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Biomedical subjects

C Haglund

Publications and source records attributed to C Haglund.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cellular fibronectin concentration in the plasma of patients with malignant and benign diseases: a comparison with CA 19-9 and CEA.

EDAcFN enzyme immunoassay (EIA) is a new tumour marker assay measuring the extra domain A-containing isoform of cellular fibronectin (cFN), a component mainly found in extracellular matrices. The concentration cFN was measured in plasma and serum from 468 patients with malignant and benign diseases. The concentrations of cFN were higher in plasma than in serum. Using receiver operating characteristic (ROC) curve analysis, determination from plasma was superior to serum at specificity levels higher than 78% and was chosen for further analysis. The highest frequencies of elevated cFN values were seen in patients with hepato-pancreato-biliary malignancies (50-67%). In pancreatic and bile duct cancers, cFN provided little further information to that obtained by CA 19-9. The greatest advantage over CA 19-9 and CEA was seen in patients with local colorectal cancer and in hepatocellular carcinomas. Four out of nine patients with Dukes' stage B colorectal cancer had an elevated cFn level, but only one had an abnormal CEA level. In hepatocellular carcinomas, cFN was also compared with alpha-fetoprotein. The sensitivity of cFN (72%) was superior to that of AFP (61%), and concomitant use of cFN and AFP raised the sensitivity to 83%. The highest frequencies of elevated values in patients with benign diseases were observed in those with severe liver disease (32%) and biliary (17%) and pancreatic (24%) diseases. A combination of cFN and CA 19-9 showed the highest overall sensitivity of 47%, compared with 31% for cFN and 33% for CA 19-9. The corresponding specificities were 76% for cFN +/- CA 19-9, 85% for cFN and 83% for CA 19-9. The accuracy of a combination of cFN and CA 19-9 or CEA (60% respectively) was higher than that of cFN (55%), CA 19-9 (55%) or CEA (45%) alone. In conclusion, the results of the new cFN test are encouraging and further studies on larger patient materials have been started.

Biomarkers, Tumor↗
PubMed1997

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

The prognostic value of Ki-67, p53 and ER immunohistochemical labelling and flow-cytometric S-phase fraction and ploidy was evaluated in 212 pT1N0M0 breast carcinomas. The mean follow-up time was 8.3 years. Patients with breast carcinomas with high Ki-67 expression (> or = 10%) had a less favourable disease-free survival than those with low Ki-67 expression (< 10%) (p = 0.008). A positive p53 staining and high SPF were associated with a less favourable disease-free survival although it did not reach statistical significance. The subset of patients with ER negative, Ki-67 > or = 10% and p53 > or = 20% tumours, had a shorter disease-free survival compared with that of all the other patients (p = 0.03). We conclude that the potential value of Ki-67 labelling for prognostic evaluation of T1N0M0 breast carcinoma is good.

Adult↗
PubMed1996

A risk score for predicting outcome in patients with gastric cancer, based on stage, sialyl-Tn immunoreactivity and ploidy--a multivariate analysis.

Twelve variables were studied for possible prognostic value in 242 patients with adenocarcinoma of the stomach. Eight of these had a statistically significant effect on survival in univariate analyses. A multivariate analysis of 196 patients showed that the most significant differences in survival could be explained by 3 independent variables acting simultaneously, namely stage of disease, Sialyl Tn antigen (STn) expression and aneuploidy of the tumour cells. By adding scores for stage (1-4 points), STn expression (0-1 points) and ploidy (0-1 points) a risk score based on these 3 variables defined the patients into 6 different risk groups with statistically highly significant differences in survival (chi 2 = 107.74, DF = 1, p < 0.0001). Application of the risk score improves the prediction of outcome, may help in choosing patients for different treatment modalities, and allows more accurate stratification in clinical trials.

Aged↗
PubMed1996

Serum trypsinogen-2 and trypsin-2-alpha(1)-antitrypsin complex in malignant and benign digestive-tract diseases. Preferential elevation in patients with cholangiocarcinomas.

Serum concentrations of trypsinogen-2 and trypsin-2-alpha(1)-antitrypsin (trypsin-2-AAT) were determined in 145 patients with malignant and 61 with benign digestive-tract diseases. The validity of these tests for detection of cancer was compared with that of CA 19-9 and CEA. Elevated levels of trypsinogen-2 (>90 micrograms/l) and trypsin-2-AAT (>25 micrograms/l) were found in 46% and 42%, respectively, of patients with malignant disease and the levels of trypsinogen-2 were significantly higher than in those with benign disease (p<0.005). High trypsinogen-2 and trypsin-2-AAT concentrations were found most often in patients with biliary and pancreatic cancer, but also in benign obstructive biliary disease. Our results suggest that trypsinogen-2 and trypsin-2-AAT are new potential markers for cholangiocarcinomas.

Amylases↗
PubMed1996

Sialyl Tn antigen is an independent predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of Sialyl Tn antigen (STn) was evaluated in 242 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody C1282, produced by immunization with ovine submaxillary mucin (OSM). Positive immunoreactivity for STn was observed in 149 (62%) patients. The expression of STn did not correlate with stage of disease (TNM), tumour location, presence of lymph-node or distant metastases, histological type, age or gender. STn immunoreactivity correlated strongly with overall survival in univariate analysis. The median survival in the STn-positive group was 21 months, in comparison to 38 months in the STn-negative group. The difference in survival between STn-negative and STn-positive tumours was significant in patients with stage-I cancer, but not in patients with stage-II -III or -IV disease. STn immunoreactivity emerged as an independent prognostic factor in Cox multivariate analysis. It is concluded that the immunohistochemical expression of STn is a good marker in the prediction of survival in patients with stage-I gastric carcinoma.

Adenocarcinoma↗
PubMed1996

Expression of p53 protein as a prognostic factor in patients with gastric cancer.

The prognostic value of overexpression of the p53-encoded protein was evaluated in 242 patients with gastric cancer. Formalin-fixed paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody DO-7. 95 patients (39%) showed a high level of immunoreactivity (> or = 20% of cell nuclei staining positively), suggesting the presence of a mutation in the TP53 coding sequence. Overexpression of the p53 protein correlated significantly with stage of disease (P = 0.01), the presence of distant metastases (P = 0.04) and with the intestinal type of cancer (P = 0.04). No correlation between p53 overexpression and age, gender or the presence of the lymph node metastases was found. In univariate analysis, p53 immunoreactivity correlated significantly with survival (P = 0.0005). The median survival in the p53 high-level group was 19 months compared with 65 months in the p53 low-level group. In multivariate analyses, stage of disease and the presence of distant metastases emerged as independent prognostic factors, whereas p53 immunoreactivity did not (P = 0.08). The present results indicate that overexpression of the p53 protein is not an independent prognostic factor in patients with gastric cancer.

Adenocarcinoma↗
PubMed1996

Pre-operative serum levels of CA 242 and CEA predict outcome in colorectal cancer.

The prognostic value of the preoperative serum levels of CA 242 and CEA in patients with colorectal cancer was investigated. The serum concentrations of CA 242 and CEA were determined from preoperative serum samples of 259 patients with colorectal cancer (39 Dukes' A, 100 Dukes' B, 59 Dukes' C and 61 Dukes' D). Survival data of these patients were obtained to the end of 1993. There was a significantly longer survival in patients with a CA 242 level below 20 U/ml compared with patients with an elevated serum level. A difference was seen in overall survival (P < 0.0001), and in Dukes' B (P = 0.016) and Dukes' D (P = 0.009) stages. In Dukes' A and C colorectal cancer, the difference was not significant (P = 0.67 and P = 0.07, respectively). When 5 ng/ml was used as cut-off value for CEA, there was a significant difference in overall survival (P < 0.0001), but not within the different Dukes' stages. The prognosis was considerably worse in patients with concomitant elevation of CA 242 and CEA, compared with the prognosis of patients with normal levels or only one marker elevated (P < 0.0001). When analysing according to stage, a significant difference was seen in Dukes' B (P = 0.0004) and Dukes' C (P = 0.0007) stages. In a multivariate analysis, CA 242 was an independent prognostic factor (P < 0.0001). CEA was also an independent prognostic factor (P = 0.03), but only after exclusion of CA 242. Concomitant rise of CA 242 and CEA was found to be a strong independent prognostic factor (P < 0.0001). This study shows that the pre-operative serum CA 242 level is an independent prognostic factor in patients with colorectal cancer and that the prognosis of patients having a concomitant pre-operative elevation of CA 242 and CEA is poor.

Adult↗
PubMed1996

Independent prognostic value of preoperative serum markers CA 242, specific tissue polypeptide antigen and human chorionic gonadotrophin beta, but not of carcinoembryonic antigen or tissue polypeptide antigen in colorectal cancer.

The prognostic value of preoperative serum concentrations of carcinoembryonic antigen (CEA), CA 242, tissue polypeptide antigen (TPA), specific tissue polypeptide antigen (TPS) and human chorionic gonadotrophin beta (hCG beta) in 251 patients with colorectal cancer (39 Dukes' A, 98 Dukes' B, 56 Dukes' C and 58 Dukes' D) was investigated. When using the cut-off levels recommended for diagnostic purposes, there was a significantly longer overall survival in patients with low tumour marker levels compared with patients with elevated serum levels for all the investigated markers. In Dukes' stage B, C and D CA 242 emerged as a significant predictor of survival, whereas TPA, TPS and hCG beta showed a value only in Dukes' D. Unfortunately, no marker provided prognostic information in Dukes' A. In multivariate analysis, entering the tumour markers as continuous variables, Dukes' stage was the strongest prognostic factor, followed by CA 242. TPS, hCG beta and localisation of the tumour were also independent prognostic factors, whereas age, gender, CEA and TPA were not.

Adult↗
PubMed1996

Laparoscopic cholecystectomy: the Finnish experience.

Between January 1992 and December 1994, 5,742 patients were treated by laparoscopic cholecystectomy in 35 Finnish hospitals. The operation was converted to open laparotomy in 360 (6.3%) patients, the most common causes for conversion being technical difficulties in dissection of the gall bladder (2.8%), bleeding (0.9%) and bile duct injury (0.48%). Intraoperative cholangiography was performed selectively in 18%, and common bile duct stones were found in 10.2% of these cases. Postoperative complications occurred in 208 (3.6%) patients, of whom 65 (1.1%) required reoperation. Twenty-eight (0.48%) of these patients had common bile duct injury. In eighteen patients bilio-digestive Roux-en-Y reconstruction was performed, whereas 10 cases could be handled by endoscopic drainage or suturing and T-tube drainage. Thus, the total number of patients with bile duct injury was 56 (0.96%). The reported hospital mortality was 0.08%. The mean hospital stay and the mean sick leave were three days (range 1-41) and 13 days (range 1-60), respectively. These data demonstrate that laparoscopic cholecystectomy can be performed with acceptable morbidity and mortality rates as a routine method in various different hospitals.

Absenteeism↗
PubMed1995

An improved method for quantification of extra domain A-containing cellular fibronectin (EDAcFN) in different body fluids.

A quantitative direct enzyme immunoassay for the extra domain A-containing isoform of cellular fibronectin (EDAcFN) was established for screening of large series of blood samples and various body fluids of different pH and viscosity. The method is based on the monoclonal antibody DH1 recognizing the extra domain A in cellular fibronectin (EDAcFN). Studies on the effect of dilution of plasma and serum samples in this direct assay indicated that the measured concentration of cFN in the samples greatly depend on the ratio of sample dilution. The linearity of the assay was improved with sample dilution and the optimal dilution was 1:5. Stored diluted samples retained their cFN content at +4 degrees C, and -20 degrees C and -70 degrees C for months in contrast to samples stored undiluted. With this direct EIA the detection limit was 0.05 micrograms/ml and the linear portion of the standard curve could be extended above 30 micrograms/ml. Thus, the cFN concentration of blood samples could be measured reliably without inhibition also in samples with very high concentration of cFN. This is particularly important when measuring blood samples from cancer patients, since these samples may contain more than 20 micrograms/ml EDAcFN. The assay was standardized for blood samples but, due to the possibility of sample dilution, it also enabled reliable quantification of EDAcFN in various other body fluids. Undiluted some of the samples with non-neutral pH (urine, bile) or with high viscosity (seminal plasma) interfered with the assay. In addition to blood samples, the EDAcFN concentration was determined in samples of urine, bile, amniotic fluid, cervicovaginal secretions, seminal fluid, cerebrospinal fluid, bronchoalveolar lavage fluid, pleural fluid and saliva. Thereby, this modified method was shown to be applicable to various body fluids.

Amniotic Fluid↗
PubMed1995

Enzyme immunoassay for quantification of tenascin in biologic samples.

An enzyme immunoassay was developed for quantification of tenascin in biologic samples. An enzyme conjugate prepared by coupling peroxidase to a well-characterized, affinity-purified monoclonal antibody EB2 to human tenascin was used as principal reagent. The assay comprises 96-well microtitration strip plates with immobilized monoclonal antibody DB7 to human tenascin. By using a novel monoclonal antibody suppressing human-anti-mouse-factor, MAK33, in the sample buffer, the specificity of the test could be improved. The method has a minimum detectable sensitivity of 1.5 ng tenascin and permits determination of tenascin in various biologic samples. The coefficients of variation within run and between run ranged from 0.9% to 5.0%. The average tenascin concentration in normal plasma was 0.97 mg/L (n = 200) and in serum 0.73 mg/L (n = 200). The tenascin concentrations were also determined in samples of urine, bile, amniotic fluid, seminal fluid, cerebrospinal fluid, bronchoalveolar lavage (BAL) fluid, and pleural fluid showing general applicability of the assay. The method permits the determination of tenascin in samples of different body fluids from various diseases, including cancer, showing increased amounts of the protein at the tissue level.

Antibodies, Monoclonal↗
PubMed1995

A prognostic value of CA 19-9 but not of CEA in patients with gastric cancer.

The diagnostic and prognostic value of tumour markers CEA and CA 19-9 was studied in patients with gastric cancer. Pre-operative serum concentrations of CEA and CA 19-9 were determined in 100 gastric cancer patients and in 77 patients with relevant benign diseases. The sensitivity of both CEA (cut-off level 3 ng/ml) and CA 19-9 (cut-off level 37 U/ml) for gastric cancer was 30%. The specificities were 73% and 87%, respectively. There was a significant difference in prognosis, for both CEA (cut-off level 3 ng/ml, P < 0.05) and CA 19-9 (cut-off level 37 U/ml, P < 0.01), between patients with high vs low pre-operative serum levels. The overall 5-year survival was 26% and that of patients with low marker levels was 30% (CEA) and 35% (CA 19-9) compared with 15% (CEA) and 0% (CA 19-9) for patients with high marker levels. To evaluate whether the high vs low serum marker level was an independent prognostic factor, the patients were compared within the same stage of disease. There was still a significant difference in 5-year survival in stages II, III and IV between patients with high vs low pre-operative serum levels for CA 19-9 (P < 0.05), but not for CEA. In stage I, no differences in survival could be found for either marker. In conclusion, high pre-operative serum levels of CEA seem to predict higher stage of disease, whereas CA 19-9 might have an independent prognostic value in patients within the stage of II, III or IV gastric cancer. The diagnostic value of both CEA and CA 19-9 is limited.

Adult↗
PubMed1995

Cellular fibronectin in serum and plasma: a potential new tumour marker?

The concentration of cellular fibronectin (cFN) containing the extra domain A (EDA) was measured in 479 plasma and 300 serum samples from healthy blood donors by a competitive enzyme immunoassay (EIA). Serum and plasma samples contained low concentrations of EDAcFN. The mean concentration of EDAcFN was higher in plasma (2.46 mg l-1) than in serum (0.30 mg l-1). No significant differences between sexes or age groups were found. The EDAcFN concentrations were also measured in 120 patients with various malignancies. The mean values in serum were 4.28 mg l-1, 2.01 mg l-1 and 5.18 mg l-1 in patients with digestive tract malignancies, breast cancer and a group of miscellaneous cancers respectively. In plasma, the corresponding values were 12.26 mg l-1, 4.38 mg l-1 and 11.12 mg l-1 respectively. The serum EDAcFN concentration was higher than the 97.5th percentile level of healthy blood donors in 86% of patients with digestive tract and in 76% with miscellaneous malignancies. In patients with breast cancer 60% had elevated levels of EDAcFN. The corresponding figures for plasma samples in patients with digestive tract and miscellaneous malignancies were 79% and 71% respectively. In patients with breast cancer only 30% had elevated plasma levels of EDAcFN. The mean values in serum and plasma of 20 patients with benign diseases were below the cut-off levels. Consistent with the EIA results, Western blotting revealed increased amounts of EDAcFN in blood samples from cancer patients. Pregnancy did not affect the EDAcFN concentration. The mean values in 20 pregnant women were below the cut-off levels.

Antibodies, Monoclonal↗
PubMed1995

Preoperative serum levels of CEA and CA 242 in colorectal cancer.

Preoperative serum levels of CEA and CA 242 were determined in 260 patients with colorectal cancer and in 92 patients with benign colorectal diseases. The overall sensitivity of the CEA test was 43% and of the CA 242 test 39%. The corresponding specificities were 90% and 87% respectively, using 5 ng ml-1 as cut-off level for CEA and 20 U ml-1 for CA 242. The sensitivity of CEA was 26%, 32%, 38% and 77% for Dukes A, B, C and D colorectal cancer, and the sensitivity of CA 242 was 26%, 26%, 40% and 67%, respectively. The correlation between CEA and CA 242 was low. Concomitant elevation of both markers was seen in 5%, 12%, 18% and 59% of patients with Dukes A, B, C and D colorectal cancer, respectively. Of all the patients, 23% showed elevation of both the CEA and the CA 242 level, whereas CEA alone was elevated in 20% and CA 242 alone in 15% of the patients with colorectal cancer. Combined use of both markers raised the overall sensitivity from 43% to 58%, but reduced the specificity from 90% to 80%. The increase in sensitivity by combining the two markers was most marked in Dukes A, B and C colorectal cancer. Either or both of the markers were elevated in 46%, 46% and 60% of the patients respectively. The clinical value of combining CEA and CA 242 seems very promising and should be further investigated in prospective studies.

Adenoma↗
PubMed1995

Effect of intraperitoneal bupivacaine on pain after laparoscopic cholecystectomy.

The effect of intraperitoneal bupivacaine on postoperative pain was studied in 60 ASA 1-2 patients undergoing elective laparoscopic cholecystectomy. The patients were randomly selected (20 patients in each group) to receive in double-blind fashion 100 mo of either plain 0.15% bupivacaine (150 mg.100 ml-1) or the same solution with adrenaline (1.5 micrograms ml-1), or the same volume of saline into the right subdiaphragmatic space at the end of surgery. The patients were kept in the Trendelenburg's position for 20 min after the instillation. Venous blood samples for the determination of bupivacaine plasma concentrations were drawn up to 180 min. Plasma bupivacaine concentrations peaked at 30 min (highest individual value 2.6 micrograms ml-1) after instillation. Bupivacaine concentrations were significantly lower in the bupivacaine-adrenaline group. During the follow-up no difference between the groups occurred as to the time to first demand of analgesia, severity of postoperative pain, amount of consumed analgesics during 7 days, and length of hospitalization. In all groups, 30-45% of the patients complained of right shoulder pain. After the first 24 hours, pain at rest and during moving was reported as mild and was managed with oral ketoprofen. It is concluded that postsurgical intraperitoneal instillation of 150 mg bupivacaine in 100 ml of saline had no effect on pain after laparoscopic cholecystectomy.

Abdominal Pain↗
PubMed1994

CA 242, a new tumour marker for pancreatic cancer: a comparison with CA 19-9, CA 50 and CEA.

The serum expression of a novel tumour marker, CA 242, defined by monoclonal antibody C 242, was studied in 179 patients with pancreatic cancer. The results were compared with CA 19-9, CA 50 and CEA. CA 242 is a carbohydrate closely related, but not identical, to CA 19-9 and CA 50. The overall sensitivity of the CA 242 assay was 74%: 55% in stage I, 83% in stage II-III and 78% in stage IV disease. The specificity calculated from 112 patients with benign diseases was 91%. CA 19-9 had a higher sensitivity of 83%, but the specificity was only 81%. When comparing the markers by receiver operating characteristic analysis, the sensitivities were almost identical at all specificity levels. The CA 242 level was elevated in 7%, 15% and 7% of patients with benign pancreatic, biliary and liver disease respectively. The corresponding figures for CA 19-9 were 19%, 28% and 15% respectively. The sensitivity of CA 242 was higher than that of CA 50 and CEA at all specificity levels. In conclusion, tumour marker CA 242 seems to be a useful diagnostic tool for the diagnosis of pancreatic cancer, and is an alternative to CA 19-9. The advantage of CA 242 over CA 19-9 is its higher specificity when using the recommended cut-off levels of the assays.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients with pancreatic cancer.

The prognostic value of preoperative serum levels of CA 19-9 and CEA was evaluated in 160 patients with pancreatic cancer. The survival of patients whose tumour marker value was below a certain cut-off level was compared with the survival of those with a higher value using the log-rank test. The lowest cut-off level dividing patients into groups with significant difference in survival (P < 0.05) was determined by graphical analysis of chi-square values at different cut-off levels. If stage of disease was not taken into account, there was a significant difference in survival between patients with low vs high preoperative CA 19-9 and CEA levels. When patients were classified according to stage, a difference was found for CA 19-9 in stage II-III patients. Patients with preoperative CA 19-9 below 370 U ml-1 had a significantly better prognosis than those with a higher level (P < 0.05). In stage I and stage IV patients, no significant difference was found between the groups at any cut-off level. The analysis of CEA showed a significant difference in survival only in stage IV patients, with CEA above 15 ng ml-1 being associated with shorter survival. In conclusion, in patients with stage II-III disease, particularly in patients with a non-resectable tumour, in whom the exact spread of the disease may be difficult to evaluate even at operation, the preoperative CA 19-9 level seems to have a prognostic value.

Antigens, Tumor-Associated, Carbohydrate↗