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1.
Clin Breast Cancer ; 22(8): e922-e927, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36055918

RESUMEN

BACKGROUND: Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of MPP regarding short-term complications after mastectomy remains an area of ongoing investigation. PATIENTS AND METHODS: A single-institution, retrospective chart review of patients undergoing unilateral mastectomy without reconstruction from January 2019 to 2021 was performed. Primary endpoints included antibiotic prescription, seroma or abscess drainage, readmission, wound dehiscence, and time to drain removal within 30 days of initial surgery. Wilcoxon rank sum test or Student t test was used for group comparisons for continuous variables; Chi-square test or Fisher exact test was used to evaluate the associations among categorical variables. RESULTS: One hundred ninety patients were included; 119 received MPP and 71 did not. There was no difference in antibiotic prescription, infection drainage, hematoma, readmission, dehiscence, or time to drain removal with regards to MPP use. MPP treated patients were older (65.8 years vs. 59.1, P < .001) and had lower albumin levels (4.1 g/dL vs. 4.3, P = .025). Patients who underwent abscess drainage had higher body mass index ( mean 36.1 vs. 30.1 P = .036). Patients requiring seroma drainage were more likely to be diabetic (12.8% vs. 4%, P = .035) and to have been treated with lymphovenous anastomosis (LVA, 15.6% vs. 3.8%, P = .009). Patients who had LVA were significantly less likely to receive MPP when compared to other groups (3.1% vs. 74.7% P < .001). CONCLUSION: Consider utilizing MPP in patients at higher risk of seroma, such as those undergoing axillary surgery including LVA.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Humanos , Femenino , Mastectomía/efectos adversos , Seroma/epidemiología , Seroma/etiología , Estudios Retrospectivos , Absceso/complicaciones , Neoplasias de la Mama/complicaciones , Drenaje , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Polisacáridos , Antibacterianos
2.
Biol Res Nurs ; 24(4): 433-447, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35499926

RESUMEN

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Disfunción Cognitiva , Cardiopatías , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Cognición/fisiología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/genética , Disfunción Cognitiva/psicología , Femenino , Perfil Genético , Genómica , Cardiopatías/inducido químicamente , Humanos , Proteínas Serina-Treonina Quinasas , Sobrevivientes/psicología
3.
Am J Transplant ; 22(3): 717-730, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34668635

RESUMEN

Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable allo-inactivation. AJI-100 significantly reduces the frequency of skin-homing CLA+ donor T cells, limiting allograft invasion and tissue destruction by T effectors. AJI-100 also suppresses pathogenic Th1 and Th17 cells in the spleen yet spares beneficial regulatory T cells. We show dual JAK2/Aurora kinase A blockade enhances human type 2 innate lymphoid cell (ILC2) responses, which are capable of tissue repair. ILC2 differentiation mediated by GATA3 requires STAT5 phosphorylation (pSTAT5) but is opposed by STAT3. Further, we demonstrate that Aurora kinase A activation correlates with low pSTAT5 in ILC2s. Importantly, AJI-100 maintains pSTAT5 levels in ILC2s by blocking Aurora kinase A and reduces interference by STAT3. Therefore, combined JAK2/Aurora kinase A inhibition is an innovative strategy to merge immune suppression with tissue repair after transplantation.


Asunto(s)
Aurora Quinasa A , Inmunidad Innata , Animales , Aurora Quinasa A/metabolismo , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Humanos , Janus Quinasa 2 , Ratones , Ratones Endogámicos C57BL , Células Th17 , Trasplante Homólogo
4.
Cancer Med ; 10(21): 7665-7672, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34590788

RESUMEN

BACKGROUND: Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real-world benefit of first-line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. METHODS: This study included HR-positive, HER2-negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression-free survival (PFS) was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time-dependent variable. RESULTS: In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93-NR). Median PFS for patients with bone-only metastases (n = 54) was not reached (95% CI 18.21-NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33-33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71-0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97-1.18, p = 0.203). CONCLUSION: The effectiveness of palbociclib and endocrine therapy in the treatment of HR-positive, HER2-negative mBC in the real-world setting is similar to the efficacy reported in the PALOMA-2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Letrozol/uso terapéutico , Neutropenia/inducido químicamente , Piperazinas/uso terapéutico , Piridinas/uso terapéutico , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Letrozol/efectos adversos , Recuento de Leucocitos , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutrófilos , Piperazinas/efectos adversos , Supervivencia sin Progresión , Piridinas/efectos adversos , Receptor ErbB-2/análisis , Factores de Transcripción/análisis
5.
J Natl Compr Canc Netw ; 19(1): 40-47, 2021 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-33406495

RESUMEN

BACKGROUND: Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. MATERIALS AND METHODS: A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). RESULTS: Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CONCLUSIONS: CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.


Asunto(s)
Neoplasias de la Mama , Escisión del Ganglio Linfático , Biopsia del Ganglio Linfático Centinela , Axila , Neoplasias de la Mama/cirugía , Disección , Femenino , Humanos , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos
6.
Clin Breast Cancer ; 21(1): 74-79, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32917535

RESUMEN

BACKGROUND: The standard of care for clinically node-negative (cN0) patients following positive sentinel lymph node biopsy (SLNB) was completion axillary lymph node dissection (CALND). Publication of ACOSOG Z0011 in 2010 changed this standard for patients undergoing lumpectomy. Clinicians have since expanded this practice to mastectomy patients, and ongoing prospective studies are seeking to validate this practice. Here, we evaluate patient and tumor characteristics that led surgeons to forego a second surgery for CALND in cN0 mastectomy patients with positive SLNB. PATIENTS AND METHODS: A single institution, retrospective review of cN0 patients with invasive primary breast cancer and positive SLNB from 2010 to 2016 was performed. Patients with T4 disease, positive preoperative axillary biopsy, prior neoadjuvant therapy or axillary surgery were excluded. Patients with positive SLNB undergoing CALND were compared with patients for whom CALND was omitted. Statistical analysis was performed using Kruskal-Wallis tests for continuous variables and χ2 tests or Fischer exact tests for categorical variables. RESULTS: Of 259 patients with positive SLNB, 180 (69.4%) patients underwent mastectomy. CALND was performed at the time of mastectomy in 54 (30%) patients, at time of second operation in 22 (12.2%) patients, and not performed in 104 (57%) patients. Delayed CALND was significantly associated with younger age, larger tumors, increased number of positive sentinel nodes, invasive lobular carcinoma, extranodal extension, and lymphovascular invasion. CONCLUSIONS: The management of cN0 patients with positive SLNB that do not meet ACOSOG Z0011 criteria is evolving and is influenced by tumor and patient characteristics in an attempt to balance the morbidity of CALND with the low rate of local regional recurrence.


Asunto(s)
Neoplasias de la Mama/cirugía , Metástasis Linfática/terapia , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Ganglio Linfático Centinela/cirugía , Adulto , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Metástasis Linfática/patología , Persona de Mediana Edad , Selección de Paciente , Estudios Retrospectivos , Ganglio Linfático Centinela/patología
7.
Clin Breast Cancer ; 21(3): e189-e193, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32893094

RESUMEN

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is commonly used for patients with clinically detected nodal metastases. Sentinel lymph node biopsy (SLNB) after NAC is feasible. Excision of biopsy-proven positive lymph nodes in addition to SLNB, termed targeted axillary dissection (TAD), decreases the false-negative rate of SLNB alone. Positive nodes can be marked with radar reflector-localization (RRL) clips. We report our institutional experience with RRL-guided TAD and demonstrate its safety and feasibility. PATIENTS AND METHODS: We performed an institutional review board-approved retrospective review of consecutive clinically node-positive female patients with breast cancer treated with NAC and RRL-guided TAD between January 2017 and September 2019. Clinicopathologic and treatment data were collected; descriptive statistics are reported. RESULTS: Forty-five patients were analyzed; the median age was 55 years (range, 20-72 years), and the median body mass index was 27.2 kg/m2 (range, 16.5-40.4 kg/m2). All patients received NAC, primary breast surgery, and TAD. All clinically detected nodal metastases were confirmed with percutaneous biopsy and marked with a biopsy clip. RRL clips were implanted a median of 8 days (range, 1-167 days) prior to surgery; all were retrieved without complications. The RRL node was identified as the sentinel lymph node in 36 (80%) patients. Twenty-five patients had positive nodes, of which 24 were identified by RRL node excision, and 1 (4%) patient had a positive node identified by SLNB but not RRL. Over a median follow-up time of 29.6 months, 5 patients recurred (1 local, 4 distant). CONCLUSIONS: RRL-guided TAD after NAC is safe and feasible. This technique allows for adequate assessment of the nodal basin and helps confirm excision of the previously biopsied positive axillary node.


Asunto(s)
Neoplasias de la Mama/patología , Escisión del Ganglio Linfático/métodos , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela/métodos , Resultado del Tratamiento , Adulto Joven
8.
J Surg Res ; 254: 378-383, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32535256

RESUMEN

BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS. METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence. CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.


Asunto(s)
Neoplasias de la Mama/patología , Mama/patología , Carcinoma Ductal de Mama/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/terapia , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos
9.
JCI Insight ; 5(9)2020 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-32255769

RESUMEN

Immunosuppressive donor Tregs can prevent graft-versus-host disease (GVHD) or solid-organ allograft rejection. We previously demonstrated that inhibiting STAT3 phosphorylation (pSTAT3) augments FOXP3 expression, stabilizing induced Tregs (iTregs). Here we report that human pSTAT3-inhibited iTregs prevent human skin graft rejection and xenogeneic GVHD yet spare donor antileukemia immunity. pSTAT3-inhibited iTregs express increased levels of skin-homing cutaneous lymphocyte-associated antigen, immunosuppressive GARP and PD-1, and IL-9 that supports tolerizing mast cells. Further, pSTAT3-inhibited iTregs significantly reduced alloreactive conventional T cells, Th1, and Th17 cells implicated in GVHD and tissue rejection and impaired infiltration by pathogenic Th2 cells. Mechanistically, pSTAT3 inhibition of iTregs provoked a shift in metabolism from oxidative phosphorylation (OxPhos) to glycolysis and reduced electron transport chain activity. Strikingly, cotreatment with coenzyme Q10 restored OxPhos in pSTAT3-inhibited iTregs and augmented their suppressive potency. These findings support the rationale for clinically testing the safety and efficacy of metabolically tuned, human pSTAT3-inhibited iTregs to control alloreactive T cells.


Asunto(s)
Rechazo de Injerto , Enfermedad Injerto contra Huésped , Factor de Transcripción STAT3/fisiología , Linfocitos T Reguladores , Animales , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Ratones , Oxidación-Reducción , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo
10.
Breast J ; 26(3): 514-516, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31495018

RESUMEN

Postoperative chyle leak is an exceedingly rare complication following breast and axillary surgery. We present the first described case of chyle leak following breast-conserving surgery and sentinel lymph node biopsy. Management should begin with appropriated conservative measures aimed at reduction of lymph production and flow. Intervention is warranted when conservative strategies fail and include sclerotherapy, lymphangiography, embolization, and surgery. Breast surgeons should be mindful of this potential complication when operating in the axilla and be familiar with its stepwise management.


Asunto(s)
Neoplasias de la Mama , Quilo , Axila , Neoplasias de la Mama/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Mastectomía Segmentaria , Biopsia del Ganglio Linfático Centinela/efectos adversos
11.
Clin Breast Cancer ; 20(1): e14-e19, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31780380

RESUMEN

INTRODUCTION: Implant-sparing mastectomy (ISM) is a skin-sparing mastectomy that preserves a retropectoral implant and potentially eliminates the need for tissue expansion or complex reconstruction. This study aimed to determine oncologic and surgical outcomes and reconstructive patterns in patients undergoing ISM. PATIENTS AND METHODS: A single-institution, retrospective review of patients undergoing ISM from 2006 to 2018 was performed. Patient/tumor characteristics, stage, adjuvant therapy use, 90-day complication rates, reconstruction type, and disease recurrence were collected. RESULTS: A total of 121 ISMs in 73 women were performed. Seventy (57.9%) ISMs were for breast cancer (BC) treatment and 51 (42.1%) for prophylaxis. Among BC cases, 72.3% were cT1/cT2 and 73.8% were cN0; 72.3% received systemic therapy and 33.8% received radiation therapy. There were 3 deaths owing to BC at the median follow-up of 35 months. Among 5 recurrences, only 1 was local. There was no BC identified after prophylactic ISM. Total 90-day complication rate per ISM was 15.7%. Rates were 0.8% for both seroma and wound infection, 2.5% for wound dehiscence, 3.3% for hematoma, and 8.2% for skin necrosis. The majority (72.6%) of patients required only implant exchange for reconstruction. Overall use of autologous reconstruction was low (12.3%); 77.8% of flaps were performed in patients receiving radiation therapy. CONCLUSION: ISM is a unique approach for patients pursuing mastectomy for BC treatment or prevention with equivalent oncologic outcomes and complication rates to mastectomy with reconstruction. Reconstruction for the majority was markedly simplified by elimination of tissue expansion while maintaining a low rate of flap reconstruction.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama/terapia , Mamoplastia/métodos , Mastectomía Subcutánea/efectos adversos , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Mama/patología , Mama/cirugía , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Mamoplastia/instrumentación , Mastectomía Subcutánea/métodos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/prevención & control , Complicaciones Posoperatorias/etiología , Radioterapia Adyuvante , Estudios Retrospectivos , Colgajos Quirúrgicos/trasplante , Resultado del Tratamiento , Adulto Joven
12.
World J Surg ; 43(3): 839-845, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30456482

RESUMEN

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to improve surgical, anesthetic, and economic outcomes in intermediate-to-high-risk surgeries. Its influence on length of stay and cost of low-risk surgeries has yet to be robustly studied. As value-based patient care comes to the forefront of anesthesiology research, the focus shifts to strategies that maintain quality while effectively containing cost. METHODS: In July 2016, we implemented an ERAS for mastectomy protocol consisting of limiting fasting state, preoperative multimodal analgesia, and pectoralis I and II blocks. After 1 year, patient records were retrospectively reviewed for length of stay, opioid consumption, pain scores, and hospital charges. RESULTS: Implementation of an ERAS protocol for mastectomies led to a decrease in opioid consumption, and statistically significant decrease in length of stay (1.19 vs. 1.44, p = 0.01). No significant change in hospital charges was observed ($25,787 vs. $25,863, p = 0.97); however, the variance of charges was significantly decreased (6.8 × 107 vs. 1.5 × 108, p = 0.002). The decrease in length of stay translated to an extra 100 hospital bed days which can provide up to an additional $2,100,000 in gross patient service revenue from additional mastectomy volume. CONCLUSION: ERAS protocols for mastectomies may prove beneficial by allowing growing hospitals to increase bed capacity and consequently surgical volume. Despite no change in hospital charges, we predict a potential increase in gross patient service revenue of $2.1 million due to saved hospital bed days.


Asunto(s)
Neoplasias de la Mama/cirugía , Tiempo de Internación/economía , Mastectomía/economía , Atención Perioperativa/métodos , Anciano , Analgésicos Opioides/uso terapéutico , Neoplasias de la Mama Masculina/cirugía , Femenino , Precios de Hospital , Humanos , Masculino , Mastectomía/efectos adversos , Persona de Mediana Edad , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Retrospectivos
13.
Front Immunol ; 9: 2887, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30574153

RESUMEN

Acute graft- vs. -host disease (GVHD) is an important cause of morbidity and death after allogeneic hematopoietic cell transplantation (HCT). We identify a new approach to prevent GVHD that impairs monocyte-derived dendritic cell (moDC) alloactivation of T cells, yet preserves graft- vs.-leukemia (GVL). Exceeding endoplasmic reticulum (ER) capacity results in a spliced form of X-box binding protein-1 (XBP-1s). XBP-1s mediates ER stress and inflammatory responses. We demonstrate that siRNA targeting XBP-1 in moDCs abrogates their stimulation of allogeneic T cells. B-I09, an inositol-requiring enzyme-1α (IRE1α) inhibitor that prevents XBP-1 splicing, reduces human moDC migration, allo-stimulatory potency, and curtails moDC IL-1ß, TGFß, and p40 cytokines, suppressing Th1 and Th17 cell priming. B-I09-treated moDCs reduce responder T cell activation via calcium flux without interfering with regulatory T cell (Treg) function or GVL effects by cytotoxic T lymphocytes (CTL) and NK cells. In a human T cell mediated xenogeneic GVHD model, B-I09 inhibition of XBP-1s reduced target-organ damage and pathogenic Th1 and Th17 cells without impacting donor Tregs or anti-tumor CTL. DC XBP-1s inhibition provides an innovative strategy to prevent GVHD and retain GVL.


Asunto(s)
Células Dendríticas/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia de Inmunosupresión/métodos , Leucemia/terapia , Proteína 1 de Unión a la X-Box/antagonistas & inhibidores , Animales , Línea Celular Tumoral , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/inmunología , Endorribonucleasas/antagonistas & inhibidores , Endorribonucleasas/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Técnicas de Silenciamiento del Gen , Enfermedad Injerto contra Huésped/inmunología , Efecto Injerto vs Leucemia/inmunología , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/inmunología , Inflamasomas/metabolismo , Isoanticuerpos/inmunología , Isoanticuerpos/metabolismo , Isoantígenos/inmunología , Leucemia/inmunología , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Interferente Pequeño/metabolismo , Trasplante de Piel , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Quimera por Trasplante , Trasplante Homólogo/efectos adversos , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/inmunología , Proteína 1 de Unión a la X-Box/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
14.
JAMA Surg ; 153(2): 123-129, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28903167

RESUMEN

Importance: Nipple-sparing mastectomy (NSM) offers superior cosmetic outcomes and has been gaining wide acceptance; however, its role among patients with BRCA mutations remains controversial. Objective: To report on the oncologic safety of NSM and provide evidence-based data to patients and health care professionals regarding preservation of the nipple-areolar complex during a risk-reducing mastectomy in a population with BRCA mutations. Design, Setting, and Participants: We retrospectively reviewed the outcomes of 9 institutions' experience with prophylactic NSM from 1968 to 2013 in a cohort of patients with BRCA mutations. Patients with breast cancer were included if they underwent contralateral risk-reducing mastectomy; however, only the prophylactic side was considered in the analysis. Patients found to have an occult primary breast cancer at the time of risk-reducing mastectomy, those having variant(s) of unknown significance, and those undergoing free nipple grafts were excluded. Main Outcomes and Measures: The primary outcome measure was development of a new breast cancer after risk-reducing NSM. Three reference data sources were used to model the expected number of events, and this was compared with our observed number of events. Results: A total of 548 risk-reducing NSMs in 346 patients were performed at 9 institutions. The median age at NSM was 41 years (interquartile range, 34.5-47.5 years). Bilateral prophylactic NSMs were performed in 202 patients (58.4%), and 144 patients (41.6%) underwent a unilateral risk-reducing NSM secondary to cancer in the contralateral breast. Overall, 201 patients with BRCA1 mutations and 145 with BRCA2 mutations were included. With median and mean follow-up of 34 and 56 months, respectively, no ipsilateral breast cancers occurred after prophylactic NSM. Breast cancer did not develop in any patients undergoing bilateral risk-reducing NSMs. Using risk models for BRCA1/2 mutation carriers, approximately 22 new primary breast cancers were expected without prophylactic NSM. Prophylactic NSM resulted in a significant reduction in breast cancer events (test of observed vs expected events, P < .001). Conclusions and Relevance: Nipple-sparing mastectomies are highly preventive against breast cancer in a BRCA population. Although the follow-up remains relatively short, NSM should be offered as a breast cancer risk-reducing strategy to appropriate patients with BRCA mutations.


Asunto(s)
Neoplasias Primarias Secundarias/prevención & control , Pezones , Tratamientos Conservadores del Órgano , Mastectomía Profiláctica/métodos , Neoplasias de Mama Unilaterales/cirugía , Adulto , Femenino , Estudios de Seguimiento , Genes BRCA1 , Genes BRCA2 , Humanos , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Neoplasias de Mama Unilaterales/genética
15.
South Med J ; 110(10): 660-666, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28973708

RESUMEN

BACKGROUND: Breast-conserving surgery with adjuvant radiation therapy (BCT) has been established as safe oncologically. Oncoplastic breast surgery uses both oncologic and plastic surgery techniques for breast conservation to improve cosmetic outcomes. We evaluated the risk factors associated with complications after oncoplastic breast reduction. METHODS: A single-institution, institutional review board-approved, retrospective review of electronic medical records of female patients with breast cancer who underwent oncoplastic breast reduction from 2008 to 2014. A review of electronic medical records collected relevant medical history, clinical and pathological information, and data on postoperative complications within 6 months stratified into major or minor complications. Categorical variables analyzed with the χ2 exact method; continuous variables were analyzed with the Wilcoxon rank sum test exact method. RESULTS: We identified 59 patients; 4 required re-excision for positive margins, and 1 moved on to completion mastectomy. The overall complication rate was 33.9% (n = 20): 12 major (20.3%) and 8 minor (13.6%). Of the continuous variables (age, body mass index, and tissue removed), increased age was associated with minor complications (P = 0.02). Among the categorical variables (stratified body mass index, prior breast surgery, hypertension, diabetes mellitus, hyperlipidemia, vascular disease, pulmonary disease, and stratified weight of tissue removed), none were associated with overall or major complications. Pulmonary disease was associated with minor complications (P = 0.03). Bilateral versus unilateral oncoplastic breast reduction showed no statistically significant increase in complications. CONCLUSIONS: The overall complication rate after oncoplastic breast reduction was markedly higher than that in nationally published data for breast-conserving surgery. The complication rate resembled more closely the complication rate after bilateral mastectomy with immediate reconstruction. No risk factors were associated with major or overall complications. Age and pulmonary disease were associated with minor complications. Patients should be selected and counseled appropriately when considering oncoplastic breast reduction.


Asunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia , Mastectomía Segmentaria , Complicaciones Posoperatorias/epidemiología , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Hiperlipidemias/epidemiología , Hipertensión/epidemiología , Enfermedades Pulmonares/epidemiología , Márgenes de Escisión , Mastectomía , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Radioterapia Adyuvante , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Carga Tumoral
16.
Breast J ; 23(6): 647-655, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28397344

RESUMEN

Patients with a diagnosis of invasive breast cancer are increasingly undergoing breast magnetic resonance imaging (MRI) for preoperative staging including evaluation of axillary lymph node metastases (ALNM). This retrospective study aims to evaluate the utility of adding axillary ultrasound (AUS) in the preoperative setting when an MRI is planned or has already been performed. This IRB approved, HIPAA compliant study reviewed a total of 271 patients with a new diagnosis of invasive breast cancer at a single institution, between June 1, 2010 and June 30, 2013. The study included patients who received both AUS and MRI for preoperative staging. Data were divided into two cohorts, patients who underwent MRI prior to AUS and those who underwent AUS prior to MRI. AUS and MRI reports were categorized according to BI-RADS criteria as "suspicious" or "not suspicious" for ALNM. In the setting of a negative MRI and subsequent positive AUS, only one out of 25 cases (4%) were positive for metastases after correlating with histologic pathology. MRI detected metastatic disease in four out of 27 (15%) patients who had false-negative AUS performed prior to MRI. Our results indicate the addition of AUS after preoperative MRI does not contribute significantly to increased detection of missed disease. MRI could serve as the initial staging imaging method of the axilla in the setting that AUS is not initially performed and may be valuable in identification of lymph nodes not identified on AUS.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Axila/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Reacciones Falso Negativas , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Ultrasonografía
17.
Ultrasound Med Biol ; 43(4): 775-781, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28187928

RESUMEN

Ultrasound (US) allows real-time tumor assessment. We evaluated the volumetric limits of 2-D and 3-D US, compared with magnetic resonance imaging (MRI), with a prospective institutional review board-approved clinical evaluation of US-to-MRI volumetric correlation. US images of pre- and post-neoadjuvant breast cancers were obtained. Volume discrepancy was evaluated with the non-parametric Wilcoxon signed-rank test. Expected inter-observer variability <14% was evaluated as relative paired difference (RPD); clinical relevance was gauged with the volumetric standard error of the mean (SEM). For 42 patients, 133 of 170 US examinations were evaluable. For tumors ≤20 cm3, both highly correlated to MRI with RPD within inter-observer variability and Pearson's correlation up to 0.86 (0.80 before and 0.86 after neoadjuvant chemotherapy, respectively). Lesions 20-40 cm3 had US-to-MRI discrepancy within inter-observer variability for 2-D (RPD: 13%), but not 3-D (RPD: 27%) US (SEM: 1.47 cm3 for 2-D, SEM: 2.28 cm3 for 3-D), suggesting clinical utility. Tumors >40 cm3 correlated poorly. Tumor volumes ≤20 cm3 exhibited a good correlation to MRI. Studies of clinical applications are warranted.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Imagenología Tridimensional/métodos , Carga Tumoral , Ultrasonografía Mamaria/métodos , Adulto , Mama/diagnóstico por imagen , Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
18.
Clin Breast Cancer ; 17(3): 180-187, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27956116

RESUMEN

BACKGROUND: Breast magnetic resonance imaging (MRI) for assessment of regional breast cancer metastasis is controversial owing to the variable specificity. We evaluated breast MRI for axillary metastasis in neoadjuvant chemotherapy patients. MATERIALS AND METHODS: A single-institution, institutional review board-approved prospective trial enrolled female breast cancer patients receiving neoadjuvant chemotherapy from 2008 to 2012 and collected the pre- and post-treatment MRI, pretreatment axillary ultrasound, axillary biopsy, and surgical pathologic findings. The kappa coefficient was used to evaluate the strength of the agreement between the 2 modalities and Fisher's exact test was used to evaluate the association. RESULTS: A total of 43 patients were included. Of these 45 patients, 35 had stage N1-N2 before treatment. Comparing the abnormal results on the pretreatment MRI scans and axillary biopsy examinations, a consistent diagnosis was found for 92%, with a moderate strength of agreement (kappa coefficient, 0.54). The pretreatment MRI findings were significantly associated with the axillary biopsy results (P = .014). The false-positive rate, false-negative rate, sensitivity, and specificity were 50%, 3%, 97%, 50%, respectively. Comparing the post-treatment MRI and surgical pathologic findings revealed a consistent diagnosis rate of, with a slight strength of agreement (kappa, 0.16). The false-positive rate, false-negative rate, sensitivity, and specificity were 38%, 46%, 55%, and 63%, respectively. The post-treatment MRI findings were not associated with the pathologic lymph node results (P = .342). CONCLUSION: Pretreatment breast MRI was more specific for axillary metastasis than was axillary ultrasonography. However, post-treatment breast MRI was not predictive of residual axillary disease and should be used cautiously when altering treatment plans.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/secundario , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante , Adulto , Axila , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto Joven
19.
Cancer Control ; 23(4): 373-382, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27842326

RESUMEN

BACKGROUND: Breast cancer is a leading cause of cancer-related mortality in women. Limited research exists on the impact of sexual orientation on overall risk of and mortality from breast cancer. We sought to summarize the medical literature on breast cancer in sexual minority women and identify possible disparities in this population. METHODS: A comprehensive literature search was conducted for English-language studies in peer-reviewed medical journals that referenced breast cancer and sexual minority, lesbian, bisexual, or transgender individuals. Articles published between January 2000 and November 2015 were included. They were reviewed for relevance to breast cancer risk stratification, breast cancer mortality, breast reconstruction, and transgender issues. RESULTS: Behavioral risks, reproductive risks, and risks associated with decreased access to health care may all affect outcomes for sexual minorities with breast cancer. Limited studies have mixed results regarding mortality associated with breast cancer in sexual minorities due to an inconsistent reporting of sexual orientation. CONCLUSIONS: Overall, the research examining breast cancer in sexual minority women remains limited. This finding is likely due to limitations in the reporting of sexual orientation within large databases, thus making broader-scale research difficult.


Asunto(s)
Neoplasias de la Mama/epidemiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Factores de Riesgo , Minorías Sexuales y de Género , Resultado del Tratamiento , Adulto Joven
20.
Am J Surg ; 210(4): 685-93, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26210706

RESUMEN

BACKGROUND: American College of Surgeons Oncology Group Z0011 trial of select node-positive breast cancer patients demonstrated no survival or recurrence differences between SLN/axillary lymph node dissection (ALND) vs SLN. Our comparable node-positive lumpectomy and mastectomy populations should have similar outcomes. METHODS: An Institutional Review Board approved, retrospective review of pathologic SLN (N1) cases was performed. Treatment, recurrence, and survival were collected. Statistics was analyzed via exact chi-square test with Monte Carlo estimation, Kaplan-Meier curves, and log-rank tests. RESULTS: Of 528 node-positive patients, 318 patients met criteria: 28 (21.7%) lumpectomy, 32 (16.9%) mastectomy had SLN; 101 (78.2%) lumpectomy, 157 (83.0%) mastectomy had SLN + ALND. Median age was 57.5 years for SLN and 53 years for SLN + ALND (P = .003). Mean positive nodes were 1.1 for SLN and 1.47 for SLN + ALND (P = .0018). Chemotherapy use differed (SLN = 73.5%, SLN + ALND = 89.7%, P = .0032). Stage and recurrence were higher for SLN + ALND (P = .0001, P = .007). No difference in comorbidities, nodes retrieved, extracapsular extension, radiation, hormone therapy, or overall survival was observed. CONCLUSION: In clinically node-negative breast cancer patients, ALND for N1 disease has no impact on short-term recurrence or survival.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma/secundario , Carcinoma/cirugía , Escisión del Ganglio Linfático , Mastectomía , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/mortalidad , Carcinoma/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
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