Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy.

PURPOSE: Risk-reducing surgery for cancer prevention in solid tumors is a pressing clinical topic because of the increasing availability of germline genetic testing. We examined the short- and long-term outcomes of risk-reducing total gastrectomy (RRTG) and its lesser-known impacts on health-related quality of life (QOL) in individuals with hereditary diffuse gastric cancer syndrome. METHODS: Individuals who underwent RRTG as part of a single-institution natural history study of hereditary gastric cancers were examined. Clinicopathologic details, acute and chronic operative morbidity, and health-related QOL were assessed. Validated questionnaires were used to determine QOL scores and psycho-social-spiritual measures of healing. RESULTS: One hundred twenty-six individuals underwent RRTG because of a pathogenic or likely pathogenic germline CDH1 variant between October 2017 and December 2021. Most patients (87.3%; 110/126) had pT1aN0 gastric carcinoma with signet ring cell features on final pathology. Acute (<30 days) postoperative major morbidity was low (5.6%; 7/126) and nearly all patients (98.4%) lost weight after total gastrectomy. At 2 years after gastrectomy, 94% (64/68) of patients exhibited at least one chronic complication (ie, bile reflux, dysphagia, and micronutrient deficiency). Occupation change (23.5%), divorce (3%), and alcohol dependence (1.5%) were life-altering consequences attributed to total gastrectomy by some patients. In patients with a median follow-up of 24 months, QOL scores decreased at 1 month after gastrectomy and returned to baseline by 6-12 months. CONCLUSION: RRTG is associated with life-changing adverse events that should be discussed when counseling patients with CDH1 variants about gastric cancer prevention. The risks of cancer-prevention surgery should not only be judged in the context of likelihood of death due to disease if left untreated, but also based on the real consequences of organ removal.

Community-Led Response to Address Economic Vulnerability due to COVID-19 with, for, and by Transgender Women of Color: A Qualitative Pilot Evaluation.

Purpose: Intersectional stigma fuels inequities among transgender women of color, which have been exacerbated by coronavirus disease 2019 (COVID-19). This study evaluated a community-led emergency assistance program for transgender women of color. Methods: We conducted a pilot program evaluation (n=8). Results: Retention was 87.5% over the follow-up. Funds were primarily used for bills, food, and housing. Requesting and receiving funds was described as "somewhat to extremely easy." Participants identified the need for economic empowerment components in future programming, specifically gender affirmation, skill-building for education and employment, and entrepreneurial opportunities. Conclusion: Findings highlight the need to invest in community-led strategies to address inequities experienced by transgender women of color.

Improving Access to Legal Gender Affirmation for Transgender Women Involved in the Criminal-Legal System.

Transgender women of color experience interlocking systems of oppression rooted in racism and transphobia, which fuel economic vulnerability and overrepresentation in the criminal-legal system. Legal gender affirmation, which refers to changing one's name and gender marker on official documents, has the potential to mitigate these issues by improving access to employment, housing, education, health care, and social services. These services are particularly important for transgender women of color with criminal records, a history of incarceration, or other legal infractions; however, 23 states have policies that restrict access to legal gender affirmation for these individuals. Alongside eliminating restrictive policies to obtain legal gender affirmation, medical-legal partnerships in these states may address recidivism and health inequities among transgender women of color.

Cytoreduction and HIPEC for Gastric Carcinomatosis: Multi-institutional Analysis of Two Phase II Clinical Trials.

INTRODUCTION: There are no approved locoregional therapies for peritoneal carcinomatosis from gastric adenocarcinoma (GA). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents a potential treatment for advanced GA with isolated peritoneal metastasis. PATIENTS AND METHODS: Two separate single-institution phase II, single-arm studies evaluating CRS-HIPEC using cisplatin with mitomycin C (NIH: NCT03092518, MDACC: NCT02891447) in patients with GA and confirmed peritoneal metastasis were analyzed. The primary endpoint of each trial was overall survival (OS). Clinical, pathologic, and treatment variables were analyzed for association with outcomes. RESULTS: Over 4 years, 41 patients with peritoneal carcinomatosis from GA underwent CRS-HIPEC. All patients had synchronous peritoneal metastasis and received systemic chemotherapy as front-line therapy. A total of 23 patients also received laparoscopic HIPEC prior to open CRS-HIPEC. The majority (63%, n = 26) were male, and median PCI score at CRS-HIPEC was 2. Median OS was 24.9 months from diagnosis and 14.4 months from CRS-HIPEC. Three-year OS was 25% from diagnosis and 22% from CRS-HIPEC. Median RFS was 7.4 months. The rate of 30-day Clavien-Dindo grade ≥ 3 complications was 32%; specifically, the rate of anastomotic leak was 22%. Multivariable analysis identified the number of pathologically positive lymph nodes as an independent predictor of postoperative OS. CONCLUSIONS: In patients with gastric adenocarcinoma and isolated peritoneal metastasis treated with CRS-HIPEC, 3-year OS was 22% from CRS-HIPEC, and complications were common. The number of pathologic lymph node metastases was inversely correlated with overall survival. Further investigation of CRS-HIPEC for GA should include patient selection based on response to systemic chemotherapy or incorporate novel intraperitoneal treatment strategies.

The ethical imperative to reduce HIV stigma through community-engaged, status-neutral interventions designed with and for transgender women of colour in the United States.

INTRODUCTION: In the era of biomedical HIV prevention and treatment technologies, such as treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP), there is momentum to develop and rigorously evaluate interventions focused on PrEP among those at risk for HIV acquisition and antiretroviral therapy (ART) adherence among people living with HIV. While HIV status-specific interventions focused on PrEP or ART provide valuable information, status-segregated interventions can create, perpetuate, and even increase HIV stigma among transgender women of colour and other marginalized communities in the United States (US). DISCUSSION: Due largely to community advocacy, discourses that support status-neutral approaches have emerged in the scientific literature. Although US-based funding mechanisms have typically designated awards focused on a specific HIV status, intervention developers and implementing agencies find creative ways to design and implement status-neutral programmes despite such restrictions. We present our experience with intervention research in New York, Detroit, New Orleans, Puerto Rico and the San Francisco Bay Area, all Ending the HIV Epidemic (EHE) priority jurisdictions. Kickin it with the Gurlz' was developed to be status-neutral through two grants due to community demands for a unifying approach. The Transgender Women Engagement and Entry to (TWEET) Care Project was designed to improve HIV care engagement for transgender women living with HIV, but developers realized the importance of including participants of any HIV status. Healthy Divas was designed for transgender women living with HIV but subsequent implementing agencies prioritized adapting it to be status-neutral. These examples support the urgency of designing, implementing and evaluating status-neutral interventions. CONCLUSIONS: Community-based organizations strive for inclusivity in their programming and are rightly often reluctant to segregate services based on the HIV status of their clients. As researchers, we have an ethical imperative to work to reduce HIV stigma and respond to the needs of those most impacted by HIV, including transgender women of colour. As such, we call upon funders to develop mechanisms that support the development and testing of HIV status-neutral interventions to reduce HIV stigma and support community building, thereby increasing the possibility of fully realizing the benefits of biomedical HIV prevention and treatment technologies for all.

Super-Spreaders or Victims of Circumstance? Childhood in Canadian Media Reporting of the COVID-19 Pandemic: A Critical Content Analysis.

This qualitative research study, a critical content analysis, explores Canadian media reporting of childhood in Canada during the COVID-19 global pandemic. Popular media plays an important role in representing and perpetuating the dominant social discourse in highly literate societies. In Canadian media, the effects of the pandemic on children and adolescents' health and wellbeing are overshadowed by discussions of the potential risk they pose to adults. The results of this empirical research highlight how young people in Canada have been uniquely impacted by the COVID-19 global pandemic. Two dominant narratives emerged from the data: children were presented "as a risk" to vulnerable persons and older adults and "at risk" of adverse health outcomes from contracting COVID-19 and from pandemic lockdown restrictions. This reflects how childhood was constructed in Canadian society during the pandemic, particularly how children's experiences are described in relation to adults. Throughout the pandemic, media reports emphasized the role of young people's compliance with public health measures to prevent the spread of COVID-19 and save the lives of older persons.

Nivolumab Induced Psoriasis Successfully Treated With Acitretin.

Immunotherapy is emerging as a promising alternative treatment for a variety of solid tumors. Its beneficial effects are mediated through hijacking the immune system to mount an anti-tumor response. One of the mechanisms of increasing anti-tumour immunity is through immune checkpoint blockade.

Evaluation of confocal laser endomicroscopy for detection of occult gastric carcinoma in CDH1 variant carriers.

BACKGROUND: Hereditary diffuse gastric cancer syndrome, attributed to inactivating germline CDH1 variants, is associated with an elevated lifetime risk of gastric cancer. We sought to evaluate cancer detection using probe-based confocal laser endomicroscopy (pCLE) during endoscopic surveillance. METHODS: A prospective, single-institution study was conducted in asymptomatic adults with pathogenic or likely pathogenic (P/LP) CDH1 variants. Subjects received endoscopic gastric surveillance using pCLE in conjunction with the Cambridge method (CM). Abnormalities visualized by pCLE were biopsied, followed by non-targeted mucosal biopsies according to the CM. Primary endpoint was to determine pCLE sensitivity for detection of occult SRC carcinoma compared to CM. RESULTS: Thirty-six patients with P/LP CDH1 variants underwent endoscopy using pCLE and CM. Majority were female (75%) with median age 47 years. Targeted biopsies of focal abnormalities on WLE were negative for carcinoma. Overall, 19.4% (7/36) patients had SRC detected on ≥1 biopsy. Non-targeted CM biopsies revealed SRC in 11.1% (4/36), whereas pCLE revealed SRC in 16.7% (6/36). Fifteen patients underwent total gastrectomy; all 15 explants contained occult carcinoma. In those 15 patients, the false-negative SRC detection rates for pCLE and CM were 67% and 87%, respectively. CONCLUSIONS: Confocal endomicroscopy alone has low sensitivity for occult cancer detection in CDH1 variant carriers, although it appeared no worse than the current recommended method and required fewer biopsies per patient. A more reliable endoscopic surveillance is needed as a viable alternative to surgery in this high-risk population (ClinicalTrials.gov, Number: NCT03648879).

Trait Perfectionism and Dance Goals Among Young Female Dancers: An Application of the 2 × 2 Model of Perfectionism.

This study provided the first test of the 2 × 2 model of perfectionism with respect to dancers' goals for dancing in competitive dance. Four hundred twenty-five young female North American competitive dancers (M = 11.33 years; SD = 2.14) completed questionnaires assessing multidimensional perfectionism and goals for participation in dance. The latent moderated structural equations approach along with procedures outlined by Gaudreau indicated partial support for the 2 × 2 model of perfectionism. Pure Evaluative Concerns Perfectionism was associated with fewer intrinsic goals for dance and greater extrinsic goals for dance relative to nonperfectionism. Pure Personal Standards Perfectionism was related to less endorsement of extrinsic goals relative to nonperfectionism. Findings were complex with respect to mixed perfectionism, with this form of perfectionism being related to greater endorsement of both intrinsic and extrinsic goals for dance. Results provide partial support for the 2 × 2 model in youth dance.

High Levels of Psychological Distress, Sleep Disturbance, and Alcohol Use Disorder in Adults With Atopic Dermatitis.

BACKGROUND: The burden of illness associated with atopic dermatitis (AD) is significant and multidimensional, especially in those with moderate to severe disease. OBJECTIVE: Our objective was to evaluate the disease burden of patients with AD in relation to psychological distress, sleep disturbance, and alcohol misuse. METHODS: Patients with AD, attending 2 tertiary referral centers in Dublin, Ireland, were recruited. A series of validated questionnaires were used including the Patient-Oriented Eczema Measure, Dermatology Life Quality Index (DLQI), Center for Epidemiologic Studies-Depression Scale, Quality of Life in Atopic Dermatitis Questionnaire, Alcohol Use Disorders Identification Test, and Pittsburgh Sleep Quality Index. The Eczema Area and Severity Index was calculated contemporaneously with the questionnaire completion. RESULTS: One hundred patients completed the questionnaire, of whom 52% were female. Sixty-three percent of patients experienced impaired quality of life as measured by the DLQI. Higher DLQI scores correlated with decreasing age (r = 0.3277, P < 0.0009). Thirty percent were found to be at risk of clinical depression, and higher Center for Epidemiologic Studies-Depression Scale scores correlated with a younger age and eczema severity. Sleep disturbance was greater in those at risk of depression (mean = 10.40 vs 5.79, P < 0.0001). Patients with moderate to severe AD were more likely to score higher on the Alcohol Use Disorders Identification Test, and 25% met the criteria for alcohol use disorder. In relation to sleep, 73% of patients scored higher than 5 on the Pittsburgh Sleep Quality Index, which signifies poor sleep quality. CONCLUSIONS: Patients with AD endure a significant burden on health with regard to mental well-being, alcohol use, and sleep quality. Clinicians should consider screening patients for these comorbidities.

Outcomes of a PrEP Demonstration Project with LGBTQ Youth in a Community-Based Clinic Setting with Integrated Gender-Affirming Care.

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) youth are disproportionately affected by HIV, and young transgender women (YTW) are especially impacted. The purpose of this small demonstration project was to measure pre-exposure prophylaxis (PrEP) adherence in a community-based clinic for LGBTQ youth in which PrEP services are integrated with gender-affirming care. Of the 50 enrolled participants, 38 had a serum drug assay performed after three or more months and 26% of those had laboratory evidence of highly protective levels of medication. Low adherence highlights the need for culturally tailored follow-up efforts and assistance with the structural barriers to health experienced by LGBTQ youth, especially YTW.

Evaluation of confocal endoscopic microscopy for detection of early-stage gastric cancer in hereditary diffuse gastric cancer (HDGC) syndrome.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) syndrome results most often from a mutation in the CDH1 tumor suppressor gene and confers a 56-70% lifetime risk of gastric cancer. In asymptomatic carriers HDGC is characterized by multiple foci of signet ring cancer cells (SRCC) throughout the gastric mucosa. Because SRCC foci are less than 1 mm in diameter, and often make up less than 2% of the gastric mucosa, they are undetectable on standard screening endoscopy. International consensus guidelines recommend thorough white light endoscopic gastric mapping with a systematic method for gastric biopsies. Despite a painstaking approach to gastric mapping, retrospective analyses have demonstrated a low rate of detection and poor sensitivity of standard white light endoscopy for detecting occult cancer cells. Therefore, a more sensitive cancer screening tool is needed for these high-risk patients. Confocal endoscopic microscopy (CEM) allows for real-time, in vivo histologic imaging of gastrointestinal mucosa during upper endoscopy. Clinical application has demonstrated the ability of CEM to differentiate normal mucosal cells and cancer cells. METHODS: A phase II clinical trial is currently underway to compare CEM to standard endoscopic gastric mapping in an effort to reduce the false negative detection rate of SRCC in patients diagnosed with HDGC. After an upper endoscopy with gastric mapping is performed, patients will undergo probe-based CEM. The endoscopist will scan the anatomic zones of the stomach in a similar fashion to the systematic gastric mapping approach. Any abnormal areas visualized with the CEM probe will be biopsied and sent for permanent pathologic analysis. The primary endpoint is to determine if CEM affords a higher sensitivity for detection of SRCC in CDH1 germline mutation carriers compared to white light endoscopy with gastric mapping. DISCUSSION: This novel screening technique is expected to provide greater sensitivity for detecting occult cancer in patients with HDGC, thereby improving cancer risk-assessment and overall cancer care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648879 (registration date: August 28, 2018, clinicaltrials.gov).

Refractory pemphigus foliaceous treated with rituximab.

Autoimmune blistering diseases are rare but potentially life-threatening conditions. Pemphigus foliaceus is one of these conditions, characterised by superficial erosions of the skin without mucosal involvement. We report the case of a 57-year-old woman who presented with a 4-week history of rash affecting her scalp with associated hair loss. Clinical and histopathological findings were in keeping with pemphigus foliaceus. She was successfully treated with rituximab, a chimeric monoclonal antibody against CD20, leading to a transient depletion of B cells. After 5 months of follow-up, her rash had cleared, and her hair had completely regrown.