Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

PURPOSE: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. METHODS: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. RESULTS: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. CONCLUSION: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer.

Effects of cerebrolysin on motor-neuron-like NSC-34 cells.

Although the peripheral nervous system is capable of regeneration, this capability is limited. As a potential means of augmenting nerve regeneration, the effects of cerebrolysin (CL)--a proteolytic peptide fraction--were tested in vitro on the motor-neuron-like NSC-34 cell line and organotypic spinal cord cultures. Therefore, NSC-34 cells were subjected to mechanical stress by changing media and metabolic stress by oxygen glucose deprivation. Afterwards, cell survival/proliferation using MTT and BrdU-labeling (FACS) and neurite sprouting using ImageJ analysis were evaluated. Calpain-1, Src and α-spectrin protein expression were analyzed by Western blot. In organotypic cultures, the effect of CL on motor neuron survival and neurite sprouting was tested by immunohistochemistry. CL had a temporary anti-proliferative but initially neuroprotective effect on OGD-stressed NSC-34 cells. High-dosed or repeatedly applied CL was deleterious for cell survival. CL amplified neurite reconstruction to limited extent, affected calpain-1 protein expression and influenced calpain-mediated spectrin cleavage as a function of Src expression. In organotypic spinal cord slice cultures, CL was not able to support motor neuron survival/neurite sprouting. Moreover, it hampered astroglia and microglia activities. The data suggest that CL may have only isolated positive effects on injured spinal motor neurons. High-dosed or accumulated CL seemed to have adverse effects in treatment of spinal cord injury. Further experiments are required to optimize the conditions for a safe clinical administration of CL in spinal cord injuries.

ERBB2-amplified lobular breast carcinoma exhibits concomitant CDK12 co-amplification associated with poor prognostic features.

Most invasive lobular breast carcinomas (ILBCs) are luminal-type carcinomas with an HER2-negative phenotype (ERBB2 or HER2 un-amplified) and CDH1 mutations. Rare variants include ERBB2-amplified subtypes associated with an unfavorable prognosis and less response to anti-HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2-amplified ILBC and compared these characteristics with ERBB2-unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin-embedded formalin-fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast-specific markers was tested by immunohistochemistry (IHC). Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2-amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2-unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2-positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2-amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2-amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2-unamplified ILBC. CDK12/ERBB2 co-amplification may explain the poor prognosis and therapy resistance of ERBB2-amplified ILBC.

Computed tomographic angiography imaging and clinical implications of internal mammary artery perforator vessels as recipient vessels in autologous breast reconstruction.

The internal mammary artery (IMA) is the standard recipient vessel for autologous breast reconstruction. To save the IMA for bypass surgery, to keep flap pedicles short, and to allow better flap positioning, the IMA perforators were used. Forty-six flaps for immediate breast reconstructions were performed in 39 patients. In the first 22 patients, the decision to use the perforators was clinically based. In the second group of 17 patients, all patients received a thoracic computed tomographic angiography (CTA) to determine the perforators. In 13 flaps (6 deep inferior epigastric artery perforator, 3 superficial inferior epigastric artery, and 4 transverse myocutaneous gracilis), the perforators were used as recipient vessels. Of these flaps, 5 were anastomosed to perforators before the CTA was applied and 8 after the CTA was established. The CTA revealed the IMA and the perforators in detail. In immediate reconstructions, the IMA perforators can be used as recipient vessels. They allow better flap positioning for superficial inferior epigastric artery and transverse myocutaneous gracilis flaps in particular; moreover, it decreases donor site and recipient site morbidity. After introducing the CTA, the perforators were used more frequently for anastomosis.

The Scarless Neo-Umbilicus in DIEP-Flap Breast Reconstruction.

While the DIEP (deep inferior epigastric perforator) flap has become the gold standard in autologous breast reconstruction due to its favourable tissue characteristics and preserved abdominal wall function, a constant attempt is done to improve the outcome of the donor site. Even if just a small detail, the umbilicus has a big impact on the overall aesthetic outcome of the donor site. As an already established technique in abdominoplasties, we introduced the neo-umbilicus as the standard procedure for DIEP donor site closure. The aim of this study was to assess the aesthetic outcome of this neo-umbilicoplasty technique in DIEP-flaps. This is a single-center cohort study. A total of 30 consecutive breast cancer patients were treated during a period of 9 months with a mastectomy and an immediate reconstruction with a DIEP-flap. In all patients, the reconstruction of the umbilicus was done by an immediate neo-umbilicoplasty technique, consisting of a cylindrical fat resection at the new loco typico and fixation of the dermis directly to the rectus fascia. All patients were photographed in a standardised setting. Subjective patient satisfaction was assessed with a survey consisting of three questions and aesthetic outcome was evaluated by an independent professional panel consisting of three plastic surgeons. The results were compared to a previous cohort of conventional umbilicoplasties in DIEP-flap patients. Twenty-six patients participated in the follow-up study. There were no wound complications associated with the neo-umbilicus. Questionnaire results demonstrated high but not statistically significant different patient satisfaction. The panel scores were statistically significant (p < 0.05) better for the neo-umbilicus reconstructions. The aesthetic outcome was rated higher in patients with a higher BMI compared to those in patients with a low BMI. The creation of a neo-umbilicus at the donor site after DIEP-flap breast reconstruction is a quick and safe technique and leads to a superior aesthetic donor site result.

[Skin Wrinkling on Hands and Feet: Theory and Practice]. / Skin wrinkling an Händen und Füßen ­ Theorie und Praxis.

The wrinkling of the skin on hands and feet when submersed in water is a well-known phenomenon. However, the explanation for this is not quite trivial. The peripheral nervous system seems to have an influence. In case of nerve injuries, it is often observed that skin wrinkling does not occur. In this report, three cases are presented in which wrinkling of the hand was absent after a nerve injury. In addition, we provide an overview of the studies on this topic.

The transverse myocutaneous gracilis flap (TMG) for breast reconstruction: ipsi vs. contralateral harvest-aesthetic outcome and refinement procedures.

BACKGROUND: The TMG flap is a popular choice for breast reconstruction. However, it remains unclear whether the side of flap harvest, subsequent flap shaping and inset impacts breast appearance and volume dispersion. This study compares the aesthetic outcome of the reconstructed breast following TMG flap harvest from the ipsilateral or contralateral thigh. PATIENT AND METHODS: A retrospective matched-pair multi-center study was conducted. Patients were grouped according to the side of flap harvest (ipsilateral vs. contralateral) and matched for age, BMI and mastectomy type. Between 01/2013 and 03/2020, 384 TMG breast reconstructions were performed, of which 86 were included (43 ipsilateral vs. 43 contralateral). Standardized pre- and postoperative photographs were evaluated using a modified assessment scale comprising of a symmetry score (SymS, max. 20 points), a volume discrepancy score (VDS, max. 8 points) and an aesthetic appearance score (AS, max. 10 points). Autologous fat grafting (AFG) procedures for breast refinement were compared. RESULTS: Pleasing breast symmetry (SymS Ipsi: 14.5/20; Contra: 14.9/20), volume (VDS Ipsi: 3.3/8; Contra: 2.4/8) and aesthetic appearance (AS Ipsi: 6.7/10; Contra: 6.7/10) were achieved with both surgical methods. No significant changes were present regarding the VDS (F(1.82) = 2.848, p = 0.095) or the SymS (F(1.82) = 1.031, p = 0.313) pre- to postoperatively. Significantly more autologous fat grafting was done in the contralateral group (p < 0.001). CONCLUSION: The side of the TMG flap harvest, different shaping and inset techniques do not impact the aesthetic breast outcome. Both surgical methods result in pleasing breast symmetry and volume. Secondary procedures are common and should be entailed in the reconstructive strategy.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Magnetic nanoparticles in primary neural cell cultures are mainly taken up by microglia.

BACKGROUND: Magnetic nanoparticles (MNPs) offer a large range of applications in life sciences. Applications in neurosciences are one focus of interest. Unfortunately, not all groups have access to nanoparticles or the possibility to develop and produce them for their applications. Hence, they have to focus on commercially available particles. Little is known about the uptake of nanoparticles in primary cells. Previously studies mostly reported cellular uptake in cell lines. Here we present a systematic study on the uptake of magnetic nanoparticles (MNPs) by primary cells of the nervous system. RESULTS: We assessed the internalization in different cell types with confocal and electron microscopy. The analysis confirmed the uptake of MNPs in the cells, probably with endocytotic mechanisms. Furthermore, we compared the uptake in PC12 cells, a rat pheochromocytoma cell line, which is often used as a neuronal cell model, with primary neuronal cells. It was found that the percentage of PC12 cells loaded with MNPs was significantly higher than for neurons. Uptake studies in primary mixed neuronal/glial cultures revealed predominant uptake of MNPs by microglia and an increase in their number. The number of astroglia and oligodendroglia which incorporated MNPs was lower and stable. Primary mixed Schwann cell/fibroblast cultures showed similar MNP uptake of both cell types, but the Schwann cell number decreased after MNP incubation. Organotypic co-cultures of spinal cord slices and peripheral nerve grafts resembled the results of the dispersed primary cell cultures. CONCLUSIONS: The commercial MNPs used activated microglial phagocytosis in both disperse and organotypic culture systems. It can be assumed that in vivo application would induce immune system reactivity, too. Because of this, their usefulness for in vivo neuroscientific implementations can be questioned. Future studies will need to overcome this issue with the use of cell-specific targeting strategies. Additionally, we found that PC12 cells took up significantly more MNPs than primary neurons. This difference indicates that PC12 cells are not a suitable model for natural neuronal uptake of nanoparticles and qualify previous results in PC12 cells.

Autologous Breast Reconstruction with Free Nipple-Areola Graft after Circumareolar (Skin Reducing) Mastectomy.

Introduction of skin-sparing mastectomy (SSM) led to a paradigm shift in breast reconstruction. Primary reconstructions have become the therapy of choice. At the same time, immediate autologous reconstructions are oncologically safe and aesthetically pleasing. Our preferred SSM incision is the circumareolar with removal of nipple and areola (NAC). Adjustment of the skin envelope is well accomplished in mild-to-moderate ptotic breasts. We describe our technique consisting of circumareolar incision in SSM, keeping the NAC as a free graft, and immediate autologous reconstruction and immediate free NAC grafting on the flap. Aesthetic indications are slight asymmetries, ptotic breasts, large breasts where the reconstructed breast will be smaller than the original breast and where a Wise pattern is not indicated. Oncologic indications are risk-reducing mastectomies and tumors close to the NAC where resection would compromise the vitality of the NAC. We evaluated the healing of the NAC and the NAC position with regard to the breast shape. From 2019-2022, 296 autologous flaps were used for breast reconstruction. In 36 flaps, this technique was applied. Eighteen flaps were bilateral (nine patients). In total, we performed 15 inner thigh flaps and 21 DIEP flaps. No flap or NAC loss occurred. There was no wound healing complication at the breast, and no adjuvant chemotherapy or radiation therapy needed to be postponed. The advantages of this technique are (1) scar reduction with only one periareolar scar on the breast, which is also well concealed; (2) oncological safety in relation to the nipple and optimal visibility of the mastectomy cavity, which allows a meticulous mastectomy, especially important in risk-reducing mastectomies; (3) generally, fewer wound healing problems, especially fewer than with Wise pattern incision; (4) primary adjustment of the skin envelope and positioning of the NAC are easier to perform than in a secondary procedure; and (5) that the NAC is spared, and no secondary reconstruction is necessary. Disadvantages are that (1) the NAC must heal as a free graft and (2) that the sensitivity of the NAC is lower than in pedicled NAC transposition.

Identification of Independent Risk Factors for Skin Complications in a Multifactorial Logistic Regression Analysis of Simultaneous Immediate Autologous Breast Reconstruction and Skin Reduction Mastectomy in Large and Ptotic Breasts Using an Inferiorly Based Deepithelialized Dermal Breast Flap.

Autologous immediate breast reconstruction in large and ptotic breasts remains challenging. We aimed to identify independent risk factors for impaired wound healing and nipple necrosis after skin reducing wise pattern mastectomy in autologous reconstruction with an auxiliary deepithelialized inferiorly based dermal flap (IBDF). METHODS: This retrospective study examined patients with wise pattern mastectomy with autologous immediate breast reconstruction (IBR) between 2017 and 2019. All cases of large and ptotic breasts were included. Demographic, oncologic, reconstructive, and surgical data were compiled, and multifactorial binary logistic regression models identified independent predictors for skin complications and nipple areolar complex (NAC) necrosis. RESULTS: Of 591 autologous breast reconstructions, 62 (11%) met the inclusion criteria. Overall wound complication rate was 32% (n = 20, DIEP 11, thigh 9, p = 0.99), including 26% minor (n = 16, non-surgically treated) and 7% major complications (n = 4, surgically treated). Complete NAC necrosis occurred in one case. Nipple sparing mastectomy (NSM) (p = 0.003), high BMI (p = 0.019), longer operation time (p = 0.044) and higher patient age (p = 0.045) were independent risk factors for skin complications. Using internal mammary artery perforators (IMAP) as recipient vessels did not result in increased complication rates (p = 0.59). CONCLUSION: Higher patient age, BMI, and operation time (OT) significantly increase the risk for skin complications in combined reduction wise pattern mastectomies with autologous IBR. In this context, IBDFs help preserve the inframammary fold, providing vasculature to the T-junction and the mastectomy skin flaps. Acceptable complication rates can be achieved in large and ptotic breasts, regardless of preoperative chemotherapy or radiation. Gentle tissue handling with minimal thermal trauma preserves internal mammary artery perforators (IMAPs) as recipient vessels. In cases of flap failure and alloplastic conversion, the IBDF can serve as an autoderm, protecting the implant from exposure.

Enhanced Recovery after Surgery (ERAS) in DIEP-Flap Breast Reconstructions-A Comparison of Two Reconstructive Centers with and without ERAS-Protocol.

Enhanced recovery after surgery (ERAS) is established for autologous breast reconstruction. ERAS leads to a shortened hospital stay and improved outcome after elective surgery. In this retrospective, two-center case−control study, we compared two different treatment regimens for patients undergoing a DIEP-flap breast reconstruction from two centers, one with an established ERAS protocol and one without. All patients with DIEP breast reconstructions over the period of 12 months were included. The primary outcome measure was the length of hospital stay (LOS) in days. A total of 79 patients with 95 DIEP-flaps were analyzed. In group A (ERAS) 42 patients were operated with DIEP flaps, in group B (non-ERAS) 37 patients. LOS was significantly reduced in the ERAS group (4.51 days) compared to the non-ERAS group (6.32; p < 0.001). Multivariate analysis showed that, in group A, LOS is significantly affected by surgery duration. BMI in the ERAS group had no effect on LOS. In group B a higher BMI resulted in a significantly higher LOS. In multivariate analysis, neither age nor type for surgery (primary/secondary/after neoadjuvant therapy, etc.) affected LOS. In both groups, no systemic or flap-related complications were observed. Comparing two reconstructive centers with and without implemented ERAS, ERAS led to a significantly decreased LOS for all patients. ERAS implementation does not result in an increased complication rate or flap loss. Postoperative pain can be well managed with basic analgesia using NSAID when intraoperative blocks are applied. The reduced use of opioids was well tolerated. With implementation of ERAS the recovery experience can be enhanced making autologous breast reconstructions more available and attractive for various patients.

The Ryanodine receptor stabilizer S107 fails to support motor neuronal neuritogenesis in vitro.

Calcium homeostasis is essential for neuronal cell survival/differentiation. Imbalance of the Ca2+ homeostasis due to excessive Ca2+ overload is essential for spinal cord injury (SCI). The overload resulted from Ca2+ flux across the plasma membrane and from internal Ca2+ store release (mitochondria, endoplasmic reticulum, ER). Inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) are involved in releasing Ca2+ from ER contributing to axonal degeneration following SCI. In turn, block of both receptors is axoprotective. The calstabin RyR subunit, stabilizing the channel in a state of reduced activity, prevents pathological Ca2+ release too. We investigated whether S107, a RyR-stabilizing compound (Rycal), is beneficial for survival and neuritogenesis of spinal cord motor neurons in vitro. We used a spinal cord slice model and the motor neuron-like NSC-34 cell line. Effects of S107 were tested by propidium iodide/fluorescein diacetate vital staining, mitotic index determination via BrdU-incorporation, and neurite sprouting parameters. Results showed that S107 (i) had no effect on gliosis resulting from slices preparation; (ii) had no effect on motor neuronal survival and proliferation; and (iii) impaired neurite sprouting, no matter whether it was a differentiation (NSC-34 cells) or regeneration (spinal cord slices) process. The results underline the need for a flexible Ca2+homeostasis provided by the ER for re-initiation of neuritogenesis.

Overall Complication Rates of DIEP Flap Breast Reconstructions in Germany-A Multi-Center Analysis Based on the DGPRÄC Prospective National Online Registry for Microsurgical Breast Reconstructions.

While autologous breast reconstruction has gained momentum over recent years, there is limited data on the structure and quality of care of microsurgical breast reconstruction in Germany. Using the breast reconstruction database established by the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC), the presented study investigated the overall outcomes of deep inferior epigastric perforator (DIEP) flap reconstructions in Germany. Data of 3926 patients and 4577 DIEP flaps performed by 22 centers were included in this study. Demographics, patient characteristics, perioperative details and postoperative outcomes were accounted for. Centers performing < Ø 40 (low-volume (LV)) vs. ≥ Ø 40 (high-volume (HV)) annual DIEP flaps were analyzed separately. Overall, total and partial flap loss rates were as low as 2.0% and 1.1% respectively, and emergent vascular revision surgery was performed in 4.3% of cases. Revision surgery due to wound complications was conducted in 8.3% of all cases. Mean operative time and length of hospital stay was significantly shorter in the HV group (LV: 385.82 min vs. HV: 287.14 min; LV: 9.04 (18.87) days vs. HV: 8.21 (5.04) days; both p < 0.05). The outcome and complication rates deduced from the national registry underline the high standard of microsurgical breast reconstruction on a national level in Germany.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

[End-to-side venous anastomosis with a coupler device in microvascular free flaps]. / Die venöse End zu Seit Anastomose mit einem Coupler Device bei freien mikrovaskulären Lappenplastiken.

The aim of this study was to describe our results and experience with end-to-side venous anastomosis using a coupler device in microvascular free flaps.

Internal Mammary Artery and Vein Perforator Vessels as Troubleshooter Recipient Vessels.

In autologous breast reconstruction, the internal mammary artery (IMA) and internal mammary vein (IMV) are the standard recipient vessels. Recently, the perforator vessels of the IMA and IMV were found to be a safe alternative as recipient vessels cause less morbidity and allow adequate flap. We describe 2 cases in which the IMA and IMV perforators were used as additional recipient vessels to overcome intraoperatively occurred complications. The IMA and IMV perforators have some advantages over the IMA/IMV: (1) the dissection is done superficially and directly from the mastectomy site. Flap positioning is facilitated. (2) There is no need to remove a rib, which reduces postoperative pain and possible contour deformities. (3) Possible injuries to the pleura are avoided. (4) The IMA is spared for possible cardiac revascularization. Disadvantages can be that (1) the IMA perforators are not always present with the required caliber, (2) the position of the perforators is not suitable to adequately position the flap, and (3) dissection of the IMA perforators and their anastomoses has a learning curve. In the presented cases, the IMA and IMV perforators have proven to offer a simple solution to avoid complications. The additional dissection is done from the same recipient site, and there is no further dissection or incision necessary at the axilla or to explore the cephalic vein. This keeps morbidity and operation time low. Therefore, we suggest keeping the IMA and IMV perforators in mind not only as primary recipient vessels but also as a possible solution for intraoperatively occurred complications.

[Profitability of reconstructive microsurgery: position paper of the German-Speaking Group for Microsurgery of Peripheral Nerves and Vessels]. / Wirtschaftlichkeit der rekonstruktiven Mikrochirurgie: Positionspapier der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie ­ (DAM).

The profitability of medical treatment has gained increasing importance in health politics and likewise has become a considerable part of a microsurgeon's daily practice. The resulting cost pressure leads to microsurgeons having to justify their often complex and expensive treatments against hospital providers and health insurances. In this position paper of the German Speaking Group for Microsurgery of Peripheral Nerves and Vessels, we analyze the current status of profitability of microsurgical extremity and breast reconstruction, and its impact on choice of therapy and residency training. We specifically highlight the available literature, that shows often reduced long-term treatment costs after microsurgical reconstruction in comparison to cheaper initial treatments. The statements are based on a consensus workshop on the 40th meeting of the DAM in Lugano, Switzerland.

[Smartphone-based thermography for perforator localisation in microvascular breast reconstruction]. / Die Smartphone-basierte Thermographie zur Lokalisation von Perforatoren bei der mikrovaskulären Brustrekonstruktion.

BACKGROUND: Thermography permits non-invasive examination and presentation of cutaneous temperature differences. When planning microvascular flaps, thermography may illustrate these differences and may portray patterns of blood circulation near to perforators. As an additional tool, thermography may enhance quality and diversity in free flaps. PATIENTS AND METHODS: In this prospective study, we examined 10 patients with 13 free DIEP-flaps for breast reconstruction. With smartphone-based thermography, we analysed preoperative abdominal "hot spots" of skin circulation (entrance of perforators). The results were compared with preoperative computed tomographic angiography (CTA) and intraoperative anatomical findings. RESULTS: Thermography was succesfully performed on all patients. Areas of perfusion were reliably shown in the raised area ("hot spot"). Each perforator selected by thermography was also selected for the DIEP free flap on the basis of intraoperative findings. Moreover, the identified main perforators were identical to perforators found at the CTA. CONCLUSION: Smartphone-based thermography provides an easy, rapid and non-invasive method to present cutaneous differences in temperature. "Hot spots" can reliably illustrate the entrance of perforators. When selecting a suitable perforator, thermography provides additional information for imaging perforator-based flaps.

Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells.

Bone marrow stromal cells (MSC) are multipotent stem cells that differentiate into cells of the mesodermal lineage. Although adult, their differentiation potential is remarkable, and they are able to transdifferentiate. Transdifferentiated cultivated rat MSC (tMSC) changed morphologically into cells resembling typical spindle-shaped Schwann cells (SC) with enhanced expression of LNGF receptor, Krox-20, CD104 and S100beta protein and decreased expression of bone morphogenetic protein receptor-1A compared to untreated rat MSC (rMSC). Transdifferentiation was reversible and repeatable. To evaluate the myelinating capacity, rMSC, tMSC, or SC cultured from male rats were grafted into an autologous muscle conduit bridging a 2-cm gap in the female rat sciatic nerve. The presence of the male-specific SRY gene (as revealed by PCR analysis) and S100 immunoreactivity of pre-labeled tMSC confirmed the presence of the implanted cells in the grafts. Three weeks after grafting, an appropriate regeneration was noted in the SC and in the tMSC groups, while regeneration in the rMSC group and in the control group without any cells was impaired. In contrast to SC, in some cases, single tMSC were able to myelinate more than one axon. Our findings demonstrate that it may be possible to differentiate MSC into therapeutically useful cells for clinical applications.