Patient-reported outcomes in bilateral prophylactic mastectomy with breast reconstruction: A narrative review.

In women at high risk of developing breast cancer, bilateral prophylactic mastectomy (BPM) 1 significantly reduces the risk; simultaneously, breast reconstruction preserves body integrity. Given the complex and personal nature of such surgical procedures, patient assessment of satisfaction and health-related quality of life (HRQoL) 2 is essential in evaluation of surgical outcomes. With this review, we aim to organize the current knowledge on patient-reported outcomes (PROs) 3 in bilateral prophylactic surgery. Literature search was conducted using the databases Google Scholar, PubMed, and Web of Science to address the following questions, which can help clinicians and women undergoing the procedures navigate their healthcare decision-making process: How does BPM with reconstruction influence cancer-related distress? How does the surgery impact patient satisfaction and HRQoL? How do preoperative PROs differ from postoperative outcomes? Does the type of BPM and the type of reconstruction impact patient satisfaction and HRQoL? Furthermore, we summarize available patient-reported outcome measures (PROMs) 4 that can be administered to women undergoing BPM with reconstruction. In addition, we discuss possible future directions for PRO research in prophylactic breast surgery.

Novel Patient-Reported Outcome Measures for the Assessment of Patient Satisfaction and Health-Related Quality of Life Following Postmastectomy Breast Reconstruction.

BACKGROUND: Patient-reported outcome measures (PROMs) have become an integral part of the evaluation of reconstruction surgery outcomes. However, there are limitations in current PROMs when it comes to the assessment of well-being during inpatient stay, patient perception of health, relationship with partner, and vitality (i.e., mood and ability to work and pursue hobbies, carry out daily tasks, and sleep) following breast reconstructive surgery. The aim was to develop a novel set of measures to compare patient satisfaction and health-related quality of life following different types of postmastectomy breast reconstruction. METHODS: A novel questionnaire was created and refined through cognitive interviews with patients and expert feedback. A field test study was conducted, including patients who had undergone delayed postmastectomy breast reconstruction with implant, autologous tissue, or combination of implant and autologous tissue. Based on the results, confirmatory factor analysis and examination of reliability of the questionnaire were conducted. Results of patient responses were analyzed using Chi-square test, Kruskal-Wallis test, and Mann-Whitney U test. RESULTS: Confirmatory factor analysis showed good model fit, and Cronbach's alpha indicated high internal consistency of the questionnaire. Besides that, patients with combination reconstruction reported significantly lower vitality than patients with implant and autologous reconstruction (p = 0.048). CONCLUSIONS: This novel questionnaire expands the current knowledge base of postmastectomy breast reconstruction PROMs. Results of the field test study showed that combination reconstruction was associated with lower patient vitality than other reconstruction types. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multiscale analysis of craniomaxillofacial bone repair: A preclinical mini-pig study.

BACKGROUND: The rate of reparative osteogenesis controls when an implant is sufficiently stable as to allow functional loading. Using a mini pig model, the rate of reparative osteogenesis in two types of implant sites for example, an osteotomy versus a fresh extraction socket were compared. METHODS: Eight adult mini pigs were used for the study. In phase I, three premolars were extracted on one side of the oral cavity; 12 weeks later, in phase II, osteotomies were produced in healed extraction sites, and contralateral premolars were extracted. Animals were sacrificed 1, 5, and 12 weeks after phase II. Bone repair and remodeling were evaluated using quantitative micro-computed tomographic imaging, histology, and histochemical assays coupled with quantitative dynamic histomorphometry. RESULTS: One week after surgery, extraction sockets and osteotomy sites exhibited similar patterns of new bone deposition. Five weeks after surgery, mineral apposition rates (MARs) were elevated at the injury sites relative to intact bone. Twelve weeks after surgery, the density of new bone in both injury sites was equivalent to intact bone but quantitative dynamic histomorphometry and cellular activity assays demonstrated bone remodeling was still underway. CONCLUSIONS: The mechanisms and rates of reparative osteogenesis were equivalent between fresh extraction sockets and osteotomies. The volume of new bone required to fill a socket, however, was significantly greater than the volume required to fill an osteotomy. These data provide a framework for estimating the rate of reparative osteogenesis and the time to loading of implants placed in healed sites versus fresh extraction sockets.

Evaluation of the Number of Follow-up Surgical Procedures and Time Required for Delayed Breast Reconstruction by Clinical Risk Factors, Type of Oncological Therapy, and Reconstruction Approach.

BACKGROUND: Breast reconstructive surgery is often a multistage process. The aim was to understand which factors might increase the number of follow-up surgeries and the length of time required to complete the reconstruction process. METHODS: A cross-sectional analysis was performed. Clinical data of 110 patients who underwent delayed postmastectomy breast reconstruction with a 5-year examination period were reviewed retrospectively. Impact of clinical risk factors, oncological therapy, and reconstruction approach on the number of surgeries and the length of required time was analyzed. Mann-Whitney U test and Kruskal-Wallis rank sum test were used. RESULTS: In patients undergoing perioperative hormone therapy, an average of 2.9 surgeries and length of 20.2 months were required compared to 2.3 surgeries and 14.0 months in patients without hormone therapy (P = 0.003; P = 0.005). Previous abdominal surgery was associated with an increased number of breast reconstruction stages of 3.1 per patient (P = 0.056) and a longer reconstruction time of 23.0 months (P = 0.050). Patients undergoing nipple reconstruction or implant revision required an increased number of surgeries (P < 0.001; P = 0.012) and a longer reconstruction time (P = 0.002; P < 0.001). Contralateral breast surgery and flap revision were associated only with an increased number of surgeries (P < 0.001; P < 0.001). CONCLUSION: Perioperative hormone therapy was associated with a significantly higher number of surgeries and duration of time required to complete the reconstruction process. The highest increase in the number of surgeries was in patients with flap revision including anastomosis revision and necrectomy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Animal Models Used in the Research of Vascularized Lymph Node Transfer: A Systematic Review.

BACKGROUND: Lymphedema is a common adverse consequence of breast cancer therapy, while still relatively little is known about its pathophysiology. Several treatment options emerged over the past decades, and among them, vascularized lymph node transfer (VLNT) seems to be particularly promising. Animal models are indispensable to improve our understanding of the underlying processes surrounding the transplantation of a vascularized lymph node. This review aimed to systematically evaluate animal models of VLNT and compare their advantages and disadvantages. MATERIALS AND METHODS: A systematic review of literature in the Scopus, Web of Science, and Ovid MEDLINE databases was conducted according to the PRISMA guidelines to identify all studies on animal models used for the research of VLNT. The algorithm used in search of articles was "Vascularized Lymph Node Transfer" AND "Model". Articles were manually verified for relevance to the topic. The resulting models were assessed for their suitability for VLNT research. RESULTS: The literature search yielded a total of 233 studies after duplicates removal. Of those, 217 were excluded based on title and abstract review. Another study was excluded after reviewing the full-text article leaving 15 eligible studies to be included in this review article. CONCLUSIONS: Rats were found to be the most dominantly used animal model in the VLNT research, although other models had their benefits. The main areas of study were the functionality of VLNT within or without a preinduced lymphedema, its response to ischemia, and clarification of lymphatic pathways reestablishment following VLNT.

A novel cryo-embedding method for in-depth analysis of craniofacial mini pig bone specimens.

The disconnect between preclinical and clinical results underscores the imperative for establishing good animal models, then gleaning all available data on efficacy, safety, and potential toxicities associated with a device or drug. Mini pigs are a commonly used animal model for testing orthopedic and dental devices because their skeletons are large enough to accommodate human-sized implants. The challenge comes with the analyses of their hard tissues: current methods are time-consuming, destructive, and largely limited to histological observations made from the analysis of very few tissue sections. We developed and employed cryo-based methods that preserved the microarchitecture and the cellular/molecular integrity of mini pig hard tissues, then demonstrated that the results of these histological, histochemical, immunohistochemical, and dynamic histomorphometric analyses e.g., mineral apposition rates were comparable with similar data from preclinical rodent models. Thus, the ability to assess static and dynamic bone states increases the translational value of mini pig and other large animal model studies. In sum, this method represents logical means to minimize the number of animals in a study while simultaneously maximizing the amount of information collected from each specimen.

Patient-Reported Outcomes of Three Different Types of Breast Reconstruction with Correlation to the Clinical Data 5 Years Postoperatively.

BACKGROUND: The aim of this study was to compare long-term clinical and patient-reported outcomes in terms of satisfaction and health-related quality of life (HRQoL) following postmastectomy breast reconstruction using BREAST-Q in patients undergoing implant-based reconstruction, abdominal-based autologous reconstruction, and combined reconstruction (with implant and LD flap or implant and TDAP flap). METHODS: A cross-sectional study was conducted. Patients had undergone delayed postmastectomy breast reconstruction and completed the BREAST-Q reconstruction module. The results were related to the clinical data obtained from the clinic's patient record system. A 5-year examination was included. Mean scores and standard deviations were calculated. Kruskal-Wallis test, Chi-square goodness of fit test and Chi-square test were used for the statistical analysis. RESULTS: Overall, 110 patients (n = 24 implant, n = 38 autologous, n = 48 combination) were included. Patients with autologous reconstruction reported greater postoperative satisfaction with breasts (p < 0.001), satisfaction with outcome (p < 0.001), psychosocial well-being (p = 0.001), and sexual well-being (p = 0.051). CONCLUSION: This study represents a comprehensive long-term examination of postmastectomy breast reconstruction. Autologous reconstruction patients had higher postoperative satisfaction and HRQoL than patients receiving other types of reconstruction despite having more intense oncological therapy and the highest mean number of follow-up surgical procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Interspecies comparison of alveolar bone biology: Tooth extraction socket healing in mini pigs and mice.

BACKGROUND: in an effort to identify and validate which animal models are best suited for dental implant research, we used multiscale analyses to examine tooth extraction wound healing in a well-accepted model, the Yucatan mini pig and a more controversial model, the laboratory mouse. METHODS: first molar extractions were performed in adult, skeletally mature mini pigs and mice. Alveolar bone repair was evaluated at early, intermediate and late timepoints using quantitative micro-computed tomographic (µCT) imaging, histology, molecular, and cellular assays. Vital dye labeling was employed to quantify mineral apposition rates (MAR) in both species. RESULTS: Despite a 3000-fold difference in weight, the relative proportions of the mini pig and murine maxillae and are equivalent. Quantitative µCT demonstrated that within the posterior alveolar bone, the volume of mineralized bone was lower in mini pig than in the mice; during healing, however, the bone volume fraction was equivalent. The histologic appearance of healing sites was also comparable, and alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP) staining showed a similar temporal and spatial distribution of bone remodeling. Vital dye labeling indicated equivalent MAR between the species. The absolute duration of the healing period differed: in mice, complete healing was accomplished in ∼21 days. In mini pigs, the same process took four times longer. CONCLUSIONS: Extraction socket healing is histologically equivalent between mini pigs and mice, supporting the hypothesis that the underlying mechanisms of alveolar bone healing are conserved among species.

Wnt-Responsive Stem Cell Fates in the Oral Mucosa.

Epithelia of the oral cavity exhibit variations in morphologies and turnover rates. Are these differences related to environment or to region-specific stem cell populations? A lineage-tracing strategy allowed visualization of Wnt-responsive cells, and their progeny, in the hard and soft palates. In both anatomic locations, Wnt-responsive basal cells self-renewed and gave rise to supra-basal cells. Palatal injuries triggered an enlargement of this population, and their descendants were responsible for wound re-epithelialization. Compared with the hard palate, soft palate stem cells exhibited an earlier, more robust burst in proliferation, culminating in significantly faster repair. Thereafter, excess Wnt-responsive basal cells were removed, and stem cell numbers were restored back to homeostatic level. Thus, we uncovered a stem cell population in oral mucosa, and its relative abundance is correlate with the rate of oral wound healing. Besides the activation during injury, an endogenous mechanism exists to constrain the stem cell pool after repair.