Nf1 deficiency modulates the stromal environment in the pretumorigenic rat mammary gland.

Background: Neurofibromin, coded by the NF1 tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)-a tumor predisposition syndrome caused by a germline NF1 mutation-have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which NF1 mutations lead to breast cancer tumorigenesis is not well understood. Therefore, the objective of this work was to identify stromal alterations before tumor formation that result in the increased risk and poorer outcome seen among NF1 patients with breast cancer. Approach: To accurately model the germline monoallelic NF1 mutations in NF1 patients, we utilized an Nf1-deficient rat model with accelerated mammary development before presenting with highly penetrant breast cancer. Results: We identified increased collagen content in Nf1-deficient rat mammary glands before tumor formation that correlated with age of tumor onset. Additionally, gene expression analysis revealed that Nf1-deficient mature adipocytes in the rat mammary gland have increased collagen expression and shifted to a fibroblast and preadipocyte expression profile. This alteration in lineage commitment was also observed with in vitro differentiation, however, flow cytometry analysis did not show a change in mammary adipose-derived mesenchymal stem cell abundance. Conclusion: Collectively, this study uncovered the previously undescribed role of Nf1 in mammary collagen deposition and regulating adipocyte differentiation. In addition to unraveling the mechanism of tumor formation, further investigation of adipocytes and collagen modifications in preneoplastic mammary glands will create a foundation for developing early detection strategies of breast cancer among NF1 patients.

Opioid Use in Patients With Cervical Cancer at a Tertiary Academic Medical Center.

BACKGROUND/AIM: Opioids are a common treatment for cancer-related pain and information is limited on the rates of opioid use for cervical cancer patients. This study aimed to analyze outpatient opioid use and various predictors among patients with cervical cancer at a tertiary academic medical center. PATIENTS AND METHODS: Data from patients with cervical cancer receiving treatment at a single institution, from August 2019 to July 2022, were retrospectively collected. Women with unrelated chronic opioid use or opioid use associated with acute inpatient stays were excluded. Charts were reviewed for patient demographics, disease characteristics, treatment characteristics, disease outcomes, and opioid prescriptions. The primary endpoint was duration of opioid use ≥6 months. Pearson's chi-squared testing, Welch's two-sample t-testing and Fisher's exact testing were used to determine predictors of opioid use ≥6 months. RESULTS: In total, 108 patients with cervical cancer (76.1%) of the 142 that received treatment were prescribed opioids. In women who were prescribed outpatient opioids, the median duration of opioid use was 69 days (interquartile range=5-359 days). In total, 40 (37.0%) had prescriptions for ≥180 days and 27 (25.0%) had prescriptions ≥365 days. On bivariate analysis, lower stage and receipt of surgery were associated with opioid use duration <6 months. Age, race, histology, substance/tobacco/alcohol use, depression/anxiety, and the receipt of brachytherapy/radiation were not associated with length of opioid prescriptions. CONCLUSION: This study demonstrated that 37% of patients with cervical cancer were using opioids for cancer-related pain longer than 6 months. Higher stage was associated with opioid use duration ≥6 months.

The Effectiveness of Hot Bead Sterilization in Maintaining Sterile Surgical Instrument Tips across Sequential Mouse Surgeries.

One strategy commonly employed for rodent surgeries is a "tips-only" surgical technique, which restricts the surgeon to using only the sterile working ends of the surgical instruments to manipulate the surgical field and sterilizes instrument tips with a hot bead sterilizer between consecutive rodents. Despite the common use of the "tips-only" technique, research is lacking on the number of sequential surgeries for which the same set of hot bead-sterilized instruments can be used before introducing bacterial contamination. We performed serial mouse surgeries using the "tips-only" technique under 3 different conditions (aseptic, fur contamination, or cecal contamination) and assessed aerobic bacterial growth before and after each round of hot bead sterilization. Instrument tips showed an increasing probability of contamination of at least one instrument in a series of consecutive surgeries. The probability that all surgical instrument tips in the series were sterile after hot bead sterilization fell by 4% for each surgery involving inadvertent or fur contamination and by 11.5% for each surgery with contamination for all surgical types combined (including entering the gastrointestinal tract). Based on our results, hot bead sterilization is not adequate for surgeries associated with gross contamination. Under our experimental conditions and assuming independence of outcomes between consecutive surgeries, up to 5 surgeries associated with minor or inadvertent contamination could be performed in series with a probability higher than 80% that all instrument tips were sterile for all surgeries. A case-by-case risk assessment should be conducted to derive institutional guidelines for the maximal number of surgeries that can be performed in sequence using the "tips-only" technique with hot bead sterilization of the same set of surgical instruments between surgeries. Full sterilization of instruments after every surgery provides the greatest confidence in maintaining sterility.