Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer.

PURPOSE: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. PATIENTS AND METHODS: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. RESULTS: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. CONCLUSION: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

Detection of isolated tumor cells in BM from breast-cancer patients: significance of anterior and posterior iliac crest aspirations and the number of mononuclear cells analyzed.

BACKGROUND: The aim of this study was to determine the influence and significance of different aspiration sites and the number of mononuclear cells (MNC) analyzed on the frequency of isolated tumor cell (ITC) detection by immunocytochemistry (ICC) in BM aspirates from breast-cancer patients. METHODS: BM aspirates were collected from the two anterior and two posterior crests just prior to primary surgery. The BM was processed separately from the anterior and the posterior crests, and cytospins (2 x 10(6) MNC) were prepared for ICC examination. The remaining cells were pooled, followed by cytospin preparation and ICC analysis (2 x 10(6) MNC/test). In addition, a fraction of the pooled cells were further processed by negative immunomagnetic selection, for enrichment of ITC. Out of 100 patients selected, 97 were further analyzed. RESULTS: The ICC examination from the separate crests revealed 37 positive BMs from the anterior iliac crest and 30 positive from the posterior crest. Twenty-one of the samples were positive at both sides. Five patients had 10 or more ITCs detected. In these, an unequal distribution of ITCs between the sides was observed, but in favor of neither. ICC analysis of 2, 4 and 6 x 10(6) MNC revealed respectively 22, 46 and 52 positive BMs out of the 97 analyzed. These results were correlated to the clinical outcome after a median 43 months follow-up. Thirteen of the patients underwent systemic relapse. Analyzing 2 x 10(6) MNC by ICC, 27.3% of the BM+ patients developed systemic disease, compared with 9.3% of the BM+ patients (P = 0.0056, log rank test). Analyzing 6 x 10(6) MNC reduced the correlation between ITC in BM and clinical outcome. CONCLUSION: No significant difference in the detection rate of ITCs from the anterior and the posterior iliac crests was found, although the distribution of ITCs did show a great variability. Analyzing a higher number of BM cells increased the number of positive BM specimens detected. However, this increased detection rate reduces the prediction by ICC of early systemic relapse.

Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients.

The axillary lymph nodes of 100 lymph node-negative breast cancer patients with known bone marrow status have been re-examined to explore the presence of micrometastasis in lymph nodes and the covariance of micrometastasis to bone marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100 microm, followed by immunohistological (two sections) and haematoxylin-eosin staining (one section). Tumours were mainly T1 and T2, and the patients had on average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was detected in one node. Another 25 patients possessed single positive immunostained cells mimicking tumour cells. These cells have been shown to be false positive cells by Perl and melanin staining. One patient had metastasis to several nodes missed by the original examination. Immunocytochemical detection of micrometastasis in bone marrow revealed 11 marrow-positive patients. This study has identified a low frequency of micrometastasis to lymph nodes, and no covariance with micrometastasis in the bone marrow was seen. Bone marrow micrometastasis may be an independent prognostic variable, separate from axillary node status.

[Patients with diagnosed colonic diverticulitis admitted to a department of surgery]. / Pasienter med diagnosen colondivertikulitt innlagt i kirurgisk avdeling.

In 1995-96, 148 patients with the diagnosis diverticulitis of the colon were admitted a total of 176 times to the Department of Gastroenterologic Surgery at Ullevaal Hospital in Oslo. Data on treatment and outcome were recorded retrospectively from patient files. 92% of the hospitalisations were emergency cases of abdominal pain. In 113 hospitalisations, patients were initially treated with intravenous antibiotics, aspiration of the stomach, later oral antibiotics. No deaths were recorded. In 8 out of 64 patients (13%) hospitalised with diverticulitis for the first time, the diagnosis could not be verified by coloscopy or bowel enema. In 63 hospitalisations (36%), the patients underwent surgery. Hartmann's procedure was performed in 31 out of 49 emergency cases. 22 patients undergoing surgery in an emergency setting had perforated diverticulitis; 5 of these patients died within 15 days. 14 patients had planned surgery with bowel resection and 15 patients had a planned closing of the stoma. Two of these 29 patients died post-operatively. Acute diverticulitis is a serious condition, especially when the bowel has perforated. Complications develop both after emergency and elective surgery. We recommend careful selection of patients.

Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy.

OBJECTIVE: Our purpose was to investigate the cytokines, tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy and labor. STUDY DESIGN: Bioassays were used to measure these factors in extraembryonic coelomic fluid, amniotic fluid, placenta, and maternal and cord serum. RESULTS: Little or no tumor necrosis factor, interleukin-1, or interleukin-6 was found in coelomic fluid or amniotic fluid in the first trimester. Interleukin-6 appeared in second-trimester amniotic fluid. At term tumor necrosis factor was present (median 17 pg/ml) and increased with the onset of labor (median 58 pg/ml), as did interleukin-1 (median 188 to 680 pg/ml) and interleukin-6 (median 399 to 4800 pg/ml). Maternal serum interleukin-6 increased during pregnancy with a further increment with the onset of labor. Cord interleukin-6 also increased with labor but at a lower level. CONCLUSION: The cytokines tumor necrosis factor, interleukin-1, and interleukin-6 may play a role in the onset of normal labor.