Ghana 3D Telemedicine International MDT: A proof-of-concept study.

A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration. METHODS: A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients. RESULTS: Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries. CONCLUSIONS: This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations.

Differential impact of cytoplasmic vs. nuclear RAD51 expression on breast cancer progression and patient prognosis.

RAD51 recombinase is one of the DNA damage repair proteins associated with breast cancer risk. Apart from its function to maintain genomic integrity within the cell nucleus, RAD51 localized to the cytoplasm has also been implicated in breast malignancy. However, limited information exists on the roles of cytoplasmic vs. nuclear RAD51 in breast cancer progression and patient prognosis. In the present study, the association of cytoplasmic and nuclear RAD51 with clinical outcomes of patients with breast cancer was analyzed, revealing that elevated cytoplasmic RAD51 expression was associated with breast cancer progression, including increased cancer stage, grade, tumor size, lymph node metastasis and chemoresistance, along with reduced patient survival. By contrast, elevated nuclear RAD51 expression largely had the inverse effect. Results from in vitro investigations supported the cancer­promoting effect of RAD51, showing that overexpression of RAD51 promoted breast cancer cell growth, chemoresistance and metastatic ability, while knockdown of RAD51 repressed these malignant behaviors. The current data suggest that differential expression of subcellular RAD51 had a distinct impact on breast cancer progression and patient survival. Specifically, cytoplasmic RAD51 in contrast to nuclear RAD51 was potentially an adverse marker in breast cancer.

Tenosynovial giant cell tumor: a case report.

BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.

Effect of differing flap reconstruction strategies in perineal closure following advanced pelvic oncological resection: a retrospective cohort study.

INTRODUCTION: Advancing approaches to locally invasive pelvic malignancy creates a large tissue defect resulting in perineal wound complications, dehiscence, and perineal hernia. Use of reconstructive flaps such as vertical rectus abdominus myocutaneous (VRAM) flap, gracilis, anterolateral thigh and gluteal flaps have been utilised in our institution to address perineal closure. The authors compared outcomes using different flap techniques along with primary perineal closure in advanced pelvic oncological resection. METHODS: A prospectively maintained database of patients undergoing advanced pelvic oncological resection in a single tertiary hospital was retrospectively analysed. This study included consecutive patients between 2014 and 2021 according to the Strengthening The Reporting of Cohort Studies in Surgery (STROCSS) criteria. Primary outcome measures were the frequency of postoperative perineal complications between primary closure, VRAM, gluteal and thigh (anterolateral thigh and gracilis) reconstruction. RESULTS: One hundred twenty-two patients underwent advanced pelvic resection with perineal closure. Of these, 40 patients underwent extra-levator abdominoperineal resection, and 70 patients underwent pelvic exenteration. Sixty-four patients received reconstructive flap closure, which included VRAM (22), gluteal (21) and thigh flaps (19). Perineal infection and dehiscence rates were low. Infection rates were lower in the flap group despite a higher rate of radiotherapy ( P <0.050). Reoperation rates were infrequent (<10%) but specific for each flap, such as donor-site hernia following VRAM and flap dehiscence after thigh flap reconstruction. CONCLUSIONS: In patients who are at high risk of postoperative perineal infections, reconstructive flap closure offers acceptable outcomes. VRAM, gluteal and thigh flaps offer comparable outcomes and can be tailored to the individual patient.

IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway.

BACKGROUND: Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated. METHODS: Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan-Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry. RESULTS: Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin-a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes-reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin. CONCLUSIONS: The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.

In search of the ideal periosteal flap for bone non-union: The chimeric fibula-periosteal flap.

Vascularised periosteal flaps may increase the union rates in recalcitrant long bone non-union. The fibula-periosteal chimeric flap utilises the periosteum raised on an independent periosteal vessel. This allows the periosteum to be inset freely around the osteotomy site, thereby facilitating bone consolidation. PATIENTS AND METHODS: Ten patients underwent fibula-periosteal chimeric flaps (2016-2022) at the Canniesburn Plastic Surgery Unit, UK. Preceding non-union 18.6 months, with mean bone gap of 7.5 cm. Patients underwent preoperative CT angiography to identify the periosteal branches. A case-control approach was used. Patients acted as their own controls, with one osteotomy covered by the chimeric periosteal flap and one without, although in two patients both the osteotomies were covered using a long periosteal flap. RESULTS: A chimeric periosteal flap was used in 12 of the 20 osteotomy sites. Periosteal flap osteotomies had a primary union rate of 100% (11/11) versus those without flaps at 28.6% (2/7) (p = 0.0025). Union occurred in the chimeric periosteal flaps at 8.5 months versus 16.75 months in the control group (p = 0.023). One case was excluded from primary analysis due to recurrent mycetoma. The number needed to treat = 2, indicating that 2 patients would require a chimeric periosteal flap to avoid one non-union. Survival curves with a hazard ratio of 4.1 were observed, equating to a 4 times higher chance of union with periosteal flaps (log-rank p = 0.0016). CONCLUSIONS: The chimeric fibula-periosteal flap may increase the consolidation rates in difficult cases of recalcitrant non-union. This elegant modification of the fibula flap uses periosteum that is normally discarded, and this adds to the accumulating data supporting the use of vascularised periosteal flaps in non-union.

[Plastic-surgical reconstruction of the lower extremity in senior patients]. / Plastisch-chirurgische Rekonstruktion der unteren Extremität bei alten Patienten.

The proportion of patients in the population beyond the 7th decade of life is increasing worldwide, especially in highly developed countries. Consequently, there is also an increasing need for complex lower extremity reconstructions after trauma, tumors, or infections in this age group. The reconstruction of soft tissue defects of the lower extremity should be performed according to the principle of the plastic-reconstructive ladder or elevator. The goal of reconstruction is to restore anatomy and function of the lower extremity to enable pain-free and stable standing and walking; however, for older patients in particular, a careful preoperative multidisciplinary planning, detailed preoperative assessment and optimization of comorbidities, such as diabetes, malnutrition or pathological vascular alterations, as well an age-adapted perioperative management are necessary. By implementing these principles, older and very old patients can maintain their mobility and autonomy, which are crucial for a high quality of life.

Participatory development of a 3D telemedicine system during COVID: The future of remote consultations.

BACKGROUND: The COVID pandemic brought the need for more realistic remote consultations into focus. 2D Telemedicine solutions fail to replicate the fluency or authenticity of in-person consultations. This research reports on an international collaboration on the participatory development and first validated clinical use of a novel, real-time 360-degree 3D Telemedicine system worldwide. The development of the system - leveraging Microsoft's Holoportation™ communication technology - commenced at the Canniesburn Plastic Surgery Unit, Glasgow, in March 2020. METHODS: The research followed the VR CORE guidelines on the development of digital health trials, placing patients at the heart of the development process. This consisted of three separate studies - a clinician feedback study (23 clinicians, Nov-Dec 2020), a patient feedback study (26 patients, Jul-Oct 2021), and a cohort study focusing on safety and reliability (40 patients, Oct 2021-Mar 2022). "Lose, Keep, and Change" feedback prompts were used to engage patients in the development process and guide incremental improvements. RESULTS: Participatory testing demonstrated improved patient metrics with 3D in comparison to 2D Telemedicine, including validated measures of satisfaction (p<0.0001), realism or 'presence' (Single Item Presence scale, p<0.0001), and quality (Telehealth Usability Questionnaire, p = 0.0002). The safety and clinical concordance (95%) of 3D Telemedicine with a face-to-face consultation were equivalent or exceeded estimates for 2D Telemedicine. CONCLUSIONS: One of the ultimate goals of telemedicine is for the quality of remote consultations to get closer to the experience of face-to-face consultations. These data provide the first evidence that Holoportation™ communication technology brings 3D Telemedicine closer to this goal than a 2D equivalent.

The Cleft Lip Education with Augmented Reality (CLEAR) VR Phase 2 Trial: A Pilot Randomized Crossover Trial of a Novel Patient Information Leaflet.

BACKGROUND: The Cleft Lip Education with Augmented Reality (CLEAR) project centers around the use of augmented reality (AR) in patient leaflets, as a visual means to overcome the "health literacy" gap. This trial followed Virtual Reality (VR CORE) guidelines for VR Phase 2 (Pilot) trials. METHODS: Participants included families of children treated for Cleft Lip and Palate at the Royal Hospital for Children, Glasgow. Interventions were AR leaflet or Traditional Leaflet. Objectives were to calculate sample sizes, assess outcome instruments, trial design, and acceptability to patients. Primary outcome measure was Mental Effort Rating Scale, and secondary outcomes were Patient Satisfaction (Visual Analogue Scale), Usefulness Scale for Patient Information Material (USE) scale, and Instructional Materials Motivation Survey (IMMS). Randomization was by block randomization. The trial was single blinded with assessors blinded to group assignment. RESULTS: 12 Participants were randomized, with crossover design permitting analysis of 12 per group. Primary outcome with Mental Effort Rating Scale indicated higher mental effort with Traditional compared to AR Leaflet (4.75 vs 2.00, P = .0003). Secondary outcomes for Satisfaction were Traditional 54.50 versus AR 93.50 (P = .0001); USE scale 49.42 versus 74.08 (P = .0011); and IMMS 112.50 versus 161.75 (P = .0003). Subjective interviews noted overwhelmingly positive patient comments regarding the AR leaflet. Outcome instruments and trial design were acceptable to participants. No harms were recorded. CONCLUSIONS: The CLEAR pilot trial provides early evidence of clinical efficacy of AR leaflets in patient education. It is hoped that this will provide a future paradigm shift in the way patient education is delivered.

ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model.

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.

Functional quadriceps reconstruction: 3D gait analysis, EMG and environmental simulator outcomes.

OBJECT: Limited objective evidence exists on the benefits of functional muscle transfers following quadriceps resection in sarcoma. In particular, no studies have compared patients with functional transfers to those without. In this study, objective and subjective assessments were performed with 3D Gait Analysis, Environmental Simulator, Electromyography (EMG) and Patient-Reported Outcomes. METHODS: Thirty-four patients at the Scottish Sarcoma Network Glasgow Centre/ Canniesburn Plastic Surgery Unit underwent quadriceps resection for sarcoma between 2009 - 2019, including 24 patients with functional reconstruction and 10 without. Both groups were equivalent for the extent of quadriceps resection (2.58 versus 2.85 components, p=0.47). Primary outcome measure was 3D Gait Analysis and Gait Profile Score (GPS), and secondary outcome was the Toronto Extremity Salvage Score (TESS) score. Ancillary analyses included environmental simulation with the Motek CAREN system and EMG of transferred muscles. RESULTS: Outcomes measures were better in functional reconstruction patients when compared to those without - the GPS score was 8.04 versus 10.2 (p=0.0019), and the TESS score was 81.85 versus 71.17 (p=0.028). Environmental simulator tasks found that functional reconstruction patients could complete activities of daily living including shopping and collision avoidance tasks, without significantly slowing their walking speed. Patients without a functional reconstruction could not complete weighted shopping tasks. EMG showed that transferred hamstrings co-activated with the ipsilateral rectus femoris during the gait cycle. CONCLUSIONS: These are the first objective data demonstrating the superiority of muscle transfers for functional restoration in quadriceps resection versus patients without functional transfers. Critically, these also provide answers to patient-oriented questions relating to the recovery of function and activities of daily living.

What Matters to Us: Impact of Telemedicine During the Pandemic in the Care of Patients With Sarcoma Across Scotland.

PURPOSE: In Scotland, approximately 350 sarcoma cases are diagnosed per year and treated in one of the five specialist centers. Many patients are required to travel long distances to access specialist care. The COVID-19 pandemic brought a number of rapid changes into the care for patients with cancer, with increasing utilization of telemedicine. We aimed to evaluate how the utilization of telemedicine affects professionals and patients across Scotland and care delivery, at the Beatson West of Scotland Cancer Centre Sarcoma Unit. METHODS: Between June 8 and August 25, 2020, we invited patients and professional sarcoma multidisciplinary team members to participate in separate online anonymous survey questionnaires, to assess their attitudes toward telemedicine. Data were extracted, and descriptive statistics were performed. RESULTS: Patient satisfaction (n = 64) with telemedicine was high (mean = 9.4/10) and comparable with traditional face-to-face appointments (mean = 9.5/10). Patients were receptive to the use of telemedicine in certain situations, with patients strongly opposed to being told bad news via telemedicine (88%). Providers recommended the use of telemedicine in certain patient populations and reported largely equivalent workloads when compared with traditional consultations. Providers reported that telemedicine should be integrated into regular practice (66%), with patients echoing this indicating a preference for a majority of telemedicine appointments (57%). CONCLUSION: Telemedicine in sarcoma care is favorable from both clinician and patient perspectives. Utilization of telemedicine for patients with rare cancers such as sarcomas is an innovative approach to the delivery of care, especially considering the time and financial pressures on patients who often live a distance away from specialist centers. Patients and providers are keen to move toward a more flexible, mixed system of care.

MRE11 as a molecular signature and therapeutic target for cancer treatment with radiotherapy.

MRE11, the core of the MRE11/RAD50/NBS1 complex, is one of key DNA damage response proteins. Increasing evidence suggests that its expression in cancer cells is critical to developing radioresistance; as such, MRE11 is an emerging marker for targeted radiosensitization strategies. Elevated MRE11 in tumor tissues has been associated with poor survival in patients undergoing radiotherapy, although in some cancer types, the opposite has been noted. The recent discovery of ionizing radiation-induced truncation of MRE11, which decreases its efficacy, may explain some of these paradoxical findings. The progress of research on the biological modulation of MRE11 expression is also discussed, with the potential application of small molecule or large molecule inhibitors of MRE11 for enhancing radiosensitivity. Current research has further highlighted both nuclease and non-nuclease activities of MRE11 in cancer cells treated with ionizing radiation, and differentiation between these is essential to verify the targeting effects of radiosensitizing agents. These updates clarify our understanding of how MRE11 expression may be utilized in future stratification of cancer patients for radiotherapy, and how it may be leveraged in shaping novel radiosensitization strategies.

MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner.

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.

Combination targeting of subthalamic nucleus and ventral intermediate thalamic nucleus with a single trajectory in deep brain stimulation for tremor-dominant Parkinson's disease.

Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat Parkinson's disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory and electrode to treat patients with tremor-dominant PD, yet outcome data for this procedure remains sparse. Our objective is to determine the safety and efficacy of combination STN-VIM DBS. We conducted a single-center retrospective case series of all patients who underwent combined STN-VIM DBS. Demographic, perioperative, and outcome data, including Unified Parkinson Disease Rating Scale-III (UPDRS) and tremor scores (OFF-medication), and levodopa equivalent daily dose (LEDD), were collected and analyzed. Nineteen patients underwent this procedure. Patients were 89% male and 11% female, with a mean age of 63.6 years. Mean preoperative UPDRS was 24.1, and LEDD was 811.8. At a mean follow-up of 33.8 months, UPDRS and LEDD decreased by an average of 9.2 (38.2%) and 326.3 (40.2%), respectively. Tremor scores decreased by 4.9 (59.0%), and 58% were able to decrease total medication burden. One patient developed transient left-sided weakness, yielding a complication rate of 5.3%. Combined targeting of STN and VIM thalamus via a single frontal trajectory for tremor-dominant Parkinson's Disease results in similar UPDRS outcomes to STN DBS and improved control of tremor symptoms. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.

A need for clarity on surgical management of breast sarcoma: Scottish sarcoma network guidelines and regional audit.

Currently, there are no comprehensive breast sarcoma guidelines in the UK. There is therefore a need for guidelines to clarify surgical management, which we have based on data from our regional audit, current evidence, and consensus between West of Scotland Breast Cancer and Scottish Sarcoma Managed Clinical Networks. Methods and results: From 2007 to 2019, 46 patients were treated with breast sarcoma in the West of Scotland. Sarcoma Centre versus Peripheral Hospitals: Incomplete excision rate was 0% at sarcoma centre and 50% at peripheral hospitals (p = 0.0002, Odds Ratio 43). For angiosarcoma, 0% positive margin at the sarcoma centre versus 62.5% at the peripheral unit (p = 0.0036, odds ratio 39.3). Tumours treated at the sarcoma centre were larger than those treated at peripheral hospitals (92.5 versus 39.7 mm, p = 0.0009). WLE (wide local excision) versus mastectomy: Out of eight WLE patients, seven (87.5%) had positive margins, with 6 of these patients proceeding to mastectomy (i.e. 75% WLE patients ultimately had a mastectomy). The positive margin rate was significantly higher in WLE (87.5%) than in mastectomy (10.3%) (p = 0.0001, odds ratio 60.7). Survival: No difference was noted between the sarcoma centre and peripheral hospitals for overall survival (p = 0.43), stratified for tumours <5 cm (p = 0.16), and disease-free survival (p = 0.45). Conclusions: Our data strongly suggest that specific guidelines are needed for breast sarcoma, and that managing these patients according to breast carcinoma protocols in peripheral hospitals is sub-optimal. We recommend centralisation of breast sarcoma patient care to a specialist sarcoma centre, with WLE not recommended as a firstline surgical option given both the high rates of incomplete excision and subsequent need for completion mastectomy.

Adipocytokines visfatin and resistin in breast cancer: Clinical relevance, biological mechanisms, and therapeutic potential.

Obesity is one of the major modifiable risk factors in breast cancer, with obese adipose tissue showing a pathological role in breast cancer development and malignancy via the release of secretory factors, such as proinflammatory cytokines and adipocytokines. The current article focuses on visfatin and resistin, two such adipocytokines that have emerged over the last two decades as leading breast cancer promoting factors in obesity. The clinical association of circulating visfatin and resistin with breast cancer and their biological mechanisms are reviewed, in addition to their role in the context of tumor-stromal interactions in the breast cancer microenvironment. Recent findings have unraveled several mediators of visfatin and resistin that are involved in the crosstalk between breast cancer cells and adipose tissue in the breast tumor microenvironment, including growth differentiation factor 15 (GDF15), interleukin 6 (IL-6), and toll-like receptor 4 (TLR4). Finally, current therapeutics targeting visfatin and resistin and their respective pathways are discussed, including future therapeutic strategies such as new drug design or neutralizing peptides that target extracellular visfatin or resistin. These hold promise in the development of novel breast cancer therapies and are of increasing relevance as the prevalence of obesity-related breast cancer increases worldwide.

Does muscle improve validated outcome measures in open tibial fractures? New insights from a cohort study of the anterolateral thigh flap (ALT) versus ALT-Vastus lateralis flaps.

The benefits of the muscle in open lower limb fractures remain to be determined. This study compared statistically equivalent groups of open tibial fractures treated by free anterolateral thigh (ALT) flaps or ALT flaps incorporating muscle (ALT-Vastus lateralis/ALT- VL). Method and Results: Chang Gung Memorial Hospital, Taiwan, 2004-2008, 49 free flaps in open lower limb fractures (38 open tibial) were specifically reconstructed with free ALT or ALT-VL flaps. Risk factors for non-union: equivalent between the two groups, with no differences in smoking, steroids, diabetes, time to flap and the AO classification of soft tissue and bone injury. Comparison of union rates: no difference was noted between groups in the Radiographic Union Score in Tibial Fractures (RUST) at 3, 6, 9 and 12 months. The only factor significantly associated with non-union was presence of a SPRINT trial defined 'critical' bone defect with odds ratio 14.4 (95% CI 1.36 - 131.5), with no association with AO bone classification, flap type, comorbidity or flap size. Patient-reported outcomes: the ALT-VL group showed improved patient satisfaction (p = 0.01, Cohen's d = 1.1). Functional outcomes (Enneking score) were not statistically significant, but the ALT-VL group trended towards significance in function and skin quality domains. Conclusions: Based on the results of this study, one can conclude that the degree of bone injury (specifically a 'critical' defect) is of greater relevance than flap choice with regard to fracture consolidation. Muscle does not result in improvements to union, the speed of union or deep infection. However, better PROMs may be related to the inclusion of the muscle around the fracture site.

Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages.

Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent-tumor-associated macrophages-and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages.