Contributions of cancer treatment, comorbidities, and obesity to aging-related disease risks among non-Hodgkin lymphoma survivors.

PURPOSE: It is unknown whether cancer treatment contributes more to long-term disease risk than lifestyle factors and comorbidities among B-cell non-Hodgkin lymphoma (B-NHL) survivors. METHODS: B-NHL survivors were identified in the Utah Cancer Registry from 1997 to 2015. Population attributable fractions (PAF) were calculated to assess the role of clinical and lifestyle factors for six cardiovascular, pulmonary, and renal diseases. RESULTS: Cancer treatment contributed to 11% of heart and pulmonary conditions and 14.1% of chronic kidney disease. Charlson Comorbidity Index (CCI) at baseline contributed to all six diseases with a range of 9.9% of heart disease to 26.5% of chronic kidney disease. High BMI at baseline contributed to 18.4% of congestive heart failure and 7.9% of pneumonia, while smoking contributed to 4.8% of COPD risk. CONCLUSION: Cancer treatment contributed more to heart disease, COPD, and chronic kidney disease than lifestyle factors and comorbidities among B-NHL survivors. High BMI at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, whereas smoking at baseline was not a major contributor in this B-NHL survivor cohort. Baseline comorbidities consistently demonstrated high attributable risks for these diseases, demonstrating a strong association between preexisting comorbidities and aging-related disease risks.

Clinical and hemodynamic effects of oral sildenafil on biventricular function on patients with left ventricular systolic dysfunction.

BACKGROUND: We explore the dual benefits of sildenafil on bi-ventricular functions in the form of improvement of ejection fraction, pulmonary vascular resistance and functional capacity of systolic heart failure patients either related to dilated or ischemic cardiomyopathy. AIM OF THE WORK: To evaluate the effect of oral sildenafil on biventricular function in patients with left ventricular systolic dysfunction. PATIENTS AND METHODS: The prospective randomised case-control study included 80 patients with left ventricular systolic dysfunction resulting from dilated or ischemic cardiomyopathy were equally randomised to one of the treatment groups in (1:1) who were collected from the outpatient clinic of cardiac care unit (CCU) of Beni-Suef University hospital; each group contained 40 patients: The first group (control group): received the guideline-recommended treatment of heart failure with reduced ejection fraction which consists of [angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), beta-blockers, aldosterone receptor antagonist, digoxin]. The second group (sildenafil group): received the previously mentioned guideline-recommended treatment in the control group plus sildenafil 25 mg three times per day. All patients were subjected to detailed history taking, baseline transthorathic echocardiography and exercise ECG using the Naughton protocol. Follow-up transthorathic echocardiography and exercise ECG was conducted after 3 months. RESULTS: Sildenafil improves heart failure symptoms such as dyspnea or orthopnea or increasing the functional capacity of myocardium which is measured by estimated metabolic equivalents of task (METS) (P = .017), and exercise duration (P = .013). Sildenafil increased cardiac output (P = .033), which is considered one of the desirable targets in heart failure patients. CONCLUSION: In patients with left ventricular systolic dysfunction secondary to dilated or ischemic cardiomyopathy, relatively small doses of sildenafil significantly enhances exercise period and functional ability, with substantial improvement in left ventricular systolic function irrespective of the existence of major pulmonary hypertension.

Adverse respiratory outcomes among head and neck cancer survivors in the Utah Cancer Survivors Study.

BACKGROUND: The number of head and neck cancer (HNC) survivors has been increasing because of improving survival in the United States. The aim of this study was to evaluate the incidence of respiratory disease diagnoses in HNC survivors in comparison with cancer-free individuals. A second aim was to investigate risk factors for respiratory disease among HNC survivors. METHODS: Patients with HNC diagnosed from 1996 to 2012 were identified in the Utah Cancer Registry (n = 1901). Up to 5 cancer-free individuals from the general population (n = 7796) were matched to each HNC survivor by birth year, sex, birth state, and follow-up time. Electronic medical records and statewide health care facility data were used to identify a disease diagnosis after the cancer diagnosis. Cox proportional hazards models were used to estimate the risks of respiratory diseases. RESULTS: The median follow-up times were 4.5 years for HNC survivors and 7.8 years for the general population cohort. The risks of respiratory infection (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.40-1.90), chronic obstructive pulmonary diseases and bronchiectasis (HR, 2.65; 95% CI, 2.13-3.29), and aspiration pneumonitis (HR, 6.21; 95% CI, 3.98-9.68) were higher among HNC survivors than the general population cohort more than 5 years after the cancer diagnosis. Age at diagnosis, baseline body mass index, sex, baseline smoking status, treatment modality, primary site, and stage were associated with the risk of adverse respiratory outcomes among HNC survivors. CONCLUSIONS: The risk of adverse respiratory outcomes was much higher among HNC survivors than the general population cohort. Multidisciplinary care is needed to prevent the occurrence of adverse respiratory outcomes among HNC survivors.

Genitourinary disease risks among ovarian cancer survivors in a population-based cohort study.

OBJECTIVE: While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. METHODS: We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. RESULTS: Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. CONCLUSIONS: Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.

Effect of cold application versus transcutaneous nerve stimulation on chemotherapy induced diabetic peripheral neuropathy post mastectomy.

BACKGROUND: The adverse effects of chemotherapy-induced diabetic peripheral neuropathy (CIDPN) are rather prevalent. There is no known pharmaceutical treatment that can stop CIDPN. OBJECTIVE: This study compared the effects of cold application and transcutaneous nerve stimulation (Transcutaneous electrical nerve stimulation (TENS)) on individuals who had undergone mastectomy following CIDPN. SUBJECTS AND METHODS: Between Mars 2021 and September 2021, a randomised controlled experiment was carried out at physical therapy clinics at the Modern University for Technology and Information. 30 patients were randomly split into two equal groups (A and B). Both lower limbs received cold application (Group A) three times per week for 12 weeks and TENS application (Group B) three times each week for 12 weeks. The Visual Analogue Scale and nerve conduction velocity for the sural nerve were used to assess patients before and after 12 weeks of therapy. RESULTS: The results showed that Group A significantly (p < 0.05) decreased pain intensity after treatment by 70.83% compared with Group B by 55.17%. Moreover, Group A improved significantly (p < 0.05) the sural nerve amplitude by 44.12% compared with group B which recorded 26.87%. After treatment, both pain intensity and sural nerve amplitude significantly (p < 0.05) changed between Group A versus Group B. CONCLUSION: Cold application has a better effect on pain in CIDPN post mastectomy.

Assessment of serum levels of anti-gliadin (IgA and IgG) antibodies in patients with lichen planus: A pilot study.

Despite the fact that anti-gliadin antibodies (AGA) play a key role in coeliac disease (CD) screening, elevated AGA levels have been reported in several immune-mediated cutaneous conditions even in the absence of gastrointestinal disease clinical manifestations. A gluten-free diet led to improvements in some of these disorders. The link between oral lichen planus (LP) and CD was revealed, but there is currently no information available regarding the association between cutaneous LP and gluten sensitivity. This study aimed to assess the AGA (IgA and IgG) serum levels in LP patients compared to controls and to determine their correlation with LP severity. The study included 20 patients with cutaneous LP and 20 age- and sex-matched controls, both free of CD manifestations. The enzyme-linked immunosorbent assay (ELISA) technique was utilized for the evaluation of AGA (IgA and IgG) serum levels. Hepatitis C virus (HCV) antibodies in LP patients were evaluated qualitatively using a chromatographic immunoassay. In LP patients, AGA (IgA and IgG) serum levels were significantly elevated compared to controls (p = 0.015 and p=0.016, respectively). A significant positive correlation between AGA (IgG) serum levels and the age of patients (p= 0.024), duration of disease (p= 0.02), and LP severity index (p< 0.0001) was found. AGA serum levels were insignificantly different between HCV-positive and HCV-negative LP patients (p= 0.054). In conclusion, the significant elevation of serum AGA levels in LP patients reflects a possible link between LP and occult CD. Serum AGA (IgG) levels can be used as a marker of LP severity..

Age-Related Disease Risks in Younger versus Older B-Cell Non-Hodgkin's Lymphoma Survivors.

BACKGROUND: Younger cancer survivors may develop age-related diseases due to the cancer treatment that they undergo. The aim of this population-based study is to estimate incidence of age-related diseases besides cardiovascular disease among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. METHODS: Survivors of B-NHL were diagnosed between 1997 and 2015 from the Utah Cancer Registry. Using the Utah Population Database, up to 5 cancer-free individuals from the general population were matched with a B-NHL survivor on sex, birth year, and state of birth. Hazard ratios (HR) for age-related disease outcomes, which were identified from medical records and statewide health care facility data, were estimated using Cox Proportional Hazards models for B-NHL survivors diagnosed at <65 years versus ≥65 years at least 5 years since B-NHL diagnosis. RESULTS: Comparing 2,129 B-NHL survivors with 8,969 individuals from the general population, younger B-NHL survivors had higher relative risks of acute renal failure [HR, 2.24; 99% confidence interval (CI), 1.48-3.39; P heterogeneity = 0.017), pneumonia (HR, 2.42; 99% CI, 1.68-3.49; P heterogeneity = 0.055), and nutritional deficiencies (HR, 2.08; 99% CI, 1.48-2.92; P heterogeneity = 0.051) ≥5 years after cancer diagnosis. CONCLUSION: Younger B-NHL survivors had higher relative risks of acute renal failure, pneumonia, and nutritional deficiencies than older B-NHL survivors compared with their respective general population cohorts, ≥5 years after cancer diagnosis.

Cardiovascular disease risks in younger versus older adult B-cell non-Hodgkin's lymphoma survivors.

INTRODUCTION: Young cancer survivors may be at increased risk of early-onset chronic health conditions. The aim of this population-based study is to estimate cardiovascular disease (CVD) risk among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. METHODS: B-NHL survivors diagnosed from 1997 to 2015 in the Utah Cancer Registry were matched with up to five cancer-free individuals on birth year, sex, and birth state, using the statewide Utah Population Database. Electronic medical records and statewide health care facility data were used to identify disease outcomes ≥5 years after cancer diagnosis. Cox Proportional Hazards models were used to estimate hazard ratios for B-NHL survivors diagnosed at <65 years and ≥65 years old. RESULTS: Younger B-NHL survivors had higher relative risks than older cancer survivors of chronic rheumatic disease of the heart valves (HR = 4.14, 99% CI = 2.17-7.89; P valueheterogeneity = 0.004); peri-, endo-, and myocarditis (HR = 2.43, 99% CI = 1.38-4.28; P valueheterogeneity = 0.016); diseases of the arteries (HR = 1.63, 99% CI = 1.21-2.21; P valueheterogeneity = 0.044); and hypotension (HR = 2.44, 99% CI = 1.58-3.75; P valueheterogeneity = 0.048). B-NHL survivors of both age groups had elevated relative risks of heart disease overall and congestive heart failure. CONCLUSION: Younger B-NHL survivors had higher risks than older B-NHL survivors of specific cardiovascular diseases compared to their respective general population cohorts.

Individualized prediction of late-onset dysphagia in head and neck cancer survivors.

BACKGROUND: Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia. METHODS: From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model. RESULTS: Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors. CONCLUSION: We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia.

Rates of Dysphagia-Related Diagnoses in Long-Term Survivors of Head and Neck Cancers.

OBJECTIVE: To estimate long-term prevalence of new dysphagia-related diagnoses in a large cohort of head and neck cancer survivors. STUDY DESIGN: Retrospective cohort. SETTING: Population based. SUBJECTS AND METHODS: In total, 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow-up were compared with 7796 controls matched for age, sex, and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2 to 5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed. RESULTS: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2 to 5 years, increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% confidence interval [CI], 5.08-17.87) and 12.57 (7.17-22.04), respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45-197.33) to 35.2 (7.81-158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50-4.42) to 2.12 (1.63-2.75). Treatment with radiation therapy and age older than 65 years were associated with increased hazard ratio for dysphagia-related diagnoses. CONCLUSION: Our data suggest that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.

Mental Health Disorders are More Common in Colorectal Cancer Survivors and Associated With Decreased Overall Survival.

OBJECTIVES: To determine the risk and risk factors for mental illness among colorectal cancer (CRC) survivors across short-term and long-term follow-up periods. METHODS: We used the Utah Cancer Registry to identify CRC survivors diagnosed between 1997 and 2013. Mental health diagnoses were available in electronic medical records and statewide facilities data that were linked by the Utah Population Database. CRC survivors were matched to individuals from a general population cohort. The risk of developing a mental illness was compared between cohorts. The association between mental illness and mortality was also analyzed. RESULTS: In total, 8961 CRC survivors and 35,897 individuals in a general population cohort were identified. CRC survivors were at increased risk for any mental health diagnosis at 0 to 2 years (hazard ratio [HR], 3.70; 95% confidence interval [CI], 3.47-3.95), >2 to 5 years (HR, 1.23; 95% CI, 1.09-1.38), and >5 years (HR, 1.20; 95% CI, 1.07-1.36) after cancer diagnosis. CRC survivors were also at increased risk of depressive disorders specifically during the same time periods. At >5 years, CRC survivors still had an increased risk of developing many mental health diagnoses. Factors associated with increased risk of any mental health disorder among CRC survivors included colostomy and Charlson Comorbidity Index of 1+. There was an increased risk of death for CRC survivors diagnosed with any mental health disorder (HR, 2.18; 95% CI, 2.02-2.35) and depression (HR, 2.10; 95% CI, 1.92-2.28). CONCLUSIONS: CRC survivors are at increased risk for mental health disorders in the short-term and long-term. Survivors who develop mental health disorders also experience decreased survival.

Evolutionary selected Tibetan variants of HIF pathway and risk of lung cancer.

Tibetans existed in high altitude for ~25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. EGLN1/PHD2 and EPAS1/HIF-2α, both crucial components of hypoxia sensing, are the two best-established loci contributing to high altitude adaptation. The co-adapted Tibetan-specific haplotype encoding for PHD2:p.[D4E/C127S] promotes increased HIF degradation under hypoxic conditions. The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay; however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/HIF-2α have not yet been identified. Since HIF modulates the behavior of cancer cells, we hypothesized that these Tibetan selected genomic variants may modify cancer risk predisposition. Here, we ascertained the frequencies of EGLN1D4E/C127S and EGLN1C127S variants and ten EPAS1/HIF-2α variants in lung cancer patients and controls in Nepal, whose population consists of people with Indo-Aryan origin and Tibetan-related Mongoloid origin. We observed a significant association between the selected Tibetan EGLN1/PHD2 haplotype and lung cancer (p=0.0012 for D4E, p=0.0002 for C127S), corresponding to a two-fold increase in lung cancer risk. We also observed a two-fold or greater increased risk for two of the ten EPAS1/HIF-2α variants, although the association was not significant after correcting for multiple comparisons (p=0.12). Although these data cannot address the role of these genetic variants on lung cancer initiation or progression, we conclude that some selected Tibetan variants are strongly associated with a modified risk of lung cancer.

Long-term health effects among testicular cancer survivors.

PURPOSE: Testicular cancer is diagnosed at a young age and survival rates are high; thus, the long-term effects of cancer treatment need to be assessed. Our objectives are to estimate the incidence rates and determinants of late effects in testicular cancer survivors. METHODS: We conducted a population-based cohort study of testicular cancer survivors, diagnosed 1991-2007, followed up for a median of 10 years. We identified 785 testicular cancer patients who survived ≥5 years and 3323 men free of cancer for the comparison group. Multivariate Cox regression analysis was used to compare the hazard ratio between the cases and the comparison group and for internal analysis among case patients. RESULTS: Testicular cancer survivors experienced a 24 % increase in risk of long-term health effects >5 years after diagnosis. The overall incidence rate of late effects among testicular cancer survivors was 66.3 per 1000 person years. Higher risks were observed among testicular cancer survivors for hypercholesterolemia, infertility, and orchitis. Chemotherapy and retroperitoneal lymph node dissection appeared to increase the risk of late effects. Being obese prior to cancer diagnosis appeared to be the strongest factor associated with late effects. CONCLUSIONS: Testicular cancer survivors were more likely to develop chronic health conditions when compared to cancer-free men. IMPLICATIONS FOR CANCER SURVIVORS: While the late effects risk was increased among testicular cancer survivors, the incidence rates of late effects after cancer diagnosis was fairly low.