Citations

Abstract Background The most severe complications following soft tissue filler injections result from the intraarterial administration of the filler product. Although hyaluronic acid–based filler can be trans-arterially dissolved with hyaluronidase, no information is available on calcium hydroxylapatite (CaHA)-based fillers. Objective The authors sought to test whether CaHA-based fillers can be trans-arterially dissolved by sodium thiosulfate (STS) when evaluated in cadaveric and in vitro models. Methods Human cadaveric facial arterial segments were each filled with 0.2 cc of commercially available CaHA product and submerged for 24 hours in 4 different STS-containing solutions: 10 cc STS (300 mg/cc) (pure, 1:1 dilution, 1:2 dilution), 0.9% saline and 10 cc STS (300 mg/cc), and 300 IU (bovine) hyaluronidase in a 1:1 ratio. Results Intraarterial CaHA was detected in human facial artery segments after 24 hours independent of the STS concentration employed. Submerging the arterial segments in STS (300 mg/cc) and 300 IU (bovine) hyaluronidase (1:1 ratio) also did not dissolve the intraarterial CaHA product. Gray scale analyses did show, however, that increasing concentrations of STS resulted in increased disintegration of CaHA in an in vitro experimental setting. Conclusions The results of this study indicate that STS is limited in its potential to dissolve intraarterial CaHA of cadaveric human facial arteries, despite the fact that it appears effective when in direct contact with the CaHA. Adverse events caused by intraarterial administration of CaHA-based fillers still lack a suitable antidote.

Abstract Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72–0.86)]; >0–<5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

Abstract Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10−7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

Abstract Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case–Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98–1.02; arachidonic acid OR = 1.00, 95% CI = 0.99–1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87–1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

Advanced postgraduate medical education for health‐care professionals is constantly evolving. Understanding facial anatomy and especially its vascular system is crucial when performing soft tissue filler injections to avoid adverse events including tissue loss or irreversible blindness. Standard anatomical resources often fall short of elucidating clinically relevant concepts in more highly specialized areas of interest. A novel dissection approach for demonstrating the anatomy of the lateral orbit was presented at scientific meetings to participants from dermatology, plastic surgery, and general practice. Results from the post‐course online survey (n = 52) were analyzed. The results of the survey reveal a high educational impact and a high clinical relevance of the novel dissection approach. In addition, the majority of respondents (97.7%; n = 51) felt that the exposed anatomical structure of the orbit and face improved their ability to safely perform cosmetic procedures on the face. More experienced respondents who had previously attended at least five cadaveric dissections were more likely to strongly agree that reviewing anatomy through this novel dissection approach increased their confidence in avoiding periorbital vascular danger zones. As minimally invasive outpatient procedures continue to evolve, practicing physicians and mid‐level providers often face the challenge of having to reconcile preexisting anatomical knowledge with new clinical practice. Skills required to navigate high impact anatomy include visualization of structures that form the navigational landscape and avoidance of key danger zones. The novel dissection approach to the lateral orbit reflects the increasing focus on revisiting, reforming, and redesigning anatomy for continuing professional development activities.

Abstract Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low‐density lipoprotein [LDL] and high‐density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels ( P < 5 × 10 −8 ) were identified as instrumental variables, and assessed using genome‐wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non‐endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non‐endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non‐endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non‐endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

Abstract Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values &lt; 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10−6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. Significance: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

Purpose The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. Methods We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. Results The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. Conclusions We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.

Abstract Background Glabellar soft tissue filler injections have been shown to be associated with a high risk of causing injection-related visual compromise. Objectives The aim of this study was to identify the course of the superficial branch of the supratrochlear and of the deep branch of the supraorbital artery in relation to the ipsilateral vertical glabellar line and to test whether an artery is located deep to this line. Methods Forty-one healthy volunteers with a mean age of 26.17 [9.6] years and a mean BMI of 23.09 [2.3] kg/m2 were analyzed. Ultrasound imaging was applied to measure the diameters, distance from skin surface, distance between the midline, distance between vertical glabella lines, and the cutaneous projection of the supratrochlear/supraorbital arteries at rest and upon frowning. Results The mean distance between the superficial branch of the supratrochlear artery and the ipsilateral vertical glabellar line was 10.59 [4.0] mm in males and 8.21 [4.0] mm in females, whereas it was 22.38 [5.5] mm for the supraorbital artery in males and 20.73 [5.6] mm in females. Upon frowning, a medial shift in supratrochlear arterial position of 1.63 mm in males and 1.84 mm in females and of 3.9 mm in supraorbital arterial position for both genders was observed. The mean depth of the supratrochlear artery was 3.34 [0.6] mm at rest, whereas the depth of the supraorbital artery was 3.54 [0.8] mm. Conclusions The hypothesis that injecting soft tissue fillers next to the vertical glabellar line is safe because the supratrochlear artery courses deep to the crease should be rejected. Additionally, the glabella and the supraorbital region should be considered as an area of mobile, rather than static, soft tissues.

Abstract Background Lips are considered a key element of facial attractiveness due to their central position in the face and their elemental role in verbal and nonverbal communication. Objectives The authors sought to provide clinically relevant information on the 3-dimensional pathway of the superior and inferior labial arteries within the lips to increase safety during labial soft tissue filler injections. Methods The study enrolled 41 healthy volunteers with a mean age of 26.17 ± 9.6 years and a mean body mass index of 23.09 ± 2.3 kg/m2. Ultrasound imaging was performed at 6 different locations. The position of the labial arteries within the lips, depth of the arteries, cranio-caudal location of each artery in relation to the vermilion border, and diameter of the superior/inferior labial arteries were recorded. Results The most frequent location of both the superior and inferior labial arteries was the submucosal plane (58.5%) followed by intramuscular (36.2%) and subcutaneous (5.3%) planes. The depth of the superior labial artery in the upper lip was 5.6 ± 0.13 mm, whereas the depth of the inferior labial artery in the lower lip was 5.2 ± 0.14 mm. Both arteries were more frequently located within the red lip: upper lip (83% vs 18.7%) and lower lip (86.2% vs 13.8%). In the midline, the artery coursed within the red lip in all investigated volunteers. Conclusions Clinically, results of this study favor a superficial injection plane for lip volumization procedures. A perpendicular approach to the lip (coming from the cutaneous lip) might increase safety because the artery is located most frequently within the red lip.