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Biomedical subjects

E Skovlund

Publications and source records attributed to E Skovlund.

At least 19 recordsLinked to original sources

Inflammatory markers in bronchoalveolar lavage fluid from human volunteers 2 hours after hydrogen fluoride exposure.

Fluoride has been in focus as a possible causal agent for respiratory symptoms amongst aluminium potroom workers for several decades. Previously, using bronchoalveolar lavage (BAL), we demonstrated airway inflammation in healthy volunteers 24 hours after exposure to hydrogen fluoride (HF). The objective of the present study was to examine early lung responses to HF exposure. Bronchoscopy with BAL was performed 2 hours after the end of 1-hour exposure to HE Significant reductions in the total cell number and the number of neutrophils and lymphocytes were observed in bronchoalveolar portion (BAP), whereas there were no significant changes in the bronchial portion (BP). Significantly decreased concentrations of beta2-MG, IL-6 and total protein were found in both BAP and BP. Additionally, IL-8 was significantly reduced in BP, and ICAM-1 and albumin were present in lower concentrations in BAP. Lung function measurements were not affected by HF exposure. These reported effects are presumably transitory, as many were not present in the airways 24 hours after a similar HF exposure.

Administration, Inhalation↗

Pregnancy and breast cancer: a population-based study.

The incidence of pregnancy-associated breast cancer, i.e. during pregnancy and lactation, and of pregnancy subsequent to a breast-cancer diagnosis will increase as more women choose childbearing at a later age. Few larger series are published on pregnancy-associated breast cancer. In a population-based study, we evaluated the outcome and prognostic factors in 173 breast-cancer patients. One hundred and twenty-two patients had pregnancy-associated breast cancer (20 coincident with pregnancy and 102 during lactation) and 51 patients had pregnancy subsequent to breast cancer. The median follow-up time was 151 months. Histopathological parameters and immunoreactivity for oestrogen and progesterone receptors c-erbB-2 and c-erbB-4 were studied. All three groups had tumours with high histological grade, low frequency of hormone receptors and high expression of c-erbB-2. The pregnancy and lactation groups were near identical with regard to all histopathological parameters and outcome. In the two pregnancy-associated breast-cancer groups, tumours were significantly larger, with more extensive lymph-node involvement. For node-negative tumours the respective 5- and 10-year survival rates were 62% and 50% in the pregnancy group and 60% and 50% in the lactation group. For node-positive tumours, respective 5- and 10-year survival rates were 50% and 34% in the pregnancy group and 50% and 33% in the lactation group. In the subsequent group, overall survival was high in both node-negative and -positive groups, with 5- and 10-year survival rates of 80% and 73% and 86% and 76%, respectively. Tumour size, lymph-node status, histological grade, progesterone receptor, oestrogen receptor and c-erbB-2 were significant prognostic factors in the pregnancy-associated breast-cancer patients.

Adenocarcinoma↗

Quality of life during radiotherapy for rectal cancer.

The aim of this study was to assess symptoms and health-related quality of life (HRQL) during (neo)adjuvant radiotherapy for rectal cancer. Patients receiving pelvic radiotherapy 50 Gy for rectal cancer, were studied prospectively (n=42). The European Organization for Research and Treatment of Cancer (EORTC) questionnaires quality of life-core 30 QLQ-C30 and QLQ-CR38 and a 5-day symptom diary were completed at the start and end of radiotherapy and 4-6 weeks later. At the end of radiotherapy, mean scores of diarrhoea, fatigue and appetite loss had significantly increased (P<0.01) compared with pretreatment scores, but this was not observed for scores for nausea or pain. At the end of radiotherapy, diarrhoea, fatigue, appetite loss, physical function, social function and global quality of life (QL) were significantly worse than the population-based norms. 64% of the patients reported an increase in fatigue and 52% an increase in diarrhoea during radiotherapy. HRQL scores had returned to pre-treatment levels 4-6 weeks after radiotherapy. Thus, diarrhoea, fatigue and appetite loss increased transiently during pelvic radiotherapy.

Adult↗

Change of immunoglobulins and complement factors in patients with self-injurious behaviour.

OBJECTIVE: As stress activates the inflammatory response system, and attempted suicide is connected with severe stress, we hypothesized that patients hospitalized for self-injurious behaviour have changed immunocompetence. METHOD: The concentration of immunoglobulins IgG, IgA, IgM, and the complement components C3 and C4 in 73 patients hospitalized for self-injurious behaviour was compared with those of 122 healthy controls. The immunoglobulins and complement were quantified by nephelometric technique. RESULTS: The levels of IgG and IgM were significantly lower, and the complement C3 and C4 were significantly higher in self-injurious patients compared with controls. This was valid in both genders and the effects did not interact with gender. CONCLUSIONS: This controlled study showed that the concentrations of immunoglobulins were reduced and complement components were increased in patients who are admitted to hospital for self-injurious behaviour.

Adult↗

Inter-endoscopist variation in polyp and neoplasia pick-up rates in flexible sigmoidoscopy screening for colorectal cancer.

BACKGROUND: The Norwegian Colorectal Cancer Prevention study is an ongoing flexible sigmoidoscopy (FS) screening trial for colorectal cancer. Twenty-one thousand average-risk individuals, aged 50-64 years, living in two separate areas in Norway were randomly drawn from the Population Registry and invited to once-only screening flexible sigmoidoscopy. Examinations were performed over 3 years, at 2 centres, by 8 different endoscopists, using the same type of equipment. The aim of the present study was to investigate possible differences between endoscopists in detecting individuals with polyps, adenomas and advanced lesions (adenomas with severe dysplasia and/or villous components and/or size larger than 9 mm and carcinoma) in flexible sigmoidoscopy screening. METHODS: The present trial comprises data from 8822 individuals, aged 55-64 years, who have undergone a flexible sigmoidoscopy. In the study period, all lesions detected by the different endoscopists were registered. Tissue samples were taken from all lesions detected. RESULTS: Detection rates varied significantly between endoscopists, ranging from 36.4% to 65.5% for individuals with any polyp, from 12.7% to 21.2% for any adenoma and from 2.9% to 5.0% for advanced lesions. In a multiple logistic regression model, the performing endoscopist was a strong independent predictor for detection of individuals with polyps (P < 0.001 ), adenomas (P < 0.001) and advanced lesions (P = 0.01). CONCLUSION: Detection rates for colorectal lesions vary significantly between endoscopists in colorectal cancer screening. Establishing systems for monitoring performance in screening programmes is important. Supervised training and re-certification for endoscopists with poor performance should be considered.

Clinical Competence↗

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

OBJECTIVE: To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. DESIGN: Randomised, placebo-controlled, double-blind, parallel group, single centre study. SETTING: Primary care in Joensuu, North Karelia, Finland. SUBJECTS: Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. INTERVENTION: The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. RESULTS: Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. CONCLUSION: Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

Adolescent↗

Adjuvant endocrine treatment (goserelin vs tamoxifen) in pre-menopausal patients with operable node positive stage II breast cancer. A prospective randomized national multicenter study.

AIMS: To evaluate possible differences in effect on time to recurrence and overall survival in node positive pre-menopausal breast cancer patients (age < or = 50 years) receiving LHRH analogue or tamoxifen as adjuvant endocrine treatment. METHODS: Between January 1989 and July 1994, 320 patients with node positive (pN(+)) and hormone receptor positive or receptor status unknown tumors were included and randomized in a national multicenter study to receive either tamoxifen or goserelin as adjuvant treatment for two years. Primary surgical treatment was employed according to current standards. Final follow-up was completed as of December 2000. Time to events were estimated by the Kaplan-Meier method, and compared by the log rank test. Relative risks were estimated by the Cox's proportional hazards model. RESULTS: No differences in time to first recurrence or overall survival were observed between treatment groups. Proportions of patients in each group having a second breast cancer were also similar. CONCLUSIONS: Standard adjuvant treatment with tamoxifen as compared to adjuvant LHRH analogue therapy employed in this group of breast cancer patients gave similar outcomes, but the number of patients was too small to formally exclude a potentially clinically relevant difference in survival.

Adult↗

Use of a disposable sheath system for flexible sigmoidoscopy in decentralized colorectal cancer screening.

BACKGROUND AND STUDY AIMS: To prevent transmission of infectious agents and to reduce instrument reprocessing time, the use of disposable sheath systems instead of conventionally reprocessed endoscopes has been promoted for flexible sigmoidoscopy. This trial primarily investigated the feasibility of a disposable sheath system for flexible sigmoidoscopy in decentralized colorectal cancer screening. PATIENTS AND METHODS: In an ongoing colorectal cancer screening trial, 226 consecutive participants were randomly allocated to have their flexible sigmoidoscopy performed with either a fiberoptic sigmoidoscope covered with a disposable sheath ("EndoSheath group") or a conventional video colonoscope ("standard colonoscope group"). All examinations were performed at a temporary screening center. The patients' experience was documented using a questionnaire. The feasibility of running temporary screening units was evaluated. RESULTS: Examinations beyond the 60-cm level were excluded. Thus, 113 patients (examined with the disposable instrument) and 87 (standard instrument) were eligible for analysis. When the sheathed system was used, all the devices needed could be satisfactorily transported. A screening center could be set up within a few hours. No differences were observed in patient discomfort. Fewer patients with polyps were observed in the EndoSheath group (48 [42%]), compared with 55 (63%) in the standard colonoscope group; P = 0.005). No significant differences were observed for polyps larger than 5 mm (14 [12%] in the EndoSheath group, 13 [15%] in the standard colonoscope group; P = 0.6). CONCLUSIONS: Using the disposable system, decentralized colorectal cancer screening was easily established. However, fewer polyps were found, possibly due to the fiberoptic nature of the instrument. Sheathed video instruments are desirable and may increase the diagnostic yield.

Colorectal Neoplasms↗

Carbon dioxide insufflation reduces discomfort due to flexible sigmoidoscopy in colorectal cancer screening.

BACKGROUND: Flexible sigmoidoscopy is currently recommended as a screening modality for colorectal cancer. However, a substantial number of patients experience discomfort because of the procedure. possibly limiting compliance and thus screening success. During endoscopy, air is commonly used to insufflate the bowel. Carbon dioxide rather than air insufflation has been shown to reduce procedure-related pain and discomfort in colonoscopy. The aim of the present study was to evaluate whether carbon dioxide insufflation reduces discomfort during and after flexible sigmoidoscopy for colorectal cancer screening. METHODS: In a randomized, double-blinded design, 230 consecutive participants in a population-based flexible sigmoidoscopy colorectal cancer screening trial were assigned to have their examination performed with either carbon dioxide or air insufflation. Patients were asked to grade discomfort experienced both during and in the hours after the procedure on a visual analogue scale. RESULTS: Carbon dioxide insufflation significantly reduced the amount of discomfort at 1, 3 and 6 h after the sigmoidoscopy. One hour after the examination. 84% of patients in the CO2 group reported no discomfort, compared to 64% in the air group (P = 0.006). No differences between the groups were observed during the examination. CONCLUSIONS: Carbon dioxide insufflation significantly reduced post-examination discomfort. The use of carbon dioxide rather than air insufflation may contribute to better public acceptance for flexible sigmoidoscopy screening.

Carbon Dioxide↗

Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention).

BACKGROUND: In the past three decades, the incidence of colorectal cancer (CRC) in Norway has doubled, surpassing all other Nordic countries for both men and women to become the most frequently diagnosed cancer. A small-scale, randomized study on flexible sigmoidoscopy (FS) screening in Telemark, Norway, has shown a reduction in accumulated CRC incidence after 13 years. The aim of our study was to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy), and to test out the management and organization mimicking a countrywide screening service. A total of 13,823 men and women (1:1), age 55-64 years, were drawn randomly from the population registries in Oslo (urban) and the county of Telemark (mixed urban and rural) and invited to have a screening examination. The rest of the relevant age cohorts constituted the control groups. In the screening group, 535 individuals were excluded according to exclusion criteria, rendering 13,288 individuals eligible for screening examination. METHODS: A once only screening model was used. In the screening group, individuals were randomized to have a once only FS or a combination of FS and faecal occult blood test (FOBT). RESULTS: The overall attendance rate was 8,849 out of 13,288 (67%); 73% in Telemark and 60% in Oslo. Attendance for FS only was 68% and 65% for combined FS&FOBT. CONCLUSIONS: The present FSIFS&FOBT screening study obtained a high acceptance rate for both screening modalities. The attendance rate was stable throughout the trial, suggesting an acceptable model for management of future countrywide screening.

Colonic Polyps↗

Human exposure to hydrogen fluoride induces acute neutrophilic, eicosanoid, and antioxidant changes in nasal lavage fluid.

The development of asthmalike symptoms among aluminum potroom workers has been associated with exposure to fluorides. In the present study, the immediate nasal response in humans was examined subsequent to short-term hydrogen fluoride (HF) exposure. Ten healthy subjects were exposed to HF (3.3-3.9 mg/m(3)) for 1 h. Nasal lavage (NAL) was performed before, immediately after, and 1.5 h after the end of exposure. Control lavages were performed on the same subjects at the same time points but without HF exposure. At the end of HF exposure, 7 of 10 individuals reported upper airway symptoms. A significant increase was observed in the number of neutrophils and total cells, while there was a decrease in cell viability. The changes in neutrophil numbers correlated significantly with the reported airway symptoms. HF also induced a significant increase in tumor necrosis factor-alpha and the total protein content of NAL fluid. Among the eicosanoids, prostaglandin E(2), leukotriene B(4), and peptide leukotrienes were elevated after exposure. Of the antioxidants measured, the concentration of uric acid increased after exposure. In conclusion, exposure to HF induced immediate nasal inflammatory and antioxidant responses in healthy human volunteers. These findings may contribute to a further understanding of the way HF exerts damage to the airways and show that HF could represent an occupational hazard.

Acute Disease↗

Central nervous system involvement following diagnosis of non-Hodgkin's lymphoma: a risk model.

BACKGROUND: To determine the incidence and risk factors for central nervous system (CNS) relapse in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patient records were registered prospectively in successive patients with NHL admitted to the Norwegian Radium Hospital from 1980 to 1996. A total of 2514 patients had no CNS involvement at diagnosis and were treated according to standard protocols. The incidence and risk factors for CNS progression or relapse were examined retrospectively. RESULTS: In low-grade (L)-NHL, the risk of CNS involvement was low (2.8%). In high-grade (H)-NHL, lymphoblastic and Burkitt's NHL patients had a high risk of CNS recurrence (24.4%) at 5 years, and prophylaxis seemed to reduce this risk. For the other patients with H-NHL, the proportion with CNS involvement at 5 years was 5.2%. Multivariate analysis identified five independent risk factors, each present in >5% of patients: elevated serum lactate dehydrogenase, serum albumin <35 g/l, <60 years of age, retroperitoneal lymph node involvement and involvement of more than one extranodal site. If four or five of these risk factors were present, the risk of CNS recurrence was in excess of 25% at 5 years. CONCLUSIONS: The risk of CNS involvement in this study is comparable with the results from other large series. CNS prophylaxis is not recommended in any subgroup of L-NHL. The risk of CNS involvement among patients with either Burkitt's or lymphoblastic lymphomas is considerable and these patients should therefore receive intensive chemotherapy including systemic and intrathecal methotrexate. Patients with other types of H-NHL should receive adequate CNS prophylaxis if at least four of the five risk factors identified are present.

Adolescent↗

NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy.

BACKGROUND: To eliminate the risk of combustion during electrosurgical procedures and to reduce patient discomfort, carbon dioxide (CO2) insufflation has been recommended during colonoscopy. However, air insufflation is still the standard method, perhaps due to the lack of suitable equipment and shortage of randomised studies. AIMS: This randomised controlled trial was conducted to assess patient tolerance and safety when using CO2 insufflation during colonoscopy. PATIENTS: Over an eight month period a successive series of patients referred for a baseline colonoscopy due to findings in a flexible sigmoidoscopy screening trial were randomly assigned to the use of either air or CO2 insufflation during colonoscopy. METHODS: End tidal CO2 (ETCO2), a non-invasive parameter of arterial pCO2, was registered before and repeatedly during and after the examination. The patient's experience of pain during and after the examination was registered using a visual analogue scale (VAS). Sedation was not used routinely. RESULTS: CO2 insufflation was used in 121 patients (51%) and air in 119 patients (49%). The groups were similar in age, sex, and caecal intubation rate. No rise in ETCO2 was registered. There were statistically significant differences in VAS scores between the groups with less pain reported when using CO2. CONCLUSIONS: This randomised study of unsedated patients shows that CO2 insufflation is safe during colonoscopy with no rise in ETCO2 level. CO2 was found to be superior to air in terms of pain experienced after the examination.

Air↗

Histologic subtype has minor importance for overall survival in patients with adenocarcinoma of the uterine cervix: a population-based study of prognostic factors in 505 patients with nonsquamous cell carcinomas of the cervix.

BACKGROUND: The incidence of adenocarcinoma of the uterine cervix is increasing. For better prognostic information, the authors studied all nonsquamous cell carcinomas (non-SCCs) in the Norwegian population over a total of 15 years. METHODS: All non-SCCs from three 5-year periods (1966-1970, 1976-1980, and 1986-1990) were reviewed and classified according to the World Health Organization classification system, and histopathologic and clinical parameters were registered. Tissue blocks were available from all patients. RESULTS: Of 505 patients, 417 had tumors classified as adenocarcinoma, and 88 had tumors classified as other non-SCC. The mean ages were 53 years and 52 years for patients with adenocarcinoma and non-SCC, respectively. Sixty-two percent of the staged patients had clinical Stage I disease according to the classification system of the International Federation of Gynecology and Obstetrics (FIGO). In univariate analyses, histology, architectural and nuclear grade, extension to the vagina or corpus uteri, tumor length (> 20 mm) or tumor volume (> 3000 mm(3)), infiltration depth (in thirds of the cervical wall), thickness of the remaining wall (< 3 mm), vascular invasion, lymph node metastases, treatment, and patient age were significant variables in patients with FIGO Stage I disease. Variables with no significance in patients with Stage I disease were number of mitoses, state of resection margins, infiltration to ectocervix, tumor thickness, lymphoid reaction, earlier or concomitant cervical intraepithelial neoplasia, stump carcinoma, DNA ploidy or DNA index, or time period. Multivariate analyses of patients with FIGO Stage I disease identified small cell carcinoma, corpus infiltration, vascular invasion, and positive lymph nodes as independent prognostic factors. CONCLUSIONS: Small cell carcinoma was the only histologic subgroup of independent importance for prognosis in patients with non-SCC of the uterine cervix. No significant difference between major subtypes of adenocarcinoma favored a simplified classification. Extension to the corpus in patients with early-stage disease was of independent significance and should be acknowledged in planning treatment.

Adenocarcinoma↗

Prognostic significance of histologic grading in patients with prostate carcinoma who are assessed by the Gleason and World Health Organization grading systems in needle biopsies obtained prior to radiotherapy.

BACKGROUND: The current study was conducted to evaluate and compare the impact of two major histologic grading systems on failure-free survival in patients with prostate carcinoma who are treated with definitive radiation. METHODS: Eligible patients for the current study had localized adenocarcinoma of the prostate (T1-4pN0M0, T3/4: 67%, median observation time: 69 months) and were treated with intent-to-cure external radiotherapy between 1989 and 1995. The specimens from 178 patients, obtained by needle biopsies, were reviewed simultaneously by two pathologists assigning World Health Organization (WHO) and Gleason grades. Three-tiered Gleason grouping distributed patients into three groups (those with a score < 7, those with a score of 7, and those with a score of 8--10), whereas two-tiered Gleason categorization distributed patients into two groups (those with a Gleason score of 7A, major 3 + minor 4 patients were added to the group of patients with a Gleason score < 7 and patients with a Gleason score of 7B, major 4 + minor 3 were added to the group of patients with a Gleason score of 8--10). Univariate and multivariate analyses were performed. A P value < 0.05 was considered to be statistically significant. RESULTS: Three-tiered Gleason grouping resulted in a relatively even distribution of the patients (44 patients had a Gleason score < 7, 58 patients had a Gleason score of 7, and 76 patients had a Gleason score of 8--10) whereas 130 patients were determined to have Grade 2 tumors based on WHO criteria. Separating those patients with a Gleason score of 7 (score 3+4 vs. score 4+3) led to the two-tiered Gleason grouping (88 patients in the favorable group and 90 patients in the unfavorable group). The two-tiered Gleason grouping displayed differences with regard to failure-free survival with the lowest P values for all patients and separately for T1/2 versus T3/4 tumors. Together with T category and pretreatment prostate specific antigen, WHO grading, three-tiered Gleason grouping, and two-tiered Gleason grouping resulted in independent parameters in the Cox regression model. The proportional variance estimate confirmed the superior discrimination for survival of two-tiered Gleason grouping. CONCLUSIONS: The equal allocation of patients to subgroups based on the Gleason system helps the clinician to overcome the dilemma of overrepresentation of Grade 2 patients as occurs with WHO grading. The Gleason grading system and, most likely, the two-tiered Gleason grouping appear to result in better prognostic separation of patients referred to radiotherapy for relatively advanced primary tumors. Therefore the authors recommend the routine use of Gleason grading for these patients.

Adenocarcinoma↗

Prognostic value of neuroendocrine serum markers and PSA in irradiated patients with pN0 localized prostate cancer.

BACKGROUND: The prognosis of patients with localized prostate cancer depends on clinical stage, histological grade, and pretreatment prostate-specific antigen (PSA). We evaluated the additional prognostic impact of serum levels of neuron-specific enolase (NSE) and chromograninA (CgA) after curative radiotherapy and the importance of serum PSA, analyzed 3 months after irradiation. METHODS: From 1988 to 1995, 161 patients with localized T1-4, pN0M0, prostate adenocarcinoma were treated with external radiation (66Gy, 2Gy/5 fractions per week). Frozen serum samples were assessed for CgA, NSE, and PSA before and 3 months after radiotherapy. CgA was analyzed in only 100 patients. NSE and CgA were determined by a immunometric assay. Total PSA was measured by a time-resolved fluoro-immunometric assay. RESULTS: Prior to radiotherapy CgA was elevated in 16 of 100 patients, and NSE was elevated in 33 of the 161 patients. There was no association between grade, T category or pretreatment PSA and the levels of neuroendocrine markers. Pretreatment-elevated serum NSE, but not initial CgA, identified patients with an unfavorable prognosis. A < 50% reduction of PSA 3 months after radiotherapy was associated with decreased failure-free 10 years urvival. Multivariate analysis demonstrated an increased risk of failure for patients with elevated pretreatment NSE and PSA values, T3 category, and decline of PSA less than 50% 3 months after radiotherapy. The presence of none or several risk factors (1-4) defined clearly separable groups. CONCLUSIONS: Together with T category and pretreatment serum PSA values, serum NSE values before radiotherapy and decrease of serum PSA 3 months after radiotherapy represent easily assessable prognostic parameters in patients undergoing curative radiation treatment for prostate cancer.

Adenocarcinoma↗

Immunobead-based detection and characterization of circulating tumor cells in melanoma patients.

The presence of circulating tumor cells in bone marrow and peripheral blood of cancer patients may reflect the aggressiveness of the disease. This also applies to cancers that rarely give rise to overt bone marrow metastases. The clinical validity of micrometastasis detection for staging and prognostication depends on the sensitivity and reliability of the detection method. In malignant melanoma, most studies have used reverse transcriptase polymerase chain reaction (RT-PCR) techniques, commonly with tyrosinase mRNA as the target molecule. Unfortunately, highly inconsistent results have been reported, raising doubts about this approach. In a study of 81 melanoma patients with metastatic disease, we used an immunobead rosetting method in which live melanoma cells are selected and identified by binding of paramagnetic beads coated with the 9.2.27 antibody against the high molecular weight melanoma-associated antigen. In bone marrow samples obtained from 60 patients, 14 (23.3%) were positive, compared to only two of 81 in blood. A highly significant correlation (p = 0.0001, log rank test) was found between micrometastasis positivity and overall survival from time of removal of the primary tumor. Moreover, in regression analysis it was found that the presence of micrometastatic cells was an independent and the most important indicator of poor prognosis, with a relative risk of 5.38. The immunomagnetic method is simple, rapid, and highly sensitive and will be used in further prospective clinical studies.

Antibodies, Monoclonal↗