Anal dysplasia and anal cancer screening practices among liver transplant centers in the United States: Results of an online survey.

BACKGROUND: Solid organ transplant recipients are at an increased risk for anogenital Human Papillomavirus (HPV)-related disease, including anal high-grade squamous intraepithelial lesions (HSIL) and anal squamous cell cancer (ASCC). Guidelines for ASCC screening in transplant recipients are limited. Our aim was to understand current practice of ASCC screening in adult liver transplant (LT) candidates and recipients at transplant centers across the United States. METHODS: We surveyed medical directors of 113 LT centers across the United States which had publicly available contact information. The survey evaluated center perceptions on cancer and HPV disease risk in transplant populations, ASCC screening, barriers and facilitators for ASCC screening and HPV vaccination practices. RESULTS: We received 26/113 (23%) responses, of which 24 were complete and included in the analysis. Eleven of 24 (46%) centers reported screening for ASCC and 3/24 (12.5%) centers reported having formal guidelines. Centers who perform ASCC screening were more likely to perform transplants in people living with HIV and were more aware of the burden of HPV disease in transplant populations. All respondents believed that additional data on the impact of screening on ASCC incidence would support screening decisions. Increased access to specialists for screening/high-resolution anoscopy was also perceived as a facilitator. Only 7/24 (29%) centers regularly evaluated HPV vaccination status of their patients. CONCLUSION: This national survey of LT centers reveals non-standardized ASCC screening practices, and identified data, educational and resource needs to improve prevention of ASCC in this population.

A phase I study of intra-anal artesunate (suppositories) to treat anal high-grade squamous intraepithelial lesions.

BACKGROUND: Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed. METHODS: This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL. RESULTS: The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate suppositories were Grade 1. At the 600-mg dose, patients experienced clinically significant nausea. CONCLUSION: Artesunate suppositories are a safe treatment option for anal HSIL.

A Phase 3, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate Safety, Tolerability, and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Allogeneic Hematopoietic Cell Transplant Recipients (PNEU-STEM).

BACKGROUND: Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE; Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients. METHODS: Participants received 3 doses of V114 or PCV13 (Prevnar 13; Wyeth LLC) in 1-month intervals starting 3-6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAX 23 or a fourth dose of PCV (if they experienced chronic graft vs host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group. RESULTS: A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at day 90. CONCLUSIONS: V114 was well tolerated in allo-HCT recipients, with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and was higher for V114 serotypes 22F and 33F. Study results support the use of V114 in allo-HCT recipients. Clinical Trials Registration. clinicaltrials.gov (NCT03565900) and European Union at EudraCT 2018-000066-11.

Predictors of in-hospital mortality in a cohort of people living with HIV (PLHIV) admitted to an academic medical intensive care unit from 2009 to 2014: A retrospective cohort study.

Outcomes for critically ill people living with human immunodeficiency virus (PLHIV) have changed with the use of antiretroviral therapy (ART). To identify these outcomes and correlates of mortality in a contemporary critically ill cohort in an urban academic medical center in Baltimore, a city with a high burden of HIV, we conducted a retrospective cohort study of individuals admitted to a medical intensive care unit (MICU) at a tertiary care center between 2009 and 2014. PLHIV who were at least 18 years of age with an index MICU admission of ≥24 hours during the 5-year study period were included in this analysis. Data were obtained for participants from the time of MICU admission until hospital discharge and up to 180 days after MICU admission. Logistic regression was used to identify independent predictors of hospital mortality. Between June 2009 and June 2014, 318 PLHIV admitted to the MICU met inclusion criteria. Eighty-six percent of the patients were non-Hispanic Blacks. Poorly controlled HIV was very common with 70.2% of patients having a CD4 cell count <200 cells/mm3 within 3 months prior to admission and only 34% of patients having an undetectable HIV viral load. Hospital mortality for the cohort was 17%. In a univariate model, mortality did not differ by demographic variables, CD4 cell count, HIV viral load, or ART use. Regression analysis adjusted by relevant covariates revealed that MICU patients admitted from the hospital ward were 6.4 times more likely to die in hospital than those admitted from emergency department. Other positive predictors were a diagnosis of end-stage liver disease, cardiac arrest, ventilator-dependent respiratory failure, vasopressor requirement, non-Hodgkin lymphoma, and symptomatic cytomegalovirus disease. In conclusion, in this critically ill cohort with HIV infection, most predictors of mortality were not directly related to HIV and were similar to those for the general population.

The importance of anal cancer screening and high-resolution anoscopy to gastroenterology practice.

PURPOSE OF REVIEW: Although human papillomavirus (HPV)-related anal squamous cell cancer (ASCC) is rare, its incidence has been rising and in high-risk populations exceeds the incidence of cancers for which screening programs are implemented. Therefore, targeted screening techniques are being evaluated with high-resolution anoscopy (HRA) as the current gold standard because of its ability to detect anal intraepithelial dysplasia (AIN) and premalignant high-grade squamous intraepithelial lesions (HSILs). However, a scarcity of trained providers presents a barrier to screening. RECENT FINDINGS: ASCC incidence is rising especially in elderly women and young black men. Premalignant HSIL may not only progress to ASCC but also regress. Biomarkers such as HPV type, p16 immunostaining and DNA methylation markers may emerge as predictors of disease progression.HRA with acetic acid and Lugol's iodine staining can be used to detect HSIL and ASCC. Recent studies suggest that anal cancer screening may have an impact on the stage of ASCC at diagnosis and the incidence of anal cancer.The Anal Cancer HSIL Outcomes Research (ANCHOR) study is underway to determine whether treating HSIL effects ASCC incidence. SUMMARY: Although there are no consensus screening guidelines for anal cancer, it is reasonable to screen high-risk populations with physical examination, anal cytology and HRA. Gastroenterologists can support anal cancer screening programmes through identifying patients at risk, performing noninvasive screening and considering to incorporate endoscopic techniques to examine the anal canal. VIDEO ABSTRACT: http://links.lww.com/COG/A32.

Establishing an Anal Cancer Screening Program in an Outpatient HIV Clinic: Referral Patterns and Patient Perceptions Survey.

People living with HIV are at high risk for anal cancer (AC); however, the impact of screening for and treatment of precancerous anal lesions on AC incidence remains uncertain. In 2013, we conducted a survey of HIV providers evaluating the perceived need for an institutional AC screening program. Based on an overwhelmingly positive response, we established a dedicated AC screening clinic (including provision of high-resolution anoscopies) embedded within the institutional HIV clinic. Here, we describe that referral of high-risk patients in the first 3 years was lower than expected. Referral patterns suggest that screening practices vary widely among HIV providers within the institution. Anal cancer clinic patients who completed a perception survey rated the value of AC screening as high, with perceived positive health impact, and identified their providers as the main source of information on AC and AC screening. Our findings imply remaining provider-related barriers to AC screening.

Cryptococcus neoformans infection in malignancy.

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

Anal Cancer Screening in an Urban HIV Clinic: Provider Perceptions and Practice.

In this article, we sought to understand the perceptions and practice of providers on anal cancer screening in HIV-infected patients. Providers in an academic outpatient HIV practice were surveyed. Data were analyzed to determine the acceptability and perceptions of providers on anal Papanicolaou tests. Survey response rate was 55.3% (60.7% among male and 47.4% among female providers). One-third of the providers had received screening requests from patients. Female providers had higher self-rated comfort with anal Papanicolaou tests, with a mean score of 7.1 (95% confidence interval [CI] 4.7-9.5) compared to 3.6 (95% CI 1.5-5.7) for male providers, P = .02. Sixty-seven percent of male providers and 37.5% of female providers would like to refer their patients for screening rather than perform the test themselves. Only 54.2% of our providers have ever performed anal cytology examination. Our survey revealed that not all providers were comfortable performing anal cancer screening for their patients.