Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Anaplastic large cell lymphoma in human immunodeficiency virus-infected people and solid organ transplant recipients.

Human immunodeficiency virus (HIV)-infected people and solid organ transplant recipients have elevated risk of anaplastic large cell lymphoma (ALCL). Little is known regarding ALCL risk factors in immunosuppressed populations. We used data from US cancer registries linked to HIV registries (1996-2016) and to the national transplant registry (1992-2017). ALCL risk in HIV-infected people and transplant recipients relative to the general population was calculated as a standardized incidence ratio (SIR). ALCL risk factors were evaluated using Poisson regression. We identified 121 incident ALCL cases in the HIV (n = 86) and transplant (n = 35) populations. We reviewed pathology reports for 45 cases and most (86·7%) were confirmed as ALCL. Epstein-Barr virus tested positive in 1/8 (12·5%) cases. Compared to the general population, ALCL risk was strongly elevated among HIV-infected people [SIR 5·43; 95% confidence interval (CI) 4·27-6·81] and transplant recipients (5·96; 4·03-8·49). Among HIV-infected people, ALCL incidence was strongly related to CD4 count [adjusted incidence rate ratio (aIRR) 0·15 for ≥500 vs. <200 cells/µl; P trend < 0·001]. Among transplant recipients, risk was highest within the first year (aIRR 6·82) and 10+ years post-transplant (5·99). In conclusion, ALCL risk is strongly increased in these immunosuppressed populations but may be unrelated to EBV infection based on limited reports.

Assessment of Anal Cancer Screening Tools in Detecting High-Grade Anal Squamous Intraepithelial Lesions in Women.

OBJECTIVE: The aim of the study was to evaluate the validity of anal cytology against high-resolution anoscopy in the detection of anal high-grade squamous intraepithelial lesions (HSILs) among women in a clinical setting in Puerto Rico, alone and in combination with high-risk human papillomavirus (HR-HPV) typing. MATERIALS AND METHODS: A cross-sectional study was done among 128 eligible women who attended the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Center between 2014 and 2019. Kappa (κ) coefficient, sensitivity, specificity, positive predictive value, and negative predictive value were calculated using high-resolution anoscopy with biopsy as the criterion standard test. Poisson regression was used to estimate the adjusted prevalence ratio of anal HR-HPV infection. RESULTS: Overall, 71.1% of women were HIV infected and 78.9% had anal HR-HPV infection. Squamous intraepithelial lesions were detected with anal cytology and histology in 70.3% and 81.3% of women, respectively. The κ statistic between the tests (cytology and histology) was 0.32 (p < .05). Measured against the results from histology, the sensitivity of anal cytology alone to detect HSIL was 85.4% (95% CI = 72.2%-93.9%), whereas specificity was 38.8% (95% CI = 28.1%-50.3%). Although the sensitivity of the 2 tests combined (anal cytology and HR-HPV typing) to detect histologically confirmed HSIL increased (100.0%, 95% CI = 92.6%-100.0%), the specificity decreased (16.3%, 95% CI = 9.0%-26.2%). Meanwhile, women with HSIL had a higher prevalence of anal HR-HPV infection than those with no SIL/LSIL (prevalence ratio = 6.23, 95% CI = 1.50-25.83). CONCLUSIONS: Anal cytology in combination with HR-HPV typing for the screening of anal intraepithelial neoplasia improved the detection of HSIL in women.

Human Papillomavirus Correlates With Histologic Anal High-Grade Squamous Intraepithelial Lesions in Hispanics With HIV.

OBJECTIVE: To estimate the magnitude of association between anal infection with high-risk human papilloma virus (HR-HPV) types and severity of biopsy-confirmed histopathological anal squamous intraepithelial lesions (SILs) among a clinic-based sample of HIV-infected adults in Puerto Rico. METHODS: This cross-sectional study analyzed data from medical records of adult patients who visited a specialized anal neoplasia clinic from June 2015 to December 2017 (n = 239); sociodemographics, behavioral risk factors, medical history, clinical data, and pathology reports were collected. The magnitude of association between anal HR-HPV and severity of anal SIL, adjusted for potential confounders, was assessed using a multinomial logistic model. RESULTS: A 78.7% of patients had anal HR-HPV infection, 43.9% had histopathological low-grade SIL (LSIL), and 37.7% had histopathological high-grade SIL (HSIL). The prevalence of anal HR-HPV infection was 63.6% among patients with no anal SIL, 70.5% for those with LSIL and 95.6% for those with HSIL. After adjusting for different predictors, patients with anal HR-HPV infection were more likely to have HSIL (odds ratio, 11.0; 95% confidence interval, 3.2-37.2) than those without anal HR-HPV infection, whereas no significant excess was observed for LSIL (odds ratio, 1.4; 95% confidence interval, 0.6-3.1). CONCLUSIONS: This study showed a strong association between anal HR-HPV infection and HSIL. Likewise, a high prevalence of anal HR-HPV infection and presence of anal SIL was observed among HIV-infected individuals. Our result highlights the importance of screening for anal HR-HPV infection and anal SIL and optimizing strategies for HPV vaccination in HIV-infected individuals.

The Health related Quality of Life of Puerto Ricans during Cancer Treatments; A Pilot Study.

OBJECTIVE: To examine the health related quality of life (HRQOL) experienced by 79 Puerto Rican adults during cancer treatments. METHODS: This study used a descriptive, cross-sectional design. Participants completed a demographics form and the Functional Assessment of Cancer Therapy-General QOL questionnaire (FACT-G). Descriptive statistics were generated. RESULTS: Participants were ages 28-78; most of the participants had breast (38.0%), prostate (14.0%) and cervical and ovarian cancers (10.1%) treated with chemotherapy (45.6%). The participants had a mean total score on the FACT-G of 75.2 (SD = 18.9). As a group, the functional well-being was the most affected (mean 17.2, SD 6.8), and the Social/Familial was the least affected (mean 20.7, SD 6.0). CONCLUSION: Cancer is the leading cause of death in the island of Puerto Rico. Female Puerto Rican cancer patients in this study sample had increased risk for experiencing worse: overall HRQOL, physical well-being and emotional well-being compared to males. Given that the Hispanic oncology population does not always report symptoms, risking under-assessment and under management, this suggests there may be a greater need for HRQOL surveillance for this population.

Longitudinal social cognitive influences on physical activity and sedentary time in Hispanic breast cancer survivors.

OBJECTIVE: This study evaluated the effect of two home-based exercise interventions (one culturally adapted and one standard) on changes in social cognitive theory (SCT) variables, physical activity (PA), and sedentary time (ST), and determined the association between changes in SCT variables and changes in PA and ST in Hispanic breast cancer survivors. METHOD: Project VIVA! was a 16-week randomized controlled pilot study to test the effectiveness and feasibility of a culturally adapted exercise intervention for Mexican American and Puerto Rican breast cancer survivors in Houston, Texas and San Juan, Puerto Rico, respectively. Women (N = 89) completed questionnaires on SCT variables, PA, and ST and were then randomized to a 16-week culturally adapted exercise program, a non-culturally adapted standard exercise intervention or a wait-list control group. Multiple regression models were used to determine associations between changes in SCT variables and changes in PA and ST. RESULTS: Participants were in their late 50s (58.5 ± 9.2 years) and obese (31.0 ± 6.5 kg/m2 ). Women reported doing roughly 34.5 min/day of PA and spending over 11 h/day in sedentary activities. Across groups, women reported significant increases in exercise self-efficacy and moderate-intensity, vigorous-intensity, and total PA from baseline to follow-up (p < 0.05). Increased social support from family was associated with increases in vigorous-intensity PA. Increases in social modeling were associated with increases in moderate-intensity and total PA and with decreases in ST from baseline to follow-up (p < 0.05). CONCLUSIONS: Hispanic cancer survivors benefit from PA interventions that focus on increasing social support from family and friends and social modeling. Copyright © 2015 John Wiley & Sons, Ltd.

Factors Associated to Invasive Fungal Infection in Hispanic Patients with Hematological Malignancies.

Fungal infections represent a serious complication for immunosuppressed patients resulting in an increased morbidity and mortality. A non-concurrent prospective study was performed to evaluate the factors associated to invasive fungal infection (IFI) in patients with hematological malignancies admitted to the University Hospital in San Juan, Puerto Rico from January 1st, 2011 through June 15th, 2014. The medical records of 84 patients were evaluated. Fifty-nine patients with IFI and twenty-five without IFI. The majority were men between 35 to 55 years old. The main hematological diagnosis was acute myelogenous leukemia (AML) followed by acute lymphoblastic leukemia (ALL). Seventy-percent developed IFI. The most common fungi were C. albicans followed by non-albicans species, Fusarium and, Aspergillus species, respectively. About 63% of the patients with AML and 81% without AML had IFI. Those who received steroids were more likely to develop IFI. After adjusting for AML and age, the odds of IFI among patients using steroids were 3.33 higher than those not using steroids. Patients who were exposed to different antifungal medication had 72% lower odds to develop IFI.

Physical Activity in Puerto Rican Breast Cancer Survivors.

OBJECTIVE: Breast cancer survivors do not engage in appropriate levels of physical activity, despite the known benefits of such activity. This study aims to describe physical-activity levels and the barriers to it in a group of Puerto Rican breast cancer survivors, as well as detailing their preferences for an intervention. METHODS: Participants who finished their chemotherapy and/or radiotherapy for breast cancer at least 4 months prior to the study were included. Demographic, anthropometric, and clinical data were obtained. The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and questionnaires on exercise self-efficacy, barriers to self-efficacy, modeling, and social support were filled out by study participants. Data on access to exercise equipment and preferences regarding a physical-activity intervention were collected. Descriptive statistics and correlation analyses were performed. RESULTS: Fifty breast cancer survivors were recruited. Almost all the participants reported that they did not engage in any kind of strenuous physical activity (94%), with more than three fourths (76%) reporting that they did not even participate in any kind of moderate physical activity. The GLTEQ score was associated with barriers to selfefficacy, while the association with exercise self-efficacy approached significance (p = 0.055). Nearly half of the patients (44%) had access to exercise equipment. Preferred methods for the delivery of physical-activity interventions were participating in group settings (72%) and receiving material in the postal mail (44%). CONCLUSION: The study described herein reports on the low levels of physical activity being practiced by a group of Puerto Rican breast cancer survivors, despite the fact that many of them had access to exercise equipment and facilities. Further studies aimed at understanding breast cancer survivors' barriers to physical activity and at developing culturally competent interventions to increase the levels of such activity are warranted.

Quality of life-in patients with differentiated thyroid cancer at the general endocrinology clinics of the University Hospital of Puerto Rico.

UNLABELLED: Differentiated thyroid cancer (DTC) can compromise the quality of life of patients. Our purpose is to investigate if the quality of life, in a cohort of patients in Puerto Rico, is affected by the diagnosis and/or treatment modalities received for DTC. METHODS: This is a cross-sectional study of 75 subjects with DTC. A Spanish version of the University of Washington Quality of Life Questionnaire was used, including multiple aspects of physical and social functioning. Descriptive and bivariate analysis between domain scores and variables of interest were performed. RESULTS: 82.7% of the patients reported that their health was the same or better than it was before treatment. The mean composite score obtained was 82.3, reflecting an overall little effect on quality of life. Patients diagnosed with DTC at an age of > or =45 years reported a significantly better score on the pain domain when compared with those diagnosed earlier (p < 0.05). Patient who received >150 mCi of radioiodine had a tendency towards a worse score on the same domain (p = 0.05). CONCLUSIONS: Our cohort reported an overall minimal effect on the quality of life of patients with DTC. Future treatment strategies should include periodic quality of life evaluations, in order to tailor therapy in this growing population.

Effect of type of health insurance coverage on leukemia survival in adults in Puerto Rico.

OBJECTIVE: In Puerto Rico, leukemia is among the top 10 cancers in terms of incidence and mortality. The aim of the study described herein was to establish the overall leukemia survival rate in Puerto Rico and determine whether there are differences in leukemia survival by type of health insurance coverage. METHODS: Data for adult patients (aged > or = 20 years) diagnosed with leukemia were provided by the Puerto Rico Central Cancer Registry. The relative survival rates (1, 3, and 5 years) were estimated for leukemia patients (diagnosed from 2004 through 2006) by type of health insurance (government health plan [GHP] or non-government health plan [NGHP]). Relative survival is defined as observed survival in the cohort divided by expected survival in the cohort. A Poisson regression model was used to analyze the relative excess risk of death for both the GHP and the NGHP groups. RESULTS: A total of 516 leukemia patients were eligible for analysis. The overall survival rates of leukemia patients in PR for 1, 3, and 5 years after diagnosis were 55.8%, 40.5%, and 34.7%, respectively. Relative survival rates were lower for patients with GHP (1 year = 52.8%; 3 years = 36.4%; 5 years = 32.2%) than they were in people with NGHP (1 year = 57.5%; 3 years = 42.8%; 5 years = 36.1%). Among patients aged 65+ years, those with GHP had a 1.58-fold (95% CI: 1.11-2.27) higher risk of death than did those patients with NGHP. CONCLUSION: Several factors could explain the disparities observed in leukemia survival rates (as grouped by health insurance status) in PR. Some of them include differences in patterns of healthcare coverage, in delays in treatment, in quality of service, in risk factors, and co-morbidities present in the older population studied.

Clinical and pathological features of colorectal cancer in patients at a community hospital in Puerto Rico.

OBJECTIVE: Colorectal cancer (CRC) is among the most common cancers in Puerto Rico. Few studies have correlated clinical and pathological variables with the overall survival of CRC patients in Puerto Rico. We report the clinical and pathological characteristics of patients who underwent surgical resection at a community hospital in Puerto Rico. METHODS: Demographic and pathological variables of patients who underwent CRC surgery at Hospital del Maestro from 2006 through 2011 were reviewed. Descriptive statistics (mean, range, and frequency) and the Cox proportional hazards model were used to determine the influence of demographic and pathological variables on survival, after adjusting for age. RESULTS: Two hundred and five CRC pathology reports were reviewed. Adenocarcinoma represented the most common pathology (202/205; 98.5%). Females represented 52% of the population (106/202) while males represented 48% (96/202). The median age was 71 years (30-96). The right colon was the most common site of presentation (49.7%; 100/201). Stage III was the most common stage at presentation. The presence of mucin, perineural or lymphatic invasion and tumor size were not related to decreased survival. Being male, having a higher stage at diagnosis, and having a moderately or poorly differentiated tumor were characteristics related to decreased survival. CONCLUSION: This study provides information on clinical and pathological variables and their influence on the overall survival of CRC patients at a community hospital in Puerto Rico. Further research must be performed to identify potential disparities and their influence on the prognosis of this patients.

Association of tobacco use and the presence of anal warts in people who attend the anal Neoplasia clinic in Puerto Rico.

Background: Limited research exists regarding the association between smoking and anal warts. In this study, we evaluated this association among a clinic-based Hispanic population in Puerto Rico. Methods: Cross-sectional study among eligible patients seen at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (2016-2023) (n = 920). Sociodemographic and clinical variables were collected from medical records. Patients underwent a high-resolution anoscopy (HRA) during the clinical visit; physicians assessed anal condylomas on HRA. Poisson regression models with robust standard errors were used to evaluate the association between smoking and anal warts. Demographic and clinical factors were also assessed. Results: The mean age of participants was 45.8 ± 13.1 years, 66.4 % were men, and 21.6 % were current smokers. While 10.8 % self-reported a history of anogenital condylomas, 18.9 % had anal condylomas on clinical evaluation. A higher prevalence of anal condylomas was observed among current smokers (PR = 1.28, 95 % CI: 0.94-1.75) in comparison to non-smokers in adjusted analysis, but this was not statistically significant. However, a higher prevalence of anal condylomas was observed among younger individuals (PR = 0.96, 95 % CI: 0.96-0.98) and individuals with anal high-grade squamous intraepithelial lesions (HSIL) as compared to those with benign histology (PR = 1.74. 95 % CI: 1.09-2.77). Conclusions: Although current smoking seemed to be positively associated with anal condylomas in this high-risk Hispanic population, this finding was not statistically significant as the power to detect an association was limited. However, younger age and HSIL diagnosis were associated with a higher prevalence of anal condylomas.

Development of a multivariable prediction model for anal high-grade squamous intraepithelial lesions in persons living with HIV in Puerto Rico: a cross-sectional study.

Background: Persons living with HIV (PLWH) are at high risk of developing anal high-grade squamous intraepithelial lesions (HSIL). We aimed to develop a prediction model for anal HSIL based on individual characteristics of PLWH. Methods: Cross-sectional study of PLWH aged ≥21 years who attended the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center from 2016 to 2022. The primary outcome was biopsy-confirmed anal HSIL. For each sex, relations between potential predictors and HSIL were examined using univariate (ULRM) and multivariable (MLRM) logistic regression models. Risk modelling was performed with MLRM and validated with bootstrapping techniques. The area under the ROC Curves (AUC) was estimated with 95% CI. Findings: HSIL was detected among 45.11% of patients, 68.48% were males, and 59.42% were ≥45 aged. Multivariable analysis showed that, in women, the only significant predictor for HSIL was having a previous abnormal anal cytology (p = 0.01). In men, significant predictors for HSIL were having a previous abnormal anal cytology (p < 0.001) and a history of infection with any gonorrhoea (p = 0.002). Other suggestive predictors for HSIL among women were obesity and smoking. No association between smoking and HSIL among men was observed (p < 0.05). The AUC estimated among women (0.732, 95% CI: 0.651-0.811) was higher than in men (0.689, 95% CI: 0.629-0.748). Interpretation: Our results support that the inclusion of individual characteristics into the prediction model will adequately predict the presence of HSIL in PLWH. Funding: This work was supported by the NCI (Grants #U54CA096297, #R25CA240120), the NIGMS (Grant #U54GM133807), and the NIMHD (Grant #U54MD007587).

Evaluating the performance of anal cytology and high-risk HPV genotyping for detecting anal HSIL in a clinic-based sample of people living with and without HIV in Puerto Rico.

BACKGROUND: Given the disproportionately elevated anal cancer risk in high-risk populations, it is important to assess the performance of commonly used anal cancer screening tools to improve the effectiveness of detection and treatment methods. This study evaluates 1) the concordance between anal cytology and histology results and 2) the performance of cytology and high-risk human papillomavirus (HR-HPV) genotyping as screening tools for detecting histologically confirmed anal high-grade squamous intraepithelial lesions (HSIL). METHODS: Data from the Anal Neoplasia Clinic in Puerto Rico (2014-2021; n = 466) was used. The clinical performance of anal cytology and HR-HPV genotyping to detect HSIL was compared to the gold standard: high-resolution anoscopy-guided biopsy. Sensitivity, specificity, positive predictive value, negative predictive value, and κ coefficients were calculated. RESULTS: A total of 66.95% of the patients were men, 74.0% were people living with HIV, 76.2% had anal HR-HPV infection, and 40.34% had histologically confirmed anal HSIL. The weighted κ statistic between the tests (cytology and histology) was 0.25 (p < .001). The sensitivity and specificity of cytology alone to detect anal HSIL were 84.3% (95% confidence interval [CI], 78.3%-89.1%) and 36.0% (95% CI, 30.3%-42.0%), respectively. Anal HR-HPV genotyping had higher sensitivity (92.2%; 95% CI, 87.4%-95.6%) and similar specificity (34.8%; 95% CI, 29.2%-40.7%) compared to cytology. The two tests combined (positive results following cytology or HR-HPV test) improved sensitivity to detect anal HSIL (97.9%; 95% CI, 94.8%-99.4%), but specificity was compromised (19.2%; 95% CI, 14.7%-24.4%). CONCLUSION: Although HR-HPV genotyping improved the detection of anal HSIL, HR-HPV testing had lower specificity than anal cytology alone.

Lower Gastrointestinal Bleeding Because of Kasabach-Merritt Syndrome Showing an Impressive Response to Sirolimus.

Kasabach-Merritt syndrome is a rare but life-threatening disease in which a rapidly growing vascular tumor induces localized intravascular coagulation, causing thrombocytopenia, microangiopathic hemolytic anemia, and consumption coagulopathy. It presents mainly in infants and young children. We present an adult with recurrent and severe lower gastrointestinal bleeding due to Kasabach-Merritt syndrome, treated successfully with sirolimus after multiple other failed interventions.

Association of smoking with anal high-risk HPV infection and histologically confirmed anal high-grade squamous intraepithelial lesions among a clinic-based population in Puerto Rico.

INTRODUCTION: Current smoking is a risk factor for anal cancer. Yet, its association with anal human papillomavirus infection (HPV) and anal high-grade squamous intraepithelial lesions (HSIL) remains unclear. We assessed the association of smoking with 1) anal high-risk HPV (HR-HPV) infection and 2) anal HSIL. METHODS: Data from the baseline visit of patients from the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (May 2015- June 2021) was analyzed. Patients were eligible if they had information on smoking status, complete high-resolution anoscopy (HRA) with biopsy, and HR-HPV testing (n =  427). Logistic regression models estimated the odds ratio (OR) with 95% confidence intervals (CIs) adjusting for covariates. RESULTS: Mean age was 44 ± 13 years, 69% were men, 74% were HIV-infected, and 25% reported being current smokers. 74% had anal HR-HPV infection. HSIL was diagnosed in 40% of patients. Current smokers had significantly higher odds (OR: 1.71, 95% CI: 1.04-2.82) of having HSIL compared to non-smokers after adjusting for age, sexual risk group, lifetime number of sexual partners, HIV status, and HR-HPV infection. Smoking was not associated with HR-HPV infection (OR: 1.56, 95% CI: 0.83-2.95) after adjusting for age, sexual risk group, lifetime number of sexual partners, and HIV status. CONCLUSIONS: Current smoking was associated with histologically confirmed HSIL but not with HR-HPV infection among this high-risk Hispanic population. Results highlight the need to explore targeted smoking cessation campaigns among populations at higher risk of developing HSIL, as an anal cancer prevention strategy.

Co-Occurrence of Symptoms and Gut Microbiota Composition Before Neoadjuvant Chemotherapy and Radiation Therapy for Rectal Cancer: A Proof of Concept.

PURPOSE: To examine a) whether there are significant differences in gut microbial diversity and in the abundance of gut microbial taxa; and b) differences in predicted functional pathways of the gut microbiome between those participants with high co-occurring symptoms and those with low co-occurring symptoms, prior to neoadjuvant chemotherapy and radiation therapy (CRT) for rectal cancer. METHODS: Rectal cancer patients (n = 41) provided stool samples for 16 S rRNA gene sequencing and symptom ratings for fatigue, sleep disturbance, and depressive symptoms prior to CRT. Descriptive statistics were computed for symptoms. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. RESULTS: Participants with high co-occurring symptoms (n = 19) had significantly higher bacterial abundances of Ezakiella, Clostridium sensu stricto, Porphyromonas, Barnesiella, Coriobacteriales Incertae Sedis, Synergistiaceae, Echerichia-Shigella, and Turicibacter compared to those with low co-occurring symptoms before CRT (n = 22). Biosynthesis pathways for lipopolysaccharide, L-tryptophan, and colanic acid building blocks were enriched in participants with high co-occurring symptoms. Participants with low co-occurring symptoms showed enriched abundances of Enterococcus and Lachnospiraceae, as well as pathways for ß-D-glucoronosides, hexuronide/hexuronate, and nicotinate degradation, methanogenesis, and L-lysine biosynthesis. CONCLUSION: A number of bacterial taxa and predicted functional pathways were differentially abundant in patients with high co-occurring symptoms compared to those with low co-occurring symptoms before CRT for rectal cancer. Detailed examination of bacterial taxa and pathways mediating co-occurring symptoms is warranted.

Effectiveness of a Home-Based Exercise Intervention in the Fitness Profile of Hispanic Survivors of Breast Cancer.

BACKGROUND: Home-based exercise interventions might be a desirable long-term option for breast cancer survivors to enhance compliance and long-term health benefits. PURPOSE: To assess the effectiveness of a home-based intervention aimed at helping survivors of breast cancer meet the physical activity guidelines of the American College of Sports Medicine. METHODS: Eighty-nine women (age: 55.4 ± 10 years; BMI: 31 ± 6.5 kg/m2) from two cancer centers serving Hispanic women participated in this study. Women performed a baseline assessment of cardiorespiratory fitness, muscle endurance and strength, flexibility, range of motion, and extremity disability. After baseline measures, women were randomized into a control (C) or exercise (E) group. The exercise intervention consisted of a walking program, elastic band strengthening, and flexibility exercises performed at home. The outcome measures were reassessed 16 weeks after baseline measures. RESULTS: The intervention showed a strong effect of time on muscle strength and shoulder range of motion, and time and group for self-reported disability. There were no differences in sedentary behavior, physical fitness, and disability measures across intervention groups, including both exercise groups combined and changes over time between intervention groups. CONCLUSION: It appears that a home-based intervention affects only upper body strength and related disability, indicating that other components might need closer monitoring for significant changes to occur across time.

Association of Radiotherapy-Related Intestinal Injury and Cancer-related Fatigue: A Brief Review and Commentary.

Radiotherapy treatment-induced intestinal injury and gut microbial perturbation/dysbiosis have been implicated in the pathobiology of cancer-related fatigue. The objective of this brief review was to explore the available evidence of the relationship between intestinal injury and self-reported fatigue, especially among cancer patients. The scientific evidence-including our own-linking gut mucosal barrier dysfunction and gut microbial perturbation/dysbiosis induced by cancer treatment with worsening of cancer related fatigue (perhaps through the gut-brain axis) is limited but promising. Emerging data suggest that lifestyle interventions and the administration of specific probiotics may favorably modulate the gut microbiota and potentially mediate beneficial effects leading to improvements in fatigue.

Programmed cell death-4 tumor suppressor protein contributes to retinoic acid-induced terminal granulocytic differentiation of human myeloid leukemia cells.

Programmed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. We investigated the role and the regulation of PDCD4 in the terminal differentiation of acute myeloid leukemia (AML) cells. Expression of PDCD4 was markedly up-regulated during all-trans retinoic acid (ATRA)-induced granulocytic differentiation in NB4 and HL60 AML cell lines and in primary human promyelocytic leukemia (AML-M3) and CD34(+) hematopoietic progenitor cells but not in differentiation-resistant NB4.R1 and HL60R cells. Induction of PDCD4 expression was associated with nuclear translocation of PDCD4 in NB4 cells undergoing granulocytic differentiation but not in NB4.R1 cells. Other granulocytic differentiation inducers such as DMSO and arsenic trioxide also induced PDCD4 expression in NB4 cells. In contrast, PDCD4 was not up-regulated during monocytic/macrophagic differentiation induced by 1,25-dihydroxyvitamin D3 or 12-O-tetradecanoyl-phorbol-13-acetate in NB4 cells or by ATRA in THP1 myelomonoblastic cells. Knockdown of PDCD4 by RNA interference (siRNA) inhibited ATRA-induced granulocytic differentiation and reduced expression of key proteins known to be regulated by ATRA, including p27(Kip1) and DAP5/p97, and induced c-myc and Wilms' tumor 1, but did not alter expression of c-jun, p21(Waf1/Cip1), and tissue transglutaminase (TG2). Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. In conclusion, our data suggest that PDCD4 expression contributes to ATRA-induced granulocytic but not monocytic/macrophagic differentiation. The PI3K/Akt/mTOR pathway constitutively represses PDCD4 expression in AML, and ATRA induces PDCD4 through inhibition of this pathway.