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Background and aims Although inflammatory bowel diseases (IBD) significantly impact the patient's quality of life, no European-level data exists on patients' perspectives. The primary objective of this survey was to obtain an international perspective of the impact of IBD on patients' lives. Secondary objectives included obtaining a better understanding of the quality of care, access to care, and differences between countries, age groups, and sub-groups of IBD. Methods The survey questionnaire consisted of 52 questions in six categories. The survey was translated into ten languages, tested on volunteers, and promoted across 25 national IBD associations. Data was collected anonymously online, and participation was optional. Results 4670 patients completed the survey. Most respondents received a final diagnosis within a year from noticing first symptoms, but 67% had to visit emergency clinic at least once before diagnosis. 85% had been hospitalized in the last five years. 64% felt that gastroenterologists should ask more probing questions and 54% that they did not get to tell something potentially important to their physician. Most respondents experienced symptoms weekly also in remission. Most had been absent from work due to IBD and 24% had received unfair comments about their work performance. 45% felt that IBD had negatively affected their performance in educational settings. Conclusions The results of this survey can be used in defining strategic priorities and planning projects and awareness raising activities. The unmet needs of IBD patients can be better demonstrated and communicated to the public, health service managers and politicians.

This article proposes a business game taxonomy. The taxonomy creates a comprehensive definition of business games in general and identifies their parameter-defining characteristics. A successful taxonomy can facilitate the comparison of different game-based educational tools and can direct application-based research to a game’s most learning-associated components. The field’s existing taxonomies within the literature are inadequate for both purposes. The genesis of our five-part taxonomy of business games was both literature-based and intuitive. It is hoped that this taxonomy will serve to develop a global database to be built collaboratively by the community of business game users and developers.

Summary This article is aimed at supporting the management in the strategic planning of investments on critical value drivers, taking into consideration their impact on competitive advantage and the cumulative investments made on them. We describe a framework through a step-by-step procedure. No previous strategic management framework has adopted a holistic approach to the strategic analysis of value drivers. In fact, unlike many other strategic management models, our framework adopts a competitive advantage perspective considering both the wholeness of organizational value drivers and the interdependencies among the value drivers. Managers are asked to make pairwise comparisons that are synthesized through the analytic network process. The outputs of the synthesis are analyzed both qualitatively (synoptic analysis) and quantitatively (Spearman’s and Kendall’s non-parametric rank correlation coefficients). The analysis of the resulting values turns in useful strategic suggestions for the top management in order to enhance the organizational strategic coherence.

This article proposes a framework designed to support the top management in the tactical and strategic planning of the investments on critical ICAs. The framework consists of a sequence of steps, which aim at assessing the organisational intellectual capital. The framework takes into consideration the impact of intellectual capital assets on the value creation process. The framework resorts to the analytic network process in order to synthesise the interdependences among intellectual capital assets and identify the individual impact of each intellectual capital asset. The implementation of the proposed framework provides managers with strategic considerations, which can be drawn from the results and compared through a synoptic analysis and through a cost/benefit analysis.

Esta investigación pretende analizar, desde un punto de vista histórico, el corpus literario de la novela colonial francesa entre 1870 y 1931. La primera parte es dedicada a las practicas culturales que se mueven alrededor de los libros y de la lectura, al mismo tiempo otorga atención al contexto histórico. Los primeros dos capítulos se centran alrededor de dos grandes actitudes: la tendencia francesa a comparar la experiencia africana con el mundo y la sociedad clásica y medieval europea y el arte de la denigración, es decir la costumbre de rebajar y quitar valor a las sociedades africanas. El tercer capitulo se centra en el discurso anticolonial. En ese apartado se evidencia como el anticolonialismo fue un hecho marginal. La cuarta sección es dedicada a los personajes de la novela colonial. El cazador, el soldado, el científico, el cura, el viajero y el publico funcionario son las principales figura de la novela que se han analizado. En el epilogo se examinan los vicios y las virtudes de ese tipo de literatura, su utilidad para la historia cultural de las representaciones., The research analyzes, through a historical approach, the literary corpus of the colonial French novel between 1870 and 1931. The first part is dedicated to the cultural practices that revolve around books and reading, and tries to pay attention to the historical context. The first two chapters are focused on two large attitudes: the French tendency to compare the African experience with classical or medieval world and the art of denigration, namely the custom to degrade and remove value to the African societies. The third chapter focuses on all anti-colonial literary events. In this section we show how anti-colonialism was rather marginal. The fourth part is dedicated to the characters of the colonial novel: the hunter, the soldier, the scientist, the priest, the traveller, the civil servant, being the main figures of the novel, are the main subjects analysed. In the epilogue, vices and virtues of this type of literature are discussed, as well as its importance for the cultural history of representations.

Background The conservative treatment of operable breast cancer has gradually become well-established during the last 20 years as it offers adequate loco-regional control of the disease and saves the brest. Moreover, larger, demolishing operations have not shown to decrease the risk of distant metastases.

Purpose : The influence of radiotherapy in the cosmetic outcome after conservative surgery for breast cancer was evaluated using an objective method of calculating the asymmetry between the two breasts. Methods and Materials : One hundred and one patients treated with the same conservative surgery were evaluated for cosmetic outcome. Sixty-one of them received external radiotherapy (50 + 10 Gy) to the residual breast ; the remaining 40 underwent surgery only. The aspect of the patients' breasts was objectively assessed for symmetry by means of a computerized technique. A subjective assessment of the cosmetic outcome was performed both by physician and patient. These objective and subjective assessments were compared in the two groups treated with or without radiotherapy. Results : The results obtained did not show significant differences in terms of cosmetic outcome in the two groups. Skin telangectasia was noted in two radiotherapy patients, while hypertrophic breast scars were only noted in six nonirradiated patients. Conclusions : We found that standard radiotherapy does not seem to influence the symmetry and the cosmetic results in breast conservative treatment when compared to a similar group of patients with the same quadrantectomy procedure and no radiotherapy.

The profiles of functional (proliferative rate and cell distribution in the cell cycle) and phenotypic (nuclear DNA content and hormone receptor status) biological markers and the expression of P53 and Bcl-2 proteins were prospectively evaluated in breast cancers before and after different regimens of primary chemotherapy. Overall, changes induced on the 2 proliferation indices (3H-thymidine labelling index, 3H-dT LI, and flow-cytometric S-phase fraction, FCM-S) mainly consisted of a decrease for rapidly proliferating tumours and an increase or no change for slowly proliferating tumours. However, when considered as a function of treatment type, changes of 3H-dT LI and FCM-S were superimposable in rapidly proliferating tumours, regardless of the type of treatment, and in slowly proliferating tumours only after anthracycline-including regimens. Conversely, following CMF, FCM-S was increased in 90% of the cases and 3H-dT LI in only 50%. Our data imply that the 2 proliferation indices could reflect different phenomena: an actual variation of proliferative activity by 3H-dT LI and an accumulation of cells in the S-phase by FCM-S. In addition, a higher accumulation of cells in G2-M phases could be detected by FCM after anthracycline-including regimens than after CMF. The fraction of P53-positive cells was reduced by primary chemotherapy in about 50% of P53-positive tumours, whereas Bcl-2 expression was only marginally affected. DNA ploidy and hormone receptor status did not change in about 75% of cases, regardless of the chemotherapeutic regimen. © 1995 Wiley-Liss, Inc.

Although the food and drink (F&D) industry is Europe's largest manufacturing sector, few studies have explored its innovation activities so far. Starting from the widespread assumption that F&D manufacturers are supplier dominated 'à la Pavitt', we formulated hypotheses about their innovation activities. These were tested through Wilcoxon and Mann-Whitney tests on data drawn from a sample of 54,088 manufacturing firms (7,301 of which operating in the F&D industry) in 14 European countries, participating in Eurostat's 2008 Community Innovation Survey. The results confirm the supplier dominated nature of F&D firms, although also show that some largely anecdotal assumptions about the F&D industry's pattern of innovation cannot be empirically supported.

Life expectancy in Italy is estimated to rise to 77.9 and 84.4 years in next years. Increased life expectancy is associated with a greater frailty of elderly people and an increased prevalence of chronic and degenerative illnesses such as cardiovascular diseases and osteoporosis. The impact of osteoporotic hip fractures in Italy is very similar to that of acute myocardial infarction (AMI), and there is a need for further epidemiological investigations concerning both the pathologies, as well as for a better understanding of possible mechanisms of their cosegregation. Actually, calcium metabolism is involved both in the development of osteoporosis and in the raise of cardiovascular risk. We have reviewed the most recent publications concerning epidemiological trends of both osteoporosis and acute myocardial infarction (AMI), and also the trials addressing cosegregation of these pathologies. According to the publications examined, in the Italian population (both ≥ 45 and > 65 years old), the number of hospitalizations following hip fracture and AMI are comparable. Both hip fractures and cardiovascular diseases represent in Italy a serious medical problem and a leading health cost driver, according to what has already been reported for many other Countries in the industrialized world, thus requiring a global clinical approach. Low calcium intake could represent one of the possible pathogenic paths underlining the association between hypertension and osteoporosis. Low calcium serum levels has been proved to enhance PTH and vitamin D3 production, which result in a remarkable lypogenesis performed by adypocites and switch on mechanisms leading to the raise of blood systolic pressure, the development of atherosclerotic plaques and cardiovascular events. Although many trials have suggested that bone mineral density may be included in the list of cardiovascular risk factors, more studies are needed in order to deeply investigate the causal relationships between calcium metabolism and cardiovascular diseases.

L'Agenda Strategica della Ricerca (ASR) riporta una panoramica completa delle priorità di ricerca e sviluppo in agricoltura biologica nel nostro paese in una prospettiva strategica ed in coerenza con quelle definite in sede europea dalla Strategic Research Agenda della Piattaforma TP Organics. L'Agenda Strategica della Ricerca individua 3 aree e 13 tematiche prioritarie a cui afferiscono 71 Temi specifici di ricerca, che investono ampi campi d'indagini con promettenti ricadute sia sul lato economico che in termini di sostenibilità, tenendo in considerazione il valore dell'agricoltura biologica anche in ragione della salvaguardia di un bene comune. In base alle considerazioni riportate, l'Agenda Strategica della Ricerca di PTBio Italia intende fornire un contributo efficace per affrontare le vaste problematiche che investono l'intero complesso agroalimentare, ritenendo che la ricerca e l'innovazione nel campo dell'agricoltura biologica aiuti anche allo sviluppo di un sistema di produzione a ridotto impatto ambientale e con minor uso di risorse, alla produzione di alimenti sicuri e di alta qualità, alla crescita di un sistema agroalimentare valido, dinamico e sostenibile ed alla diffusione di comportamenti alimentari più sani. Questo avrà ricadute importanti sulle grandi sfide globali del prossimo decennio e che riguardano l'insicurezza alimentare, l'obesità, la qualità e la salubrità del cibo, i cambiamenti climatici, la perdita della biodiversità, la degradazione del suolo e la ridotta disponibilità d'acqua.

An objective evaluation of the cosmetic outcome after conservative treatment for breast cancer was applied on 136 patients treated with quadrantectomy, axillary dissection and radiotherapy. Differences in the symmetry between the operated and non-operated breasts were calculated and expressed by an ‘asymmetry index’. This value represented a parameter of the asymmetry between the two breasts. The ‘asymmetry index’ reflected the qualitative judgment expressed by the observer and the patient's self-assessment. These combined systems of evaluation proved quadrantectomy to have satisfactory cosmetic results despite the large amount of tissue removed by this procedure.

People with IBD have a right to clear, unbiased, high-quality knowledge about their condition and its management, and they should be assisted in accessing a range of resources available by health care professionals as well as in developing resource interpretive skills and tools for critical appraisal. “Resourceful patients” are increasing in number and can interpret medical knowledge; information for patients and for health care professionals need not necessarily be separate. The inclusion of the patient experience is vital for successful resources. People with IBD should be supported in accessing communities and groups in real life and/or online, and the process should be facilitated at specific clinics or by individual clinicians.

The theme of conflict resolution using Analytic Hierarchy Process (AHP) is widely examined in scientific literature, but as yet insufficient attention has been paid to the quantitative aspect of AHP contribution. In this paper we aim to quantify AHP helpfulness in conflict negotiations: how much does AHP actually facilitate a conflict resolution and help negotiators to find win-win agreements? Following this lead, we realized a role playing experiment simulating a "Union versus Management" negotiation problem and compared two groups: a control group that negotiated without any structured decision support system and another group that negotiated with the support of AHP. In order to compare the agreements obtained by means of negotiation and AHP, we acted as an arbiter in the AHP decision process, following Saaty’s assumptions on the psychological attitudes of negotiating parties in a conflict. The results showed that AHP agreements are more frequently Pareto-efficient than those achieved by negotiators, and are characterized by higher average utilities.

Reputation enables different parties to establish a trusting and cooperative relationship, a key factor in integrative negotiations referred to as “win-win” negotiations. Thus, a good reputation mechanism can bring simulations closer to reality. In this study, the authors review the reputation mechanisms applied to the online business game WIN WIN MANAGER, where the players’ reputations are decided by their counterparts at the end of each negotiation. Then, the authors compare two reputation mechanisms and hypothesize that the best mechanism will be more positively correlated with the negotiation outcome, which is measured by a scoring algorithm. Using nonparametric statistics, it is highlighted that the reputation mechanism in earlier versions of the game seems to produce values unrelated to the score, whereas the new mechanism produces values significantly positively correlated with the score. Such results can be useful to scholars who conduct experiments on negotiation, as well as online markets in which users are allowed to negotiate with one another.

We followed 777 consecutive patients with breast carcinoma and positive axillary nodes for a mean of 60 months to evaluate the prognostic weight of both the total number of involved nodes and their distribution by level. Quadrantectomy was performed in 223 cases and mastectomy in 552. Complete axillary dissection was performed in all cases with identification and removal of the three levels of lymph nodes. Metastases at level I were identified in 420 patients (54%), at levels I and II 175 patients (22.5%), and at all 3 levels in 173 (22.3%). In 9 patients (1.2%) there was involvement of level II nodes in the absence of level I involvement (skip metastases). In 18 other patients (2.3%) axillary involvement was discontinuous in that the first and third levels were involved while the second level was free. Overall survival for patients with 1–3, 4–10 and >10 metastatic nodes was 80%, 62% and 35% respectively; and when level I only, levels I and II, and all 3 levels were involved, overall survival was 82%, 52% and 38% respectively. Both the total number of involved axillary nodes and the extent of axillary invasion by level had strong prognostic significance. Multivariate analysis showed that the prognostic power of levels of nodal involvement, measured as hazard ratios, is superior to that of the number of involved nodes. It is therefore recommended that surgeons and pathologists record this important information whenever axillary dissection is performed.

Background and Methods Conservative surgery and radiotherapy have become well-established treatments for breast cancer, and many trials in progress are attempting to define the most acceptable type of procedure. Between 1987 and 1989 we randomly assigned 567 women with small breast cancers (

(Cancer Sci 2010; 101: 826–830) The purpose was to ascertain whether the recurrence risk patterns for patients with estrogen receptor (ER)-positive (P) and ER-negative (N) breast cancer support the ER-related clinical divergence suggested by the observed different mortality patterns and gene expression profiles. Both recurrence and death were considered in a series of 771 patients undergoing mastectomy. ER status was available for 539 patients. The hazard rates for recurrence and mortality throughout 15 years of follow-up were assessed. The recurrence dynamics displays a bimodal pattern for both ERP and ERN tumors with comparable peak timings. The two curves cross during the 3rd year. By contrast, the mortality dynamics are definitely different for ERP and ERN tumors: during the early follow-up period ERN patients have their highest mortality risk, while ERP patients have their lowest mortality risk. The two curves cross during the 5th year. In spite of the different mortality dynamics, the recurrence dynamics do not demonstrate a major distinction in timing between ERP and ERN breast cancers, suggesting that the metastasis development process following mastectomy is apparently similar for both ER categories. The observed differences in the mortality risk are plausibly attributable to ER-related factors influencing the clinical course from recurrence to death. These clinical findings apparently contradict the occurrence of two different types of breast cancer, notwithstanding the distinct epidemiological, clinical, and molecular features linked to ERP and ERN tumors, although ER levels may concur to establish the event risk levels.

The aim of this study is to evaluate the variations of respiratory gas concentration with transcutaneous blood gas measurements (tcm PO2; tcm PCO2) during intermittent positive pressure ventilation (I.P.P.V.) and aerosol therapy in patients (5 female, 5 male; 43–75 years) with chronic obstructive pulmonary diseases (COPD) with haemo gas analysis values PO2

Purpose To evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy. Patients and Methods A total of 1,355 women with operable breast cancer were randomly assigned to one of three treatments: surgery followed by adjuvant doxorubicin (75 mg/m2) followed by cyclophosphamide, methotrexate, and fluorouracil (CMF; arm A); surgery followed by adjuvant paclitaxel (200 mg/m2) plus doxorubicin (60 mg/m2), followed by CMF (arm B); or paclitaxel (200 mg/m2) plus doxorubicin (60 mg/m2) followed by CMF followed by surgery (arm C). The two coprimary objectives were to assess the effects on relapse-free survival (RFS) of the addition of paclitaxel to postoperative chemotherapy (arm B v arm A) and primary chemotherapy versus adjuvant chemotherapy (arm B v arm C). Results Doxorubicin plus paclitaxel followed by CMF was well-tolerated as adjuvant or as primary chemotherapy. The addition of paclitaxel to adjuvant doxorubicin followed by CMF significantly improved RFS compared with adjuvant doxorubicin alone followed by CMF (hazard ratio [HR], 0.73; P = .03). Distant RFS was similarly improved (HR, 0.70; P = .027). There was no significant difference in RFS when the paclitaxel/doxorubicin/CMF chemotherapy was given before surgery compared with the same regimen given after surgery (HR, 1.21; P = .18). However, the rate of breast-conserving surgery was significantly higher with preoperative chemotherapy (63% v 34%; P < .001). Conclusion Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.

This cross-sectional study investigated with two-dimensional gel electrophoresis coupled to MALDI-TOF and 15 MRI the relationship between PBMCs protein expression profile and whole brain atrophy in 16 unselected 16 RR-MS IFN-treated patients compared with 6 RRIFN-untreated and 12 matched healthy control subjects. 17 Grey/white matter fraction, T1/T2 lesion load and clinical variables were considered too. 18 Twenty six proteins showed significant differential expression among RR IFN-treated patients and control 19 samples. Four of these (IN35, GANAB, PP1B, SEPT2) resulted correlated with clinical and MRI findings in RR 20 IFN-treated MS patients. 21 Future clinical applications remain to be validated by other techniques and confirmed by a larger study.

L’Ultramar italià va ser el testimoni d'un racisme institucional particular, d'una política del racisme o del racisme polític, vinculat a les grans eleccions de la política colonial italiana, liberal i feixista. Les ètnies i les races han censades, descrites i inventades. La "política de les races " a Itàlia va ser precoç. Va ser una obra constant i sistemàtica, conscient de l'explotació de les diferències. La més petita de les potències colonials, el més petit i més breu dels imperis d'ultramar va aconseguir codificar normes i pràctiques que semblen sense proporció amb el seu imperi. L'afirmació que "italians són bones persones" no resisteix a un examen històric seriós. El sentiment pretès d'una dolçor i d'una humanitat que Itàlia exportava també on no havia de, ha estat reflectit en diverses històries populistes i nacionalistes. Precisament el racisme diari i difós i que prové de la massa de la societat colonial ens mostra que el mite «italiani brava gente» descobreix el seu caràcter ideològic i la invenció de la tradició., El Ultramar italiano fue el testigo de un racismo institucional particular, de una política del racismo o del racismo político, vinculado a las grandes elecciones de la política colonial italiana, liberal y fascista. Las etnias y las razas han censadas, descritas e inventadas. La "política de las razas " en Italia fue precoz. Fue una obra constante y sistemática, consciente de la explotación de las diferencias. La más pequeña de las potencias coloniales, el más pequeño y más breve de los imperios de ultramar consiguió codificar normas y prácticas que parecen sin proporción con su imperio. La afirmación que "italianos son buenas personas" no resiste a un examen histórico serio. El sentimiento pretendido de una dulzura y de una humanidad que Italia exportaba también donde no debía, ha sido reflejado en varias historias populistas y nacionalistas. Precisamente el racismo diario y difundido y que proviene de la masa de la sociedad colonial nos muestra que el mito «italiani brava gente» descubre su carácter ideológico y la invención de la tradición.

The use of Role-Playing is becoming prominent in Serious Games due to its positive effects on learning. In this chapter the author will provide a comprehensive definition of role-playing games, drawing inspiration from the many different definitions provided in the existing literature. Then, will propose a five-dimension taxonomy for Serious Role Playing Games, applying it to a small selection of successful Serious Games in five different domains. An overview of the literature will help the reader understand when Role-Playing should be used, and when it might be useless or detrimental. Finally, a brief analysis will be performed on the reviewed games, in order to point out the correlations among the taxonomy dimensions and the domains of application.

Long-term survival of 1986 consecutive patients with infiltrating duct carcinoma of the breast treated at the National Cancer Institute of Milano (Italy) in two periods of time (1971 to 1972 and 1977 to 1978) was comparatively evaluated to verify if the evolving concepts in the management of breast cancer had an impact on survival. The authors found that 10-year survival of our patients increased from 59.4% of the first period of time to 65% of the second (P = 0.005). Both node-negative (N-) and node-positive (N+) patients had an improvement of survival rates at 10 years of the same magnitude: 6.8% and 5.9% respectively. Taking into consideration both the maximum diameter of the primary tumor and the status of axillary nodes it was found that in (1) both N- and N+ patients with a primary tumor of no more than 2 cm in greatest diameter, the improvement of survival was not statistically significant; and (2) both N- and N+ patients with a primary greater than 2 cm in maximum diameter had a better chance of survival in the second time period.

Purpose: Local relapse (LR) remains an important concern in breast cancer surveillance. Given the unique opportunity to study local recurrences in the breast in the absence of irradiation, we tested the possibility of identifying a particular tumor feature that might account for LR. Experimental Design: Archival specimens from 235 patients belonging to the control arm (no radiotherapy) of the Milan 3 Trial were retrieved and included in this study. H&E-stained histologic slides were reviewed for diagnostic reassessment. A panel of biological variables was assessed by immunohistochemical/cytochemical staining. Results: Onset of LR was significantly linked only to patient's age, with a hazard ratio (HR) to relapse reduced by 60% in patients >50 years of age (P = 0.002). Univariate and multivariate Cox analyses in women ≤50 years of age indicated that only expression of hyaluronan in tumor cells was associated with LR risk (HR, 2.48; P = 0.0364 and HR, 2.34; P = 0.0580, respectively). In patients >50 years of age, lymph node and estrogen receptor status were significantly predictive of LR (HR, 3.34; P = 0.0113 and HR, 0.39; P = 0.0424, respectively). Multivariate analysis indicated that apart from lymph node positivity (HR, 3.48; P = 0.0120), none of the variables associated with LR in univariate analysis displayed an independent LR-predictive power. LR had a strong prognostic impact on distant metastasis in patients >50 years of age, whereas in younger women, LR did not affect the risk of metastasis. Conclusions: These results support the notion that LR arises from two distinct mechanisms, one that is more frequent in young patients, associated with host characteristics, and is not linked with prognosis, and another that is less frequent, but is associated with tumor aggressiveness which represents a peculiar and distinct marker of breast tumor malignancy.

In 165 women with breast cancer who were candidates for mastectomy because the largest diameter of the tumor was 3 cm or more, we administered primary chemotherapy in the attempt to substitute conservative for mutilating surgery. We then systematically quantitated tumor reduction by clinical, radiologic, and histopathologic evaluations. Five consecutive groups of 33 patients received cyclophosphamide, methotrexate, and fluorouracil (CMF); fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC); or fluorouracil, epirubicin, and cyclophosphamide (FEC). The regimens for the five groups were as follows: group 1, three cycles of CMF; group 2, four cycles of CMF; group 3, three cycles of FAC; group 4, four cycles of FAC; and group 5, three cycles of FEC. In response to primary chemotherapy, 157 of the 161 assessable patients showed measurable tumor shrinkage; progressive disease was documented in four. Tumor shrinkage to less than 3 cm was documented in 127 (81%) of the 157 women subjected to surgery, thus allowing a breast-saving procedure, rather than modified radical mastectomy, in these 127 women. Histopathologic complete remission was documented in seven patients. Tumor response was unrelated to age, menopausal status, DNA content (ploidy), [3H]thymidine-labeling index, drug combination used, or number of treatment cycles in excess of three. The degree of response was inversely proportional to the initial tumor size, and the frequency of response was greater in receptor-negative tumors. Severe vomiting and hair loss were less frequent with CMF than with anthracycline-containing regimens, and the frequency of severe leukopenia and thrombocytopenia was minimal. Our results challenge the classical indication for primary mastectomy by showing that use of full-dose primary chemotherapy, sequentially combined with conservative surgery and radiation, can offer an effective and safe alternative to women concerned about the preservation of body integrity.

BACKGROUND. In elderly patients with early breast cancer and a clinically clear axilla, axillary surgery, sentinel lymph node biopsy, and postoperative radiotherapy to the residual breast may not be necessary because of reduced life expectancy, effectiveness of hormone therapy in achieving long-term disease control, and generally favorable biologic behavior of breast cancer in elderly patients. METHODS. The authors followed 354 prospectively recruited women aged ≥70 years who had primary, operable breast cancer and no palpable axillary lymph nodes. All 354 women were treated with conservative surgery and adjuvant tamoxifen and without axillary dissection or postoperative radiotherapy. Women who had resection margins in tumor tissue were excluded. Endpoints were cumulative incidence of axillary disease, cumulative incidence of ipsilateral breast tumor recurrence (IBTR), and breast cancer mortality. RESULTS. After a median follow-up of 15 years (interquartile range, 14–17 years), the crude cumulative incidence was 4.2% (4% in pathologic T1 [pT1] tumors) for axillary disease, 8.3% (7.3% in pT1 tumors) for IBTR, and 17% for breast cancer mortality. Of the 268 patients who died during follow-up, 222 patients (83%) died from causes unrelated to breast cancer. CONCLUSIONS. Elderly patients with early breast cancer and no palpable axillary lymph nodes may be safely treated safety by conservative surgery without axillary dissection and without postoperative radiotherapy, provided that surgical margins are in tumor-free tissue and that hormone therapy is administered. Sentinel lymph node biopsy is also unnecessary because of the low cumulative incidence of axillary disease, and axillary surgery can be reserved for the small proportion of patients who later develop overt axillary disease. Cancer 2008. © 2007 American Cancer Society.

Pregnancy associated breast cancer includes cancers concurrent with pregnancy and those diagnosed up to 1 year after delivery. The incidence of breast carcinoma in pregnancy is estimated to be approximately 1 in 3000 pregnancies. Due to the difficulties of clinical breast examination, diagnosis is frequently delayed and made when the cancer stage has progressed. Consequently, prognosis is usually poor. Treatment options are limited by concern about harming the fetus and depend on gestational age. We present the case of a 34-year-old woman who was diagnosed with cancer of the right breast in the 28th week of gestation. The patient underwent modified radical mastectomy. This association is uncommon but is not exceptional. Knowledge of cases such as that reported herein will allow early diagnosis and improve the prognosis of these patients.

Skin-reducing mastectomy Background: The authors propose a combined flap technique to reconstruct large and medium-sized ptoic breasts in a single-stage operation by use of anatomical permanent implants. Methods: The authors enrolled 28 patients fulfilling criteria for skin-sparing mastectomy and presenting with ptoic breasts whose areola-to-inframammary fold distance was more than 8 cm. All reconstructions were performed as a single-stage procedure. after preoperative planning, a large area in the lower half of the breast was deepithelialized according to the conventional Wise pattern. Mastectomy was then carried out. To perform reconstructions, the inferomedial fibers of the pectoralis major muscle were dissected and sutured to the superior border of the inferior dermal flap. An anatomical implant was then inserted into the pouch, which was closed laterally with the previously harvested serratus anterior fascia. Skin flaps were finally closed down to the inframammary fold. Results: The authors performed 30 procedures on 28 patients. The medium size anatomical implants was 433 cc. Twelve women achieved symmetrization in a single stage ending in a symmetric inverted-T scar. The overall complication rate was 20 percent, with four cases (13 percent) complicated by severe, extensive necrosis of the skin flaps requiring implant removal. Conclusions: Breast cancer treatment must nowadays optimize cosmetic results. This can be accomplished in selected cases by means of a single-stage operation that the authors call "skin-reducing mastectomy." The final scars imitate those of cosmetic surgery. Careful patient selection and improvement in the learning curve may reduce the complication rate.

Lobular carcinoma in situ was first described over 60 years ago. Despite the long history, it continues to pose significant difficulties in screening, diagnosis, management and treatment. This is partly due its multi-focal and bilateral presentation, an incomplete understanding of its biology and natural history and perpetuation of misconceptions gathered over the last decades. In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion.

Purpose: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin → CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel → CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate. Methods: A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C. Results: Grade 3 or 4 National Cancer Institute toxicities were low ( Conclusions: Doxorubicin/paclitaxel → CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.

It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =65 years old) women with nonmetastatic, ER-alpha-positive (by immunohistochemistry) primary breast cancers (> 2 cm in diameter) entered a neoadjuvant hormone therapy protocol (60 mg/day toremifene for 3 months). ER-alpha and ER-beta (ERs) mRNA was determined by semiquantitative RT-PCR, before (on core needle biopsy) and after (on surgical specimens) neoadjuvant treatment. Study end points included: (1) relation between treatment response and ER mRNA expression; and (2) changes in ER expression after treatment. The response was clinically assessed as tumor size change at the end of the preoperative treatment. ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively. ER-beta was co-expressed with ER-alpha at variable levels and significantly correlated only with progesterone receptor (P = 0.0285). Objective clinical response, including patients with minor change (> or =25

Summary Objective Clinical and experimental data have suggested that surgical removal of primary tumours promotes the growth of metastatic lesions. We assessed the effect of surgery on proliferation of breast carcinomas, in particular those overexpressing HER2 oncoprotein. Methods Proliferation of breast carcinoma cells was assessed by MIB-1 immunohistochemistry in sections of primary breast carcinomas and in residual tumour found in re-excision specimens, and in in-vitro cell lines by colorimetric assay. Epidermal growth factor (EGF)-like growth factors were measured by displacement of radiolabelled EGF from its receptor. Cellular damage was measured in terms of creatine phosphokinase level. Downmodulation of HER2 was investigated by cytoplasmic expression of anti-HER2 antibody and by inhibition with anti-HER2 antibody trastuzumab. Findings Residual breast carcinomas that had been surgically removed within 48 days after first surgery showed a significant increase in proliferation if they were HER2-positive. Wound drainage fluid and postsurgical serum samples from patients stimulated in-vitro growth of HER2-overexpressing breast carcinoma cells. Removal of HER2 from the cell membrane led to a striking reduction of the induced proliferation. The amount of EGF-like growth factors in post-surgical serum samples, as well as the extent of drainage-fluid-induced proliferation, directly correlated with the amount of surgical damage assessed by creatine phosphokinase levels ( r =0·77, p=0·002 and r =0·69, p=0·009, respectively). Treatment of HER2 positive tumour cells with trastuzumab before adding the growth stimulus abolished drainage-fluid-induced proliferation. Interpretation HER2 overexpression by breast carcinoma cells has a role in postsurgery stimulation of growth of breast carcinoma cells.

Opposing interests, bounded rationality and decisional bias may severely hinder conflict resolution. When the commitment for an agreement is high, opponents can resort to the intervention of a third party, such as a mediator. We propose a methodology to enhance conflict resolution, which is based on the analytic hierarchy process (AHP) and takes into account the psychological attitudes of the conflicting parties. The AHP Technique for Highly Eligible Negotiation Agreements (ATHENA) supports a third party in selecting, among potential negotiation agreements, those proposals having the best chances to be accepted by adverse parties. We illustrate an implementation of ATHENA that involved 160 students simulating 'Union versus Management' negotiations. A control group of 40 couples negotiated without any decision support system, while the other 40 couples were supported by ATHENA. The results show that the procedure implementation outperformed unsupported negotiation by increasing the number and the fairness of agreements.

The aim of this study was to establish the most sensitive and specific screening method for celiac disease. We tested three methods based on different principles, which all detect autoantibodies against the same antigen (tissue transglutaminase).Sixty-two celiac children at the first biopsy (group 1), 78 celiac children on a gluten-free diet (group 2), 14 celiac children on a gluten-challenge (group 3), and 56 controls with a normal duodenal mucosa (group 4) were studied. The methods used were: 1) radioimmunoprecipitation assay using recombinant tissue transglutaminase (RIA); 2) commercial enzyme immunoassay using guinea pig tissue transglutaminase (ELISA); and 3) indirect immunofluorescence method for detection of antiendomysium antibodies (IF-EMA).RIA antitransglutaminase autoantibodies were detected in 100% of group 1, 43.6% of group 2, 100% of group 3, and none of the control subjects. ELISA antitransglutaminase autoantibodies were detected in 90.3% of group 1, 9% of group 2, 78.6% of group 3, and in none of the control subjects. IF-EMA were detected in 95.2% of group 1, 11.5% of group 2, 92.3% of group 3, and 1.8% of the controls.Our results demonstrate a very high sensitivity and specificity of the RIA method to detect antitransglutaminase autoantibodies in comparison to ELISA and IF-EMA assays. We can explain this finding with the use of human recombinant antigen and the increased capacity of the RIA method to detect low titers of autoantibodies. If our data are confirmed by studies on larger series, tissue transglutaminase RIA could be proposed as the best screening method for celiac patients.

In the diagnosis of breast disease, mammography in radiologically dense breasts in frequently of little value and where a suspicious lump is palpated, ultrasound may resolve the diagnosis. 140 patients with palpable breast masses, in whom the mammograms were intensely radiopaque, were examined using breast ultrasound. 42 were considered benign and checked at 4 monthly intervals. The accuracy of ultrasound in the remaining 98 patients with intensely radiopaque breasts was evaluated by comparison with cyto/histological findings. The 90 benign lesions found were correctly diagnosed by ultrasound in 69 instances (76.6%). It is concluded that in the presence of a palpable mass, ultrasound is a useful adjunct to mammography in the differential diagnosis of benign non-inflammatory breast pathology. However, mammography remains the first line diagnostic tool.

From June to December 1990, 110 consecutive patients with breast cancer underwent a modified radical mastectomy (n=33) or quadrantectomy (n=77) combined with a complete axillary dissection and removal or interpectoral lymphatic tissue. The average number of lymph nodes removed from the axilla and interpectoral region was 22: 12.5 at Level I, 6.4 at Level II, 3.7 at Level III and 1.5 from the interpectoral tissue. In 59 110 patients fatty tissue only was found in the interpectoral region and in the remaining 51 patients, interpectoral lymph nodes were identified and these were involved in 22 patients (37.3% of total group). In 3 patients these were the only nodes involved. During axillary dissection the interpectoral space should be explored and palpable interpectoral nodes removed and submitted for histology.

We report a case of cutaneous Stage I melanoma associated with occult breast cancer detected incidentally during a sentinel node biopsy. A brief review of the literature is presented with particular emphasis on this association and on an examination of the theoretical link which may exist between melanoma and breast cancer.