Colorectal cancer screening: A review of current screening options, timing, and guidelines.

Screening for colon and rectal cancer has been associated with reduced incidence over the past few decades. However, shown a paradoxical increase in colon and rectal cancer in those younger than 50 years has also been recently shown. This information, along with the introduction of new screening modalities, has lead to updates in the current recommendations. We present some of the data supporting the use of current screening modalities, as well as summarize current guidelines.

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer.

Objective: This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics. Methods: Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan-Meier technique, Cox regression analysis, LinkedOmics, Pearson's correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein-protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors. Results: In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors. Conclusion: FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

Effect of a family-based multimedia intervention on the uptake of faecal immunohistochemical test among South Asian older adults: A cluster-randomised controlled trial.

BACKGROUND: Colorectal cancer screening, including faecal immunohistochemical test, is an effective method for detecting colorectal cancer early. Nevertheless, faecal immunohistochemical test uptake among South Asian ethnic minorities is low because they have limited knowledge of and face barriers in accessing colorectal cancer screening. Tailored education and appropriate messaging has potential to convey to this population group the importance of colorectal cancer screening. OBJECTIVES: This study aimed to assess the acceptability and effectiveness of a family-based multimedia intervention to raise awareness of colorectal cancer screening and increase the uptake of faecal immunochemical tests among South Asian older adults. DESIGN: A cluster-randomised controlled trial with a wait-list control group. PARTICIPANTS: Three-hundred and twenty dyads of South Asian older adults and their younger family members were recruited at South Asian community centres and non-governmental organisations providing support services to local South Asians in six Hong Kong districts. METHODS: Group allocation of dyads during cluster randomisation was based on the group assignment of the district where they were recruited. The intervention comprised a multimedia health talk, conveying the importance of colorectal cancer screening and support from younger family members in encouraging their older relatives to undergo screening. Site coordinators assisted participants in accessing faecal immunohistochemical test. The primary outcome was increased uptake of faecal immunohistochemical test among South Asian older adults. Secondary outcomes included younger family members' encouragement of their older relatives to undergo faecal immunohistochemical test and their readiness to assist their relatives with the test. Acceptability of the intervention was measured by dyad satisfaction with the intervention. RESULTS: The proportion of older adults participating in faecal immunohistochemical testing was significantly higher among intervention dyads compared with controls (71.8% vs 6.8%, p < 0.001). No significant within-group change was observed on the willingness of younger family members in the intervention group to encourage older adults to undergo faecal immunohistochemical test, nor their readiness to assist older adults in doing so, although a decrease in both outcomes was observed among the control group. Most participants (>86%) were satisfied with the intervention. CONCLUSIONS: Our findings demonstrate the acceptability and effectiveness of the intervention in enhancing faecal immunohistochemical test uptake among South Asian older adults, and the benefit of using a family-based approach in the implementation of cancer screening interventions for these individuals. Implementation of the intervention as a component of usual care within South Asian communities is recommended. Trial registration ISRCTN72829325, 10 July 2018.

Study on the expression of TOP2A in hepatocellular carcinoma and its relationship with patient prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. However, the molecular mechanism of HCC formation remains to be explored and studied. OBJECTIVE: To investigate the expression of TOP2A in hepatocellular carcinoma (HCC) and its prognosis. METHODS: The data set of hepatocellular carcinoma was downloaded from GEO database for differential gene analysis, and hub gene was identified by Cytoscape. GEPIA was used to verify the expression of HUB gene and evaluate its prognostic value. Then TOP2A was selected as the research object of this paper by combining literature and clinical sample results. Firstly, TIMER database was used to study TOP2A, and the differential expression of TOP2A gene between normal tissues and cancer tissues was analyzed, as well as the correlation between TOP2A gene expression and immune infiltration of HCC cells. Then, the expression of top2a-related antibodies was analyzed using the Human Protein Atlas database, and the differential expression of TOP2A was verified by immunohistochemistry. Then, SRTING database and Cytoscape were used to establish PPI network for TOP2A and protein-protein interaction analysis was performed. The Oncomine database and cBioPortal were used to express and identify TOP2A mutation-related analyses. The expression differences of TOP2A gene were identified by LinkedOmics, and the GO and KEGG pathways were analyzed in combination with related genes. Finally, Kaplan-Meier survival analysis was performed to analyze the clinical and prognosis of HCC patients. RESULTS: TOP2A may be a new biomarker and therapeutic target for hepatocellular carcinoma.

FIT negative cancers: A right-sided problem? Implications for screening and whether iron deficiency anaemia has a role to play.

INTRODUCTION: Faecal Immunohistochemistry Testing (FIT) is recommended as an adjunct to guide referrals from Primary Care for individuals without rectal bleeding, who do not meet the suspected cancer pathway referral guidelines. It has largely replaced Faecal Occult Blood Testing. AIMS: To assess the specificity of FIT. To understand the characteristics of FIT negative cancer patients and whether they have predominantly right sided cancers. Evaluating the efficacy of FIT and Iron deficiency anaemia in combination to capture patients with colorectal cancers. METHODS: A study of 1000 symptomatic patients, undergoing FIT by Clinicians during the 'Digital rectal examination'. Inclusion criteria; all patients referred via our cancer referral pathway. FIT positivity was set at 10 µg g of faeces. RESULTS: There were 7 FIT negative cancers in this cohort; 1 was a lymphoma and the other 6 were caecal adenocarcinomas. 5 were anaemic. The positive predictive value of IDA was 34% compared with 'other symptoms'; 18%. The negative predictive value of FIT was 99.05% in this cohort. Specificity for FIT was 86.9% (CI 96%). CONCLUSION: Two separate referral pathways for IDA and FIT positive tests, would have captured all patients except 2; the lymphoma and 1 advanced caecal adenocarcinoma. FIT is an excellent triage tool prior to colonoscopy however capturing right sided disease remains a weak point. Multivariate analysis of patients in addition to IDA and FIT should improve capture of this subgroup.

In Vitro and In Vivo Studies of Biodegradability and Biocompatibility of Poly(εCL)-b-Poly(EtOEP)-Based Films.

The control of surface bioadhesive properties of the subcutaneous implants is essential for the development of biosensors and controlled drug release devices. Poly(alkyl ethylene phosphate)-based (co)polymers are structurally versatile, biocompatible and biodegradable, and may be regarded as an alternative to poly(ethylene glycol) (PEG) copolymers in the creation of antiadhesive materials. The present work reports the synthesis of block copolymers of ε-caprolactone (εCL) and 2-ethoxy-1,3,2-dioxaphospholane-2-oxide (ethyl ethylene phosphate, EtOEP) with different content of EtOEP fragments, preparation of polymer films, and the results of the study of the impact of EtOEP/εCL ratio on the hydrophilicity (contact angle of wetting), hydrolytic stability, cytotoxicity, protein and cell adhesion, and cell proliferation using umbilical cord multipotent stem cells. It was found that the increase of EtOEP/εCL ratio results in increase of hydrophilicity of the polymer films with lowering of the protein and cell adhesion. MTT cytotoxicity test showed no significant deviations in toxicity of poly(εCL) and poly(εCL)-b-poly(EtOEP)-based films. The influence of the length of poly(EtOEP)chain in block-copolymers on fibrotic reactions was analyzed using subcutaneous implantation experiments (Wistar line rats), the increase of the width of the fibrous capsule correlated with higher EtOEP/εCL ratio. However, the copolymer-based film with highest content of polyphosphate had been subjected to faster degradation with a formation of developed contact surface of poly(εCL). The rate of the degradation of polyphosphate in vivo was significantly higher than the rate of the degradation of polyphosphate in vitro, which only confirms an objective value of in vivo experiments in the development of polymer materials for biomedical applications.

TRIM24 as an independent prognostic biomarker for prostate cancer.

INTRODUCTION: Simply applicable biomarkers for prostate cancer patients predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen receptor signaling and to correlate with an aggressive prostate cancer phenotype. Based on these data, we proofed TRIM24 as a prognostic biomarker for risk stratification. MATERIALS AND METHODS: We performed TRIM24 immunohistochemistry on 2 independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases, and 129 benign prostatic samples from 497 patients as well as on 246 prostate needle biopsies. Expression data were correlated with clinic-pathological data including biochemical recurrence-free survival (bRFS) as endpoint. RESULTS: Benign samples show no or low TRIM24 expression in 94%, while tumor tissues demonstrate significant higher levels. Strongest expression is observed in advanced and metastatic tumors. In multivariate analyses, TRIM24 up-regulation on radical prostatectomy specimens correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher grade group, positive nodal status and extraprostatic tumor growth. TRIM24 assessment on prostate needle biopsies taken prior to treatment decision at time of initial diagnosis significantly correlates with recurrence after surgery. CONCLUSION: Using 2 large independent radical prostatectomy specimen cohorts, we found that TRIM24 expression predicts patients' risk to develop disease recurrence with high accuracy and independent from other established biomarkers. Further, this is the first study exploring TRIM24 expression on prostate needle biopsies which represents the clinically relevant tissue type on which biomarkers guide treatment decisions. Thus, we strongly suggest introducing TRIM24 evaluation in prostate needle biopsies in clinical routine as an inexpensive and simple immunohistochemical test.

Additional Progress in the Development and Application of a Direct, Rapid Immunohistochemical Test for Rabies Diagnosis.

Laboratory-based surveillance is fundamental to effective rabies prevention and control. The direct fluorescent antibody (AB) test (FAT) is the gold standard for rabies diagnosis. Recently, additional tests besides the FAT have been developed, such as the direct rapid immunohistochemical test (DRIT). In this study, our objective was to further refine technical aspects of the DRIT using a combination of two monoclonal ABs (MABs), 502 and 802, conduct additional testing among rabies reference laboratories using a diversity of animal species and rabies virus (RV) variants and compare the potential utility of the DRIT for end users via proficiency testing (PT) against the FAT. Considering the ideal molar ratios of biotin to AB in formulation of the DRIT conjugate, 3.9 was found to be superior to 7.4, for detection of RV antigens in the brain of a naturally infected raccoon. Optimization of the DRIT conjugate may also be dependent upon the apparent choice of specific viral antigens for testing, as a gray fox RV variant reacted less strongly than a raccoon RV variant in determining the working dilution of the MAB cocktail. Using the same MABs and protocol, the DRIT was compared to the FAT using more than 800 samples of mammalian brains, representative of more than 25 taxa, including in excess of 250 animal rabies cases from Europe and North America. Sensitivity was determined at 98% (96⁻100%, 95% CI) and specificity was calculated at 95% (92⁻96%, 95% CI). In a comparison among end users, PT of laboratory personnel resulted in values of 77⁻100% sensitivity and 86-100% specificity. Based upon these and previously reported results, the DRIT appears to be a suitable alternative to the FAT for use in lyssavirus diagnosis.

Bowel cancer screening for women at midlife.

In Australia one in 15 women will be diagnosed with colorectal cancer in their lifetime because of the high incidences of lifestyle risk factors. The risk could be reduced by taking aspirin. Evidence-based Clinical Practice Guidelines for the prevention, early detection and management of colorectal cancer produced by Cancer Council Australia and approved by the National Health and Medical Research Council recommended that 'population screening in Australia, directed at those at average risk of colorectal cancer and without relevant symptoms, is immunochemical fecal occult blood testing every 2 years, starting at age 50 years and continuing to age 74 years.' Women at high risk because of family history will need more intense screening. At the current 40% participation rate, it is estimated that biennial screening with fecal immunohistochemical tests (FIT) reduces colorectal cancer incidence by 23% and mortality by 36%. The major adverse effects of screening are the psychological impact of a positive FIT that does not prove to be cancer, or adenomas on colonoscopy (47.7%), and the rare side-effects of colonoscopy of hemorrhage, bleeding or even death. A range of factors that could increase a woman's participation rate includes advice to screen from her general practitioner and more information about the nature of the screening tests.

Evaluation of monoclonal antibody-based direct, rapid immunohistochemical test for rabies diagnosis.

Rabies is a major public health problem in developing countries in Asia and Africa. Although a number of laboratory diagnoses can be used for rabies control, the WHO and OIE recommended gold standard for rabies diagnosis is the direct fluorescent antibody test (FAT). However, FAT is not widely used in developing countries because of deficient financial sources to procure fluorescent microscope. Recently the direct rapid immunohistochemical test (dRIT) has been developed and has a worldwide promising application, particularly in developing countries, since its result can be read by inexpensive light microscopy, in addition to be consistent with that of FAT. However, no commercial conjugated antibody is available to meet the laboratory demand. We describe here the production of a monoclonal antibody (MAb) against rabies virus (RABV) N protein and its use as a biotinylated conjugate in a dRIT. Tested against a batch of 107 brain specimens representing a wide phylogenetic diversity of RABV collected from different animal species with multiple geographical origins in China, results showed that the dRIT had 100% specificity (95% CI 0.93-1.00) and 96.49% sensitivity (95% CI 0.88-1.00) as compared with the gold standard FAT. It therefore provides a simple, economical alternative to FAT, particularly for use in rabies diagnosis in developing countries.

Evaluation of a Direct Rapid Immunohistochemical Test (dRIT) for Rapid Diagnosis of Rabies in Animals and Humans / 中国病毒学·英文版

Presently the gold standard diagnostic technique for rabies is the direct immunofluorescence assay (dFA) which is very expensive and requires a high level of expertise.There is a need for more economical and user friendly tests,particularly for use in developing countries.We have established one such test called the direct rapid immunohistochemical test (dRIT) for diagnosis of rabies using brain tissue.The test is based on capture of rabies nucleoprotein (N) antigen in brain smears using a cocktail of biotinylated monoclonal antibodies specific for the N protein and color development by streptavidin peroxidase-amino ethyl carbazole and counter staining with haematoxollin.The test was done in parallel with standard FAT dFA using 400 brain samples from different animals and humans.The rabies virus N protein appears under light microscope as reddish brown particles against a light blue background.There was 100 ％ correlation between the results obtained by the two tests.Also,interpretation of results by dRIT was easier and only required a light microscope.To conclude,this newly developed dRIT technique promises to be a simple,cost effective diagnostic tool for rabies and will have applicability in field conditions prevalent in developing countries.

Resultados preliminares del pesquisaje neonatal inmunohistoquímico para la detección del síndrome de frágil X / Preliminary results of the immunohistochemical neonatal screening for detecting the fragile X syndrome

El síndrome de frágil X constituye la entidad genética que ocupa el primer lugar como causa de retraso mental hereditario, caracterizado por un fenotipo físico y psiconeuroconductual muy peculiar. Han sido innumerables los estudios que se han realizado con el fin de dilucidar la función del gen y la localización de la proteína que la misma codifica relacionado con esta afección, entre los cuales se encuentran las técnicas inmunohistoquímicas. Se aplicó la técnica inmunohistoquímica con el objetivo de detectar individuos con riesgo genético de presentar el síndrome de frágil X a través de un pesquisaje neonatal en un período de 14 meses. Se pesquisaron un total de 2 914 recién nacidos varones, de los cuales 2 414 obtuvieron resultados inmunohistoquímicos. Diez casos fueron proteína negativos, en los cuales su desarrollo psicomotor fue evaluado exhaustivamente durante un período de 3 años, y fue normal; no se detectó ningún individuo con la enfermedad.

The Fragile X syndrome is the genetic entity that is the first cause of hereditary mental retardation characterized by a very peculiar physical and psychoneuroconductal phenotype. Innumerable studies, including the immunohistochemical techniques, have been conducted aimed at dilucidating the gene's function and the localization of the protein that it codified related to this affection. The immunohistochemical techique was used in order to detect individuals at genetical risk for presenting Fragile X syndrome by neonatal screening in 14 months. A total of 2 914 male infants were screened of whom 2 414 showed histochemical results. 10 cases tested negative protein. Their psychomotor development was exhaustively evaluated for 3 years and it was normal. The disease was not detected in any individual.