Sentinel node biopsy after primary chemotherapy in cT2 N0/1 breast cancer patients: Long-term results of a retrospective study.

BACKGROUND: It is controversial whether sentinel node biopsy (SNB) is adequate in breast cancer patients who become cN0 after primary chemotherapy. To address this we retrospectively compared outcomes in T2 cases given primary chemotherapy, comparing those given axillary dissection (AD) with those given SNB but no AD if sentinel nodes were clinically negative post-chemotherapy. METHODS: We examined overall survival (OS), disease-free survival (DFS), and axillary failure in 317 consecutive cT2 cN0/1 patients given primary chemotherapy followed by quadrantectomy/mastectomy, between January 2002 and December 2007. The approach to the axilla changed over time allowing division into three groups: 101 (31.9%) given upfront AD; 139 (43.8%) given SNB + AD; and 77 (24.3%) given SNB only because the SNs were negative. RESULTS: After median follow-ups of 92 (AD), 99 (SNB + AD) and 72 months (SNB-only), OS (p = 0.131) and DFS (p = 0.087) did not differ between the 3 groups, or between SNB-only and the ypN1 and ypN0 subgroups of SNB + AD, or between the cN0 and cN1 subgroups (before chemotherapy) of the SNB-only group. No SNB-only patient had axillary failure. OS (p = 0.004) and DFS (p = 0.002) were better in patients with complete response than those with partial response or stable/progressive disease. CONCLUSIONS: SNB is adequate in T2 patients who are cN0 after primary chemotherapy, irrespective of axillary status before. Better outcomes after complete pathological remission confirm the prognostic importance of response to primary chemotherapy, and suggest that all T2 patients should receive primary chemotherapy.

Quantification of natural and synthetic glucocorticoids in calf urine following different growth-promoting prednisolone treatments.

Over the last few years, low levels of prednisolone have been reported in several cattle urine samples by a number of laboratories within the EU at an average concentration of 2.0 ng mL(-1). The occurrence of prednisolone residues together with increased levels of hydrocortisone and cortisone in urine and tissue samples of untreated animals seems to demonstrate that traces of this steroid can be produced endogenously during stressful situations. Therefore, the endogenous origin of prednisolone makes difficult to correlate positive samples to a potential illicit treatment. An experimental study was developed to investigate the presence of natural and synthetic glucocorticoids and to evaluate levels of excreted prednisolone following growth-promoting treatments. Urine samples from calves undergone oral treatment with prednisolone, alone and in association with dexamethasone, were analyzed by a LC-MS/MS method, validated according to the Commission Decision 2002/657/EC. We also investigated if urinary free 6ß-hydroxyhydrocortisone/hydrocortisone ratio could be a reliable biomarker of illicit treatment with prednisolone and dexamethasone in calves. Our data revealed that urinary levels of prednisolone after both oral prednisolone treatments, never exceeded the value of 1.1 ng mL(-1). Similar prednisolone levels were found in urine samples of untreated calves. Moreover the presence of 6ß-hydroxyhydrocortisone below the CCα value made possible to estimate the 6ß-hydroxyhydrocortisone/hydrocortisone ratio only in a very limited number of samples. Obtained data suggest that further criteria have to be considered to allow correct decisions about the urinary presence of prednisolone during control activities.

Development of an enhanced histopathological approach to detect low-dose dexamethasone illicit treatment in veal calves.

Dexamethasone is one of a number of synthetic corticosteroids illegally used to promote growth in food-producing animals. Since these low-level drug cocktails evade detection by currently available chemical methods, simple biological indicators that can aid in laboratory analysis are needed. In an attempt to devise an accurate biological method that could detect illicit drug treatment in food-producing animals, we characterized microscopic morphologic alterations of the thymus in veal calves administered low-dose dexamethasone versus control animals. For this purpose, 122 male calves were farmed for 6 months in controlled condition: 81 animals were orally administered dexamethasone (0.4 mg day(-1)) for 20 days during the sixth month and the remaining 41 were kept as control. Urine samples were collected systematically during the treatment period, the suspension period and at the slaughterhouse. All animals were slaughtered 10 per day starting from 10 days after the last dexamethasone administration and the thymus was sampled for histological examination. The difference between the two animal groups was evaluated by means of a non-parametric test of hypothesis. No residues were detected in the urines collected since the third day after the last administration, whereas morphometric analysis of the thoracic thymus revealed a significant decrease in the cortex:medulla ratio in the treated animals (p<0.0005). We can conclude that this histological approach offers encouraging prospects as a screening method to overcome current limitations in controlling growth promoter abuse.

Benign breast lesions: Ultrasound.

Benign breast diseases constitute a heterogeneous group of lesions arising in the mammary epithelium or in other mammary tissues, and they may also be linked to vascular, inflammatory or traumatic pathologies. Most lesions found in women consulting a physician are benign. Ultrasound (US) diagnostic criteria indicating a benign lesion are described as well as US findings in the most frequent benign breast lesions.

In vitro activity of cefditoren versus other antibiotics against S. pneumoniae clinical strains isolated in Italy.

Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 micrograms/ml obtained could be particularly significant in therms of therapeutic predictivity.

Excretion profile of boldenone and its metabolites after oral administration to veal calves.

The residue profiles of boldenone (17beta-Bol), its epimer (17alpha-Bol) and the related compound androsta-1,4-diene-3,17-dione (ADD), were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in urine of male calves orally treated with boldenone, boldenone esters, and/or ADD. In all the experiments with the administered steroids residues of 17alpha-Bol decreased rapidly after end of treatment; detectable amounts of 17alpha-Bol were however noticed along the withdrawal observation period after end of treatment. Differently, residues of 17beta-Bol were detectable only shortly after administration. This in vivo research concerning oral treatments of cattle with boldenone related substances proves ADD to be a very active boldenone precursor in bovine animals.

Excretion profile of boldenone in urine of veal calves fed two different milk replacers.

The residue profiles of 17alpha-/17beta-boldenone conjugated (17alpha/beta-Bol) and ADD were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in urine of male veal calves fed two commercial milk replacers, with different content of cholesterol and phytosterols. The urine samples were collected within 4 h after feeding and further from all the animals. Detectable amounts of 17alpha-Bol conjugated were measured in urine collected from all calves, but the concentrations of 17alpha-Bol were higher in urine from calves receiving the milk replacer with the greater amount of phytosterols. During the whole experiment, 17beta-Bol and ADD were never detected in urine samples collected.

Analysis of anabolic steroids in hair by GC/MS/MS.

A simple and sensitive gas chromatography/tandem mass spectrometry (GC/MS/MS) method is described for the detection of anabolic steroids, usually found in keratin matrix at very low concentrations. Hair samples from seven athletes who spontaneously reported their abuse of anabolic steroids, and in a single case cocaine, were analyzed for methyltestosterone, nandrolone, boldenone, fluoxymesterolone, cocaine and its metabolite benzoylecgonine. Anabolic steroids were determinate by digestion of hair samples in 1 m NaOH for 15 min at 95 degrees C. After cooling, samples were purificated by solid-phase and liquid-liquid extraction, then anabolic steroids were converted to their trimethylsilyl derivative and finally analyzed by GC/MS/MS. For detection of cocaine and benzoylecgonine, hair samples were extracted with methanol in an ultrasonic bath for 2 h at 56 degrees C then overnight in a thermostatic bath at the same temperature. After the incubation, methanol was evaporated to dryness, and benzoylecgonine was converted to its trimethylsilyl derivative prior of GC/MS/MS analysis. Results obtained are in agreement with the athletes' reports, confirming that hair is a valid biological matrix to establish long-term intake of drugs.

Changes in plasma level of human leukocyte elastase during leukocytosis from physical effort.

Physical exercise is known to induce immunological changes, mainly leukocytosis and neutrophil activation. However, it is not known to what extent the leukocytosis, observed after exertion, is associated with an increase in plasma neutrophil elastase, an early marker of inflammatory response and neutrophil degranulation. In the present study changes in circulating leukocyte and neutrophil counts and human neutrophil elastase plasma levels were evaluated in volley-ball players before and after 2 h and 12 h prolonged training, during a competition season. For comparison, the same parameters were evaluated in untrained subjects before and after a jogging session. Basal white blood cell WBC, polymorpho nuclear PMN, and human polymorpho nuclear-elastase PMN-ELA values were within the normal healthy reference range and no significant differences were found between the two groups studied. Venous blood samples of nine volley-ball players showed a statistically significant increase in blood WBCs after 2 h exercise. This effect was paralleled by a statistically significant increase in PMN-ELA concentration compared to the values observed in the same individuals at rest. The exercise did not significantly change the basal correlation parameters between PMN level and PMN-ELA concentration. More pronounced WBC, PMN, and PMN-ELA increases were observed in the seven inactive subjects after 2 h jogging. There was no linear correlation between increased PMN counts and increased PMN-ELA concentrations in untrained subjects after exercise. The results show that not only the leukocyte count but also PMN-ELA plasma levels can be higher after physical effort. This has a practical significance as regards differential diagnosis demonstrating that determination of these two laboratory parameters can give abnormally high values even in the absence of an existing inflammatory process. Besides, lack of correlation between PMN count and PMN-ELA plasma levels in the untrained group suggest a state in which activation of the neutrophils is not connected with their number in peripheral blood.

Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer.

Non-palpable breast cancers are often in situ or smaller and have less nodal and distant metastases than palpable lesions. They represent a heterogeneous group of tumours, which may have different prognostic behaviour. We analysed a retrospective series of 982 non-palpable breast cancers assessed histologically at the National Cancer Institute of Milan from 1985 to 1995, following pre-operative mammography-guided localization. The association between mammographic data (parenchymal pattern and findings), patient age and tumour histology was investigated by review of clinical records and statistical modelling. We also investigated the association between the presence or absence of microcalcification as a mammographic finding and pathological tumour characteristics (tumour size, axillary nodes status and grading) or receptor status for oestrogen (ER) and progesterone (PgR). In situ disease or invasive tumour with an intraductal component, whether extensive or not, were commoner in young women and mammography more frequently showed a dense parenchymal pattern and microcalcifications in these cases. In older women (55 years or more), a fatty breast pattern, nodular opacities with or without microcalcifications, and invasive tumours of the ductal, lobular, mixed or other types were closely related. When the relationships between mammographic findings, pathological tumour characteristics and receptor status were investigated for invasive cancers, there was an association between the presence of microcalcifications and less favourable tumour characteristics.

Intermediate doses of cyclophosphamide alone or following adriamycin in advanced breast cancer. A pilot study.

Cyclophosphamide (CTX) is an active drug in breast cancer and presents a well-established dose-response relationship. To explore further this relationship, the present pilot study investigated the therapeutic efficacy of cyclophosphamide at intermediate dose in two groups of untreated patients with advanced breast cancer. Nine women received the drug alone at 3-4 g/m2 i.v. every 2 weeks for a total of three doses. The same dose schedule was also given to 11 women following the administration of four cycles of Adriamycin, at 75 mg/m2 i.v. every 3 weeks. We documented one partial remission in untreated women and four partial responses in Adriamycin-treated patients. The major toxicity was represented by leukopenia and neutropenia. Myelosuppression was relevant but of short duration, and the use of G-CSF appeared useful in controlling this side effect. In spite of the high dose intensity of the present cyclophosphamide dose schedule (9 g/m2 in 4 weeks), i.e., almost three times superior to that conventionally employed, present results do not suggest its superiority over the current chemotherapeutic regimens utilized in advanced disease.

[Microcalcifications in non-palpable breast carcinoma. Analysis of 427 cases]. / Le microcalcificazioni nei carcinomi mammari non palpabili. Analisi di 427 casi.

Of 836 nonpalpable breast lesions histologically assessed between 1985 and 1991 at the Milan Cancer Institute, 427 were malignant (51%). Microcalcifications were present in 283 tumors (66%), alone in 200 cases or associated with a mass (72 cases) or within a focal distortion (11 cases). Several mammographic, clinical and histological features were analyzed, comparing the 283 lesions with microcalcifications with the 144 tumors represented only by nodular opacities or distortions. This was done to assess the existence of morphologic and prognostic characters differentiating the two subsets and to investigate the reliability of mammography in estimating lesion size. On the average, in our series of cases, the patients with microcalcifications were younger, had a higher rate of dense breasts and a large number of partially or totally intraductal carcinomas. In situ carcinomas were frequent and minimal lesions (< 5 mm) accounted for 43% of the whole at pathologic examination. However, the lesions with microcalcifications were associated with more positive nodes (32% vs 18%). Therefore, microcalcifications, although generally representing an early sign of cancer, appear to suggest a less favorable prognosis.

[Direct radiographic enlargement in mammography in everyday practice. Indications and limitations]. / Ingrandimento radiografico diretto nella mammografia nella pratica quotidiana. Indicazioni e limiti.

One thousand mammograms of non-preselected patients were reviewed in order to assess in how many and which cases an equivocal diagnosis can be made unquestionable and to test the value of follow-up exams with direct radiographic magnification. Direct radiographic magnification was used in all questionable cases (3%): 18 lesions were characterized by microcalcifications and 12 by nodules. Four cases were diagnosed as unquestionable (13%)-1 microcalcification and 3 nodules-while 13 patients were reexamined with mammography only. Even though the percentage variation from equivocal to unquestionable diagnoses is modest but significant, direct radiographic magnification is always useful in the follow-up.

Mammographic patterns in breast cancer chemoprevention with fenretinide (4-HPR).

In 1987 a chemoprevention trial was started at the Istituto Nazionale Tumori of Milan to evaluate the efficacy of fenretinide or 4-HPR (an effective agent against carcinogen-induced epithelial tumours in experimental animals) in reducing the incidence of contralateral breast cancer in women previously treated for an early breast cancer (pT1, pT2, N-). Patients were randomised into two groups: 4-HPR 200 mg/day vs. no treatment. We reviewed the mammograms of 149 patients who received 4-HPR for at least 4 years to examine whether changes seen in the mammary glands of rats could also be seen in women. For each patient, at least five mammograms (one at baseline and four annual controls) of the contralateral breast were classified according to Wolfe's parenchymal patterns (N1, P1, P2, DY). With the daily dosage of 200 mg and after follow-up, no changes in mammographic patterns were observed.

[Microcalcifications in the diagnosis and follow-up after the primary chemotherapy of breast neoplasms]. / Le microcalcificazioni nella diagnosi e nel follow-up dopo chemioterapia primaria delle neoplasie mammarie.

Since 1998, at the National Cancer Institute (Milan, Italy), a study has been carried on relative to primary chemotherapy for locally advanced breast cancers (greater than 3 cm diameter). Aim of the study is to obtain tumor reduction and thus allow a conservative treatment to be performed. The measures of the two greatest diameters of the tumor by means of mammography, at diagnosis and after chemotherapy, are important parameters for treatment planning. Among the 213 patients who completed the whole diagnostic-therapeutic procedures by December 1990, the authors chose 94 cases (44%) presenting breast cancers with microcalcifications and reviewed the relative mammograms. The review was aimed at analyzing morphology, number and extent of the microcalcifications and at assessing their value as reliable parameters of cancer response to primary chemotherapy. In their experience, the authors found that increased visibility of the microcalcifications after chemotherapy is often due to a reduction in both edema and lesion opacity. On the contrary, fewer microcalcifications may be correlated with incisional diagnostic biopsies. In conclusion, if microcalcifications are a useful parameter for diagnosis, they alone are less important when evaluating response to primary chemotherapy, since they probably represent a permanent sign of the extent of the primary lesion. All follow-up mammograms of the patients who underwent conservative surgery were also reviewed: no residual microcalcifications or other suspicious abnormalities were observed.

[Nonpalpable breast lesions. General considerations and a review of the literature in the light of the authors' own experience with 344 cases located preoperatively]. / Lesioni mammarie non palpabili. Considerazioni generali e revisione della letteratura alla luce della esperienza personale su 344 casi di localizzazione preoperatoria.

The widespread use of mammography in breast cancer screening has increased the number of non-palpable breast lesions being detected in which the differential diagnosis between benign and malignant cases requires surgical biopsy. In order to remove these mammographically identified lesions the surgeon must be guided, which is why the techniques guiding the surgeon during lesions ablation have become most important. Accurate preoperative lesion localization must be done so that the excision can be complete and with the best cosmetic result. In this report we discuss localization methods, from the simplest to the most complicated ones. The commonest method has the advantage of employing no special instruments, and it is very simple, safe and fast. It requires a skilled hand and a little training. Instrumental methods are then discussed, from the simple dedicated compressor to the stereotactic techniques and, finally, the role of ultrasonography both in preoperative localization and in cytologic biopsy. The importance of mammographic examination of the surgical specimen is also stressed.

Preoperative localization and surgical approach in 344 cases of non-palpable breast lesions.

From June 1985 to August 1989, 344 cases of mammographic non-palpable breast lesions were operated on at the National Cancer Institute in Milan. The mammographic findings consisted of clusters of microcalcifications in 162 cases (42.1%), suspicious opacities with irregular borders in 116 cases (37.7%) and opacities containing microcalcifications in 66 cases (19.2%). The mean age of the patients was 51 years (range 31-77 years). In all patients localization was performed 1 day before the operation, introducing a self-retaining anchor wire into the mammary parenchyma. The histological findings showed benign breast disease in 184 cases (53.4%); proliferative dysplasia without atypia in 150 cases (81.5%); proliferative dysplasia with atypia in 22 cases (12%); fibroadenoma in nine and papilloma in three cases. Of 160 patients with carcinoma, 37 had non-infiltrating carcinoma: 28 of these cases (17.5%) had non-infiltrating ductal carcinoma and nine cases (5.6%) had lobular carcinoma in situ. In the 123 cases with infiltrating breast cancer the histological types were ductal infiltrating carcinoma (32.5%), lobular infiltrating carcinoma (9.8%), and 34.1% of the cases an associated or prevalent intraductal carcinoma was found. In 138 cases (85.6%) a conservative surgical procedure (quadrantectomy or more limited excision) was done, and in 22 (14.4%) cases a total mastectomy was necessary because of the extent of the disease. Axillary dissection was performed in 116 of the 123 patients with histological invasive carcinoma. Nodal metastases were found in 24 cases (20.7%), and only one node was involved in nine of the cases (37.5%), two to three nodes in nine cases (37.5%) and four to ten nodes in six cases (25%).