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.

Assessing estrogen and progesterone receptor status in fine needle aspirates from breast carcinomas. Results on six years of material and correlation with biochemical assay.

OBJECTIVE: To evaluate the usefulness of immunocytochemical staining on breast fine needle aspiration (FNA) cytology as a routine procedure for determination of estrogen (ER) and progesterone (PR) receptor status. STUDY DESIGN: FNA cytology material from 864 patients was immunostained for ER and PR using Abbott ER/PR-ICA kits. Percentage of stained nuclei, staining intensity and staining pattern was evaluated. In 259 cases comparison with biochemical assay was possible. RESULTS: Of the cases, 75.6% were ER positive and 65% PR positive, and 61.6% were both ER and PR positive. Approximately 4% of the smears were inconclusive because of scant cellularity. Concordance between the immunostaining and biochemical method was 84% for ER and 71% for PR. Kappa values were 0.61 and 0.4, respectively. Major discrepancies were found in 7.7% of the specimens. CONCLUSION: Inconclusive smears due to scant cellularity is a minor problem. Technical difficulties are few, and false negative and positive staining is rarely seen. The results are comparable to those from the biochemical method, and immunostaining of ER/PR on breast cancer FNA cytology smears is useful as a routine procedure for receptor determination.

Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group.

BACKGROUND: The purpose of the present study was to investigate whether a 1-month regimen of postoperative radiotherapy combined with 5-fluorouracil could reduce the local recurrence rate and improve survival in patients with Dukes B and C rectal cancer. METHODS: One hundred and forty-four patients were randomized to surgery alone or surgery combined with postoperative radiotherapy (46 Gy) and bolus 5-fluorouracil 30 min before six of the radiotherapy fractions. One hundred and thirty-six patients were eligible. RESULTS: The adjuvant treatment was well tolerated. After an observation time of 4-8 years, patients in the adjuvant treatment group had a cumulative local recurrence rate of 12 per cent compared with 30 per cent in the group that had surgery only (P = 0.01). The 5-year recurrence-free and overall survival rate was 64 per cent in the adjuvant group compared with 46 per cent (P = 0.01) and 50 per cent (P = 0.05) respectively in the surgery group. The adjusted relative risk of recurrence and death for the adjuvant group was 0.48 (95 per cent confidence interval 0.28-0.82) and 0.56 (0.33-0.94) respectively. CONCLUSION: The 1-month postoperative combination regimen improved treatment results in patients with Dukes B and C rectal cancer, in terms of local recurrence rate, recurrence-free survival and overall survival, without serious side-effects.

Coagulation inhibition and activation in pancreatic cancer. Changes during progress of disease.

BACKGROUND: To elucidate the disturbed hemostatic balance in patients with pancreatic cancer, the levels of plasma coagulation inhibition and coagulation activation were determined. METHODS: Twenty-one patients with adenocarcinoma of the pancreas were followed from time of diagnosis until death, using plasma analyses of coagulation inhibitors and a molecular marker of coagulation activation (thrombin-antithrombin complex, TAT). RESULTS: TAT was increased significantly at the time of diagnosis of pancreatic cancer compared with age-adjusted healthy control subjects (mean, 6.2 +/- 4.6 micrograms/l [standard deviation] versus 2.0 +/- 0.7 micrograms/l). It increased with disease progression (mean in the terminal phase, 14.1 micrograms/l; P < 0.05). Plasma levels of tissue factor pathway inhibitor (TFPI) also were increased significantly at the time of diagnosis compared with the control group (mean, 176 +/- 80% versus 127 +/- 29%; P < 0.05). The TFPI decreased to normal levels (121 +/- 40%) after surgical removal of the pancreatic tumor (n = 4) or relief of the cholestasis using a bypass procedure (n = 6). The TFPI levels increased significantly as the malignant disease progressed (from 1-3 months postoperatively to the terminal phase of disease; mean, 114 +/- 52% versus 154 +/- 60%). There was a significant positive correlation between TFPI levels and bilirubin levels; the correlation coefficient at diagnosis was 0.70 (P < 0.001). The levels of the coagulation inhibitors antithrombin, heparin cofactor II, protein C, and free protein S decreased significantly with disease progression compared with the normal values found at diagnosis. CONCLUSIONS: The mechanism for TFPI increase in cancer is not known. It may be related to the preoperative cholestasis seen in this study, but the increased degree of coagulation activation also may contribute.

[Late diagnosis of advanced breast cancer--a challenge for health services]. / Sent oppdaget cancer mammae en utfordring for helsevesenet.

From 1982 to 1987, 1,637 cancers of the breast were diagnosed in Oslo. 235 were classified as advanced according to one or more of the following criteria: tumour size greater than or equal to 5 cm (T3) or T4, metastasis within 4 months, pathological diagnosis pT3, pT4 or pN2. These were further studied. The distribution of women with advanced cancer mammae was uneven. For no obvious reason, incidence was significantly higher in one out of four hospitals in Oslo. 169 of the patients discovered the tumour themselves. Many patients delayed seeking help. 93 waited for more than eight weeks before doing so. For patients with metastasis at time of diagnosis, survival was slightly more than one year, and for patients without metastasis it was four and a half year. The length of stay in hospital increased with increasing admissions.

[Esophageal cancer. Treatment and results]. / Cancer oesophagi. Behandling og resultater.

Between 1979 and 1989, 38 patients were treated for cancer of the oesophagus. 25% (21/38) of the patients underwent resection of the oesophagus with either curative or palliative measures. 12 patients were treated radically, of whom two (17%) have lived free of recurrence for more than five years. Radical thoracoabdominal oesophageal resection is recommended as long as the operative mortality is low. Careful preoperative evaluation is necessary to select patients who should be treated by palliative procedures, such as oesophageal resection, by-pass procedures, laser coagulation and/or local irradiation.

High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer.

Serial determinations of plasma coagulation inhibitor levels were performed with chromogenic substrate activity assays in 7 patients with cancer. At time of diagnosis normal median activities of Antithrombin, Protein C, Heparin Cofactor II and Extrinsic Pathway Inhibitor were found. The inhibitor activities changed significantly with the progress of malignant disease; Antithrombin, Protein C and Heparin Cofactor II decreased whereas Extrinsic Pathway Inhibitor increased. Determinations in 13 additional patients in the terminal phase of cancer confirmed this finding. The inhibitor activities were expressed in per cent of a pooled reference plasma. In the total series of 20 patients studied, median activity of Extrinsic Pathway Inhibitor was 183% (range 61-378%) and significantly (p less than 0.005) above age-adjusted normal reference 10 days (range 1-20 days) prior to death. Median activities of Antithrombin was 59% (range 20-109%), of Protein C 54% (range 24-130%) and Heparin Cofactor II 59% (range 33-110%), all significantly below age adjusted normal reference (p less than 0.001). The coagulation inhibitor levels seem related to the stage of disease in patients with cancer.

The surgical treatment of gastric cancer: a retrospective study with special reference to total gastrectomy.

A retrospective study of 312 consecutive cases of gastric malignancy treated from 1974 to 1984 is presented. Eighteen patients (6%) had gastrointestinal lymphoma of the stomach. Among the remaining 294 cases with gastric carcinoma, 46 (16%) had carcinoma of the gastric stump after previous resection for peptic ulcer. Fifty-seven percent (167/294) had no distant metastases (MO). Early gastric carcinoma (pT1) occurred in 16 patients (5.8%), among whom four had distant metastases (pT1M1) and another two patients had regional lymph node metastases (pT1N1). Thirty-three percent of the patients had either no surgical treatment or an explorative laparotomy only, and 9% had a palliative bypass operation performed. A curative (48%) or palliative (10%) resection of the stomach was possible in 171/294 patients. Thus, the resectability rate was 58%. Total gastrectomy was performed in 108 cases with either curative (100) or palliative (eight) intention. The 30-day mortality was two and one patients, respectively (2.8%). Crude survival in the whole series was 16% and 11% at 5 and 10 years. After non-randomized curative total gastrectomy (100 cases) or gastric resection (40 cases) crude survival was 40% and 22% at 5 years, and 24% and 16% at 10 years, respectively (P greater than 0.05, n.s.). We found that total gastrectomy with extensive dissection and end-to-end esophago-jejunostomy by the EEA stapler can be performed with a low mortality rate (2% after curative operation) even in the upper age groups.

Pharmacokinetics of metronidazole and its major metabolite after a high intravenous dose.

The pharmacokinetics of metronidazole (M) and hydroxy-metronidazole (OH-M) were determined in 8 healthy volunteers after a single dose of 1.5 g metronidazole given as an intravenous infusion during 50 min. High-pressure liquid chromatography was used for the assays. The serum concentration determined 1 h after the start of infusion was 40.21 +/- 6.54 mg/1. The peak concentrations of the metabolite were observed after 8-12 h. The serum concentrations of M and OH-M were detectable throughout the 48 h monitored. The serum half-life of M was 7.6 h and of OH-M 13.3 h. The terminal phase distribution volume was 43.2 lit and the total body clearance 4.0 lit./h. The prophylactic use of 1.5 g of metronidazole given as a single intravenous dose 1 h prior to surgery is supported by the pharmacokinetic assessments in this study.