Prospective assessment of the quality of life and nipple sensation after gender-affirming chest surgery.

BACKGROUND: In the existing literature, assessing transgender patients' quality of life after surgery, especially using standardized surveys, is rare. The nipple sensation regarding the operating technique has neither been studied in a prospective nor standardized way. METHODS: For one year, we prospectively assessed transgender patients operated on for a gender-affirming chest surgery in our unit. Each patient answered the BREAST-Q© survey and the BODY-Q© chest module survey before and six months after the surgery. In addition, a measure of nipple sensation was performed using Semmes-Weinstein monofilaments pre-and post-operatively to compare surgical techniques. RESULTS: Fifty-one patients (102 breasts) were included in our study. The average age was 23.1 years and the average BMI was 24.8 kg/m2. Twenty-one patients (45%) had double incision and free nipple graft mastectomy, 14 (27%) patients had double incision and inferior pedicle mastectomy, while the 14 (27%) other patients had a semi-circular technique. Our study shows an improvement in all the scores of the surveys after surgery (p < 0.0001). Patients with double incision and inferior pedicle mastectomies rated a significantly higher satisfaction with nipples (p = 0.013) and significantly better sexual well-being (p = 0.007) than other techniques. In addition, preservation of nipple sensation was shown in patients operated by semi-circular technique (p < 0.001) and inferior pedicle technique (p < 0.0001). CONCLUSIONS: Our prospective study confirms the significant improvement in the quality of life of transgender patients after chest gender-affirming surgery. Double incision with inferior pedicle seems to provide better satisfaction with nipples, higher sexual well-being, and preservation of nipple sensation.

Knee Joint Rescue in a Traumatic Amputation With Coverage by a Fillet-Free Flap From the Amputated Leg.

Traumatic amputation is a severe injury that requires urgent surgical care. A fillet-free flap from the amputated limb is the most conservative way to ensure proper coverage of the stump when replantation is not possible. We report the case of a male patient who suffered from a traumatic limb amputation in a motorcycle accident. A free fillet flap from the posterior compartment of the leg carrying the posterior tibial pedicle, the soleus muscle, and skin tissue harvested from the amputated limb was performed to cover the amputation stump and thus allow preservation of the knee joint. In our case report, the patient conserved almost maximal knee joint range of motion (130°). He regained the ability to walk only two months after the initial trauma. Prosthetic fitting occurred quickly and without any particular issues throughout the process. Regarding quality of life, after one year, our patient had a five-level EQ-5D version (EQ-5D-5L) score of 21,221, and his 36-Item Short Form Survey (SF-36) score was divided between the five components in 85 points in physical functioning, 100 points in role limitations due to physical health, 100 points in role limitations due to emotional problems, 50 points in energy/fatigue, 68 points in emotional well-being, 75 points in social functioning, 45 points in pain, and 95 points in general health. This technique helped provide good coverage of the stump while preserving a functional knee joint, allowing for effective prosthetic fitting in the future and therefore optimizing our patient's quality of life.

Breast reconstruction using DIEP flap: The free flap alone be enough? Quality of life and satisfaction analysis after complementary surgeries.

INTRODUCTION: Breast reconstruction using Deep Inferior Epigastric Perforator (DIEP) flap involves complementary surgeries such as lipofilling, symmetrization, and nipple-areolar complex (NAC) reconstruction. Their role and impact have not been explored yet after the DIEP flap use. MATERIAL AND METHODS: A retrospective study was performed to evaluate the impact of complementary surgeries on the quality of life of 75 patients after DIEP flap breast reconstruction between 2012 and 2021, comparing the BREAST-Q© score of two groups, patients with DIEP flap only reconstruction and patients with DIEP flap and additional surgeries. Satisfaction for each surgery was assessed using a numeric visual scale on five dimensions (esthetic, self-image, confidence in society, pain, and intimate relationship). Complications and healthcare pathways were also recorded. RESULTS: Psychosocial well-being (Q1 BREAST-Q©), satisfaction with medical team (Q9) and with surgeon (Q11) was superior in group 2 (p = 0041, p = 0.001 and p = 0.001 respectively). NAC reconstruction improved BREAST-Q© (p = 0029) by regression analysis and was deemed indispensable by 64% of the patients. An important satisfaction is observed after each surgery (DIEP flap, symmetrization, lipofilling and NAC reconstruction). Complications were uncommon (0-4%) for lipofilling and NAC reconstruction and notable but harmless for symmetrization (wound dressings more than a month in 17%). CONCLUSION: Complementary surgeries, especially NAC reconstruction, improved BREAST-Q© score, and have a major impact on satisfaction with minor complications. These surgeries should always be proposed to the patients to assess a satisfactory breast reconstruction using DIEP flap.

How to measure vessel caliber in microsurgery and super-microsurgery? Metrological study of three methods applicable in clinical practice.

INTRODUCTION: The microsurgical literature reports the vascular calibers of the vessels studied even though the method of measurement of these vessels is very rarely reported. MATERIAL AND METHOD: We performed a metrological study evaluating three methods to measure the external calibers of catheters corresponding to microsurgical and super-microsurgical vessels (1.2 mm, 0.8 mm, and 0.6 mm). Six evaluators measured 15 catheters of three different hidden diameters by each of the three methods applicable in clinical practice: standard graduated ruler, Shinwa® micrometric ruler, and ImageJ® software from a photograph. Accuracy and reliability of the measurements were assessed by studying the inter- and intra-rater and inter-method coefficients (variants of the intra-class coefficient (ICC)) and analysis of the IC95% of the ICCs. RESULTS: Intra class correlation ICC "intra-rater" coefficient finds for the standard rule 0.81 [0.65-0.93], Shinwa® rule 0.86 [0.67-0.96], and for the ImageJ® software 0.97 [0.94-0.99]. The "Inter-rater" ICC shows respectively the coefficient 0.51 [0.23 and max 0.93], 0.87 [0.75-0.95], and 0.95 [0.89-0.98]. It appears that the graduated decimeter is the least reliable method of measurement, the Shinwa® ruler presents acceptable reliability but requires the purchase of equipment. The reliability of ImageJ® software is the best and appears to be the most reliable method. CONCLUSION: Our original study, with no equivalent in the scientific literature, demonstrates objectively the great accuracy and reliability of a method of measurement of vascular calibers in micro and super microsurgery using intraoperative photography and the use of free computer software.

Rat Perforator and Skin Vessels Vascular Mapping: An Original Anatomical Study About 140 Vessels and Literature Review.

INTRODUCTION: Recent microsurgical reconstruction techniques benefit from the use of skin and perforator flaps that spare the donor sites. Studies on these skin flaps in rat models are numerous but there is currently no reference regarding the position of the perforators, their caliber, and the length of the vascular pedicles. METHODS: We performed an anatomical study on 10 Wistar rats and 140 vessels: cranial epigastric (CE), superficial inferior epigastric (SIE), lateral thoracic (LT), posterior thigh (PT), deep iliac circumflex (DCI) and posterior intercostal (PIC) vessels. The evaluation criteria were the external caliber, the length of the pedicle, and the position of the vessels reported on the skin surface. RESULTS: Data from the six perforator vascular pedicles are reported, with figures illustrating the orthonormal reference frame, the representation of the vessel's position, the cloud of points corresponding to the various measurements, and the average representation of the collected data. The analysis of the literature does not find similar studies; the different vascular pedicles are discussed as well as the limitations of our study: evaluation of cadaver specimen, presence of the very mobile panniculus carnosus, other perforator vessels not evaluated as well as the precise definition of perforating vessels. CONCLUSIONS: Our work describes the vascular calibers, pedicle lengths, and location of birth and arrival at the skin of the perforator vessels PT, DCI, PIC, LT, SIE, and CE in rat animal models. This work, without an equivalent in the literature, lays the foundation for future studies about flap perfusion, microsurgery, and super microsurgery learning.

Baseline Characteristics of a National French E-Cohort of Hidradenitis Suppurativa in ComPaRe and Comparison with Other Large Hidradenitis Suppurativa Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition substantially impacting patients' quality of life; the pathogenesis remains unclear, and treatment is complex and not yet standardized. Observational data are increasingly being used to evaluate therapeutics in "real-life" interventions, and the development of e-cohorts is offering new tools for epidemiological studies at the population level. OBJECTIVE: The aim of this study was to describe the clinical characteristics and treatment history of HS participants in the Community of Patients for Research (ComPaRe) cohort and to compare these to other cohorts. METHODS: We performed a cross-sectional study of the baseline data of HS participants in ComPaRe, an e-cohort of patients with chronic diseases. Data were collected using patient-reported questionnaires about clinical-dem-ographic aspects, quality of life, and treatment history. RESULTS: A total of 396 participants (339 females, 57 males) were included (mean age 38 years); 83 (21%) had a family history of HS, 227 (57.3%) were current smokers, and 241 (60.9%) were overweight or obese. Most of the participants declared a Hurley stage II (n = 263, 66.4%) or III (n = 76, 20.3%). The breast was more frequently affected in women than men (37.5 vs. 5.3%, p < 0.0001), whereas the dorsal region was more frequently affected in men (39.5 vs. 10.9%, p < 0.0001). Increased disease stage was associated with obesity (25.9 vs. 33.8 vs. 51.3%, p = 0.02) and some HS localizations (genital [p < 0.005], pubis [p < 0.007], gluteal fold [p = 0.02], and groin [p < 0.0001]). The most frequently prescribed treatments were oral antibiotics (n = 362, 91.4%), especially amoxicillin-clavulanic acid and cyclins. Less than 10% of participants received biologics. Most of these results were consistent with previously published cohorts. CONCLUSION: Recruitment of participants by such a web platform can be a faster way to get relevant scientific data for a wide variety of patients that could be used for epidemiological studies and to evaluate therapeutics in "real-life" interventions.

Management of Congenital Melanocytic Naevi in Children: A French National Survey Using Clinical Vignettes.

Management of congenital melanocytic naevi in childhood may vary depending on the habits and experience of the treating clinician. The aim of this study was to assess current practice and determinants of surgical excision decision-making among French physicians. A national survey was conducted among dermatologists, paediatricians and surgeons, using clinical vignettes illustrating 29 scenarios. The primary outcome was the decision to perform surgical excision in each vignette. Of the 11,310 decisions made by the 390 participants (257 dermatologists, 35 surgeons, and 98 paediatricians) surgical excision was chosen in 33% of cases. The stated motivations for performing surgical excision were: melanoma risk, aesthetic/psychosocial risk, or both, in 39%, 34% and 27% of cases, respectively. Physicians with a higher level of experience in oncodermatology were more likely to opt for surgical excision. The age of the child, the size of the congenital melanocytic naevi, and the visibility of the lesion had no influence on the decision to perform surgical excision.

A Novel Absorbable Stapler Provides Patient-Reported Outcomes and Cost-Effectiveness Noninferior to Subcuticular Skin Closure: A Prospective, Single-Blind, Randomized Clinical Trial.

BACKGROUND: Deep dermal suturing is critical for scar quality outcomes. The authors evaluated a new, fast medical device for dermal suturing, with the hypothesis of noninferiority with regard to clinical scar and cost-effectiveness. METHODS: A prospective, patient-blind, randomized, multicenter noninferiority study in 26 French hospitals was conducted. Patients were randomized 1:1 to suturing with conventional thread or a semiautomatic stapler. The Patient Scar Assessment Scale was rated at 3 months for primary endpoint effectiveness. Secondary endpoints were cost-effectiveness of the two suturing methods, prevalence of complications, suturing/operating time, Observer Scar Assessment Scale and Patient Scar Assessment Scale score, scar aesthetic quality 18 months after surgery, and occupational exposure to blood during surgery. RESULTS: Six hundred sixty-four patients were enrolled, 660 were randomized, and 649 constituted the full analysis (stapler arm, n = 324; needle arm, n = 325). Primary endpoint Patient Scar Assessment Scale score in the stapler arm was not inferior to that in the needle arm at 3 months or after 18 months. The mean operating time was 180 minutes in the stapler arm and 179 minutes in the needle arm (p = not significant). The mean suturing time was significantly lower in the stapler arm (p < 0.001). There were seven occupational exposures to blood in the needle arm and one in the stapler arm. The two arms did not differ significantly in terms of complications (p = 0.41). The additional cost of using the device was &OV0556;51.57 for the complete-case population. CONCLUSION: Wound healing outcome was no worse than with conventional suturing using a semiautomatic stapler and associated with less occupational exposure to blood. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Feasibility and impact of the implementation of a clinical scale-based sedation-analgesia protocol in severe burn patients undergoing mechanical ventilation. A before-after bi-center study.

BACKGROUND: Severe burn patients undergo prolonged administration of sedatives and analgesics for burn care. There are currently no guidelines for the dose adaptation of sedation-analgesia in severe burn patients. METHODS: We performed a before-after 2-center study to demonstrate the feasibility and efficacy of a sedation-analgesia scale-based protocol in severely burned patients receiving ≥24h of invasive mechanical ventilation. Before the intervention, continuous infusion of hypnotic and morphine derivatives was continued. During the Intervention phase, general anesthesia was relayed from day 1 by RASS/BPS-titrated continuous infusion of hypnotic and morphine derivatives and with short half-life drugs adminstered for daily burn dressings. The primary outcome was the duration of invasive mechanical ventilation in the ICU. RESULTS: Eighty-seven (46.2%) patients were included in the Control phase and 101 (53.7%) in the Intervention phase. The median burned cutaneous surface was 20% [11%-38%] and median ABSI was 7 [5-9]. The durations of hypnotic and opioid infusions were not statistically different between the 2 phases (8 days [2-24] vs. 6 days [2-17] (P=0.3) and 17 days [4-32] vs. 8 days [3-23] (P=0.06), respectively). The duration of mechanical ventilation was 14 days [3-29] in the Control phase and 7 days [2-24] in the Intervention phase (P=0.7). When taking into account the competition between mortality and weaning from mechanical ventilation, we found no significant difference between the 2 phases (Gray test, P=0.4). The time-series analysis showed no difference for the duration of mechanical ventilation in the Intervention phase (P=0.6). Eighteen (20.7%) patients died in the Control phase, and 18 (18%) in the Intervention phase (P=0.6). CONCLUSION: Scale-based lightening of continuous sedation-analgesia with repeated short general anesthesia for dressing is feasible in severe burn patients but failed to demonstrate a decrease in the duration of invasive mechanical ventilation.

Epinephrine Infiltration of Adipose Tissue Impacts MCF7 Breast Cancer Cells and Total Lipid Content.

BACKGROUND: Considering the positive or negative potential effects of adipocytes, depending on their lipid composition, on breast tumor progression, it is important to evaluate whether adipose tissue (AT) harvesting procedures, including epinephrine infiltration, may influence breast cancer progression. METHODS: Culture medium conditioned with epinephrine-infiltrated adipose tissue was tested on human Michigan Cancer Foundation-7 (MCF7) breast cancer cells, cultured in monolayer or in oncospheres. Lipid composition was evaluated depending on epinephrine-infiltration for five patients. Epinephrine-infiltrated adipose tissue (EI-AT) or corresponding conditioned medium (EI-CM) were injected into orthotopic breast carcinoma induced in athymic mouse. RESULTS: EI-CM significantly increased the proliferation rate of MCF7 cells Moreover EI-CM induced an output of the quiescent state of MCF7 cells, but it could be either an activator or inhibitor of the epithelial mesenchymal transition as indicated by gene expression changes. EI-CM presented a significantly higher lipid total weight compared with the conditioned medium obtained from non-infiltrated-AT of paired-patients. In vivo, neither the EI-CM or EI-AT injection significantly promoted MCF7-induced tumor growth. CONCLUSIONS: Even though conditioned media are widely used to mimic the secretome of cells or tissues, they may produce different effects on tumor progression, which may explain some of the discrepancy observed between in vitro, preclinical and clinical data using AT samples.

CICAFAST: comparison of a biological dressing composed of fetal fibroblasts and keratinocytes on a split-thickness skin graft donor site versus a traditional dressing: a randomized controlled trial.

BACKGROUND: Wound repair is one of the most complex biological processes of human life. Allogeneic cell-based engineered skin substitutes provide off-the-shelf temporary wound coverage and act as biologically active dressings, releasing growth factors, cytokines and extracellular matrix components essential for proper wound healing. However, they are susceptible to immune rejection and this is their major weakness. Thanks to their low immunogenicity and high effectiveness in regeneration, fetal skin cells represent an attractive alternative to the commonly used autologous and allogeneic skin grafts. METHODS/DESIGN: We developed a new dressing comprising a collagen matrix seeded with a specific ratio of active fetal fibroblasts and keratinocytes. These produce a variety of healing growth factors and cytokines which will increase the speed of wound healing and induce an immunotolerant state, with a slight inflammatory reaction and a reduction in pain. The objective of this study is to demonstrate that the use of this biological dressing for wound healing at the split-thickness skin graft (STSG) donor site, reduces the time to healing, decreases other co-morbidities, such as pain, and improves the appearance of the scar. This investigation will be conducted as part of a randomized study comparing our new biological dressing with a conventional treatment in a single patient, thus avoiding the factors that may influence the healing of a graft donor site. DISCUSSION: This clinical trial should enable the development of a new strategy for STSG donor-wound healing based on a regenerative dressing. The pain experienced in the first few days of STSG healing is well known due to the exposure of sensory nerve endings. Reducing this pain will also reduce analgesic drug intake and the duration of sick leave. Our biological dressing will meet the essential need of surgeons to "re-crop" from existing donor sites, e.g., for thermal-burn patients. By accelerating healing, improving the appearance of the scar and reducing pain, we hope to improve the conditions of treatment for skin grafts. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03334656 . Registered on 7 November 2017.

Ten-Year Safety Data for Eurosilicone's Round and Anatomical Silicone Gel Breast Implants.

BACKGROUND: Although silicone breast implants have been available for over 60 years, their safety and efficacy continue to be assessed via long-term clinical and vigilance studies. Complications often associated with breast implant surgery include but are not limited to capsular contracture and rupture. OBJECTIVE: The authors investigate and evaluate the safety and performance of Eurosilicone's (Eurosilicone S.A.S, Apt Cedex, France) Cristalline Paragel breast implants at least 10 years postimplantation. METHODS: Nine hundred and ninety-five of Eurosilicone's textured mammary implants were implanted in 526 women undergoing primary (423 patients) and revision surgery (103 patients) at 17 centers throughout France. Complications were recorded at 3 months and annually thereafter for 10 years. Descriptive statistics were used and the Kaplan-Meier method was utilized to analyze key complications. RESULTS: Seventy-four women (98 implants) experienced capsular contracture across all cohorts. The Kaplan-Meier 10-year cumulative risk of capsular contracture (Baker Grade III/IV) per implant was 11.5% in the primary augmentation cohort and 25.2% in the primary reconstruction cohort. Sixteen implant ruptures were observed by surgeon examination giving a Kaplan-Meier risk of 3.8% per patient and 3.5% per implant. Surgical re-intervention (explantation/exchange) was reported 80 times resulting in a Kaplan-Meier cumulative risk of 13.3% and 31.6% for primary augmentation and primary reconstruction, respectively, per patient. Local complication rates including infection and seroma were low with risk rates of 0.6% and 0.2% by subject. CONCLUSIONS: This multicenter clinical study demonstrates the long-term safety and efficacy profile through 10 years for Eurosilicone round and anatomical silicone gel breast implants.

Eight-Year Safety Data for Round and Anatomical Silicone Gel Breast Implants.

BACKGROUND: The safety and efficacy of all medical devices, including breast implants, is important and consistent performance is best shown by undertaking long-term clinical and vigilance studies. Local complications such as capsular contracture and rupture are risks often associated with breast implant surgery. OBJECTIVES: The authors investigate and evaluate the safety and performance of Eurosilicone's (Eurosilicone S.A.S, Apt Cedex, France) Cristalline Paragel breast implants at 8 years postimplantation. METHODS: In this prospective clinical study, 995 Eurosilicone textured cohesive Cristalline Paragel mammary implants were implanted in 526 women undergoing augmentation and reconstructive surgery at 17 centers across France. Complications were recorded at 3 months and annually thereafter for 8 years. Descriptive statistics were used and key complications were analysed using the Kaplan-Meier method. RESULTS: Capsular contracture was reported in 8.5% of implants across all cohorts through 8 years. The Kaplan-Meier risk of capsular contracture (Baker Grade III/IV) per implant was 8.4% in the primary augmentation cohort and 18.0% in the primary reconstruction cohort. Eight implant ruptures were identified by surgeon examination during this follow-up period. The Kaplan-Meier risk of rupture occurring within 8 years postimplantation, across all cohorts, was 1.4% per patient and 0.9% per implant. Actual implant removal rate (explantation/exchange) was 6.0% and 13.8% for primary augmentation and primary reconstruction, respectively. Actual rates of local complications including infection and seroma were low with risk rates of 0.6% and 0.2% by subject. CONCLUSIONS: This multicenter clinical study involving Eurosilicone's silicone gel breast implants in both round and shaped profiles demonstrates an excellent safety and efficacy profile through 8 years.

Management of finger deep burns: The interest of local flaps.

INTRODUCTION: The management of finger deep burns is still problematic for the surgeon. Due to the fineness and the thickness of the subcutaneous tissue, after excision there is an important risk of exposure of the underlying tissue like bone, nerve or tendons. Local flaps (random pattern flap and pedicle flap) allowed ensuring a good quality covering with a tissue with many advantages (good thickness, sensitivity). On the contrary of all other techniques, flaps can be used independently from the vascular quality of the wound bed. Despite those advantages, the literature is poor to report the experience of flap in the management of finger deep burn. MATERIAL AND METHODS: We report our experience in the use of such technique with a series of 49 flaps. The cohort consisted of 34 patients (22 men and 12 women) who were treated in our unit between 2003 and 2012. RESULTS: Of the 49 flaps made, 71,4% were homodactyl flaps. 22,5% were heterodactyl flaps and 6,1% were intermetacarpian (second space) flaps. The rate of success was 87,8%. We reviewed 16 patients out of 34 patients operated, 20 of the 49 flaps performed (40,8%). The patients were reviewed by an independent surgeon. The average follow-up at this consultation was 4,25±2,46 years. The monofilament test was positive for 17 flaps (85% of cases). For the Weber's test, we found a normal perception threshold for 11 flaps (55%), with an average test at 2,8mm (2-4mm). Normal motricity was found at the donor site in 14 of the 16 patients evaluated for 18 of the 20 revised flaps (90% of cases). In terms of cosmetic result, the average overall score obtained at the patient's own evaluation was 0.85. That obtained by the evaluator was equal to 0.55, with no significant difference (scale range from 0 best results to 5 worse results). DISCUSSION: Hand and finger burns are frequent and benefit from rapid, high-quality coverage, enabling early mobilization to combat secondary stiffness problems. The high success rate of our series, as well as the quality of the functional and cosmetic results obtained, demonstrate the reliability and the interest of the digital flaps.

Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status.

Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose-derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG-HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence.

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16- Human Blood Monocytes in Serum-Free Condition.

Langerhans cells (LCs) are epithelial APCs that sense danger signals and in turn trigger specific immune responses. In steady-state, they participate in the maintenance of peripheral tolerance to self-antigens whereas under inflammation LCs efficiently trigger immune responses in secondary lymphoid organs. It has been demonstrated in mice that LC-deprived epithelia are rapidly replenished by short half-life langerin-expressing monocyte-derived LCs (MDLCs). These surrogate LCs are thought to be progressively replaced by langerin(high) LCs arising from self-renewing epithelial precursors of hematopoietic origin. How LCs arise from blood monocytes is not fully understood. Hence, we sought to characterize key factors that induce differentiation of langerin(high)-expressing monocyte-derived Langerhans-like cells. We identified GM-CSF and TGF-ß1 as key cytokines to generate langerin(high)-expressing cells but only in serum-free conditions. These cells were shown to express the LC-specific TROP-2 and Axl surface markers and contained Birbeck granules. Surprisingly, E-cadherin was not spontaneously expressed by these cells but required a direct contact with keratinocytes to be stably induced. MDLCs induced stronger allogeneic T cell proliferations but released low amounts of inflammatory cytokines upon TLR stimulation compared with donor-paired monocyte-derived dendritic cells. Immature langerin(high) MDLCs were responsive to MIP-3ß/CCL20 and CTAC/CCL27 chemokine stimulations. Finally, we demonstrated that those cells behaved as bona fide LCs when inserted in a three-dimensional rebuilt epithelium by becoming activated upon TLR or UV light stimulations. Collectively, these results prompt us to propose these langerin(high) MDLCs as a relevant model to address LC biology-related questions.

ΔNp63α Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGFß-Induced Metastasis.

Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an antimetastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, ΔNp63α, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which ΔNp63α-expressing cells within a TGFß-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of ΔNp63α-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that ΔNp63α repressed miR-527 and miR-665, leading to the upregulation of two TGFß effectors, SMAD4 and TßRII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for ΔNp63α in the normal wound-healing response. We show that ΔNp63α-mediated repression of miR-527/665 controls a TGFß-dependent signaling node that switches off antimigratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel miRNA network involved in the regulation of physiologic wound-healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination. Cancer Res; 76(11); 3236-51. ©2016 AACR.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

BACKGROUND: Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. METHODS: Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. RESULTS: Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. CONCLUSIONS: This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Life-threatening hemorrhaging in neonatal ulcerated congenital hemangioma: two case reports.

IMPORTANCE: Congenital hemangiomas (CHs) are rare benign vascular tumors that differ from common infantile hemangiomas in that they grow in utero and are fully developed at birth. While ulceration is a common, predominantly benign complication in infantile hemangioma, little is known about the prognosis of ulcerated CH. However, it has been observed that ulcerated CH may be complicated by life-threatening bleeding episodes. OBSERVATIONS: We report 2 cases of ulcerated rapidly involuting congenital hemangiomas (RICH) that were complicated by life-threatening bleeding episodes in the neonatal period. In both cases, the CHs were fed by high-flow vessels and the ensuing massive bleeding was due to superficial vessel wall erosion induced by the ulceration. Both patients were successfully treated with intravascular embolization; one patient underwent additional hemostatic surgery. CONCLUSIONS AND RELEVANCE: These 2 cases highlight the importance of closely monitoring children with ulcerated CH because of the risk of severe bleeding. Embolization is the treatment of choice in the case of severe bleeding, as the natural history of RICH is to spontaneously regress.