Disparity in Breast Cancer Care: Current State of Access to Screening, Genetic Testing, Oncofertility, and Reconstruction.

Breast cancer is the most common cancer diagnosed in women, accounting for an estimated 30% of all new cancer diagnoses in women in 2022. Advances in breast cancer treatment have reduced the mortality rate over the past 25 years by up to 34% but not all groups have benefitted equally from these improvements. These disparities span the continuum of care from screening to the receipt of guideline-concordant therapy and survivorship. At the 2022 American College of Surgeons Clinical Congress, a panel session was dedicated to educating and discussing methods of addressing these disparities in a coordinated manner. While there are multilevel solutions to address these disparities, this article focuses on screening, genetic testing, reconstruction, and oncofertility.

What happens after referral? Completion rates of genetic counseling evaluations in breast cancer patients.

Breast cancer (BC) is a common and often life-altering diagnosis for affected women and their families. Studies have indicated approximately 10% of breast cancer cases are inheritable. When patients are aware of their genetic status early, they are better equipped to make therapy decisions related to their cancer. Additionally, if patients are aware of pathogenic mutations, they can evaluate options such as chemoprevention with endocrine agents, prophylactic surgery, and have the ability to inform family members of their potential risk. Unfortunately, the shortage of genetic counselors has led to a large clinical demand delaying consultation. Although our institution employs genetic counselors on staff, the national shortage of counselors with this expertise has led to a disproportionate availability of providers to meet the clinical volume. This can lead to genetic counseling consultation often occurring beyond the patient's cancer treatment phase. Therefore, we sought to evaluate our referral patterns in an effort to determine whether qualifying patients were scheduled, evaluate delays in consultation, examine completion rates for genetic testing, and assess whether genetic counseling affected their subsequent care.

Phytochemical Profile and Antioxidant and Antiproliferative Activity of Sedum dendroideum on Pterygium Fibroblasts.

BACKGROUND: Sedum dendroideum has antioxidant effects that are beneficial for different diseases. We aimed to analyze the antiproliferative activity of S. dendroideum in human pterygium fibroblasts (HPFs). METHODS: HPFs were treated for 24 h with 0-1000 µg/mL of S. dendroideum lyophilized to analyze its effect on cell viability using the CellTiter assay. RNA from HPF treated with 250 µg/mL of S. dendroideum lyophilized was isolated, and the expression of VEGF and CTGF genes was evaluated by qPCR. A dermal fibroblast cell line (HDFa) was used as a healthy control. The total phenolic content, antioxidant activity, and chemical profile of S. dendroideum lyophilized were determined. RESULTS: Viability of HPF decreased after 24 h treatment of S. dendroideum in a dose-dependent manner. The expression of VEGF and CTGF significantly decreased (P < 0.01) in HPF treated with 250 µg/mL of S. dendroideum when compared with untreated HPF. The total phenolic concentration in the S. dendroideum lyophilized was 33.67 mg gallic acid equivalents (GAE)/g. Antioxidant activity was 384.49 mM Trolox equivalents/mL. The main phenolic compounds identified by HPLC analysis were the kaempferol-3-O-glycoside, kaempferol-3-O-rhamnoside, kaempferol-3-O-neohesperidoside-7-O-α-rhamnopyranoside, and kaempferol-3-O-glycoside-7-O-rhamnoside. CONCLUSIONS: S. dendroideum decreases the proliferation of HPF and the expression of VEGF and CTGF. The phenolic compound concentration, antioxidant activity, and phytochemical profile may play a role in these effects.

Purification of Modified Therapeutic Proteins Available on the Market: An Analysis of Chromatography-Based Strategies.

Proteins, which have inherent biorecognition properties, have long been used as therapeutic agents for the treatment of a wide variety of clinical indications. Protein modification through covalent attachment to different moieties improves the therapeutic's pharmacokinetic properties, affinity, stability, confers protection against proteolytic degradation, and increases circulation half-life. Nowadays, several modified therapeutic proteins, including PEGylated, Fc-fused, lipidated, albumin-fused, and glycosylated proteins have obtained regulatory approval for commercialization. During its manufacturing, the purification steps of the therapeutic agent are decisive to ensure the quality, effectiveness, potency, and safety of the final product. Due to the robustness, selectivity, and high resolution of chromatographic methods, these are recognized as the gold standard in the downstream processing of therapeutic proteins. Moreover, depending on the modification strategy, the protein will suffer different physicochemical changes, which must be considered to define a purification approach. This review aims to deeply analyze the purification methods employed for modified therapeutic proteins that are currently available on the market, to understand why the selected strategies were successful. Emphasis is placed on chromatographic methods since they govern the purification processes within the pharmaceutical industry. Furthermore, to discuss how the modification type strongly influences the purification strategy, the purification processes of three different modified versions of coagulation factor IX are contrasted.

Development of aqueous two-phase systems-based approaches for the selective recovery of metalloproteases and phospholipases A2 toxins from Crotalus molossus nigrescens venom.

Snake venoms are rich sources of proteins with potential biotechnological and pharmaceutical applications. Among them, metalloproteases (MPs) and phospholipases A2 (PLA2) are the most abundant. Their isolation involves a multistep chromatographic approach, which has proven to be effective, however implies high operating costs and long processing times. In this study, a cost-effective and simple method based on aqueous two-phase systems (ATPS) was developed to recover MPs and PLA2 from Crotalus molossus nigrescens venom. A system with PEG 400 g mol-1, volume ratio (VR) 1, tie line length (TLL) 25% w/w and pH 7 showed the best performance for PLA2 recovery. In systems with PEG 400 g mol-1, VR 1, TLL 15% w/w, pH 7 and 1 and 3% w/w of NaCl, selective recovery of MP subtype P-III was achieved; whereas, in a system with PEG 400 g mol-1, VR 1, TLL 25% w/w and pH 8.5, MP subtypes P-I and P-III were recovered. Due to their low costs, ethanol-salt systems were also evaluated, however, failed to differentially partition PLA2 and MPs. The use of ATPS could contribute to the simplification and cost reduction of protein isolation processes from snake venoms and other toxin fluids, as well as potentially aid their biochemical, proteomic and biological analyses.

Corrigendum: Immobilization of Growth Factors for Cell Therapy Manufacturing.

[This corrects the article DOI: 10.3389/fbioe.2020.00620.].

Immobilization of Growth Factors for Cell Therapy Manufacturing.

Cell therapy products exhibit great therapeutic potential but come with a deterring price tag partly caused by their costly manufacturing processes. The development of strategies that lead to cost-effective cell production is key to expand the reach of cell therapies. Growth factors are critical culture media components required for the maintenance and differentiation of cells in culture and are widely employed in cell therapy manufacturing. However, they are expensive, and their common use in soluble form is often associated with decreased stability and bioactivity. Immobilization has emerged as a possible strategy to optimize growth factor use in cell culture. To date, several immobilization techniques have been reported for attaching growth factors onto a variety of biomaterials, but these have been focused on tissue engineering. This review briefly summarizes the current landscape of cell therapy manufacturing, before describing the types of chemistry that can be used to immobilize growth factors for cell culture. Emphasis is placed to identify strategies that could reduce growth factor usage and enhance bioactivity. Finally, we describe a case study for stem cell factor.

Depressive symptoms in pregnant women with high trait and state anxiety during pregnancy and postpartum.

Background: Depression and anxiety are frequent during pregnancy, and epidemiological studies demonstrate high rates of co-morbidity. Aims: To evaluate the association between the trait and state anxiety and depressive symptoms in women during the perinatal period. Method: A transversal study was conducted at the National Institute of Perinatology (INPer, Mexico City) from 2012 and 2015. Pregnant women diagnosed with Major Depressive Disorder (MDD) were included (N=128). Depressive and anxiety symptoms were evaluated using CES-D and STAI, respectively. Patients were sub-classified according to percentile 75 for Low and High Trait Anxiety (LTA, HTA) and Low and High State Anxiety (LSA, HSA); depressive symptoms were compared between pregnant women and women in the postpartum, by state and trait levels. Results: CES-D scores differed according to state and trait anxiety levels: while we observed that depressive scores (CES-D) were higher in HTA patients compared to LTA prenatally (35.9±9,5 vs 21.2±10,8 respectively; p=0.001), this finding was not observed in the postpartum period. In the case of state anxiety depressive scores were elevated among HSA versus LSA groups before delivery (33.0±11.3 vs 14.0±6.7 respectively; p=0.008) and after partum (35.1±8.06 vs 10.0±6.0; p=0.005). Conclusions: Patients showed higher scores of depressive symptoms when high trait or state anxiety comorbidity is present during the perinatal period. In the postpartum period, even low trait anxiety scores were associated with high depressive scores.

The Angel Wings Incision: A novel solution for mastectomy patients with increased lateral adiposity.

Many techniques have been proposed to address the problem of increased lateral adiposity in patients undergoing mastectomy, however, there is no standard approach. This cosmetic deformity at the lateral end of the mastectomy scar, also known as a dog ear, is especially common in obese patients. This defect can be unsightly and uncomfortable. We describe a technique for creating a winged incision to eliminate the dog ear deformity. The Angel Wings Incision results in tissue flaps that create a smooth body contour upon closure in patients with increased lateral adiposity. The technique is reproducible, aesthetically pleasing, and improves patient satisfaction.

Silicone breast implant associated fibromatosis.

Extra-abdominal desmoid tumors, also known as aggressive or deep fibromatosis, are uncommon soft tissue tumors that rarely involve the breast. Although the exact etiology is unknown, the development of these tumors has been correlated with sites of previous trauma, surgery or in association with familial adenomatous polyposis. Clinically, breast fibromatosis is often mistaken for carcinoma but lacks metastatic potential. It is locally aggressive with high rates of recurrence. The treatment is primarily wide local excision with negative margins. Adjuvant treatments have been suggested and include radiotherapy, chemotherapy and hormonal therapy, however, there are no evidence-based treatment protocols to support their use. Here, we describe a case of fibromatosis that developed within the capsule around a silicone breast implant treated with surgical excision alone. The patient remains recurrence free at 3 months post-operative magnetic resonance imaging.

Cutting Healthcare Costs with Hematoma-Directed Ultrasound-Guided Breast Lumpectomy.

BACKGROUND: Localization of nonpalpable breast lesions for breast-conserving surgery (BCS) remains highly variable and includes needle/wire localization (NL), radioactive seed localization, radar localization, and hematoma-directed ultrasound-guided (HUG) lumpectomy. The superiority of HUG lumpectomy over NL has been demonstrated repeatedly in terms of safety, accuracy, low positive margin rates, cosmesis, and patient satisfaction. In this study, we evaluate the cost effectiveness of HUG lumpectomy over NL for nonpalpable breast lesions. METHODS: We performed a retrospective review of 569 patients who underwent lumpectomy at the University of Arkansas for Medical Sciences from May 2014 through December 2017. Lumpectomies were stratified by localization technique, i.e. NL versus HUG. A cost-savings estimate was determined for the HUG localization technique, and a total amount of dollars saved over the study period was calculated. RESULTS: Overall, 569 lumpectomies were performed: 501 (88.0%) via HUG and 68 (12.0%) via NL. Intraoperative ultrasound was used in 566 operations (99.5%). Of the lumpectomies performed by HUG, 190 lesions (33.4%) were visible only on mammogram or breast magnetic resonance imaging prior to diagnostic core needle biopsy (CNB). Cost estimates comparing HUG with NL demonstrated a cost savings of $497.00 per procedure, the cost of preoperative needle localization by a radiologist, and a total of $94,430.00 for the study period. CONCLUSION: In utilizing HUG lumpectomy, the initial CNB serves as the diagnostic and localization procedure, thus saving time and a painful second procedure on the day of operation. HUG lumpectomy is safe, accurate, reduces healthcare costs, and results in a better patient experience for the surgical removal of nonpalpable breast lesions.

Demographics and Psychological Factors Associated with Adiposity in Nurses.

Adiposity-based chronic disease (ABCD), overweight-Ow- or obesity-Ob-) in health personnel is as frequent as in the general population, even though they understand well the importance of maintaining a healthy weight. Thus, it is highly likely that certain demographic and psychological conditions, independently of knowledge, are contributing to develop ABCD. The aim of this study was to examine the association between these factors and ABCD in nurses. Data were collected from a cross-sectional study conducted in a tertiary level institute in Mexico City from 2012 to 2013. All the nurses of the institute of any age, shift, service area and seniority were invited to participate and 55% (265) accepted. We found that ABCD was present in 79.6%, and low self-esteem and emotional distress in 26% and 10%, respectively. Working in the night shift (p = 0.031), labor seniority ≥15 years (p = 0.006), having 1 or more children (p = 0.021) and sessions of physical activity <30 min (p = 0.03) were associated with ABCD. Low self-esteem (OR = 2, 95% CI 1.150–3.07, p = 0.023) and emotional distress (OR = 4, 95% CI 1.472–13.078, p = 0.012) were associated with unhealthy lifestyle (less of 3 days per week and/or less of 30 min per session of physical activity and poor dietary habits). Therefore, strategies to prevent and treat ABCD must consider each context among nurses and psychological disorders need be identified to avoid an unhealthy lifestyle.

Abordaje Terapéutico de la Hipomineralización Molar - Incisal. Revisión Narrativa / Peripheral Odontogenic Fibroma: Case Report

RESUMEN: Hipomineralización Molar-Incisal (MIH) es un trastorno del desarrollo dentario asociado a factores sistémicos, producido por una incompleta mineralización y maduración del esmalte. La prevalencia en niños, a nivel mundial, varía en la literatura entre el 2,4 % y el 40,2 %. Este trastorno que implica al menos un primer molar permanente, pudiendo también verse afectados los incisivos, dependiendo del momento, la duración, la susceptibilidad del individuo y la gravedad de la injuria prenatal, perinatal o postnatal. El esmalte presenta un grado variable de alteración en la translucidez, siendo éste de un espesor normal y de color blanco, o café-amarillo. Si bien se encuentra intacto en el momento de la erupción, puede sufrir fracturas post eruptivas debido a las fuerzas de la masticación, dejando límites definidos. Por lo general, los molares gravemente afectados son extremadamente hipersensibles, propensos a lesiones de caries de rápida progresión, y pueden ser difíciles de tratar en pacientes jóvenes. La atención debe abordar el comportamiento y la ansiedad del niño, con el objetivo de proporcionar restauraciones duraderas en condiciones libres de dolor. La ejecución de medidas preventivas individuales puede posponer el inicio del tratamiento restaurador y reducir la incomodidad del paciente a largo plazo. El diagnóstico precoz permitirá el seguimiento y la instauración de dichas medidas preventivas tan pronto las superficies afectadas sean accesibles. Pese a que los enfoques de tratamiento para MIH han comenzado a ser más claros y los avances en los materiales dentales han proporcionado soluciones clínicas en los casos que se consideraban sin posibilidad de restauración en el pasado, deben llevarse a cabo ensayos clínicos a largo plazo para facilitar aún más el manejo clínico de este cuadro.

ABSTRACT: Molar Incisor Hypomineralization (MIH) is a tooth development disorder, which is associated with systemic factors, produced by incomplete enamel mineralization and maturation below the enamel surface that is intact at the time of eruption. In literature, the prevalence in children worldwide varies between 2.4 % and 40.2 %. This disorder which involves at least one first permanent molar, and depending on duration, the child's susceptibility as well as the severity of prenatal, perinatal or postnatal insult may also compromise incisors. The defect reveals a variable degree of alteration in the translucency of the enamel, that has initially normal thickness and can be white, yellow or brown. Enamel surface may breakdown after eruption, due to masticatory forces, leaving sharp borders. Usually, severely affected molars are extremely hypersensitive, prone to rapid caries development, and can be difficult to manage in young patients. The complex care involved must address the child's behavior and anxiety, aiming to provide pain free treatment and durable restorations. Intensive individually prescribed preventive programs may postpone the onset of restorative treatment and reduce patient discomfort in the long term. Early identification of such children will allow monitoring and implementation of preventive measures as soon as affected surfaces are accessible. Although treatment approaches for MIH have become more clear, and advances in dental materials have provided clinical solutions in cases that in the past were regarded as unrestorable, long-term clinical trials should be realized to further facilitate clinical management of this dental defect.

Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?

BACKGROUND: We hypothesized that disconcerting lymphedema rates in both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) may be because of unrecognized vunerable variations in arm lymphatic drainage within the axilla. Axillary reverse mapping (ARM) facilitates identification and avoidance of arm lymphatics within the axilla and its use may reduce lymphedema. METHODS: This institutional review board-approved study from June 2007 to December 2013 involved patients undergoing SLNB with or without ALND, or ALND alone. Technetium is injected subareolarly for localization of the breast SLN and isosulfan blue dye (5 mL) is injected in the ipsilateral upper arm for localization of nonbreast lymphatics. Data were collected on identification and preservation of arm lymphatics, crossover rates, blue node metastases, axillary recurrence, and lymphedema as measured by volume displacement. RESULTS: A total of 654 patients prospectively underwent 685 ARM procedures with a SLNB and/or ALND. Objective lymphedema rates for SLNB and ALND were 0.8% and 6.5% respectively, with 26-month median follow up. Blue lymphatics were identified in 29.2% (138/472) of SLNB and 71.8% (153/213) of ALND. Crossover was seen in 3.8% (18/472) of SLNB and 5.6% (12/213) of ALND. Blue node metastases rate was 4.5% (2/44). Axillary recurrence rate was 0.2% and 1.4% for SLNB and ALND, respectively. CONCLUSIONS: ARM allows frequent identification of arm lymphatics in the axilla, which would have been transected during routine surgery. Rates of metastases in noncrossover nodes and axillary recurrences are low. Lymphedema rates are dramatically reduced using ARM when compared with accepted standards.

The SAVE review: sonographic analysis versus excision for axillary staging in breast cancer.

BACKGROUND: Health care reform goals involve more cost-effective methods of delivering health care. The cost-effectiveness of axillary ultrasound-guided core needle biopsy (AUS-CNB) was compared with sentinel lymph node biopsy (SLNB) when evaluating the status of the axilla in operable invasive breast cancer. STUDY DESIGN: We performed an IRB-approved retrospective review of patients undergoing ultrasound of the axilla plus core needle biopsy at our institution from 2007 to 2012. An accuracy of technique and cost analysis (TreeAge Pro 2009) of AUS-CNB vs SLNB was conducted. RESULTS: The cohort of 95 patients was divided into 2 groups: clinically positive (CP) (32%) and negative (CN) (68%) axilla. In the CP group, 83% had a suspicious AUS, of which 90% were positive. In the CN group, AUS was suspicious in 70%, with a positive biopsy in 59%. The sensitivity and specificity of AUS-CNB were 90% (95% CI 84.8% to 98.8%) and 100% (95% CI 27% to 59.1%), respectively. Cost estimates comparing AUS-CNB with SLNB demonstrated a cost saving of $236,517 in the CP axilla and $248,490 in the CN axilla, for a total cost savings of $485,007. CONCLUSIONS: Axillary ultrasound-guided core needle biopsy is a sensitive, diagnostic, surgeon-performed procedure. It is time-saving, cost-efficient, and less invasive, making it a viable option when evaluating the status of the axilla in invasive breast cancer or staging before neoadjuvant chemotherapy.

Axillary reverse mapping: five-year experience.

BACKGROUND: We hypothesize that mapping the lymphatic drainage of the arm with blue dye (axillary reverse mapping [ARM]) during axillary lymphadenectomy decreases the likelihood of disruption of lymphatics and subsequent lymphedema. METHODS: This institutional review board-approved study involved 360 patients undergoing sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) from May 2006 to October 2011. Technetium sulfur colloid (4 mL) was injected subareolarly, and 5 mL of blue dye was injected subcutaneously in the volar surface ipsilateral upper extremity (ARM). Data were collected on variations in lymphatic drainage, successful identification and protection of arm lymphatics, crossover, and occurrence of lymphedema. RESULTS: A group of 360 patients underwent SLNB and/or ALND, 348 of whom underwent a SLNB. Of those, 237 (68.1%) had a SLNB only, and 111 (31.9%) went on to an ALND owing to a positive axilla. An additional 12 of 360 (3.3%) axilla had ALND owing to a clinically positive axilla/preoperative core needle biopsy. In 96% of patients with SLNB (334/348), breast SLNs were hot but not blue; crossover (SLN hot and blue) was seen in 14 of 348 patients (4%). Blue lymphatics were identified in 80 of 237 SLN incisions (33.7%) and in 93 of 123 ALND (75.4%). Average follow-up was 12 months (range, 3-48) and resulted in a SLNB lymphedema rate of 1.7% (4/237) and ALND of 2.4% (3/123). CONCLUSION: ARM identified substantial lymphatic variations draining the upper extremities and facilitated preservation. Metastases in ARM-identified lymph nodes were acceptably low, indicating that ARM is safe. ARM added to present-day ALND and SLNB may be useful to lesser rates of lymphedema.

Advanced locoregional therapies in breast.

BACKGROUND: Advanced locoregional therapies continue to advance the treatment of breast cancer. These techniques are geared towards optimizing oncologic and aesthetic outcome as well as decreasing and treating morbidity. We present a selection of specialized locoregional therapies dedicated to the optimization of breast cancer treatment. METHODS: Locoregional therapies for breast cancer are presented to address breast conservation techniques, lipofilling techniques, reconstruction techniques for nipple-sparing mastectomy, re-irradiating the breast, axillary reverse mapping, and vascularized lymph node transfer. RESULTS: We present a synopsis of identified breast locoregional therapies targeted to address optimal oncologic and aesthetic outcome as well as decrease and treat morbidity.