Biomedical subjects

O Kaalhus

Publications and source records attributed to O Kaalhus.

At least 37 records · Page 2Linked to original sources

PubMed1995

Up-regulation of the oligosaccharide sialyl LewisX: a new prognostic parameter in metastatic prostate cancer.

Metastatic prostate cancer has an unpredictable long-term prognosis. At present, there are few specific predictors to indicate the outcome for the individual patient. We have studied immunoreactivity for type-2 carbohydrate structures, known to be involved in various cell adhesion processes, in patients with metastatic prostate cancer. One group of patients (n = 26) did not progress within 3 years after orchiectomy, while another group of patients (n = 33) progressed within 1 year following castration and survived less than 2 years. Among the parameters studied, sialyl LewisX carbohydrate up-regulation was the only variable showing significant association with poor prognosis (P < 0.01). Sialyl LewisX discriminated between these two outcome groups with 71% predictability and 96% specificity. Our results indicate that up-regulation of sialyl LewisX is associated with hormonal-resistant, aggressive disease. This prognostic marker may, therefore, have an important role in selecting proper treatment for patients with metastatic prostate cancer.

Adenocarcinoma↗

PubMed1995

Immunohistochemical detection of nm23/NDP kinase and cathepsin D in medullary carcinomas of the thyroid gland.

Reduced expression of nm23/NDP kinase and increased expression of cathepsin D seem to be correlated with the high metastatic potential in a variety of malignancies. The expression of nm23/NDP kinase and that of cathepsin D have been evaluated by means of an immunohistochemical technique in paraffin-embedded tissues from 44 primary medullary carcinomas of the thyroid gland (MCT) and from the corresponding lymph node metastases in 32 of these cases. In addition, lymph node metastases from 4 cases were studied. We found that 36 of 44 (82%) primary and 26 of 36 (72%) lymph node metastatic MCT were nm23/NDP kinase positive, whereas 14 of the 44 (32%) primary and 17 of the 36 (47%) lymph node metastatic MCT were cathepsin D positive. We found no indication that the nm23/NDP kinase level has any prognostic significance in MCT. The cathepsin D level is close to being prognostically significant in this study, and we cannot exclude the possibility that it could be of prognostic value. However, it seems to be quite weak, and therefore of little use in a clinical situation.

Adolescent↗

PubMed1995

MRI of human tumor xenografts in vivo: proton relaxation times and extracellular tumor volume.

Proton T1 and T2 differ substantially between tumors, but the tumor properties causing heterogeneity in T1 and T2 have not been fully recognized. The purpose of the study reported here was to investigate whether differences in T1 and T2 between tumors are mainly a consequence of differences in the fractional volume of the extracellular compartment. The study was performed using a single human tumor xenograft line showing large naturally occurring intratumor heterogeneity in the size of the extracellular compartment. The size of the extracellular compartment was calculated from the volume and the density of the tumor cells. Cell volume was measured by an electronic particle counter. Cell density was determined by stereological analysis of histological preparations. T1 and T2 were measured by MRI in vivo both in the absence and presence of Gd-DTPA. Two spin-echo pulse sequences were used, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60, and 80 ms and the other with a TR of 2,000 ms and TEs of 20, 40, 60, and 80 ms. Measurements of T1 and T2 in the presence of Gd-DTPA were performed in a state of semi-equilibrium between uptake and clearance of Gd-DTPA. MR-images and histological preparations of tumor subregions homogeneous in extracellular volume were analysed in pairs. The extracellular volume differed between tumor subregions from 5 to 70%. T1 and T2 measured in the absence of Gd-DTPA differed between tumor subregions by a factor of approximately 1.5 and increased with increasing extracellular volume. The relative decrease in T1 caused by Gd-DTPA, represented by (T1 control-T1 Gd-DTPA)/T1 control, also increased with increasing extracellular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Detection of necrosis in human tumour xenografts by proton magnetic resonance imaging.

Tumours with necrotic regions have an inadequate blood supply and are expected to differ from well-vascularised tumours in response to treatment. The purpose of the present work was to investigate whether proton magnetic resonance imaging (MRI) might be used to detect necrotic regions in tumours. MR images and histological sections from individual tumours of three different amelanotic human melanoma xenograft lines (BEX-t, HUX-t, SAX-t) were analysed in pairs. MRI was performed at 1.5 T using two spin-echo pulse sequences, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60 and 80 ms and the other with a TR of 2000 ms and TEs of 20, 40, 60 and 80 ms. Spin-lattice relaxation time (T1), spin-spin relaxation time (T2) and proton density (N0) were calculated for each volume element corresponding to a pixel. Synthetic MR images, pure T1, T2 and N0 images and spin-echo images with chosen values for TR and TE were generated from these data. T1, T2 and N0 distributions of tumour subregions, corresponding to necrotic regions and regions of viable tissue as defined by histological criteria, were also generated. T1 and T2 were significantly shorter in the necrotic regions than in the regions of viable tissue in all tumours. These differences were sufficiently large to allow the generation of synthetic spin-echo images showing clear contrast between necrosis and viable tissue. Maximum contrast was achieved with TRs within the range 2800-4000 ms and TEs within the range 160-200 ms. Necrotic tissue could also be distinguished from viable tissue in pure T1 and T2 images. Consequently, the possibility exists that MRI might be used for detection of necrotic regions in tumours and hence for prediction of tumour treatment response.

Animals↗

PubMed1995

Extent of disease based on initial bone scan: important prognostic predictor for patients with metastatic prostatic cancer. Experience from the Scandinavian Prostatic Cancer Group Study No. 2 (SPCG-2).

The skeleton is the most frequent site of metastases from prostate cancer. Quantitation of the amount of tumor burden has a great prognostic value and is of importance for clinical trials. The present study reviews 194 bone scans from the SPCG-2 study which consisted of 294 patients entered into a randomized prospective multicenter trial, comparing total androgen suppression with standard treatment in patients with metastatic prostatic cancer (orchiectomy plus cyproterone acetate vs. orchiectomy plus placebo). Evaluation of the initial bone scans based on the extension of the disease (EOD) as proposed by Soloway and associates gives a convenient stratification of the patients. With regard to time to progression and cancer-related as well as overall survival, this EOD grading system had a significant prognostic value (p < 0.001). There was no statistical difference between the two treatment arms in the different categories of the EOD grading system with regard to time to progression and time to death. By analyzing exclusively the subgroup of patients with minimal disease (EOD I) and good performance status (WHO score 0), there was a nonsignificant trend toward a better 2-year progression-free survival as well as a better 2-year cancer-related survival for those who were subjected to total androgen suppression as compared with the patients subjected to the standard treatment (orchiectomy).

Androgen Antagonists↗

PubMed1994

Functional differences between CD38- and DR- subfractions of CD34+ bone marrow cells.

Several studies have previously demonstrated enrichment in primitive progenitor cells in subfractions of CD34+ bone marrow (BM) cells not expressing CD38 or HLA-DR (DR) antigens. However, no studies have directly compared these two cell populations with regard to their content of primitive and more committed progenitor cells. Flow cytometric analysis of immunomagnetic isolated CD34+ cells demonstrated little overlap between CD34+CD38- and CD34+DR- progenitor subpopulations in that only 12% to 14% of total CD34+DR- and CD34+CD38- cells were double negative (CD34+CD38-DR-). Although the number of committed myeloid progenitor cells (colony-forming units granulocyte-macrophage) was reduced in both subpopulations, only CD34+CD38- cells were significantly depleted in committed erythroid progenitor cells (burst-forming units-erythroid). In single-cell assay, CD34+CD38- cells showed consistently poorer response to single as opposed to multiple hematopoietic growth factors as compared with unfractionated CD34+ cells, indicating that the CD34+CD38- subset is relatively enriched in primitive hematopoietic progenitor cells. Furthermore, CD34+CD38- and CD34+DR- cells, respectively, formed 3.2-fold and 1.6-fold more high proliferative potential colony-forming cell (HPP-CFC) colonies than did unfractionated CD34+ cells. Finally, CD34+CD38-DR- cells were depleted in HPP-CFCs as compared with CD34+CD38+DR+ cells. The results of the present study suggest that both the CD38- and DR- subfractions of CD34+ bone marrow cells are enriched in primitive hematopoietic progenitor cells, with the CD34+CD38- subpopulation being more highly enriched than CD34+DR- cells.

ADP-ribosyl Cyclase↗

PubMed1994

Magnetic resonance imaging of human melanoma xenografts in vivo: proton spin-lattice and spin-spin relaxation times versus fractional tumour water content and fraction of necrotic tumour tissue.

Proton nuclear magnetic resonance (1H-nmr) imaging is used routinely in clinical oncology to provide macroscopic anatomical information, whereas its potential to provide physiological information about tumours is not well explored. To evaluate the potential usefulness of 1H-nmr imaging in the prediction of tumour treatment resistance caused by unfavourable microenvironmental conditions, possible correlations between proton spin-lattice and spin-spin relaxation times (T1 and T2) and physiological parameters of the tumour microenvironment were investigated. Tumours from six human melanoma xenograft lines were included in the study. 1H-nmr imaging was performed at 1.5 T using spin-echo pulse sequences. T1- and T2-distributions were generated from the images. Fractional tumour water content and the fraction of necrotic tumour tissue were measured immediately after 1H-nmr imaging. Significant correlations across tumour lines were found for T1 and T2 versus fractional tumour water content (p < 0.001) as well as for T1 and T2 versus fraction of necrotic tumour tissue (p < 0.05). Tumours with high fractional water contents had high values of T1 and T2, probably caused by free water in the tumour interstitium. Fractional water content is correlated to interstitial fluid pressure in tumours, high interstitial fluid pressure being indicative of high vascular resistance. Tumours with high fractional water contents are thus expected to show regions with radiobiologically hypoxic cells as well as poor intravascular and interstitial transport of many therapeutic agents. T1 and T2 decreased with increasing fraction of necrotic tumour tissue, perhaps because complexed paramagnetic ions were released during development of necrosis. Viable tumour cells adjacent to necrotic regions are usually chronically hypoxic. Tumours with high fractions of necrotic tissue are thus expected to contain significant proportions of radiobiologically hypoxic cells. Consequently, quantitative 1H-nmr imaging has the potential to be developed as an efficient clinical tool in prediction of tumour treatment resistance caused by hypoxia and/or transport barriers for therapeutic agents. However, much work remains to be done before this potential can be adequately evaluated. One problem is that high fractional tumour water contents result in longer T1 and T2 whereas high fractions of necrotic tumour tissue result in shorter T1 and T2; i.e. the two parameters which are indicative of treatment resistance contribute in opposite directions. Another problem is that the correlations for T1 and T2 versus fraction of necrotic tumour tissue are not particularly strong.

Animals↗

PubMed1993

Pre- and post-treatment sexual life in testicular cancer patients: a descriptive investigation.

Aspects of sexuality were assessed by questionnaires in 76 testicular cancer patients after orchiectomy before further treatment and, respectively, 6, 12 and 36 months after therapy. Before treatment 11% of the patients reported dissatisfaction with sexual life. About 20% of the patients sometimes experienced reduced libido and erectile difficulties. Six months after therapy significantly more patients (27%) recorded an unsatisfactory sexual life as compared to the pretreatment situation. At the 36 months' evaluation 22 of 76 evaluable patients (18%) still stated that their sexual life was inferior to the pretreatment experience. Libido and erectile function decreased transiently during the first year after treatment in most patients. Twelve patients reported permanent 'dry ejaculation' after bilateral retroperitoneal lymph node dissection. Other sexual disturbances could not be related to specified treatment modalities. Increased age at the time of diagnosis and psychological distress tended to correlate with the incidence of sexual problems. For about 60% of the patients the discussion of expected and experienced sexual life problems was an important issue to be discussed before their treatment for testicular cancer and during follow-up. The high frequency of any kind of long-lasting sexual problems (30%), though often of minor degree, warrants an adequate counselling of these patients before and after treatment.

Adult↗

PubMed1991

Clinical stage I carcinoma of the cervix: value of MR imaging in determining degree of invasiveness.

The depth of tumor invasion measured at histologic examination is the most important prognostic factor in early-stage carcinoma of the uterine cervix. The ability of MR to estimate the depth of tumor invasion was studied in 47 patients who subsequently underwent radical hysterectomy. In two patients, MR failed to detect tumors with infiltration depths of 2 and 4 mm. The maximum sagittal tumor length along the axis of the cervix (D) and the maximum tumor area on sagittal (S) and axial (A) images were measured with MR. The depth of tumor infiltration determined histologically (I) correlated with the degree of infiltration noted on MR images. The univariate correlation coefficients for log I vs log D, log S, and log A were .87, .84, and .77, respectively. By stepwise inclusion of the variables in a multivariate analysis, the contributions to the coefficient of determination from including log S and log A after log D were less than 1%. The regression analysis showed that the best estimate for the depth of invasion was close to half of the sagittal tumor length measured on MR, I = D/2. Our experience shows that MR is valuable in determining the degree of invasiveness in clinical stage I tumors.

Adult↗

PubMed1991

Features of irradiated urinary bladder tumors and their correlation with malignancy observed on computed tomography.

CT features of 42 masses in the bladder wall were characterized and subjected to analysis to find indicators of malignancy. A CT technique with thin slices and intravenous contrast medium was used. Multiple regression and multivariate analysis showed good ability of contrast-enhanced CT to discriminate between benign and malignant masses in the bladder wall. Protrusion of a mass into the perivesical fat had some importance in discriminating between malignant tumors with and without perivesical growth although the detection of perivesical growth was less certain.

Humans↗

PubMed1990

Role of catalase and oxidative stress in hepatic peroxisome proliferator-induced morphological transformation of Syrian hamster embryo cells.

Several hepatic peroxisome proliferators (HHPs) such as di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)-phthalate, clofibrate and tiadenol, induce morphological transformation of Syrian hamster embryo (SHE) cells in vitro. According to one hypothesis, the hepatocarcinogenic effect of HPPs is caused by an oxidative stress due to increased H2O2-production from the strongly induced peroxisomal beta-oxidation of fatty acids. Thus, increased transformation frequencies by HPPs should be obtained when catalase was inhibited by 3-amino-1,2,4-triazole (amitrole). However, co-exposure to HPPs and amitrole did not enhance the transformation frequencies for any of the HPPs. The sensitivity of SHE cells for oxidative agents was studied by using menadione and H2O2. Menadione only induced transformation at a toxic concentration, while H2O2 induced transformation at non-toxic concentrations. To study the generation of oxidative radicals in SHE cells, electron spin resonance was employed. No oxidative radical formation was detected in tiadenol- or DEHP-exposed SHE cells. When menadione or H2O2 were added during the measurements, oxidative radicals were found. A transmission electron microscopic study showed a small number of peroxisomes, and did not reveal any increase in the number of peroxisomes in clofibrate-treated SHE cells.

Amitrole↗

PubMed1990

Prognosis in patients with metastatic non-seminomatous testicular cancer.

155 patients with metastatic non-seminomatous testicular cancer were treated with cisplatin-based chemotherapy which in most cases was combined with surgery. The 5 year crude survival was 90% for all patients (98 patients with small volume disease: 97%; 32 patients with large volume disease: 91%; 25 patients with very large volume disease: 64%). High pre-chemotherapy serum tumour marker levels (AFP greater than 500 micrograms/l; and/or HCG greater than 1000 U/l) decreased the survival rates in all groups. Only 4 of 17 relapsing patients were rendered tumour-free by salvage chemotherapy. In a multivariate analysis, a pre-chemotherapy alpha-foetoprotein (AFP) level greater than 500 micrograms/l was associated with poor survival as was the presence of a retroperitoneal tumour greater than 10 cm, lung metastases greater than 3 cm and/or extrapulmonary hematogenous metastases. It is concluded that easily assessable clinical pre-treatment variables can be used to define high risk or low risk patients with metastatic testicular cancer. Treatment intensity should be adjusted in accordance to such prognostic factors.

Adolescent↗

PubMed1990

Long-term somatic side-effects and morbidity in testicular cancer patients.

In order to evaluate long-term somatic morbidity after treatment for testicular cancer 149 patients with NED greater than or equal to 3 years answered a questionnaire. The patients had been treated with surgery only (32 patients, radiotherapy only (39 patients), cisplatin-based chemotherapy plus surgery (46 patients) or chemotherapy plus radiotherapy with or without surgery (32 patients). Raynaud-like phenomena were the most frequent side-effect occurring significantly more often after cisplatin-based chemotherapy than after surgery or radiotherapy (33/72 patients versus 5/68 patients). Peripheral sensory 'neuropathy' was reported by 18% of all the patients. Seventeen per cent and 11% complained of pulmonary symptoms and auditory symptoms, respectively. Gastrointestinal side-effects were more frequent after any type of cytotoxic therapy than after surgery only (34/47 patients versus 5/22 patients). Twenty-six patients had fathered children after treatment. About 80% of the patients were in full time wage-earning activity when they answered the questionnaire. In conclusion, 3-7 years after treatment for testicular cancer, 30-50% of the patients had minor somatic complaints whereas serious side-effects seldom occurred.

Adolescent↗

PubMed1990

Is routine primary retroperitoneal lymph node dissection still justified in patients with low stage non-seminomatous testicular cancer?

We present 8 years' experience of primary retroperitoneal lymph node dissection (RLND) in 190 patients with low stage non-seminoma; 154 patients had clinical stage I (CSI) and 36 had clinical stage IIa (CSIIa) disease. Of the 154 patients with CSI tumours, 33 had increased serum AFP and/or HCG before RLND (CSIM+) and 121 had normal tumour markers (CSIM-). Retroperitoneal lymph node metastases (pathological stage II) (PSII) were found in 38 of 121 patients with CSIM-, in 19 of 33 patients with CSIIM+ and in 26 of 36 patients with CSIIa. In a multivariate analysis, the presence of small vessel infiltration (demonstrated in histological sections of the primary tumour) and a prolonged tumour marker half-life were predictive factors for PSII. These 2 factors enabled a group of non-seminoma patients with CSI disease to be identified who had a 15% risk of retroperitoneal tumour growth (low risk group) as compared with a high risk group where 60 to 70% of patients had retroperitoneal lymph node metastases. Relapses occurred in 7 of 107 patients with PSI and in 6 of 83 patients with PSII disease; in the latter group, 5 relapses developed before the start of routine adjuvant chemotherapy; 6% of patients developed major post-operative complications. In addition, "dry ejaculation" was the principal side effect following RLND (unilateral RLND: 20/132 patients; bilateral RLND: 50/54 patients). The comparative cost to the health service during the first year of follow-up was estimated for low risk non-seminoma patients with CSI subjected to RLND and for those in whom a surveillance policy was adopted. The latter approach was preferable. It was concluded that a surveillance policy should be followed in low risk non-seminoma CSI patients provided that frequent follow-up is possible. A more active policy is recommended in high risk patients (e.g. adjuvant chemotherapy without RLND). Nerve-sparing RLND may be considered in patients with CSIIa disease and negative tumour markers.

Adolescent↗

PubMed1990

Distribution of retroperitoneal lymph node metastases in patients with non-seminomatous testicular cancer in clinical stage I.

118 Patients with non-seminomatous testicular cancer (NSTC) in clinical stage I (CSI = no metastases by clinical, radiological and biochemical evaluation) underwent retroperitoneal lymph node dissection (RLND). The operation was done unilaterally (95 patients) in peroperatively tumor-free patients or in those with limited metastatic growth. In 23 patients with more extensive metastases, bilateral RLND was performed. Metastatic lymph nodes were found in 36 patients, and these patients received 3-4 cycles of a cisplatin-based combination chemotherapy. If no metastases were detected the patients had no further treatment. The 5-year disease-free survival rate was 100%. 8 of 82 patients without detected metastases in the operation specimen relapsed (all outside the retroperitoneal space), but were cured by salvage chemotherapy. Solitary metastases were found in 11 patients, whereas 25 patients had more than 1 metastatic lymph node. The size of the largest metastasis ranged from 0.3 to 40 mm. Metastases from right-sided tumors were detected at all levels of the lumbar region, predominantly to the right of the inferior vena cava and/or within the interaortocaval space. Left-sided tumors metastasized to the upper two thirds of the lumbar space, only rarely crossing the midline. This anatomical distribution of metastatic lymph nodes indicates that the presacral sympathetic nerve plexus and the sympathetic nerve fibers around the aortic bifurcation can be spared from extensive resection in the majority of patients with NSTC in CSI. Unilateral RLND or other nerve-sparing techniques are thus possible, preserving antegrade ejaculation in greater than 80% of the patients. This RLND represents a reasonable alternative to the 'surveillance' policy in NSTC.

Adult↗

PubMed1990

Primary irradiation, surgery or combined therapy in squamous cell carcinoma of the larynx. A comparison of treatment results from two centers.

We compared two groups of patients with squamous cell carcinoma of the larynx. Group 1 consisted of 483 patients treated from 1958 through 1978. Primary surgery was selected in 41% pre- or postoperative radiation therapy in 16% and primary radiation therapy in 43%. Group 2 consisted of 247 patients treated from 1978 through 1983. Primary surgery was selected in only 1.6%, pre- or postoperative radiation therapy in 23%, and primary radiation therapy, with surgery in reserve for residual or recurrent carcinoma, in 76%. Although the results were comparable for patients with early stage tumors in the two groups, significantly higher local-regional tumor control rates and corrected survival rates were recorded for patients with advanced tumors in group 2. More patients survived with a cancer-free functional larynx, the surgical salvage rates were higher, the complication rates and the death rates lower in group 2 compared to group 1.

Aged↗

PubMed1990

Computed tomography of the urinary bladder shortly after radiation therapy for rectal carcinoma.

Eighteen patients with rectal carcinoma were examined with computed tomography (CT), before and shortly after preoperative irradiation. Changes in the bladder that could be mistaken for tumor growth did not occur at CT. However, considerable individual variations were seen. Radiation therapy did not result in increased contrast enhancement of the bladder wall after irradiation. The bladder wall thickness increased somewhat during and after treatment and the bladder volume was reduced. Localized thickening with little contrast enhancement was seen in the anterior bladder wall in 3 patients. One case of irradiation cystitis was noted. Edema was seen in the perivesical fat, but could in no case be mistaken for tumor growth.

Aged↗

PubMed1989

Long-term morbidity after infradiaphragmatic radiotherapy in young men with testicular cancer.

Long-term morbidity was evaluated in 357 patients with testicular cancer who were treated by infradiaphragmatic radiotherapy between 1970 and 1982. Myelopathy developed in four patients, radiation osteomyelitis in one, and radiation hepatitis in another after treatment. Posttreatment gastrointestinal symptoms were recorded in the medical records of 4% of patients but were mentioned by 41% of 199 who answered a questionnaire. The moderate gastrointestinal problems were recorded by 17% of the patients compared with 6% in a control group of healthy men. Postirradiation peptic ulcer occurred in 9%. A dose relationship existed, the risk of posttreatment gastrointestinal problems being less when the midplane dose was less than 40 Gy. Forty-one of 63 men who wished to do so fathered at least one child after their radiotherapy. The overall posttreatment quality of life was comparable to that of the control group. The authors conclude that the risk of major posttreatment morbidity is minimal for testicular cancer patients who undergo infradiaphragmatic radiotherapy after orchiectomy. Slight gastrointestinal symptoms are relatively common without major impact on quality of life. Gonadal toxicity is not a significant complication. Infradiaphragmatic radiotherapy is a safe, routine adjuvant treatment of seminoma in orchiectomized patients with Stage I seminoma. The midplane dose should not exceed 36 Gy in these patients.

Adolescent↗