Search

Purpose: Patterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy are not well described., Methods and Materials: We identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure [LRF], distant failure, progression-free survival, colostomy-free survival, and overall survival [OS]), patterns of failure, and salvage therapies were collected. Failures were analyzed using competing risk methods, whereas survival endpoints were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months of completing IMRT., Results: A total of 375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for the American Joint Committee on Cancer stages 0 to I, II, and III, respectively. Six-year rates of LRF, distant failure, progression-free survival, colostomy-free survival, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse 6-year OS than patients without LRF (44% vs 86%, P < .0001). Approximately 30% of patients who underwent salvage therapy were alive to 10 years after recurrence, compared with none of the patients who were managed with chemotherapy alone or the best supportive care., Conclusions: This large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Anal squamous cell carcinoma (ASCC) is a rare cancer with increased occurrence of multiple cancers before and after the ASCC diagnosis. However, there is limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after ASCC, time trends, impact on survival, and identify prognostic factors., Material and Methods: Initial primary malignancy (IPM) was defined as a malignancy occurring before the ASCC. Second primary malignancy (SPM) was defined as a distinct primary cancer that developed after ASCC diagnosis. Retrospective multi-institutional chart review was done. Progression free survival (PFS), overall survival (OS) and prognostic factors were evaluated., Results: 647 patients with ASCC treated with curative intent were analyzed. Median age was 61.23 years with 72% as females. 150 patients (23.3%) had multiple malignancies with IPM in 16% and SPM in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, p = .011) and OS (81% vs 69%, p = .008) compared to those with prior cancer. SPMs had a significant adverse impact on PFS (HR 4.22) and OS (HR 3.56). Females had better 5-year PFS (82% vs 70%, p = .016) as compared to males. The median time interval for developing ASCC (as SPM) after IPM was 9.32 years., Conclusions: ASCC patients have increased risk of multiple malignancies. Patients with prior cancer have inferior outcomes. SPM is a poor prognostic factor in patients without any prior cancer. SPM can develop years after treatment of primary ASCC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract: Leave passes provide authorized leave for hospitalized patients from a psychiatric inpatient unit. Although providing day passes was once a relatively common practice, there are relatively few data describing their safety and efficacy. This descriptive study examines the use of leave passes in an adult inpatient unit at a university hospital between 2017 and 2021, with attention to reasons for granting the day pass, duration, and outcome of the pass. During the study period, 10 patients with primary psychotic or mood disorders received 12 passes for housing coordination, COVID-19 vaccination, or major family events. There were no fatalities or abscondments. One patient experienced severe agitation and engaged in nonsuicidal self-injurious behavior. A second patient showed mild, redirectable psychomotor agitation upon return to the unit. The remaining 10 passes were uneventful. Our findings support the view that patients with diverse diagnoses can safely be provided leave from an inpatient setting with adequate planning and support, yielding a low incidence of adverse events., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The PI3K pathway integrates extracellular stimuli to phosphorylate effectors such as AKT and serum-and-glucocorticoid-regulated kinase (SGK1). We have previously reported that the PI3K pathway regulates estrogen receptor (ER)-dependent transcription in breast cancer through the phosphorylation of the lysine methyltransferase KMT2D by AKT. Here, we show that PI3Kα inhibition, via a negative-feedback loop, activates SGK1 to promote chromatin-based regulation of ER-dependent transcription. PI3K/AKT inhibitors activate ER, which promotes SGK1 transcription through direct binding to its promoter. Elevated SGK1, in turn, phosphorylates KMT2D, suppressing its function, leading to a loss of methylation of lysine 4 on histone H3 (H3K4) and a repressive chromatin state at ER loci to attenuate ER activity. Thus, SGK1 regulates the chromatin landscape and ER-dependent transcription via the direct phosphorylation of KMT2D. These findings reveal an ER-SGK1-KMT2D signaling circuit aimed to attenuate ER response through a role for SGK1 to program chromatin and ER transcriptional output., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)