Italian Men Tested for BRCA1/2 Mutation: Psychological Distress during 6-Month Follow-Up.

Introduction. Male breast cancer (MBC) is a rare disease, whose main risk factor is genetic vulnerability. Despite care of men with MBC is modeled on care of women, men's experiences with the disease and concerns related to the status of genetic mutation carrier are unique. So far, little is known concerning the psychological impact in BRCA1/2 testing, especially with regard to specific subset of individuals, such as male subjects and the elderly. METHODS: We assessed self-reported anxiety and depression levels in 26 male subjects presenting at Unit of Breast Surgery in Breast Unit of AOUI Verona (MBC patients, n = 7; high-risk unaffected subjects, n = 7; high-risk unaffected subjects. RESULTS: Among the 17 unaffected men tested, 7 (41%) received a positive test (either BRCA1 or BRCA2 pathogenic variant) and 10 (59%) a negative test. Of the 9 MBC patients tested, only one subject received a positive test result. No significant differences were observed in mean scores, mean change from baseline to follow-up, either for those with T+ or T- test results. Discussion. Genetic testing for BRCA1/2 mutation was not associated in our sample with increased level of psychological distress as measured with HADS in a short-term evaluation.

Secondary breast angiosarcoma: A multicentre retrospective survey by the national Italian association of Breast Surgeons (ANISC).

BACKGROUND: Breast angiosarcoma is a malignant mesenchymal neoplasm, which accounts for approximately 2% of all soft tissue sarcomas. Secondary breast angiosarcoma (SBA) may be related to chronic lymphedema after a mastectomy with lymph node dissection (Stewart Treves syndrome) and previous radiotherapy for complications from breast radiation treatment. It is a very rare condition; therefore, diagnosis and management are still a challenge. METHODS: The ANISC collected SBA data by means of a survey sent to all Italian breast centres in the ANISC. The clinicopathological characteristics and the management of this disease were analysed. RESULTS: Twenty-four centres participated in this survey in which 112 cases of SBA were analysed. The median age of the women with SBA was 68.9 years and it appeared approximately 90 months after the first irradiation for breast cancer. In 92% of cases, a mastectomy was performed without axillary dissection for those patients having a high grade of SBA (74.2%). The prognosis was worse in the high-grade cases (overall survival-OS: 36 months) as compared with the low-grade cases (OS: 48 months). After a follow-up of 5 years, 50.5% of the patients were still alive. Disease-free survival (DFS) was 35 months, and there were no differences between the groups of patients with either high- or low-grade histology. CONCLUSIONS: Secondary breast angiosarcoma is a very aggressive disease associated with a short survival outcome. The surgical approach still remains an important step in the course of treatment; furthermore, an accurate histological examination is helpful in establishing the prognosis of the patient. A mastectomy is mandatory. A longer OS was observed in patients with low-grade angiosarcoma as compared to high-grade angiosarcoma (C.I. 40-57 vs. 31-41 months).

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey.

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014-2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

Inflammatory breast carcinoma and locally advanced breast carcinoma: characterisation with MR imaging.

PURPOSE: This study was done to identify the typical magnetic resonance (MR) imaging findings of inflammatory breast carcinoma (IBC) in comparison with noninflammatory locally advanced breast carcinoma (LABC). MATERIALS AND METHODS: MR images of 30 patients with IBC (T4d) were compared with those of a cohort of 30 patients with LABC (T3/T4a-c). The age distribution was approximately equal in the two groups. MR images were assessed for the following features: skin thickening (>4 mm), skin oedema, architectural distortion, enhancement pattern (mass-like/non-mass-like), time-signal intensity curve (continuous-persistent type/wash-out type), skin enhancement. Fisher's exact text was used to compare MR imaging appearances of IBC and LABC (significant p value <0.05). RESULTS: Skin involvement and enhancement pattern differed between groups: skin thickening was present in 16/30 IBC (53%) vs 8/30 LABC cases (27%, p=0.06), skin oedema was present in 26/30 IBC (87%) vs 8/30 LABC (27%, p < 0.0001), and skin enhancement in 10/30 IBC (33%) vs 2/30 LABC (7%, p=0.02); non-mass-like enhancement was present in 22/30 IBC (73%) vs 12/30 LABC (40%, p=0.02). CONCLUSIONS: IBC is a distinct clinical and pathological entity resulting in typical MR imaging features. Skin changes (thickening, oedema, enhancement) related to neoplastic involvement of the dermal lymphatics are suggestive of IBC and should prompt a skin biopsy to confirm or rule out the diagnosis.

Intra-operative frozen section technique for breast cancer: end of an era.

Data on 2436 primary breast carcinomas diagnosed between 1992 and 2006 were collected to evaluate the rate of frozen section procedures performed over time. Frozen section procedures performed to evaluate resection margins for conservative surgery or sentinel node status were excluded. Over time, there was a decrease in the use of frozen sections indistinctly extended to all pT cancer categories. The rate of cancers diagnosed with frozen sections was 51.2% in 1999, and 0% in 2005-2006. In the same period, the adoption of cytology and core biopsy for breast cancer diagnosis increased from 40% in 1992 to more than 90% since 1999. In an audited diagnostic activity on breast pathology, the routine use of frozen sections on primary lesions was considered inappropriate, particularly in assessment of clinically non-palpable lesions, and should be limited to cases with inadequate pre-surgical sampling.

Inflammatory breast cancer: MR imaging findings.

PURPOSE: This paper describes the magnetic resonance (MR) imaging features of primary inflammatory breast cancer (IBC). MATERIALS AND METHODS: Two radiologists reviewed the MR examinations of 14 women with a pathological diagnosis of IBC. Images were assessed for skin thickening, oedema, nipple retraction, architectural distortion, type and extent of parenchymal and cutaneous enhancement and enhancement kinetics over time, axillary and internal mammary lymphadenopathy, pectoral muscle enhancement and additional findings. RESULTS: Skin thickening was identified in eight patients (58%), oedema in nine (64%), nipple retraction in two (14%), architectural distortion in eight (58%), mass-like enhancement in five (36%), non-mass-like enhancement in nine (64%) with washout enhancement curve in 12 (86%) and plateau curve in two (14%), axillary lymphadenopathy in 12 (86%) and internal mammary artery lymphadenopathy in two (14%), and pectoral muscle enhancement in one (7%). Additional findings included increased breast volume in two patients (14%), prepectoral fluid in four (28%) and hypertrophic internal mammary artery in three (21%). CONCLUSIONS: The most characteristic MR findings of IBC are skin thickening, oedema, architectural distortion, mass-like enhancement with washout curve and axillary lymphadenopathy; less frequent ones are nipple retraction, mass-like enhancement and internal mammary lymphadenopathy. Prepectoral fluid is frequent but is not a sign of infiltration.

Comparative in vitro activity of garenoxacin against Chlamydia spp.

The in vitro susceptibilities of 33 isolates of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci to a new quinolone drug, garenoxacin (BMS-284756), in comparison with levofloxacin, ciprofloxacin, doxycycline, erythromycin and roxithromycin, were determined. Garenoxacin was the most active of the quinolone drugs tested, with identical MIC and MBC, which ranged from 0.007 to 0.03 mg/L. The MIC and MBC of the other two quinolones tested, levofloxacin and ciprofloxacin, were also identical, ranging from 0.25 to 2 mg/L. The MICs and MBCs of doxycycline, erythromycin and roxithromycin were also determined.

A new synthetic approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one(J-113397), the first non-peptide ORL-1 receptor antagonist..

An efficient approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one (J-113397) 1, the first non-peptide ORL-1 receptor antagonist described in literature, is outlined. After construction of the piperidine framework through Dieckmann cyclization of the Michael adduct 8 of cyclooctylmethylamine to methyl acrylate, condensation with o-phenylendiamine produced the beta-enamino ester 2, which has been conveniently used to construct the benzimidazolone substituent at C-4. Catalytic hydrogenation of intermediate 11 followed by base-promoted cis--trans isomerization of the key compound 12 led to the formation of ester 13, which was converted to the racemic title compound by LiAlH(4) reduction. The pure enantiomers were obtained by chiral preparative HPLC separation using a derivatized cellulose-based stationary phase.

Solid-phase synthesis of indolizidine and quinolizidine derivatives.

An efficient method for the construction of simple indolizidine and quinolizidine derivatives on solid support has been developed. An intramolecular tandem Michael reaction initiated by the nucleophilic attack of a suitably placed amino group on the tethered Wittig condensation products between 4- or 5-aminoaldehydes attached to a trityl chloride resin and 4-[(4-methylphenyl)sulfonyl]-1-(triphenylphosphoranylidene)-2-b utanon e is the key step.

[Surgical repair of pectus excavatum by internal metal strut fixation. Clinical experience in 51 cases]. / Riparazione chirurgica del petto escavato mediante fissazione interna con barre metalliche. Esperienza clinica su 51 casi.

BACKGROUND: Broad is the spectrum of congenital chest wall deformities. Fortunately the severe life-threatening deformities (i.e. ectopia cordis and Jeune's disease) are rarer than the more frequent pectus excavatum and carinatum. Funnel chest is the most common anterior chest wall deformity, it results from posterior depression of the sternum and cartilages, from the third to the eighth; it occurs more frequently in boys than in girls (4:1 ratio). While the deformity may be recognizable at birth, especially during crying spells, it progressively worsens during childhood, producing, sometimes, respiratory and cardiac impairment. METHODS: The authors report their experience, from April 1970 to December 1998, in correction of Pectus Excavatum using a single surgical technique, at the Borgo Roma Hospital of Verona. During this period 51 patients (mean age 14 years) affected by this deformity, were treated performing a sterno-chondroplasty with internal fixation. Most of the patients (94%) required operation for the esthetic and psychological reasons only. The grade of funnel chest (according to the Chin Classification) was: type I in 59.6% of patients, type II in 31.4% and type III in 11.7%. The surgical technique consisted in the modification of the Ravitch's technique (subperichondrial cartilage resection, transverse osteotomy with internal stainless steel strut fixation). We considered the intervention advisable to correct an existing defect or to prevent its progression. We don't think, in fact, that spontaneous recession of the deformity may occur. RESULTS: The follow-up varied from 4 to 18 years. The result was classified according to the classification of Humphreys and it was excellent in 64.7%, good in 17.7%, fair in 9.8% and poor in 7.8%. CONCLUSIONS: This technique proved to be safe and effective, it can be performed with no mortality, very low complication rate and satisfactory results.

Prognostic significance of estrogen receptors in 405 primary breast cancers: a comparison of immunohistochemical and biochemical methods.

Over the last few years, estrogen receptor determination by means of immunohistochemistry has been extensively used. The aim of this study was to compare this technique with estrogen receptor determination by means of dextran-coated charcoal, and to evaluate whether one of the two methods is more predictive of prognosis. Estrogen receptors were determined by means of both the dextran-coated charcoal method and immunohistochemistry in 405 patients with primary breast cancer; age, pathological tumor size, nodal status, and progesteron receptors by dextran-coated charcoal method were also recorded. The disease-free and overall survival probabilities were estimated using the product-limit method; Cox's proportional hazard model was used to evaluate the prognostic role of estrogen receptors as determined by the two methods. There appears to be a close association between estrogen receptor determination by the two methods (81.5% of concordant results) and their prognostic role was similar, even when the patients were divided into different groups (on the basis of their estrogen receptor status) and adjustments for the effect of other prognostic variables were taken into account. Our study shows that the two methods can be used indifferently to evaluate estrogen receptor status as a prognostic factor in breast cancer patients.

[Role of macrophages in papillomavirus infections]. / Rôle des macrophages dans les infections a papillomavirus.

Papillomaviruses have naturally a strict tropism to epithelial cells in which they replicate during the cell differentiation. There is no histological evidence of any inflammatory reaction. No leucocyte recruitment is observed and thus, the role of macrophages during the early infectious process in the epithelium remains unknown. This silent, subacute or chronic infectious disease is characterized fundamentally by a dual pathogenic process, including an infectious process leading to the production of infective virus particles during the differentiation of infected epithelial cells, on the one hand, and an oncogenic process due to interactions of viral oncogenes with host cell regulatory proteins after integration of the virus to the cellular genome. The role of activated macrophages on the oncogenic process is clearly established. They contribute to regulate negatively the transcription of the non structural E6 E7 viral oncogenes and have cytotoxic effects to transformed cells by a direct intercellular contact without evidence of an effect due to a soluble factor such as tumor-necrotizing factor (TNF). Macrophages have, hence, a prominent role as cellular effectors of protective immunity against lesions due to papillomaviruses and particularly against the oncogenic process complicating these infections.

[Evaluation of the tolerance of a lipid emulsion administrated during total parenteral nutrition in surgical patients]. / Valutazione della tollerabilità di una emulsione lipidica somministrata in corso di nutrizione parenterale totale in pazienti chirurgici.

Tolerance's evaluation of a lipid emulsion given in course of parenteral total nutrition in surgical patient's. The first fat emulsions for intravenous application were thrown on the market in the 1920's years. Authors make a study on a limited sample of surgical patients about type and incidence of both immediate and late adverse reactions versus intravenous administration of Lipofundin S. They also suggest, on the same time, a protocol for the survey of these reactions. The results suggest a good tolerance to Lipofundin S intravenous administration and no influence on haematic biochemical parameters.

[Rare colonic occlusions: volvulus of the splenic flexure]. / Occlusioni coliche rare: il volvolo della flessura splenica.

Authors report a case of perforated splenic flexure volvulus, treated with resection, end colostomy and closure of the distal stump. From the revision of literature it comes out the case reported is the 30th recorded till now, the 6th with ischemic complications, and the only one with perforation. Actual pathogenetic trends and various therapeutic options are reported.

Estrogen and progesterone receptors in breast cancer: correlation with clinical and pathological features and with prognosis.

Estrogen and progesterone receptor status was reviewed in 405 patients from prior adjuvant breast cancer trials at the University of Verona. Only 233 patients were actually examined with respect to hormone status and outcome. No relationship between hormone receptor status and most of the commonly followed prognostic signs, i.e. tumor size, nodal status, and age, was found. Overall survival was correlated with hormone receptor positivity for patients with more than 4 positive axillary nodes. Disease-free survival was correlated only with PgR positivity, in premenopausal and in T1 groups.

Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice.

The protection by pyroglutamic acid (CAS 98-79-3) and derivatives Ia-i (injected i.p.) against glutamate- and NMDA (N-methyl-D-aspartate) (i.c.v.) induced seizures in mice has been studied in comparison with known antiepileptics and antagonists of excitatory aminoacids. The potency of pyroglutamic acid and some derivatives (Id,f,g,h) against glutamate-induced convulsions was similar to that shown by glutamic acid diethylester and by valproic acid. Interestingly, pyroglutamic acid did not affect NMDA-induced convulsions which were well antagonized by both 2-amino-5-phosphono valeric acid and by diazepam. Thus, pyroglutamic acid may represent the starting for synthesis of excitatory aminoacid antagonists acting at non NMDA receptors.

Coronary heart disease risk score and ECG abnormalities in apparently healthy workers from petrochemical industry. The Pavia Study.

The purpose of the study undertaken was to define the vulnerable fraction of the industrial population in northern Italy using the CHD risk score profile. In addition, ECG examinations were carried out in order to see whether there is a correlation between cardiovascular risk profile and the frequency of ECG abnormalities. The study covered in total 1443 male workers employed in various petrochemical plants. The calculation of the CHD risk score was based on age, relative weight, serum cholesterol, systolic blood pressure, smoking habit, physical activity at work and at home, and heredity factors. The study demonstrated that on an average 47.3% of male workers in the petrochemical industry have high or very high risk of cardiovascular disease and this draws the attention to the urgent need to develop the better and more effective primary preventive strategy against cardiovascular diseases, specially among manual workers. The study disclosed also that the persons with elevated risk score displayed more frequently ECG repolarization disorders.

Erythrocytes parameters due to aging, smoking, alcohol consumption and occupational activity in a working population of petrochemical industry. The Pavia Study.

The main purpose of the study was to assess the red blood cell disorders in works employed in the petrochemical industry in the Lombardia region (ENI). In the analysis of the data the confounding factors such as age, smoking habit, alcohol consumption, nutritional status based on body mass index have also been taken into consideration. In total, material consisted of 1175 male workers in whom red blood cell examination of the peripheral fasting blood was carried out. The results of the study showed that clinical anemia has been found in 1.7% of subjects examined. The distribution of anemia cases was not related to job category or physical occupational activity, neither to age, smoking or alcohol consumption. However, the results of the study suggest that aging processes are associated with weakening of hemopoietic system which affect in a great extent hemoglobin production. The effect of smoking on hemopoietic system appeared to have different features from that attributed to aging. Smoking increased hemoglobin level and hematocrit significantly in comparison to nonsmokers, but had no effect on the number of erythrocytes. It was concluded that adaptation to carbon monoxide inhaled with cigarette smoke is reflected by an increased red cell mass and hemoglobin. Occupational factors measured by the type of job (manual vs nonmanual) appeared to have no harmful effect on the hemopoietic system, however, respondents who reported working physically in an intensive way, showed significantly lower mean corpuscular concentration hemoglobin level than those having a sedentary job or engaged in very small physical activity at work.