A Histological Assessment Tool for Breast Implant Capsules Validated in 480 Patients with and Without Capsular Contracture.

BACKGROUND: Understanding the impact of breast implants on the histological response in the surrounding fibrous capsule is important; however, consensus is lacking on how to analyze implant capsules histologically. We aimed to develop a standardized histological assessment tool to be used in research potentially improving diagnostic accuracy and treatment strategies for capsular contracture. METHODS: Biopsies of breast implant capsules from 480 patients who had undergone breast augmentation or reconstruction were collected and stained with hematoxylin and eosin. Initially, biopsies from 100 patients were analyzed to select histological parameters demonstrating the highest relevance and reproducibility. Then, biopsies from the remaining 380 patients were used to determine intra- and interobserver agreements of two blinded observers and agreement with a pathologist. Finally, we tested the association between the parameters and capsular contracture. RESULTS: The histological assessment tool included ten parameters assessing the inflammatory, fibrotic, and foreign-body reaction to breast implants, each graded on two-, three-, or four-point scales. Intra- and interobserver agreements were almost perfect (0.83 and 0.80), and agreement with the pathologist was substantial (0.67). Four parameters were significantly correlated with capsular contracture, namely chronic inflammation with lymphocyte infiltration (p < 0.01), thickness of the collagen layer (p < 0.0001), fiber organization (p < 0.01), and calcification (p < 0.001). CONCLUSIONS: This is the first validated histological assessment tool for breast implant capsules. The validated tool not only advances our understanding of capsular contracture but also sets a new standard for histological evaluation in breast implant research and clinical diagnostics. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Development and Validation of a Diagnostic Histopathological Scoring System for Capsular Contracture Based on 720 Breast Implant Capsules.

BACKGROUND: Capsular contracture is traditionally evaluated with the Baker classification, but this has notable limitations regarding reproducibility and objectivity. OBJECTIVES: The aim of this study was to develop and validate procedure-specific histopathological scoring systems to assess capsular contracture severity. METHODS: Biopsies of breast implant capsules were used to develop histopathological scoring systems for patients following breast augmentation and breast reconstruction. Ten histological parameters were evaluated by multivariable logistic regression to identify those most associated with capsular contracture. Significant parameters (P < .05) were selected for the scoring systems and assigned weighted scores (1-10). Validation was assessed from the area under the curve (AUC) and the mean absolute error (MAE). RESULTS: A total of 720 biopsies from 542 patients were included. Four parameters were selected for the augmentation scoring system, namely, collagen layer thickness, fiber organization, inflammatory infiltration, and calcification, providing a combined maximum score of 26. The AUC and MAE for the augmentation scoring system were 81% and 0.8%, which is considered strong. Three parameters were selected for the reconstruction scoring system, namely, fiber organization, collagen layer cellularity, and inflammatory infiltration, providing a combined maximum score of 19. The AUC and MAE of the reconstruction scoring system were 72% and 7.1%, which is considered good. CONCLUSIONS: The new histopathological scoring systems provide an objective, reproducible, and accurate assessment of capsular contracture severity. We propose these novel scoring systems as a valuable tool for confirming capsular contracture diagnosis in the clinical setting, for research, and for implant manufacturers and insurance providers in need of a confirmed capsular contracture diagnosis.

Oncoplastic breast surgery versus conventional breast conserving surgery - a prospective follow-up study of subjective loco-regional late morbidity.

Background and aim: Few studies have focused on the symptoms of loco-regional morbidity in shoulders, arms, and breasts related to oncoplastic breast surgery (OPS). This study aimed to determine if a difference exists in the prevalence or variety of subjective symptoms of shoulder, arm, and breast morbidity in patients undergoing OPS compared with patients receiving conventional breast conserving surgery (C-BCS). Cosmetic result and body image were included as secondary endpoints.Methods: This prospective follow-up study with 18 months of questionnaire-based follow-up included women with breast cancer or ductal carcinoma in situ. They were divided into two groups - C-BCS or OPS - depending on type of surgery performed. Furthermore, patient, disease, and treatment characteristics were recorded.Results: Among 334 completers, 229 (69%) received C-BCS and 105 (31%) received OPS. Participants were comparable regarding age, comorbidity, BMI, re-excision rate (15-16%), and axillary surgery. As for tumor characteristics, a more advanced disease stage was shown in the OPS than in the C-BCS group with larger tumor and lumpectomy size, more multifocality, and the corresponding following systemic adjuvant therapy.The questionnaire revealed that the two groups were comparable with no significant differences in frequency or variety of symptoms of shoulder and arm morbidity. Overall, participants were highly satisfied with the cosmetic results in both groups and no significant inter-group differences were observed.Conclusion: In patients with larger tumors, breast conserving surgery utilizing oncoplastic techniques yields results regarding subjective shoulder, arm, and breast morbidity as well as cosmetic outcome comparable with those of C-BCS performed on smaller tumors.Trial registration: ClinicalTrials.gov, registration number: NCT02159274 (2014).HIGHLIGHTSSubjective symptoms of shoulder, arm, and breast morbidity are comparable when oncoplastic breast surgery is compared to conventional breast conserving surgery.The variety of symptoms of shoulder and arm morbidity following oncoplastic surgery does not differ from symptoms following conventional breast conserving surgery.The cosmetic outcome following oncoplastic breast surgery is comparable to breast conserving surgery without oncoplastic techniques.

Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption.

The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination.

Long-term follow-up on shoulder and arm morbidity in patients treated for early breast cancer.

Background: A prospective study on shoulder and arm morbidity was conducted in Denmark in 2003-2005. This study demonstrated that sentinel lymph node biopsy was associated with better outcomes than axillary lymph node dissection 18 months after surgery. We here aimed to describe subjective symptoms and objective findings in these patients 10+ years after they underwent breast cancer surgery and to assess how symptoms and findings developed during this period.Material and methods: Participants in the prospective study completed a questionnaire and underwent an objective, bilateral examination of their shoulder and arm morbidity, which included measurement of arm volume, range of motion, and sensibility.Results: Seventy participants completed follow-up. Thirty-four (49%) had one or more functional impairments, and 64% had one or more subjective loco regional symptoms like pain, swelling of the arm, and decreased shoulder mobility. Objective evaluation showed 34 ml's of increased arm volumes and 3-25% had severe reduced shoulder mobility on the operated side. Compared to the findings at 18 months postoperatively, small but significant differences in occurrence of subjective findings were observed. A significant progression regarding most objective findings was revealed.Conclusion: More than 11 years after breast cancer surgery, the majority of participants complained of one or more subjective symptoms of shoulder and arm morbidity. Objective findings were mild or modest in most cases. During the prolonged follow-up period of 10 years, a worsening in symptoms and objective findings was observed.HIGHLIGHTSShoulder and arm morbidity in relation to breast cancer treatment seems to progress beyond 10 years.The most frequent symptoms were pain, swelling or heaviness of the arm, and decreased shoulder mobility.The objective evaluation showed higher arm volumes and reduced shoulder mobility on the operated side.Objective findings are mild and modest but may affect activities of daily living, and most participants with late symptoms stated that this was a daily problem.

A Systematic Review and Meta-analysis of Functional Shoulder Impairment After Latissimus Dorsi Breast Reconstruction.

PURPOSE: The latissimus dorsi flap (LDF) is a very reliable flap and may be used for a multitude of reconstructive purposes. It is widely used for breast reconstruction when performed. It has few complications, except for a possible impact on shoulder function. The aims of this study were to evaluate the validity of the literature by investigating the level of evidence and to perform a meta-analysis. METHODS: A systematic literature search was conducted using the databases PubMed, Scopus, and Web of Science. Predictor variables were shoulder function after breast reconstruction with the LDF. Articles were chosen according to 4 different outcomes: shoulder range of motion (ROM), shoulder strength, DASH score, and subjective evaluation. RESULTS: Twenty-six articles were found, including 1045 patients: 8 level II, 16 level III, 1 level IV, and 1 level V articles. The meta-analysis showed that both ROMs for flexion and abduction are significantly impaired at less than or at 3 months of follow-up. CONCLUSIONS: There are several influencing factors, such as age, smoking, obesity, radiotherapy, and physiotherapy. Moreover, the impact on shoulder function seemed influenced by the type of thoracodorsal vessel-based flap. From the level of evidence analysis, there is a tendency that the LDF transfer does affect shoulder function. This limitation seems to be minimal, and few patients experience a major impact on shoulder function. However, the existing literature on total shoulder impairment after breast reconstruction with LDF is insufficient to draw any final conclusion. There is a need for future studies and current articles that suggest that the initial measurement should be performed preoperatively (preferably at the time of diagnosis or initial biopsy) and follow-ups with measurements at 6, 12, and 24 months (long-term effect) after surgery. We recommend measurements of both operated and nonoperated sides. Each measurement should be accompanied by a history with special emphasis on shoulder function. The methods of measuring outcomes of recommendation are DASH score, ROM with use of a goniometer preferably by a physiotherapist or a health care professional trained by a physiotherapist, and strength measured by, for example, a handheld dynamometer.

Local and systemic coagulation marker response to musculocutaneous flap ischemia-reperfusion injury and remote ischemic conditioning: An experimental study in a porcine model.

BACKGROUND: Remote ischemic conditioning (RIC) administered by non-lethal periods of extremity ischemia and reperfusion attenuates ischemia-reperfusion injury. We aimed to investigate the local and systemic coagulation marker response to flap ischemia-reperfusion injury, and the effects of RIC on coagulation markers following flap ischemia-reperfusion injury. METHODS: A musculocutaneous latissimus dorsi flap was subjected to 4 h of ischemia followed by 7 h of reperfusion in 16 female Danish Landrace pigs (39 kg). Systemic venous blood samples were collected 1 h before flap reperfusion. Flap and systemic venous blood samples were collected at reperfusion and hourly during reperfusion. We measured thrombin generation, fibrinogen, von Willebrand factor, antithrombin, thrombin-antithrombin complex, activated partial thromboplastin time (aPTT), and prothrombin time (PT). RIC was performed 1 h before flap reperfusion in the intervention group by three 10-min periods of hind limb ischemia and reperfusion (n = 8). RIC was not performed in the control group (n = 8). RESULTS: Local and systemic coagulation marker changes were comparable following flap ischemia-reperfusion injury. Flap ischemia-reperfusion injury reduced thrombin generation lag time from 2.0 ± 0.3 to 1.6 ± 0.3 min (P < .001), time-to-peak thrombin from 3.5 ± 0.3 to 3.0 ± 0.5 min (P = .001), peak thrombin from 79.6 ± 8.1 to 74.5 ± 7.1 nM (P = .033), endogenous thrombin potential from 211 ± 24 to 197 ± 19 nM × min (P = .01), antithrombin from 0.91 ± 0.07 to 0.79 ± 0.06 103 IU/l (P = .002), and aPTT from 37 ± 21 to 21 ± 9 s (P = .017). RIC increased peak thrombin (P < .001), endogenous thrombin potential (P < .001), and aPTT (P = .019). CONCLUSIONS: The local coagulation marker response to musculocutaneous flap ischemia-reperfusion could be measured systemically by moderate hypercoagulation. RIC did not substantially influence coagulation markers following musculocutaneous flap ischemia-reperfusion injury.

Unilateral breast reconstruction after mastectomy - patient satisfaction, aesthetic outcome and quality of life.

BACKGROUND: An increasing number of women undergo a breast reconstruction (BR) after treatment for breast cancer. The aim of the present study was to evaluate patient-reported esthetic satisfaction, quality of life (QoL), and the association between these, following different types of BR. MATERIALS AND METHODS: All women who underwent unilateral BR in Central Denmark Region between January 2005 and July 2011 were included. Participants were sent a questionnaire package, which included the Body Image Scale, The Beck Depression Inventory, the Impact of Event Scale, and a study-specific patient-reported esthetic satisfaction scale. Additionally, patients were asked if they experienced a change in QoL owing to the BR. Based on reconstructive method and timing, participants were divided into four groups, three delayed: an abdominal flap group, a latissimus dorsi flap group, an implant ± thoracodorsal flap group; and one immediate BR group. RESULTS: Of 166 eligible participants, a total of 144 women (87%) completed the questionnaire. The mean follow-up was 3.8 years. Esthetic satisfaction differed significantly between groups [F(3,139) = 8.55; p < 0.001], with abdominal flap recipients reporting the highest levels of esthetic satisfaction. No between-group differences were observed for the remaining psychosocial measures. Higher satisfaction with esthetic outcome was associated with reporting higher QoL owing to the BR (odds ratio 1.10, p<0.001; 95% CI 1.06-1.15). CONCLUSIONS: Abdominal flap recipients expressed higher satisfaction with their esthetic outcome, compared to the remaining BR types. Higher esthetic satisfaction was strongly associated with reporting an experience of higher QoL.

Loss of E-cadherin as Part of a Migratory Phenotype in Melanoma Is Associated With Ulceration.

It has been suggested that embryogenic properties of migratory cells are reactivated during wound healing and metastasis in adults. This might explain the association between wound-induced inflammation and poor survival in patients with ulcerated melanoma. Linking inflammation with a migratory phenotype, we characterize the infiltration of innate inflammatory cells, loss of cell-to-cell adhesion (E-cadherin), factors associated with extracellular matrix degradation [matrix metalloproteinase-9 (MMP-9), and neutrophil elastase (NE)], and spindle-shaped cell morphology, between ulcerated (n = 179) and nonulcerated (n = 206) melanoma. In addition, the presence of "extravascular migratory metastasis" (angiotropism) and tumor-vessel density were evaluated as important factors for tumor cell dispersal in ulcerated melanoma. We showed a correlation between expression of the granulocyte marker cd66b+ and the expression of NE and MMP-9, reflecting activated neutrophils. Ulcerated melanoma correlated with a low global E-cadherin score (P = 0.041) and weak-spot score (P = 0.0004). Thus, 28% of the nonulcerated, 42% of the minimally/moderately ulcerated melanoma, and 53% of the excessively ulcerated melanoma presented low scores as opposed to a high E-cadherin score. In addition, the presence of ulceration was correlated with angiotropism (P < 0.0001) and spindle-shaped morphology (P = 0.021). There were no differences in MMP-9 expression or intratumoral vessel density between the ulcerated and nonulcerated group. In conclusion, expression of migratory cell properties showed a highly heterogeneous pattern, which was associated with ulcerated areas and inflammatory cells, in general and with neutrophils in particular. We, therefore, suggest that wound-associated inflammation may be involved in the induction of migratory cell transition and tumor cell dispersal in ulcerated melanoma.

Remote ischemic perconditioning attenuates acute inflammation of experimental musculocutaneous flaps following ischemia-reperfusion injury.

BACKGROUND: In free flap reconstruction and replantation surgery, prolonged ischemia time may lead to flap or replantation failure. The aim of the study was to investigate the effects of hypothermic flap ischemia or remote ischemic perconditioning (RIPER) during normothermic ischemia on acute inflammation of musculocutaneous flaps subjected to ischemia-reperfusion injury. MATERIALS AND METHODS: In 24 pigs, a musculocutaneous latissimus dorsi flap was dissected and subjected to 4 hours of arterial ischemia and 7 hours of reperfusion. The animals were allocated into two experimental groups: hypothermic flap ischemia at 4°C (n = 8) or normothermic flap ischemia with RIPER (n = 8), and one control group with normothermic flap ischemia (n = 8). The hypothermic ischemic flaps were cooled in a basin with fresh water and ice. RIPER was initiated 1 hour before reperfusion, by inducing three 10 min cycles of hind limb ischemia with a tourniquet, each separated by 10 min of reperfusion. Acute inflammation was described by inflammatory cytokine secretion (IL-1ß, IL-6, IL-10, IL-12p40, and TNF-α) from the flap during reperfusion, and by quantitative determination of macrophages in flap biopsies of dermis, subcutaneous tissue, and skeletal muscle following reperfusion. RESULTS: No significant differences were found between normothermic and hypothermic flap ischemia in inflammatory cytokine secretion. However, the IL-6 secretion was significantly reduced in the RIPER group compared with the control group at 5 hours of reperfusion (P = 0.036), and in the RIPER group compared with the hypothermic ischemia group at 3 (P = 0 0.0063), 5 (P = 0.0026), and 7 hours of reperfusion (P = 0.028). The IL-12p40 secretion was significantly reduced in the RIPER group compared with the control group (P = 0.0054) as well as the hypothermic ischemia group (P = 0.028) at 5 hours of reperfusion. No significant difference was found among groups in macrophage infiltration. CONCLUSION: RIPER reduced IL-6 and IL-12p40 secretion during reperfusion of porcine musculocutaneous flaps, when compared with hypothermic ischemic flaps and normothermic ischemic flaps without RIPER. © 2016 Wiley Periodicals, Inc. Microsurgery 37:148-155, 2017.

Consumption of the epidermis: a suggested precursor of ulceration associated with increased proliferation of melanoma cells.

It has recently been demonstrated that the extent of ulceration and the presence of epidermal involvement that theoretically precede ulceration (consumption of epidermis, COE) or seen subsequent to inflammation (reactive epidermal hyperplasia or re-epithelialization) allowed better prognostic stratification of ulcerated melanoma. Understanding why these histopathologic markers have prognostic potential is important, not least because accurate consensual assessment of ulceration lies at the root of proper staging and clinical management. The authors therefore performed immunohistochemical analyses of tumor cell proliferation (Melan-A/Ki67) and infiltration of inflammatory cells (CD66b neutrophils and CD163 macrophages) to better understand the biology of the epidermal changes described. Tumors with a COE configuration showed 37% (95% CI: 4-54, P = 0.0046) increased tumor cell proliferation compared with tumors of normal epidermal configuration. COE is therefore suggested a precursor of ulceration associated with increased proliferation of melanoma cells. There was no observed correlation between COE and an increased inflammatory response (CD163 macrophages or CD66b neutrophils), which supports that the proliferation drive is noninflammatory. In contrast, the presence of re-epithelialization and/or reactive epidermal hyperplasia demonstrated an 18% (95% CI: 6-53, P = 0.0021) increased density of neutrophils compared with tumor with no evidence of these possibly prolonged late-stage or resolved ulcerations. These results further support the relevance of including these epidermal changes into the definition of ulceration and to define ulceration of a primary melanoma as loss of epidermis with evidence of a host response (infiltration of neutrophils or fibrin deposition) and thinning, effacement, or reactive hyperplasia of the surrounding epidermis.

Direct comparison of postoperative monitoring of free flaps with microdialysis, implantable cook-swartz Doppler probe, and clinical monitoring in 20 consecutive patients.

BACKGROUND: There is an increasing demand for successful free tissue transfer, with postoperative monitoring of flaps a key to early salvage. Monitoring methods have ranged from clinical techniques to invasive options, of which two are particularly applicable to buried flaps (Cook-Swartz Doppler probe and microdialysis). The evidence for these options has been represented largely in separate cohort studies, with no single study comparing these three techniques. We aim to perform this comparison in a single cohort of patients. METHODS: A prospective, consecutive cohort study comparing clinical monitoring, microdialysis and the implantable Doppler probe was undertaken. In 20 patients receiving 22 flaps, 21 flaps were monitored with microdialysis, 18 flaps with clinical observation, and 21 flaps with the Cook-Swartz Implantable Doppler probe. Exclusion was based on applicability and availability intra-operatively. Efficacy was assessed through sensitivity, specificity, positive, and negative predictive values. RESULTS: Nineteen of 22 flaps had no suspected anastomotic problems; 3 of 22 flaps were explored for anastomotic problems, with two salvaged and one lost. The implantable Doppler and microdialysis were found to detect flap statistically earlier than clinical assessment, with microdialysis better at detecting flap compromise: 100% specificity (confidence interval 31-100%) when compared to the implantable probe and clinical assessment (67%: 13-98% and 33%: 2-87%, respectively). CONCLUSIONS: Each of the Cook-Swartz Doppler probe, microdialysis and clinical assessment was found suitable for monitoring in free tissue transfer. The implantable Doppler and microdialysis offer the potential for earlier detection of flap compromise.

Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.

INTRODUCTION: Despite similar clinical and pathological features, large numbers of breast cancer patients experience different outcomes of the disease. This, together with the fact that the incidence of breast cancer is growing worldwide, emphasizes an urgent need for identification of new biomarkers for early cancer detection and stratification of patients. METHODS: We used ultrahigh-resolution microarrays to compare genomewide methylation patterns of breast carcinomas (n = 20) and nonmalignant breast tissue (n = 5). Biomarker properties of a subset of discovered differentially methylated regions (DMRs) were validated using methylation-sensitive high-resolution melting (MS-HRM) in a case-control study on a panel of breast carcinomas (n = 275) and non-malignant controls (n = 74). RESULTS: On the basis of microarray results, we selected 19 DMRs for large-scale screening of cases and controls. Analysis of the screening results showed that all DMRs tested displayed significant gains of methylation in the cancer tissue compared to the levels in control tissue. Interestingly, we observed two types of locus-specific methylation, with loci undergoing either predominantly full or heterogeneous methylation during carcinogenesis. Almost all tested DMRs (17 of 19) displayed low-level methylation in nonmalignant breast tissue, independently of locus-specific methylation patterns in cases. CONCLUSIONS: Specific loci can undergo either heterogeneous or full methylation during carcinogenesis, and loci hypermethylated in cancer frequently show low-level methylation in nonmalignant tissue.

Breast reconstruction after mastectomy.

Patients requesting breast reconstruction after mastectomy is an increasing group at plastic- and breast surgery departments in Denmark. This review summarises the present surgical techniques for reconstruction with/without postoperative chemotherapy and/or radiation therapy. These surgical techniques are continuously updated. The most determining factor when selecting a reconstructive technique, is postoperative radiation therapy. Each patient is unique, and an individual assessment is made when planning surgery. The concept of a "babysitter implant" is currently being investigated in Denmark and might be an option for selected patients.

Surgical treatment algorithm for breast cancer lymphedema-a systematic review.

Background: Various surgical treatments are increasingly adopted and gaining popularity for lymphedema treatment. However, challenges persist in selecting appropriate treatment modalities targeted for individual patients and achieving consensus on choice of treatment as well as outcomes. The systematic review aimed to create a treatment algorithm incorporating the latest scientific knowledge, to provide healthcare professionals and patients with a tool for informed decision-making, when selecting between treatments or combining them in a relevant manner. This systematic review evaluated and synthesized the evidence on the effectiveness of three surgical treatments for breast cancer-related lymphedema (BCRL): lymphovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and liposuction. Methods: We conducted a systematic search of electronic databases on 18 June 2023, including Medline, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.org. Eligible studies were randomized controlled trials, non-randomized comparative studies, and observational studies that assessed the outcomes of LVA, VLNT, or liposuction in managing BCRL. The primary results of interest were changes in arm volume, lymphatic flow, and quality of life. Two independent reviewers performed the study selection and data extraction. Following this, we systematically reviewed and conducted a risk of bias assessment. Results were qualitatively presented, and a treatment algorithm was developed based on the available data. Results: We identified 16,593 papers, after removal of duplicates. Following assessment of studies, 73 articles met the inclusion criteria, including 2,373 patients. We were not able to conduct a meta-analysis due to considerable heterogeneity in the methodologies and outcome measures across the studies. Liposuction appears effective for patients presenting with non-pitting lymphedema. LVA indicates variable success rate, with some evidence indicating a reduction in limb volume and symptomatic relief amongst early stages of lymphedema. VLNT showed promising results for limb volume reduction and symptom improvement in patients presenting with mild and moderate lymphedema. Conclusions: Liposuction, LVA, and VLNT seem to be effective treatments for BCRL, when targeted for the appropriate patient. Well-conducted high evidence clinical studies in the field are still lacking to uncover the efficacy of surgical treatment for BCRL.

Silicone Leakage from Breast Implants Is Determined by Silicone Cohesiveness: A Histological Study of 493 Patients.

BACKGROUND: Silicone leakage from breast implants is a concern with potential implications for patient health. This study aimed to quantify and model silicone leakage from implants to the breast implant capsule and to investigate whether silicone cohesiveness affected the silicone leakage rate. METHODS: Silicone content in the breast implant capsule was quantified histologically by measuring the area of silicone deposits. This was used to model silicone leakage over time based on the time of implantation. The effect of cohesiveness on silicone leakage was investigated across all implant brands with declared cohesiveness and in a subanalysis comparing only Mentor cohesive I implants with cohesive II and III implants. RESULTS: The study included 493 patients with 872 breasts and a median time of implantation of 13.0 years (range 0.4 to 51 years). The modeling of silicone leakage from intact implants showed that leakage and the acceleration of the leakage rate were significantly higher in low-cohesive implants than in highly cohesive implants (p<0.05). This was confirmed when analyzing only Mentor implants (p<0.05) and in the case of implant rupture (p<0.01) where low-cohesive implants also leaked significantly more than highly cohesive implants. CONCLUSIONS: Our results suggest that highly cohesive implants are superior to low-cohesive implants in preventing silicone leakage. Due to the accelerating rate of silicone leakage especially found in low-cohesive implants, we propose that exchange of low-cohesive implants could be discussed with patients 10 to 15 years after implantation to minimize silicone leakage even in the absence of implant rupture.

Breast reconstruction with mentor anatomical implants and the risk of implant rotation: A retrospective study of 1134 women.

BACKGROUND: Implant rotation is a known complication to breast reconstruction using anatomical implants. However, there is a lack of large studies investigating the risk of implant rotation and potential predisposing risk factors. METHOD: We reviewed the medical records of all patients who underwent breast reconstruction with Mentor anatomical implants from 2010 to 2021 at two Danish hospitals. We compared the risk of implant rotation between one- and two-stage breast reconstruction using univariate logistic regression. We analyzed the effect of biological mesh, immediate versus delayed reconstruction, and use of a higher final expander volume than the permanent implant volume on the risk of implant rotation. Finally, we analyzed the success rate of revision surgery for implant rotation. RESULTS: In total, 1134 patients were enrolled. Patients who underwent two-stage breast reconstruction (n = 720) had a significantly higher risk of implant rotation than those who underwent one-stage breast reconstruction (n = 426; 11% vs. 5%, p < 0.01). There was no significant association between implant rotation and the use of biological mesh, immediate breast reconstruction, or use of a higher final expander volume than the permanent implant volume. The success rate of revision surgery after implant rotation was 73% (62/85 rotations). CONCLUSIONS: Two-stage breast reconstruction significantly increased the risk of implant rotation compared to one-stage breast reconstruction. The overall risk of implant rotation was low and success rate of revision surgery was high. These findings suggest that anatomical implants are safe to use for breast reconstruction. However, surgeons and patients should be aware of the increased risk of implant rotation after two-stage reconstruction.

Long-term follow-up of late morbidity, cosmetic outcome and body image after breast conserving therapy. A study from the Danish Breast Cancer Cooperative Group (DBCG).

UNLABELLED: The Danish Breast Cancer Cooperative Group (DBCG) introduced BCT as a standard treatment in Denmark in 1990. The aim of this study was to investigate late morbidity, cosmetic outcome, and body image after BCT and to associate these outcome variables with patient, tumor, and treatment characteristics. MATERIAL AND METHODS: A total of 214 patients treated with BCT from 1989-2002 participated in a long-term follow-up visit comprising an interview, clinical examination, photos of the breast region and completion of a questionnaire on Body Image. RESULTS: Median follow-up time was 12 years (range 7-20). Moderate to severe fibrosis was found in 23% of patients and was associated with chemotherapy [OR 2.6, CI (1.1; 5.9), p = 0.02], large breast size [OR 3.2, CI (1.6; 6.4), p = 0.001], and smoking [OR 2.4, CI (1.1; 4.9), p = 0.02]. Patients with a satisfactory cosmetic outcome, when assessed by a clinician, were characterized by small tumors [OR 3.2, CI (1.5; 6.8), p = 0.003] and small to medium sized breasts [OR 2.0, CI (1.1; 3.5), p = 0.002]. Fifty percent of patients scored good or excellent when assessed by a clinician compared to 88% when reported by the patients themselves. Patients satisfied with their own cosmetic outcome were the younger patients [< 50 years; OR 3.2, CI (1.1; 8.6), p = 0.03] with no postoperative complications [OR 3.3, CI (1.2; 9.2), p = 0.02]. Regarding body image 15% felt less feminine, 25% felt less sexually attractive, and 28% of patients had changed their clothing habits as a result of the disease or treatment. CONCLUSION: The majority of patients were satisfied with their cosmetic outcome after BCT, whereas only half of the patients were found to have a good or excellent cosmetic outcome when assessed by the clinician. Body image was found to be only minimally disturbed in the majority of patients. The level of moderate to severe fibrosis was acceptable compared to both national and international studies with similar patient compositions.

Donor-site morbidity after pedicled TRAM breast reconstruction: a comparison of two different types of mesh.

Many different approaches have been used to minimize the risk of bulge or hernia formation when using autologous abdominal tissue for breast reconstruction. Studies have shown that further reinforcement of the abdominal wall using a mesh may decrease the complication rate.The current study included 40 consecutive patients having unilateral breast reconstruction with the pedicled transverse rectus abdominus musculocutaneous flap. The defect in the abdominal fascia was closed primarily and further reinforced using a Prolene mesh (Ethicon), n = 20, or using a self-fixating Parietex ProGrip mesh (Covidien), n = 20. The patients were examined at an outpatient consultation, with a minimum follow-up of 1 year and questioned about donor-site symptoms using a standardized questionnaire.Of the 20 patients in the Prolene group, 2 (10%) developed abdominal wall bulging, and of the 20 patients in the ProGrip group, 11 (55%) developed abdominal wall bulging (P = 0.006). In both the Prolene and the ProGrip group, most patients reported having continued donor-site symptoms at the time of the follow-up (70% and 80%, respectively); 15% and 30%, respectively, reported having symptoms that influenced their daily or physical activities (not a significant difference). All but 1 patient in our study reported being very happy with the reconstruction and would have done it again, had they known what they did at the time of the follow-up.We conclude that the self-gripping properties of the Parietex ProGrip mesh are not sufficient in withstanding the abdominal wall tension at the donor site after transverse rectus abdominus musculocutaneous-flap harvest and do not recommend using the Parietex ProGrip mesh without fixating sutures for this procedure.

The impact of neoadjuvant chemotherapy on surgical outcomes following autologous and implant-based immediate breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on the complication rate after implant-based and autologous breast reconstruction remains unclear. The aim of this study was to systematically review and perform a meta-analysis of previously published studies on immediate breast reconstruction (IBR) in breast cancer patients treated with NACT compared with controls. METHODS: PubMed and EMBASE were searched to identify studies assessing the impact of NACT on major and minor complications after IBR. The primary effect measures were relative risk (RR), 95% confidence interval (95% CI), and p-value. RESULTS: Eight studies comprising 51,731 patients were included in the meta-analysis. Of these, 5161 patients received NACT and 46,570 patients did not receive NACT. In regard to major complications, NACT did not statistically significant increase the rate of reconstructive failure (RR = 1.35, 95% CI = 0.96-1.91, p = 0.09), the rate of mastectomy skin-flap necrosis (RR = 1.39, 95% CI = 0.61-3.17, p = 0.44), or the rate of reoperation (RR = 1.09, 95% CI = 0.87-1.37, p = 0.45). Regarding minor complications, NACT did not significantly increase the rate of wound complications (RR = 1.05, 95% CI = 0.87-1.28, p = 0.62). In a subgroup analysis of implant-based breast reconstruction following NACT, single-stage direct-to-implant (DTI) had a significantly lower implant failure rate compared with two-staged tissue expander/implant (TE/I) (RR = 0.43, 95% CI = 0.26-0.71, p = 0.0011). CONCLUSION: NACT did not increase the major or minor complication rate after IBR with either autologous tissue or implants. Thus, NACT and IBR should be considered safe procedures. The review of studies describing patients undergoing implant-based breast reconstruction following NACT could indicate that single-stage DTI was a safer procedure than two-staged TE/I. However, the association requires further evaluation.