Biomedical subjects

A E Stenwig

Publications and source records attributed to A E Stenwig.

At least 37 records · Page 2Linked to original sources

PubMed1996

[Prognosis in primary tumors of the central nervous system. A patient material from the Norwegian Radium Hospital 1960-94].

We present the results of a retrospective survey of 1,218 patients treated at the Norwegian Radium Hospital during the years 1980-94 for primary tumours of the central nervous system. Median survival for patients with glioblastoma (n = 492) was 12 months, for patients with anaplastic astrocytoma (n = 83) 25 months, astrocytoma (n = 260) 95 months, oligodendroglioma (n = 85) 74 months, mixed glioma (n = 68) 65 months, and medulloblastoma (n = 53) 109 months. Median survival for patients with brain stem tumours (n = 37) was nine months, while 74% of patients with tumours in the pineal region (n = 38) survived for five years. The histology and localisation of the tumour, as well as age and functional status, are important prognostic factors for survival in patients with primary CNS tumours.

Adolescent↗

PubMed1996

The prognostic significance of surgery, tumor size, malignancy grade, menopausal status, and DNA ploidy in endometrial stromal sarcoma.

To evaluate the prognostic significance of DNA ploidy in endometrial stromal sarcoma, the traditional clinical and histopathological prognostic variables and DNA ploidy in 48 patients with histologically verified endometrial stromal sarcoma were analyzed. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the tumor were obtained in 47 patients. In univariate analysis, malignancy grade (P < 0.001), cellular atypia (P < 0.001), tumor diameter (P = 0.001), and mitotic count (P = 0.002) were highly significant. Also menopausal status (P = 0.011), FIGO stage (P = 0.035), and free resection margins at primary surgery (P = 0.026) obtained significance, while vessel invasion and age did not. DNA ploidy was not significant. In Cox multivariate analysis, free resection margins at primary surgery were found to be the most important prognostic factor (P < 0.001), followed by malignancy grade (P = 0.002), tumor diameter (P = 0.019), and menopausal status (P = 0.019). DNA ploidy did not obtain significance. Free resection margins at primary surgery, malignancy grade, tumor diameter, and menopausal status are important prognostic factors in endometrial stromal sarcoma.

DNA, Neoplasm↗

PubMed1995

Systemic relapse of patients with osteogenic sarcoma. Prognostic factors for long term survival.

BACKGROUND: A retrospective study of long term outcome after the development of metastases from osteosarcoma was performed, with emphasis on the impact of different treatment strategies and the identification of prognostic factors. METHODS: From 1975 to 1993, a population-based series of 60 patients with distant metastases (relapse) from high grade, extremity-localized osteosarcoma was treated at The Norwegian Radium Hospital. Six patients relapsed after surgery alone, 28 patients relapsed after primary chemotherapy of low potency, and 26 patients after modern, intensive chemotherapy. Lung metastases were present in 88% of the patients, 52% had bilateral lesions, and the median number of lesions was three (range, 1-25 lesions). Forty-seven percent of patients had complete surgical excision of all identifiable metastatic nodules and 54% of these had additional second line chemotherapy defined as adequate. Adequate chemotherapy included further dose escalations of methotrexate in approximately half of the patients, usually from 8 to 12 g. The rest were exposed to novel agents such as cisplatin, etoposide, and ifosfamide. Of the operated patients, 43% had additional thoracotomies after subsequent relapses. RESULTS: The projected 5-year survival rate from the first metastatic event was 24% for all patients and 50% for patients who underwent complete metastasectomy. In a multivariate analysis, the factors with independent predictive value for improved overall survival were the presence of a solitary metastasis, the accomplishment of complete metastasectomy, and the administration of adequate salvage chemotherapy. CONCLUSIONS: Complete metastasectomy is mandatory for long term survival of patients with metastatic osteosarcoma, and repeated lung resections are necessary in nearly half the patients. Second line chemotherapy and following primary treatment with modern intensive chemotherapy protocols may improve survival further.

Adolescent↗

PubMed1995

The prognostic significance of stage, tumor size, cellular atypia and DNA ploidy in uterine leiomyosarcoma.

To analyze the significance of DNA ploidy in uterine leiomyosarcoma, the traditional clinical and histopathological prognostic variables and DNA ploidy were studied in 70 patients with histologically verified uterine leiomyosarcoma. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the tumor were obtained in 58 patients. In univariate analysis tumor diameter, FIGO stage and presence of residual disease after primary surgery were highly significant (p < 0.001) and also DNA ploidy (p = 0.043), age (p = 0.017), and menopause status (p = 0.028) obtained significance. Cellular atypia was almost significant (p = 0.056), while mitotic count, malignancy grade and vessel invasion were not. In Cox's multivariate analysis, FIGO-stage was found to be the most important prognostic factor (p < 0.001), followed by cellular atypia (p = 0.007) and tumor diameter (p = 0.016). DNA ploidy did not obtain significance when categorized as diploid/non-diploid. Patients with tumors with multiple aneuploid cell populations had a very poor prognosis. When categorized as multiple aneuploidy versus all other ploidy groups, DNA ploidy obtained marginal significance in multivariate analysis (p = 0.054). Tumor diameter, stage and cellular atypia are important prognostic parameters in uterine leiomyosarcomas.

Adult↗

PubMed1995

Molecular genetic changes in human male germ cell tumors.

BACKGROUND: An isochromosome for the short arm of chromosome 12, i(12p), is the most common and characteristic cytogenetic aberration in testicular germ cell tumors. Little is known about the molecular genetic abnormalities of these neoplasms. EXPERIMENTAL DESIGN: A total of 32 loci were studied in DNA from 31 primary testicular germ cell tumors and compared with corresponding normal DNA. The loci map to 17 different chromosome arms, including seven that contain known tumor suppressor genes. Southern blot analysis and PCR-based methods were used. Several microsatellite loci were included to investigate instability (seen as new alleles) at repeat loci. The TP53 tumor suppressor gene was analyzed for point mutations by constant denaturant gel electrophoresis and for expression by immunohistochemistry. Histologic sections of the tumor biopsies were evaluated with regard to components and percentage of intact tumor cells. The growth fraction, representing one component of proliferative activity of the tumor, was assessed by the Ki-67 index. RESULTS: Changes were found at all chromosome arms investigated but at very different frequencies, 5-56% of all tumors. The most frequently affected chromosome arms, those showing loss of heterozygosity or allelic imbalance in more than 40% of the tumors, were 2q, 3p, 3q, 11p, 12p, 18q, and 22q. Complete loss of one allele was often seen at 3p and 11p loci, whereas allelic imbalances dominated on the 2p, 3q, 12p, 18q, and 22q loci tested. No mutations were detected within four known mutational hot spots of TP53, but positive immunostaining with two TP53 Ab was seen in 9 of 14 tumors. Most tumors (26 of 31) showed positive immunostaining with Ki-67. Microsatellite instability was not observed. CONCLUSIONS: High frequencies of loss of heterozygosity and allelic imbalance at several loci indicate that inactivation of several tumor suppressor genes may be of importance in developing testicular germ cell tumors. The increase in copynumber of 12p alleles seen in several tumors is likely to reflect one or more 12p isochromosomes. Our findings do not indicate that TP53 plays any major pathogenic role in this tumor type, nor was there any indication that defect repair genes, causing microsatellite instability in other cancers, participate in the progression of testicular cancer.

Alleles↗

PubMed1994

[Treatment of chondrosarcoma. A retrospective study at the Norwegian Radium Hospital].

The authors present a retrospective analysis of 59 chondrosarcoma patients treated at the Norwegian Radium Hospital during the period 1981 to 1993. 31 patients were admitted with untouched tumour, seven after fine needle cytology and 20 after open biopsy or partial excision. One patient had recurrent local disease. Only 20% of the tumours were of high grade malignancy. 51 patients were treated by surgery. Reconstructions were performed in 16 patients, using allografts or endoprostheses. Amputations were performed in six cases and wide excision in 12 cases. In these 18 patients local recurrence appeared in one case, and two developed lung metastases. Only one of the 18 patients operated by amputation or wide excision has since died from chondrosarcoma. Marginal excisions were performed in 26 cases. Nine of these patients developed a local recurrence, five developed metastases and three have died. Six patients had partial excisions. Postoperative radiotherapy was given to one patient only. Five of the six are alive. In one case, the quality of the margins could not be evaluated. A total of 45 of the 51 patients treated for the primary tumour by surgery are alive. The median observation time is four years. Treatment of nonmetastatic chondrosarcoma should be surgical. Chondrosarcoma patients show wider variations in age, localization of tumour and tumour growth rate than patients with other bone sarcomas. Although wide excisions provide the best local control of any grade of malignancy, the mutilation or risk involved may be so great that some patients may benefit from marginal or even partial excision.

Adult↗

PubMed1994

How safe is surveillance in patients with histologically low-risk non-seminomatous testicular cancer in a geographically extended country with limited computerised tomographic resources?

In patients with clinical stage I non-seminomatous testicular cancer only limited information is available about the administrative problems with the surveillance programme, in particular if this policy is to be implemented in a geographically extended country with limited computerised tomography (CT) resources. One hundred and two patients with non-seminomatous testicular cancer clinical stage I and low-risk histology (MRC criteria, UK) were followed by the surveillance policy for at least 1 year after orchiectomy (median 47 months, range 21-81 months). Twenty-two patients (22%) relapsed after a median time of 5 months (range 2-18 months), 14 of them in the retroperitoneal space. Serum alpha-fetoprotein and/or human chorionic gonadotrophin were elevated in eight of the 22 relapsing patients. The progression-free and cancer-corrected survival rates were 78% and 99% respectively. Patient non-compliance did not represent a major problem, whereas the regular and adequate performance of necessary CT examinations yielded some administrative difficulties. One and 3 years after orchiectomy about 50% of the relapse-free patients had no psychological problems and were satisfied with the surveillance programme, whereas 46% reported minor and 4% major psychological distress. Despite non-negligible administrative difficulties in geographically extended countries, surveillance is feasible and safe in compliant patients with low-risk non-seminomatous testicular cancer stage I. The responsible cancer centre and the local hospitals should establish a high degree of cooperation and enable adequate follow-up examinations in these patients.

Biomarkers, Tumor↗

PubMed1993

[Diagnostic aspects of subacute osteomyelitis in children and adolescents. Clinical and radiographic resemblance to primary malignant tumors].

During a six-year period, 17 patients younger than 20 years of age, with a final diagnosis of subacute osteomyelitis, were admitted to the Norwegian Radium Hospital because of an initial suspicion of primary malignant bone tumour. The most common localizations were the metaphyses of long bones (eight patients) and the clavicle (four patients). Pain was the dominating symptom. Common radiological findings were localized osteolysis and/or sclerosis, cortical bone destruction, periosteal reaction and an adjacent, often palpable soft tissue mass. Clinical signs of infection were generally absent, and a positive bacterial culture was obtained from the biopsy material in only one patient. Following extensive investigations, a malignant bone tumour (especially Ewing's sarcoma) remained a differential diagnosis, and open biopsy was indicated in all cases. The patient material illustrates the difficulty in distinguishing between subacute osteomyelitis and malignant bone tumours, and it is stressed that diagnostic investigations for this type of patients should be performed in an oncological centre with experience of bone tumours.

Adolescent↗

PubMed1993

Frequent loss of 11p13 and 11p15 loci in male germ cell tumours.

Deletions within the short arm of the human chromosome 11 have been found to be involved in the genesis of several tumours, including different urogenital neoplasms. We have studied 31 male germ cell tumours (19 seminomas and 12 nonseminomas), and observed loss of heterozygosity at 11p loci in 40% (12/30) of these tumours [35% (9/26) at 11p13 and 31% (8/26) at 11p15]. Our data suggest that inactivation of one or more tumour suppressor genes on 11p are involved in the genesis of testicular cancer. In addition, identification of the parental origin of the allelic losses revealed a paternal loss in six patients and a maternal loss in one case.

Carcinoma in Situ↗

PubMed1993

Genetic alterations in a malignant schwannoma from a patient with neurofibromatosis (NF1).

In a patient with neurofibromatosis (von Recklinghausen disease; NF1), normal lymphocytes, five cutaneous neurofibromas, and tumour tissue from a recurrence of a malignant schwannoma were analysed for genetic alterations. Eleven DNA markers located on chromosome 17 and nine randomly chosen markers representing chromosomes 1, 2, 3, 4, 5, 6, and 11, were analysed. High resolution Giemsa banding of lymphocytes revealed no chromosomal rearrangement. The DNA from the neurofibromas were all found to have the same restricted fragment length polymorphism pattern as the constitutional DNA from the patient. In the malignant schwannoma a complete loss of one allele was found at polymorphic loci on chromosome arm 17p. One gene copy of the TP53 gene (17p13.1) and the NF1 gene (17q11.2) was lost, as was one copy of the PGA gene (11q13). No mutations were detected in the mutational hotspots of the TP53 gene. Partial losses were detected at three loci on chromosomes 1, 2 and 6, indicating a clonal variation within the tumour since histological evaluation disclosed no normal tissue in the analysed specimen. Our data indicate that the NF1 gene may function as a tumour suppressor gene, and that, either by effect of dose reduction or complete inactivation, both the NF1 gene and the TP53 gene may be critical for the progression of a neurofibroma to a malignant schwannoma. The observations made are consistent with the concept of stepwise multigenetic changes in tumour progression.

Adult↗

PubMed1993

Salvage treatment in male patients with germ cell tumours.

The outcome of salvage treatment was reviewed in 55 patients relapsing during or after their primary chemotherapy for advanced malignant germ cell tumours. Fifty-two patients had been given cisplatin-based chemotherapy as their primary treatment, whereas three patients had received carboplatin-based chemotherapy. The median time to relapse was 2 months (range: 0-96 months) from discontinuation of the primary treatment. Two patients underwent radical surgery only, and one patient had radiotherapy to a brain metastasis as his only curatively intended salvage treatment. Six patients did not receive any treatment for their recurrent malignancy (refusal, terminal condition) except for purely palliative measures. The disease-free survival for the total group was 27% at 5 years. Complete response to primary treatment lasting for > or = 6 months was the only parameter which significantly predicted a favourable outcome (45% 5 year disease-free survival in 12 eligible patients).

Adolescent↗

PubMed1993

Prognosis of localised prostatic cancer managed by "watch and wait" policy.

Progression (within 2-7 years) and cancer-specific mortality (within 4-9 years) were examined in 94 patients with localised (T0-T2 NXM0) prostatic cancer. The patients received no initial anti-cancer treatment. A significant difference was found according to the initial T category both in progression (T0 focal 1/13, T0 diffuse 9/53, T1-2 13/28) and in cancer-related death (T0 focal 0/13, T0 diffuse 3/53, T1-2 6/28). Progression (G1 4/48, G2 17/42, G3 2/4) and cancer-related deaths (G1 1/48, G2 7/42, G3 1/4) also showed significant differences according to histological differentiation. No difference could be demonstrated according to age.

Age Factors↗

PubMed1993

Testicular ultrasonography and 18G biopty biopsy for clinically undetected cancer or carcinoma in situ in patients with germ cell tumours.

The 18G Biopty biopsy has been evaluated as a tool to detect carcinoma in situ in the remaining testes of patients with extragonadal germ cell tumours or unilateral germ cell tumours. In all, 68 biopsies were performed in 57 selected patients. Five carcinomas in situ and 1 infiltrative seminoma were detected. The biopsies were performed under local anaesthesia. Pain and/or haematomas occurred after 9 of the 68 biopsies but none of the haematomas required invasive measures. This method of performing biopsies from clinically tumour-free testes seems promising but longer follow-up is required to evaluate the sensitivity of the method compared with open surgical biopsy.

Adult↗

PubMed1992

Molecular genetic studies of tumor suppressor gene regions on chromosomes 13 and 17 in colorectal tumors.

BACKGROUND: In the majority of colorectal carcinomas, both copies of the tumor suppressor gene TP53 (tumor protein 53) are known to be inactivated. In contrast to a loss of tumor suppressor function, it has been suggested that an increased copy number of the RB1 gene is involved in the progression of these tumors. PURPOSE: To determine genetic alterations at chromosomes 13 and 17 in colorectal tumors, we have studied several loci on these chromosomes, with special focus on the RB1 and TP53 genes at both the level of DNA sequence and the level of gene expression. METHODS: Restriction fragment length polymorphism analysis was performed after alkaline Southern blotting of the DNA fragments and hybridization (in 7% sodium dodecyl sulfate and 0.5 M NaPO4) of the nylon membranes with multiprimed, radioactively labeled probes. Total RNA was extracted from tissue biopsy specimens by homogenization of the samples in guanidinium thiocyanate followed by separation in a CsCl gradient. By use of an image-processing system, x-ray film signals were measured densitometrically. Point mutations within the TP53 gene were detected by use of polymerase chain reaction (PCR) in combination with constant denaturant gel electrophoresis. Direct sequencing of PCR products revealed the exact nature of the mutations. Protein expression of TP53 was seen by immunostaining of sections from paraffin-embedded material using a mouse monoclonal antibody. The two-sided Fisher's Exact Test was used for statistical analysis. RESULTS: An increase in allelic copy number at 13q loci was seen in 10 (32%) of 31 tumors. In the majority of the cases, this increase probably reflected a change in the diploid status of chromosome 13; in some cases, however, only part of the 13q seemed to be involved. The RB1 gene showed an elevated level of RNA compared with the beta-actin signal. Fourteen (48%) of 29 tumors showed loss of heterozygosity at loci on 17p, and base mutations within the TP53 gene were seen in 14 (42%) of 33 tumors. RNA and protein analyses of TP53 revealed an increased level of expression in the tumors compared with normal mucosa. Allelic variations seen at 13q and 17p were not associated (P = .7). CONCLUSIONS: Our results suggest that, in addition to aneuploidy, gain of specific chromosome 13 sequences is involved in the tumorigenesis of the colon and rectum. In addition, they confirm the importance of TP53 mutations for the progression of such tumors and support the view that accumulation of events is more important than the order of events. The genetic changes observed at chromosome arms 13q and 17p seem to be independent of each other.

Adolescent↗

PubMed1992

Long-term survival in patients with follicular thyroid carcinoma. The Oslo experience: variations with encapsulation, growth pattern, time of diagnosis, sex, age, and previous thyroid surgery.

In 98 follicular thyroid carcinoma patients with a follow-up of 10-32 years, 10-year survival varied in subgroups from 15.5-63.4%. Survival with encapsulated primary tumors was 46.7%, compared to 26.9% in widely invasive tumors, and varied from 59.9-35.8% with growth pattern. In patients younger than 60 years of age at diagnosis 10-year survival was 68% of expected survival, compared to 32% in patients older than 60. Patients treated after 1970 had an improved survival of 24.2%. Thirty-one patients had previous thyroid operations for benign lesions. Review of histopathologic slides and medical records demonstrated follicular adenomas in 17 cases, and overlooked carcinomas in 11. Calculating survival from the first surgical intervention improved reported 10-year survival by 14.5%. Papillary carcinoma patients matched for age and sex had significantly better 10-year survival.

Adenocarcinoma↗

PubMed1992

Retroperitoneal surgery in patients with nonseminomatous testicular cancer and minimal residual tumor.

In the period 1980-1991, 78 patients with advanced nonseminomatous testicular cancer underwent retroperitoneal lymphadenectomy for post-chemotherapy residual masses less than 2 cm. To decrease the frequency of "dry ejaculation" in these patients with no or limited residual disease, the extent of dissection was reduced during the period, with bilateral dissections (49 cases, 1980-1986) being initially replaced by unilateral procedures (19 cases, 1983-1990) and subsequently by nerve-sparing techniques (10 cases, 1990-1991). As expected, a higher total number of lymph nodes was found in the retroperitoneal specimens after bilateral (44 (13-100)) than after unilateral (21 (7-35)) and nerve-sparing (18 (7-60)) procedures. The number of lymph nodes with pathological changes was low, with 3 (1-16) after bilateral, 2 (1-9) after unilateral, and 2 (1-4) after nerve-sparing operations. Histological examination revealed only necrosis/fibrosis in 65% of the patients, elements of mature teratoma in 28%, and remnants of viable malignant tumor in 6%. There were no major postoperative complications. "Dry ejaculation" was reported by 84% of the patients with bilateral operations, but was generally avoided after the unilateral (16%) and nerve-sparing (nil) procedures. After a mean follow-up of 83 (5-138) months, 6 patients have developed a recurrence, only one of them primarily in the retroperitoneal space. It is concluded that in patients with minimal residual retroperitoneal tumor, postchemotherapy lymphadenectomy using a unilateral or nerve-sparing technique seems to offer an effective therapeutic alternative with acceptable postoperative morbidity and preserved ejaculation.

Adolescent↗

PubMed1992

Deoxyribonucleic acid cytometry and histological findings before and after 125iodine implantation of primary prostate cancer.

Deoxyribonucleic acid (DNA) flow cytometry and light microscopy were performed in pre-radiotherapy and post-radiotherapy biopsies obtained from the primary tumor in 31 patients with prostate cancer. Radiotherapy was applied by means of transperineal 125iodine (125I) implantation. Of the patients 21 had pretreatment biopsies and in 19 of these biopsies also were performed 1 and/or 1 1/2 years after the 125I implantation. Posttreatment biopsies were available for DNA flow cytometry in 12 additional patients without pretreatment DNA flow cytometry assessment. Of the 21 pretreatment biopsies 7 were diploid, 6 tetraploid and 8 aneuploid. All 31 posttreatment biopsies were either tetraploid (21) or aneuploid (10). All 6 pretreatment diploid tumors became tetraploid after radiotherapy. At 1 and/or 1 1/2 years after 125I implantation residual tumors were found in 28 of 31 prostatic glands. The high frequency of nondiploid DNA stemlines 1 or more years after 125I implantation and the high rate of residual tumor leave some doubt about the radiocurability of prostate cancer by the chosen radiotherapy technique.

Biopsy↗

PubMed1992

High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study.

From 1984 to 1989, 63 patients with diffuse, malignant mesothelioma of the pleura were treated with 4-8 courses of high-dose methotrexate (HDMTX, 3 g total dose) and citrovorum factor rescue. There were 61 male and two female patients of median age 60 years. CT scan was performed before and after treatment and used for response evaluation. Of 60 patients evaluable for response, 37% showed partial or complete remission, 32% showed no change and 32% showed progressive disease. Median survival from start of treatment for all patients was 11 months, for 42 patients with the epithelial type 12 months, and for 20 patients with sarcomatous or mixed types only 5 months. Toxicity was acceptable, with only five patients (8%) terminating therapy due to toxicity. One toxic death occurred. We conclude that HDMTX is an active regimen in malignant pleural mesothelioma. The significantly shorter survival for patients with the sarcomatous or mixed subtypes indicates that further investigations on the activity of HDMTX in mesothelioma should be limited to patients with the epithelial subtype.

Dose-Response Relationship, Drug↗