No Clinical Efficacy of Adipose-Derived Regenerative Cells and Lipotransfer in Breast Cancer-Related Lymphedema: A double-blinded placebo-controlled phase-II trial.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela affecting up to one in three breast cancer survivors. Current treatments are palliative and does not address the underlying lymphatic injury. Recently, preclinical and non-randomized studies have shown promising results using Adipose-Derived Regenerative Cells (ADRCs) and lipotransfer in alleviating BCRL through regeneration of lymphatic tissue. However no randomized controlled trial has been performed in an attempt to eliminate a placebo effect. METHODS: This randomized, double-blinded, placebo-controlled trial included patients with no-option, persistent disabling unilateral BCRL. Patients were randomly assigned in a 1:1 ratio to receive either autologous ADRCs (4.20x10 7±1.75x10 7 cells) and 30cc lipotransfer or placebo (saline) to the axilla. The primary outcome was a change in BCRL volume one year after treatment. Secondary outcomes included changes in the quality of life, indocyanine green lymphangiography stage, bioimpedance, and safety. RESULTS: Eighty patients were included, of which 39 were allocated to ADRCs and lipotransfer treatment and 41 to placebo treatment. Baseline characteristics were similar in both groups. One year after treatment, no objective improvements were observed in the treatment or placebo groups. In contrast, significant subjective improvements were noted for both the treatment and placebo groups. CONCLUSION: This trial failed to confirm a benefit of ADRCs and lipotransfer in the treatment of BCRL. These non-confirmatory results suggest that ADRC and lipotransfer should not be recommended for alleviating BCRL at this time. However, we cannot exclude that repeated treatments or higher doses of ADRCs or lipotransfer could yield a clinical effect.

Local flaps of the hand.

Hand injuries are common, and due to the complex functions of the hand, soft tissue defects present a surgical challenge in reconstruction. Hand defects exposing deeper structures warrant reconstruction with local flaps, but in Denmark, reconstruction surgery of the hand is routinely managed within the orthopaedic specialty alone with no plastic surgical involvement. This review aims at describing the most common local flaps of the hand and forearm and encourage to stronger collaboration between hand- and plastic surgeons in Denmark.

CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects.

Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31- and parent ADRCs. When CD31+, CD31- and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs.

Factors Influencing Patient Satisfaction With Breast Augmentation: A BREAST-Q Effect of Magnitude Analysis.

BACKGROUND: Breast augmentation is one of the most performed cosmetic surgeries. Despite this, patient satisfaction following breast augmentation is poorly understood. OBJECTIVES: The aim of this study was to investigate what patient and surgical factors influence patient satisfaction following primary breast augmentation. METHODS: The BREAST-Q Augmentation module was sent to all females undergoing primary breast augmentation at a single private clinic (Amalieklinikken, Copenhagen, Denmark) between 2012 and 2019. Patient and surgical characteristics at the time of surgery were obtained from the patients' medical records, and data on factors that occurred after the surgery (eg, breastfeeding) were obtained by patient contact. Multivariate linear regression modeled the impact of these factors on BREAST-Q outcomes. RESULTS: A total of 554 females with a mean follow-up time of 5 years after primary breast augmentation were included in this study. Implant type and volume did not affect patient satisfaction. However, higher patient age was associated with significantly higher postoperative patient satisfaction, psychosocial well-being, and sexual well-being (P < .05). Conversely, higher patient BMI, postoperative weight gain, and breastfeeding were associated with significantly lower satisfaction (P < .05). Additionally, subglandular implant placement was associated with significantly lower satisfaction than submuscular implant placement (P < .05). CONCLUSIONS: Implant type and volume did not affect patient satisfaction with breast augmentation. However, young age, higher BMI, subglandular implant placement, and postoperative weight gain were associated with lower patient satisfaction. These factors should be considered when aligning outcome expectations with breast augmentation.

Prepectoral Breast Reconstruction without Acellular Dermal Matrix: Have We Come Full Circle?

Breast reconstruction is an integral part of breast cancer treatment [...].

Can prophylactic incisional negative pressure wound therapy Reduce Wound Complications After Inguinal Lymph Node Dissection for Melanoma? Results from a Randomized Controlled Trial.

Background: Inguinal lymph node dissection (ILND) is associated with a high complication rate. Retrospective studies suggest that incisional negative pressure wound therapy (iNPWT) might reduce complications, especially seroma, following ILND. Methods: This was a prospective multicenter, randomized (1:1), open-labeled, parallel-group trial. Patients with macrometastic melanoma to the inguinal lymph nodes and eligible for ILND were randomized to receive either iNPWT for 14 postoperative days or conventional wound dressing. The primary outcome was seroma incidence. Secondary outcomes included surgical-site infection, wound rupture, wound necrosis, hematoma, rehospitalization and readmission rates between groups. All outcomes were registered 3 months after ILND and analyzed according to the intention-to-treat principle. Results: The trial was terminated early due to a low recruitment rate as a consequence of a change in the national treatment protocol, and the estimated sample size was not reached. Twenty patients were included and randomized in the study. The trial showed less seroma formation between the iNPWT 6/11 (55%) and control 7/9 (78%) groups; however, this was not statistically significant (p = 0.29). Similarly, there were no differences in the rates of surgical-site infection (p = 0.63), wound rupture (p = 0.19), wound necrosis (p = 0.82), hematoma (p = 0.19), reoperation (p = 0.82) or readmission (p = 0.34) between groups. Conclusion: There was a tendency toward fewer complications in the iNPWT group, however this trial was underpowered and could not confirm the hypothesis that iNPWT reduces complications after ILND. Future randomized controlled trials are required to fully evaluate the treatment potential of iNPWT. Trial registration: The trial was prospectively registered at https://clinicaltrials.gov/ct2/show/NCT03433937.

Autologous Fat Grafting as Treatment of Postmastectomy Pain Syndrome: A Randomized Controlled Trial.

BACKGROUND: Postmastectomy pain syndrome is a common and disabling side effect of breast cancer treatment. Medical treatment seems to be insufficient for a considerable proportion of patients. Fat grafting has shown promise in relieving pain from postmastectomy pain syndrome, but no randomized clinical trial comparing fat grafting to a sham operation has been performed to date. The authors' objective was to compare the effect of fat grafting compared to a sham operation for treating postmastectomy pain syndrome. METHODS: The authors conducted a single-center, double-blind, randomized clinical trial with two arms between October of 2017 and September of 2020. The authors assessed four patients suffering from postmastectomy pain syndrome for inclusion. The intervention group received scar-releasing rigottomy and fat grafting to the area of pain. The control group received scar-releasing rigottomy and a placebo of saline solution. The primary outcome was the degree of pain measured using the Numerical Rating Scale. The secondary outcomes were the degree and quality of neuropathic pain (Neuropathic Pain Symptom Inventory) and quality of life (36-Item Short-Form Health Survey). Follow-up was 6 months. RESULTS: Thirty-five participants completed follow-up: 18 participants in the intervention group and 17 in the control group. The authors detected no statistically significant changes in average and maximum pain or neuropathic pain. Regarding quality of life, the control group reported a statistically significant improvement in emotional problem parameters, whereas the intervention group reported a deterioration. The authors observed no serious adverse effects. CONCLUSION: The authors did not find evidence to support that fat grafting is superior to a placebo when treating postmastectomy pain syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Patients Decision-Making Characteristics Affects Gynecomastia Treatment Satisfaction: A Multicenter Study Using the BODY-Q Chest Module.

BACKGROUND: Patient satisfaction is the most critical outcome in gynecomastia treatment. However, patient satisfaction may be affected by the patient's decision-making trait, such as exhaustively searching for the best outcome or being content with an outcome that satisfies a preconceived requirement. OBJECTIVE: To assess whether patient's decision-making characteristic affect their satisfaction with gynecomastia treatment. METHODS: This was a cross-sectional study including patients treated for gynecomastia between January 2009 and December 2019 at two tertiary hospitals in Denmark. Alive patients were sent the BODY-Q: Chest module, the SF-36 questionnaire, and the Maximizer/Satisficer decision-making survey. Patients were classified as Maximizers if they scored more than 40 points on the Maximizer/Satisficer survey. Percentage score differences (PDs) in quality of life scales were calculated between Maximizers and Satisficers. RESULTS: In total, 192 gynecomastia patients were included in this study and classified as Maximizers (n = 152) or Satisficers (n = 40). Maximizers were younger and more had gynecomastia following abuse of anabolic steroids than Satisficers (p < 0.05). With respect to bodily satisfaction, Maximizers showed significantly worse satisfaction with nipples (PDs: - 12.98%), psychological function (PDs: - 13.68%) and social function (PDs: - 8.77%, p < 0.05). In addition, Maximizers had significantly worse emotional role functioning (- 11.03%), vitality (PDs: - 11.72%) and mental health (PDs: - 10.00%, p < 0.05). CONCLUSION: Patients exhibiting maximizing-type decision-making characteristics have worse satisfaction with gynecomastia treatment and poorer psychosocial health. This information may facilitate patient counseling and alignment of treatment expectations. 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 .

The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment.

The impact of breast cancer-related lymphedema (BCRL) on long-term quality of life is unknown. The aim of this study was to investigate the impact of BCRL on health-related quality of life (HRQoL) up to 10 years after breast cancer treatment. This regional population-based study enrolled patients treated for breast cancer with axillary lymph node dissection between January 1st 2007 and December 31th 2017. Follow up and assessments of the included patients were conducted between January 2019 and May 2020. The study outcome was HRQoL, evaluated with the Lymphedema Functioning, Disability and Health Questionnaire, the Disabilities of the Arm, Shoulder and Hand Questionnaire and the Short Form (36) Health Survey Questionnaire. Multivariate linear logistic regression models adjusted for confounders provided mean score differences (MDs) with 95% confidence intervals in each HRQoL scale and item. This study enrolled 244 patients with BCRL and 823 patients without BCRL. Patients with BCRL had significantly poorer HRQoL than patients without BCRL in 16 out of 18 HRQoL subscales, for example, in physical function (MDs 27, 95%CI: 24; 30), mental health (MDs 24, 95%CI: 21; 27) and social role functioning (MDs 20, 95%CI: 17; 23). Age, BMI, BCRL severity, hand and dominant arm affection had only minor impact on HRQoL (MDs < 5), suggesting a high degree of inter-individual variation in coping with lymphedema. This study showed that BCRL is associated with long-term impairments in HRQoL, especially affecting the physical and psychosocial domains. Surprisingly, BCRL diagnosis rather than clinical severity drove the largest impairments in HRQoL.

Superomedial Reduction Mammoplasty Affects Patients' Ability to Breastfeed in a Distinct Manner: A Multicenter Study of 303 Patients.

BACKGROUND: Breast reduction by the superomedial technique can relieve symptoms related to breast hypertrophy; however, as the lateral and inferior portion of the breast parenchyma is removed and displaced, reduction mammoplasty may lead to an impaired ability to breastfeed. OBJECTIVES: The aim of this study was to assess patients' ability to breastfeed after superomedial reduction mammoplasty. METHODS: This was a cross-sectional study including patients treated with superomedial reduction mammoplasty between January 2009 and December 2018 at 2 tertiary hospitals in Denmark. Patients were stratified into 2 cohorts, depending on whether they had experienced childbirth before or after their reduction mammoplasty. Patients were sent specific questionnaires regarding maternity, breastfeeding before and after reduction mammoplasty, nipple sensitivity, and current demographic information. Operative details were retrieved from electronic medical records. RESULTS: In total, 303 patients were identified as eligible for this study (37 patients giving birth after and 266 before reduction mammoplasty). Fewer patients were able to breastfeed exclusively for the recommended 6 months after reduction mammoplasty (2/37, 5.41%) compared with before (92/266, 34.59%; P < 0.05). In addition, fewer patients were able to breastfeed at all after reduction mammoplasty (18/37, 48.64%) compared with before mammoplasty (241/266, 90.60%; P < 0.001). Patients unable to breastfeed after reduction mammoplasty had lower nipple sensitivity and more breast tissue excised (P < 0.05). CONCLUSIONS: Superomedial reduction mammoplasty seems to impair the patient's ability to breastfeed exclusively for the recommended 6 months. Patients of childbearing age considering reduction mammoplasty should be made aware that reduction mammoplasty reduces their breastfeeding capacity.

Prospective Validation of Indocyanine Green Lymphangiography Staging of Breast Cancer-Related Lymphedema.

Indocyanine green lymphangiography (ICG-L) allows real-time investigation of lymphatics. Plastic surgeons performing lymphatic reconstruction use the ICG-L for patient selection and stratification using the MD Anderson (MDA) and the Arm Dermal Backflow (ADB) grading systems. However, the applicability of ICG-L in evaluating breast cancer-related lymphedema (BCRL) is sparse and not well established. This study comprehensively examines the usability of ICG-L in the assessment of BCRL. We prospectively performed ICG-L in 237 BCRL patients between January 2019 and February 2020. The aim of this study was to assess the interrater and intrarater agreement and interscale consensus of ratings made using the MDA and ADB scales. Three independent raters performed a total of 2607 ICG-L assessments. The ICG-L stage for each grading system was correlated to the lymphedema volume to assess the agreement between the ICG-L stage and clinical severity. The interrater agreement was near perfect for the MDA scale (kappa 0.82-0.90) and the ADB scale (kappa 0.80-0.91). Similarly, we found a near-perfect intrarater agreement for the MDA scale (kappa 0.84-0.94) and the ADB scale (kappa 0.88-0.89). The agreement between the MDA and the ADB scales was substantial (kappa 0.65-0.68); however, the ADB scale systematically overestimated lower ICG-L stages compared to the MDA scale. The volume of lymphedema correlated slightly with MDA stage (Spearmans rho = 0.44, p < 0.001) and ADB stage (rs = 0.35, p < 0.001). No serious adverse events occurred. The staging of BCRL with ICG-L is reliable, safe, and provides unique disease information unobtainable with clinical measurements alone. The MDA scale seems to provide better disease stratification compared to the ADB scale.

Adipose-derived regenerative cells and lipotransfer in alleviating breast cancer-related lymphedema: An open-label phase I trial with 4 years of follow-up.

Patients with breast cancer-related lymphedema (BCRL) have reduced quality of life and arm function. Current treatments are palliative, and treatments improving lymphedema are lacking. Preclinical studies have suggested that adipose-derived regenerative cells (ADRCs) can alleviate lymphedema. We, therefore, aimed to assess whether ADRCs can alleviate lymphedema in clinical reality with long-term follow-up. We treated 10 patients with BCRL using ADRCs and a scar-releasing lipotransfer to the axillary region, and all patients were followed 1, 3, 6, 12, and 48 months after treatment. The primary endpoint was change in arm volume. Secondary endpoints were safety, change in lymphedema symptoms, quality of life, lymphedema-associated cellulitis, and conservative treatment use. There was no significant decrease in BCRL volume after treatment. However, self-reported upper extremity disability and arm heaviness and tension improved. Six patients reduced their use of conservative BCRL treatment. Five patients felt that their BCRL had improved substantially, and four of these would redo the treatment. We did not observe any cases of locoregional breast cancer recurrence. In this phase I study with 4 years of follow-up, axillary delivered ADRCs and lipotransfer were safe and feasible and improved BCRL symptoms and upper extremity function. Randomized controlled trials are needed to confirm the results of this study.

Age and Body Mass Index Affect Patient Satisfaction Following Reduction Mammoplasty: A Multicenter Study Using BREAST-Q.

BACKGROUND: Reduction mammoplasty effectively improves quality of life for women with macromastia. However, little is known whether surgical- or patient-related factors affect satisfaction. OBJECTIVE: The authors sought to investigate factors associated with altered patient satisfaction following reduction mammoplasty. METHODS: A cross-section study was performed by sending the BREAST-Q Reduction module to all patients who had undergone reduction mammoplasty between January 2009 and December 2018 at 2 tertiary Danish hospitals. Demographics and pre-, peri-, and postoperative details were gathered from electronic medical records. RESULTS: A total of 393 patients returned the questionnaire and were eligible for the study. Increasing age at the time of surgery was associated with higher satisfaction with breasts nipples, headache, psychosocial well-being, and outcome. Increased body mass index at the time of surgery negatively affected satisfaction with breasts and psychosocial well-being. Increase in body mass index after surgery was further associated with lower satisfaction with breasts, nipples, sexual well-being, and more pain in the breast area. Postoperative scar revision and wound infection was more common following inferior pedicle technique than superomedial technique and negatively affected satisfaction with outcome and pain in the breast area. CONCLUSIONS: Patients should be motivated to optimize their weight prior to reduction mammoplasty to achieve optimal satisfaction. Age was associated with improved patient satisfaction, which should considered when operating on younger patients. Postoperative complications affect patient satisfaction, and the superomedial technique seems to be a better choice than the inferior pedicle technique in medium-large breasts.

Autologous versus implant-based breast reconstruction: A systematic review and meta-analysis of Breast-Q patient-reported outcomes.

OBJECTIVE: Breast reconstruction following mastectomy can increase the quality of life of patients. Reconstruction methods can broadly be divided into implant-based and autologous tissue reconstruction. Patient-reported outcomes following breast reconstruction are one of the most important success parameters. In this systematic review and meta-analysis, we aimed to compare the two methods using the recognized Breast-Q questionnaire. METHODS: We performed a systematic search in PubMed and EMBASE databases. Meta-analysis was performed on the five most commonly reported Breast-Q modules. RevMan 5.3 was used for statistical analysis. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. RESULTS: The search strategy resulted in 219 studies of which nine studies were included in the analysis, yielding 2129 implant-based and 825 autologous breast reconstructions. Overall satisfaction with outcome as well as breast was significantly higher among patients with autologous breast reconstructions (mean Breast-Q difference between the two groups was 9.82 [3.09, 16.54], p = 0.004, and 10.33 [95% CI 5.93, 14.74], p<0.00001, respectively). Sexual and psychosocial well-being was higher among autologous breast reconstructions. There was no difference in the physical well-being. CONCLUSION: This is the first systematic review and meta-analysis to compare patient-reported outcomes of implant-based and autologous breast reconstruction. We found that autologous reconstruction yields a higher satisfaction with overall outcome and breast. These findings can aid clinicians when discussing breast reconstruction options with patients.

Risk of skin cancer in patients with vitiligo in Denmark: A nationwide cohort study.

BACKGROUND: Vitiligo is a depigmentation disorder associated with genetic loss of melanocytes and decreased melanin synthesis. The current literature is conflicting in regard to vitiligo patients' risk of cutaneous malignant melanoma and keratinocyte cancer. OBJECTIVE: To investigate the risk of cutaneous malignant melanoma and keratinocyte cancer in vitiligo patients. METHODS: We conducted a population-based study, including 2,339 subjects with a first-time vitiligo diagnosis between 1994 and 2017 and 23,293 age- and sex-matched (1:10) controls. To address surveillance bias, we included 12,380 subjects with a first-time diagnosis of lichen planus. RESULTS: Age was the only significant factor for cutaneous malignant melanoma in comparison of vitiligo with controls and lichen planus (hazard ratio 1.04, 95% confidence interval [CI] 1.03-1.05; and hazard ratio 1.02, 95% CI 1.01-1.04, respectively). Similarly, age was a significant factor for keratinocyte cancer in comparison of vitiligo with controls and lichen planus (hazard ratio 1.07, 95% CI 1.06-1.07; and hazard ratio 1.06, 95% CI 1.05-1.07). Male sex was an additional factor for keratinocyte cancer in comparison of vitiligo with lichen planus (hazard ratio 1.38; 95% CI 1.09-1.75). Phototherapy did not increase the risk of receiving a diagnosis of cutaneous malignant melanoma or keratinocyte cancer in the vitiligo cohort. CONCLUSION: We observed no significant difference in cutaneous malignant melanoma or keratinocyte cancer risk among vitiligo subjects. Phototherapy use was not associated with a higher skin cancer risk in vitiligo compared with other skin diseases.

Submental Island Flap versus Free Flap Reconstruction for Complex Head and Neck Defects.

OBJECTIVE: Complex soft tissue reconstruction of the head and neck requires a viable, versatile, and dependable flap. Free flaps, such as the radial forearm and anterolateral thigh flap, have been the mainstay of complex head and neck reconstruction. However, a local pedicled flap, such as the submental island flap (SIF), could be a more effective and less demanding alternative. This systematic review and meta-analysis aim to compare free tissue transfer (FTT) with the SIF for head and neck reconstruction. DATA SOURCES: We performed a systematic search in PubMed and EMBASE databases. Meta-analysis was performed on outcomes reported in ≥3 studies. REVIEW METHODS: Candidate articles were assessed for eligibility by 2 authors. Three authors performed data extraction and methodological quality of the included studies using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. RESULTS: The search strategy resulted in 450 studies, of which 7 were included in the analysis, yielding 155 SIF and 198 FTT cases. Operating time and length of stay were significantly lower for the SIF than for FTT (P = .05 and P = .0008). There was no significant difference between the groups for complete flap loss, debulking revisions, and oncologic recurrence. CONCLUSION: These results suggest that the SIF reduces length of stay and operating time as compared with FTT in head and neck reconstruction. These findings suggest that the SIF can be considered an alternative reconstructive option to FTT when evaluating intraoral, lateral facial, skull base, and parotidectomy defects, given comparable defect size and tumor biology.