Cancer-free Patients Research Articles

Influence of surgical trauma on neopterin concentrations in gastric carcinoma patients.

Impairment of immune surveillance in the immediate postoperative period may accelerate the growth of tumor cells that remain despite radical resection in advanced cases. The present study was undertaken to evaluate the impact of major surgical trauma on host cellular immunity of gastric carcinoma cases. Sixty-eight consecutive patients with gastric carcinoma were divided into three subgroups according to the classification of the American Joint Committee on Cancer Staging, and they underwent surgery with a curative intent. Thirty-eight cancer-free patients served as controls, and they underwent surgical management for benign diseases. Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) risk adjustment system was used to estimate the operative and physiological scores of patients. Plasma cortisol, serum interleukin-6 and high-sensitive C-reactive protein levels were determined in order to assess the severity of trauma-related inflammatory response. The frequency of increased neopterin concentrations of cancer patients was estimated by comparison with the average values of controls. Response of interleukin-6 to surgery was closely related with the postoperative cortisol of cancer patients, but not correlated with neopterin and high-sensitive C-reactive protein levels. Although the extent of tumor invasion might have gradually decreased the macrophage response to surgical trauma, the overall increase in postoperative neopterin levels of cancer cases was highly significant. However, maximal frequency of increased neopterin concentration was obtained in advanced group. Macrophages might recognize the traumatic challenges in every stage of gastric cancer. Increasing individual neopterin concentration was not solely specific for tumor growth, but it was partially predictive of immune competence even in advanced cases.

Detection of sputum cofilin-1 as indicator of malignancy.

Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%). Several IMs exhibited hypermethylation at DNA methylation valleys; however, IMs generally lack intragenic hypomethylation signatures of advanced malignancy. IM patients with shortened telomeres and chromosomal alterations were associated with subsequent dysplasia or GC; conversely patients exhibiting normal-like epigenomic patterns were associated with regression.

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis

Background:Detection of metastatic spread of head and neck cancer to cervical lymph nodes is essential for optimal design of therapy. Undetected metastases lead to mortality, which can be prevented by better detection methods.Methods:We analysed 41 lymph nodes from 19 patients with oral squamous cell carcinoma (OSCC). Each lymph node was divided in two, one half processed for histopathology and the other half dissociated into single-cell suspension, stained for the carcinoma cell markers cytokeratin 5/8 (CK5/8), epithelial cell adhesion molecule (EpCAM) and epithelial mucin (MUC-1), and analysed with flow cytometry. Flow cytometry data were compared with histopathology performed on serial sections and immunohistochemistry. Six cervical lymph nodes from cancer-free patients were used to establish baseline levels in flow cytometry.Results:Flow cytometry analysis (fluorescence-activated cell sorting; FACS) detected all six metastases confirmed by histopathology as well as the histologically negative nodes. Importantly, among nine sentinel lymph nodes, FACS analysis detected <1% malignant cells in four cases, not found in histopathology. Results from flow cytometry analysis can be obtained within 3 h of the time of biopsy.Conclusions:We show that flow cytometric analysis of nodal tissue is sensitive and reliable in identifying metastases of OSCC. Flow cytometry is inexpensive and fast, providing a possibility of perioperative diagnostics and immediate treatment planning.

Impaired Enterohormone Response Following a Liquid Test Meal in Gastrectomized Patients

Background: Total gastrectomy (TG) is responsible for symptoms or disturbance of alimentary status (changes in body weight, food intake per meal and frequency of meal per day) which, in turn are responsible for weight loss and malnutrition. The study evaluates the gut hormone responses in totally gastrectomized (TG) patients after a liquid meal test. Methods: Twenty total gastrectomized cancer-free patients (12 M, 8 F, 56.4 ± 10.2 years, BMI 21.4 ± 2.2 kg/m²) and 10 healthy volunteers (4 M, 6 F, 48.0 ± 12.7 years, BMI 26.7 ± 3.0 kg/m² ) drank a liquid meal (1.25 kcal/mL) at the rate of 50 mL/5′ min for a maximum of 30 min. Satiety score was assessed and blood sample was taken at different time points. Results: The time response course, particularly for insulin, glucose-like pepetide-1, and cholecystokinin, significantly differed between TG patients and controls. Conclusions: Our results may help to better understand hormone responses triggered by the faster arrival of nutrients in the small bowel and to explain some post-TG symptoms.

Evaluation of peripheral blood T lymphocyte surface activation markers and transcription factors in patients with early stage non-small cell lung cancer

Lung cancer cells harboring multiple mutations as a consequence of long-term damage by different etiologic factors are responsible for high immunogenicity. Immune checkpoint inhibitors significantly improve treatment results in non-small cell lung cancer (NSCLC). Unfortunately, the role of T-lymphocytes in early NSCLC has not been sufficiently elucidated. The aim of this study was to characterize peripheral blood T cells expressing several selected surface antigens (CD4, CD8, CD25, CD28, PD-1, CTLA-4) and transcription factors (T-bet, ROR-yt, Fox-P3, GATA-3) in this patient population. The study group (LC) consisted of 80 treatment-naïve patients with T1/2aN0M0 NSCLC and was compared with 40 cancer-free patients matched for non-oncological diseases and demographic parameters (CG). Significantly higher counts of CTLA-4+cells (in both CD4+and CD8+subtypes), a lower proportion of PD-1 expressing cells and a significantly higher percentage of Fox-P3+CD4+cells were found in the LC group. The high proportion of CD4+PD-1+cells significantly correlated with poor outcomes in LC group, while low CD4/CD8 ratio predicted a better prognosis. Based on our results it seems that NSCLC even at early stages of development initiate changes in the proportions of T cells that may have a significant impact on the clinical outcome.

Label-free electrochemical aptasensing platform based on mesoporous silica thin film for the detection of prostate specific antigen

We report the development of a novel label-free electrochemical aptasensing platform to detect prostate specific antigen (PSA) based on mesoporous silica thin film-coated gold electrodes as a sensing interface. The aptasensing approach relies on hindering the diffusion of [Fe(CN)6]3/4− redox probe through the nanochannels of the mesoporous film gated by the recognition of the target biomarker by its anti-PSA specific DNA aptamer covalently attachment onto the outer surface of the silica nanopores. The aptasensing platform was found to be very sensitive to PSA in the range from 1 to 300ngmL−1 with a detection limit of 280pgmL−1. The aptasensor also showed high specificity, reproducibility and storage stability, and was successfully validated in spiked artificial urine samples and in blood serum from a prostate cancer-free male patient.

The overexpression of salivary cytokeratins as potential diagnostic biomarkers in head and neck squamous cell carcinomas.

BackgroundCytokeratin (CK) intermediate filaments are demonstrated to have enormous potential in regulating cellular motility and cancer progression. There are more than 20 divergent CKs that have been identified, of which CK 8, 17, 18 and 19 are reported to be elevated in the tumour biopsies of head and neck cancer squamous cell carcinoma (HNSCC) patients. However, CK expression profiles in the saliva of HNSCC patients have not been investigated. We aim to investigate the mRNA expression profiles of CKs in saliva collected from healthy controls, HPV-negative and -positive HNSCC patients.MethodsOral rinse samples were collected from 42 cancer-free healthy controls (age-matched) and patients who have been diagnosed with HPV-negative (n = 20) and -positive (n = 48) HNSCC.ResultsHere, we report that the mRNA expression profiles of CKs differed in saliva collected from healthy controls and HNSCC patients. The mRNA expression levels of CK 8 and 18 were significantly elevated in saliva collected from HPV-negative HNSCC patients; whilst, CK 17 and 19 were expressed at a higher mRNA level in saliva collected from HPV-positive HNSCC patients compared to healthy controls. Importantly, receiver operating characteristic (ROC) analysis showed salivary CK 8 and 18 to have superior sensitivity and specificity in discriminating the HPV-negative HNSCC patients from healthy controls (80% and 86%) as well as between HPV-negative and -positive HNSCC patients (75% and 81%).ConclusionIn summary, we have demonstrated that an aberrant expression of salivary CKs may serve as a potential non-invasive diagnostic biomarker in HNSCC.

Jugulodigastric lymph node size by age on CT in an adult cancer-free population

PurposeEvaluate jugulodigastric node size in cancer-free patients. MethodsRetrospective review of 234 neck CT angiograms was performed. Known neoplasm, inflammation or poor imaging were excluded. Maximal diameter of the largest jugulodigastric node in the axial plane bilaterally was measured. Results172 patients (median age=62) were included. Jugulodigastric node size decreased with age and was statistically significant between those above and below 62years. Patients 20–30years had mean 14.4mm (7.5–20.1mm). ConclusionsAlthough 15mm is considered the normal maximum long-axis size of the jugulodigastric node in cancer patients, average size in younger cancer-free patients is commonly above 15mm.

Abstract 238: Evidence of early colorectal cancer risk and prevention pathways in the fecal microbiome of colonoscopy patients: associations with diet and circulating adipocytokines

Abstract Accumulating evidence suggests that the gut microbiome’s role in early colorectal cancer etiology extends beyond the pro-carcinogenic activities of specific pathogens and is largely influenced by the wider microbial community of commensal bacteria. To identify early microbiome-related pathways and potential dietary intervention targets, we conducted an epidemiologic study among cancer-free colonoscopy patients at known and varied risk of colorectal neoplasia. Sporadic patients undergoing colonoscopy screening provided consent and fasting blood. Polyps, if found, were removed at colonoscopy and ~1 month later (prior studies show the effect of the colonoscopy prep dissipates within this time period), eligible patients provided a stool sample via mail kit (n=47). Patients completed comprehensive dietary assessments and clinicopathologic factors, including screening history, were abstracted from electronic medical records. We characterized the fecal microbiome via whole genome shotgun sequencing (Illumina HiSeq) and circulating blood adipocytokines via Luminex multiplex assays (Millipore). Majority of the patients were female and recently diagnosed with precancerous polyps, primarily tubular and sessile serrated adenomas. Polyp patients were more likely to be obese and to not consume alcohol, but otherwise similar by age, diet composition, and other risk factors to patients with normal colonoscopy findings. We observed no effects of time interval between colonoscopy and fecal sample collection, or of recent polyp diagnosis/removal, on microbial alpha or beta diversity. Correlation networks between species revealed that Faecalibacterium prausnitzii inversely correlated with E. coli, the most abundant species in our sample, and co-occurred with other short chain fatty acid-metabolizing bacteria, including Anaerostipes hadrus and Roseburia hominis, known butyrate-producers. Among recurrent patients (n=14), Bacteroides fragilis co-occurred with Bilophila wadsworthia (r=0.6; P=0.02). Higher intake of fiber and/or overall diet quality, as defined by the Healthy Eating Index, was associated with several bacteria largely linked to butyrate production (e.g., Bifidobacterium animalis, F. prausnitzii, Roseburia intestinalis, Coprococcus eutactus, Eubacterium eligens). These same dietary factors were inversely correlated with Blautia hydrogenotrophica, an acetogen, and other bacteria implicated in inflammation and colorectal cancer (e.g., B. fragilis). Biologically plausible associations between microbial (functional gene content) pathways important to cancer risk (e.g., one-carbon, lysine, carbohydrate and fatty acid metabolism) with dietary factors and circulating adipocytokines involved in immunity, inflammation, and glucose metabolism support the functionality of these diet-microbe relationships. Citation Format: Carrie R. Daniel, Kristi L. Hoffman, G S. Raju, Samir M. Hanash, Diane S. Hutchinson, Nadim J. Ajami, Richard G. Fowler, Gladys J. Browman, Akhil Sood, Paul Scheet, Xifeng Wu, Joseph F. Petrosino. Evidence of early colorectal cancer risk and prevention pathways in the fecal microbiome of colonoscopy patients: associations with diet and circulating adipocytokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 238. doi:10.1158/1538-7445.AM2017-238

Relation of Coronary Artery Calcium Score and Risk of Cancer (from a Danish Population-Based Follow-up Study in Patients Who Underwent Cardiac Computed Tomography)

Evidence of a causal link between atherosclerosis and cancer is sparse and conflicting. Therefore, we examined the association between extent of coronary atherosclerosis determined by coronary artery calcium score (CACS) and risk of cancer. We conducted a historical population-based cohort study of 28,549 cancer-free patients identified in the Western Denmark Heart Registry. All patients underwent cardiac computed tomography for measurement of CACS for suspected coronary artery disease. The outcome was an incident cancer diagnosis: total, tobacco-related, lung, prostate, breast, and colorectal. We used Cox proportional hazards regression analyses stratified by gender to estimate hazard ratios (HRs) for relations between CACS and cancer with 95% confidence intervals (95% CI). During follow-up, 455 men and 527 women had a cancer diagnosis. In a multivariable model (reference group: CACS 0), adjusted hazard ratios (95% confidence interval) for total cancer were as follows: CACS 1 to 99: 1.07 (0.83 to 1.39), CACS 100 to 399: 1.24 (0.94 to 1.63), CACS 400 to 999: 0.88 (0.62 to 1.25), CACS ≥1,000: 0.96 (0.66 to 1.41) in men; and CACS 1 to 99: 0.96 (0.77 to 1.19), CACS 100 to 399: 0.99 (0.75 to 1.31), CACS 400 to 999: 1.11 (0.76 to 1.62), and CACS ≥1,000: 1.16 (0.73 to 1.83) in women. We found no significant association between CACS and the specified outcomes for men or women, except for an increased risk of lung cancer among women with a high CACS. In conclusion, extent of coronary atherosclerosis determined by CACS was not associated with development of total, tobacco-related, lung, prostate, breast, or colorectal cancer. However, we did observe an association between CACS and risk of lung cancer in women.

D‐dimer at venous thrombosis diagnosis is associated with risk of recurrence

Essentials Whether D-dimer at incident venous thromboembolism (VTE) can predict recurrence-risk is unknown. We explored this association in 454 cancer-free patients with a first lifetime VTE. A low D-dimer at first VTE diagnosis was associated with a low recurrence risk. The association was predominant in patients with deep vein thrombosis and unprovoked VTE. Click to hear Dr Cannegieter's presentation on venous thrombosis: prediction of recurrence SUMMARY: Background Venous thromboembolism (VTE) is a common disease with a high recurrence rate. D-dimer measured after cessation of anticoagulant therapy predicts recurrence, and is used to decide on treatment prolongation. However, whether D-dimer measured at first VTE diagnosis can be used to assess recurrence-risk is unknown. Aims To investigate the association between D-dimer, measured at first VTE diagnosis and risk of recurrent VTE. Methods Information on clinical risk factors and laboratory markers were collected in 454 cancer-free patients with a first VTE. Recurrent VTEs and deaths during follow-up (1994-2012) were recorded. Results During a median follow-up of 3.9 years, 84 patients experienced a recurrent VTE. The crude recurrence rate was 1.7 (95% confidence interval [CI], 1.0-2.9) per 100 person-years in the lower quartile of D-dimer (≤ 1500 ng mL-1 ), and 4.9 (95% CI, 3.9-6.1) per 100 person-years in the upper three quartiles combined, yielding an absolute risk difference of 3.2 per 100 person-years. Patients with D-dimer ≤ 1500 ng mL-1 had 54% lower recurrence-risk than patients with D-dimer > 1500 ng mL-1 (HR, 0.46; 95% CI, 0.25-0.82). The association was particularly pronounced among patients with unprovoked events and deep vein thrombosis, showing a 66% (HR, 0.34; 95% CI, 0.15-0.74) and 68% (HR, 0.32; 95% CI, 0.14-0.71) lower recurrence risk among patients with D-dimer ≤ 1500 ng mL-1 , respectively. Conclusions A low D-dimer (≤ 1500 ng mL-1 ) measured at first VTE diagnosis was associated with a low recurrence risk, particularly among patients with DVT and unprovoked events. Our findings suggest that a clinical decision to avoid prolonged anticoagulant treatment could be considered based on low D-dimer at the time of VTE diagnosis.

Prospective and longitudinal evaluations of telomere length of circulating DNA as a risk predictor of hepatocellular carcinoma in HBV patients.

Prospective and longitudinal epidemiological evidence is needed to assess the association between telomere length and risk of hepatocellular carcinoma (HCC). In 323 cancer-free Korean-American HBV patients with 1-year exclusion window (followed for >1 year and did not develop HCC within 1 year), we measured the relative telomere length (RTL) in baseline serum DNAs and conducted extensive prospective and longitudinal analyses to assess RTL-HCC relationship. We found that long baseline RTL conferred an increased HCC risk compared to short RTL [hazard ratio (HR) = 4.93, P = 0.0005). The association remained prominent when the analysis was restricted to patients with a more stringent 5-year exclusion window (HR = 7.51, P = 0.012), indicating that the association was unlikely due to including undetected HCC patients in the cohort, thus minimizing the reverse-causation limitation in most retrospective studies. Adding baseline RTL to demographic variables increased the discrimination accuracy of the time-dependent receiver operating characteristic analysis from 0.769 to 0.868 (P = 1.0 × 10-5). In a nested longitudinal subcohort of 16 matched cases-control pairs, using a mixed effects model, we observed a trend of increased RTL in cases and decreased RTL in controls along 5 years of follow-up, with a significant interaction of case/control status with time (P for interaction=0.002) and confirmed the association between long RTL and HCC risk [odds ratio [OR] = 3.63, P = 0.016]. In summary, serum DNA RTL may be a novel non-invasive prospective marker of HBV-related HCC. Independent studies are necessary to validate and generalize this finding in diverse populations and assess the clinical applicability of RTL in HCC prediction.

Abstract A26: Diet quality vs quantity in relation to the fecal microbiome among colonoscopy patients

Abstract Diet remains a promising target with the potential to impact colorectal cancer risk via the balance of energy and body weight, as well via specific food components with known anti-carcinogenic properties. Growing evidence implicates the importance of the gut microbiome in the interaction of diet, energy balance, and inflammation—key mechanisms associated with colorectal cancer development. The tight coupling of diet and the gut microbiota may hold new answers for colorectal cancer prevention. Methods: We conducted a pilot epidemiologic study among 50 cancer-free MD Anderson colonoscopy patients with no underlying familial/genetic or chronic inflammatory bowel conditions. With the overall goal to identify dietary intervention targets in obese and lean individuals at varied risk of colorectal neoplasia, patients provided fasting blood at colonoscopy, stool samples via mail ~ 1 month post-polypectomy, and comprehensive dietary assessments. Total energy intake was derived from responses to both the Diet History (DH) and 24-hour dietary recalls (24HR) and diet quality was defined by the Healthy Eating Index (HEI). We conducted 16S rRNA gene sequencing of the fecal microbiota and measured circulating blood adipocytokines via Luminex multiplex assays (Millipore). Results: Majority of colonoscopy patients recruited into the study were female (67%) and diagnosed with precancerous colorectal polyps (57%), primarily tubular and sessile serrated adenomas. Patients with precancerous polyps removed at colonoscopy were more likely to be obese than patients without precancerous polyps, but otherwise similar by age, macronutrient composition, and HEI. Differences in the overall composition of the fecal microbiome via weighted and unweighted unifrac were observed by reason for colonoscopy (symptomatic vs asymptomatic screening), chronic medication use (yes vs. no), total energy and alcohol intake (tertiles); and effects of each these factors were considered in subsequent analyses. No differences were observed by other clinicopathologic features, demographics, or lifestyle factors. High total energy intake was significantly correlated with higher alpha diversity of the fecal microbiome. This linear relationship remained following adjustment for diet quality and was consistent across colonoscopy status, BMI, medication use and alcohol intake (FDR-adj P&amp;lt;0.05). Total energy intake was inversely correlated with the relative abundance of Bacteroides (r2=0.27; FDR-adj P&amp;lt;0.001), while diet quality was positively associated with multiple bacteria involved in short chain fatty acid metabolism, including Faecalibacterium, Subdoligranulum, and Pseudobutyrivibrio (all P&amp;lt;0.05). Many of these same bacteria were significantly correlated with blood levels of circulating adipocytokines, including C-peptide, TNF-alpha, lipocalin-2, and PAI-1. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis further revealed that gut bacteria may mediate the relationship between diet quality and adipocytokine signaling pathways. Conclusion: Modifiable aspects of diet quality and quantity were more closely linked to the composition of the gut microbiome than obesity or a recent diagnosis of precancerous colorectal polyps. In general, low microbial diversity has been associated with states of disease/poor health, but in our case, eating more may mean exposure to a more varied diet, promoting proliferation of a number of distinct bacteria, both “good” and “bad”. We plan to further explore functional relationships and pathways between diet, the microbiome, and adipocytokines with ongoing metagenomic analysis of the fecal microbiome. Citation Format: Carrie R. Daniel, Kristi L. Hoffman, Akhil Sood, G.S. Raju, Samir M. Hanash, Xifeng Wu, Joseph F. Petrosino. Diet quality vs quantity in relation to the fecal microbiome among colonoscopy patients. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A26.

Prevalence of human papillomavirus in tonsil brushings and gargles in cancer-free patients: The SPLIT study

ObjectiveTo evaluate human papillomavirus (HPV) prevalence in the tonsil using extensive ex vivo brushing and gargling in a large age-stratified sample of cancer-free patients. Materials and methodsFrom 2012 to 2016, consecutive patients undergoing tonsillectomy for benign indications in 19 French University Hospitals were invited to participate in the SPLIT study. Immediately after resection, half-tonsils were extensively brushed at the pathology laboratories on the surface epithelium and in tonsil crypts to collect exfoliated cells. In 11 centers, patients aged 15 and over (adults) were also asked to provide gargle samples before surgery. HPV-DNA detection used a very sensitive Luminex technology to evaluate 21 HPV types. ResultsTonsil brushings from 692 patients aged 1–70 years and gargles from 268 adults were tested for HPV. Among adults, overall HPV prevalence was 3.6% in tonsil brushings and 13.1% in gargles and HPV16 prevalence was 2.2% and 4.1%, respectively. Among 139 children, tonsil brushings were positive in two girls (1.4%). Percent agreement in HPV detection in paired tonsil brushings and gargles in adults was 85.8% and positive agreement 9.5%. HPV prevalence in gargles significantly varied by sex (prevalence ratio in men vs women=2.1; 95% confidence interval; 1.1–4.1) and tonsillectomy indication (non-infectious vs. infectious=4.9; 1.4–17.0). ConclusionHPV infection is infrequent in tonsil brushings of cancer-free children and adults. In contrast, HPV infection in gargles in adults is rather common. Low agreement in paired tonsil brushings and gargles suggests that gargle is not representative of HPV prevalence in the tonsil.

Comprehensive DNA Methylation Profiling of Inflammatory Mucosa in Ulcerative Colitis.

Aberrant DNA methylation frequently occurs in the inflammatory mucosa in ulcerative colitis (UC) and is involved in UC-related tumorigenesis. We performed comprehensive DNA methylation profiling of the promoter regions of the inflamed rectal mucosae of patients with UC. The methylation status of the promoter CpG islands (CGIs) of 45 cancer/inflammation or age-related candidate genes and the LINE1 repetitive element were examined in the colonic mucosae of 84 cancer-free patients with UC by bisulfite pyrosequencing. Methylation status of selected genes (DPYS, N33, MIR1247, GSTP1, and SOX11) was also determined in 14 neoplastic lesions (5 with high-grade dysplasia and 9 with carcinoma) and 8 adjacent tissues derived from 12 patients. An Infinium HumanMethylation450 BeadChip array was used to characterize the methylation status of >450,000 CpG sites for 10 patients with UC. Clustering analysis based on the methylation status of the candidate genes clearly distinguished the inflammatory samples from the noninflammatory samples. The hypermethylation of the promoter CGIs strongly correlated with increased disease duration, which is a known risk factor for the development of colon cancer. Genome-wide methylation analyses revealed a high rate of hypermethylation in the severe phenotype of UC, particularly at the CGIs. Exclusively hypermethylated promoter CGIs in the severe phenotypes were significantly related to genes involved in biosynthetic processes, the regulation of metabolic processes, and nitrogen compound metabolic processes. Our findings suggest the potential utility of DNA methylation as a molecular marker and therapeutic target for UC-related tumorigenesis.

Quality of life outcome measures using University of Washington questionnaire version 4 in early T1/T2 anterior tongue cancers with and without radiotherapy: A cross-sectional study.

To evaluate the quality of life (QOL) outcome measures in disease-free survivors of pathological T1/T2 tongue cancers and to compare QOL in patients treated with only surgery and with adjuvant treatment. Cross-sectional survey. All pathological T1/T2 anterior tongue cancer cases with follow-up from January 2011 till December 2015, who had locoregionally controlled disease with a minimum disease-free survival period of 1 year, were included in the study. A total of 36 patients, 28 are males and 8 are females with an age range of 24-66 years (median age of 43) were enrolled in the study. The patients were divided into two groups with (n = 26) and without adjuvant postoperative radiotherapy (RT) (n = 10) and the University of Washington-QOL questionnaire version 4 for physical and social domains, global questions and three important domains were analyzed. On the physical and social domain scores, the surgery-alone group outscored the combined modality group on all scales and the differences were statistically significant for specific physical domains such as saliva (0.0001), taste (P = 0.0001), chewing (P = 0.0004), swallowing (P = 0.0026), and social domains such as mood (0.0001), pain (P = 0.0001), and shoulder function (P = 0.0061). The overall global QOL scores were also better for the surgical group compared with group which received adjuvant RT but was not statistically significant. All patients chose saliva as their top priority domain in the group which received radiation, and 60% chose "swallowing ability" as the preferred top priority domain in the only surgical group. Although locoregional control and disease-free survival are the major treatment-related endpoints for cancer management, QOL outcome measures have to assess to determine the impact of a treatment modality on patients well-being and for better rehabilitation of cancer-free patients.

Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case-control study.

Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant-related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE. We designed a retrospective nested case-control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching. The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer-free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls. Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose-dependent manner.

'Am I really gonna go sixty years without getting cancer again?' Uncertainty and liminality in young women's accounts of living with a history of breast cancer.

Although much research has examined the experience of breast cancer, the distinctive perspectives and lives of young women have been relatively neglected. Women diagnosed with breast cancer under the age of 45, and who had completed their initial treatment, were interviewed, and social constructionist grounded theory methods were used to analyse the data. The end of initial treatment was accompanied by a sense of unease and uncertainty in relation to recurrence and survival, and also fertility and menopausal status. The young women's perceptions about the future were altered, and their fears about recurrence were magnified by the possibility of many decades ahead during which breast cancer could recur. The implications for the young women's life course, in terms of whether they would be able to have children, would not become clear for several years after initial treatment. This resulted in a liminal state, in which young women found themselves neither cancer-free nor cancer patients, neither pre- nor post-menopausal, neither definitively fertile nor infertile. This liminal state had a profound impact on young women's identities and sense of agency. This extends previous understanding of life after cancer, exploring the age-related dimensions of liminality.