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I J Christensen

Publications and source records attributed to I J Christensen.

At least 19 recordsLinked to original sources
PubMed2004

Association between preoperative plasma levels of tissue inhibitor of metalloproteinases 1 and rectal cancer patient survival. a validation study.

The level of the tissue inhibitor of metalloproteinases 1 (TIMP-1) has previously been demonstrated to predict the survival of early stage colorectal cancer patients. The present study was undertaken to further validate plasma TIMP-1 as a prognostic marker in rectal cancer. Preoperative plasma from 352 rectal cancer patients were analysed using an immunoassay for TIMP-1. The TIMP-1 immunoassay demonstrated robustness and good reproducibility with low interassay coefficients of variation (CV). The rectal cancer patients had a mean plasma TIMP-1 level of 184 microg/l (standard deviation (SD): 70 microg/l). There were no significant differences in TIMP-1 levels between patients with Dukes' stage A, B or C disease, whereas Dukes' stage D patients had significantly increased TIMP-1 levels (P<0.0001); however, high levels of TIMP-1 were not restricted to those with advanced disease. Univariate analysis demonstrated an increasing risk of mortality with increasing TIMP-1 levels Hazard Ratio (HR)=2.9; 95% Confidence Interval (CI): 1.7-5.0; P<0.0001). Including additional covariates, multivariate analysis identified plasma TIMP-1 as an independent prognostic marker (HR=2.2; 95% CI: 1.2-4.1 (P=0.01). This study showed a highly significant and independent association between preoperative plasma TIMP-1 levels and survival in rectal cancer patients, thus confirming our previous findings. Furthermore, the TIMP-1 immunoassay proved to be stable and reproducible in this confirmatory study.

Adult↗
PubMed2003

Recurrence and survival after mesorectal excision for rectal cancer.

BACKGROUND: Mesorectal excision for rectal cancer has resulted in local recurrence rates of 3-11 per cent compared with up to 38 per cent after conventional methods. The results of a prospective Danish study with a historical control group are presented. METHODS: Three hundred and eleven patients with a mobile rectal cancer had mesorectal excision with curative intent performed by certified surgeons and were followed for 3 years. Demographic, perioperative and follow-up data were recorded prospectively. A series of patients who had conventional operations for rectal cancer served as a control group. RESULTS: The cumulative 3-year local recurrence rate was 11 per cent after mesorectal excision compared with 30 per cent after conventional surgery (hazard ratio (HR) 0.33 (95 per cent confidence interval (c.i.) 0.21 to 0.52); P < 0.001). Multivariate regression analysis showed that only advanced age (HR 0.97 (95 per cent c.i. 0.94 to 1.00); P = 0.048) and tumour in the lower third of the rectum (HR 0.21 (95 per cent c.i. 0.04 to 1.97); P = 0.075) were marginal independent predictors of local recurrence after mesorectal excision. The cumulative crude 3-year survival rate was 77 per cent after mesorectal excision and 62 per cent after conventional surgery (HR 0.58 (95 per cent c.i. 0.43 to 0.77); P < 0.001). Age was the only independent predictor of death after mesorectal excision (HR 1.04 (95 per cent c.i. 1.02 to 1.07); P = 0.001). CONCLUSION: Mesorectal excision is associated with a considerably lower risk of local recurrence and a better survival rate than conventional surgery, and is the optimum method for rectal cancer resection.

Adenocarcinoma↗
PubMed2002

Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma.

In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml(-1)) was significantly (P=0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml(-1)) in the healthy blood donors. In serum, no significant (P=0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml(-1)) and healthy blood donors (220 pg ml(-1)). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml(-1), serum=533 pg ml(-1)). In univariate survival analyses, both high plasma vascular endothelial growth factor (>112 pg ml(-1)) and high serum vascular endothelial growth factor (>533 pg ml(-1)) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml(-1)) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular endothelial growth factor (>112 pg ml(-1)) did not (HR=1.27, P=0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor.

Adult↗
PubMed2002

Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis.

OBJECTIVE AND DESIGN: An evaluation of angiogenesis related molecules during open treatment of psoriasis. MATERIALS AND SUBJECTS: Plasma samples and skin biopsies from 16 patients with psoriasis and plasma samples from 13 healthy controls. TREATMENT: Ranitidine 300 mg orally twice daily for 6 months. METHODS: Vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA methods in plasma collected from the patients before treatment and after 1, 3 and 6 months. Vessel counts were performed in biopsies from affected skin areas taken before treatment and after 3 and 6 months. The results were compared to simultaneous PASI scores. RESULTS: Pre-treatment plasma levels of VEGF and PAI-1 were significantly elevated in patients compared with levels in healthy persons (p = 0.02 and p = 0.04, respectively). The plasma levels decreased significantly during treatment (p = 0.03 and p = 0.01, respectively), and the decrease in combined levels correlated with the decrease in PASI score. However, the vessel density in affected skin did not change during treatment. CONCLUSIONS: Increased pre-treatment levels of VEGF and PAI-1 and decrease during improvement of the disease suggest that the two molecules may play a role in pathogenesis of psoriasis.

Adult↗
PubMed2002

Ranitidine as adjuvant treatment in colorectal cancer.

BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS: Patients scheduled for elective resection of primary tumours were consecutively included in a randomized double-blind placebo-controlled clinical study designed to evaluate the effect of ranitidine on survival. Before skin incision ranitidine 100 mg or placebo was given intravenously twice daily followed by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the protocol. The patient cohort has been followed continuously without loss of any patient, and a final statistical analysis was performed on an intention-to-treat basis after more than 5 years; this included a subgroup analysis of perioperative blood transfusion and postoperative infectious complications. RESULTS: The median observation period of the 740 patients included was 6.8 (range 5.4-7.9) years. A univariate analysis of all 740 patients and of the subgroup of 560 who underwent curative resection showed no significant effect of ranitidine on survival. Furthermore, ranitidine had no survival benefit in curatively resected patients who received a perioperative blood transfusion (n = 358), but it improved the survival of non-transfused patients (n = 202; hazard ratio (HR) 0.6 (95 per cent confidence interval (c.i.) 0.4 to 0.9), P = 0.02) and of non-transfused patients who did not develop postoperative infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had an independent, beneficial effect on survival (HR 0.6 (95 per cent c.i. 0.4 to 1.0), P = 0.04) within the subgroup of patients who did not receive perioperative blood transfusion and did not develop postoperative infectious complications. CONCLUSION: Ranitidine may prolong the survival of patients who undergo curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications.

Adult↗
PubMed2002

Levels of tissue inhibitor of metalloproteinases-1 in blood transfusion components.

Blood transfusion during surgery for solid tumors may reduce patient survival because of various bioactive substances present in blood preparations. The anti-proteolytic protein tissue inhibitor of metalloproteinases-1 (TIMP-1) present in large quantities in platelets has been shown to stimulate cell growth and to inhibit apoptosis and may therefore be considered to influence tumor progression. We measured TIMP-1 levels in blood transfusion preparations. especially in platelet-containing preparations, before and after leucofiltration and at different time-points during storage. The mean TIMP-1 levels in whole blood (WB) and platelet-rich plasma (PRP) were slightly reduced by leucofiltration; WB: 41.6 microg/L versus 34.9 microg/L. PRP: 139.8 microg/L versus 127.2 microg/L. However, with prestorage leucofiltration. TIMP-1 levels in buffy-coat-derived platelet (BCP) pools were significantly reduced from 134.2 microg/L to 102.2 microg/L (p=0.0013). In saline-adenine-glucose-mannitol (SAG-M) blood preparations in which the platelet content is reduced by more than 99%,. TIMP-1 could not be detected. Extracellular TIMP-1 accumulated significantly in non-filtered WB and in aferesis platelet concentrates (APC), but TIMP-1 was at no time detectable in SAG-M blood during storage. In conclusion. TIMP-1 is present in various platelet-containing blood preparations, but not in platelet-free preparations such as SAG-M, indicating that most of the TIMP-1 measured in blood preparations originates from platelets. Furthermore, TIMP-1 levels increased during storage in preparations containing platelets. which suggests a continuous disintegration of platelets. These data imply that information on preoperative blood transfusions should be taken into account when evaluating plasma TIMP-1 levels in patients.

Blood Component Transfusion↗
PubMed2002

Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets.

AIM: The sources of increased vascular endothelial growth factor (VEGF) concentrations in peripheral blood from cancer patients are not known in detail. The aim of the present study was to evaluate correlations between the VEGF content in isolated leucocyte subpopulations and VEGF concentrations in plasma, serum and lysed whole blood. METHODS: In 51 colorectal cancer (CRC) patients, circulating T-lymphocytes, B-lymphocytes, monocytes, and granulocytes were isolated by means of immunomagnetic separation. Subsequently, the isolated cells were lysed and VEGF contents in the lysates were determined. In corresponding blood samples, automated complete blood count was performed, and the number of each cell type was correlated to VEGF concentrations in plasma, serum and lysed whole blood. Finally, the impact of increasing clotting time on the release of VEGF to serum was analysed. RESULTS: Isolated neutrophils contained considerable amounts of VEGF. In isolated lymphocytes and monocytes, VEGF was not present in measurable amounts. The number of neutrophils was significantly (p<0.0001) correlated to VEGF concentrations in lysed whole blood, but not to VEGF concentrations in plasma or serum. The number of platelets was significantly correlated to VEGF concentrations in serum and lysed whole blood (p=0.002 and p=0.02, respectively) but not to VEGF concentrations in plasma. Finally, in serum, VEGF concentrations increased with increasing clotting time. However, a plateau was reached between 2 and 6 h of in vitro clotting. CONCLUSION: Circulating neutrophils contain considerable amounts of VEGF that contribute to high VEGF levels in lysed whole blood. VEGF in circulating platelets contributes to high VEGF levels in serum and lysed whole blood. Allowing whole blood samples to clot for between 2 and 6 h before serum is collected reduces time-dependent, non-uniform release of VEGF.

Adult↗
PubMed2001

[Sigmoidoscopy as primary examination in patients with bowel symptoms].

INTRODUCTION: Flexible sigmoidoscopy is recommended in the literature and is now officially recommended as the primary diagnostic method in patients with symptoms consistent with colorectal cancer. Sigmoidoscopy can detect two-thirds of all colorectal cancers. MATERIAL AND METHODS: We carried out a retrospective analysis of prospective data on symptoms and findings at FS in 682 patients, above the age of 40 years, referred to a private specialist for rectal bleeding, change in bowel habits, or unspecific abdominal symptoms. The chi 2-test and logistic multivariate regression analysis were used to estimate the predictive value of symptoms for neoplasia. RESULTS: Carcinoma was found in 31 (5%) and adenoma in 76 (11%), i.e., neoplasia in 16%. Logistic multivariate regression showed that bleeding in or on the faeces (p < 0.0001, OR 10.6 and 11.6), mucous discharge (p = 0.02, OR 3.0), and change in bowel habits (p = 0.02, OR 3.0) were independent risk factors of cancer, and bleeding on the faeces (p = 0.0002, OR 3.2) or in the faeces (p = 0.02, OR 2.7) were independent risk factors of adenoma. DISCUSSION: On the basis of the literature and the present results, we conclude that sigmoidoscopy is a suitable primary diagnostic method for the detection of neoplasia in the rectum and left colon in patients with bowel symptoms. Bleeding, mucous discharge, and change in bowel habits are independent risk factors for carcinoma and bleeding for adenoma.

Adult↗
PubMed2001

Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) in the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model.

Several studies have indicated an interaction between tumor cells and infiltrating stromal cells regarding the urokinase plasminogen activation (uPA) system. By developing combined uPA gene-disrupted and immunodeficient mice, we have studied the role of stromal uPA for the growth of the MDA-MB-435 BAG human tumor xenograft. Subcutaneous tumor growth and lung metastasis were compared between wild-type immunodeficient mice and mice with the combined deficiencies. Tumor growth was evaluated by volume measurements and plasma beta-galactosidase activity and metastasis was evaluated by counting lung surface metastases. Although no differences appeared in primary tumor take between the two groups of mice, a significant difference was observed in primary tumor growth, with tumors in uPA-/- mice growing significantly more slowly. In addition, a nonsignificant trend toward fewer lung metastases in uPA-/- mice was observed. The present data points to a critical role of stromal-derived uPA in the primary tumor growth of MDA-MB-435 BAG xenografts, whereas only a trend toward fewer lung metastases in uPA gene-disrupted mice was found.

Animals↗
PubMed2001

Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases.

OBJECTIVE: The present study was planned to measure preoperative levels of soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients with gynecological diseases, and to test for a relationship to clinical and biochemical patient characteristics. METHODS: Using a specific and sensitive kinetic ELISA, suPAR levels were determined in preoperative citrate plasma samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17 patients with benign ovarian tumors, and 28 patients with benign endometrial diseases. In addition, suPAR was measured in citrate samples from 31 female blood donors. RESULTS: suPAR was measurable in all samples. No significant difference was found between plasma suPAR in the blood donors and the patients with benign diseases (P = 0.58). The groups of cancer patients had suPAR levels that were significantly higher than those found in the blood donors (P < 0.0001, P < 0.0001, and P = 0.001 for patients with ovarian, endometrial, and cervical cancer, respectively). In all groups of cancer patients a trend toward increasing suPAR levels with increasing FIGO stage was noted (P = 0.0003, P = 0.02, and P = 0.01 for patients with ovarian, endometrial, and cervical cancer, respectively). Using the median suPAR level to dichotomize the ovarian cancer patients, FIGO stages I-III, a significantly increased risk of progression/relapse was found for patients with high suPAR levels (Hazard ratio (HR) = 3.1, 95% CI: 1.1-8.8, P = 0.03). A multivariate analysis was performed, including suPAR, FIGO stage, and CA-125. Only FIGO stage III compared with FIGO stage I was significant (HR = 15, 95% CI: 1.8-129, P = 0.01). Survival analyses were not performed in the endometrial or cervical cancer patients due to few progressions/relapses during the follow-up period. CONCLUSION: This study concludes that patients with gynecological cancers have elevated plasma suPAR levels as compared with healthy female blood donors and patients with benign gynecological diseases. In addition, high preoperative plasma levels of suPAR are significantly associated with poor outcome of ovarian cancer patients. However, additional studies are needed to further validate the clinical usefulness of plasma suPAR measurements in the management of ovarian cancer patients.

Adult↗
PubMed2001

A precise and efficient stereological method for determining murine lung metastasis volumes.

We have developed a computer-assisted stereological method based on unbiased principles for estimating metastasis volumes in mouse lungs. We evaluated this method using the transplantable Lewis lung carcinoma. Twenty-one days after subcutaneous inoculation of 10(6) Lewis lung cells into C57BL/6J mice, the mice had primary tumors with an average volume of 2300 mm(3). After perfusion fixation, the lungs were removed, embedded in OCT compound, snap-frozen, and processed for stereology. The metastasis volumes were estimated by application of the Cavalieri principle after evaluation of single sections from several evenly distributed tissue levels. The metastasis volume in a group of nine mice varied between 0.01 and 14.4 mm(3), with an average of 6.1 mm(3). The coefficient of variation was 0.9. The coefficient of error of the volume estimation was determined in five cases and varied from 0.08 to 0.23. Thus, the variation on the metastasis volumes that is achieved by this method contributes very little, 2.5%, to the total variance within the group of mice. In conclusion, we have developed an efficient and unbiased method to determine the metastasis burden in mouse lungs.

Animals↗
PubMed2001

Prognostic importance of the soluble plasminogen activator receptor, suPAR, in plasma from rectal cancer patients.

Colorectal cancer is one of the most common tumour types with approximately one third of the tumours located within the rectum. Rectal cancer differs somewhat from colon cancer, e.g. regarding the method of operation and the use of preoperative radiotherapy due to a tendency for local tumour recurrence. Proteolytic enzymes have been identified as key molecules in tumour invasion and metastasis, and factors within the urokinase-plasminogen activation (uPA) system have been associated with prognosis in several tumour types, including colorectal cancer. Recently, methods have been developed to analyse the soluble fraction of the plasminogen activator receptor (suPAR) in blood samples. An association between elevated suPAR levels and poor prognosis has recently been demonstrated in colorectal cancer. We have measured suPAR levels in pretreatment plasma samples from 173 rectal cancer patients in order to confirm its prognostic strength in this clinical entity. suPAR levels were determined in ethylenediamine tetraacetic acid (EDTA) plasma by a kinetic enzyme-linked immunosorbent assay (ELISA) and analysed with respect to sex, age, Dukes' stage, tumour differentiation grade and survival. In a univariate analysis, continuous suPAR plasma levels were associated with survival (P<0.001) with shorter survival among patients with high suPAR values. Patients with suPAR values within the upper quartile had significantly shorter survival (hazard ratio (HR) 2.2, 95% confidence interval (CI) 1.3-43.7, P=0.002). In a multivariate Cox analysis, increasing suPAR values predicted shorter survival independent from Dukes' stage and tumour differentiation grade with an adjusted HR of 2.2 per ng/ml suPAR (95% CI 1.2-4.0, P=0.01). This study thus confirms that measurement of suPAR in preoperative plasma samples gives independent prognostic information in rectal cancer patients, higher values being associated with shorter survival.

Adult↗
PubMed2001

The association between preoperative concentration of soluble vascular endothelial growth factor, perioperative blood transfusion, and survival in patients with primary colorectal cancer.

OBJECTIVE: To investigate a possible association between the preoperative concentration of soluble vascular endothelial growth factor (sVEGF), perioperative blood transfusion, and survival in patients operated on for colorectal cancer. DESIGN: Retrospective study. SETTING: University hospital, Denmark. SUBJECTS: 614 patients operated on for primary colorectal cancer. MAIN OUTCOME MEASURES: Association between preoperative blood transfusion and preoperative concentration of sVEGF. Association between perioperative blood transfusion and survival. RESULTS: Blood transfused up to one month before preoperative serum samples were obtained was significantly (p = 0.02) associated with high preoperative concentrations of sVEGF. The frequency of perioperative blood transfusion was significantly (p = 0.0007) higher in patients with rectal cancer than in patients with colon cancer. A multivariate analysis showed that intraoperative or postoperative blood transfusion or both, were significantly (p = 0.03) associated with poor survival in patients with Dukes stage A, B and C rectal cancers, while this association was not found in patients with colon cancer. CONCLUSIONS: Preoperative blood transfusion may be associated with high preoperative concentrations of sVEGF in patients with colorectal cancer. Transfusion during or after the operation is associated with poor survival in patients with Dukes stage A, B, and C rectal cancers.

Adult↗
PubMed2000

The complex between urokinase and its type-1 inhibitor in primary breast cancer: relation to survival.

We examined the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival of breast cancer patients. The study included 342 axillary lymph node-negative and -positive primary breast cancer patients with a median follow-up of 67 months. Using a newly established ELISA, the levels of preformed uPA-PAI-1 complex were measured in tumor tissue extracts and analyzed with respect to total uPA, total PAI-1, and clinicopathological parameters, including survival. uPA-PAI-1 complex comprised a minor, variable fraction of both total uPA and PAI-1 levels. The complex levels were higher in node-negative tumors than in node-positive tumors and higher in small and low-grade tumors (all, P < or = 0.002). The tumor levels of complex, uPA, and PAI-1 were all associated with survival; high complex levels predicted longer recurrence-free survival (P = 0.03) and overall survival [OS (P = 0.005)], whereas high uPA or PAI-1 levels significantly predicted shorter survival. In multivariate Cox analysis, the only parameters that independently predicted survival were total PAI-1 level and lymph node status for recurrence-free survival and OS and, additionally, steroid hormone receptor status and grade for OS. This is the first demonstration of a relationship between uPA.PAI-1 complex tumor level and patient survival. However, total PAI-1 level showed superior prognostic power. Additional studies are needed to understand the relationship of these parameters to cancer biology and to assess the clinical utility of the uPA PAI-1 complex.

Adult↗
PubMed2000

Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer. The RANX05 Colorectal Cancer Study Group.

BACKGROUND: Preoperative plasma plasminogen activator inhibitor-1 (PAI-1) is a prognostic variable in patients with colorectal cancer. It has been suggested, however, that plasma PAI-1 is a nonspecific prognostic parameter similar to the acute-phase reactant C-reactive protein (CRP). In the present study we analyzed the association between plasma PAI-1 and serum CRP in patients scheduled for elective resection of colorectal cancer. In addition, the prognostic value of PAI-1 and CRP was studied in this patient cohort. METHODS: PAI-1 and CRP were analyzed in citrated plasma and serum, respectively, obtained preoperatively from 594 patients. Patients who required preoperative blood transfusion received SAGM blood, in which soluble PAI-1 is not present. None of the patients received pre- or postoperative adjuvant chemotherapy, and all were followed in the outpatient clinic for at least 5 years or until death. The association of PAI-1 and CRP, respectively, with survival was tested using the median value of PAI-1 and the upper normal limit for CRP. Analyses were performed by inclusion of all patients, and in the subgroup of patients, who underwent curative resection. RESULTS: The median follow-up period was 6.8 (5.4-7.9) years. The median value of plasma PAI-1 was 35.8 ng/ml, and values greater than 94 nmol/L identified patients with increased CRP levels. Comparison of the molecules showed that PAI-1 was weakly correlated with CRP (r = .26; P <.0001). Both molecules showed a Dukes independent distribution. In univariate survival analyses high levels of PAI-1 were found associated with poor prognosis and low levels with good prognosis (P = .02, HR: 1.3). Similarly, high levels of CRP were found associated with poor prognosis and low levels with good prognosis (P <.0001, HR: 1.9). In a multivariate statistical analysis including Dukes classification, gender, age, tumor location, perioperative blood transfusion, PAI-1 and CRP, plasma PAI-1 was a dependent prognostic variable, while serum CRP (P <.0001; HR: 1.4; 95% CI: 1.3-1.5) was found to be a Dukes independent prognostic variable. Similar analyses, excluding patients with Dukes' D disease showed serum CRP to be an independent prognostic variable (P <.0001; HR: 1.3: 95% CI: 1.2-1.5). CONCLUSIONS: This study did not show a strong correlation between plasma PAI-1 and serum CRP in patients with colorectal cancer. Serum CRP was found to be a Dukes independent prognostic variable in this patient cohort, and was found to identify a subgroup of curatively resected patients at risk for short survival.

Adult↗
PubMed2000

Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy.

In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.

Biomarkers, Tumor↗
PubMed2000

Carcinoma in situ of the female breast. 10 year follow-up results of a prospective nationwide study.

In a Danish nationwide prospective study of in situ carcinoma of the breast, a total of 275 women, treated with excision alone, were registered from 1982 to 1989. The series included 142 cases of ductal carcinoma in situ (DCIS), 100 cases of lobular carcinoma in situ (LCIS), 26 cases of DCIS+LCIS, and seven cases of atypical hyperplasia (AH). Within a median follow-up of 120 months, a crude recurrence rate of 28% (76 cases) was found, of which 53% (40 cases) recurred as invasive carcinomas (IC) and 47% (36 cases) as CIS. CIS recurrences appeared after median 18 months, compared to median 42 months for IC recurrences. No statistical difference was found with respect to development of IC between the three groups of DCIS, DCIS+LCIS, and LCIS. The majority of recurrences were ipsilateral, also for LCIS. Forty four of 49 recurrences following DCIS, and seven of nine recurrences following DCIS+LCIS occurred as local recurrences. Histopathologically, in DCIS a strong association was found between large nuclear size and comedonecrosis. Univariate analysis showed a significant association to recurrence for nuclear size, comedonecrosis, and size of the original lesion. Multivariate analysis showed that only comedonecrosis and size of lesion were independent predictors of recurrence, however, specimen margins were not included in the analysis, as this parameter could not be adequately evaluated in the present series. Nuclear size of original DCIS lesion was related to histologic grade of the IC recurrence. The recurrence rate for DCIS of small nuclear size increased from 6% at five years of follow-up to 16% at 10 years, possibly due to a slower growth rate and a continued but delayed risk. Similarities were found between LCIS and DCIS of small nuclear size, both showing a continued risk and comparable rate of recurrence. Further, progression to IC of similar, highly differentiated type was seen, indicating a linkage between biological behavior of the two histological types.

Adult↗