Mastectomía preservadora de piel con colgajo dermograso desepitelizado (técnica de Spira modificada) y reconstrucción mediante implante directo

Introducción La técnica de Spira es un tipo de mastectomía preservadora de piel que permite la reconstrucción inmediata (RMI), ideal en mamas ptósicas. Si bien, persiste controversia sobre resultados oncológicos en el cáncer de mama. El objetivo es analizar complicaciones, secuelas cosméticas, causas de reintervención y resultados oncológicos. Métodos Estudio observacional retrospectivo de pacientes intervenidas durante 2003-2018 en nuestro centro. La población de estudio la constituyen pacientes con carcinoma de mama o sometidas a mastectomía profiláctica por alto riesgo, en las que se realizó una mastectomía preservadora de piel con colgajo dermograso desepitelizado (técnica de Spira modificada) y reconstrucción mediante implante directo. Se analiza la presencia de complicaciones precoces y tardías, secuelas, recidiva tumoral y supervivencia. Resultados Se realizaron 247 mastectomías con reconstrucción en 139 pacientes, 216 bilaterales (87, 4%) y 31 unilaterales (12, 5%); 121 terapéuticas (49%) y 126 profilácticas (51%). La mediana de seguimiento fue de 81 meses. Se observaron complicaciones en un 16, 2%; necrosis cutánea en 5, 3% y cinco casos de necrosis del CAP (2%). La tasa de reintervención por secuelas cosméticas fue del 17, 4% (la más frecuente fue contractura capsular 11, 3%) y, de ellas, el 39, 3% recibieron RT. La tasa de recidiva fue del 14% (0, 8% cutánea, 3, 3% locorregional y 9, 9% a distancia). Ocho pacientes fallecieron (6, 6%). La SLE y SG fue del 92, 6% y 93, 3% a cinco años. Conclusión La técnica de Spira constituye una opción segura y ofrece buenos resultados cosméticos y oncológicos como tratamiento y profilaxis de cáncer de mama en mamas ptósicas de moderado a gran tamaño. Introduction: Spira technique is a type of nipple-sparing mastectomy that allows immediate reconstruction (IBR), ideal for ptosic breasts. Although, controversy persists regarding oncological results in breast cancer. The aim is to analyze complications, cosmetic outcomes, causes of reoperation and oncological results. Methods: Retrospective observational analysis of patients undergone surgery during 2003-2018 in our center. Study population is based on patients with breast carcinoma or undergoing prophylactic mastectomy due to high-risk, in which a skin-sparing mastectomy with a de-epithelialized derma-fat flap (modified Spira technique) and direct to implant reconstruction was performed. Short and long-term complications, sequelae, tumor recurrence and survival rates are analyzed. results: A total of 247 mastectomies with immediate reconstruction in 139 patients, 216 bilateral (87.4%) and 31 unilateral (12.5%) were performed. 121 therapeutic (49%) and 126 prophylactic (51%). Median follow-up 81 months. Complications were observed in 16.2%; skin necrosis 5.3% and 5 cases of NAC necrosis (2%). Reoperation rate due to cosmetic sequelae was 17.4% (capsular contracture was the most frequent, 11.3%) and a 39.3% of these patients have received RT. Recurrence of 14% (0.8% skin, 3.3% locoregional and 9.9% metastatic), 8 patients died (6.6%). Rates of FSD and OS were 92.6% and 93.3% respectively. Conclusion: Spira mastectomy is a safe option and provides good cosmetic and oncologic results as breast cancer treatment and prophylaxis in moderate-large ptosic breasts

Mastectomía ahorradora de piel y pezón en carcinoma ductal in situ. Seguridad oncológica a 10 años

Objetivo El objetivo es evaluar la seguridad oncológica a 10 años de la mastectomía ahorradora de piel y pezón (MAP) en pacientes con carcinoma ductal in situ (CDIS). Método Análisis observacional retrospectivo. Se realizaron 35 MAP en pacientes con CDIS durante 2005-2018. Evaluamos resultados histológicos, oncológicos y de morbilidad. Resultados Las indicaciones más frecuentes fueron márgenes afectos tras tumorectomía (31, 5%), multifocalidad/multicéntricidad (22, 8%), tumor >3 cm (8, 6%) correlación desfavorable tamaño tumoral/mama (8, 6%) y decisión de la paciente (8, 6%). La técnica más usada fue incisión lateral externa en 11 pacientes, seguida de técnica de Spira en nueve casos. La presencia de CDIS se confirmó en 22 pacientes y en 11 no se encontró tumor en la pieza de mastectomía. La tasa de complicaciones fue 22, 8%. Tras una mediana de seguimiento de 104 meses (DE 69, 9) no se observó necrosis del pezón. Un 20% de pacientes precisó reintervención a largo plazo. Once pacientes (31, 4%) recibieron tratamiento adyuvante (QT y/o RT). Solamente una paciente presentó recurrencia local (2, 8%) 28 meses tras la intervención. Una paciente presentó metástasis tras 78 meses de SLE. Las tasas de SLE y SG fueron 94, 3% y 97, 22%. El análisis univariante mostró dos factores de riesgo de recurrencia: edad <40 [OR (IC95) 2, 529 (1, 230 - 5, 199)] y márgenes afectos [OR (IC95) 5, 242 (2, 041 - 13, 464)]. Conclusión La MAP es factible y segura en pacientes con CDIS no candidatas a cirugía conservadora. Objective: The aim of this study was to assess the oncological safety of nipple-sparing mastectomy (NSM) in patients with ductal in situ carcinoma (DCIS) over a 10-year period. Method: Retrospective observational analysis. A total of 35 NSM were performed in patients with DCIS from 2005 - 2018. We assessed the histological, oncological and morbidity results. Results: The most frequent indications were margin involvement after lumpectomy (31.5%), multifocality / multicentricity (22.8%), tumour size >3 cm (8.6%) unfavourable tumour / breast size correlation (8.6%) and patient choice (8.6%). The most commonly used technique was external lateral incision in 11 patients, followed by the Spira technique in 9 patients. DCIS was confirmed in 22 patients and no tumour was found in mastectomy specimen in 11 patients. The complication rate was 22.8%. After a median follow-up of 104 months (SD 69.9) there was no nipple necrosis. In all, 20% of the patients required long-term reintervention. Eleven patients (31.4%) underwent adjuvant treatment (chemotherapy and / or radiotherapy). Only one patient showed local recurrence (2.8%) 28 months after the intervention. One patient developed metastases after 78 months of disease-free survival (DFS). DFS and overall survival rates were 94.3% and 97.22%. Univariate analysis showed two risk factors for recurrence: age <40 years [OR (95% CI) 2.529 (1.230-5.199)] and margin involvement [OR (95% CI) 5.242 (2.041 - 13.464)]. Conclusion: NSM is safe and feasible in patients with DCIS who are not candidates for conservative surgery

Anti-CCP2 Antibodies: An Overview and Perspective of the Diagnostic Abilities of this Serological Marker for Early Rheumatoid Arthritis

The literature of the last 4 years confirms that the anti-CCP2 test is a very useful marker for the early and specific diagnosis of rheumatoid arthritis (RA). The anti-CCP2 test is very specific for RA (95–99%) and has sensitivity comparable to that of the rheumatoid factor (70–75%). The antibodies can be detected very early in the disease and can be used as an indicator for the progression and prognosis of RA. In this review, these interesting properties and some future possibilities of this diagnostic test are discussed

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil =4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology

VE-statin/egfl7 Expression in Endothelial Cells Is Regulated by a Distal Enhancer and a Proximal Promoter under the Direct Control of Erg and GATA-2

Angiogenesis is the process by which new blood vessels arise from existing ones by the budding out of endothelial cell capillaries from the luminal side of blood vessels. Blood vessel formation is essential for organ development during embryogenesis and is associated with several physiological and pathological processes, such as wound healing and tumor development. The VE-statin/egfl7 gene is specifically expressed in endothelial cells during embryonic development and in the adult. We studied here the regulatory mechanisms that control this tissue-specific expression. RT-qPCR analyses showed that the specificity of expression of VE-statin/egfl7 in endothelial cells is not shared with its closest neighbor genes notch1 and agpat2 on the mouse chromosome 2. Chromatin-immunoprecipitation analysis of histone modifications at the VE-statin/egfl7 locus showed that the chromatin is specifically opened in endothelial cells, but not in fibroblasts at the transcription start sites. A 13 kb genomic fragment of promoter was cloned and analyzed by gene reporter assays which showed that two conserved regions are important for the specific expression of VE-statin/egfl7 in endothelial cells; a −8409/−7563 enhancer and the −252/+38 region encompassing the exon-1b transcription start site. The latter contains essential GATA and ETS-binding sites, as assessed by linker-scanning analysis and site-directed mutagenesis. An analysis of expression of the ETS and GATA transcription factors showed that Erg, Fli-1 and GATA-2 are the most highly expressed factors in endothelial cells. Erg and GATA-2 directly control the expression of the endogenous VE-statin/egfl7 while Fli-1 probably exerts an indirect control, as assessed by RNA interference and chromatin immunoprecipitation. This first detailed analysis of the mechanisms that govern the expression of the VE-statin/egfl7 gene in endothelial cells pinpoints the specific importance of ETS and GATA factors in the specific regulation of genes in this cell lineage

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Objective: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. Methods: HICs were identified in COHERE on the basis of \ue2\u89\ua55 consecutive viral loads (VL) \ue2\u89\ua4500 copies/mL over \ue2\u89\ua51 year whilst ART-naive, with the last VL \ue2\u89\ua4500 copies/mL measured \ue2\u89\ua55 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL &gt;2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. Results: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Discussion: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design