The occurrence of bone marrow carcinosis was investigated in 380 patients at the time of first recurrence of breast cancer. Results were related to results from radiographic bone survey, 99mTc MDP bone scintigraphy, clinical examination and serum alkaline phosphatase and serum calcium levels. Eighty-seven patients (23%) had tumor cells in the bone marrow. X-rays showed metastases in 78% of the patients with and in 16% of the patients without bone marrow carcinosis. The diagnostic efficiency of x-rays with bone marrow biopsy as the key diagnostic factor was 83%, and it was superior to that of other investigation methods. Bone tissue biopsies were positive alone in 15 patients (17%) and marrow aspirations were positive alone in seven patients (8%). Imprint preparations were positive alone in 7% of the patients and bone tissue biopsy in 5% of the patients. Heavy tumor infiltration (250%) of the bone marrow was associated with the occurrence of numerous regions of radiographically involved bone lesions and with histopathologic evidence of bone destruction. Furthermore, pronounced bone formation and marrow fibrosis were more commonly seen in patients with osteosclerotic bone metastases than in patients with osteolytic bone metastases. This study provides evidence that the primary soil of meta-static bone disease in human breast cancer is the bone marrow and that radiographic evidence of bone metastases is a result of an invasion and destruction of the bone tissue matrix by tumor cells from the marrow cavity. Cancer 60~306-1312, 1987. TAGING PROCEDURES for patients with first recurS rence of breast cancer are important prerequisites both for determining the clinical course to be followed and for establishing a thorough baseline evaluation before the onset of treatment.'-3 Moreover, the fact that most agents used in the treatment of recurrent breast cancer are myelosuppressive stresses the importance of evaluating the condition of the bone marrow before treatment is started.' Usually, x-rays and/or bone scin-tigraphy are used to evaluate the occurrence of bone metastases. However, histopathologic evidence of bone marrow carcinosis is not always associated with radio-graphic and scintigraphic abn~rmalities.~-' Previous clinical studies have shown a variation of 3% to 40% in the frequency of positive bone marrow exami-From the Departments of *Oncology ONA, ?Pathology, $Radiol-ogy, and §Clinical Physiology,

Conclusions-Good agreement was found between increased bone uptake and MR detected subchondral lesion. The agreement between increased bone uptake and osteophytes or cartilage defects was in general poor as well as the agreement between the grade of bone uptake and the grade of the MR findings. (Ann Rheum Dis 1999;58:20-26) Osteoarthritis (OA) is a multifactorial process 1 aVecting cartilage and subchondral bone.

SummaryLung function was evaluated in a representative population sample of 50-year-old men living in one Swedish city. Twenty-four smoking and 15 non-smoking men heterozygous for alpha,-antitrypsin deficiencythat is, with the protease-inhibitor (Pi) phenotype MZ-were carefully matched for weight and smoking habit with Pi M controls. The pulmonary function of non-smoking Pi MZ subjects did not differ from that of non-smoking Pi M controls. In contrast, smoking heterozygotes showed a significant loss of elastic recoil, enlarged residual volumes, and increased closing capacity but no signs of obstructive ventilatory impairment. Most smoking Pi MZ individuals reported mild exertional dyspnoea.The

The occurrence of liver metastases was evaluated by ultrasonic scanning and correlated with prognostic factors, pattern of metastases, clinical examination, biochemical liver function tests from serum, and liver biopsy specimens in 394 consecutive evaluable patients with first recurrence of breast cancer. Fifty-nine patients (15%) had a positive scan, and liver metastases were the only sign of recurrent disease in 11 of these patients. The presence of liver metastases was not associated with age, menopausal status, size of the primary tumor, regional lymph node status, or the length of the recurrence-free interval; but patients with liver metastases were significantly closer to the menopause than those without (P = 0.02). The diagnostic value of clinical examinations was comparable to that of serum bilirubin and serum aspartate aminotransferase (ASAT) analyses, but was significantly better than alkaline phosphatase (AP) and lactate dehydrogenase (LDH) analyses. Analysis of serum AP was not a valuable diagnostic tool in the diagnosis of liver metastases, since it was elevated in 58% of the patients with bone metastases, and since metastases in this site were found in one third of the patients without liver metastases. If all four tests were negative, liver metastases were excluded in 99% of the patients, and if more than two of the four tests were positive, liver metastases were found in 95%. Valid (9 0 %) diagnosis of liver metastases by serum LDH or serum ASAT alone, required an elevation of three or five times the upper normal limits, respectively. Thirty-nine patients with positive ultrasonography results underwent biopsy. The ultrason-ographic diagnosis could not be confirmed histologically in three patients (8%). If ultrasonic scanning had not been performed routinely, only one of 213 patients (0.5%) with soft tissue metastases would have been offered local therapy rather than systemic treatment. These data suggest that ultrasonic scanning of the liver should not be a routine diagnostic tool in examination of patients with first recurrence of breast cancer. However, whenever indicated by clinical signs or elevated blood tests, scanning should be performed to confirm the presence of liver metastases, particularly in patients entering therapeutical trials, since liver metastases demonstrated by ultrasound examinations may serve as a measurable parameter. Cancer 59:1524-1529, 1987. HE ACCURATE DETERMINATION of the extent and Site T of metastases in recurrent breast cancer is an important prerequisite for rational treatment.' Therefore, routine staging procedures should be able to identify me-tastases at the most common sites of recurrence with a high degree of certainty. Liver metastases are found in only a few percent of patients in clinical studies, whereas 40% to 60% of the patients are found to have liver me-tastases in autopsy studies.' To some extent, the differences in these figures may reflect the development of new From the

Metastatic bone disease was evaluated in 380 consecutive patients at the time of first metastasis of breast cancer. Studies included radiographic examination, radionuclide examination, and bone marrow biopsy. Radiographs of the skeleton demonstrated metastases in 120 patients (32%), and in 40 of these patients (13%) the bone was the only site of metastases. The diagnostic efficiency was 82% for bone scanning, 80% for pain evaluation, 59% for s-calcium analyses, and 77% for s-alkaline phosphatase analyses. Bone scanning is an effective method to exclude metastatic bone disease (sensitivity: 96%). A positive scan, however, requires radiologic confirmation (specificity: 66%). Bone scanning of the skeleton should be the initial staging procedure in all patients with recurrent breast cancer with no clinical or biochemical signs of bone metastases. Bilateral posterior iliac crest bone marrow aspirations and bone biopsies were positive in 82 out of the 320 patients who underwent biopsy. The frequency of positive bone marrow biopsy was significantly correlated with both the site of radiographic metastases and with the total number of involved bone regions. Routine bone marrow biopsies are indicated in patients with a positive bone scan, but a negative x-ray examination. In these cases biopsies should be performed bilaterally.