[Augmented psychotherapy with rTMS in functional neurological disorder]. / Psychothérapie augmentée par rTMS pour les troubles neurologiques fonctionnels.

BACKGROUND: We report the observation of a 47-year-old woman with functional neurological disorder (tetraparesis, mixed tremors and non-epileptic seizures) treated with a protocol of augmented psychotherapy in combination with repeated transcranial magnetic stimulation (rTMS). INTERVENTION: We carried out a biofeedback psychotherapy protocol with rTMS (twenty sessions, two sessions per day for ten days; 1Hz, 150% of the motor threshold, twenty minute sessions, 300 pulses per session) in which the patient visualized the motor activity of her upper limbs during stimulation of the primary motor area (PMA). The evolution of neurological symptoms was assessed using the Medical Research Council Scale for Muscle Strength (MRC). RESULTS: Symptoms were improved between the 4th and 6th days of treatment (8th and 12th sessions) with first a relief of paresis, then a secondary cascade improvement of other functional symptoms. At two months the patient no longer presented any functional neurological symptoms. DISCUSSION & CONCLUSION: We propose several hypotheses concerning the effectiveness of this type of biofeedback protocol using rTMS. We also suggest that this type of protocol should be systematically associated with psychotherapeutic support on biographical elements for holistic management. This observation underlines the interest of potentiating cognitive-behavioral therapies using the principle of operant conditioning with the aid of brain stimulation in functional neurological disorders, and motivates the realization of future studies.

[Mental Health and sexual orientation in adolescents in a school environment]. / Santé mentale des adolescents selon leur attirance sexuelle : enquête en milieu scolaire.

INTRODUCTION: Although homosexuality is a subject often addressed by the media, little is said about homosexuality in adolescents who are particularly affected by the question of sexual orientation. This work aims to study the mental health of adolescents who report being exclusively attracted to members of the same sex. We explore the evidence for an association between homosexuality and depression, suicide attempts, and consulting a psychiatrist or a psychologist. METHODS: We used data from the cross-sectional study "Adolescent Portraits - A Multicenter Epidemiological Survey in Schools in 2013" (CHU Fondation Vallée, Inserm CESP U1018). Data were gathered through the use of an anonymous, self-administered questionnaire (348 questions) given to students between the "4e" and "terminaleschool" years (comparable to the 8th and 12th grade in the U.S. education system) in three contrasting French geographical areas. The risk of depression was measured using the Adolescent Depression Rating Scale (ADRS). RESULTS: The results reflect the survey responses provided by 15,235 young people. Of these, 1.5 % reported only being attracted to members of the same sex (homosexual group). This group contained twice as many girls as boys. Students who did not report sexual attraction, who reported bisexual attraction, or who did not answer the question were excluded from the results (830 students). In the homosexual group, 24 % presented with depression versus 11.5 % of those attracted exclusively to members of the opposite sex (heterosexual group). There is also a significant difference between sexes: 13.2 % of boys in the homosexual group were depressed compared to 29.3 % of girls in the same group; 6.7 % of boys in the heterosexual group reported being depressed versus 16.1 % of girls in the same group. In the heterosexual group, 10.7 % of respondents reported having already made at least one suicide attempt versus 20.7 % of those in the homosexual group. There was a difference according to sex, since 6.3 % of boys in the heterosexual group had a history of attempted suicide versus 14.9 % of girls in the same group. This gap disappeared completely within the homosexual group, as 21.4 % of boys and 20.4 % of girls had already made at least one suicide attempt at the time of the survey. Depressed adolescents in the homosexual group also reported a higher number of previous suicide attempts than those in the heterosexual group (46.9 % versus 31.6 %). In terms of sex, 25.3 % of depressed boys in the heterosexual group made at least one suicide attempt versus 34.1 % of girls. In the homosexual group, 44.4 % of depressed boys reported having made at least one suicide attempt versus 47.5 % of depressed girls. Adolescents in the homosexual group were significantly more likely to report having consulted a psychiatrist or psychologist than those in the heterosexual group (14.6 % versus 6.5 %), regardless of sex (16.7 % versus 4.7 % for boys; 13.5 % versus 8.2 % for girls). This difference was also found among depressed subjects (26.0 % in the homosexual group versus 15.4 % in the heterosexual group). Sexual activity (having already had sex) was higher in the homosexual group than in the heterosexual group (53.7 % versus 37.5 %), and this difference remained significant after adjusting for age. Fifty percent of the sexually active homosexual respondents reported having engaged in sexual activity of a homosexual nature versus 0.7 % of sexually active heterosexual respondents. In the homosexual group, mental suffering appeared to be more severe among sexually active subjects, in terms of dark thoughts (64 % versus 46 %) and a prior history of attempted suicide (29.3 % versus 10 %), but not in terms of depression (27.9 % versus 18.9 %; NS). CONCLUSION: Young people who reported being exclusively attracted to members of the same sex presented a higher level of mental distress compared to those who reported being attracted to members of the opposite sex. This was especially the case for boys. These findings led to the identification of risk and protective factors that can inform the development of appropriate preventive measures.

The cost of diabetic foot ulcers and amputations to the National Health Service in England.

AIM: To estimate the healthcare costs of diabetic foot disease in England. METHODS: Patient-level data sets at a national and local level, and evidence from clinical studies, were used to estimate the annual cost of health care for foot ulceration and amputation in people with diabetes in England in 2014-2015. RESULTS: The cost of health care for ulceration and amputation in diabetes in 2014-2015 is estimated at between £837 million and £962 million; 0.8% to 0.9% of the National Health Service (NHS) budget for England. More than 90% of expenditure was related to ulceration, and 60% was for care in community, outpatient and primary settings. For inpatients, multiple regression analysis suggested that ulceration was associated with a length of stay 8.04 days longer (95% confidence interval 7.65 to 8.42) than that for diabetes admissions without ulceration. CONCLUSIONS: Diabetic foot care accounts for a substantial proportion of healthcare expenditure in England, more than the combined cost of breast, prostate and lung cancers. Much of this expenditure arises through prolonged and severe ulceration. If the NHS were to reduce the prevalence of diabetic foot ulcers in England by one-third, the gross annual saving would be more than £250 million. Diabetic foot ulceration is a large and growing problem globally, and it is likely that there is potential to improve outcomes and reduce expenditure in many countries.

Progress of the Healthier You: NHS Diabetes Prevention Programme: referrals, uptake and participant characteristics.

AIMS: To describe early progress of the Healthier You: NHS Diabetes Prevention Programme, a behavioural intervention designed to prevent or delay onset of Type 2 diabetes in people in England already identified to be at high risk, to assess numbers of referrals received by Programme providers and the proportion that attended the initial assessment, and to identify the factors associated with attendance rates. METHODS: These analyses examine the data for referrals received between June 2016 and March 2017. RESULTS: There were 43 603 referrals received, 16% higher than expected. Of those referred, 49% attended the initial assessment, higher than the 40% modelled uptake. Of those referred, there was no significant difference in uptake by sex (P=0.061); however, attendance per 100 000 population varied significantly by sex, age group, ethnicity and deprivation; it was significantly lower for men (P<0.001), higher as age increased (P<0.001) and higher for individuals from Asian, Afro-Caribbean, mixed and other ethnic groups compared with individuals from white European groups (P<0.001). There was significant interaction between attendance rates by ethnicity and deprivation (P<0.001) such that attendance rates were significantly higher in the most deprived quintile vs the least deprived quintile for Asian, Afro-Caribbean, mixed and other ethnic groups but not significantly different for white European ethnic groups. CONCLUSION: The analyses show that referral numbers and percentage uptake are in excess of prior modelled values. Characteristics of attendees suggest that the programme is reaching those who are both at greater risk of developing Type 2 diabetes and who typically access healthcare less effectively.

A comparison of the patient and surgeon opinion on the long-term aesthetic outcome of reduction mammaplasty: have we improved over 15 years?

In 1996 we published a study evaluating the difference between patient and surgeon opinion on the aesthetic outcome of reduction mammaplasty (see Ref. 1). The patients rated the aesthetic outcome of their surgery as significantly higher than the consultant panel. The surgical panel suggested scope for improvement. Areas of dissatisfaction were poor scarring, high placement of the nipple areola complex and high rates of revision surgery. Fifteen years on, the same team has regrouped to repeat this assessment. In 1996 the consultants scored their own patient results. In 2011 they graded the results of their former trainee who has modified her operative technique to address aesthetic problems highlighted in the first study. Forty-four patients attended a review clinic at least one year post reduction mammaplasty. Patient scored their satisfaction using the original questionnaire employed in 1996. The cohort were photographed and their images graded blindly by the original surgical panel. Statistical analysis was performed by the original statistician. The patients graded aesthetic aspects of body harmony, breast mound appearance, nipple areolar complex appearance and post-operative scarring significantly more positively (p<0.01) than both the 1996 patient cohort and surgical panel. The consultant panel showed a trend for more positive grades for all aesthetic features assessed versus their previous views but this was only significant for breast mound symmetry. They expressed that there was a decrease in post-operative breast ptosis (p<0.04) and improvement in the nipple areolar complex position (p=0.02). The rate of revision surgery has decreased from 53% to 16% between the studies. In keeping with clinical audit, outcomes have been assessed and modifications implemented to address aesthetic concerns. Assessment of outcomes following the modifications demonstrates a trend for increased patient and surgeon satisfaction. Patient satisfaction however still exceeds that of the surgeons.

Fracture healing following high energy tibial trauma: Ilizarov versus Taylor Spatial Frame.

INTRODUCTION: The optimal treatment of high energy tibial fractures remains controversial and a challenging orthopaedic problem. The role of external fixators for all these tibial fractures has been shown to be crucial. METHODS: A five-year consecutive series was reviewed retrospectively, identifying two treatment groups: Ilizarov and Taylor Spatial Frame (TSF; Smith & Nephew, Memphis, TN, US). Fracture healing time was the primary outcome measure. RESULTS: A total of 112 patients (85 Ilizarov, 37 TSF) were identified for the review with a mean age of 45 years. This was higher in women (57 years) than in men (41 years). There was no significant difference between frame types (p=0.83). The median healing time was 163 days in both groups. There was no significant difference in healing time between smokers and non-smokers (180 vs 165 days respectively, p=0.07), open or closed fractures (p=0.13) or age and healing time (Spearman's r=0.12, p=0.18). There was no incidence of non-union or re-fracture following frame removal in either group. CONCLUSIONS: Despite the assumption of the rigid construct of the TSF, the median time to union was similar to that of the Ilizarov frame and the TSF therefore can play a significant role in complex tibial fractures.

Cost implications of the physiotherapy management of complex tibial fractures treated with circular frames.

Seventy-three consecutive patients with complex tibial fractures treated with an Ilizarov frame or Taylor Spatial Frame received physiotherapy between April 2008 and April 2010. Data were collected prospectively, and physiotherapy input was recorded (in minutes) for the patients identified. This included treatment received as an inpatient as well as an outpatient. The data were categorized for proximal, middle and distal third tibial fractures for analysis. The average cost of physiotherapy for an inpatient with an Ilizarov frame is £121.82 per case, whereas that for an outpatient receiving treatment for trauma was calculated as £404.60. The combined average cost of physiotherapy to support treatment of a complex tibial fracture with a fine wire fixator is £546.27. Treatment involving circular frames is complex and expensive, and the high physiotherapy cost is not reflected in Healthcare Resource Group codes. This cost calculation will help service units, and NHS Trusts develop realistic costing plans to support treatment. Cost implications of the physiotherapy management of complex tibial fractures using the Ilizarov technique.

Finding out what matters: validity of quality of life measurement in young people with ASD.

BACKGROUND: Compared with other conditions there has been a lack of focus on quality of life (QoL) as an outcome measure for children and young people with Autism Spectrum Disorder (ASD). This pilot study aimed to evaluate the validity of existing QoL questionnaires for use with children with ASD aged 8-12 years. METHODS: A literature review (1990-2011) identified the PedsQL (Pediatric Quality of Life Inventory) and Kidscreen as robust measures used with children with neurodevelopmental disorders. These measures were completed by 10 children and 11 parents. In addition semi-structured interviews were conducted with 10 parents and four children to explore their experience of completing the QoL questionnaires. RESULTS: Young people with ASD, and their parents, report lower child QoL compared with a normative sample. Framework analysis of the data highlighted six key themes which may affect the validity of generic QoL measures when administered within an ASD sample and which warrant further investigation. CONCLUSIONS: Our results indicate that a new condition-specific measure of QoL, grounded in ASD children's own perspectives of their lives, is needed and that such a measure should assess experiences of anxiety and access to special interests when measuring QoL of children with ASD. Active involvement of young people and their families is critical for the development of a theoretical framework for QoL within ASD, and any future development of an ASD-specific measure.

Three-dimensional ultrasound in the diagnosis of Müllerian duct anomalies and concordance with magnetic resonance imaging.

OBJECTIVES: To demonstrate the value of three-dimensional (3D) ultrasound in the diagnosis of uterine malformations and its concordance with magnetic resonance imaging (MRI). METHODS: This study included 286 women diagnosed with uterine malformation by 3D ultrasound, having been referred to our clinics on suspicion of uterine malformation following clinical and/or conventional two-dimensional ultrasound examination. With the exception of three with intact hymen, patients underwent both bimanual examination and speculoscopy before and/or after sonography. MRI was performed in 65 cases. We analyzed the diagnostic concordance between the techniques in the study of uterine malformations. RESULTS: Using 3D ultrasound we diagnosed: one case with uterine agenesis; 10 with unicornuate uterus, four of which also underwent MRI; six with didelphic uterus, one of which had MRI; 45 with bicornuate uterus, 12 of which had MRI; 125 with septate uterus (18 with two cervices), 42 of which had MRI (six with two cervices); 96 with arcuate uterus, three of which had MRI; and three with diethylstilbestrol (DES) iatrogenic uterine malformations, all of which had MRI. Among the 65 which underwent MRI, the diagnosis was: four cases with unicornuate uterus, 10 with bicornuate uterus (two with two cervices), 45 with septate uterus (five with two cervices), three with arcuate uterus and three with DES-related uterine malformations. The concordance between 3D ultrasound and MRI was very good (kappa index, 0.880 (95% CI, 0.769-0.993)). Discrepancies in diagnosis between the two techniques occurred in four cases. There was very good concordance in the diagnosis of associated findings (kappa index, 0.878 (95% CI, 0.775-0.980)), this analysis identifying differences in two cases. CONCLUSIONS: There is a high degree of concordance between 3D ultrasound and MRI in the diagnosis of uterine malformations, the relationship between cavity and fundus being visualized equally well with both techniques. 3D ultrasound should be complemented by careful gynecological exploration in order to identify any alterations in the cervix.

Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis.

Neurodegenerative diseases are often associated with dysfunction in protein quality control. The endoplasmic reticulum (ER), a key site for protein synthesis, senses stressful conditions by activating the unfolded protein response (UPR). In this study we report the creation of a novel mouse model in which GRP78/BiP, a major ER chaperone and master regulator of UPR, is specifically eliminated in Purkinje cells (PCs). GRP78-depleted PCs activate UPR including the induction of GRP94, PDI, CHOP and GADD34, feedback suppression of eIF2alpha phosphorylation and apoptotic cell death. In contrast to current models of protein misfolding in which an abnormal accumulation of ubiquitinated protein is prominent, cytosolic ubiquitin staining is dramatically reduced in GRP78-null PCs. Ultrastructural evaluation reveals that the ER shows prominent dilatation with focal accumulation of electron-dense material within the ER. The mice show retarded growth and severe motor coordination defect by week 5 and cerebellar atrophy by week 13. Our studies uncover a novel link between GRP78 depletion and reduction in cytosolic ubiquitination and establish a novel mouse model of accelerated cerebellar degeneration with basic and clinical applications.

The case for re-evaluating the upper limit value for selenium in drinking water in Europe.

Selenium is an essential trace element for life, which can be toxic for humans when intakes reach a certain amount. Therefore, since the margin between healthy intake and toxic intake is narrow, the selenium concentration of tap water is a parameter that must be monitored because of its potential for increased intake. The present work gives an overview of the different approaches used to calculate safe limits for selenium. As recommended by WHO, the guidelines for drinking water form the basis of national legislated standards for drinking water. Before setting a maximum acceptable level in drinking water, it is necessary to take into account the total intake of selenium in both food and beverage. The limit value of 10 microg l(-1) for drinking water laid down in the European regulations for all countries should be adapted depending on geographic area, as previously recommended by WHO.

Three-dimensional ultrasound diagnosis of cleft palate: 'reverse face', 'flipped face' or 'oblique face'--which method is best?

OBJECTIVES: To compare the performance of three sonographic techniques, the 'reverse-face', 'flipped-face' and 'oblique-face' methods, for visualizing the hard and soft palate in diagnosing cleft lip and palate (CLP). METHODS: A total of 60 fetuses (10 with CLP) with a gestational age ranging from 20 to 33 weeks were examined. We compared visualization of the secondary palate with the previously described reverse-face and flipped-face methods (the latter modified by us) and the oblique-face method developed by us using Oblique View imaging technology. RESULTS: Among the 10 fetuses with CLP the defect involved the lip, alveolus and secondary palate in seven, and the primary palate only in the remaining three. The upper lip and alveolar ridge were well visualized in all cases with all three methods. Involvement of the hard palate was diagnosed correctly in 71% (5/7) of the cases using the reverse-face view, in 86% (6/7) with the flipped-face view, and in 100% (7/7) with the oblique-face view; the hard palate was correctly found to be intact in 78%, 84% and 86%, respectively, of the 50 normal fetuses examined with each view. Involvement of the soft palate was diagnosed correctly in only one of the seven fetuses with defects of the secondary palate in flipped-face and oblique-face views, and was correctly considered intact in only 16% of normal fetuses in flipped-face view and in 26% in oblique-face images. CONCLUSIONS: Accurate visualization of the soft palate requires an excellent initially acquired volume, fluid between the fetal tongue and palate, and curving of the plane to follow the structure of the palate. The oblique-face or flipped-face views make it possible to visualize the soft palate well in selected cases.

The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells.

In mammalian cells, endoplasmic reticulum (ER) stress has recently been shown to induce autophagy and the induction requires the unfolded protein response (UPR) signaling pathways. However, little is known whether autophagy regulates UPR pathways and how specific UPR targets might control autophagy. Here, we demonstrated that although ER stress-induced autophagy was suppressed by class III phosphatidylinositol-3'-kinase (PI3KC3) inhibitor 3-methyladenine (3-MA), wortmannin and knockdown of Beclin1 using small interfering RNA (siRNA), only 3-MA suppressed UPR activation. We discovered that the UPR regulator and ER chaperone GRP78/BiP is required for stress-induced autophagy. In cells in which GRP78 expression was knocked down by siRNA, despite spontaneous activation of UPR pathways and LC3 conversion, autophagosome formation induced by ER stress as well as by nutrition starvation was inhibited. GRP78 knockdown did not disrupt PI3KC3-Beclin1 association. However, electron microscopic analysis of the intracellular organelle structure reveals that the ER, a putative membrane source for generating autophagosomal double membrane, was massively expanded and disorganized in cells in which GRP78 was knocked down. ER expansion is known to be dependent on the UPR transcription factor XBP-1. Simultaneous knockdown of GRP78 and XBP-1 recovered normal levels of stress-induced autophagosome formation. Thus, these studies uncover 3-MA as an inhibitor of UPR activation and establish GRP78 as a novel obligatory component of autophagy in mammalian cells.

Palliation for suspected unresectable hilar cholangiocarcinoma.

AIM: The aim of this study was to evaluate the outcome of different techniques of palliation for patients with hilar cholangiocarcinoma. METHOD: All patients treated with palliative intent between 1988 and 2004 at the Royal Infirmary of Edinburgh were reviewed. Patients were analysed on an intention to treat basis. Demographics, procedure and outcome (including re-admissions) were recorded. RESULTS: Two hundred and thirty-three patients underwent palliative treatment for suspected hilar cholangiocarcinoma. The diagnosis was confirmed histologically in 109 patients. The procedure related morbidity and mortality was 54/225 and 18/207 respectively. Seventy-one patients required re-admission. Twenty patients underwent surgical biliary bypass for jaundice. Those undergoing surgical palliation had a longer median (95% CI) time to re-admission (16 (0-36) vs.7 (2-12) weeks, p=0.001). Endoscopic retrograde cholangio-pancreatography (ERCP) and stenting was only successful in 28 patients and was associated with a significantly higher re-admission rate compared to patients in whom ERCP was not performed (60/179 vs. 4/27, p=0.050). The overall median (95% CI) survival was 145 (124-185) days. CONCLUSION: Current options for palliation of hilar cholangiocarcinoma provide good short term success but are all associated with significant early and late morbidity. Due to its low success and association with an increased re-admission rate, ERCP for definitive palliation should not be used in the first line staging and management of these patients.

Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy.

AIMS: To determine whether hepatocyte growth factor (HGF) and connective tissue growth factor (CTGF) are expressed in human specimens of proliferative vitreoretinopathy (PVR) and to propose a model of PVR pathogenesis based upon the known activities of these growth factors. Methods Immunohistochemical methods (ABC Elite) were used to demonstrate the presence of HGF and CTGF in cryostat sections of five human PVR membranes. RESULTS: In each of the five PVR membranes, stromal cells were immunohistochemically positive for both HGF and CTGF. Based upon this information and the known actions of these growth factors, a model of PVR pathogenesis was developed. In this model, injury of the retina induces an inflammatory response that upregulates HGF expression inducing the formation of multilayered groups of migratory retinal pigment epithelial cells (RPE). These RPE, present in a provisional extracellular matrix, come in contact with vitreous containing TGF-beta. The TGF-beta is activated, upregulating expression of CTGF. Under the influence of TGF-beta and CTGF, RPE become myofibroblastic and fibrosis ensues. Retinal traction induces further detachment continuing the cycle of retinal injury. CONCLUSIONS: HGF and CTGF are expressed in PVR membranes and may play important roles in the pathogenesis of PVR. The expression and function of these growth factors should be critically examined in human PVR specimens, in in vitro cultures of RPE, and in animal models of PVR.

Synthesis and biological evaluation of destruxin A and related analogs.

This report describes the development of an efficient solid-phase synthesis protocol and adaptation of reported solution phase procedures for the synthesis of the cyclic depsihexapeptide destruxin A and related analogs. The solid-phase method described is based on standard Fmoc peptide chemistry, including a new synthetic method for the assembly of the depsi bond-containing unit. In order to select analogs of destruxin A for synthesis and evaluation of insecticidal activity, the work of Hellberg et al., describing a set of Z-descriptors for amino acid side-chains comparing their physicochemical properties, was utilized. Destruxin A and 27 different analogs with structural variations in four residues were synthesized and insecticidal activity was evaluated via injections into tobacco budworm (Heliothis virescens) larvae. Several destruxin A analogs were found to be at least as potent as the native compound.

Zinc nasal gel for the treatment of common cold symptoms: a double-blind, placebo-controlled trial.

Effective treatment for the common cold have been difficult to develop because so many different types of virus are responsible for this condition. Oral zinc has been studied as a possible means of preventing or alleviating symptoms, with mixed results. We studied a new approach to zinc therapy--an over-the-counter nasal gel formulation (Zicam)--to independently evaluate its efficacy as a treatment for the common cold. Our study was conducted at four sites over a 5-month period. The study group consisted of 213 patients with recent-onset(< or = 24) cold symptoms; 108 patients received zinc therapy, and 105 reviewed placebo. Symptom charts were used to track the duration and severity of each patient's symptoms. At study's end, the duration of symptoms was 2.3 days (+/-0.9)in the zinc group and 9.0 days (+/-2.5)in the control group--a statistically significant difference (p <0.05). These results provide evidence that zinc nasal gel is effective in shortening the duration of common cold symptoms off when taken within 24 hours of their onset.

La anatomía patológica como factor pronóstico en el carcinoma lobulillar invasivo de la mama / Invasive lobular carcinoma of the breast : histopathology as a prognostic factor

Propósito: El carcinoma lobulillar invasivo de la mama presenta características únicas que lo diferencian del carcinoma ductal, como los hallazgos frecuentes de multicentricidad, bilateralidad, afectación de la mama contralateral, la positividad de los márgenes de la pieza y un teórico mayor porcentaje de afectación a nivel regional, que podrían influir en el pronóstico de la enfermedad. Material y métodos: Con el ánimo de evaluar las características definitorias del pronóstico en este tipo tumoral, se han estudiado ciertos factores de la anatomía patológica, como lo son el tamaño tumoral, el nivel de afectación axilar, el grado de malignidad tumoral, la afectación de los márgenes de la pieza, la muticentridad y la positividad de los receptores tumorales, para relacionarlos con la supervivencia a largo plazo en una población de 390 casos de carcinoma lobulillar invasivo de la mama en un estudio multicéntrico que refiere los resultados del período 1980-1997. Resultados y conclusiones: En conclusión, se observa que el pronóstico del carcinoma lobulillar se determina por el nivel de afectación regional, el tamaño tumoral y el grado de malignidad tumoral principalmente; la afectación axilar demuestra esta influencia en períodos avanzados del seguimiento de la paciente la positividad de los márgenes tumorales y la multicentricidad no se relacionan significativamente con el pronóstico (AU)