Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

BACKGROUND: We examined the association between immunotherapy-containing and standard chemotherapy regimens with treatment delays and postoperative complications in stage II-III triple-negative breast cancer. The effect of immune-related adverse events (irAEs) was compared. PATIENTS AND METHODS: We compared 139 women treated with neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522 regimen) from August 2021 to September 2022 with 287 consecutive patients who received neoadjuvant chemotherapy alone prior to July 2021 and underwent surgery. Baseline characteristics, time to treatments, and surgical complications were compared using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Logistic regression identified factors associated with surgical complications. RESULTS: Age, body mass index, race, American Society of Anesthesiologists (ASA) class, and mastectomy rates were similar among cohorts. No clinically relevant difference in time from end of neoadjuvant treatment to surgery was observed [KEYNOTE-522: median 32 (IQR 27, 43) days; non-KEYNOTE-522: median 31 (IQR 26, 37) days; P = 0.048]. Time to radiation did not differ (P = 0.7). A total of 26 patients (9%; non-KEYNOTE-522) versus 11 (8%; KEYNOTE-522) experienced postoperative complications (P = 0.6). In the KEYNOTE-522 cohort, 59 (43%) of 137 patients experienced 82 irAEs; 40 (68%) required treatment. Older age (P = 0.018) and ASA class 4 (P = 0.007) were associated with delays to surgery after adjusting for clinical factors. Experiencing ≥ 1 irAE was associated with delay to radiation (P = 0.029). IrAEs were not associated with surgical complications (P = 0.4). CONCLUSIONS: We observed no clinically meaningful difference between times to surgery/adjuvant radiation or postoperative complications and type of preoperative chemotherapy. IrAEs were associated with delay to adjuvant radiation but not with postoperative complications or delay to surgery.

Bilateral Diffuse Pseudoangiomatous Stromal Hyperplasia Necessitating Mastectomy.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign breast lesion often diagnosed incidentally and frequently mistaken for fibroadenoma given similar radiographic appearance. Histopathology classically reveals diffuse, dense fibrous stromal background with a complex network of spindle cells forming slit-like spaces, giving it the appearance of angiomatous proliferation. Surgical excision is generally not necessary. Here we present two unusual cases of PASH: an adolescent patient with bilateral rapid onset of symptoms, and a premenopausal patient with bilateral, diffuse, recurrent PASH. Both required mastectomy. We aim to highlight the variable nature of presentation and briefly review current management options.

Impact of the COVID-19 Pandemic on Breast Cancer Screening and Operative Treatment.

INTRODUCTION: The COVID-19 pandemic has impacted many areas of health care and had a significant impact on care delivery, including breast cancer. METHODS: To better understand the changes to detection and treatment of breast cancer at our institution, we analyzed mammogram rates (screening and diagnostic) and breast cancer operations in 2019-2020. Mammography rates were calculated using county level census data for eligible women (Z-test). For breast cancer staging, a stage severity score was analyzed with a Mann-Whitney U-test (two-tail, P < .05) with proportions derived from WFBH operative volume quarterly reports. Results: Data revealed a relative decline from 2019 to 2020 in breast cancer screening. Screening mammograms decreased by 44% or 1558 fewer screening mammograms (Z = 4.75, P < .00001) and by 21% or 771 fewer for diagnostic mammograms (Z = 2.16, P = .03). With regards to breast cancer operations, we did not identify a statistically significant difference in number of new breast cancer operations at WFBH with 340 cases in 2020 as compared to 384 cases in 2019 (P = .9905). We compared a breast cancer severity score (weighted by stage at time of operation), which did not reveal statistically significant difference in clinical stage of breast cancer at time of operation (P = .71, U = 28). CONCLUSION: Mammography was impacted more than breast surgery cases by the COVID-19 pandemic. More data needs to be collected to evaluate future morbidity and mortality related to breast cancer operations and persistent disparities related to delay in breast cancer care due to COVID-19.

Primary Breast Neuroendocrine Tumor.

Breast primary neuroendocrine tumors (BNETs) are rare, making up less than 1% of all breast carcinoma diagnosis. Their detection relies on physical exams and mammography. Diagnosis of primary BNET requires findings of no other source of neuroendocrine tumor (eg, pancreatic, lung, and appendix). Histopathologically, they typically stain positive for chromogranin A and/or synaptophysin, as do most neuroendocrine tumors. Currently, there are no agreed upon and standardized treatment protocols as it is a rare diagnosis. Treatment protocols are often built on anecdotal evidence and small case reports and series. Here we discuss a case of BNET in a 51-year-old female and discuss commonly encountered treatment protocols.

Antipsychotic Medications for Low-Income Preschoolers: Long Duration and Psychotropic Medication Polypharmacy.

OBJECTIVE: This study aimed to evaluate prescribing patterns of antipsychotic medication and factors that predict duration of use among low-income, preschool-age children. METHODS: State Medicaid claims from 2012 to 2017 were used to identify antipsychotic medication use for children <6 years old. ICD-9 and ICD-10 codes were used to describe child diagnoses. Descriptive and multivariable analyses were used to determine patterns of antipsychotic medication use and factors that predicted duration of use. RESULTS: In 2012, 316 children <6 years of age started an antipsychotic medication in a southeastern state. Most were non-Hispanic White (N=202, 64%) and boys (N=231, 73%). Diagnoses included attention-deficit hyperactivity disorder (N=288, 91%), neurodevelopmental disorders (N=208, 66%), anxiety and trauma-related diagnoses (N=202, 64%), and autism spectrum disorders (ASDs) (N=137, 43%). The mean±SD duration of exposure to antipsychotic medication for children in the cohort was 2.6±1.7 years, but 86 children (27%) had >4 years of exposure. Almost one-third (N=97, 31%) received polypharmacy of four or more medication classes, and 42% (N=131) received metabolic screening. Being male, being in foster care, and having a diagnosis of ASD or disruptive mood dysregulation disorder were significantly associated with duration of use of antipsychotic medications; race-ethnicity was not significantly associated with duration of use. Emergency department visits (N=277, 88%) and inpatient hospitalizations (N=107, 34%) were observed during the study period. CONCLUSIONS: Many preschoolers received antipsychotic medications for substantial periods. Further research is needed to identify evidence-based practices to reduce medication use and improve outcomes.

Breast Reconstruction and Nipple-Sparing Mastectomy: Technical Modifications and Their Outcomes Over Time at an Academic Breast Center.

BACKGROUND: Superior aesthetic outcomes can be achieved with mastectomy techniques that maximize breast envelope preservation and maintain the nipple-areolar complex. This is the impetus for the popularization of the nipple-sparing mastectomy (NSM). Nipple-sparing mastectomy is a challenging procedure due to potential ischemia of the mastectomy flap (which includes the nipple-areolar complex) and the risk of incomplete oncologic resection. We review our experience with NSM, identify technique modifications used over time, and evaluate reconstructive outcomes of NSM and its modifications. METHODS: A retrospective review of consecutive patients with NSM and breast reconstruction over an 8-year period was completed. RESULTS: Fifty-five patients underwent 95 NSMs. Indications included invasive and in situ cancer, atypical ductal hyperplasia, and risk reduction. In the first 4 years of experience, the most frequently used NSM incision was radial (lateral) whereas use of a variety of incision patterns was noted in the second 4 years. Overall NSM and breast reconstruction complication rate for the entire study period was 50.9% and included a full-thickness mastectomy skin flap necrosis/nipple necrosis rate of 8.4%. In situ cancer of the nipple was identified in 3.2% of the patients, and 1 patient had locoregional recurrence. Overall complication rate was lower in the second 4 years of experience with NSM and reconstruction. One third of the patients underwent intraoperative fluorescent angiography (FA) to assess mastectomy skin perfusion before reconstruction start. Of the patients who had FA due to perfusion concerns, more than 70% of studies demonstrated poor perfusion and 83.3% of these patients had reconstruction delayed based on these results. Immediate, implant-based reconstruction was performed most commonly. An average of 2.66 procedures were required to achieve reconstruction completion, and 92.4% of the patients who sought reconstruction achieved completion. CONCLUSIONS: At our institution, NSM use is increasing, NSM incision pattern types used are expanding, and complication rates are decreasing. Immediate, implant-based reconstruction is most commonly used in combination with NSM at our institution. Fluorescent angiography is used to assess mastectomy skin perfusion and likely limits mastectomy complication effects on reconstruction. Despite the occurrence of complications, most patients will complete the breast reconstruction process.

High-level psychotropic polypharmacy: a retrospective comparison of children in foster care to their peers on Medicaid.

BACKGROUND: The use of antipsychotic medication and psychotropic polypharmacy has increased in the United States over the last two decades especially for children from low-income families and those in foster care. Although attention has been paid to providing greater insight, prescribing patterns remain concerning since there is a lack of evidence related to safety and efficacy. High-level psychotropic polypharmacy has not been described. We aim to compare the use of HLPP for children receiving Medicaid services and those in foster care and identify factors associated with the duration of use of high-level psychotropic polypharmacy. Additionally, we will examine the frequency of laboratory metabolic screening and emergency department, inpatient, and outpatient visits. METHODS: A cross-sectional, secondary analysis of statewide data describes trends in high-level psychotropic polypharmacy from 2012 to 2017 and the prevalence and predictors of high-level psychotropic polypharmacy duration and resource use in 2017 for all children on Medicaid and those in foster care. High-level psychotropic polypharmacy included concurrent use, at least four classes of medications including an antipsychotic, and at least 30 days duration. RESULTS: High-level psychotropic polypharmacy increased from 2012 to 2014 for both groups but stabilized in 2015-2016. Children in foster care showed a slight increase compared to their peers in 2017. There was no association between duration and demographic characteristics or foster care status. Diagnoses predicted duration. Neither group received metabolic monitoring at an acceptable rate. CONCLUSIONS: Concerning patterns of high-level psychotropic polypharmacy and metabolic monitoring were identified. Cautious use of high-level psychotropic polypharmacy and greater oversight to ensure that these children are receiving comprehensive services like behavioral health, primary care, and primary prevention.

A clinical perspective on adipose-derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery.

Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed. A cell-mediated, coordinated response to hypoxia drives these adaptive processes, restoring a tissue's normoxic homeostasis via de novo vasculogenesis, sprouting angiogenesis, and stabilizing arterialization. As cells exert prolonged and coordinated effects on site, their use as biological agents merit translational consideration of sourcing angio-competent cells and delivering them to territories enduring microcirculatory acclimatization. Angio-competent cells abound in adipose tissue: a reliable, accessible, and expendable source of adipose-derived cells (ADC). When subject to enzymatic digestion and centrifugation, adipose tissue separates its various ADC: A subset of buoyant oil-dense adipocytes (the tissue's parenchymal component) accumulates on a supra-natant layer, whereas the mesenchymal component remains in the infra-natant sediment, containing the tissue's stromal vascular fraction (SVF), where angio-component cells abound. The SVF can be further manipulated, selected, or culture expanded into more specific stromal subsets (herein defined as adipose stromal cells, ASC). While promising clinical applications for ADC await clinical proof and regulatory authorization, basic science investigation is needed to elucidate the specific ADC mechanisms that influence microvascular growth, remodeling, and function following flap surgery. The objective of this article is to share the clinical perspectives of reconstructive plastic surgeons regarding the use of ADC-based therapies to help with flap tissue integration, revascularization, and wound healing. Specifically, the focus will be on considering the potential for ADC as therapeutic agents and how their clinical application motivates basic science opportunities.

Indigenous cancer patient and staff attitudes towards unmet needs screening using the SCNAT-IP.

INTRODUCTION: Indigenous Australians have a higher cancer incidence, worse mortality and are less likely to receive optimal cancer treatment compared with non-Indigenous Australians. Culturally appropriate supportive care helps ensure that Indigenous patients engage in and receive optimal care. However, many existing supportive care needs tools lack cultural relevance for Indigenous people, and their feasibility with Indigenous people has not been demonstrated. The Supportive Care Needs Assessment Tool for Indigenous People (SCNAT-IP) assesses the unmet supportive care needs of Indigenous cancer patients. PURPOSE: This descriptive study evaluates the clinical implementation of the SCNAT-IP in routine care. METHODS: Two large tertiary cancer treatment centres and two regional oncology clinics participated. Participants included 10 clinical staff and 36 adult Indigenous cancer patients (mean age 54 years). Patients and clinicians completed brief, purpose-designed questionnaires and interviews. RESULTS: Patients reported high ratings (means >8/10) for acceptability, helpfulness and timing items. The majority (≥80%) of staff agreed that the SCNAT-IP was useful to clinical practice, should be used in routine care and was acceptable to their patients. CONCLUSIONS: The study provides empirical support for the feasibility and acceptability of the SCNAT-IP in routine cancer care with Indigenous Australians. Routine screening with the SCNAT-IP has the potential to improve cancer care for Indigenous people with cancer.

Convergent effects of mouse Pet-1 deletion and human PET-1 variation on amygdala fear and threat processing.

Serotonin is critical for shaping the development of neural circuits regulating emotion. Pet-1 (FEV-1) is an ETS-domain transcription factor essential for differentiation and forebrain targeting of serotonin neurons. Constitutive Pet-1 knockout (KO) causes major loss of serotonin neurons and forebrain serotonin availability, and behavioral abnormalities. We phenotyped Pet-1 KO mice for fear conditioning and extinction, and on a battery of assays for anxiety- and depression-related behaviors. Morphology of Golgi-stained neurons in basolateral amygdala (BLA) and prelimbic cortex was examined. Using human imaging genetics, a common variant (rs860573) in the PET-1 (FEV) gene was tested for effects on threat-related amygdala reactivity and psychopathology in 88 Asian-ancestry subjects. Pet-1 KO mice exhibited increased acquisition and expression of fear, and elevated fear recovery following extinction, relative to wild-type (WT). BLA dendrites of Pet-1 KO mice were significantly longer than in WT. Human PET-1 variation associated with differences in amygdala threat processing and psychopathology. This novel evidence for the role of Pet-1 in fear processing and dendritic organization of amygdala neurons and in human amygdala threat processing extends a growing literature demonstrating the influence of genetic variation in the serotonin system on emotional regulation via effects on structure and function of underlying corticolimbic circuitry.

An exploratory study of 2 parenting styles and family health behaviors.

OBJECTIVE: To examine the relationships between 2 parenting styles and family nutrition and physical activity. METHODS: Parents of elementary/primary school children in the southeastern United States (N = 145) completed surveys regarding family relationships and health behaviors. RESULTS: Parents exhibiting a laissez-faire parenting style reported lower levels of family nutrition and physical activity. In addition, parent BMI moderated the relationship between laissez-faire parenting and these health behaviors. CONCLUSIONS: This study indicates that family-oriented nutrition and physical activity programs may benefit from including a focus on decreasing laissez-faire parenting, as well as helping overweight parents reduce their BMIs.

Wound healing following combined radiation and cetuximab therapy in head and neck cancer patients.

OBJECTIVE: This study set out to determine if cetuximab treatment increases the risk of wound healing complications when combined with radiation therapy. METHOD: We performed a retrospective chart review of head and neck cancer patients who received salvage neck dissections between 1999 and 2007, at two academic tertiary care centres. Complications from wound healing were compared between radiation and combined therapy groups. RESULTS: A total of 35 patients received radiation (n=20) or combined radiation and cetuximab therapy (n=15) prior to neck dissection. The treatment groups were similar in regard to demographic and primary tumour-related characteristics. The time between treatment and salvage neck dissection did not differ between the radiation (3.9 months) and combination treatment (3.0 months) groups (p=0.15). Wound healing complications occurred in 13% (2/15) of the patients treated with radiation and cetuximab and there were no complications in patients who received radiation alone (p=0.20). CONCLUSION: Cetuximab did not significantly increase the risk of post-surgical wound complications, although a higher absolute number of wound complications was observed in the group treated with cetuximab and radiation therapy, compared with the group treated with radiation alone. CONFLICT OF INTEREST: This work was supported by a grant from the National Institute of Health (2T32 CA091078-06). One of the authors, JAB, is an occasional consultant and honoraria for ImClone and Bristol-Meyers Squibb.

Agreement and reasons for disagreement between photographic and hospital biomicroscopy grading of diabetic retinopathy.

AIMS: To compare agreement level and identify reasons for disagreement between grading of mydriatic digital photographs in a diabetic retinopathy screening service and hospital eye service biomicroscopy grading. METHODS: Structured examination findings leading to automatically calculated National Screening Committee grades recorded on an electronic medical record system in the hospital eye service at the first clinic visit after diabetic retinopathy screening service referral between April 2006 and November 2007 were retrospectively compared with the grade at the screening visit that prompted referral. In cases of disagreement, screening images were reviewed. RESULTS: Data on 452 eyes (226 patients) were analysed. For retinopathy, hospital eye service slit-lamp biomicroscopy grades were: R0 (no diabetic retinopathy) in 63 eyes; R1 (background retinopathy) in 251 eyes; R2 (pre-proliferative) in 129 eyes and R3 (proliferative) in nine eyes. Diabetic retinopathy screening service grades were in agreement in 350 eyes (77.4%), showed a lower grade in 59 eyes and a higher grade in 43. Agreement was moderate (κ=0.60). The most common reason for disagreement was overgrading of R1 by clinicians. Hospital eye service biomicroscopy maculopathy grades were: M0 (no maculopathy) in 366 eyes and M1 (maculopathy) in 86 eyes. Diabetic retinopathy screening service grades were in agreement in 327 eyes (72.3%), showed a lower grading in five eyes and a higher grade in 120 eyes. Agreement was moderate (κ=0.41). The commonest cause for disagreement was clinicians failing to identify fine macular exudates. CONCLUSIONS: This study of routine clinical services demonstrates moderate agreement between non-medical grading of mydriatic digital retinal photography images and hospital slit-lamp biomicroscopy grading of patients referred with diabetic retinopathy. The majority of errors in grading were attributable to errors by hospital doctors, usually in the direction of under-grading which could be a potential source of clinical risk if treatment is delayed.

Reverse portal flow after liver transplantation--ominous or acceptable?

Reversal of portal flow or hepatofugal flow after liver transplantation is a rare complication after liver transplantation. The available reports in the literature suggest that it is an ominous condition that requires immediate operative intervention, failing which prognosis would be grim. We report two children from two different centers who developed hepatofugal flow in the immediate post-operative period after liver transplantation. The possible etiologies in these patients were acute rejection in one and absence of an MHV causing inadequate hepatic venous outflow in the other. Both patients were treated non-operatively with steroids and immunosuppression. Spontaneous reversal to a normal hepatopetal flow occurred in both and the patients continue to be well six months after the transplant. Our experience contradicts the viewpoint that hepatofugal flow equates to mortality in the absence of surgical intervention. It remains to be defined as to which patients with hepatofugal flow will benefit from surgical intervention.

Malignant fungating wounds: an analysis of the lived experience.

OBJECTIVE: The current understanding of living with a malignant fungating wound is derived from professionals' rather than the patient's perspective. An appreciation of the lived experience may assist in the development of more empathetic support approaches. This paper reports upon a study that aimed to illuminate the meaning and experience of living with a malignant fungating wound. METHOD: A Heideggerian hermeneutic phenomenological approach was used as the philosophical framework. Unstructured interviews were conducted with a purposive sample of five participants. Content hermeneutic analysis was adopted to analyse the data. RESULT: Four themes were identified: representing the worst part of the patient's cancer; living within a body that cannot be trusted; a changing relationship with the patient's family and friends; and a loss of identity while continuously striving to be normal, yet feeling different. CONCLUSION: Health care professionals must possess a heightened awareness of: the importance of the impact of the wound upon day-to-day living, identity and purpose; the value of adopting the phrase used by the patient to describe their wound; and to focus more upon the subjective meaning of a visibly changing wound rather than objective measurement.