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INTRODUCTION: Breast conservation (BC) rates have been utilized as a quality metric, yet mastectomy rates have been noted to be increasing nationwide. The purpose of this study was to evaluate the factors associated with BC in 437 US breast centers surveyed by the National Accreditation Program of Breast Centers (NAPBC). METHODS: From 2006 to 2010, 437 breast centers across the US were surveyed by the NAPBC. At each center, annual data regarding BC rates were reported in the Survey Application Record (SAR) for patients with Stage 0-II breast cancer. We evaluated characteristics of breast centers including geographic location, volume of patients treated, therapeutic modalities provided, and center organizational relationships. Non-parametric statistical analyses were performed to determine factors associated with BC rates in this cohort. RESULTS: Among the 437 breast centers surveyed from 2006-2011, data on 77,248 patients with Stage 0-II were reported. The median number of Stage 0-II breast cancer patients per center was 149 (range; 10-891). The median proportion of these patients who underwent BC was 64.8% (range; 33-100%). No significant differences in median BC rate was noted over the six years of the study (range; 64.2% in 2006 - 67.1% in 2011, p = 0.788). However, significant regional variations were noted in median BC rates: 62.2% in the West (N = 59 centers), 63.8% in the South (N = 145 centers), 64.1% in the Midwest (N = 118 centers), and 70.8% in the Northeast (N = 104 centers), p < 0.001. There was no difference noted in BC rates between high volume (≥ 150 Stage 0-II cases/yr) and low volume (< 150 Stage 0-II cases/yr) centers (median 65.1% vs. 64.6%, respectively, p = 0.584). No differences in BC rate was noted between centers that referred vs. provided implant-based (p = 0.259), TRAM flap (p = 0.069), latissimus dorsi flap (p = 0.108) or DIEP/free flap (p = 0.324) reconstruction. Similarly, there was no difference noted in BC rates between centers who referred vs. provided whole breast radiation therapy (p = 0.224) and accelerated partial breast irradiation (p = 0.964). Centers that were affiliated with a hospital (N = 195) had a lower rate of BC than those that were not (n = 232); median 63.9% vs. 66.3%, p = 0.037. The majority of centers surveyed were also accredited by the Commission on Cancer (CoC; N=395); however, no differences were noted between these centers and those who were not CoC accredited in terms of BC rates (64.9% vs. 65.8%, respectively, p = 0.748). In a multivariate linear regression model, both region (p = 0.008) and hospital affiliation (p = 0.004) remained significant independent predictors of BC. CONCLUSION: Across 437 US breast centers, data from 77,248 patients demonstrate a national BC rate of 64.8%. While the rate does not seem to be varying significantly over time, variation in BC was noted between regions and between centers associated with hospitals vs. not. Rates of BC do not vary, however, by center volume, availability of reconstruction or radiation, nor by CoC accreditation status. These data suggest that patient choice, rather than the availability of radiation and reconstruction, is the driving force in surgical decision-making. [ABSTRACT FROM AUTHOR]

Neurofibromatosis Type II (NF2) is an autosomal dominant cancer predisposition syndrome in which germline haploinsufficiency at the NF2 gene confers a greatly increased propensity for tumor development arising from tissues of neural crest derived origin. NF2 encodes the tumor suppressor, Merlin, and its biochemical function is incompletely understood. One well-established function of Merlin is as a negative regulator of group A serine/threonine p21-activated kinases (PAKs). In these studies we explore the role of PAK1 and its closely related paralog, PAK2, both pharmacologically and genetically, in Merlin-deficient Schwann cells and in a genetically engineered mouse model (GEMM) that develops spontaneous vestibular and spinal schwannomas. We demonstrate that PAK1 and PAK2 are both hyper activated in Merlin-deficient murine schwannomas. In preclinical trials, a pan Group A PAK inhibitor, FRAX-1036, transiently reduced PAK1 and PAK2 phosphorylation in vitro, but had insignificant efficacy in vivo. NVS-PAK1-1, a PAK1 selective inhibitor, had a greater but still minimal effect on our GEMM phenotype. However, genetic ablation of Pak1 but not Pak2 reduced tumor formation in our NF2 GEMM. Moreover, germline genetic deletion of Pak1 was well tolerated, while conditional deletion of Pak2 in Schwann cells resulted in significant morbidity and mortality. These data support the further development of PAK1-specific small molecule inhibitors and the therapeutic targeting of PAK1 in vestibular schwannomas and argue against PAK1 and PAK2 existing as functionally redundant protein isoforms in Schwann cells., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cutaneous collagenous vasculopathy (CCV) is a rare benign microangiopathy of the superficial dermal vessels. Clinically, it is characterized by widespread, asymptomatic development of cutaneous telangiectasia in the absence of systemic symptoms. Morphologically, it most resembles generalized essential telangiectasia and other telangiectatic syndromes such as telangiectasia macularis eruptiva perstans (TMEP), ataxia telangiectasia, and hereditary hemorrhagic telangiectasia. It is distinctive in its histology, showing characteristic dilated thick-walled blood vessels in the superficial dermis. The thickened walls of these superficial dermal blood vessels demonstrate reduplication of the basement membrane on PAS staining. We report a 63-year-old man with CCV with this condition for 20 years, starting in 1996. He was diagnosed in the past as having essential telangiectasia. The development of the telangectasias occurred after coronary artery bypass grafting, also performed in 1996. This case not only demonstrates the characteristic clinical and histologic findings, but also suggests a possible mechanism. Moreover, it illustrates that cases of generalized essential telangiectasia may in fact be CCV that are misclassified.

The influence of dietary pectin on iron absorption and retention was studied in rats. Basal diet with low and normal iron levels were fed with and without addition of 2% citrus pectin. After 40 days rats were fasted for 24 hours and were given 59Fe in dilute HCl with or without 2% pectin by gavage. Whole-body counting techniques were employed to monitor 59Fe absorption and turnover. Rats maintained on low iron diet absorbed and retained a much higher proportion of 59Fe than rats maintained on normal level of iron. Dietary pectin at the level fed in this study had no influence on iron uptake and/or turnover in rats.