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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 127 records · Page 7Linked to original sources

Multiple transrectal ultrasound-guided biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion.

A total of 251 men with suspected prostate cancer were examined by transrectal ultrasound (TRUS) in order to evaluate the usefulness of TRUS and core biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion (SVI). Biopsies targeting hypoechoic lesions were taken in combination with systematic biopsies obtained from six standardized locations. Bilateral seminal vesicle biopsies were obtained from 168 of the men. A total of 26 patients underwent surgery and a comparison between the results of the histopathological evaluation of core biopsies and the prostatectomy specimen was performed. A total of 137 cancers were detected. In 34 patients (25%) the tumors were diagnosed by systematic biopsies alone. Tumor volume as estimated by TRUS underestimated the volume when compared to a planimetric technique. Correlation between the two methods was not found by regression analysis. Systematic biopsies did not improve grading compared to the grading of prostatectomy specimens. A total of 24 SVIs were detected. Valuable information was obtained for the diagnosis of prostate cancer by taking systematic biopsies.

Adult↗

Screening for osteopenia and osteoporosis: selection by body composition.

There is a great need for simple means of identifying persons at low risk of developing osteoporosis, in order to exclude them from screening with bone mineral measurements, since this procedure is too expensive and time-consuming for general use in the unselected population. We have determined the relationships between body measure (weight, height, body mass index, lean tissue mass, fat mass, waist-to-hip ratio) and bone mineral density (BMD) in 175 women of ages 28-74 years in a cross-sectional study in a county in central Sweden. Dual-energy X-ray absorptiometry was performed at three sites: total body, L2-4 region of lumbar spine, and neck region of the proximal femur. Using multiple linear regression models, the relationship between the dependent variable, BMD, and each of the body measures was determined, with adjustment for confounding factors. Weight alone, in a multivariate model, explained 28%, 21% and 15% of the variance in BMD of total body, at the lumbar spine and at the femoral neck according to these models. The WHO definition of osteopenia was used to dichotomize BMD, which made it possible, in multivariate logistic regression models, to estimate the risk of osteopenia with different body measures categorized into tertiles. Weight of over 71 kg was associated with a very low risk of being osteopenic compared with women weighing less than 64 kg, with odds ratios (OR) of 0.01 (95% confidence interval (CI) 0.00-0.09), 0.06 (CI 0.02-0.22) and 0.13 (CI 0.04-0.42) for osteopenia of total body, lumbar spine and femoral neck, respectively. Furthermore a sensitivity/specificity analysis revealed that, in this population, a woman weighing over 70 kg is not likely to have osteoporosis. Test specifics of a weight under 70 kg for osteoporosis (BMD less than 2.5 SD compared with normal young women) of femoral neck among the postmenopausal women showed a sensitivity of 0.94, a specificity of 0.36, positive predictive value (PPV) of 0.21, and negative predictive value (NPV) of 0.97. Thus, exclusion of the 33% of women with the highest weight meant only that 3% of osteoporotic cases were missed. The corresponding figures for lumbar spine were sensitivity 0.89, specificity 0.38, PPV 0.33, and NPV 0.91. All women who were defined as being osteoporotic of total body weighed under 62 kg. When the intention was to identify those with osteopenia of total body among the postmenopausal women we attained a sensitivity of 0.92 and a NPV of 0.91 for a weight under 70 kg, whereas we found that weight could not be used as an exclusion criterion for osteopenia of femoral neck and lumbar spine. Our data thus indicate that weight could be used to exclude women from a screening program for postmenopausal osteoporosis.

Absorptiometry, Photon↗

Prognostic characteristics in breast cancers after hormone replacement therapy.

We examined the influence of hormone replacement therapy (HRT) on breast tumour biology by comparing the prognostic characteristics of breast cancers and survival in 121 women prescribed replacement hormones before diagnosis with those in 1468 women without such treatment. The women receiving HRT had a lowered relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR = 0.7 (CI 0.5-1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4-1.1). These risk reductions were most pronounced and statistically significant in the women who had been prescribed a combined estradiol-progestin regimen. The patients in this compound group also had a diminished relative risk of having poorly differentiated tumours. Further, there was an indication that the women prescribed HRT, and especially those with conjugated estrogens/estradiols alone, had a decreased relative risk of developing aneuploid tumours. There was no clear pattern for women receiving the biologically weak oestriol, although risk estimates were generally higher for unfavourable tumours in comparison with those receiving the higher potency compounds. Adjustments for indications of earlier detection (i.e. lead time bias) did not influence the pattern or magnitude of the risk estimates. No association between any type of HRT and survival after breast cancer diagnosis was noted, but analyses were based only on 19 breast cancer deaths among exposed patients. We conclude that breast cancers occurring after treatment with HRT, especially the combined estrogen-progestin regimen, seem to have more favourable tumour features than tumours in non-treated women. Our findings may reflect a less aggressive biological behaviour of breast cancers in women receiving HRT, or in part be explained by the earlier detection of the tumours in these women.

Aged↗

Continuing medical education in oncology in Europe.

A European Conference on Continuing Medical Education (CME) in Oncology was designed and organised in Dublin (Ireland), on 12th and 13th October 1995 by the European School of Oncology in collaboration with University College Dublin and with the financial support of the European Commission (Europe Against Cancer Programme). Two experts were invited from each Member State and all attended the Conference with the sole exception of the representatives of Luxembourg, who did not attend due to unexpected important commitments. Observers were invited to contribute to the discussion as representatives of organisations that were involved either directly or indirectly in CME. The Conference took the format of a plenary session coupled with the identification of five discussion groups formed to debate key areas in CME at a European level in oncology (Table 1). As a result of these discussions and subsequent consultations, an agreement was reached on the following statements: (a) Continuing Medical Education (CME) is an ethical duty and an individual responsibility for each doctor. Although CME should remain voluntary at the present time, it is nevertheless a professional obligation since almost 50% of medical knowledge becomes obsolete after ten years. It should be organised with clear guidelines for medical personnel working in hospitals, in primary health care and in private practice. (b) The CME system within the European Union (EU) should remain self-directed without the necessity for interval examinations: it should be interdisciplinary and must be driven and controlled by the profession itself. (c) A common concept and system within a CME framework may have a considerable impact on EU integration. It should certainly be developed, maintained and monitored at national level but on the basis of a common European model to ensure scientific and cultural interchange among Member States. (d) It was agree that a credit system is needed to help doctors keep track of their CME activities: the system should be based on the accumulation of credit points (one credit equalling one hour of continuing medical education) and monitored at a national level. Credit transfer among Member States is vital to facilitate exchange between Member States. (e) Oncology provides a very useful model of CME within which guidelines can be proposed and tested. Harmonisation of CME systems among the different European cancer organisations and scientific societies within this model system may represent a useful basis that other specialities can follow.

Education, Medical, Continuing↗

Survival in small intestinal adenocarcinoma.

All cases of adenocarcinoma in the duodenum (n = 263) and jejunum/ileum (n = 663), diagnosed between 1960 and 1988, were recruited from the Swedish Cancer Registry. Corrected and overall survival were investigated by sex, age and year of diagnosis with life-table and Cox proportional hazards analyses. The corrected 5- and 10-year survival rates were 39% and 37% for duodenal tumours and 46% and 41% for those in jejunum/ileum (P = 0.16 for difference between sites). The corrected 5- and 10-year survival rates were 52% and 48% for women and 40% and 34% for men with tumours in jejunum/ileum (P = 0.0095 for difference by sex) while no such relation was found in duodenal tumours (P = 0.84). Survival correlated with age at diagnosis for duodenal tumours (P = 0.03377). A Cox proportional hazards analysis revealed a temporal trend with more favourable prognosis in recent years. This study confirms that prognosis of small bowel adenocarcinoma is serious, but gives a more optimistic outlook than many hitherto published series.

Adenocarcinoma↗

Amputation risk and survival after embolectomy for acute arterial ischaemia. Time trends in a defined Swedish population.

OBJECTIVES: To assess the outcome of embolectomy over an 19 year period. METHODS: Time trends in the outcome of acute arterial thrombo-embolectomy of the extremities were analysed in a population-based cohort of 1190 patients operated on between 1965-83. RESULTS: A total of 262 (22%) initial amputations were performed. The limb salvage rates at 5 years postoperatively were lower between 1975-79 (61%) than between 1965-69 (81%). A proportional hazards model revealed a relative hazard (RH) of amputation of 2.2 (95% confidence interval (CI) 1.3-3.3) for 1975-79 compared with 1965-69. Operation at any district hospital entailed a 70% higher risk of amputation (RH 1.7; 95% CI 1.3-2.5) compared with the University hospital. The relative survival rate at 5 years postoperatively decreased towards the end of the study period (33% between 1975-79 compared with 43% between 1965-69). Younger age-groups had a considerably lower risk of death in the University hospital compared with the county and district hospitals. CONCLUSIONS: Contrary to the results in other hospital based reports no improvement in amputation or survival rates since 1965 could be demonstrated in this large series with no patient selection.

Acute Disease↗

Increased platelet retention in familial recurrent thrombotic thrombocytopenic purpura.

We studied two brothers with recurrent thrombotic thrombocytopenic purpura (TTP). Platelet retention, measured with a modified Adeplat S glass-bead test, was found to be increased during acute episodes of TTP and during remissions. Values of platelet retention ranged between 57 to 95% (normal range 16 to 34%). The continually elevated values enabled us to investigate which fraction of the patients' blood was responsible for the increased platelet retention and to evaluate the effect of different treatments on this parameter. We found that the patients' plasma increased the retention of normal platelets and of platelets taken from a patient with von Willebrand's disease type III. This activity was located in the cryoprecipitate fraction of plasma. Unusually large von Willebrand factor (vWF) multimers were demonstrated in both children during remission and decreased during relapse. Both fresh frozen plasma (FFP) and a commercial factor VIII/vWF concentrate reduced platelet retention when tested during remission. Treatment of both siblings with FFP or factor VIII/vWF concentrate was beneficial during recurrences. We conclude that the elevated platelet retention is due to a factor in the cryoprecipitate of the childrens' plasma, and that both FFP and factor VIII/vWF concentrate are effective in decreasing platelet retention.

Adult↗

A search for recall bias in a case-control study of diet and breast cancer.

BACKGROUND: In retrospective studies of dietary habits and breast cancer risk, recall bias is a concern since diet has been publicized as a cause of breast cancer. METHODS: In a case-control study of diet and breast cancer risk nested within a cohort of women screened with mammography, we contrasted answers to a retrospective dietary interview with answers to a dietary questionnaire which was filled out before any diagnostic procedures for breast cancer were undertaken. The source population was all women aged 40-74 in two counties in Sweden invited to mammographic screening and asked to fill out a questionnaire before the screening. Cases and controls were subsequently defined -- matched on age, county of residence, and time of mammography -- and approached for an interview. RESULTS: In all, 265 cases and 431 controls participated in the study. Means of frequencies differed between the agreement in the questionnaire's and the interview's classifications of study subjects into quartiles of monthly intake varied between 31 percent and 57 percent. Kappa statistics in all food groups were below 0.41. In a regression analysis, case subjects with low responses on the questionnaire about intake of meat, snacks, and coffee and tea gave higher responses on interview than did controls who had low questionnaire responses for these food groups. The reverse was also true: cases' responses that were high on the questionnaire were lower on interview for these food groups than were controls' responses. CONCLUSIONS: We found few signs of recall bias, and the few indications of a differential misclassification that we found were not in food groups that have been publicly discussed as causes of breast cancer.

Adult↗

Effect of prefracture versus postfracture dietary assessment on hip fracture risk estimates.

BACKGROUND: Dietary factors are presumed to have influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. METHODS: More than 65 000 women born 1914-1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. RESULTS: The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initially classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. CONCLUSION: We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information.

Age Distribution↗

High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma.

PURPOSE: To evaluate the outcome of patients with multiple myeloma (MM) who received high-dose therapy followed by autologous bone marrow (BM) or peripheral-blood stem-cell (PBSC) infusion. PATIENTS AND METHODS: Sixty-three consecutive patients with MM received autologous BM (n = 13) or PBSC with or without BM (n = 50) following regimens that contained busulfan (Bu) and cyclophosphamide (Cy) (n = 18), modified total-body irradiation (TBI) followed by Bu and Cy (n = 36), or Bu, melphalan, and thiotepa (n = 9). Two thirds of the patients had resistant disease and 69% had received more than 6 months of previous chemotherapy. RESULTS AND CONCLUSION: Recovery of peripheral-blood cell counts was more rapid in patients who received PBSC with or without BM than in patients who received BM alone. Sixteen of 63 patients (25%) died of complications of treatment within 100 days. Nineteen (40%) of 48 assessable patients achieved a complete response (CR), 23 (48%) had a partial response (PR), and six (12%) had no response. The probabilities of survival and survival without relapse or progression for all 63 patients at 3.0 years were .43 and .21, respectively. The probability of relapse or progression at 3 years was .69, and 17 patients (27%) have died of progressive MM. The probabilities of survival and relapse-free survival at 3 years for the 19 patients who achieved a CR were .42 and .17, respectively. In the multivariate analysis, beta2-microglobulin levels more than 2.5 micrograms/mL, more than two regimens of prior therapy and eight cycles of treatment, time to transplant longer than 3 years from diagnosis, and prior radiation were associated with adverse outcomes. Additional strategies, such as intervention earlier in the disease course, improved treatment regimens, sequential high-dose treatments, and posttransplant therapies may improve outcome of selected patients with MM.

Adult↗

Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53.

A long list of potential prognostic markers has been analysed for breast cancer, some of them will be reviewed in this article. The lymph node status is still the best prognostic marker. The lymph node status combined with information on tumour size, receptor- and proliferation status of the tumour should be analysed as standard for all breast cancer patients. Prognostic information for breast cancer patients has also been described for the membrane protein c-erbB2, the protease cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour suppressor genes. Some of these factors also give potential additional information on the response to different oncological therapies, and are better denoted predictive factors. In this overview we shortly describe the above mentioned prognostic factors with major focus on the tumour suppressor gene p53 and its prognostic value and potential predictive value.

Apoptosis↗

Adverse effects after radical external beam radiotherapy of localized prostatic adenocarcinoma using two-dimensional dose-planning and a limited field technique.

Adverse effects were assessed after definitive limited field, 2-dimensional CT-planned radiation treatment of localized prostatic adenocarcinoma. In 66 surviving patients, out of a total of 176 treated patients, personal interviews were performed and self-administered questionnaires distributed. The average follow-up was 6.6 years. Adverse effects with regard to bowel function and micturition were investigated, and graded 0-4 with increasing severity and impact on performance status, essentially according to the RTOG toxicity scoring system. Sexual functions were registered on visual analogue scales. The majority of adverse effects were considered minor (grade 1) and did not require any treatment. Late adverse effects on bowel and bladder or urethra that required treatment (grade 2-4) were reported in up to 8% (n = 5) of cases respectively. Late bowel side-effects that interfered with life style (grade 3-4) occurred in up to 3% (n = 2) of patients; the majority were rectal complications. Corresponding urinary side-effects were registered in up to 6% (n = 4) of the patients. Major surgical interventions were not required. Sexual functions were substantially affected in 60% of cases not administered endocrine treatment. Multivariate analyses could not identify patient or treatment risk factors related to complications.

Adenocarcinoma↗

Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease.

The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.

Adolescent↗