An Evidence-based Pathway for Body Dysmorphic Disorder in Facial Aesthetics.

Aesthetic procedures should be avoided in patients with body dysmorphic disorder (BDD) since they can negatively impact mental health and lead to further aesthetic dissatisfaction. There are no evidence-based patient pathways for BDD in facial aesthetics which can result in the failure to identify patients with BDD, leading to unsuitable treatments and suboptimal patient care. We aim to construct the first evidence-based patient pathway for BDD in surgical and nonsurgical facial aesthetics. A systematic review was performed and articles that discussed screening or patient pathways for BDD in field of facial aesthetics were included. We extracted relevant information from each article on screening tools and pathways for BDD. Data were synthesized by summarizing the data under column headings into a structured narrative and into new tables. Based on this synthesis, a practical pathway for BDD was constructed. Forty articles fulfilled the criteria for inclusion. Twenty-eight BDD screening tools were discussed in the included articles, and we provide an overview of these tools. Thirty-one articles discussed patient pathways for BDD, and we synthesized this information into a structured narrative. Combining these findings, we present an evidence-based patient pathway for BDD for patients presenting for facial aesthetic treatments. This systematic review has resulted in the first, evidence-based, patient pathway for BDD in surgical and nonsurgical facial aesthetics. This practical pathway can be used by aesthetic clinicians to identify patients with potential BDD and provide clear guidance for managing cases where BDD is suspected. It will help reduce the number of facial aesthetic procedures performed on patients with BDD, safeguard patient mental well-being, and prevent further aesthetic dissatisfaction.

Treatment of periorbital veins with vascular laser: A systematic review and retrospective case series.

INTRODUCTION: Vascular lasers may represent a promising treatment option for periorbital veins. This article aims to: (1) systematically review the literature on the safety and effectiveness of vascular laser treatment for periorbital veins and (2) assess safety and effectiveness through a retrospective case series. METHODS: Systematic review: Articles that assessed the safety and effectiveness of vascular laser treatment for periorbital veins were included and quality assessed using the Downs and Black checklist. CASE SERIES: Patient records were retrospectively reviewed from January 2020 to November 2023 to identify all patients who underwent laser treatment for periorbital veins. Outcomes assessment included percentage improvement, patient overall satisfaction and adverse effects. RESULTS: Systematic review: Three articles were included, discussing treatment of blue, periorbital veins using a 1064 nm Nd:YAG laser. Patient Fitzpatrick skin Types I-IV were treated with high patient satisfaction rates and complete clearance of treated veins. Adverse effects included pain, erythema, mild oedema, urticaria and blister formation. Quality of included studies ranged from 7 to 14 out of 21 points. CASE SERIES: Thirty-four patients with skin Types I-V were included. Blue and red periorbital veins were treated using 1064 and 532 nm wavelengths respectively. Mean percentage improvement was 4.8 (complete resolution) and patients' overall satisfaction was ranked 3 (completely satisfied). Adverse effects included erythema, oedema, and bruising. CONCLUSION: Treatment of red and blue periorbital veins using 532 and 1064 nm vascular lasers appears a safe treatment option. The procedure has a short recovery time, with patients able to resume normal activities within 1 day of treatment.

Combination radiofrequency microneedling and carbon dioxide laser for acne scarring: A systematic review and retrospective case series across two centers.

INTRODUCTION: Combination radiofrequency (RF) microneedling with fractional ablative carbon dioxide (CO2 ) laser is a new approach for acne scar treatment. AIMS: (1) to systematically review the literature on the safety and effectiveness of this treatment for acne scarring; (2) to assess safety and effectiveness in a 2-center case series. METHODS: Systematic review: Articles that assessed the safety and effectiveness of combination RF microneedling and fractional CO2 laser for acne scarring were included and quality assessed using the Downs and Black checklist. CASE SERIES: Patient records were reviewed from 2 clinics, one in London, UK, and the other in Washington D.C., United States, to identify patients who underwent a single treatment with RF microneedling and fractional CO2 laser for acne scarring. Outcome assessment was via the Scar Global Assessment (SGA) scale. RESULTS: Systematic review: Three articles were included and reported improvements in acne scar severity. Adverse effects included erythema, edema, pain, vesicle formation, erosion, petechiae, desquamation, post-inflammatory hyperpigmentation (PIH), and acne flare. Quality scores ranged from 14 to 15 (maximum of 21). CASE SERIES: Twenty-six patients were included. Mean SGA Score was 3.0 at baseline and 1.3 at follow-up. All patients had an improved SGA score. Adverse effects included erythema, pain, edema, skin crusting, PIH, and acne flare. All patients resumed normal activities within 7 days of treatment. CONCLUSION: Combination RF microneedling and fractional CO2 laser appears a safe and effective treatment for patients with acne scarring. A single treatment can result in noticeable improvements in acne scar severity with a short recovery time.

Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study.

INTRODUCTION: In women undergoing breast-conserving surgery (BCS), 20-25% require a re-operation as a result of incomplete tumour resection. An intra-operative technique to assess tumour margins accurately would be a major advantage. A novel method for intraoperative margin assessment was developed by applying a thin flexible scintillating film to specimens-flexible autoradiography (FAR) imaging. A single-arm, multi-centre study was conducted to evaluate the feasibility of intraoperative [18F]FDG FAR for the assessment of tumour margins in BCS. METHODS: Eighty-eight patients with invasive breast cancer undergoing BCS received ≤ 300 MBq of [18F]FDG 60-180 min pre-operatively. Following surgical excision, intraoperative FAR imaging was performed using the LightPath® Imaging System. The first 16 patients were familiarisation patients; the remaining 72 patients were entered into the main study. FAR images were analysed post-operatively by three independent readers. Areas of increased signal intensity were marked, mean normalised radiances and tumour-to-tissue background (TBR) determined, agreement between histopathological margin status and FAR assessed and radiation dose to operating theatre staff measured. Subgroup analyses were performed for various covariates, with thresholds set based on ROC curves. RESULTS: Data analysis was performed on 66 patients. Intraoperative margin assessment using FAR was completed on 385 margins with 46.2% sensitivity, 81.7% specificity, 8.1% PPV, 97.7% NPV and an overall accuracy of 80.5%, detecting both invasive carcinoma and DCIS. A subgroup analysis based on [18F]FDG activity present at time of imaging revealed an increased sensitivity (71.4%), PPV (9.3%) and NPV (98.4%) in the high-activity cohort with mean tumour radiance and TBR of 126.7 ± 45.7 photons/s/cm2/sr/MBq and 2.1 ± 0.5, respectively. Staff radiation exposure was low (38.2 ± 38.1 µSv). CONCLUSION: [18F]FDG FAR is a feasible and safe technique for intraoperative tumour margin assessment. Further improvements in diagnostic performance require optimising the method for scintillator positioning and/or the use of targeted radiopharmaceuticals. TRIAL REGISTRATION: Identifier: NCT02666079. Date of registration: 28 January 2016. URL: https://clinicaltrials.gov/ct2/show/NCT02666079 . ISRCTN registry: Reference: ISRCTN17778965. Date of registration: 11 February 2016. URL: http://www.isrctn.com/ISRCTN17778965 .

Invasive breast cancer over four decades reveals persisting poor metastatic outcomes in treatment resistant subgroup - the "ATRESS" phenomenon.

BACKGROUND: Major advances in breast cancer treatment have led to a reducuction in mortality. However, there are still women who are not cured. We hypothesize there is a sub-group of women with treatment-resistant cancers causing early death. METHODS: Between 1975 and 2006, 5392 women with invasive breast cancer underwent surgery at Guy's Hospital, London. Data on patient demographics, tumour characteristics, treatment regimens, local recurrence, secondary metastasis, and death were prospectively recorded. We considered four time periods (1975-1982, 1983-1990, 1991-1998, 1999-2006). Risks and time to event analysis were performed with Cox proportional hazards model and Kaplan-Meier estimation. RESULTS: Unadjusted hazard ratios for developing metastasis and overall mortality relative to the 1975-1982 cohort decreased steadily to 0.23 and 0.63, respectively in 1999-2006. However, metastasis-free interval shortened, with the proportion of women developing metastasis ≤5 years increasing from 73.9% to 83.0%. Furthermore, median post-metastatic survival decreased from 1.49 years to 0.94 years. Applying our risk criteria identified the presence of ±200 patients in each cohort who developed metastasis early and died within a much shorter time frame. CONCLUSIONS: Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. Despite this, a subpopulation with shorter metastasis-free and post-metastatic survival who are unresponsive to available treatment remains. This may be due to the ATRESS phenomenon (adjuvant therapy-related shortening of survival) secondary to preselection inherent in adjuvant therapy, successful treatment of less malignant tumour cells and treatment-induced resistance in the remaining tumour clones.

BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines.

We have identified a novel subtype of estrogen receptor (ER)-positive breast cancers with improved outcome after tamoxifen treatment and characterized by overexpression of the gene BEX2. BEX2 and its homologue BEX1 have highly correlated expression and are part of a cluster enriched for ER response and apoptosis genes. BEX2 expression is induced after estradiol (E2) treatment with a peak at 3 h, suggesting BEX2 is an estrogen-regulated gene. BEX2 belongs to a family of genes, including BEX1, NGFRAP1 (alias BEX3), BEXL1 (alias BEX4), and NGFRAP1L1 (alias BEX5). Both BEX1 and NGFRAP1 interact with p75NTR and modulate nerve growth factor (NGF) signaling through nuclear factor-kappaB (NF-kappaB) to regulate cell cycle, apoptosis, and differentiation in neural tissues. In breast cancer cells, NGF inhibits C2-induced apoptosis through binding of p75NTR and NF-kappaB activation. Here, we show that BEX2 expression is necessary and sufficient for the NGF-mediated inhibition (through NF-kappaB activation) of C2-induced apoptosis. We also show that BEX2 modulates apoptosis of breast cancer cells in response to E2 (50 nmol/L) and tamoxifen (5 and 10 micromol/L). Furthermore, BEX2 overexpression enhances the antiproliferative effect of tamoxifen at pharmacologic dose (1 micromol/L). These data suggest that a NGF/BEX2/NF-kappaB pathway is involved in regulating apoptosis in breast cancer cells and in modulating response to tamoxifen in primary tumors.

Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line.

The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic sub-population of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub-population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF-7. This sub-population is capable of growth in anchorage-independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub-population can be enriched by serial passages in anchorage-independence, and are characterized by over-expression of the adhesion molecule alpha6-integrin. Alpha-6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere-derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub-population in breast cancer cells. Furthermore, it shows alpha6-integrin as a potential therapeutic target aimed at tumour-generating subsets of breast cancer cells.

Intraoperative Assessment of Tumor Resection Margins in Breast-Conserving Surgery Using 18F-FDG Cerenkov Luminescence Imaging: A First-in-Human Feasibility Study.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by 18F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of 18F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the γ-probe background signal (cross-talk) from 18F-FDG. The cross-talk and 99mTc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured. Results: Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 ± 160 photons/s/cm2/sr and 2.41 ± 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (κ = 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 ± 15 µSv per procedure. Conclusion: Intraoperative 18F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates.

Breast cancer, stem cells and prospects for therapy.

The mammary epithelium contains multipotent stem cells that give rise to all differentiated cell types present within the tissue. Mammary epithelial stem cells have been prospectively purified from dissociated mammary epithelium on the basis of cell surface antigen expression. It has become apparent in recent years that for breast cancer and other malignancies only a small proportion of tumour cells--'cancer stem cells'--have the capacity for extensive proliferation and transferral of the tumour. We review the evidence for breast cancer stem cells, we consider their relationship to mammary epithelial stem cells and we examine the implications for current and future therapeutic strategies.

A novel model of dormancy for bone metastatic breast cancer cells.

Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy.

Diagnosis of right-sided varicocele: a retrospective comparative study between clinical examination, Doppler findings, US imaging and vascular anatomy at phlebography.

Historically varicocele is diagnosed almost exclusively on the left side. The introduction of new imaging techniques has allowed the identification and characterization of right varicocele. This study aims to compare the diagnostic accuracy of various imaging techniques to data obtained using phlebography in the diagnosis of right varicocele. Patients treated for isolated right varicocele between 1992 and 2010 were retrospectively identified. Data from clinical examination, Doppler-USS, Color-Doppler-USS and Retrograde Phlebography were collected for each patient. 133 out of 4305 patients (3.1%) presented with an isolated right varicocele. 34 of these patients (25.6%) presented with palpable right varicocele. Doppler-USS identified various degrees of type I right venous reflux in 90 patients (67.7%). Phlebography showed venous reflux in all the patients (133), although with variability in terms of internal spermatic vein anatomy. Right varicocele is characterized by predictable anatomic features. Identification and characterization of these features is useful in guiding percutaneous treatment, allowing to optimize radiological display and reducing failure rate.

Xenotransplantation of breast cancers.

Three experimental systems based on mouse models are currently used to study breast cancer: transgenic mice, carcinogen-induced models, and xenografts of breast cancers. Each of these models has advantages and limitations. This chapter focuses on xenotransplantation of breast cancers and reviews the techniques used so far in establishing this model, the advantages and limitations compared to other experimental systems, and finally, the technical questions that remain to be answered.

Audit of local recurrence following breast conservation surgery with 5-mm target margin and hypofractionated 40-Gray breast radiotherapy for invasive breast cancer.

INTRODUCTION: The risk of ipsilateral breast tumour recurrence (IBTR) following breast conservation surgery (BCS) for invasive breast cancer (IBC) and radiotherapy is dependent on patient-, tumour- and treatment-related variables. In the Cambridge Breast Unit, breast conserving surgery has been performed with a target radial margin of 5 mm for IBC, in combination with 40-Gy hypofractionated (15 fractions) breast radiotherapy, since 1999. PATIENTS AND METHODS: An audit was performed of cases treated between 1999 and 2004. A total of 563 patients underwent BCS for invasive breast cancer with 90.4% receiving radiotherapy (RT) and 60.4% of patients receiving boost RT (3 fractions of 3-Gy). RESULTS: After a median follow-up of 58 months, five of the 563 (0.9%) patients developed IBTR. The 5-year actuarial IBTR rate was 1.1%. In terms of distant disease recurrence (DDR), 29 of the 563 (5.2%) had DDR during follow-up, giving a 5-year actuarial DDR rate of 5.4%. The 5-year breast cancer specific survival was 95%, with the poorer NPI groups having worse breast cancer specific survival (Log-rank, P<0.0001). More importantly, patients with IBTR had a shorter breast cancer-specific survival than those who were IBTR-free (Log-rank, P<0.0001). CONCLUSIONS: Our treatment regimen, combining BCS with a 5-mm target margin and hypofractionated 40-Gy RT, results in an extremely low rate of IBTR, and compares favourably with the target IBTR rate of <5% defined by the Association of Breast Surgeons (ABS) at BASO guidelines.

Evaluating the link between stem cells and breast cancer.

Mammary stem cells have recently been identified and purified on the basis of surface antigens and transplantation assays. In addition, recent reports have identified a small sub-population of highly tumorigenic cells within primary and metastatic breast tumors and in a number of breast cancer cell lines. This suggests that, similarly to its normal physiological counterpart, a cancer stem cell may be at the origin of breast cancer. These observations have dramatic biological and clinical implications, as they dictate a revision of our understanding of breast cancer and of our therapeutic strategies. The aim of this article is to review recent data regarding normal mammary epithelial stem cells and evidence in support of the cancer stem cell hypothesis in the breast, and to provide further insight into how taking this subpopulation of cells into account may affect the way we treat epithelial cancers in the future.

p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels.

Activation of the tumor suppressor p53 by DNA damage induces either cell cycle arrest or apoptosis, but what determines the choice between cytostasis and death is not clear. In this report, we show that the E1A-binding p300 nucleoprotein is a key determinant of p53-dependent cell fate in colorectal cancer cells: absence of p300 increases apoptosis in response to DNA damage. In addition, p300-deficient (p300(-)) cells fail to undergo G(1)/S arrest after UV irradiation. These abnormalities are associated with prolongation of p53 stability, reduced p53-acetylation, blunting of MDM2 activation, failure to transactivate p21, and a disproportionate increase in PUMA levels. When xenografted, p300(-) cells are more sensitive to chemotherapy with doxorubicin. These results show that p300 is a key regulator of the p53 response and suggest that p300 inhibition could be used to modulate chemotherapy.