Acute renal failure (ARF) is a common complication in critically ill children. It is known as an important predictor of morbidity and mortality in this population. Data on the factors affecting the choice of renal replacement therapy (RRT) modality and its impact on mortality of children with ARF are limited.We retrospectively studied 115 children with ARF necessitating RRT during the period 1995-2005 to evaluate the effect of several prognostic factors as well as RRT type on their immediate outcome.The data collected from charts included demographics, primary disease, accompanying medical conditions, use of vasopressor support, indications for dialysis, RRT modality, and complications of dialysis. Categorical variables were analyzed using chi-square or Fisher's exact tests. Variables associated with mortality (P < 0.1) at the univariable level were studied by a multivariable logistic regression model.The most common cause of ARF was congenital heart disease (n=75). RRT modalities included peritoneal dialysis (PD) (n=81), hemodialfiltration (HDF) (n=31) and intermittent hemodialysis (IHD) (n=18). Median RRT duration was 4 days (range 1-63 days). Overall mortality was 52.2%. IHD was associated with the best survival rate (P < 0.01 vs. PD and HDF), while children treated with HDF had the worse outcome. Hemodynamic instability and systemic infections were associated with greater mortality, but the rate of these complications did not differ between the study groups.Our results suggest that IHD when applied to the right patient in an appropriate setting may be a safe and efficient RRT modality in children with ARF. Randomized prospective trials are needed to further evaluate the impact of different RRT modalities on outcome in children with ARF.
Abstract Introduction: The use of routine post-operative mammogram (RPM) in search of residual calcifications after breast conserving surgery (BCS) remains controversial due to a paucity of data and conflicting results. In our institution it is common practice is to send all patients who presented with malignant calcifications and underwent BCS with negative surgical margins for RPM before radiotherapy. Patients are also sent for post-operative mammogram if they had malignant calcifications and positive surgical margins, to look for residual calcifications and use localization to ensure their removal in the re-excision. Methods: We reviewed the records of 182 patients in our institution referred for RPM between January 7, 2018, and July 14, 2021. Continuous variables were described using medians and interquartile range (IQR). Categorical variables were described as frequencies and percentages. Logistic regression was used to examine factors associated with residual calcifications. Results: Median patient age was 59 (48-67) and 39 (21.4%) patients received neoadjuvant systemic treatment. Eighty-five (46.7%) patients had pure DCIS and 66 (36.3%) had mixed IDC with DCIS. On surgical pathology 14 (7.7%) patients had involved surgical margins and an additional 28 (15.3%) had margins less than 2 mm to pure DCIS. Tumor characteristics and RPM results are presented in table 1. Of the 19 (10.4%) patients with suspicious residual calcifications on RPM, 17 (89%) underwent biopsy of the calcifications and the other 2 (11%) patients were referred directly for re-excision. Seven (36.8%) of the patients with suspicious residual calcifications had DCIS. No patients had residual invasive disease. The pathology results of patients with residual calcifications on RPM are presented table 2. Of the 7 patients with residual DCIS, 4 underwent re-lumpectomy, 2 underwent completion mastectomy and 1 patient was lost to follow-up. Additional DCIS was found in all the re-excisions. Two patients with residual DCIS had surgical margins under 2mm from pure DCIS while 5 patients (2.7% of all patients) had no indication for postoperative imaging or re-excision and the residual disease was identified solely based on the mammographic findings. Close or involved surgical margins were not significantly associated with residual calcifications on post-operative mammogram. Age under 50 was the only factor significantly associated with residual calcifications (OR 3.2 95% CI 1.1-9.7) and residual DCIS (OR=11 95% CI 1.13-109). Conclusion: In our cohort RPM revealed a small percentage of cases of residual DCIS that would have otherwise gone untreated. Larger studies are required to better identify factors associated with residual disease on RPM and to identify its impact on local recurrences. Table 1: Tumor characteristics and RPM results Table 2: Pathological results of patients with residual suspicious calcifications on RPM Citation Format: Opher Globus, Keren Grinin, Orit Keidar-Person, Einav Nili-Gal Yam, Keren Levanon, Naama Herman. The role of routine post-operative mammogram after breast conserving surgery [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-01.
Abstract Background: Epithelial-mesenchymal transition (EMT) in breast cancer drives tumor invasion, metastasis and drug resistance. BRCA1 mutation carriers have a high risk for developing aggressive basal-like triple-negative breast cancers with EMT characteristics. It has been described that normal mammary epithelium of BRCA1-mutation carriers is comprised of aberrant luminal progenitor cell population resembling basal-like breast cancer cells. Yet, the role of BRCA1 in regulating epithelial cell plasticity in normal mammary gland remains largely obscure. Aim: Here, we used patient-derived normal and cancer organoid cultures from BRCA1-mutation carriers and noncarriers, to examine the effect of the BRCA1 mutation background on epithelial cell plasticity and the susceptibility to EMT. Methods and results: Mammary organoids were established from normal or cancer mammary tissues obtained from consenting patients undergoing lumpectomy or mastectomy. Isolated cells were plated in adherent basement membrane extract (BME) drops and overlaid with optimized organoid culture medium. EMT regulation in breast cancer is usually studied using cell lines and murine models. To determine the possibility to study EMT on patient-derived organoids, organoid culture media was optimized and established organoids were exposed to TGFβ to induce EMT. Morphological and phenotypic alterations were characterized using immunolabeling and visualization with confocal microscopy. Breast cancer organoids induced with TGFβ demonstrated EMT-like changes including the downregulation of E-Cadherin and upregulation of N-Cadherin. Moreover, breast cancer organoids showed typical cytoskeleton rearrangements. Here, the transformation from cortical actin into stress fibers formed in dedifferentiated mesenchymal cells, was visualized with actin staining. However, normal mammary organoids behaved differently. The cytoskeleton of BRCA-wild type (noncarriers) normal mammary organoids was not affected by the treatment. Curiously, normal mammary organoids derived from BRCA1-mutation carriers demonstrated EMT like changes upon exposure to TGFβ. To further determine mechanisms facilitating cell plasticity in BRCA1-mutation carriers, single cell RNA sequencing analysis on BRACA1-mutation carriers and noncarriers derived organoids is ongoing. Conclusion: The results suggest that BRCA1 germline mutation predisposes normal mammary epithelium dedifferentiation due to increased susceptibility to EMT. Citation Format: Rakefet Ruth Ben-Yishay, Naama Herman, Vered Noy, Eyal Mor, Aiham Mansur, Dana Ishay-Ronen. Normal mammary epithelium of BRCA1 mutation carriers demonstrates increased susceptibility to cell plasticity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5847.
Cellular plasticity is enhanced by dedifferentiation processes such as epithelial-mesenchymal transition (EMT). The dynamic and transient nature of EMT-like processes challenges the investigation of cell plasticity in patient-derived breast cancer models. Here, we utilized patient-derived organoids (PDOs) as a model to study the susceptibility of primary breast cancer cells to EMT. Upon induction with TGF-β, PDOs exhibited EMT-like features, including morphological changes, E-cadherin downregulation and cytoskeletal reorganization, leading to an invasive phenotype. Image analysis and the integration of deep learning algorithms enabled the implantation of microscopy-based quantifications demonstrating repetitive results between organoid lines from different breast cancer patients. Interestingly, epithelial plasticity was also expressed in terms of alterations in luminal and myoepithelial distribution upon TGF-β induction. The effective modeling of dynamic processes such as EMT in organoids and their characteristic spatial diversity highlight their potential to advance research on cancer cell plasticity in cancer patients.
