Measuring outcomes in aesthetic surgery: a comprehensive review of the literature

Outcomes research examines the end results of medical interventions, taking into account patients' experiences, preferences, and values. The purpose of assessing outcomes is to provide evidence on which to base clinical decisions. The assessment of outcomes in aesthetic surgery is especially pertinent because patient satisfaction is the predominant factor in determining success. In cosmetic surgery, various scales have been used to assess outcomes. Unfortunately, none of these methods has achieved widespread use. The adoption of broadly accepted, relevant scales to measure outcomes would be advantageous, because this would allow the comparison of techniques, quantification of positive effects, and identification of patients unlikely to benefit from surgery. The purpose of this study was to critically review the present literature to identify the appropriate instruments to assess outcomes in aesthetic surgery. After a comprehensive review of aesthetic surgery outcome instruments, the authors identified body-image and quality-of-life measures to be of the greatest value in determining aesthetic surgery outcomes. These conclusions were based on a critical evaluation of the feasibility, validity, reliability, and sensitivity to change of these measures. The Multidimensional Body-States Relations Questionnaire (MBSRQ), a psychological assessment of body image, was selected as a potential candidate for further study. Two additional body-image assessment instruments, the Facial Appearance Sorting Test (FAST) and the Breast Chest Ratings Scale (BCRS), may be useful in the assessment of rhinoplasty and breast surgery, respectively. The Derriford Scale (DAS59), an instrument that assesses appearance-related quality of life, was also selected. In addition, the authors recommend the use of a generic, utility-based quality-of-life instrument, such as the Health Utilities Index (HUI) or the EuroQol (EQ-5D).     

Cryptic phenology in plants: Case studies,implications, and recommendations

Plant phenology—the timing of cyclic or recurrent biological events in plants—offers insight into the ecology, evolution, and seasonality of plant‐mediated ecosystem processes. Traditionally studied phenologies are readily apparent, such as flowering events, germination timing, and season‐initiating budbreak. However, a broad range of phenologies that are fundamental to the ecology and evolution of plants, and to global biogeochemical cycles and climate change predictions, have been neglected because they are “cryptic”—that is, hidden from view (e.g., root production) or difficult to distinguish and interpret based on common measurements at typical scales of examination (e.g., leaf turnover in evergreen forests). We illustrate how capturing cryptic phenology can advance scientific understanding with two case studies: wood phenology in a deciduous forest of the northeastern USA and leaf phenology in tropical evergreen forests of Amazonia. Drawing on these case studies and other literature, we argue that conceptualizing and characterizing cryptic plant phenology is needed for understanding and accurate prediction at many scales from organisms to ecosystems. We recommend avenues of empirical and modeling research to accelerate discovery of cryptic phenological patterns, to understand their causes and consequences, and to represent these processes in terrestrial biosphere models.     

Usefulness of bone formation markers in breast cancer

The skeleton is the main site affected by metastases and breast cancer is the most frequent tumor to invade bone. The assessment of bone metastases is difficult and biochemical markers of bone formation (BFMs) could be a promising alternative. Although the essential role of osteoblasts in the metastatic process of bone destruction is now well established, little attention has been paid to BFMs. We conducted a Medline search for studies about BFMs in breast cancer. Our review allows us to conclude that BFMs have high specificity but low sensitivity for the diagnosis of bone metastases. The available biochemical markers cannot replace imaging techniques for the diagnosis of bone metastases. Several studies indicate that BFM serum levels reflect total tumor burden in the skeleton. BFM levels are higher in patients with blastic lesions compared to those with lytic lesions. Serial measurements of BFMs could be useful for the clinical assessment of response to antineoplastic treatment or to bisphosphonate therapy. Besides markers of bone resorption, biochemical markers of bone formation are a promising alternative for the assessment of metastatic bone disease, but large prospective studies are needed to address this important issue.     

Aesthetic outcomes in patients undergoing breast conservation therapy for the treatment of localized breast cancer

Localized breast cancer can be treated with lumpectomy and postoperative radiation therapy, also called breast conservation therapy, with an efficacy equivalent to that of mastectomy. Reports evaluating the effects of radiotherapy suggested that breast conservation therapy had "acceptable" cosmetic outcomes; thus, posttreatment evaluation for aesthetic impact has not been instituted as a standard of care. More recent reports have suggested that the effect of breast conservation therapy on aesthetic outcome is not minimal and that patients may benefit from reconstructive consultation. The purpose of this study was to measure objectively the aesthetic change in women who undergo breast conservation therapy and whether the extent of change is significant enough (objectively and subjectively) to warrant plastic surgery consultation. The authors evaluated 21 patients who had undergone breast conservation therapy. Eleven non-breast cancer patients seeking plastic surgery consultation were used as controls. Standardized five-view photographs (frontal, left and right lateral, and left and right lateral oblique views) were obtained. Patient photograph sets were compiled and evaluated independently by eight reviewers (four surgeons, two nurses, and two medical students). Reviewers evaluated the photographs using the breast asymmetry score (score range, 0 to 9) assessing breast size, ptosis, nipple-areola position, shape, scar appearance, contour deformity, and skin changes. The authors considered 2 SD above the control mean as significant. Breast conservation therapy patients also completed a 15-item questionnaire targeting objective and subjective data about treatment-related breast change. Breast conservation therapy patients had an average treatment-related asymmetry score of 1.93, with 35 percent demonstrating significant change as compared with controls. Although most patients (86 percent) were satisfied with the cancer treatment outcome, all patients noted asymmetry. The authors' data indicate that breast conservation therapy can cause significant asymmetry; thus, an option for plastic surgery consultation as part of the treatment protocol is warranted.     

Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials

Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy “curable” disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a “cell cycle response” is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials.     

Automated Tracking of Quantitative Assessments of Tumor Burden in Clinical Trials

There are two key challenges hindering effective use of quantitative assessment of imaging in cancer response assessment: 1) Radiologists usually describe the cancer lesions in imaging studies subjectively and sometimes ambiguously, and 2) it is difficult to repurpose imaging data, because lesion measurements are not recorded in a format that permits machine interpretation and interoperability. We have developed a freely available software platform on the basis of open standards, the electronic Physician Annotation Device (ePAD), to tackle these challenges in two ways. First, ePAD facilitates the radiologist in carrying out cancer lesion measurements as part of routine clinical trial image interpretation workflow. Second, ePAD records all image measurements and annotations in a data format that permits repurposing image data for analyses of alternative imaging biomarkers of treatment response. To determine the impact of ePAD on radiologist efficiency in quantitative assessment of imaging studies, a radiologist evaluated computed tomography (CT) imaging studies from 20 subjects having one baseline and three consecutive follow-up imaging studies with and without ePAD. The radiologist made measurements of target lesions in each imaging study using Response Evaluation Criteria in Solid Tumors 1.1 criteria, initially with the aid of ePAD, and then after a 30-day washout period, the exams were reread without ePAD. The mean total time required to review the images and summarize measurements of target lesions was 15% (P < .039) shorter using ePAD than without using this tool. In addition, it was possible to rapidly reanalyze the images to explore lesion cross-sectional area as an alternative imaging biomarker to linear measure.We conclude that ePAD appears promising to potentially improve reader efficiency for quantitative assessment of CT examinations, and it may enable discovery of future novel image-based biomarkers of cancer treatment response.     

Metabolic syndrome and breast cancer: an overview

Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the most important cause of cancer-related deaths among women. This disease is on the rise in Turkey. Metabolic syndrome is a cluster of metabolic disturbances including insulin resistance, dyslipidemia, hypertension, abdominal obesity and high blood sugar. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer. More recent studies have shown it to be an independent risk factor for breast cancer. It has also been associated with poorer prognosis, increased incidence, a more aggressive tumor phenotype. Basic research studies are now in progress to illuminate the molecular pathways and mechanisms that are behind this correlation. Given the fact that all of the components of metabolic syndrome are modifiable risk factors, preventive measures must be established to improve the outcome of breast cancer patients. In this review we set the background by taking into account previous studies which have identified the components of metabolic syndrome individually as breast cancer risk factors. Then we present the latest findings which elaborate possible explanations regarding how metabolic syndrome as a single entity may affect breast cancer risk.     

Local Diffusion Homogeneity (LDH): An Inter-Voxel Diffusion MRI Metric for Assessing Inter-Subject White Matter Variability

Many diffusion parameters and indices (e.g., fractional anisotropy [FA] and mean diffusivity [MD]) have been derived from diffusion magnetic resonance imaging (MRI) data. These parameters have been extensively applied as imaging markers for localizing white matter (WM) changes under various conditions (e.g., development, degeneration and disease). However, the vast majority of the existing parameters is derived from intra-voxel analyses and represents the diffusion properties solely within the voxel unit. Other types of parameters that characterize inter-voxel relationships have been largely overlooked. In the present study, we propose a novel inter-voxel metric referred to as the local diffusion homogeneity (LDH). This metric quantifies the local coherence of water molecule diffusion in a model-free manner. It can serve as an additional marker for evaluating the WM microstructural properties of the brain. To assess the distinguishing features between LDH and FA/MD, the metrics were systematically compared across space and subjects. As an example, both the LDH and FA/MD metrics were applied to measure age-related WM changes. The results indicate that LDH reveals unique inter-subject variability in specific WM regions (e.g., cerebral peduncle, internal capsule and splenium). Furthermore, there are regions in which measurements of age-related WM alterations with the LDH and FA/MD metrics yield discrepant results. These findings suggest that LDH and FA/MD have different sensitivities to specific WM microstructural properties. Taken together, the present study shows that LDH is complementary to the conventional diffusion-MRI markers and may provide additional insights into inter-subject WM variability. Further studies, however, are needed to uncover the neuronal mechanisms underlying the LDH.     

Small molecule HDAC inhibitors: Promising agents for breast cancer treatment

Breast cancer, a heterogeneous disease, is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide. Recently, epigenetic abnormalities have emerged as an important hallmark of cancer development and progression. Given that histone deacetylases (HDACs) are crucial to chromatin remodeling and epigenetics, their inhibitors have become promising potential anticancer drugs for research. Here we reviewed the mechanism and classification of histone deacetylases (HDACs), association between HDACs and breast cancer, classification and structure–activity relationship (SAR) of HDACIs, pharmacokinetic and toxicological properties of the HDACIs, and registered clinical studies for breast cancer treatment. In conclusion, HDACIs have shown desirable effects on breast cancer, especially when they are used in combination with other anticancer agents. In the coming future, more multicenter and randomized Phase III studies are expected to be conducted pushing promising new therapies closer to the market. In addition, the design and synthesis of novel HDACIs are also needed.     

Breast reconstruction with postmastectomy radiation therapy: current issues

Two recent trials have demonstrated superior locoregional control, disease-free survival, and overall survival in node-positive breast cancer patients with the addition of postmastectomy radiation therapy to mastectomy and chemotherapy. Based on these results, there has been an increased use of postmastectomy in patients with early-stage breast cancer. The inability to determine which patients will require postmastectomy radiation therapy has increased the complexity of planning for immediate breast reconstruction. There are two potential problems with performing an immediate breast reconstruction in a patient who will require postmastectomy radiation therapy. One problem is that postmastectomy radiation therapy can adversely affect the aesthetic outcome of an immediate breast reconstruction. Several studies have evaluated the outcomes of breast reconstructions that were performed before radiation therapy and have revealed a high incidence of complications and poor aesthetic outcomes. Furthermore, these studies have found that often an additional flap is required to restore breast shape and symmetry. The other potential problem is that an immediate breast reconstruction can interfere with the delivery of postmastectomy radiation therapy. During planning for immediate breast reconstruction, it is imperative to carefully review the stage of disease and the likelihood the patient will require postmastectomy radiation therapy. Unfortunately, the ability to detect and predict the presence or extent of axillary lymph node involvement is limited, and the need for postmastectomy radiation therapy is usually not known until after mastectomy. In all cases of decision making regarding possible postoperative radiation therapy and whether or not to perform immediate breast reconstruction, the situation should be discussed at a multidisciplinary conference or addressed among the various medical, surgical, and radiation teams, with active participation by the patient. Immediate breast reconstruction probably should be avoided in patients known to require postmastectomy radiation therapy and delayed until it is certain the therapy will be needed in patients who may require the therapy.     

Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers

Urokinase-type plasminogen activator (uPA) is a serine protease that is causally involved in cancer progression, especially invasion and metastasis. Multiple studies have shown that breast cancer patients whose primary cancer contains high levels of uPA have a significantly worse outcome than patients with low levels. As a prognostic marker for breast cancer the information supplied by uPA is both independent of traditionally used factors and significant in the important subgroup of axillary-node patients. Paradoxically, high levels of plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of uPA, also predict for aggressive disease. Recently, the prognostic impact of both uPA and PAI-1 in axillary node-negative breast cancer was confirmed using two different Level 1 Evidence studies, i.e. in both a randomized prospective trial and a pooled analysis. Therefore, uPA and PAI-1 appear to have fulfilled all the criteria for the routine assessment of prognosis in newly diagnosed breast cancer patients.     

Magnetic field exposure assessment: a comparison of various methods

The accurate and valid measurement of personal exposure to magnetic fields poses a major challenge for epidemiologic studies. When considering the various methods to assess exposure, it is unclear which measures are most relevant for studies of human disease, if any. Given these uncertainties, the Electromagnetic Fields and Breast Cancer on Long Island Study (EBCLIS) undertook a pilot study to develop the data collection protocol for a case-control study of breast cancer and magnetic fields. The pilot study used and compared various methods to assess residential exposures to magnetic fields, and related these measures to personal exposures. It included 31 women without breast cancer (mean age, 63+/-7 yr) who lived in their present homes for at least 15 yr. The pilot study consisted of an in-home interview, spot and 24-h magnetic field waveforms and broadband recordings, ground currents, wire coding, and personal 24-h broadband measurements. From the regression analyses, the model that best predicted personal magnetic field exposures included 24-h measurements in the bedroom and in the most lived-in room; as well as ground current test loads taken at the center of this most lived in room (r(2)=86%). The addition of other variables in this regression model yielded only small and nonsignificant increases in r(2). As a direct result of this pilot, EBCLIS will include ground current measurements in its protocol, which have not previously been collected as part of an epidemiologic study. Ground currents may be important because they may be richer in 180 Hz components than are the other currents in a power system. EBCLIS will have the opportunity to examine the ground-current hypothesis in the context of female breast cancer.     

Imaging Breast Density: Established and Emerging Modalities

Mammographic density has been proven as an independent risk factor for breast cancer. Women with dense breast tissue visible on a mammogram have a much higher cancer risk than women with little density. A great research effort has been devoted to incorporate breast density into risk prediction models to better estimate each individual’s cancer risk. In recent years, the passage of breast density notification legislation in many states in USA requires that every mammography report should provide information regarding the patient’s breast density. Accurate definition and measurement of breast density are thus important, which may allow all the potential clinical applications of breast density to be implemented. Because the two-dimensional mammography-based measurement is subject to tissue overlapping and thus not able to provide volumetric information, there is an urgent need to develop reliable quantitative measurements of breast density. Various new imaging technologies are being developed. Among these new modalities, volumetric mammographic density methods and three-dimensional magnetic resonance imaging are the most well studied. Besides, emerging modalities, including different x-ray–based, optical imaging, and ultrasound-based methods, have also been investigated. All these modalities may either overcome some fundamental problems related to mammographic density or provide additional density and/or compositional information. The present review article aimed to summarize the current established and emerging imaging techniques for the measurement of breast density and the evidence of the clinical use of these density methods from the literature.     

Quality of life, patients' satisfaction, and aesthetic outcome after pedicled or free TRAM flap breast surgery

Breast reconstructions after breast cancer surgery are primarily performed to improve patients' quality of life. This study was performed to investigate patients' satisfaction with breast reconstruction and quality of life after pedicled or free transverse rectus abdominis musculocutaneous (TRAM) flap surgery and to evaluate the aesthetic result of the breast reconstruction both objectively and subjectively.Sixty-three patients (36 with pedicled flaps and 27 with free TRAM flaps) answered two questionnaires; of this group, 53 (27 with pedicled flaps and 26 with free TRAM flaps) participated in an aesthetic evaluation. The questionnaires consisted of two parts: one study-specific part concerning satisfaction with the result of the breast reconstruction, the other a standardized health-related quality of life part, the Short Form-36 questionnaire. The aesthetic examination consisted of an objective part in which various distances on the reconstructed and contralateral breast were measured. The volumes of the breasts were measured using a thermoplastic cast system. The softness of the breasts was assessed using applanation tonometry. A panel consisting of three plastic surgeons looked at four standardized photographs of each patient and evaluated the aesthetic outcome subjectively. The panel evaluated the breast reconstruction on 10 subscales. No statistically significant difference between the surgical groups was seen regarding the patients' satisfaction with the reconstruction. In the patients' self-assessment of the cosmetic outcome, the degree of symmetry was assessed higher in the free TRAM flap group. The health-related quality of life Short Form-36 questionnaire revealed no difference between the pedicled and free flap groups. Compared with a reference population, the breast-reconstructed group felt more tired and "worn out," less peaceful, more unhappy, and more restless. The free flap group reached a higher degree of symmetry in the objective evaluation and received generally higher scores from the three-member panel, compared with the pedicled TRAM flap group. A strong correlation between the patients' and the panel's evaluations of the cosmetic outcome was seen; generally, the panel's evaluation of the cosmetic result of the breast correlated with the satisfaction of the patients.     

Precision Medicine with Imprecise Therapy: Computational Modeling for Chemotherapy in Breast Cancer

Medical oncology is in need of a mathematical modeling toolkit that can leverage clinically-available measurements to optimize treatment selection and schedules for patients. Just as the therapeutic choice has been optimized to match tumor genetics, the delivery of those therapeutics should be optimized based on patient-specific pharmacokinetic/pharmacodynamic properties. Under the current approach to treatment response planning and assessment, there does not exist an efficient method to consolidate biomarker changes into a holistic understanding of treatment response. While the majority of research on chemotherapies focus on cellular and genetic mechanisms of resistance, there are numerous patient-specific and tumor-specific measures that contribute to treatment response. New approaches that consolidate multimodal information into actionable data are needed. Mathematical modeling offers a solution to this problem. In this perspective, we first focus on the particular case of breast cancer to highlight how mathematical models have shaped the current approaches to treatment. Then we compare chemotherapy to radiation therapy. Finally, we identify opportunities to improve chemotherapy treatments using the model of radiation therapy. We posit that mathematical models can improve the application of anticancer therapeutics in the era of precision medicine. By highlighting a number of historical examples of the contributions of mathematical models to cancer therapy, we hope that this contribution serves to engage investigators who may not have previously considered how mathematical modeling can provide real insights into breast cancer therapy.     

How Big Is It Really? Assessing the Efficacy of Indirect Estimates of Body Size in Asian Elephants

Information on an organism’s body size is pivotal in understanding its life history and fitness, as well as helping inform conservation measures. However, for many species, particularly large-bodied wild animals, taking accurate body size measurements can be a challenge. Various means to estimate body size have been employed, from more direct methods such as using photogrammetry to obtain height or length measurements, to indirect prediction of weight using other body morphometrics or even the size of dung boli. It is often unclear how accurate these measures are because they cannot be compared to objective measures. Here, we investigate how well existing estimation equations predict the actual body weight of Asian elephants Elephas maximus, using body measurements (height, chest girth, length, foot circumference and neck circumference) taken directly from a large population of semi-captive animals in Myanmar (n = 404). We then define new and better fitting formulas to predict body weight in Myanmar elephants from these readily available measures. We also investigate whether the important parameters height and chest girth can be estimated from photographs (n = 151). Our results show considerable variation in the ability of existing estimation equations to predict weight, and that the equations proposed in this paper predict weight better in almost all circumstances. We also find that measurements from standardised photographs reflect body height and chest girth after applying minor adjustments. Our results have implications for size estimation of large wild animals in the field, as well as for management in captive settings.     

新一代遥感技术助力生态系统生态学研究

随着气候变化和人类活动的加剧, 生态系统正处于剧烈变化中, 生态学家需要从更大的时空尺度去理解生态系统过程和变化规律, 应对全球变化带来的威胁和挑战。传统地面调查方法主要获取的是样方尺度、离散的数据, 难以满足大尺度生态系统研究对数据时空连续性的要求。相比于传统地面调查方法, 遥感技术具有实时获取、重复监测以及多时空尺度的特点, 弥补了传统地面调查方法空间观测尺度有限的缺点。遥感通过分析电磁波信息从而识别地物属性和特征, 反演生态系统组成、能量流动和物质循环过程中的关键要素, 已逐渐成为生态学研究中必不可少的数据来源。近年来, 随着激光雷达、日光诱导叶绿素荧光等新型遥感技术以及无人机、背包等近地面遥感平台的发展, 个人化、定制化的近地面遥感观测逐渐成熟, 新一代遥感技术正在推动遥感信息“二维向三维”的转变, 为传统样地观测与卫星遥感之间搭建了尺度推绎桥梁, 这也给生态系统生态学带来了新的机遇, 推动生态系统生态学向多尺度、多过程、多学科、多途径发展。因此, 该文从生态系统生态学角度出发, 重点关注陆地生态系统中生物组分, 并分别从生态系统类型、结构、功能和生物多样性等方面, 结合作者在实际研究工作中的主要成果和该领域国际前沿动态, 阐述遥感技术在生态系统生态学中的研究现状并指出我国生态系统遥感监测领域发展方向及亟待解决的问题。     

Clinical applications of three-dimensional photography in breast surgery

Three-dimensional imaging in breast surgery has several uses clinically. The most practical applications are for the evaluation of breast asymmetries, both congenital and acquired, and for the evaluation of factors affecting breast shape in augmentation mammaplasty. Other uses of three-dimensional imaging that we have found clinically helpful are for evaluation of patients desiring reduction mammaplasty and for evaluation of patients undergoing unilateral breast reconstruction to determine the expander and permanent implant size that gives the best symmetry with the contralateral breast. We present five cases in which we investigate the use of three-dimensional imaging clinically by using the images to determine quantitative information about the breast, such as volume or projection. Overall, three-dimensional imaging is very helpful in providing objective information about the breast for use in preoperative planning. In addition, by analyzing clinical cases, it can provide objective data about the breast and surgical mammaplasty (especially augmentation mammaplasty) that may help surgeons better understand those factors that contribute to breast shape and influence surgical outcomes. There are currently some limitations of this system, influenced by patients with significant ptosis or obesity, which may introduce errors into the three-dimensional data, making them unreliable. However, we believe three-dimensional imaging has great clinical potential in surgical mammaplasty.