs varied according to type of autoimmune disease and were high in patients with Crohn's disease (SIR: 3.1 (CI: 1.2–6.4)), psoriasis (SIR: 3.1 (CI: 1.8–5.1)), polyarteritis nodosa (SIR: 8.8 (CI: 1.5–29.0)) and Wegener's granulomatosis (SIR: 12.4 (CI: 2.1–40.8)). In conclusion, we found HIV infection, solid organ transplantation, haematologic malignancies and a range of specific autoimmune diseases strongly associated with increased risk of anal SCC.

SummaryThis study was carried out in order to compare the coagulation balance in patients with colorectal cancer before and after surgical removal of tumor with an age matched non-malignancy control group. Furthermore, it was studied whether preoperative coagulation state in cancer patients was correlated to the postoperative development of deep venous thrombosis (DVT) diagnosed by venography. Plasma was collected preoperatively in 93 cancer patients and 30 controls, and postoperatively on day one, two, seven, and ninety in 88 cancer patients and 18 controls. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and total fibrin(ogen) degradation products (TDP) were quantitated in plasma by enzyme linked immunosorbent assays (ELISA). As compared to controls, patients admitted for cancer treatment displayed significantly higher levels of F1 + 2 and TAT. Patients suffering from advanced colorectal cancer had significantly higher levels of TAT and TDP as compared to patients with localized colorectal cancer. Twenty-three percent of cancer patients developed DVT postoperatively. Preoperatively these patients displayed significantly higher TDP levels, and postoperatively higher levels of F1 + 2, TAT, and TDP compared to cancer patients without DVT. The marked activation of blood coagulation and fibrinolysis observed in all patients following major abdominal surgery was even more pronounced in patients not cured for cancer.

Invasion by cancer cells requires proteases such as the serine protease plasmin to degrade the cellular matrix. Plasmin is formed from its zymogen, plasminogen, a reaction catalysed by urokinase type plasminogen activator-which is implicated in invasion 1 -and partly regulated by plasminogen activator inhibitors. The active form of the inhibitor complexes with free and receptor bound active urokinase plasminogen activator and is bound by vitronectin in plasma and extracellular matrix. 2A high concentration of plasminogen activator inhibitor-1 in biopsy specimens from tumours is associated with a poor prognosis, 3 and some patients with ovarian cancer have raised plasma concentrations of plasminogen activator inhibitor-1. 4 We studied the prognostic importance of plasma concentrations of plasminogen activator inhibitor-1 in patients with colorectal cancer. Subjects, methods, and resultsPlasma was collected preoperatively as previously described 5 from 609 patients having elective surgery for colorectal cancer. Plasma concentrations of plasminogen activator inhibitor-1 were measured by a sandwich enzyme linked immunosorbent assay (ELISA) using two monoclonal antibodies. 3The concentration was expressed as interim units of plasminogen activator inhibitor-1/mg protein. 3All patients had histologically verified colorectal cancer and complete clinical data. The median follow up time was 25 months (range 13-40). Patients were randomised into two groups. Data on 293 patients (optimisation group) were used to determine the optimal cut off value for plasminogen activator inhibitor-1 in relation to survival using Cox's proportional hazard model, and data on 316 patients (validation group) were used to validate the results obtained from the optimisation group.High plasma concentrations of plasminogen activator inhibitor-1 were associated with increasing severity of disease (Dukes's stage; 2 test, P = 0.001). The best cut off value for plasminogen activator inhibitor-1 was 0.5 interim units/mg of protein. With this value the hazard ratio was 1.5 for patients with high concentrations of plasminogen activator inhibitor-1 (178/293 (61%)) compared with those with low concentrations (115/293 (39%)). Applying this value to the validation group gave similar results (hazard ratio 1.5 (95% confidence interval 1.1 to 2.2); P = 0.02; 179/316 (57%) v 137/316 (43%)) (figure). Cox analysis of the 316 patients in the validation group showed that Dukes's stage was the strongest prognostic variable (hazard ratio 2.9 (2.3 to 3.7)), followed by age (hazard ratio 1.5 (1 to 2.1)). CommentThis study shows that high preoperative plasma concentrations of plasminogen activator inhibitor-1 are associated with shorter survival in patients with colorectal cancer. The validity of this result is strongly supported by the fact that the best cut off value for plasminogen activator inhibitor-1 obtained from one patient population gave similar prognostic information about a second independent population. It is further supported by the close correlation bet...

In the western world, colorectal cancer (CRC) is the third most common cause of cancer-related deaths. Survival is closely related to the stage of cancer at diagnosis striking the clinical need for biomarkers capable of early detection. To search for possible biological parameters for early diagnosis of CRC we evaluated protein expression for three CREC (acronym: Cab45, reticulocalbin, ERC-55, calumenin) proteins: reticulocalbin, calumenin, and ERC-55 in a cellular model consisting of a normal derived colon mucosa cell line, NCM460, and a primary adenocarcinoma cell line of the colon, SW480. Furthermore, this cellular model was analyzed by a top-down proteomic approach, 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) for novel putative diagnostic markers by identification of differentially expressed proteins between the two cell lines. A different colorectal carcinoma cell line, HCT 116, was used in a bottom-up proteomic approach with label-free quantification (LFQ) LC–MS/MS. The two cellular models gave sets of putative diagnostic CRC biomarkers. Various of these novel putative markers were verified with increased expression in CRC patient neoplastic tissue compared to the expression in a non-involved part of the colon, including reticulocalbin, calumenin, S100A6 and protein SET. Characterization of these novel identified biological features for CRC patients may have diagnostic potential and therapeutic relevance in this malignancy characterized by a still unmet clinical need.

Recent studies have suggested zinc to be a possible modulator of hormone secretion from the anterior pituitary. The three aims of the present study were: (1) to estimate the total amount of zinc in the gland by instrumental analysis; (2) to visualize the zinc at light and electron microscopical levels, and (3) to estimate the amount of zinc that can be visualized by histochemical techniques. PIXE measurement showed the total amount of zinc to be 74 ng/mg dry weight in males and 100 ng/mg dry weight in females, which is a highly significant difference. Histochemically, the zinc was shown by a modified Timm method and the selenium method to be localized to the secretory granules, and to a smaller extent to the Golgi apparatus of the somatotrophs, corticotrophs and thyrotrophs. Chelation of tissue zinc by intravital dithizone treatment effectively blocked subsequent selenium and Timm staining in the secretory granules, and PIXE assays of the chelated metal (extracted into CCU) showed it constitued less than 5% of the total zinc in the tissue. It is concluded from the study that zinc is present in the anterior pituitary of rats in rather high amounts and that loosely bound zinc, which is suggested to exert a biological effect by itself, can be located to the parts of the cells responsible for production, storing and release of hormones.

OBJECTIVES:Early assessment of the severity and the etiology is crucial in the management of acute pancreatitis. To determine the value of procalcitonin (PCT) as a prognostic marker and as an indicator of biliary etiology in the early phase of acute pancreatitis. METHODS:In a prospective study, 75 consecutive patients were included (severe pancreatitis in 12 patients, biliary etiology in 42 cases). The value of PCT as a prognostic marker was compared to C-reactive protein (CRP), hematocrit (HCT), acute physiology and chronic health evaluation (APACHE) II score, and Ranson score. The value of PCT as an indicator of biliary etiology was compared to alanine aminotransferase (ALT) and alkaline phosphatase (AP). The area under the receiver operating characteristic curve (AUC) was applied as a measure of the overall accuracy of the single markers and multiple scoring systems. RESULTS:The most accurate prediction of severe disease was provided by the APACHE II score on the day of admission ( CONCLUSIONS: PCT is of limited additional value for early assessment of severity and etiology in acute pancreatitis. CRP is found to be a reliable prognostic marker with a delay of 48 h, while ALT is validated as the best indicator of biliary etiology.(Am J Gastroenterol 2005;100:1593-1597)