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Biomedical subjects

J Andersen

Publications and source records attributed to J Andersen.

At least 253 records · Page 14Linked to original sources

Adjuvant therapy of premenopausal and menopausal high-risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group Trials 77-B and 82-B.

From September 1977 to November 1987 high-risk (i.e. with positive axillary lymph nodes, or tumor size greater than 5 cm or skin/facia invasion) premenopausal and menopausal breast cancer patients have been included in 2 randomized trials. In both trials the primary surgical treatment was total mastectomy with axillary sampling. In the first trial (DBCG 77-B) 1034 patients all received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment (0), 2) cyclophosphamide (C), or 3) cyclophosphamide + methotrexate + 5-fluorouracil (CMF). The chemotherapy was given for 1 year. With a median observation time of 7 years the actuarial survival after 9 years is 50, 60 and 65% respectively. Retrospectively, the survival benefit was observed to be most pronounced in patients with tumor size less than or equal to 5 cm and with less than or equal to 3 positive lymph nodes. In the subsequent study initiated in 1982 (82-B) all patients received CMF for 9 months. Furthermore they were randomized to 1) RT, 2) no further treatment, or 3) tamoxifen (TAM) for 1 year. As of November 1, 1987, 1308 patients have been included. At 4 years and with a median observation time of 2 years the survival is similar in the 3 groups. In conclusion, in high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT resulted in a 20-30% relative reduction in mortality at 9 years compared with RT alone. Preliminary analysis of adjuvant CMF + RT, compared with CMF alone or with CMF + TAM, shows after a median observation time of more than 2 years no significant survival differences.

Adult↗

The pattern of metastases in human breast cancer. Influence of systemic adjuvant therapy and impact on survival.

Of the 3,802 patients enrolled in the DBCG 77 protocols, 863 developed clinical recurrence within a median follow-up time of 4.9 years (range 2.0-7.0). More than 69% of these had their first recurrence confined to a single anatomical site and 12% had more than two metastatic sites. The most common sites were bone (35%), lung (23%), skin (22%), and regional lymph nodes (16%). The observation period after first recurrence was 3.6 years (range 0.8-6.4). Survival after recurrence was significantly related both to the location and the number of metastases. Patients who were given adjuvant chemotherapy (n = 134) had significantly fewer metastatic sites and significantly more frequent liver metastases than untreated patients (n = 50). Patients who received adjuvant tamoxifen (n = 154) had the same number of metastatic sites, but more often had lung metastases than untreated patients (n = 201). These results probably reflect that metastases in different anatomical locations differ with respect to sensitivity to antineoplastic treatments.

Antineoplastic Agents↗

Relationship between estrogen receptor status in the primary tumor and its regional and distant metastases. An immunohistochemical study in human breast cancer.

Treatment of metastatic breast cancer based on the estrogen receptor content (ER) of the primary tumor builds on the assumption that the ER status of the primary tumor and the metastases are largely equal. Studies addressing this question have used ligand-binding assays for ER determination and have consequently been subject to the limitations of this technique. Reported disparity rates have been 20%. In order to avoid some of these limitations, we used an immunohistochemical assay in paraffin-embedded tissue. Among a total of 92 examined regional lymph node metastases, ER status was equal with that of their 37 primaries in 84 cases (91%). Semiquantified ER content was significantly correlated in primary tumor and the metastases (r = 0.67, p less than 0.001). Among a total of 51 distant metastases, equal ER status was found in 44 (86%) cases and a quantitative relationship could not be established. Disparities can be due to methodological errors in the histochemical assay or tumor heterogeneity.

Abdominal Neoplasms↗

The isolation and characterization of RNA coded by the micF gene in Escherichia coli.

A new species of micF RNA, which contains 93 nucleotides (a 4.5S size), was isolated from Escherichia coli. The sequence of the 4.5S micF RNA corresponds to positions G82 through U174 of the micF gene. The 5' terminal end of this smaller micF RNA is triphosphorylated signifying that it is a primary transcript. Its promoter region, which is situated within the greater micF structural gene, has been identified and characterized by lacZ fusion analysis. A 6S micF RNA species, which has a base composition predicted for a transcript from the full length gene has also been detected; however, the 4.5S micF RNA is the predominant species. The work clearly shows by biochemical identification the presence of chromosomally encoded micF RNA.

Bacterial Outer Membrane Proteins↗

Radial scars in women with breast cancer.

In 84 consecutive autopsies of women with a clinical diagnosis of invasive breast cancer, radial scars were found in the contralateral breast in 35 cases (42%) by an extensive histopathologic method. Four women had radial scars on the ipsilateral side in the breast tissue available from the primary surgical procedure or at autopsy. One woman had an invasive breast cancer with morphologic features compatible with but not diagnostic of transition from a radial scar. Of the six radial scars with carcinoma in situ occurring in three women, three were of ductal and three of lobular type. In the remaining cases only radial scars with a benign appearance were found except for two with atypical hyperplasia. The frequency of radial scars was significantly higher in women with fibrocystic disease (55%) compared to women without (24%). Contralateral primary invasive and in situ breast cancer occurred in 68%. No difference in the frequency of radial scars in women with and without breast cancer was found and radial scars were not associated with any specific type of breast cancer. Our findings do not indicate a higher malignant potential of radial scars than of fibrocystic disease. It is suggested that only radial scars containing high-risk epithelial changes such as atypical hyperplasia and carcinoma in situ are associated with an increased risk of subsequent breast cancer development.

Adult↗

Stage and pattern of metastases in patients with breast cancer.

This study compares the pattern of metastases in 228 patients with initial stage I and 635 patients with initial stage II breast cancer. All these patients had recurrence within a median time of follow-up of 4.9 years (range 2.0-7.0 years). All patients were initially mastectomized, and staging was based on histopathological evaluation of mastectomy specimens. Patients with stage II disease received postoperative radiotherapy; 67% also received systemic adjuvant therapy. Locoregional recurrences were the most common sites of recurrence in stage I, whereas distant metastases occurred more often in stage II patients. Stage II patients had a significantly higher number of metastatic sites than stage I patients. Among patients with a single site of recurrence the frequency of local or regional recurrence was 62% in stage I patients compared to 16% in stage II patients. When correcting for this difference, which was ascribed to the effect of radiotherapy, the number and the distribution of metastatic sites were almost equal in stage I and II patients. The anatomical distribution of metastatic sites in different periods after mastectomy was almost the same in stage I and stage II patients; extraregional lymph node metastases, however, occurred earlier in stage II than in stage I patients. The recurrence-free interval, the survival after recurrence (SAR), and the overall survival were all significantly shorter for stage II than for stage I patients. The reduced SAR for patients with stage II disease hints that tumours of higher stages have a higher rate of progression. The progression time, however, was of the same duration in patients with initial stage I and II breast cancer. The prognostic significance of the classification of patients with breast cancer according to stage does not seem to discriminate tumours with different biological properties with regard to the rate as well as the pattern of dissemination. Postmastectomy follow-up of patients with stage I and II disease should therefore, follow the same guide-lines. Since the anatomical distribution of metastases was the same in different periods after mastectomy, the screening for recurrent disease should not be directed towards any specific sites in certain periods after initial diagnosis.

Adult↗

Direct vision internal urethrotomy. A prospective study of 81 primary strictures treated with a single urethrotomy.

The post-operative treatment of urethral strictures as well as the criteria of success have varied considerably. In order to find a solution to this problem, we undertook a prospective evaluation of 81 men treated for their first urethral stricture with a single urethrotomy. Fifty-one patients with a stricture 5 mm or less in length were catheterised post-operatively for 3 days. Patients with strictures longer than 5 mm were catheterised for 3 weeks (14 patients) or 6 weeks (16 patients). All were followed up for a minimum of 24 months. The stricture recurred in 33 patients (41%). We found that 3 days' catheter drainage was sufficient for patients with short strictures. Whether strictures measuring more than 5 mm might be treated similarly needs further investigation.

Adolescent↗

Gynecomastia. Immunohistochemical demonstration of estrogen receptors.

Immunohistochemical estrogen receptor (ER) analysis using a monoclonal ER antibody was performed on a total of 30 specimens from 26 patients with gynecomastia. Twenty-six specimens were ER-positive, 3 were ER-negative, and the analysis failed in one case. Immunohistochemical analysis proved more sensitive than biochemical ER analysis in a group of 20 patients, and in a group of 6 patients, the immunohistochemical analysis correlated well with in vitro hormonal sensitivity of the gynecomastic tissue. Semi-quantified ER content was inversely correlated with patient age. There was no relationship between ER content and either histopathologic features or hormonal status. In conclusion, this study demonstrates that the intracellular ER responsible for estrogenic stimulation is present in most gynecomastic tissue specimens, supporting the general assumption that estrogen can be one of the hormones responsible for the development of gynecomastia.

Adult↗

Treatment of central corneal ulcers by à chaud transplantation of organ culture preserved donor tissue.

In the period 1979-83 a total of 232 penetrating corneal transplantations were performed with organ culture preserved donor material. Forty-two operations were made à chaud for central corneal ulcerations. The results of these interventions are reported and discussed. The surgery presented no serious problems and on first post-operative day the anterior chamber was reformed in all cases, and pain was relieved. Patients were confined to bed only for 1 day. Graft deswelling was slightly retarded compared to planned surgery, but all functioning grafts obtained normal thickness. The overall graft survival rates after 6, 12 and 18 months were 66, 53 and 48%, respectively. For herpetic ulcers the survival after 18 months was 49% and for non-herpetic ulcers 47%. The grafts failed in all cases where it had been necessary to employ grafts of more than 10 mm. This latter group was comprised of the non-herpetic cases; were they excluded, the graft survival rate would increase to 60%. Among cases with a clear graft the median visual acuity after 18 months was 0.33 (range less than 0.1-0.67). Excluding cases with a non-corneal cause of visual reduction, the median visual acuity was 0.4 (range 0.33-0.67). It is concluded that grafting can be successfully employed in the treatment of central ulcers, as it not only restitutes tissue integrity, but also preserves useful vision.

Adolescent↗

Corneal transplantation using 4-week banked donor material. Long-term results.

Thirty-six corneal transplantations employing banked donor material maintained during prolonged storage (mean: 29.5 days) in organ culture at 31 degrees C were followed for 5 years. The overall graft survival was 80% , and graft failures were almost exclusively found in a pre-operatively defined risk group where the survival rate was 49.6% compared with 95.5% in the non-risk group. Five years after transplantation the mean central thickness of surviving grafts was 0.52 mm and the mean endothelial cell density 862 cells/mm2. All grafts were optically clear judged by slit-lamp appearance even though a higher degree of light-scatter was demonstrated compared with controls. The functional results were satisfactory with an over-all mean visual acuity of 0.67 cc. Excluding cases where low visual performance had non-corneal causes, 88% of patients obtained 0.5 cc or better. The median spherical equivalent of corneal curvature was 8.23 mm and the median astigmatism 4 diopters. Intraocular pressure was normal, and all grafts had obtained some degree of sensibility, although reduced compared with controls. The study demonstrates that banked donor material can be successfully employed for corneal transplantation achieving favourable long-term results.

Astigmatism↗

Expression of Rous sarcoma virus transforming protein pp60v-src in Saccharomyces cerevisiae cells.

The Rous sarcoma virus (RSV) pp60v-src protein was expressed in Saccharomyces cerevisiae cells either from a plasmid vector carrying the v-src gene or in yeast cells containing a single-copy v-src gene chromosomally integrated. In both yeast strains, v-src gene transcription is regulated by the galactose-inducible GAL10 promoter. Growth in galactose-containing medium resulted in constitutive expression of pp60v-src in the integrated strain and transient expression of higher levels of pp60v-src in the plasmid-bearing strain. The concentration of pp60v-src in the plasmid-bearing strain at its peak of expression was approximately threefold lower than that found in RSV-transformed mammalian cells. pp60v-src synthesized in yeast cells was phosphorylated in vivo on sites within the amino and carboxyl halves of the molecule. In immune complex kinase assays, the yeast pp60v-src was autophosphorylated on tyrosine and was able to phosphorylate exogenous substrates such as casein and enolase. The specific activity of pp60v-src synthesized in yeast cells was approximately 5- to 10-fold higher than that made in mammalian cells. Induction of pp60v-src caused the death of the plasmid-bearing yeast strain and transient inhibition of growth of the single-copy strain. Concomitantly, this induction resulted in high levels of tyrosine phosphorylation of yeast cell proteins. This indicates that pp60v-src functions as a tyrosine-specific phosphotransferase in yeast cells and suggests that hyperphosphorylation of yeast proteins is inimical to cell growth.

Avian Sarcoma Viruses↗

In situ carcinomas of the breast. Types, growth pattern, diagnosis, and treatment.

The paper presents a prospective study comprising 40 consecutive patients with in situ carcinomas of the breast and two with atypical ductal hyperplasia (ADH) who underwent operation during a 2-year period at a single hospital. Out of the 40 in situ carcinomas 13 were of the lobular type (LCIS) and 27 of the ductal type (DCIS). They made up about 9% of all newly diagnosed breast cancers. Histologically a distinction could be made between three different growth patterns: microfocal, tumour-forming, and a diffuse form. With the exception of one case, the 26 microfocal growths (2 ADH, 13 LCIS, 11 DCIS) were accidental findings in otherwise benign breast biopsies, whereas the tumour-forming and diffuse forms (16 DCIS) were diagnosed in the great majority clinically and/or by mammography. Of the tumour-forming and diffuse DCIS 25% were demonstrated solely by mammography. The surgical treatment in the 26 patients showing microfocal changes was exclusively biopsy in 23, while three had mastectomy, because of a papillary focus in two and patient preference in one. Of six patients with tumour-forming DCIS three had segmental resection and three mastectomy, the latter because of papillary foci, while all 10 with diffuse growth had mastectomy. On the basis of their experience of types and growth patterns, the authors set up a surgical strategy which might add new aspects to our knowledge about the biological nature of in situ lesions.

Adult↗

High-dose combination alkylating agent preparative regimen with autologous bone marrow support: the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

Fifty-nine patients received 61 courses of cyclophosphamide, cisplatin, and carmustine combined. The phase I study consisted of seven dose escalations. Dose levels 5 and 6 also included the attempted addition of melphalan at 40 and 80 mg/m2. The maximum tolerated dose for the three-drug combination was 5620 mg/m2 of cyclophosphamide, 165 mg/m2 of cisplatin, and 600 mg/m2 of carmustine. The dose-limiting toxic effect was fatal veno-occlusive disease of the liver in two of five patients treated at the highest dose level. Veno-occlusive disease of the liver was fatal in two of 40 patients treated at Dose level 4, the maximum tolerated dose. The median time to recovery of polymorphonuclear leukocyte counts to greater than 500/microliters and platelet counts to transfusion independence greater than 20,000/microliters was 19 and 22 days, respectively, after marrow reinfusion. Other toxic effects observed included postdischarge pulmonary toxicity, which appeared to respond to prednisone therapy. Thus, this combination of alkylating agents can be combined at close to the transplant dose of each individual agent. The response rate was high despite considerable prior treatment in most patients. Of 16 evaluable patients with breast cancer, 15 responded (six complete responses). Of six evaluable patients with sarcoma, six responded (one complete response). While patients with melanoma had had no prior treatment, 11 of 17 patients responded (65%). There are currently three patients who are disease-free. Two patients with melanoma were rendered disease-free by excisional biopsy of the only remaining nodule after good partial response, and a patient with metastatic breast cancer remains disease-free after a complete response at 36+ months.

Adult↗