Invasive Screening Methods Research Articles

Longitudinal assessment of transcranial Doppler imaging in children with sickle cell disease without neurological symptoms

IntroductionStroke is one of the most devastating complications of sickle cell disease (SCD). Transcranial Doppler Imaging (TCDI) is the least invasive screening method to predict patients at risk for developing stroke in the disease. After a 10-year follow-up, we longitudinally assessed the TCDI in children with SCD without neurological symptoms.Methods25 out of 43 pediatric patients with SCD studied 10-year previously were recruited. The remaining 18 patient were not available for follow-up, but their initial data are presented for comparison. TCDI scanning was carried out using a phased-array transducer of 1–3 MHz through the trans-temporal window. Peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged mean of the maximum velocity (TAMMV), resistive index (RI), and pulsatility index (PI) were obtained in the anterior and posterior Circle of Willis vessels.ResultsThe highest initial and follow-up TAMMV (mean ± SD) were: 77.3 ± 20.9 and 71.6 ± 9.9 in the t-ICA, 94.3 ± 25.8 and 82 ± 18.2 in the MCA, 76.6 ± 25.6 and 70.6 ± 10.7 in the ACA, and 59.1 ± 15.8 and 63.9 ± 8.5 in the PCA, respectively. There was no statistically significant difference between initial and follow-up SCD data for all vascular parameters in all vessels on each side (P > 0.05) except for RI and PI (P < 0.05). There was significant correlation between TAMMV, PSV, and EDV (P = 0.001).ConclusionThere are no absolute Doppler velocity changes between the initial and follow-up period over the years. There is a possibility that PSV and EDV could be used in parallel with TAMMV Subclinical vascular degeneration is not suggested by these vascular measures.

Insight of recent artificial intelligence-based strategy to effectively screen COVID-19

&lt;p&gt;&lt;span lang="EN-US"&gt;The recent era of pandemic by corona virus disease (COVID-19) has witnessed a faster evolution of various technological solution to thwart the life-threating situation. The most important step was to select a faster mode of screening COVID-19 using chest x-ray (CXR) which could be actually ten folds faster than conventional invasive screening methods. However, the method of determining the presence of COVID-19 from CXR is critically challenging owing to the dynamic and complex nature of disease. Such problem is attempted to be solved by harnessing the potential of artificial intelligence (AI). Hence, this paper contributes towards discussion of most recent and current implementation strategies formulated by AI models towards diagnosing COVID-19. The study outcome of this paper yields an interesting learning outcome to show that AI models’ adoption is increasing in faster pace and yet challenges do exist till date. The outcome of study will assist in better adoption of AI models towards screening COVID-19.&lt;/span&gt;&lt;/p&gt;

Toward Application to General Conversation Detection of Dementia Tendency from Conversation Based on Linguistic and Time Features of Speech

Currently, MRI examinations and neuropsychological tests by physicians and clinical psychologists are used to screen for dementia, but they are problematic because they overwhelm medical resources and are highly invasive to patients. If automatic detection of dementia from conversations becomes feasible, it will reduce the burden on medical institutions and realize a less invasive screening method. In this paper, we constructed a machine learning model to identify dementia by extracting linguistic features and time features from the elderly corpus with a control group. Random Forest (RF), Support Vector Machine (SVM), and Logistic Regression (LR) were used in the model. We compared the AUC of the single topic model and the general topic model in three cases: (I) All Features, (II) Gini Impurity, and (III) PCA + Gini Impurity. The AUC of the model constructed using RF in (III) for a single topic was 0.91, showing higher AUC than in the previous study. Furthermore, topic analysis showed that topics with high similarity in utterance content are effective in identifying MCI. In the case of the general topic, the model with AUC of 0.8 showed a high identification performance for unknown topics by cross validation on a topic-by-topic basis, indicating that the general topic model developed in this study can be applied to general conversation.

Frameshift mutations in peripheral blood as a biomarker for surveillance of Lynch syndrome.

Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome. Recurrent frameshift mutations in these regions are thought to play a central role in the increased risk of various cancers, but no biomarkers are currently available for the surveillance of high microsatellite instability-associated cancers. A frameshift mutation-based biomarker panel was developed and validated by targeted next-generation sequencing of supernatant DNA from cultured high microsatellite instability colorectal cancer cells. This panel supported selection of 122 frameshift mutation targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat samples (53 samples) and blood-derived cell-free DNA (cfDNA) (38 samples) obtained from 45 high microsatellite instability and mismatch repair-deficient patients. We also sequenced cfDNA from 84 healthy participants to assess background noise. Recurrent frameshift mutations at coding mononucleotide repeats were detectable not only in tumors but also in cfDNA from high microsatellite instability and mismatch repair-deficient patients, including a Lynch syndrome carrier, with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy participants. Receiver operating characteristic curve analysis showed high sensitivity and specificity (area under the curve = 0.94) of the investigated panel. We demonstrated that frameshift mutations can be detected in cfDNA from high microsatellite instability and mismatch repair-deficient patients and asymptomatic carriers. The 122-target frameshift mutation panel described here has promise as a tool for improved surveillance of high microsatellite instability and mismatch repair-deficient patients, with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.

MicroRNA-20a in extracellular vesicles derived from duodenal fluid is a possible biomarker for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate owing to its late diagnosis and aggression. In addition, there are relatively few minimally invasive screening methods for the early detection of PDAC, making the identification of biomarkers for this disease a critical priority. Recent studies have reported that microRNAs in extracellular vesicles (EV-miRs) from bodily fluids can be useful for the diagnosis of PDACs. Given this, we designed this study to evaluate the utility of cancer EVs extracted from duodenal fluid (DF) and their resident EV-miRs as potential biomarkers for the detection of PDAC. EV-miRs were evaluated and identified in the supernatants of various pancreatic cancer cell lines (Panc-1, SUIT2, and MIAPaca2), human pancreatic duct epithelial cells, and the DF from patients with PDAC and healthy controls. EVs were extracted using ultracentrifugation and the relative expression of EV-miR-20a was quantified. We collected a total of 34 DF samples (27 PDAC patients and seven controls) for evaluation and our data suggest that the relative expression levels of EV-miR-20a were significantly higher in patients with PDAC than in controls (p = 0.0025). In addition, EV-miR-20a expression could discriminate PDAC from control patients regardless of the location of the tumor with an area under the curve values of 0.88 and 0.88, respectively. We confirmed the presence of EVs in the DF and suggest that the expression of EV-miR-20a in these samples may act as a potential diagnostic biomarker for PDAC.

Novel time-saving OGTT sparing HbA1c-HOMA2 based algorithm for the diagnosis of cystic fibrosis-related diabetes

AimsThe diagnosis of cystic fibrosis-related diabetes (CFRD) faces several challenges. We propose a novel screening algorithm to alleviate the burden of cystic fibrosis (CF). MethodsThrough a retrospective cross-sectional single-centre study, HbA1c and HOMA2 indices were assessed in multiple models as alternative diagnostic tools from OGTT data. We sought to establish specific thresholds for CFRD screening with oral glucose tolerance test (OGTT) as gold standard. We evaluated various straightforward or sequential approaches, in terms of diagnostic accuracy while also quantify the potential reduction in OGTTs through these different methods. ResultsHOMA indices were recovered in 72 patients. We devised a composite index that combines HbA1c and HOMA-B: Diabetes Predicting Index in cystic fibrosis (DIPIc) = (HbA1c(%) × 3.455) – (HOMA-B(%) × 0.020) – 19.294. This index yields the highest screening accuracy according to receiver-operating characteristics curves. Using a stepwise algorithm that incorporates DIPIc decreases the requirement for annual OGTTs. A CFRD exclusion cutoff less than −1.7445 (sensitivity 98 %), in conjunction with a CFRD diagnostic threshold greater than 0.4543 (specificity 98 %) allows for 71 % OGTT sparing. ConclusionThe composite index DIPIc is a suitable, less invasive screening method for CFRD, which enables to avoid many OGTTs.

Using groundwater monitoring wells for rapid application of soil gas radon deficit technique to evaluate residual LNAPL

The application of the 222Radon (Rn) deficit technique using subsurface soil gas probes for the identification and quantification of light non-aqueous phase liquids (LNAPL) has provided positive outcomes in recent years. This study presents an alternative method for applying this technique in the headspace of groundwater monitoring wells. The developed protocol, designed for groundwater monitoring wells with a portion of their screen in the vadose zone, is based on the use of portable equipment that allows rapid measurement of the Rn soil gas activity in the vadose zone close to the water table (i.e., smear zone) where LNAPL is typically expected. The paper first describes the step-by-step procedure to be followed for the application of this method. Then, a preliminary assessment of the potential of the method was carried out at two Italian sites characterized by accidental gasoline and diesel spills into the subsurface from underground storage tanks. Although the number of tests conducted does not allow for definitive conclusions, the results obtained suggest that, from a qualitative point of view, Rn monitoring in the headspace of monitoring wells is a promising, fast, and minimally invasive screening method that could also potentially reduce the costs associated with field data acquisition. This method proves to be suitable for detecting the presence of LNAPL in both the mobile and residual phases with results consistent with the other lines of evidence available at the sites, such as groundwater and soil gas monitoring. Future efforts should be directed toward evaluating the accuracy of this method for a quantitative assessment of residual LNAPL saturations.

GaEsSeer: Early detection of gastric and esophageal cancer by integrating methylation and fragmentomics signatures in cfDNA.

4069 Background: Esophageal and gastric cancer (EC and GC) are two common cancer types that severely impact patients’ health. The 5-year survival rate for EC and GC is as low as 19% and 31%, respectively. However, early detection will significantly increase the survival rate: stage-1 EC has a 5-year survival rate of 51%, while for stage-1 GC it’s 69%. Invasive screening methods, such as endoscopy and biopsy, caused low compliance. Computational tomography and carcinoembryonic antigen were limited by low sensitivity. To address this problem, we developed GaEsSeer, a non-invasive targeted-sequencing-based assay that utilizes multiple methylation and fragmentomics features of cell-free DNA (cfDNA) to accurately detect EC and GC signals in blood. Methods: cfDNA was tested using the GaEsSeer panel, which was developed using in-house genome-wide sequencing data on EC and GC samples, and public datasets from databases and literature. Methylation features, which was quantified as methylation haplotypes or methylation encoding score, and fragmentomics features including copy number and end motif ratio were taken for modeling. Separate sub-models were trained utilizing each type of feature, which were eventually combined via logistic regression to establish the final predicting model. Results: A total of 1770 participants were recruited from multiple centers. This included 787 healthy individuals, 448 cancers (209 EC, 239 GC; stage I:156, -II:120, -III:78, and -IV:58), 174 benign esophageal diseases, and 361 benign gastric diseases. For cancer detection, the methylation-only model had an AUC of 0.909 and 0.897 in training (618 total) and test sets (617 total), respectively; while the AUC of the fragmentomics-based model was 0.885 and 0.911, respectively. The combinatorial model further improved performances, which achieves an AUC of 0.940 and 0.931 in the training and test cohorts, respectively. While the specificity remained at 96.7%, GaEsSeer detected 81.1% EC and 70.3% GC cases in the test cohort. It had a sensitivity of 74.2% and 48.9% for stage-I EC and GC, respectively. GaEsSeer also has high specificities of 87.9% and 89.8% for benign esophageal and gastric diseases, respectively. Additionally, the performance of GaEsSeer was compared with known serum cancer markers such as CEA, CA19-9, and CA72-4; and the results show that it had significantly higher sensitivity than any of these serum markers (54.8% vs 6.4% when against CEA; 53.5% vs 7.1% when against CA19-9; 50% and 16.7% when against CA72-4). Conclusions: In this pilot study, we developed the blood-based GaEsSeer assay and a model for EC and GC detection with high accuracy by stacking multiple methylation- and fragmentomics-based submodules together. Further optimization and validation of GaEsSeer using larger prospective cohorts are needed to validate its potentials for clinical application.

The State of Cancer Care in the United Arab Emirates in 2022.

Cancer is the third-leading cause of death in the United Arab Emirates (UAE); cancer care in the UAE has evolved dramatically over the last 40 years, from a single center in Al Ain in 1981 to more than 30 cancer centers and clinics across the UAE, with at least four comprehensive cancer centers in the UAE nowadays. Despite the significant progress in medical care, cancer quality control across the UAE is still lacking, with significant variations in cancer care across the cancer centers. Access to clinical trials is still hampered by a lack of expertise and research infrastructure and a small population, which renders patient accrual for trials a major challenge. Education and training are other areas for improvement that require immediate attention, and, in this review, we try to address these critical aspects for stakeholders to consider better cancer care in the UAE. Early cancer detection and screening are still evolving in the UAE, and a national screening program is lacking. There is also a need to address barriers to screening and to consider less invasive screening methods such as approved blood-based screening, which is likely to be more acceptable to the UAE population. In this review, we also address new topics that have not been addressed previously, including oncology medical tourism, psycho-oncology, onco-fertility, precision oncology, survivorship, oncology nursing, cancer support programs, and the oncology sector's response to the COVID-19 pandemic, all in the context of the UAE cancer landscape. Finally, we provide recommendations for policymakers, regulators, payers, patient advocacy groups, and the UAE oncology community regarding the delivery and future planning of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high-quality healthcare for its citizens and residents.

Profiling disease and tissue-specific epigenetic signatures in cell-free DNA

Abstract Programmed cell death, accidental cell degradation and active extrusion constantly lead to the release of DNA fragments into human body fluids from virtually all cell and tissue types. It is widely accepted that these cell-free DNA (cfDNA) molecules retain the cell-type specific genetic and epigenetic features. Particularly, cfDNA in plasma or serum has been utilized for molecular diagnostics. The current clinically implemented liquid biopsy approaches are mostly based on detecting genetic differences in cfDNA molecules from healthy and diseased cells. Their diagnostic potential is limited to pathologies involving genetic alterations, by the low proportion of cfDNA molecules carrying the mutation(s) relative to the total cfDNA pool, and by the detection limit of employed techniques. Recently, research efforts turned to epigenetic features of cfDNA molecules and found that the tissue-of-origin of individual cfDNA molecules can be inferred from epigenetic characteristics. Analysis of, e.g., methylation patterns, nucleosome or transcription factor binding site occupancies, fragment size distribution or fragment end motifs, and histone modifications determined the cell or tissue-of-origin of individual cfDNA molecules. With this tissue-of origin-analysis, it is possible to estimate the contributions of different tissues to the total cfDNA pool in body fluids and find tissues with increased cell death (pathologic condition), expanding the portfolio of liquid biopsies beyond genetics and towards a wide range of pathologies, such as autoimmune disorders, cardiovascular diseases, and inflammation, among many others. In this review, we give an overview on the status of tissue-of-origin approaches and focus on what is needed to exploit the full potential of liquid biopsies towards minimally invasive screening methods with broad clinical applications.

Insights on Proteomics-Driven Body Fluid-Based Biomarkers of Cervical Cancer.

Cervical cancer is one of the top malignancies in women around the globe, which still holds its place despite being preventable at early stages. Gynecological conditions, even maladies like cervical cancer, still experience scrutiny from society owing to prevalent taboo and invasive screening methods, especially in developing economies. Additionally, current diagnoses lack specificity and sensitivity, which prolong diagnosis until it is too late. Advances in omics-based technologies aid in discovering differential multi-omics profiles between healthy individuals and cancer patients, which could be utilized for the discovery of body fluid-based biomarkers. Body fluids are a promising potential alternative for early disease detection and counteracting the problems of invasiveness while also serving as a pool of potential biomarkers. In this review, we will provide details of the body fluids-based biomarkers that have been reported in cervical cancer. Here, we have presented our perspective on proteomics for global biomarker discovery by addressing several pertinent problems, including the challenges that are confronted in cervical cancer. Further, we also used bioinformatic methods to undertake a meta-analysis of significantly up-regulated biomolecular profiles in CVF from cervical cancer patients. Our analysis deciphered alterations in the biological pathways in CVF such as immune response, glycolytic processes, regulation of cell death, regulation of structural size, protein polymerization disease, and other pathways that can cumulatively contribute to cervical cancer malignancy. We believe, more extensive research on such biomarkers, will speed up the road to early identification and prevention of cervical cancer in the near future.

Multiple biomarkers are more accurate than a combination of carbohydrate antigen 125 and human epididymis protein 4 for ovarian cancer screening.

ObjectiveThe objective of this study was to compare and evaluate the diagnostic value of serum carbohydrate antigen 125 (CA125) and/or human epididymis protein 4 (HE4) and a panel of novel multiple biomarkers in patients with ovarian tumors to identify more accurate and effective markers for screening ovarian cancer.MethodsCandidate ovarian cancer biomarkers were selected based on a literature search. Dozens of candidate biomarkers were examined using 143 serum samples from patients with ovarian cancer and 157 healthy serum samples as non-cancer controls. To select the optimal marker panel for an ovarian cancer classification model, a set of biomarker panels was created with the number of possible combinations of eight biomarkers. Using the set of biomarkers as an input variable, the optimal biomarker panel was selected by examining the performance of the biomarker panel set using the Random Forest algorithm as a non-linear classification method and a 10-fold cross-validation technique.ResultsThe final selected optimal combination of five biomarkers (CA125, HE4, cancer antigen 15-3, apolipoprotein [Apo] A1, and ApoA2) exhibited a sensitivity of 93.71% and specificity of 93.63% for ovarian cancer detection during validation.ConclusionCombining multiple biomarkers is a valid strategy for ovarian cancer diagnosis and can be used as a minimally invasive screening method for early ovarian cancer. A panel of five optimal biomarkers, including CA125 and HE4, was verified in this study. These can potentially be used as clinical biomarkers for early detection of ovarian cancer.

Correlation of Dermatoglyphics with Clinical Characteristics of Cervix Carcinoma Patients at a Tertiary Care Centre in Kanpur, Uttar Pradesh, India

Introduction: Cervix cancer is most prevalent cancer in females. Early detection and regular screening methods are helpful for the prevention of cervix cancer related morbidity and mortality. Early stages of development, dermatoglyphic features are generated under genetic influences, but they can be influenced by environmental variables during the first three months of pregnancy. These trends may reflect an individual’s genetic make-up and, as a result, his or her proclivity for particular diseases. Therefore, the dermatoglyphic prints may serves as a non invasive anatomic marker of cervix cancer risk, allowing for early detection and treatment. Aim: To characterise dermatoglyphics in cervix cancer patient and correlate them to principal clinical features. Materials and Methods: This cross-sectional study included 300 cervix cancer patients, analysed the clinical presentations and dermatoglyphics prospectively after obtaining ethics approval from a tertiary care hospital, Kanpur, Uttar Pradesh, India, during December 2016-January 2020. The palmar dermatoglyphics (loops, arches, whorls and palmar angle) were obtained and evaluated for correlation with principal clinical features like vaginal discharge, postmenopausal bleeding, and intermenstrual bleeding using Spearman’s correlation test. Results: In this study, the frequencies of arches, loops and whorls were 81, 2051, 868 respectively. A strong positive correlation (r&gt;0.92) existed between whorls of palmar digits and clinical features of cervix cancer. Conclusion: Dermatoglyphic patterns could be used to investigate the genetic cause of cervix cancer and could potentially be used as a non invasive anatomical screening method in high-risk patients.

Feasibility of Plasma-Methylated SFRP2 for Early Detection of Gastric Cancer.

Gastric cancer (GC) is fifth most frequently diagnosed cancer and second leading cause of cancer in China. More than 80% of GC are diagnosed at an advanced stage due to low uptake rate of invasive screening method. The performance of methylated SFRP2 test was evaluated in 236 plasma samples, including 92 patients with GC, 16 intestinal metaplasia patients, 26 gastric fundic gland polyp patients, 13 small adenoma patients, 39 hyperplastic polyp patients, and 50 control patients. The sensitivity of plasma methylated SFRP2 was compared to serum CEA, CA72-4, CA19-9, and CA242 results in 79 patients with GC. The sensitivities for detecting GC and gastric intestinal metaplasia by methylated SFRP2 test were 60.9% and 56.3% with a specificity of 86.0%. Methylated SFRP2 test had significantly higher positive detection rate for patients with GC than gastric fundic gland polyp, small adenoma, and hyperplastic polyp patients. In 79 patients with GC, the sensitivities of CEA, CA72-4, CA19-9, and CA242 for detecting GC were 22.8%, 16.5%, 12.7%, and 11.4%. In comparison, the sensitivity of methylated SFRP2 test for detecting GC was 58.2%. Plasma methylated SFRP2 test may become a valuable tool for the noninvasive detection of GC and precursor lesions and showed higher sensitivity than serum tumor markers.

Calculated body muscle mass as a useful screening marker for low skeletal muscle mass and sarcopenia in chronic liver disease.

Sarcopenia is a harmful condition in patients with chronic liver disease. However, the evaluation of body muscle mass requires expensive instrumentation. The sarcopenia index (SI): (creatinine/cystatinC × 100) has been reported to correlate with muscle volume. A calculated body muscle mass (CBMM) using creatinine, cystatinC, and bodyweight also correlates with muscle mass. We evaluated the applicability of using SIs and CBMMs as screening methods for sarcopenia. Patients (n = 303) with liver damage were evaluated for creatinine, cystatinC, and grip strength (GS). All patients were evaluated using cross-sectional computed tomography images of the third lumbar vertebrae to determine their skeletal muscle (SM) mass. CBMMs and SIs were compared with SMs, GSs, and sarcopenia. Correlation coefficients (R) between SMI (SM/height2 [m2 ]) and CBMM, and between GS and CBMM were 0.643 and 0.723, respectively. Factors contributing to low GSs; low SM indices; and sarcopenia were age and SM; sex, age, GS, SI, and CBMM indices; and sex, bodyweight, and CBMM, respectively, in the multivariate logistic analyses. Receiver operating characteristic curve analysis between sarcopenia and CBMM showed an area under the receiver operating characteristic curve of 0.78504 in women and 0.86067 in men. Cut-off CBMM values for sarcopenia were 27.903 (sensitivity 0.73958) in women and 39.731 (sensitivity 0.7941) in men. CBMMs and SIs are simple and minimally invasive screening methods in which low levels are indicative of sarcopenia in patients with liver disease.

Repetitive Saliva Swallowing Test Predicts COPD Exacerbation.

IntroductionPredicting phenotypes at risk of chronic obstructive pulmonary disease (COPD) exacerbation is extremely important. Dysphagia is becoming recognized as one of these phenotypes. A convenient method of screening for dysphagia and COPD exacerbation risk is desired. The repetitive saliva swallowing test (RSST) is one of the least invasive dysphagia screening methods. We previously reported the possible relation between the RSST result and COPD exacerbation in a retrospective study. Based on this, we performed a prospective study to evaluate the efficacy of RSST as a predictor of COPD exacerbation and to determine its optimal cut-off value for COPD.MethodsSeventy patients with COPD were recruited. Patients underwent the following dysphagia screening tests: the 10-item Eating Assessment Tool, Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease, RSST, water swallowing test, and simple swallow provocation test. After one year, they were classified into two groups according to the presence of COPD exacerbation during the follow-up period.ResultsTwenty-seven patients had one or more exacerbations in the past year. During the follow-up period, 28 patients had one or more exacerbations (E group), and 42 had none (non-E group). There were no significant differences between the groups except for the presence of past exacerbations and the results of the RSST, when the cut-off value was set at 2, 3, 4, or 5 swallows. The number of swallows in the RSST was significantly lower in the E group than in the Non-E group. A cut-off value of 5 was the most effective. The time to first exacerbation was significantly longer in those with an RSST value of >5. The RSST was more reliable for differentiating the E group and non-E group than the presence of exacerbation in the past year (hazard ratios: 13.78 and 2.70, respectively).ConclusionAn RSST cut-off value of 5 may be a strong predictor of COPD exacerbation.

Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.

BackgroundNasopharyngeal carcinoma is a rare form of cancer across the world except in certain areas such as Southern China, Hong Kong and Malaysia. NPC is considered a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those with advanced disease. Given that early symptoms of NPC are non-specific and that the nasopharynx is relatively inaccessible, less invasive screening methods such as biomarker screening might be the key to improve NPC survival and management. A number of genes with their respective polymorphisms have been shown in past studies to be associated with survival of various cancers. hOGG1 and XPD genes encode for a DNA glycosylase and a DNA helicase respectively; both are proteins that are involved in DNA repair. ITGA2 is the alpha subunit of the transmembrane receptor integrin and is mainly responsible for cell-cell and cell-extracellular matrix interaction. TNF-α is a cytokine that is released by immune cells during inflammation.MethodsRestriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC.ResultsNPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14–3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively.ConclusionThe finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.

17 - Screening for anal dysplasia in women with a history of human papillomavirus related lower genital tract pathology

Background Women with a human papillomavirus related history of cervical, vaginal or vulvar high-grade dysplasia or cancer are at increased risk to develop anal dysplasia or anal cancer. Screening for anal cancer precursors (squamous intraepithelial lesions (SIL)) with high resolution anoscopy (HRA) in high-risk populations is subject of debate. In this study we evaluated standardized intra-anal SIL screening using HRA in high-risk female patients. Methods A retrospective observational study was performed to evaluate the prevalence of intra-anal SIL in women with a history of vulvar high-grade SIL (HSIL) and perianal HSIL diagnosed at the Netherlands Cancer Institute, who were referred for intra-anal SIL screening using HRA in the MC Slotervaart between 2015 and 2017. Results 22 female patients were screened for anal SIL using HRA. 19 females had a history of biopsy proven vulvar HSIL and 19 females had a history of biopsy proven perianal HSIL. Eleven (50%) patients had a history of multizonal HSIL at three or more perianogenital locations. No anal cancer was found at screening, 7 (32%) patients were diagnosed with anal HSIL and 7 (32%) patients with low-grade anal SIL. Conclusions We found a high prevalence of anal HSIL in women with HPV related lower genital tract dysplasia. Intra-anal SIL screening using HRA in this high risk population seems to be justified. However, HRA is an invasive screening method. Studying other, less invasive screening methods remains important.

P-187 - Erythrocyte membrane fatty acids as the potential biomarkers for detection of early-stage and progression of colorectal cancer

Introduction: Colorectal cancer (CRC) is the third most common cancer in the world. Clinical data show that 5-year survival rate of early-stage CRC postoperative patients is around 90%. However, most of CRC patients were diagnosed at advanced stage due to its asymptomatic and poor diagnostic techniques. Early screening is an effective way to reduce the morbidity and mortality. So, it is necessary to develop low-cost, less invasive, high-sensitivity, and high-specificity screening methods for early diagnosis of CRC and its progression. The study aims to assess erythrocyte membrane fatty acids (FA) as the potential biomarkers for detection of early-stage from healthy controls and progression of colorectal cancer (CRC). Methods: Erythrocyte membrane FA from 95 patients (56 + 8 years old) with colorectal adenocarcinoma and 28 healthy people (the control group) were measured using an accelerated solvent extraction and analyzed by GC/MS system triple quad Agilent 7000B (USA). Tumors were further classified into early stage (stage I or II, n = 44) and advanced stage (stage III or IV, n = 51) based on TNM classification. Results: Erythrocyte membrane levels of C14:0 (p < 0.03), C15:0 (p < 0.04), C17:0 (p < 0.02), the sum of saturated FA (p < 0.03), C16:1 (p < 0.04), the sum of monounsaturated FA (p < 0.01), C18:2 (p < 0.01), omega-6/omega-3 (p < 0,01) in early stage CRC patients were significantly decreased compared with healthy controls, whereas the levels of C20:0 (p < 0.01), C20:2, (p < 0.01), C20:3 (p < 0.001), C20:4 (p < 0.001), C22:4 (p < 0.001), C22:5 (p < 0.001), C22:6 (p < 0.001) and the sum of all unsaturated FA (p < 0,03) were significantly higher than those from the controls. CRC progression was accompanied by decrease in the content of saturated, monounsaturated as well as by increase polyunsaturated fatty acids (p < 0.001-0.05). Elevated levels of polyunsaturated fatty acids as structural components of membranes reflect a high level of their instability, which is probably associated with the process of tumor proliferation. In contrast, a decrease in the level of saturated fatty acids may be due to their consumption as an energy substrate for rapid metabolism which is necessary for tumor growth. As saturated FA do not require creation of a double bond within the beta-oxidation process it allows them for an accelerated energy production. The panel, containing the FA - C17:0, C16:1, C18:2, C20:4, C22:5, C22:6 - achieved an excellent diagnostic performance when comparing early stage patients with healthy controls with an AUC of 0.959, a sensitivity of 86.5%, and a specificity of 96.2%. A combination of C16:0, C18:1;t9, C18:3, C20:2, C20:4, C20:5, C22:5, C22:6 showed the best diagnostic ability when comparing the late stage CRC patients with early stages (AUC 0.871, sensitivity of 82.7%, specificity of 80.8%. Conclusion: Erythrocyte levels of the fatty acids should be considered as the promising biomarkers for detecting of early stages of CRC and the progression of the disease.

Validation: a critical step in bringing biomarkers to clinical fruition

Screening is vital to reducing morbidity and mortality due to cancer. A primary cause of poor survival is that many cancers are detected late and often after they have metastasized to distant sites. Therapies, therefore, become challenging for late-stage disease and are not successful for nearly all cancer types. The mortality rates from cancers where screening tools are available are lower than from cancers for which no viable screening tools exist. Even for cancers where screening tools currently exist, there is room for improvement, either in the accuracy of the tests or in increasing widespread use of screening by making the tests less invasive. For instance, despite widely available screening methods that can detect early-stage colon cancer or its precursors, only approximately 40% of newly diagnosed colon cancers are localized. It is a challenge to develop screening tests that are not only highly sensitive but also highly specific, to avoid putting patients through unnecessary biopsies and treatment. Biomarkers have great potential to improve the existing diagnostic accuracies of screening modalities and substitute invasive screening methods with noninvasive methodologies using bodily fluids such as plasma, serum, saliva, urine, etc. Biomarkers are defined by the National Institutes of Health as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” In this commentary, we discuss important measures that could be taken to increase the chances of bringing biomarkers to clinical fruition.