Breast Implant-Associated Anaplastic Large Cell Lymphoma: Two Distinct Clinical Presentations.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare CD30 positive T cell lymphoma whose incidence has recently increased. Until 2020, 733 cases of BIA-ALCL and 36 deaths have been reported around the world, with only one confirmed case in Portugal. The authors describe two clinical cases of BIA-ALCL after breast cancer reconstruction using macrotextured implants. Case 1: A 45-year-old patient, who presented with a typical late-onset seroma five years after breast reconstruction and underwent capsulectomy, confirming localized disease to the capsule. Case 2: A 43-year-old patient presented with an atypical presentation of pleural effusion and tumor mass, 14 years after reconstruction. She underwent implant removal and chemotherapy, due to metastatic disease. These clinical cases illustrate two very distinct clinical presentations of BIA-ALCL. Early diagnosis of this entity allows for effective treatment of the disease, which should be approached in a multidisciplinary setting.

O linfoma anaplásico de grandes células associado aos implantes mamários é um linfoma T CD30 positivo raro, cuja incidência tem aumentado recentemente. Até 2020, estavam registados 733 casos de BIA-ALCL e 36 mortes, em todo o mundo e apenas um caso confirmado em Portugal. Os autores descrevem dois casos de BIA-ALCL, após reconstrução mamária por cancro de mama, com próteses macrotexturadas. Caso 1: Doente com 45 anos, que se apresentou com a manifestação típica de seroma tardio, cinco anos após a colocação da prótese, tendo sido submetida a capsulectomia, que confirmou doença localizada à cápsula. Caso 2: Doente de 43 anos, que se manifestou de forma atípica com derrame pleural e massa tumoral, 14 anos após a colocação da prótese. A doente foi submetida a remoção de prótese e quimioterapia, tendo em conta a doença metastática. Os casos clínicos descritos ilustram duas formas distintas de apresentação clínica de BIA-ALCL. O diagnóstico precoce desta patologia possibilita o seu tratamento de forma eficaz e deve ser abordado em equipa multidisciplinar.

Health-Related Quality of Life After Nipple-Sparing Mastectomy: Results From the INSPIRE Registry.

INTRODUCTION: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is increasingly used for both breast cancer (TNSM) and risk reduction (RRNSM). The aim of the study is to report the results of the INSPIRE registry assessing health-related quality of life (HRQoL) comparing baseline and 1-year follow-up, regarding surgical indications and chemotherapy (CT) received. METHODS: INSPIRE is a prospective database including women undergoing NSM and IBR from 18 countries. HRQoL was measured using EORTC QLQC30 and QLQ-BR23 before surgery and after 1 year. RESULTS: A total of 677 women were included, of whom 537 (79.3%) underwent TNSM and 140 (21.6%) RRNSM: in total, 806 NSM (556 TNSM and 250 RRNSM). Nipple involvement was present in 7.73% of TNSM and incidental carcinoma in 1.2% of the RRNSM group. Out of the overall 537 patients with systemic treatment, 177 (32.96%) received neoadjuvant chemotherapy (NCT) and 118 (21.92%) adjuvant chemotherapy (CT). A total of 227 patients (28.16%) developed at least one complication postoperatively, 164 (29.5%) in the TNSM group and 63 (25.2%) in the RRNSM group. The TNSM group improved in global health status and emotional functioning after 1 year. No differences were found when comparing HRQoL at 1 year between patients who received NCT and those who received adjuvant CT. The RRNSM group showed improvement in HRQoL, with better emotional functioning and fatigue after 1 year. CONCLUSIONS: This registry reports HRQoL findings after NSM. The impact of CT on worse HRQoL is independent from its timing. Patients with RRNSM showed an improved HRQoL at 1-year follow-up. Discussion of HRQoL outcomes with patients will facilitate the informed decision-making when considering NSM.

Occurrence and severity of neck disability in individuals with different types of temporomandibular disorder.

BACKGROUND: Healthcare professionals need to know the degree of disability and severity of their patients to determine actions and therapy needed to minimize potential harm, improve their patient condition, and maximize clinical outcomes. OBJECTIVES: To evaluate the occurrence and severity of neck disability in individuals with muscular, joint, and mixed temporomandibular disorder (TMD). MATERIALS AND METHODS: Cross-sectional study with individuals divided into four groups: muscular TMD (n=20), joint TMD (n=20), mixed TMD (n=20) and control (n=20). For diagnosis and classification of TMD, it was used the Research Diagnostic Criteria (RDC) and to assess the severity of neck dysfunction the Neck Disability Index (NDI). RESULTS: Moderate neck disability was frequent in all individuals with TMD; high scores of neck disability index were evidenced in the mixed and joint TMD groups; there was a moderate positive correlation between the severity of neck disability and TMD severity (r=0.7; CI=0.32-0.78; p<0.03). CONCLUSION: The gravity of neck disability and the severity of TMD are directly proportional in the group of individuals with mixed TMD.

Optimization of Eugenia punicifolia (Kunth) D. C. leaf extraction using a simplex centroid design focused on extracting phenolics with antioxidant and antiproliferative activities.

Eugenia punicifolia (Kunth) D. C. (Myrtaceae) has been showing interesting biological activities in the literature which was correlated to its phenolic compounds. In the sense of a better recovering of phenolics with the best antioxidant and antiproliferative activities, an extraction, based on multivariate analytical approach, was developed from E. punicifolia leaves. The different extractor solvents (ethanol, methanol and water) and their binary and ternary combinations were evaluated using a simplex-centroid mixture design and surface response methodology. The optimized crude extracts were investigated for phenol and flavonoid content and compared to their antioxidant (EC50) and antiproliferative properties against HEp-2 (cell line derived from the oropharyngeal carcinoma) and mononuclear viability cells. Ethanolic extracts showed the best phenolic content with the highest antioxidant activity and moderated activity antiproliferative to HEp-2. ESI-QTOF-MS revealed the presence of quercetin and myricetin derivatives, which was correlated to activities tested. Then, simplex-centroid design allowed us to correlate the Eugenia punicifolia biological activities with the extracts obtained from solvent different polarity mixtures.

Antioxidative, Antiproliferative and Antimicrobial Activities of Phenolic Compounds from Three Myrcia Species.

Myrcia bella Cambess., Myrcia fallax (Rich.) DC. and Myrcia guianensis (Aubl.) DC. (Myrtaceae) are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in the literature connecting their phenolic composition and biological activities. In this regard, we have profiled the main phenolic constituents of Myrcia spp. leaves extracts by ESI(−)Q-TOF-MS. The main constituents found were ellagic acid (M. bella), galloyl glucose isomers (M. guianensis) and hexahydroxydiphenic (HHDP) acid derivatives (M. fallax). In addition, quercetin and myricetin derivatives were also found in all Myrcia spp. extracts. The most promising antioxidant activity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, was found for M. fallax extracts (EC50 8.61 ± 0.22 µg·mL−1), being slightly less active than quercetin and gallic acid (EC50 2.96 ± 0.17 and 2.03 ± 0.02 µg·mL−1, respectively). For in vitro antiproliferative activity, M. guianensis showed good activity against leukemia (K562 TGI = 7.45 µg·mL−1). The best antimicrobial activity was observed for M. bella and M. fallax to Escherichia coli (300 and 250 µg·mL−1, respectively). In conclusion, the activities found are closely related to the phenolic composition of these plants.

The Use of Sentinel Lymph Node Biopsy in BRCA1/2 Mutation Carriers Undergoing Prophylactic Mastectomy: A Retrospective Consecutive Case-Series Study.

INTRODUCTION: Sentinel lymph node biopsy in prophylactic mastectomy is controversial. It avoids lymphadenectomy in occult carcinoma but is associated with increased morbidity. Women with BRCA mutations have a higher incidence of occult carcinoma and our objective was to assess the clinical utility of sentinel lymph node biopsy when these women undergo prophylactic mastectomy. MATERIALS AND METHODS: Seven-year retrospective consecutive case-series study of women, with a BRCA deleterious mutation, admitted to prophylactic mastectomy, at our center. Breast MRI < 6 months before surgery was routine, unless contraindicated. RESULTS: Fifty-seven patients (43% BRCA1; 57% BRCA2) underwent 80 prophylactic mastectomies. 72% of patients had had breast cancer treated before prophylactic mastectomy or synchronously to it. The occult carcinoma incidence was 5%, and half of the cases were invasive. SLNB was performed in 19% of the prophylactic mastectomies; none of these had tumor invasion. Women with invasive carcinoma who had not undergone sentinel lymph node biopsy were followed closely with axillary ultrasound. The median follow-up was 37 months, with no local recurrence; 1 patient died of primary tumor systemic relapse. CONCLUSIONS: Our data do not support this procedure for routine (in agreement with previous literature), in this high risk for occult carcinoma population.

Eugenia aurata and Eugenia punicifolia HBK inhibit inflammatory response by reducing neutrophil adhesion, degranulation and NET release.

BACKGROUND: Eugenia spp. are used in popular medicine in the treatment of pain, diabetes, intestinal disorders and cough. The aim of the work is to evaluate, ex vivo and in vivo, the anti-inflammatory activity of the hydroethanolic extracts of the leaves of Eugenia aurata (EA) and Eugenia punicifolia HBK (EP) upon neutrophils. METHODS: Ex vivo, isolated human neutrophils were sensitized by Eugenia extracts (0.1-1000 µg/mL) and stimulated by PMA. In these conditions, different neutrophil activities related to inflammatory process were measured: adhesion, degranulation and NET release. Neutrophil viability and tumor line cells were monitored. In vivo, neutrophil influx was evaluated by peritonitis model performed in mice pretreated with different concentrations of Eugenia extracts. Phytochemical profile was assessed by mass spectrometry. RESULTS: Ex vivo, EA and EP (1000 µg/mL) reduced cell adhesion and degranulation, respectively. NET release was inhibited by EA and EP. Anti-inflammatory activities occurred in the absence of cytotoxicity. In vivo, both EA as EP inhibited neutrophil migration. The phytochemical profile revealed that EA contains myricitrin, rutin, quinic acid and quercetin derivatives. EP presents gallic acid, quercetin derivatives, syringic acid, ellagic acid, monogalloyl-glucose, glycosyringic acid, mudanoside B, HHDP glucose isomer and digalloylglucose isomer. EA and EP inhibit neutrophil migration by different pathways. CONCLUSION: Different chemical compositions may explain the anti-inflammatory effects described herein for EA and EP. Both extracts inhibit NET release but only EA reduces cell adhesion whereas EP decreases elastase secretion. This work contributes to the elucidation of cellular mechanisms related to the anti-inflammatory activity for leaves of E. aurata and E. punicifolia HBK.

Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression.

BACKGROUND: Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood. METHODS: Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis. RESULTS: Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile. CONCLUSIONS: This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.

LDL-cholesterol signaling induces breast cancer proliferation and invasion.

Lipids and cholesterol in particular, have long been associated with breast cancer (BC) onset and progression. However, the causative effects of elevated lipid levels and breast cancer remain largely undisclosed and were the subject of the present study.We took advantage of well-established in vitro and in vivo models of cholesterol enrichment to exploit the mechanism involved in LDL-cholesterol favouring BC growth and invasiveness. We analyzed its effects in models that mimic different BC subtypes and stages.Our data show that LDL-cholesterol (but not HDL-cholesterol) promotes BC cells proliferation, migration and loss of adhesion, hallmarks of the epithelial to mesenchymal transition. In vivo studies modeling cholesterol levels showed that breast tumors are consistently larger and more proliferative in hypercholesterolemic mice, which also have more frequently lung metastases. Microarray analysis revealed an over expression of intermediates of Akt and ERK pathways suggesting a survival response induced by LDL, confirmed by WB analyses. Gene expression analysis also evidenced an activation of ErbB2 signaling pathway and decreased expression of adhesion molecules (cadherin-related family member3, CD226, Claudin 7 and Ocludin) in the cells exposed to LDL.Together, the present work shows novel mechanistic evidence that high LDL-cholesterol levels promote BC progression. These data provide rationale for the clinical control of cholesterol levels in BC patients.

Enteric repair in aortoduodenal fistulas: a forgotten but often lethal player.

BACKGROUND: An aortoenteric fistula is an abnormal communication between the aorta and the bowel lumen. It is usually caused by previous aortic surgery and involves the duodenum (ADF) in most cases. The treatment of this high-mortality condition is based on the correction of enteric and vascular defects. However, enteric repair indications and impact are unknown. OBJECTIVE: We sought to characterize the surgical procedures available for duodenal repair in ADF and estimate their impact in mortality. METHODS: A literature search was conducted, between the years 1951-2010. Cases (791 from 614 references) were individually registered and analyzed to demography, enteric location, type and cause of fistula, type of surgical procedure, mortality, and cause of death. Risk factors to outcome were estimated by univariate and multivariate analysis. RESULTS: The enteric procedure was described in 331 cases: duodenorrhaphy (with or without omentum interposition; with or without enterostomy) in 266 cases, duodenal resection/reconstruction in 54 cases, antibiotic or abdominal drainage alone in 4 cases, and nothing was done in 7 cases. Vascular treatment was described in 515 cases: extra-anatomic bypass in 207 cases, in situ graft in 197 cases, direct closure of the aortic defect in 52 cases, endovascular procedures in 32 cases, and others arterial reconstructions in 27 cases. Univariate analysis revealed that mortality caused by ADF is directly associated with primary ADF type, direct closure of the aortic defect, and is inversely associated with recent publications, omentum interposition, use of an in situ graft, and endovascular prosthesis. Multivariate analysis revealed that omentum interposition and the use of an in situ graft were independent factors to the outcome, and that omentum use was the strongest factor related to survival. The most common cause of death was ADF recurrence (41.8%), which was significantly high (P = 0.036) in the patients who underwent simple duodenorrhaphy. CONCLUSIONS: The literature supports the use of omentum interposition and suggests that duodenal derivation is preferable to the simple closure of fistula. Delayed or avoided enteric repair after endovascular treatment emerged as an option, but needs additional supporting research.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening.

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties.