Isolated tumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinical outcome.

PURPOSE: The aim of the study was to explore the value of analyzing bone marrow (BM) for the presence of isolated tumor cell(s) (ITCs) in disease-free breast cancer patients 3 years after diagnosis. EXPERIMENTAL DESIGN: ITCs in BM at operation was found to be an independent prognostic factor in 817 breast cancer patients. Among these, 356 disease-free patients were analyzed with a second BM after 3 years follow-up (median 40 months, SD 3 months, range 29-52). ITC was detected by immunocytochemistry with anticytokeratine antibodies (AE1/AE3). RESULTS: The population consisted of 70% T1 and 72% node-negative patients. ITC in BM was detected in 15%. At a median of 25 months since the second BM aspiration (66 months since diagnosis), 32 patients had developed relapse, 12 local and 20 systemic. Of the patients with ITC in BM, 21% relapsed compared with 7% of the ITC-negative patients (P < 0.001). Ten patients died of breast cancer. Survival analyses showed that ITC in BM predicted reduced distant disease-free survival (DDFS) and breast cancer specific survival (BCSS; P < 0.001, log-rank test). Uni-and multivariate analyses of the prognostic value of N, T, estrogen receptor/progesterone receptor, and BM status, histological grade, vascular invasion, p53-, c-erb-B2-, and cathepsin D expression were performed. BM status was the only independent prognostic factor for both DDFS and BCSS, whereas c-erbB-2 and N status were independent for BCSS and vascular invasion and T status for DDFS. CONCLUSIONS: ITC in BM 3 years after diagnosis in disease-free breast cancer patients is an independent prognostic factor. Detection of residual disease by BM analysis at follow-up may unravel insufficient adjuvant treatment. The clinical implications should be further explored.

The prognostic value of isolated tumor cells in bone marrow in breast cancer patients: evaluation of morphological categories and the number of clinically significant cells.

UNLABELLED: PURPOSE/EXPERIMENTAL DESIGN: Immunocytochemical detection of isolated tumor cells (ITCs) in the bone marrow (BM) is a prognostic factor in breast cancer. However, hematopoietic cells (HCs) can occasionally be stained by the techniques used. Morphological evaluation improves the specificity of ITC detection, but optimal separation of ITCs from false-positive HCs needs to be determined. Here, predetermined morphological categories of immunocytochemically (ICC)-positive cells in the BM and the number of detected ITCs were analyzed for association with clinical outcome in 817 early-stage breast cancer patients (median 49 months of follow-up). All ICC+ cells detected were categorized into one of the following groups: (a) tumor cell (TC); (b) uninterpretable cell (UIC); (c) probable HC; or (d) HC. RESULTS: Among the TC+ patients, 30.6% and 25.9% experienced systemic relapse (SR) and breast cancer death (BCD), respectively, as compared with 13.3% and 8.5% of patients without TCs in the BM (survival analyses: P < 0.001, log-rank). The SR and BCD rate was 19.7% and 15.8% for TC-/UIC+ patients versus 12.5% and 7.4% for TC-/UIC- patients. Survival analyses confirmed that the UIC+ group contained clinically significant cells (P = 0.018, log-rank). No difference in clinical outcome was observed, regardless of whether probable HCs or HCs were present. Analyzing the number of ITC+ cells, SR and BCD occurred in 12.4% and 7.4% of patients with 0 ITCs present, 21.3% and 18.5% of patients with 1 ITC present, 19.4% and 16.7% of patients with 2 ITCs present, and 42.5% and 32.5% of patients with > or = 3 ITCs present. CONCLUSIONS: Morphological categorization of ICC+ cells improves the clinical value of ITC detection in the BM. The presence of only one ITC reduces survival, and a greater number of ITCs further aggravates the prognosis.

[Sentinel lymph node biopsy in breast carcinoma: the experience from the Norwegian Radium Hospital]. / Biopsi av vaktpostlymfeknute ved brystkreft.

BACKGROUND: We report our experience with sentinel lymph node (SLN) biopsy in breast carcinoma. MATERIAL AND METHODS: The series included 51 women with invasive carcinoma and 3 ductal carcinoma in situ. The first 32 patients underwent axillary lymph node dissection (ALND) independently of the results of the SLN biopsy. SLN was evaluated on frozen sections, paraffin sections and with immunohistochemistry. RESULTS: The surgical detection rate was 98 % with a combined technique of radiocolloid and blue dye. Negative SLN was seen in 36 patients. ALND was done in 19 of these patients, with no metastases found in non-SLN. Metastases were found in SLN in 18 patients, in 3 patients detected only on immunohistochemistry. ALND was done in all positive cases. Three patients had positive non-SLN. INTERPRETATION: SLN biopsy seems accurate in breast carcinoma, performed with the use of radiotracer and blue dye. Immunohistochemistry increases the sensitivity of SLN biopsy.

Significance of Candida recovered from intraoperative specimens in patients with intra-abdominal perforations.

OBJECTIVE: Determine the significance of recovering yeasts from intraoperative specimens from the abdominal cavity and to evaluate the effect of a single intraoperative dose of fluconazole on clinical outcome in patients with intra-abdominal perforations. DESIGN: Prospective, randomized, double-blind study. SETTING: Multicenter study from 13 hospitals in Norway. PATIENTS: One hundred nine patients with intra-abdominal perforations. INTERVENTIONS: Patients were randomized to receive either a single 400-mg fluconazole dose or placebo during the operation. MEASUREMENTS AND MAIN RESULTS: An intra-abdominal specimen for microbiological culture was obtained at the time of the operation. The primary response variable in the study was death. Secondary response variables were three parameters indicating a complicated postoperative period: mechanical ventilation for > or = 5 days, intensive care treatment for > or = 10 days, and use of a central venous catheter for > or = 10 days. Yeasts were recovered from a intraoperative intra-abdominal specimen from only 1 (3.5%) of 28 patients with perforated appendicitis and from 32 (39.5%) of 81 nonappendicitis patients. Excluding the appendicitis patients, the yeast recovery rate was high both for patients hospitalized at the time of the perforation (45%) and for nonhospitalized patients (32%). The overall mortality was 11% (12 patients). Single-dose intraoperative fluconazole prophylaxis did not reach a statistically significant effect on mortality (4 of 53 patients in the fluconazole group and 8 of 56 patients in the placebo group died [p = .059]). The only two explanatory variables significantly related to death were a intraoperative finding of yeast from an intra-abdominal specimen and the occurrence of a spontaneous perforation in a patient already hospitalized for nonsurgical cancer treatment. Detection of yeast was also a significant explanatory variable for a prolonged period of mechanical ventilation, intensive care treatment, and prolonged use of a central venous catheter. CONCLUSIONS: Single-dose intraoperative fluconazole prophylaxis did not have a statistically significant effect on overall mortality (odds ratio = 0.21; 95% confidence interval, 0.04-1.06; p = .059) in patients with intra-abdominal perforation. The recovery rate of yeast from intraoperative specimens from the abdominal cavity was high (>30%) and was associated with death and a complicated postoperative course.