Neutrophil-to-lymphocyte ratio as a predictor of surgical outcomes in head and neck cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation that is associated with adverse oncologic and surgical outcomes. We investigated the use of NLR as a prognostic indicator of complications of head and neck cancer (HNC) surgeries. METHODS: We conducted a retrospective study of 11 187 Veterans who underwent HNC surgery between 2000 and 2020. We calculated preoperative NLR values and fit logistic regression models adjusting for potential confounding factors, comparing high-NLR patients to low-NLR patients. RESULTS: The cohort had a median age of 63 and was 98% men. High-NLR patients had increased odds of 30-day mortality (p < 0.001), having 1+ perioperative complications (p < 0.001), sepsis (p = 0.03), failure to wean from mechanical ventilation (p = 0.04), pneumonia (p < 0.001), and pulmonary embolism (p = 0.02) compared with low-NLR patients. CONCLUSION: NLR was a robust, independent predictor of 30-day mortality, having 1+ surgical complications, sepsis, failure to wean from mechanical ventilation, pneumonia, and pulmonary embolism.

Timely adherence to follow-up after high-risk lung cancer screenings.

OBJECTIVE: To achieve the lung cancer screening (LCS) mortality benefit in clinical trials, timely, real-world follow-up of abnormal test results is necessary. Presently, annual LCS rates are lower than in trials, and adherence to follow-up after suspicious findings has not been well studied. This study examined timely adherence to follow-up recommendations after positive low-dose computed tomography (LDCT) screenings. METHODS: This retrospective study included individuals from two academic primary care practices in New York City who met United States Preventative Services Task Force LCS eligibility and had a positive LDCT scan between 2013 and 2020. They were recommended for shorter interval follow-up repeat computed tomography (CT), CT biopsy, or positron emission tomography/CT. Adherence was completion of the prescribed imaging by 15 days after the recommended 7-, 30-, and 90-day follow-up and by 30 days after the 180-day recommended follow-up. RESULTS: Among 106 individuals with a positive LDCT scan, 64 (60%) were adherent to follow-up recommendations. Adherence was 72%, 63%, and 42% for recommended follow-ups of 30, 90, and 180 days, respectively. Being male was a predictor of a lower adherence rate. Among 23 individuals newly diagnosed with lung cancer after a positive LDCT scan, 83% were adherent to follow-up testing and 82% of cancers were Stage 1A or limited stage. CONCLUSIONS: There was variable adherence to the LCS follow-up recommendations despite positive screening CT, suggesting that even in a well-established screening program there may not be an efficient, systematic approach for follow-up. The delays in repeat testing potentially undermine the benefits of early detection.

Association of Antibiotic Receipt With Survival Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Receiving Chemotherapy.

Importance: The prognosis for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is dismal, due in part to chemoresistance. Bacteria-mediated mechanisms of chemoresistance suggest a potential role for antibiotics in modulating response to chemotherapy. Objective: To evaluate whether use of peritreatment antibiotics is associated with survival among patients with metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Design, Setting, and Participants: Using the population-based Surveillance, Epidemiology, and End Results-Medicare linked database, this retrospective cohort study analyzed data for patients diagnosed with PDAC between January 1, 2007, and December 31, 2017. Data analysis was conducted between September 1, 2021, and January 15, 2023. The population-based sample included 3850 patients with primary metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Patients who received antibiotics were matched based on propensity scores to patients who did not receive antibiotics. Exposures: Receipt of 5 or more days of oral antibiotics or 1 injectable antibiotic in the month before or after beginning first-line chemotherapy. Main Outcomes and Measures: Overall survival and cancer-specific survival. The end of follow-up was December 31, 2019, for overall survival and December 31, 2018, for cancer-specific survival. Results: Of the 3850 patients treated with first-line gemcitabine (3150 [81.8%]) or fluorouracil (700 [18.2%]), 2178 (56.6%) received antibiotics. The mean (SD) age at diagnosis was 74.2 (5.8) years and patients were predominantly women (2102 [54.6%]), White (3396 [88.2%]), and from metropolitan areas (3393 [88.1%]) in the northeastern or western US (2952 [76.7%]). In total, 1672 propensity-matched pairs were analyzed. Antibiotic receipt was associated with an 11% improvement in overall survival (hazard ratio [HR], 0.89; 95% CI, 0.83-0.96; P = .003) and a 16% improvement in cancer-specific survival (HR, 0.84; 95% CI, 0.77-0.92; P < .001) among patients treated with gemcitabine. In contrast, there was no association between antibiotic receipt and overall survival (HR, 1.08; 95% CI, 0.90-1.29; P = .41) or cancer-specific survival (HR, 1.12; 95% CI, 0.90-1.36; P = .29) among patients treated with fluorouracil. In a subgroup of gemcitabine-treated patients who received antibiotics, nonpenicillin ß-lactams were associated with an 11% survival benefit (HR, 0.89; 95% CI, 0.81-0.97; P = .01). Conclusions and Relevance: In this cohort study, receipt of perichemotherapy antibiotics was associated with improved survival among patients treated with gemcitabine, but not fluorouracil, suggesting that antibiotics may modulate bacteria-mediated gemcitabine resistance and have the potential to improve PDAC outcomes.

Prophylactic feeding tube placement for squamous cell carcinoma of the head and neck.

BACKGROUND: Percutaneous endoscopic gastronomy (PEG) tubes are commonly used to administer enteral nutrition during head and neck cancer (HNC) treatment. However, the benefits of placing a prophylactic feeding tube (PFT; prior to radiotherapy [RT]) or reactive feeding tube (RFT, after RT initiation) are unclear. We sought to compare survival, body mass trends, and hospitalization rates between strategies. METHODS: We conducted a retrospective cohort study of 11,473 Veterans with stages III-IVC HNC treated with chemoradiotherapy. Patients with PEG tube placement within 30 days prior to treatment initiation (PFT) were compared to all other patients (non-PFT) or patients with PEG tube placement within 3 months after treatment initiation placement (RFT). We compared survival, longitudinal body mass changes, and hospitalization rates for PFT versus non-PFT or RFT patients in propensity score (PS)-matched Cox regression models. RESULTS: 3,186 (28 %) patients received PFT and 8,287 (72 %) were non-PFT, of which 1,874 (23 %) received RFT. After PS-matching, there were no significant differences in overall survival (HR 0.97, 95 % CI 0.92-1.02), HNC-specific survival (HR 0.98, 95 % CI 0.92-1.09), change in BMI (p = 0.24), or hospitalization rates between PFT and non-PFT groups. Significant differences in hospitalization rates between PFT and RFT groups persisted after PS-matching (-0.11 hospitalizations/month), but no differences were found for other outcomes. CONCLUSION: Timing of PEG tube placement in Veterans with HNC was not associated with any significant survival or body mass advantage. However, patients who received PFT had a lower hospitalization rate than those who received RFT.

The Great Majority of Homologous Recombination Repair-Deficient Tumors Are Accounted for by Established Causes.

Background: Gene-agnostic genomic biomarkers were recently developed to identify homologous recombination deficiency (HRD) tumors that are likely to respond to treatment with PARP inhibitors. Two machine-learning algorithms that predict HRD status, CHORD, and HRDetect, utilize various HRD-associated features extracted from whole-genome sequencing (WGS) data and show high sensitivity in detecting patients with BRCA1/2 bi-allelic inactivation in all cancer types. When using only DNA mutation data for the detection of potential causes of HRD, both HRDetect and CHORD find that 30-40% of cases that have been classified as HRD are due to unknown causes. Here, we examined the impact of tumor-specific thresholds and measurement of promoter methylation of BRCA1 and RAD51C on unexplained proportions of HRD cases across various tumor types. Methods: We gathered published CHORD and HRDetect probability scores for 828 samples from breast, ovarian, and pancreatic cancer from previous studies, as well as evidence of their biallelic inactivation (by either DNA alterations or promoter methylation) in HR-related genes. ROC curve analysis evaluated the performance of each classifier in specific cancer. Tenfold nested cross-validation was used to find the optimal threshold values of HRDetect and CHORD for classifying HR-deficient samples within each cancer type. Results: With the universal threshold, HRDetect has higher sensitivity in the detection of biallelic inactivation in BRCA1/2 than CHORD and resulted in a higher proportion of unexplained cases. When promoter methylation was excluded, in ovarian carcinoma, the proportion of unexplained cases increased from 26.8 to 48.8% for HRDetect and from 14.7 to 41.2% for CHORD. A similar increase was observed in breast cancer. Applying cancer-type-specific thresholds led to similar sensitivity and specificity for both methods. The cancer-type-specific thresholds for HRDetect reduced the number of unexplained cases from 21 to 12.3% without reducing the 96% sensitivity to known events. For CHORD, unexplained cases were reduced from 10 to 9% while sensitivity increased from 85.3 to 93.9%. Conclusion: These results suggest that WGS-based HRD classifiers should be adjusted for tumor types. When applied, only ∼10% of breast, ovarian, and pancreas cancer cases are not explained by known events in our dataset.

Sex-Related Differences in Outcomes for Oropharyngeal Squamous Cell Carcinoma by HPV Status.

Background: Overall survival for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) has differed by sex, but little is known regarding cancer-specific outcomes. We assessed the independent association of sex with cancer-specific survival in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: We identified 14,183 patients from the Surveillance, Epidemiology, and End Results (SEER) program with OPSCC and tumor HPV status. We used Kaplan-Meier methods to compare overall survival (OS) and OPSCC-specific survival (HNCSS) by patient sex and by tumor HPV status. We then separately fit multivariable survival and competing risk models evaluating the association of sex on these outcomes by tumor HPV status and stratified by the use of guideline-concordant OPSCC treatment. Results: A total of 10,210 persons with HPV-positive tumors (72.0%) and 3,973 with HPV-negative tumors (28.0%) were identified. A larger proportion of women had HPV-negative tumors (24.0%) versus HPV-positive tumors (13.2%; p < 0.001). Women with HPV-positive tumors were less likely to receive guideline-concordant treatment compared to men. In unadjusted survival analyses, women did not differ in OS or HNCSS compared to men for HPV-positive tumors but had worse OS and HNCSS for HPV-negative tumors. After adjustment, men and women with HPV-positive OPSCC did not differ in OS or HNCSS. However, women with HPV-negative tumors faced worse overall survival (hazard ratio (HR) 1.15, 95% CI 1.02-1.29) that persisted even after stratifying for stage-appropriate treatment (HR 1.28, 95% CI 1.11-1.47). Conclusions: Women with HPV-positive OPSCC had similar survival outcomes compared to men, but those with HPV-negative tumors have worse overall and cancer-specific survival.

Practices, attitudes, and confidence related to tobacco treatment interventions in HIV clinics: a multisite cross-sectional survey.

Tobacco use disorder (TUD) is a major threat to health among people with HIV (PWH), but it is often untreated. Among HIV clinicians and staff, we sought to characterize practices, attitudes, and confidence addressing TUD among PWH to identify potential opportunities to enhance provision of care. Cross-sectional deidentified, web-based surveys were administered from November 4, 2020 through December 15, 2020 in HIV clinics in three health systems in the United States Northeast. Surveys assessed provider characteristics and experience, reported practices addressing tobacco use, and knowledge and attitudes regarding medications for TUD. Chi-square tests or Fisher's exact tests were used to examine differences in responses between clinicians and staff who were prescribers versus nonprescribers and to examine factors associated with frequency of prescribing TUD medications. Among 118 survey respondents (56% prescribers), only 50% reported receiving prior training on brief smoking cessation interventions. Examining reported practices identified gaps in the delivery of TUD care, including counseling patients on the impact of smoking on HIV, knowledge of clinical practice guidelines, and implementation of assessment and brief interventions for smoking. Among prescribers, first-line medications for TUD were infrequently prescribed and concerns about medication side effects and interaction with antiretroviral treatments were associated with low frequency of prescribing. HIV clinicians and staff reported addressable gaps in their knowledge, understanding, and practices related to tobacco treatment. Additional work is needed to identify ways to ensure adequate training for providers to enhance the delivery of TUD treatment in HIV clinic settings.

Prostate Cancer Screening and Incidence among Aging Persons Living with HIV.

PURPOSE: The risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection. MATERIALS AND METHODS: We identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence. RESULTS: The mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status. CONCLUSIONS: When accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

Risks of Opportunistic Infections in People With Human Immunodeficiency Virus With Cancers Treated With Chemotherapy.

BACKGROUND: We ascertained incidence of opportunistic infections (OIs) in people with human immunodeficiency virus (PWH) with cancer undergoing chemotherapy with non-human immunodeficiency virus (HIV) comparators. METHODS: We identified 2106 PWH and 2981 uninfected Veterans with cancer who received at least 1 dose of chemotherapy between 1996 and 2017 from the Veterans Aging Cohort Study. We ascertained incident OIs within 6 months of chemotherapy amongst zoster, cytomegalovirus, tuberculosis, Candida esophagitis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, Cryptococcosis, atypical Mycobacterium infection, Salmonella bacteremia, histoplasmosis, coccidioidomycosis, or progressive multifocal leukoencephalopathy. We used Poisson methods to calculate OI incidence rates by HIV status, stratifying for hematological and nonhematological tumors. We compared OI rates by HIV status, using inverse probability weights of HIV status, further adjusting for PCP prophylaxis. RESULTS: We confirmed 106 OIs in 101 persons. Adjusted OI incidence rate ratios (IRRs) indicated higher risk in PWH for all cancers (IRR, 4.8; 95% confidence interval [CI], 2.8-8.2), hematological cancers (IRR, 8.2; 95% CI, 2.4-27.3), and nonhematological cancers (IRR, 3.9; 95% CI, 2.1-7.2). Incidence rate ratios were not significantly higher in those with CD4 >200 cells/mm3 and viral load <500 copies/mL (IRR, 1.8; 95% CI, 0.9-3.2). All PCP cases (n = 11) occurred in PWH, with 2 microbiologically unconfirmed cases among 1467 PWH with nonhematological cancers, no PCP prophylaxis, and CD4 counts >200/mm3. CONCLUSIONS: Veterans with HIV undergoing chemotherapy had higher rates of OIs than uninfected Veterans, particularly those with hematological cancers, but not in PWH with HIV controlled disease. Our study does not support systematic PCP prophylaxis in solid tumors in PWH with HIV controlled disease.

Lung Cancer Risk among Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Rationale: Chronic obstructive pulmonary disease (COPD) is a well-established independent risk factor for lung cancer; however, the literature on the association between asthma and lung cancer is mixed. Whether asthma-COPD overlap (ACO) is associated with lung cancer has not been studied. Objectives: We aimed to compare lung cancer risk among patients with ACO versus COPD and other conditions associated with airway obstruction. Methods: We studied 13,939 smokers from the National Lung Cancer Screening Trial who had baseline spirometry and used spirometric indices and history of childhood asthma to categorize participants into five specific airway disease subgroups. We used Poisson regression to compare unadjusted and adjusted lung cancer risk. Results: The incidence rate of lung cancer per 1,000 person-years was as follows: ACO, 13.2 (95% confidence interval [CI], 8.1-21.5); COPD, 11.7 (95% CI, 10.5-13.1); asthmatic smokers, 1.8 (95% CI, 0.6-5.4); Global Initiative for Chronic Obstructive Lung Disease-Unclassified, 7.7 (95% CI, 6.4-9.2); and normal spirometry smokers, 4.1 (95% CI, 3.5-4.8). Patients with ACO had increased adjusted risk of lung cancer compared with patients with asthma (incidence rate ratio [IRR], 4.5; 95% CI, 1.3-15.8) and normal spirometry smokers (IRR, 2.3; 95% CI, 1.3-4.2) in models adjusting for other risk factors. Adjusted lung cancer incidence in patients with ACO and COPD were not found to be different (IRR, 1.2; 95% CI, 0.7-2.1). Conclusions: The risk of lung cancer among patients with ACO is similar to those with COPD and higher than other groups of smokers. These results provide further evidence that COPD, with or without a history of childhood asthma, is an independent risk factor for lung cancer.

A SMARTTT approach to Treating Tobacco use disorder in persons with HIV (SMARTTT): Rationale and design for a hybrid type 1 effectiveness-implementation study.

BACKGROUND: Tobacco use disorder is a leading threat to the health of persons with HIV (PWH) on antiretroviral treatment and identifying optimal treatment approaches to promote abstinence is critical. We describe the rationale, aims, and design for a new study, "A SMART Approach to Treating Tobacco Use Disorder in Persons with HIV (SMARTTT)," a sequential multiple assignment randomized trial. METHODS: In HIV clinics within three health systems in the northeastern United States, PWH with tobacco use disorder are randomized to nicotine replacement therapy (NRT) with or without contingency management (NRT vs. NRT + CM). Participants with response (defined as exhaled carbon monoxide (eCO)-confirmed smoking abstinence at week 12), continue the same treatment for another 12 weeks. Participants with non-response, are re-randomized to either switch medications from NRT to varenicline or intensify treatment to a higher CM reward schedule. Interventions are delivered by clinical pharmacists embedded in HIV clinics. The primary outcome is eCO-confirmed smoking abstinence; secondary outcomes include CD4 cell count, HIV viral load suppression, and the Veterans Aging Cohort Study (VACS) Index 2.0 score (a validated measure of morbidity and mortality based on laboratory data). Consistent with a hybrid type 1 effectiveness-implementation design and grounded in implementation science frameworks, we will conduct an implementation-focused process evaluation in parallel. Study protocol adaptations related to the COVID-19 pandemic have been made. CONCLUSIONS: SMARTTT is expected to generate novel findings regarding the impact, cost, and implementation of an adaptive clinical pharmacist-delivered intervention involving medications and CM to promote smoking abstinence among PWH. ClinicalTrials.govidentifier:NCT04490057.

Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations.

BACKGROUND: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. METHODS: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). RESULTS: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). CONCLUSIONS: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

HIV-Infected Patients With Anal Cancer Precursors: Clinicopathological Characteristics and Human Papillomavirus Subtype Distribution.

BACKGROUND: People living with HIV have high rates of anal human papillomavirus infection and anal precancer/cancer. OBJECTIVE: This study aims to: 1) determine human papillomavirus subtype distribution among people living with HIV with anal high-grade squamous intraepithelial lesions; 2) compare the clinicopathological characteristics of patients with anal high-grade squamous intraepithelial lesions by human papillomavirus 16 status; and 3) investigate high-risk human papillomavirus negative anal high-grade squamous intraepithelial lesion cases. DESIGN: In this retrospective study, 700 people living with HIV who have biopsy-proven anal high-grade squamous intraepithelial lesions were reviewed for demographics, cytological diagnoses, and human papillomavirus testing results for human papillomavirus 16, 18, and 12 other high-risk types. For human papillomavirus-negative subjects, corresponding biopsies were genotyped by using real-time polymerase chain reaction. SETTINGS: This study was conducted in a large urban HIV clinic system and major referral center for anal cancer screening. PATIENTS: Median age was 46 years (range, 20-76). Ninety-one percent of the patients were men who have sex with men. MAIN OUTCOME MEASURES: The primary outcome measure was the association between demographic variables and human papillomavirus 16 status. RESULTS: Anal cytology was unsatisfactory (5%), benign (13%), atypical squamous cells of undetermined significance (35%), low-grade squamous intraepithelial lesion (36%), and high-grade squamous intraepithelial lesions (11%). Human papillomavirus cotesting results were negative (n = 38, 5%), human papillomavirus 16 (n = 303, 43%), human papillomavirus 18 (n = 78, 11%), or exclusively non-16/18 types (n = 281, 40%). Human papillomavirus 16 positivity was associated with ≥3 high-grade lesions and ≥ low-grade squamous intraepithelial lesion cytology (p < 0.001). Age, race/ethnicity, sex, smoking, CD4+ T-cell count, and HIV viral load did not differ by status of human papillomavirus 16 (p > 0.05). For human papillomavirus-negative cases, human papillomavirus genotyping of biopsies was positive for high-risk (n = 14, 36%) or possibly carcinogenic types (n = 12, 32%), or negative (n = 12, 32%). LIMITATIONS: This was a retrospective data analysis, and it pooled the results for 12 high-risk human papillomavirus types rather than individual types. CONCLUSIONS: Nearly all people living with HIV and anal high-grade squamous intraepithelial lesions test positive for high-risk human papillomavirus on anal swabs; negative results may be due to sampling error, L1-based polymerase chain reaction assay, or human papillomavirus types not captured by standard clinical assays. Patients who have human papillomavirus 16-positive anal high-grade squamous intraepithelial lesions are indistinguishable from others based on demographic and clinical characteristics, underscoring the potential role of human papillomavirus testing for anal cancer screening. See Video Abstract at http://links.lww.com/DCR/B208. PACIENTES PORTADORES DE VIH CON PRECURSORES DE CÁNCER DE ANO: CARACTERÍSTICAS CLINICOPATOLÓGICAS Y DISTRIBUCIÓN DEL SUBTIPO VPH: Los pacientes portadores de VIH tienen altas tasas de infección por VPH y alto riesgo de desarrolar lesiones precáncerosas / cáncerosas del ano.(1) Determinar la distribución del subtipo de VPH entre las personas portadoras de VIH con lesiones intraepiteliales escamosas anales de alto grado. (2) Comparar las características clinicopatológicas de pacientes con lesiones intraepiteliales escamosas anales de alto grado del subtipo VPH 16. (3) Investigar casos de lesiones intraepiteliales escamosas anales de alto grado negativas para el VPH de alto riesgo.Estudio retrospectivo sobre 700 personas portadoras de VIH con lesiones intraepiteliales escamosas anales de alto grado confirmadas por biopsia. Los datos fueron revisados para determinar información demográfica, diagnósticos citológicos y resultados de tipización en el VPH subtipos 16 y 18, y otros 12 tipos de alto riesgo. Para los individuos negativos al VPH, se analizó el genotipo en las biopsias correspondientes mediante test de PCR en tiempo real.Extenso sistema de clinicas urbanas tratando VIH y un importante centro de referencia para la detección del cáncer analla mediana de edad poblacional fue de 46 años (rango, 20-76). 91% eran hombres que tenían sexo con hombres.Asociación entre las variables demográficas y el estado del VPH subtipo16.la citología anal fue insatisfactoria (5%), benigna (13%), células escamosas atípicas de importancia indeterminada (35%), lesión intraepitelial escamosa de bajo grado (36%) y lesiones intraepiteliales escamosas de alto grado (11%). Los resultados de la prueba conjunta del VPH fueron negativos (n = 38, 5%), el virus del VPH subtipo 16 (n = 303, 43%), el VPH subtipo 18 (n = 78, 11%) o los subtipos exclusivamente no 16/18 (n = 281, 40%). La positividad del VPH subtipo 16 se encotraba asociado con ≥3 lesiones de alto grado y ≥ células escamosas atípicas en la prueba de citología de indeterminada importancia (p < 0.001). La edad, la raza / etnia, el sexo, el tabaquismo, el recuento de células T CD4 + y la carga viral del VIH no difirieron según el estado del VPH subtipo 16 (p > 0.05). Para los casos negativos al VPH, el genotipo del virus del papiloma humano de las biopsias fue positivo para los tipos de alto riesgo (n = 14, 36%) o posiblemente carcinogénicos (n = 12, 32%), o negativo (n = 12, 32%).Análisis de datos retrospectivos, con resultados agrupados para 12 tipos de VPH de alto riesgo en lugar de tipos individuales.Casi todas las personas portadoras de VIH con lesiones intraepiteliales escamosas anales de alto grado dan positivo para el VPH de alto riesgo al muestreo de hisopos anales; Los resultados negativos pueden deberse a un error en el muestreo y al análisis de PCR basado en L1 o subtipos de VPH no obtenidos en los ensayos clínicos estándar. Los pacientes con lesiones intraepiteliales escamosas anales de alto grado positivas para el VPH subtipo 16 no son identificables de los demás, en función de las características demográficas y clínicas, lo que minimiza el rol potencial de la prueba del VPH en la detección del cáncer anal. Consulte Video Resumen en http://links.lww.com/DCR/B208. (Traducción-Dr. Xavier Delgadillo).

Electrocautery ablation of anal high-grade squamous intraepithelial lesions: Effectiveness and key factors associated with outcomes.

BACKGROUND: Electrocautery ablation (EA) is a common treatment modality for patients with anal high-grade squamous intraepithelial lesions (HSILs), but to the authors' knowledge its effectiveness has been understudied. The objective of the current study was to determine ablation outcomes and to identify clinicopathological factors associated with postablation disease recurrence. METHODS: A total of 330 people living with HIV with de novo intra-anal HSIL who were treated with EA from 2009 to 2016 were studied retrospectively. Using long-term, surveillance high-resolution anoscopy biopsy data, treatment failures were classified as local recurrence (HSIL noted at the treated site at the time of surveillance) or overall recurrence (HSIL noted at treated or untreated sites). The associations between these outcomes and clinical factors were analyzed using Cox proportional hazards models. RESULTS: Approximately 88% of participants were men who have sex with men. The median age of study  participants was 45.5 years (range, 35-51 years) and approximately 49% had multiple index HSILs (range, 2-6 index HSILs). At a median of 12.2 months postablation (range, 6.3-20.9 months postablation), approximately 45% of participants had developed local recurrence whereas 60% had developed overall recurrence. Current cigarette smoking, HIV viremia (HIV-1 RNA ≥100 copies/mL), and multiple index HSILs were found to be predictive of local recurrence. Overall recurrence was more common in current smokers and those with multiple index lesions. In multivariable models that included human papillomavirus (HPV) genotypes, baseline and persistent infections with HPV-16 and/or HPV-18 were found to be significantly associated with both local and overall recurrence. CONCLUSIONS: EA is an effective treatment modality for anal HSIL in people living with HIV, but rates of disease recurrence are substantial. Multiple index HSILs, HIV viremia, current cigarette smoking, and both baseline and persistent infection with HPV-16 and/or HPV-18 appear to negatively impact treatment success. Ongoing surveillance is imperative to capture recurrence early and improve long-term treatment outcomes.

Short-term outcomes for lung cancer resection surgery in HIV infection.

OBJECTIVE: Lung cancer is the leading cause of cancer death in people living with HIV (PWH). Surgical resection is a key component of potentially curative treatment regimens for early-stage lung cancers, but its safety is unclear in the setting of HIV. From a national cohort, we assessed potential differences in the risk of major lung cancer surgery complications by HIV status. DESIGN: We linked clinical and cancer data from the Veterans Aging Cohort Study (VACS) and Veterans Affairs Corporate Data Warehouse to outcomes from the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and identified 8371 patients (137 PWH, 8234 uninfected) who underwent lung cancer surgeries between 2000 and 2016. METHODS: We compared rates of 15 major short-term surgical complications by HIV status. RESULTS: Use of surgical resection for early-stage lung cancer did not differ by HIV status. Lung cancer surgery postoperative (30-day) mortality was 2.0% for PWH and did not differ by HIV status (P = 0.9). Pneumonia was the most common complication for both PWH and uninfected veterans, but did not differ significantly in prevalence between groups (11.0% for PWH versus 9.4%; P = 0.5). The frequency of complications did not differ by HIV status for any complication (all P > 0.3). There were no significant predictors of postoperative complications for PWH. CONCLUSIONS: In a national antiretroviral-era cohort of lung cancer patients undergoing surgical lung resection, short-term outcomes after surgery did not differ significantly by HIV status. Concerns regarding short-term surgical complications should have limited influence on treatment decisions for PWH with lung cancer.

Increasing Access to Hepatitis C Virus Medications: A Program Model Using Patient Navigators and Specialty Pharmacy to Obtain Prior Authorization Approval.

BACKGROUND: Obtaining prior authorization (PA) approval for the new direct-acting antiviral (DAA) hepatitis C medications is time consuming and requires specific expertise. Our primary care-based program treats hepatitis C virus (HCV)-infected patients at an urban academic medical center and employs patient navigators trained in the PA process who collaborate with a nurse and specialty pharmacy to manage the PA process. OBJECTIVE: To demonstrate the rate of PA approvals for our programmatic model and determine potential predictors of PA approval. METHODS: We conducted a review of program databases and medical records of patients for whom DAA hepatitis C medications were ordered between November 1, 2014, and October 31, 2015 (n = 197). We first evaluated patient characteristics associated with the number of steps to approval. Then we used a multivariable ordinal regression to determine independent predictors of fewer steps to approval. Using Kaplan-Meier methods, we assessed patient characteristics associated with approval time and then fit a multivariable Cox regression model to determine independent predictors of time to approval. RESULTS: Of the 197 patients, 69% (n = 136) had Medicaid; 12% (n = 24) had Medicare; 10% (n = 19) had both Medicaid and Medicare; 5% (n = 10) had private insurance; and 4% (n = 8) were uninsured. Ninety-three percent of the patients were eventually approved for HCV treatment. The steps in the PA cascade were approval on first submission (37%; mean days = 30.7; SD = 29.9); approval after internal appeal (45%; mean days = 66.8; SD = 70.5); approval after external appeal (11%; mean days = 124.7; SD = 60.2); and no approval obtained (7%). Unadjusted factors found to have a P value < 0.200 in relation to fewer steps in the PA cascade were older age, female gender, non-Medicaid insurance, comorbid hypertension, comorbid diabetes, being domiciled, and being nongenotype 2. After adjustment, non-Medicaid insurance and nongenotype 2 remained significant. In survival analysis, non-Medicaid insurance and mid-range fibrosis were associated with fewer days to PA approval. CONCLUSIONS: Our program obtained 93% of PA approvals for hepatitis C medications. Patient navigators collaborating with a nurse and specialty pharmacy as a program may improve the PA approval process, although further research with a control group is necessary. DISCLOSURES: The Respectful & Equitable Access to Comprehensive Healthcare (REACH) program receives funding from the Robin Hood Foundation and the New York State Department of Health AIDS Institute. Weiss receives grant support from Gilead Sciences and has served as a consultant for AbbVie and Gilead Sciences. Vu reports speaker fees from Peer View Institute. All other authors report no conflict of interest. Study design and concept were contributed by Chasan, Sigel, Vu, and Weiss. Riazi, Ciprian, Giardina, and Gibbs collected the data, which were interpreted by Toribio, Amory, Chasan, and Sigel. The manuscript was written by Vu and Weiss and revised by Parrella, Cambe, Camacho, and Vu. Research from this study was presented as an abstract poster on November 14, 2016, at the AASLD Liver Meeting in Boston, Massachusetts.

Well differentiated grade 3 pancreatic neuroendocrine tumors compared with related neoplasms: A morphologic study.

BACKGROUND: Pancreatic neuroendocrine neoplasms with a Ki-67 labeling index greater than 20% were reclassified in 2017 by the World Health Organization into well differentiated (WD) and poorly differentiated grade 3 neuroendocrine carcinoma (NEC). The authors describe the cytologic features of grade 3 WD pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NEC. METHODS: Fine-needle aspirates from 65 pancreatic neuroendocrine neoplasms were reviewed, and their cytomorphologic features were compared across grade 2, WD grade 3, and PD small cell type (PD-S), large cell type (PD-L), and type not otherwise specified (PD-NOS) neoplasms. RESULTS: The 65 aspirates consisted of 19 grade 2 neoplasms, 32 WD grade 3 neoplasms, and 14 NECs (6 PD-S, 5 PD-L, and 3 PD-NOS). The medians Ki-67 proliferation index was 11% (range, 3.2%-17%) in grade 2 neoplasms, 40% (range, 21%-89%) in WD grade 3 neoplasms, 80% (range, 63%-95%) in PD-S neoplasms, 39% (range, 25%-61%) in PD-L neoplasms, and 70% (range, 30%-80%) in PD-NOS neoplasms. Both grade 2 and WD grade 3 neoplasms were associated with plasmacytoid morphology and smooth nuclear contours, but WD grade 3 neoplasms had significant increases in abundant cytoplasm (72% vs 17%; P = .007), nuclear tangles (75% vs 42%; P = .006), and apoptosis (86% vs 58%; P = .005). Compared with NECs, WD grade 3 neoplasms had increased plasmacytoid morphology (75% vs 7%; P < .001), smooth nuclear contours (94% vs 64%; P = .02), round nuclei (59% vs 21%; P = .01), and less pleomorphism (13% vs 50%; P = .004), molding (9% vs 79%; P < .001), and necrosis (13% vs 43%; P = .003). WD grade 3 neoplasms had less pleomorphism (13% vs 50%; P = .04), less necrosis (13% vs 60%; P = .04), and more plasmacytoid morphology (75% vs 20%; P = .03) than PD-L. CONCLUSIONS: The prevalence of cytologic features differs in WD grade 3 pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NECs, and these differences assist in the recognition of this newly classified entity. Cancer Cytopathol 2018;126:326-35. © 2018 American Cancer Society.

Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine neoplasms: A multi-institutional study.

BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic neuroendocrine neoplasms are biologically distinct entities with different therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%) have been shown to have an overlapping histology with PD neuroendocrine carcinomas. This study compared expert cytomorphologic assessments of differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health Organization classification; n = 72) were diagnosed independently by 3 cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or poorly differentiated small cell type [PD-S]) purely on the basis of cytomorphology. Their diagnoses were compared with a final classification supported by immunohistochemistry (retinoblastoma (RB), death domain- associated protein (DAXX), and α thalassemia/mental retardation syndrome X-linked (ATRX) protein expression), targeted mutation analysis (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets), prior history of G1/G2 histology, and consensus. RESULTS: The rate of agreement on differentiation was 38% (15 WD cases and 12 PD cases) for the 70 cases included (55 WD cases [n = 19 G2, n = 31 G3, and n = 5 could not be graded] and 15 PD cases [n = 6 PD-S, n = 6 PD-L, and n = 3 PD, not otherwise specified). Two cases could not be classified by the employed methods. PD carcinomas had a higher rate of agreement (10 of 15 [67%]) than WD neoplasms (15 of 55 [27%]). Round nuclei and plasmacytoid cells were associated with agreement for WD cases, whereas apoptosis and angulated nuclei were associated with disagreement. Necrosis was associated with agreement for PD cases. CONCLUSIONS: A purely morphologic approach to the distinction between G2 and G3 pancreatic neuroendocrine neoplasms based on cytology can be challenging, with disagreement found among experienced cytopathologists. Cancer Cytopathol 2018;126:44-53. © 2017 American Cancer Society.

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results.

AIM: To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. METHODS: The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response - the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response (SVR) 12] - were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression. RESULTS: SVR12 rates were as follows: 86% (95%CI: 80%-91%) among 178 patients on SMV/SOF ± RBV; 62% (95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78% (95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR12 were $174442 (standard deviation: ± $18588) for SMV/SOF ± RBV; $223003 (± $77946) for SOF/RBV; and $126496 (± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio (OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin (OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR12 (OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION: SVR12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.