Paolo Pacini

Preoperative staging of primary breast cancer. A multicentric study.

This article reports on a consecutive series of 3627 breast cancer (BC) patients undergoing preoperative staging by chest x‐ray (CXR), bone x‐ray (BXR) or bone scintigraphy (BS), and liver ecography (LE) or liver scintigraphy (LS). The detection rate (DR) of preclinical asymptomatic distant metastases depended on the T and N category (TNM classification system), and was very low (CXR: 0.30%, BXR: 0.64%, BS: 0.90%, LE: 0.24%, LS: 0.23%). The sensitivity, determined after a 6‐month follow‐up, was below 0.50% for all tests. The highest value (0.48%) was recorded for BS, which also had the lowest specificity (0.95%). The entire preoperative staging policy using the studied tests seems questionable due to poor sensitivity and an extremely low DR of distant metastases.

EFFECT OF 0.2 T STATIC MAGNETIC FIELD ON HUMAN NEURONS : REMODELING AND INHIBITION OF SIGNAL TRANSDUCTION WITHOUT GENOME INSTABILITY

We describe the effect of the static magnetic field generated by a 0.2 T magnetic resonance tomograph on a normal human neuronal cell culture (FNC-B4). After 15 min exposure cells showed dramatic changes of morphology: they formed vortexes of cells and exposed branched neurites featuring synaptic buttons. At the same time, thymidine incorporation and inositol lipid signaling were significantly reduced. Control (sham exposed) or non-neuronal cells (mouse leukemia, and human breast carcinoma cells) did not show any alteration following exposure. Endothelin-1 release from FNC-B4 cells was also dramatically reduced after 5 min exposure. However, PCR analysis of 12 DNA microsatellites selected as gauges of genome instability, did not reveal any alteration following exposure, thus ruling out a direct effect of the magnetic field on DNA stability. These data can be interpreted as a specific effect of the static magnetic field on human neuronal cells and are consistent with the induction of remodeling and differentiation; they demonstrate that fields below 0.5 T have significant biological effects on human neurons.

Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT-PCR for cytokeratin-19 mRNA

There is considerable interest in an autologous transplantation (AT) programme for patients with high‐risk breast cancer; however, the issue of the incidence of occult bone marrow (BM) micrometastasis at diagnosis, and the cancer contamination of peripheral blood stem cell (PBSC) collections used for haematological rescue, is still debated. The presence of BM micrometastasis was evaluated in bilateral BM biopsies obtained at diagnosis of 33 patients with stage II/IIIA breast cancer using: (i) a ‘nested’ reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay for cytokeratin 19 (K19) mRNA, (ii) histology, and (iii) immunohistochemistry (IHC) analysis with a panel of three monoclonal antibodies. The RT‐PCR assay only was used to determine contamination of PBSC collections obtained after priming with recombinant human granulocyte‐colony stimulating factor (rhG‐CSF). K19 transcripts in one or both BM samples  were detected in 48% of patients at diagnosis, with an overall 85% concordance with the results of IHC analysis. On the other hand, 56% of PCR‐ and IHC‐positive BM samples were diagnosed as ‘normal’ on histological analysis. 57% of patients showed K19 mRNA in at least one PBSC collection; the possibility to have contaminated PBSC collections was significantly higher in patients with K19 positivity in BM at diagnosis. In four patients who had shown K19 positivity in BM and in PBSC collections, immunoselected CD34+ cells used for haematological rescue were K19‐negative. There was a trend towards longer relapse free survival (RFS) in patients transplanted with K19‐negative PBSC collections as compared to the others. In conclusion, a substantial proportion of patients with high‐risk non‐metastatic breast cancer present occult BM micrometastasis at diagnosis and also show cancer contamination of PBSC collections used for AT. These might represent a category of patients with poorer prognosis after AT, and possible candidates for more intensive and/or alternative therapeutic regimens, including AT with purged PBSCs.

Male Breast Carcinoma: Review of a Multicenter Series of 150 Cases

The authors report on a consecutive retrospective series of 150 male breast cancers. Clinical, diagnostic and therapeutic features are compared over time and with respect to a large consecutive series of female breast cancers. Both age at diagnosis and tumor stage were more advanced in males than in females. Poor alertness of both men and doctors for this unfrequent disease may account for such a delay in diagnosis. The use of mammography increased over time and sonography or cytology were frequently and successfully employed in the last decade. Unfortunately no improvement of tumor stage at diagnosis was observed over time in the present series. A time trend was also evident for the type of surgical and postoperative treatment. Modified radical mastectomy and adjuvant chemo- or hormone therapy were increasingly adopted, although Halsted operation and postoperative radiotherapy were still common in the last decade due to the relatively high proportion of locally advanced T3-4 cancers. Both disease-free and overall survival were worse in men than in women, even after adjustment by stage at diagnosis. This study suggests that male breast cancer has a worse prognosis with respect to female breast cancer and provides no complete explanation of this finding, except for an intrinsic higher aggressivity. No evidence was found which may justify a different diagnostic or therapeutic approach with respect to female breast cancer.

Disease-Free Survival Advantage of Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil in Patients With Node-Negative, Rapidly Proliferating Breast Cancer: A Randomized Multicenter Study

PURPOSE According to one of the most recent key scientific questions concerning the use of biomarkers in clinical trials, we investigated whether node-negative breast cancer patients, defined as high-risk cases on the basis of tumor cell proliferation, could benefit from cyclophosphamide, methotrexate, and fluorouracil (CMF) adjuvant therapy. PATIENTS AND METHODS Two hundred eighty-one patients with negative nodes and rapidly proliferating tumors, defined according to thymidine labeling index (TLI), were randomized to receive six cycles of CMF or no further treatment after surgery +/- radiotherapy. RESULTS The 5-year disease-free survival (DFS) was 83% for patients treated with CMF compared with 72% in the control group (P: =.028). Adjuvant treatment reduced both locoregional and distant metastases. When clinical outcome was analyzed in cell kinetic subgroups characterized according to tertile criteria, compared with patients in the control arm, 5-year DFS was significantly higher after adjuvant CMF in patients with TLI values in the second (78% v 88%, respectively; P: =.037) and third tertiles (58% v 78%, respectively; P: =.024). CONCLUSION The results from this randomized clinical study indicate that patients with node-negative, rapidly proliferating tumors significantly benefit from adjuvant CMF.

Filippo Pacini: a determined observer.

The life of Filippo Pacini (1812-1883) and his major scientific achievements are outlined. Pacini drew attention to the corpuscles named after him in 1831, when he was a medical student, and had to struggle for many years to convince the scientific community of the reliability and importance of his findings. In 1849 Pacini became professor of anatomy at the University of Florence. Creative scientist, innovative teacher, well aware that the use of the microscope represented a revolutionary approach, Pacini pursued histological studies until his death. He also first discovered in 1854 (30 years before Robert Koch) the causative agent of cholera, and firmly believed that the disease was contagious. Strong-willed, modest, and poor, Pacini received from his colleagues more recognition in the obituaries than during his life.

Risk of endometrial cancer in breast cancer patients under long-term adjuvant treatment with tamoxifen.

Aims To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. Methods A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. Results A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and December 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screening examinations. SIR was 4.0 (95% confidence interval, 1.39.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. Conclusions This study adds evidence to the hypothesis that long-term tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach.

Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients.

Purpose: To evaluate the endocrinological and clinical activity of a new slow-release formulation of leuprolide acetate in breast cancer patients. Methods: A total of 50 pre- or perimenopausal patients with early- or late-stage breast cancer who were candidates for endocrine treatment were included in the study and randomly allocated to receive either 3.75 mg of leuprolide acetate every month or 11.25 mg of leuprolide acetate every 3 months. Patients were treated until disease recurrence or progression or for a maximum of 24 months. Treatment outcome, side effects, and serum levels of gonadotrophins, estradiol, progesterone, and Δ4-androstenedione were analyzed at different time points. Results: In all, 23 patients were allocated to the monthly formulation and 27, to the 3-monthly formulation. The median time on treatment was comparable. There was no evidence of any difference in clinical outcome or drug-induced side effects, hot flushes being recorded in about 50% of patients in both groups. Altogether, 35 patients were actively menstruating at the beginning of treatment; all of them became amenorrhoic after 3 months and remained so until treatment with leuprolide was continued, irrespective of the allocated treatment. All endocrine parameters, particularly estradiol levels, were suppressed to a similar extent. Conclusions: The present results indicate that the two formulations exert a comparable estrogen-suppressive effect and warrant further study of the 3-monthly formulation of leuprolide acetate in breast cancer patients.

In vitro effects of some differentiation inductors in metaplastic epithelium of the human nasal cavity

Abstract.The alterations in the mucociliary unit in the course of chronic inflammation of the upper respiratory tract correspond to morphologic anomalies of the respiratory epithelium and induce cuboidal and squamous metaplasia. While the squamous pattern is most probably irreversible, it is still not clear whether it is possible to restore ciliogenesis in cuboidal metaplasia. In the present study, the action of different inductors of differentiation was evaluated in vitro in isolated cells and explants from human nasal metaplastic epithelium. Polar/apolar compounds induced secretory activity, whereas retinoic acid was able to induce ciliogenesis in some cases. Therefore, the cuboidal metaplastic condition appears to be reversible, and two distinct pathways of differentiation, secretory and ciliogenetic, are identifiable.

Scanning electron microscopic evaluation of the alterations induced by polluted air in the rabbit bronchial epithelium

With the aim of evaluating the influence of polluted air on the respiratory epithelium, ten New Zealand white rabbits, from a group of fifteen kept in the country, were transported to a site located in a metropolitan area. After 40 days, all the rabbits were killed, and the bronchial mucosa studied by scanning electron microscopy (SEM). In the animals exposed to polluted air, the ciliated cells, less numerous than in normal cases, show an evident decrease in the number and size of the cilia, exposing apical microvilli. It is therefore possible to hypothesize that a part of the non-ciliated cells is made up of cells that have lost their cilia. The number of non-ciliated elements and the amount of mucous secretion appear to have noticeably increased. The considerable response of the respiratory epithelium to inhaled agents appears to be confirmed, as is the irritant effect of polluted city air.