Alternative Lymphatic Drainage Pathways in the Trunk Following Oncologic Therapy.

BACKGROUND: Anatomic and functional descriptions of trunk and breast lymphedema following breast cancer treatment are emerging as indicators of lymphatic dysfunction. Indocyanine green-lymphangiography has been instrumental in characterizing this dysfunction in the extremity and can be applied to other regions. Previous work has established a validated Pittsburgh Trunk Lymphedema Staging System to characterize such affected areas. This study aims to identify risk and protective factors for the development of truncal and upper extremity lymphedema using alternative lymphatic drainage, providing implications for medical and surgical treatment. METHODS: Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between 12/2014 and 3/2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated for axillary and inguinal lymphatic flow. A linear-weighted Cohen's kappa statistic was calculated comparing alternative drainage evaluation. Binomial regression was used to compute relative risks (RRs). Significance was assessed at alpha = 0.05. RESULTS: Eighty-six sides (46 patients) were included. Twelve sides underwent no treatment and were considered controls. Eighty-eight percent of the noncontrols had alternative lymphatic flow to the ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen's kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of developing truncal lymphedema [RR 0.78, confidence interval (CI) 0.63-0.97, P = 0.04; RR 0.32, CI 0.13-0.79, P = 0.01, respectively]. Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, P = 0.02; RR 1.92, CI 1.09-3.39, P = 0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection were associated with increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, P = 0.01; RR 2.83, CI 1.23-6.52, P = 0.01, respectively). CONCLUSIONS: Building upon previous work, this study shows risk and protective factors for the development of truncal and upper extremity lymphedema. Most prevalent alternative channels drain to the ipsilateral axilla and groin. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of truncal lymphedema. Patients with radiation, axillary dissection, and contralateral axillary drainage were associated with increased risk of upper extremity lymphedema. These findings have important clinical implications for postoperative manual lymphatic drainage and for determining eligibility for lymphovenous bypass surgery.

A Longitudinal Analysis of Pre- and Post-Operative Dysmorphology in Metopic Craniosynostosis.

OBJECTIVE: The purpose of this study is to objectively quantify the degree of overcorrection in our current practice and to evaluate longitudinal morphological changes using CranioRateTM, a novel machine learning skull morphology assessment tool.  . DESIGN: Retrospective cohort study across multiple time points. SETTING: Tertiary care children's hospital. PATIENTS: Patients with preoperative and postoperative CT scans who underwent fronto-orbital advancement (FOA) for metopic craniosynostosis. MAIN OUTCOME MEASURES: We evaluated preoperative, postoperative, and two-year follow-up skull morphology using CranioRateTM to generate a Metopic Severity Score (MSS), a measure of degree of metopic dysmorphology, and Cranial Morphology Deviation (CMD) score, a measure of deviation from normal skull morphology. RESULTS: Fifty-five patients were included, average age at surgery was 1.3 years. Sixteen patients underwent follow-up CT imaging at an average of 3.1 years. Preoperative MSS was 6.3 ± 2.5 (CMD 199.0 ± 39.1), immediate postoperative MSS was -2.0 ± 1.9 (CMD 208.0 ± 27.1), and longitudinal MSS was 1.3 ± 1.1 (CMD 179.8 ± 28.1). MSS approached normal at two-year follow-up (defined as MSS = 0). There was a significant relationship between preoperative MSS and follow-up MSS (R2 = 0.70). CONCLUSIONS: MSS quantifies overcorrection and normalization of head shape, as patients with negative values were less "metopic" than normal postoperatively and approached 0 at 2-year follow-up. CMD worsened postoperatively due to postoperative bony changes associated with surgical displacements following FOA. All patients had similar postoperative metopic dysmorphology, with no significant association with preoperative severity. More severe patients had worse longitudinal dysmorphology, reinforcing that regression to the metopic shape is a postoperative risk which increases with preoperative severity.

Maternal binge alcohol consumption leads to distinctive acute perturbations in embryonic cardiac gene expression profiles.

BACKGROUND: Excessive alcohol consumption during pregnancy is associated with high risk of congenital heart defects, but it is unclear how alcohol specifically affects heart development during the acute aftermath of a maternal binge drinking episode. We hypothesize that administration of a single maternal binge dose of alcohol to pregnant mice at embryonic day 9.5 (E9.5) causes perturbations in the expression patterns of specific genes in the developing heart in the acute period (1-3 days) following the binge episode. To test this hypothesis and identify strong candidate ethanol-sensitive target genes of interest, we adapted a mouse binge alcohol model that is associated with a high incidence of congenital heart defects as described below. METHODS/RESULTS: Pregnant mice were administered a single dose of alcohol (2.5 g/kg in saline) or control (saline alone) via oral gavage. To evaluate the impact of maternal binge alcohol on cardiac gene expression profiles, we isolated embryonic hearts from both groups (n = 5/group) at 24, 48, and 72 h post-gavage for transcriptomic analyses. RNA was extracted and evaluated using quantitative RNA-sequencing (RNA-Seq) methods. To identify a cohort of binge-altered cardiac genes, we set the threshold for change at >2.0-fold difference with adjusted p < 0.05 versus control.  RNA-Seq analysis of cardiac gene expression revealed that of the 17 genes that were altered within the first 48 h post-binge, with the largest category consisting of transcription factors (Alx1, Alx4, HoxB7, HoxD8, and Runx2), followed by signaling molecules (Adamts18, Dkk2, Rtl1, and Wnt7a). Furthermore, multiple comparative and pathway analyses suggested that several of the candidate genes identified through differential RNA-Seq analysis may interact through certain common pathways. To investigate this further, we performed gene-specific qPCR analyses for three representative candidate targets: Runx2, Wnt7a, and Mlxipl. Notably, only Wnt7a showed significantly (p < 0.05) decreased expression in response to maternal binge alcohol in the qPCR assays. CONCLUSIONS: These findings identify Wnt7a and a short list of potential other candidate genes and pathways for further study, which could provide mechanistic insights into how maternal binge alcohol consumption produces congenital cardiac malformations.

Disparities in Access to Postmastectomy Breast Reconstruction: Does Living in a Specific ZIP Code Determine the Patient's Reconstructive Journey?

BACKGROUND: Postmastectomy breast reconstruction (BR) has been shown to provide long-term quality of life and psychosocial benefits. Despite the policies initiated to improve access to BR, its delivery continues to be inequitable, suggesting that barriers to access have not been fully identified and/or addressed. The purpose of this study was to assess the influence of geographic location, socioeconomic status, and race in access to immediate BR (IBR). METHODS: An institutional review board-approved observational study was conducted. All patients who underwent breast cancer surgery from 2014 to 2019 were queried from our institutional Breast Cancer Registry. A geographical analysis was conducted using demographic characteristics and patient's ZIP codes. Euclidean distance from patient home ZIP code to UPMC Magee Women's Hospital was calculated, and χ2, Student t test, Mann-Whitney, and Kruskal-Wallis tests was used to evaluate differences between groups, as appropriate. Statistical significance was set at P < 0.05. RESULTS: Overall, 5835 patients underwent breast cancer surgery. A total of 56.7% underwent lumpectomy or segmental mastectomy, and 43.3% underwent modified, total, or radical mastectomy. From the latter group, 33.5% patients pursued BR at the time of mastectomy: 28.6% autologous, 48.1% implant-based, 19.4% a combination of autologous and implant-based, and 3.9% unspecified reconstruction. Rates of IBR varied among races: White or European (34.1%), Black or African American (27.7%), and other races (17.8%), P = 0.022. However, no difference was found between type of BR among races (P = 0.38). Moreover, patients who underwent IBR were significantly younger than those who did not pursue reconstruction (P < 0.0001). Patients who underwent reconstruction resided in ZIP codes that had approximately US $2000 more annual income, a higher percentage of White population (8% vs 11% non-White) and lower percentage of Black or African American population (1.8% vs 2.9%) than the patients who did not undergo reconstruction. CONCLUSIONS: While the use of postmastectomy BR has been steadily rising in the United States, racial and socioeconomic status disparities persist. Further efforts are needed to reduce this gap and expand the benefits of IBR to the entire population without distinction.