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Papers by M. Eskelinen

Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer

Anticancer research

S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of s... more S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF ...

Clinical Prognostic Factors in Transitional Cell Cancer of the Bladder

Urologia Internationalis, 1993

A cohort of 537 patients with transitional cell cancer of the bladder (TCC) were followed up for ... more A cohort of 537 patients with transitional cell cancer of the bladder (TCC) were followed up for a mean of 9 years and the clinicopathological data were related to prognosis. The T category (p < 0.0001), N category (p < 0.0001) and M category (p < 0.0001) were the most important clinical prognostic factors, followed by the age of the patient (p < 0.0001). Of the histological variables the WHO grade (p < 0.0001), papillary status (p < 0.0001) and the presence of R3-4 cells in voided urine (p = 0.0061) predicted unfavorable prognosis. In Ta-T1 tumors the WHO grade (p < 0.0001), papillary status (p < 0.0001) and the age of the patient (p < 0.0001) had a prognostic value in univariate analysis. In Cox's analysis independent predictors of survival were the T category (p < 0.0001), WHO grade (p < 0.0001), patient age (p < 0.0001), papillary status (p = 0.012) and the presence of symptoms before diagnosis (p = 0.033). In superficial tumors the WHO grade (p < 0.0001) and patient age (p < 0.0001) were independent predictors of survival.

Ag-NORs related to flow cytometry, morphometry and prognosis in patients with pancreatic cancer

Anticancer research

The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy s... more The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag-NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and t...

Mitotic activity index, volume corrected mitotic index and human papilloma-virus suggestive morphology are not prognostic factors in carcinoma of the oesophagus

Anticancer research

Radiation treatment, endoscopic dilatations and laser treatment offer an alternative to surgery a... more Radiation treatment, endoscopic dilatations and laser treatment offer an alternative to surgery as palliation in oesophageal cancer, and therefore it is essential to assess the prognostic factors preoperatively in order to select the treatment individually. Mitotic activity index (MAI), volume corrected mitotic index (M/V-index) and histologic evidence for human papillomavirus (HPV) involvement together with other prognostic factors were studied in 61 patients with oesophageal squamous cell carcinomas. No patient was lost from follow-up and 18% of patients were alive at the end of follow-up. Evidence for HPV involvement was found in 11 (18%) of 61 patients, which was significantly (p < 0.001) less than in a previous series of Chinese patients. Histological grade (p = 0.025), lymph node status (p = 0.002), presence of distant metastasis (p = 0.004), surgical resection (p = 0.03) and nuclear pleomorphism (p = 0.04) were significant independent prognostic factors in univariate analy...

Clinical evaluation of serum tumour markers CEA, CA 50 and CA 242 in colorectal cancer

Anticancer research

The aim of the present prospective study was to evaluate the clinical value ol serum tumour marke... more The aim of the present prospective study was to evaluate the clinical value ol serum tumour markers CEA, CA 50 and CA 242 in patients with colorectal cancer (n = 138) and patients with benign gastrointestinal disease (n = 104). The cutoff levels (90% specificity) determined for each test were 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the CEA test was 0.63, that of the CA 50 test was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. CEA, CA 50 and CA 242 tests were tested in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was CEA followed by CA 242. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.47 with a specificity of 0.88 and an efficiency of 0.67. On the basis of this study, serum CEA and CA 242 se...

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer

Anticancer research

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index... more DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour d...

A decision support system for predicting a recurrence of breast cancer; a prospective study of serum tumour markers TAG 12, CA 15-3 and MCA

Anticancer research

The aim of the present study was to evaluate the clinical value of the preoperative serum tumour ... more The aim of the present study was to evaluate the clinical value of the preoperative serum tumour markers TAG 12, CA 15-3 and MCA in predicting a recurrence of breast cancer patients. The sensitivity of the TAG 12 test was 54%, that of the CA 15-3 test 15% and that of the MCA test 15% in predicting a recurrence of breast cancer. The most important predictor of breast cancer recurrence was TAG 12. In order to evaluate the contributions of different tumour marker serum test, a stepwise discriminant analysis was carried out. The discriminant function (DF) is DF = TAG 12 x 0.061 - CA 15-3 x 0.1336 - 0.396. The sensitivity of the DF in detecting recurrence of breast cancer was 63% with a specificity of 90% and an efficiency of 75%. In conclusion, the results indicate that a new tumour marker TAG 12 is superior to CA 15-3 and MCA in predicting breast cancer recurrence. In this study the discriminant function including TAG 12 and CA 15-3 was superior to single preoperative tumour marker tes...

A prospective study of tissue polypeptide specific antigen (TPS) in breast cancer diagnosis

Anticancer research

The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in ser... more The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in sera from patients with breast cancer and patients with benign breast disease. The results for TPS were compared with those for TAG 12, CA 15-3 and MCA. The cutoff levels (90% specificity) determined for each test were 108.0 U/1 for TPS, 57.5 KU/1 for TAG 12, 24.8 KU/1 for CA 15-3 and 9.7 KU/1 for MCA. The diagnostic sensitivity of the TPS test was 0.21, for the TAG 12 test it was 0.2, 0.13 for the CA 15-3 test and 0.12 for the MCA test in detecting breast cancer. TPS, TAG 12, CA 15-3 and MCA tests were tested in a multivariate analysis to find the best combination of independent predictors of breast cancer. The most important predictor of breast cancer was TAG 12 followed by TPS. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The diagnostic score (DS) was: DS = TPS x 0.0085 x TAG 12 x 0.0596 - CA 15-3 x 0.0866 - MCA x 0.2938 + 0.1738....

Sex-Specific Diagnostic Scores for Acute Appendicitis

Scandinavian Journal of Gastroenterology, 1994

The role of clinical and computer-based decisions in the diagnosis of acute appendicitis was stud... more The role of clinical and computer-based decisions in the diagnosis of acute appendicitis was studied in connection with the survey of acute abdominal pain by the Research Committee of the World Organization of Gastroenterology (OMGE). One thousand three hundred and thirty-three patients presenting with acute abdominal pain were included in the study. Twenty-two preoperative clinical history variables, 14 clinical signs, and 3 tests were evaluated in a multivariate analysis to find the best combination of independent predictors of acute appendicitis for males and females. Independent predictors of acute appendicitis in males were tenderness, previous abdominal surgery, rebound, rigidity, location of pain at diagnosis, guarding, and body temperature. To sum up the contributions of the most significant diagnostic factors, a diagnostic score (DS) was built. When the male patients with a DS value between -2.00 and -0.48 were considered nondefined (n = 75, follow-up required before deciding to operate), the sensitivity of the computer-aided diagnosis in detecting acute appendicitis in males was 0.95, with a specificity of 0.89 and an efficiency of 0.91. In males whose leucocyte count was available (n = 476), previous abdominal surgery, leucocytosis, location of pain at diagnosis, tenderness, rigidity, rebound, guarding, rectal digital tenderness, and body temperature predicted significantly acute appendicitis. The DS reached a sensitivity of 0.94 (the cut-off level was -1.74), with a specificity of 0.80 and an efficiency of 0.84. (ABSTRACT TRUNCATED AT 250 WORDS)

Argyrophilic Nucleolar Organizer Regions May Help the Differential Diagnostic Distinction between Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma

Scandinavian Journal of Gastroenterology, 1994

The aim of this study was to determine whether the number of argyrophilic nucleolar organizer reg... more The aim of this study was to determine whether the number of argyrophilic nucleolar organizer regions (AgNORs) could be of diagnostic significance in differentiating between chronic pancreatitis and pancreatic ductal adenocarcinoma. The number of AgNORs was enumerated in biopsy specimens of normal pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma. The number of AgNORs was lower in patients with normal pancreas than in patients with chronic pancreatitis or pancreatic adenocarcinoma. In addition, the number of AgNORs was significantly lower in chronic pancreatitis than in pancreatic ductal adenocarcinoma (p &lt; 0.001). The diagnosis of pancreatic adenocarcinoma is usually clear. Difficulties can be encountered, however, in cases of chronic pancreatitis, specially when biopsy material is small. Our results suggest that the number of AgNORs may help in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma, especially in diagnostically difficult specimens.

Prognostic Factors after 5 Years Follow-Up in Female Breast Cancer

Oncology, 1992

A consecutive series of breast carcinomas (n = 595) followed up for a minimum of 7.5 years was an... more A consecutive series of breast carcinomas (n = 595) followed up for a minimum of 7.5 years was analyzed for clinical, histological and morphometric prognostic factors after 5-years&amp;amp;#39; follow-up. Tumor size, nodal status, mitotic frequency and patients&amp;amp;#39; age at diagnosis predicted survival at 7.5 years highly significantly (p less than 0.0001). Tubule formation (p = 0.002), histological grade (p = 0.026) and nuclear pleomorphism (p = 0.046) were related to prognosis as well. In N--patients mitotic frequency (p = 0.018) was the best predictor of survival at 7.5 years whereas in N + tumors tumor size (p = 0.0013), tubule formation (p = 0.003) and mitotic frequency (p = 0.0049) were the best predictors of survival at 7.5 years. In univariate survival analysis the age of the patients (p = 0.002), tubule formation (p = 0.005), axillary lymph node status (p = 0.008), lymphocyte infiltration (p = 0.049), mitotic frequency (p = 0.06) and tumor size (p = 0.08) predicted survival after 5 years&amp;amp;#39; follow-up. Tubule formation predicted survival (p = 0.025) in N - patients and in N + tumors the age of the patients was the most important predictor (p = 0.006). In Cox&amp;amp;#39;s analysis tubule formation (p = 0.13), axillary lymph node status (p = 0.033), SD of nuclear perimetry (p = 0.046) and intraductal growth (p = 0.059) predicted survival independently after 5 years&amp;amp;#39; follow-up.

Mitotic indexes as prognostic predictors in female breast cancer

Journal of Cancer Research and Clinical Oncology, 1992

A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, ax... more A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, axillary lymph node status, histological grade, histological type and two mitotic indexes (M/V; MAI) were assessed and related to disease outcome. Primary tumour size (P less than 0.0001), the volume-corrected mitotic index (M/V) (P less than 0.0001), the mitotic activity index (MAI) (P = 0.0001), and histological grade (P = 0.0074) predicted axillary lymph node status. Recurrence as well as recurrence-free survival was significantly related to the axillary lymph node status (P less than 0.0001), M/V index (P less than 0.0001), MAI (P less than 0.0001), tumour size (P = 0.0031) and histological grade (P = 0.0208). Multivariate analyses disclosed the tumour size and M/V index as independent predictors of axillary metastasis at diagnosis. Recurrence was related independently to M/V index, axillary metastasis and tumour size. Independent predictors of recurrence-free survival in Cox&amp;amp;#39;s analysis were M/V index and axillary lymph node status. Axillary lymph node status (P less than 0.0001), tumour size (P less than 0.0001), M/V index (P less than 0.0001), MAI (P less than 0.0001) and histological grade (P = 0.0009) predicted survival in that order. Cox&amp;amp;#39;s analysis showed that axillary lymph node status was the most important independent predictor of survival followed by tumour size and M/V index. In a separate Cox&amp;amp;#39;s analysis of axillary-lymph-node-negative patients the M/V index and tumour size were independently related to survival. In conclusion the M/V index is an important prognostic factor in breast cancer and also in axillary-lymph-node-negative breast tumours.

S152 Impaired Clearance and Unaltered Bioavailability of Three Oral Oxycodone Formulations in Elderly Patients

European Journal of Pain Supplements, 2011

European Journal of Cancer, 1993

The tissue expression of carbohydrate antigen CA-242 was analysed in forma&-fixed biopsy specimen... more The tissue expression of carbohydrate antigen CA-242 was analysed in forma&-fixed biopsy specimens from 147 transitional cell bladder tumours. The staining was related to established prognostic factors and survival during a mean follow-up of over 12 years and the staining results were also compared to expression of CA-SO antigen. Forty-one percent (60/147) of the tumours were negative for CA-242 and 59% (87/147) were positive. Normal bladder mucosa was positive for CA-242 and the umbrella cells in particular showed intense positive staining. In tumours, the umbrella cells were usually positive (when present) and in turnout tissue, positive cells appeared either as individual positive cells or in groups. None of the turnouts was entirely positive for CA-242. The tissue expression of CA-242 could not be significantly related to TNM classification, papillary status, WHO grade or quantitative variables (DNA ploidy, S phase fraction, mitotic frequency, nuclear factors). The tissue expression of CA-242 was significantly weaker than the expression of CA-50. The expression of CA-242 was related to favourable prognosis in survival analysis (P = 0.04). The results show that the expression of the novel tumour marker antigen CA-242 as determined in parah-embedded material is a weak prognostic factor as compared with established prognostic factors in transitional cell bladder tumours.

The Annals of Thoracic Surgery, 1991

In Vivo

Background/Aim: The diagnostic accuracy (DA) for patients with acute pancreatitis (AcPa) has been... more Background/Aim: The diagnostic accuracy (DA) for patients with acute pancreatitis (AcPa) has been rarely evaluated. Patients and Methods: In the AcPa study group, there were 22 patients versus 1,311 patients in the non-AcPa group. The clinical history-taking variables (CHT) (n=22), clinical signs & tests details (CST) (n=14), and laboratory analyses (n=3) were recorded in each patient. Meta-analytical techniques were used to detect the summary sensitivity (Se) and specificity (Sp) estimates for each data set; CHT, CST, and diagnostic scores (DS). Results: In receiver operating characteristic (ROC) analysis, the area under curve (AUC) values for i) CHT, ii) CST, and iii) DS were as follows: i) AUC=0.640 (95%CI=0.550-0.730); ii) AUC=0.588 (95%CI=0.520-0.656), and iii) AUC=0. ). The differences between these AUC values (roccomp analysis) are as follows: i) versus ii) p=0.155; i) versus iii) p<0.0001; ii) versus iii) p<0.0001. Conclusion: The new DS introduced in this study proved to be far superior to both symptoms and signs & tests in its DA for AcPa, as demonstrated by HSROC analysis. Acute pancreatitis (AcPa) is one of the most common diseases leading to hospitalization for gastroenterological reasons in the Western world (1-3). AcPa is characterized by a sudden inflammation of the pancreas, focal necrosis of the pancreatic fat, and hemorrhage. The clinical picture of AcPa ranges from mild to a severe life-threatening disease. The main causes for AcPa are excess alcohol use and/or migration of small gallstones with obstruction of bile or pancreatic enzyme flow. However, in up to 20% of AcPa patients the etiology of the disease is unknown. AcPa is diagnosed by using clinical history-taking (CHT) and clinical signs & tests (CST). Imaging studies are used to identify organ failure, offer prognostic information, and detect if fluid replacement is in balance. Upper abdominal pain, radiating to the back in 50% of patients, is usually the pre-dominant clinical symptom in AcPa following poor appetite, nausea, and vomiting (2, 3). The most common clinical signs of AcPa are fever, tachycardia, and positive clinical tests showing peritoneal irritation. In severity grading of AcPa, there are several prognostic scoring models that have been used as predictors of organ failure, complications, and survival in AcPa patients (2-6). The American College of Gastroenterology (ACG) (7) and World Society of Emergency Surgery (WSES) (8) have produced guidelines for the diagnosis and treatment of AcPa. These guidelines are mostly based on classic risk assessment tools such as Ranson criteria, which can predict disease severity and suggest treatment in AcPa, but they have a significant limitation, because many of these criteria used are not obtainable at presentation to the emergency, which makes the prediction how AcPa will progress difficult for emergency physicians (9). Therefore, due to the lack of diagnostic accuracy (DA) studies on AcPa patients, we assessed the performance of i) CHT, ii) CST, and iii) the diagnostic score (DS) in confirming AcPa.

Population-Based Molecular Detection of Hereditary Nonpolyposis Colorectal Cancer

Journal of Clinical Oncology, 2000

PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of ... more PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three fe...

Multivariate analysis of six serum tumor markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and conventional laboratory tests in the diagnosis of hepatopancreatobiliary malignancy

Anticancer research

A prospective study of 277 patients with benign (n = 212) and malignant (n = 65) hepatopancreatob... more A prospective study of 277 patients with benign (n = 212) and malignant (n = 65) hepatopancreatobiliary disease was carried out to evaluate the value of six serum tumour markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and 16 conventional laboratory tests in the distinction between benign and malignant diseases. In univariate analysis, all tumour marker tests except TATI showed significantly (p < 0.001) higher serum values in the patients with malignant disease than in the patients with benign disease. Among the conventional laboratory tests serum bilirubin, alkaline phosphatase and leucine aminopeptidase showed significantly. (p < 0.001) higher values in the patients with malignant disease, whereas serum protein and amylase levels were significantly (p < 0.01) higher in the patients with benign disease. In a multivariate analysis, serum bilirubin (p < 0.001), antithrombin III (p < 0.01) and blood hemoglobin (p < 0.05) were the most significant independent predictors o...

Sapphire probe versus bare fiber in interstitial laser hyperthermia (ILH). An experimental study with Wistar rats

Anticancer research

The aim of this study was to compare the effects of a bare laser fiber and a contact sapphire pro... more The aim of this study was to compare the effects of a bare laser fiber and a contact sapphire probe on normal Wistar rat liver in interstitial laser hyperthermia (ILH). We used two different powers (1W and 2W) and eight different exposure times (50s to 900s). The livers were examined after 3 days and in the long-term follow-up group after 2 months. The greatest necrotic lesions were achieved with 600-900J energy (2W, 300-450s) using a bare laser fiber. The diameter of the necrotic lesions plateaued with 2W power setting after 300J energy. Generally, necrotic lesions were greater using a bare fiber than a sapphire probe with equal energy levels. The lesions healed by granulation and fibrosis. No scars or necrotic lesions were found 2 months after treatment when a 1W power setting was used, whereas a power of 2W caused a clear scar in the rat liver. ILH treatment caused necrosis safely and the bare fiber produced a greater necrotic area than the sapphire probe.

Expression of C-242 antigen in pancreatic ductal adenocarcinoma

Anticancer research

This investigation was undertaken in order to analyse the expression of tumor associated antigen ... more This investigation was undertaken in order to analyse the expression of tumor associated antigen CA 242 in normal pancreas, in chronic pancreatitis and in pancreatic ductal adenocarcinoma, and to find out if the expression of CA 242 in carcinoma specimens would have prognostic significance. The expression of CA 242 was examined in the tissue specimens by the avidin-biotin-immunoperoxidase technique. According to our results, normal pancreas showed no or only weak staining for CA 242, whereas chronic pancreatitis samples stained somewhat intensely. Five out of 39 adenocarcinomas were negative for CA 242, 5 showed weak staining and 29 showed intermediate or intense staining. Positive staining was found mostly in the ductal cells as well as in intraluminal contents. We found no statistically significant difference of CA 242 expression between different grades. The staining intensity and survival had no clear statistical correlation but all carcinoma patients whose survival time was mor...

Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer

Anticancer research

S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of s... more S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF ...

Clinical Prognostic Factors in Transitional Cell Cancer of the Bladder

Urologia Internationalis, 1993

A cohort of 537 patients with transitional cell cancer of the bladder (TCC) were followed up for ... more A cohort of 537 patients with transitional cell cancer of the bladder (TCC) were followed up for a mean of 9 years and the clinicopathological data were related to prognosis. The T category (p &lt; 0.0001), N category (p &lt; 0.0001) and M category (p &lt; 0.0001) were the most important clinical prognostic factors, followed by the age of the patient (p &lt; 0.0001). Of the histological variables the WHO grade (p &lt; 0.0001), papillary status (p &lt; 0.0001) and the presence of R3-4 cells in voided urine (p = 0.0061) predicted unfavorable prognosis. In Ta-T1 tumors the WHO grade (p &lt; 0.0001), papillary status (p &lt; 0.0001) and the age of the patient (p &lt; 0.0001) had a prognostic value in univariate analysis. In Cox&#39;s analysis independent predictors of survival were the T category (p &lt; 0.0001), WHO grade (p &lt; 0.0001), patient age (p &lt; 0.0001), papillary status (p = 0.012) and the presence of symptoms before diagnosis (p = 0.033). In superficial tumors the WHO grade (p &lt; 0.0001) and patient age (p &lt; 0.0001) were independent predictors of survival.

Ag-NORs related to flow cytometry, morphometry and prognosis in patients with pancreatic cancer

Anticancer research

The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy s... more The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag-NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and t...

Mitotic activity index, volume corrected mitotic index and human papilloma-virus suggestive morphology are not prognostic factors in carcinoma of the oesophagus

Anticancer research

Radiation treatment, endoscopic dilatations and laser treatment offer an alternative to surgery a... more Radiation treatment, endoscopic dilatations and laser treatment offer an alternative to surgery as palliation in oesophageal cancer, and therefore it is essential to assess the prognostic factors preoperatively in order to select the treatment individually. Mitotic activity index (MAI), volume corrected mitotic index (M/V-index) and histologic evidence for human papillomavirus (HPV) involvement together with other prognostic factors were studied in 61 patients with oesophageal squamous cell carcinomas. No patient was lost from follow-up and 18% of patients were alive at the end of follow-up. Evidence for HPV involvement was found in 11 (18%) of 61 patients, which was significantly (p < 0.001) less than in a previous series of Chinese patients. Histological grade (p = 0.025), lymph node status (p = 0.002), presence of distant metastasis (p = 0.004), surgical resection (p = 0.03) and nuclear pleomorphism (p = 0.04) were significant independent prognostic factors in univariate analy...

Clinical evaluation of serum tumour markers CEA, CA 50 and CA 242 in colorectal cancer

Anticancer research

The aim of the present prospective study was to evaluate the clinical value ol serum tumour marke... more The aim of the present prospective study was to evaluate the clinical value ol serum tumour markers CEA, CA 50 and CA 242 in patients with colorectal cancer (n = 138) and patients with benign gastrointestinal disease (n = 104). The cutoff levels (90% specificity) determined for each test were 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the CEA test was 0.63, that of the CA 50 test was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. CEA, CA 50 and CA 242 tests were tested in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was CEA followed by CA 242. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.47 with a specificity of 0.88 and an efficiency of 0.67. On the basis of this study, serum CEA and CA 242 se...

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer

Anticancer research

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index... more DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour d...

A decision support system for predicting a recurrence of breast cancer; a prospective study of serum tumour markers TAG 12, CA 15-3 and MCA

Anticancer research

The aim of the present study was to evaluate the clinical value of the preoperative serum tumour ... more The aim of the present study was to evaluate the clinical value of the preoperative serum tumour markers TAG 12, CA 15-3 and MCA in predicting a recurrence of breast cancer patients. The sensitivity of the TAG 12 test was 54%, that of the CA 15-3 test 15% and that of the MCA test 15% in predicting a recurrence of breast cancer. The most important predictor of breast cancer recurrence was TAG 12. In order to evaluate the contributions of different tumour marker serum test, a stepwise discriminant analysis was carried out. The discriminant function (DF) is DF = TAG 12 x 0.061 - CA 15-3 x 0.1336 - 0.396. The sensitivity of the DF in detecting recurrence of breast cancer was 63% with a specificity of 90% and an efficiency of 75%. In conclusion, the results indicate that a new tumour marker TAG 12 is superior to CA 15-3 and MCA in predicting breast cancer recurrence. In this study the discriminant function including TAG 12 and CA 15-3 was superior to single preoperative tumour marker tes...

A prospective study of tissue polypeptide specific antigen (TPS) in breast cancer diagnosis

Anticancer research

The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in ser... more The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in sera from patients with breast cancer and patients with benign breast disease. The results for TPS were compared with those for TAG 12, CA 15-3 and MCA. The cutoff levels (90% specificity) determined for each test were 108.0 U/1 for TPS, 57.5 KU/1 for TAG 12, 24.8 KU/1 for CA 15-3 and 9.7 KU/1 for MCA. The diagnostic sensitivity of the TPS test was 0.21, for the TAG 12 test it was 0.2, 0.13 for the CA 15-3 test and 0.12 for the MCA test in detecting breast cancer. TPS, TAG 12, CA 15-3 and MCA tests were tested in a multivariate analysis to find the best combination of independent predictors of breast cancer. The most important predictor of breast cancer was TAG 12 followed by TPS. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The diagnostic score (DS) was: DS = TPS x 0.0085 x TAG 12 x 0.0596 - CA 15-3 x 0.0866 - MCA x 0.2938 + 0.1738....

Sex-Specific Diagnostic Scores for Acute Appendicitis

Scandinavian Journal of Gastroenterology, 1994

The role of clinical and computer-based decisions in the diagnosis of acute appendicitis was stud... more The role of clinical and computer-based decisions in the diagnosis of acute appendicitis was studied in connection with the survey of acute abdominal pain by the Research Committee of the World Organization of Gastroenterology (OMGE). One thousand three hundred and thirty-three patients presenting with acute abdominal pain were included in the study. Twenty-two preoperative clinical history variables, 14 clinical signs, and 3 tests were evaluated in a multivariate analysis to find the best combination of independent predictors of acute appendicitis for males and females. Independent predictors of acute appendicitis in males were tenderness, previous abdominal surgery, rebound, rigidity, location of pain at diagnosis, guarding, and body temperature. To sum up the contributions of the most significant diagnostic factors, a diagnostic score (DS) was built. When the male patients with a DS value between -2.00 and -0.48 were considered nondefined (n = 75, follow-up required before deciding to operate), the sensitivity of the computer-aided diagnosis in detecting acute appendicitis in males was 0.95, with a specificity of 0.89 and an efficiency of 0.91. In males whose leucocyte count was available (n = 476), previous abdominal surgery, leucocytosis, location of pain at diagnosis, tenderness, rigidity, rebound, guarding, rectal digital tenderness, and body temperature predicted significantly acute appendicitis. The DS reached a sensitivity of 0.94 (the cut-off level was -1.74), with a specificity of 0.80 and an efficiency of 0.84. (ABSTRACT TRUNCATED AT 250 WORDS)

Argyrophilic Nucleolar Organizer Regions May Help the Differential Diagnostic Distinction between Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma

Scandinavian Journal of Gastroenterology, 1994

The aim of this study was to determine whether the number of argyrophilic nucleolar organizer reg... more The aim of this study was to determine whether the number of argyrophilic nucleolar organizer regions (AgNORs) could be of diagnostic significance in differentiating between chronic pancreatitis and pancreatic ductal adenocarcinoma. The number of AgNORs was enumerated in biopsy specimens of normal pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma. The number of AgNORs was lower in patients with normal pancreas than in patients with chronic pancreatitis or pancreatic adenocarcinoma. In addition, the number of AgNORs was significantly lower in chronic pancreatitis than in pancreatic ductal adenocarcinoma (p &lt; 0.001). The diagnosis of pancreatic adenocarcinoma is usually clear. Difficulties can be encountered, however, in cases of chronic pancreatitis, specially when biopsy material is small. Our results suggest that the number of AgNORs may help in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma, especially in diagnostically difficult specimens.

Prognostic Factors after 5 Years Follow-Up in Female Breast Cancer

Oncology, 1992

A consecutive series of breast carcinomas (n = 595) followed up for a minimum of 7.5 years was an... more A consecutive series of breast carcinomas (n = 595) followed up for a minimum of 7.5 years was analyzed for clinical, histological and morphometric prognostic factors after 5-years&amp;amp;#39; follow-up. Tumor size, nodal status, mitotic frequency and patients&amp;amp;#39; age at diagnosis predicted survival at 7.5 years highly significantly (p less than 0.0001). Tubule formation (p = 0.002), histological grade (p = 0.026) and nuclear pleomorphism (p = 0.046) were related to prognosis as well. In N--patients mitotic frequency (p = 0.018) was the best predictor of survival at 7.5 years whereas in N + tumors tumor size (p = 0.0013), tubule formation (p = 0.003) and mitotic frequency (p = 0.0049) were the best predictors of survival at 7.5 years. In univariate survival analysis the age of the patients (p = 0.002), tubule formation (p = 0.005), axillary lymph node status (p = 0.008), lymphocyte infiltration (p = 0.049), mitotic frequency (p = 0.06) and tumor size (p = 0.08) predicted survival after 5 years&amp;amp;#39; follow-up. Tubule formation predicted survival (p = 0.025) in N - patients and in N + tumors the age of the patients was the most important predictor (p = 0.006). In Cox&amp;amp;#39;s analysis tubule formation (p = 0.13), axillary lymph node status (p = 0.033), SD of nuclear perimetry (p = 0.046) and intraductal growth (p = 0.059) predicted survival independently after 5 years&amp;amp;#39; follow-up.

Mitotic indexes as prognostic predictors in female breast cancer

Journal of Cancer Research and Clinical Oncology, 1992

A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, ax... more A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, axillary lymph node status, histological grade, histological type and two mitotic indexes (M/V; MAI) were assessed and related to disease outcome. Primary tumour size (P less than 0.0001), the volume-corrected mitotic index (M/V) (P less than 0.0001), the mitotic activity index (MAI) (P = 0.0001), and histological grade (P = 0.0074) predicted axillary lymph node status. Recurrence as well as recurrence-free survival was significantly related to the axillary lymph node status (P less than 0.0001), M/V index (P less than 0.0001), MAI (P less than 0.0001), tumour size (P = 0.0031) and histological grade (P = 0.0208). Multivariate analyses disclosed the tumour size and M/V index as independent predictors of axillary metastasis at diagnosis. Recurrence was related independently to M/V index, axillary metastasis and tumour size. Independent predictors of recurrence-free survival in Cox&amp;amp;#39;s analysis were M/V index and axillary lymph node status. Axillary lymph node status (P less than 0.0001), tumour size (P less than 0.0001), M/V index (P less than 0.0001), MAI (P less than 0.0001) and histological grade (P = 0.0009) predicted survival in that order. Cox&amp;amp;#39;s analysis showed that axillary lymph node status was the most important independent predictor of survival followed by tumour size and M/V index. In a separate Cox&amp;amp;#39;s analysis of axillary-lymph-node-negative patients the M/V index and tumour size were independently related to survival. In conclusion the M/V index is an important prognostic factor in breast cancer and also in axillary-lymph-node-negative breast tumours.

S152 Impaired Clearance and Unaltered Bioavailability of Three Oral Oxycodone Formulations in Elderly Patients

European Journal of Pain Supplements, 2011

European Journal of Cancer, 1993

The tissue expression of carbohydrate antigen CA-242 was analysed in forma&-fixed biopsy specimen... more The tissue expression of carbohydrate antigen CA-242 was analysed in forma&-fixed biopsy specimens from 147 transitional cell bladder tumours. The staining was related to established prognostic factors and survival during a mean follow-up of over 12 years and the staining results were also compared to expression of CA-SO antigen. Forty-one percent (60/147) of the tumours were negative for CA-242 and 59% (87/147) were positive. Normal bladder mucosa was positive for CA-242 and the umbrella cells in particular showed intense positive staining. In tumours, the umbrella cells were usually positive (when present) and in turnout tissue, positive cells appeared either as individual positive cells or in groups. None of the turnouts was entirely positive for CA-242. The tissue expression of CA-242 could not be significantly related to TNM classification, papillary status, WHO grade or quantitative variables (DNA ploidy, S phase fraction, mitotic frequency, nuclear factors). The tissue expression of CA-242 was significantly weaker than the expression of CA-50. The expression of CA-242 was related to favourable prognosis in survival analysis (P = 0.04). The results show that the expression of the novel tumour marker antigen CA-242 as determined in parah-embedded material is a weak prognostic factor as compared with established prognostic factors in transitional cell bladder tumours.

The Annals of Thoracic Surgery, 1991

In Vivo

Background/Aim: The diagnostic accuracy (DA) for patients with acute pancreatitis (AcPa) has been... more Background/Aim: The diagnostic accuracy (DA) for patients with acute pancreatitis (AcPa) has been rarely evaluated. Patients and Methods: In the AcPa study group, there were 22 patients versus 1,311 patients in the non-AcPa group. The clinical history-taking variables (CHT) (n=22), clinical signs & tests details (CST) (n=14), and laboratory analyses (n=3) were recorded in each patient. Meta-analytical techniques were used to detect the summary sensitivity (Se) and specificity (Sp) estimates for each data set; CHT, CST, and diagnostic scores (DS). Results: In receiver operating characteristic (ROC) analysis, the area under curve (AUC) values for i) CHT, ii) CST, and iii) DS were as follows: i) AUC=0.640 (95%CI=0.550-0.730); ii) AUC=0.588 (95%CI=0.520-0.656), and iii) AUC=0. ). The differences between these AUC values (roccomp analysis) are as follows: i) versus ii) p=0.155; i) versus iii) p<0.0001; ii) versus iii) p<0.0001. Conclusion: The new DS introduced in this study proved to be far superior to both symptoms and signs & tests in its DA for AcPa, as demonstrated by HSROC analysis. Acute pancreatitis (AcPa) is one of the most common diseases leading to hospitalization for gastroenterological reasons in the Western world (1-3). AcPa is characterized by a sudden inflammation of the pancreas, focal necrosis of the pancreatic fat, and hemorrhage. The clinical picture of AcPa ranges from mild to a severe life-threatening disease. The main causes for AcPa are excess alcohol use and/or migration of small gallstones with obstruction of bile or pancreatic enzyme flow. However, in up to 20% of AcPa patients the etiology of the disease is unknown. AcPa is diagnosed by using clinical history-taking (CHT) and clinical signs & tests (CST). Imaging studies are used to identify organ failure, offer prognostic information, and detect if fluid replacement is in balance. Upper abdominal pain, radiating to the back in 50% of patients, is usually the pre-dominant clinical symptom in AcPa following poor appetite, nausea, and vomiting (2, 3). The most common clinical signs of AcPa are fever, tachycardia, and positive clinical tests showing peritoneal irritation. In severity grading of AcPa, there are several prognostic scoring models that have been used as predictors of organ failure, complications, and survival in AcPa patients (2-6). The American College of Gastroenterology (ACG) (7) and World Society of Emergency Surgery (WSES) (8) have produced guidelines for the diagnosis and treatment of AcPa. These guidelines are mostly based on classic risk assessment tools such as Ranson criteria, which can predict disease severity and suggest treatment in AcPa, but they have a significant limitation, because many of these criteria used are not obtainable at presentation to the emergency, which makes the prediction how AcPa will progress difficult for emergency physicians (9). Therefore, due to the lack of diagnostic accuracy (DA) studies on AcPa patients, we assessed the performance of i) CHT, ii) CST, and iii) the diagnostic score (DS) in confirming AcPa.

Population-Based Molecular Detection of Hereditary Nonpolyposis Colorectal Cancer

Journal of Clinical Oncology, 2000

PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of ... more PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three fe...

Multivariate analysis of six serum tumor markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and conventional laboratory tests in the diagnosis of hepatopancreatobiliary malignancy

Anticancer research

A prospective study of 277 patients with benign (n = 212) and malignant (n = 65) hepatopancreatob... more A prospective study of 277 patients with benign (n = 212) and malignant (n = 65) hepatopancreatobiliary disease was carried out to evaluate the value of six serum tumour markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and 16 conventional laboratory tests in the distinction between benign and malignant diseases. In univariate analysis, all tumour marker tests except TATI showed significantly (p < 0.001) higher serum values in the patients with malignant disease than in the patients with benign disease. Among the conventional laboratory tests serum bilirubin, alkaline phosphatase and leucine aminopeptidase showed significantly. (p < 0.001) higher values in the patients with malignant disease, whereas serum protein and amylase levels were significantly (p < 0.01) higher in the patients with benign disease. In a multivariate analysis, serum bilirubin (p < 0.001), antithrombin III (p < 0.01) and blood hemoglobin (p < 0.05) were the most significant independent predictors o...

Sapphire probe versus bare fiber in interstitial laser hyperthermia (ILH). An experimental study with Wistar rats

Anticancer research

The aim of this study was to compare the effects of a bare laser fiber and a contact sapphire pro... more The aim of this study was to compare the effects of a bare laser fiber and a contact sapphire probe on normal Wistar rat liver in interstitial laser hyperthermia (ILH). We used two different powers (1W and 2W) and eight different exposure times (50s to 900s). The livers were examined after 3 days and in the long-term follow-up group after 2 months. The greatest necrotic lesions were achieved with 600-900J energy (2W, 300-450s) using a bare laser fiber. The diameter of the necrotic lesions plateaued with 2W power setting after 300J energy. Generally, necrotic lesions were greater using a bare fiber than a sapphire probe with equal energy levels. The lesions healed by granulation and fibrosis. No scars or necrotic lesions were found 2 months after treatment when a 1W power setting was used, whereas a power of 2W caused a clear scar in the rat liver. ILH treatment caused necrosis safely and the bare fiber produced a greater necrotic area than the sapphire probe.

Expression of C-242 antigen in pancreatic ductal adenocarcinoma

Anticancer research

This investigation was undertaken in order to analyse the expression of tumor associated antigen ... more This investigation was undertaken in order to analyse the expression of tumor associated antigen CA 242 in normal pancreas, in chronic pancreatitis and in pancreatic ductal adenocarcinoma, and to find out if the expression of CA 242 in carcinoma specimens would have prognostic significance. The expression of CA 242 was examined in the tissue specimens by the avidin-biotin-immunoperoxidase technique. According to our results, normal pancreas showed no or only weak staining for CA 242, whereas chronic pancreatitis samples stained somewhat intensely. Five out of 39 adenocarcinomas were negative for CA 242, 5 showed weak staining and 29 showed intermediate or intense staining. Positive staining was found mostly in the ductal cells as well as in intraluminal contents. We found no statistically significant difference of CA 242 expression between different grades. The staining intensity and survival had no clear statistical correlation but all carcinoma patients whose survival time was mor...