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Aug 2016 DOI 10.14302/issn.2471-7061.jcrc-14-426
Background: Colorectal cancer (CRC) screening by Fecal Immunohistochemical Testing (FIT) followed by colonoscopy reduces colorectal cancer mortality. Barriers to colonoscopy should be minimised. Objective: To compare psychological “risks” of colonoscopy in FIT positive (FIT+) subjects and those with Inflammatory Bowel Disease (IBD). Method: IBD patients undergoing colonoscopic CRC surveillance were age and gender matched with FIT+ individuals awaiting colonoscopy. Subjects completed Spielberger State and Trait Scales for current levels of anxiety, depression, anger and curiosity, versus long term personality tendencies. Results: 70 IBD respondents were matched with 70 FIT+ respondents, (57% male, mean age 57.6 years). FIT+ subjects demonstrated greater scores for state Anxiety (22.3 vs 20.3 p=0.024), Curiosity (24.3 vs 21.8 p=0.036), Anger (13.7 vs11.5 p=0.037) and Depression (23.8 vs21.2 p=0.002). Conclusion: FIT+ patients experience more anxiety and depression prior to their colonoscopy than IBD patients, which may reduce colonoscopy uptake and is important to address.
Mar 2022 DOI 10.14302/issn.2641-5518.jcci-22-4096
Introduction Benign duodenocolic fistula (DCF), also known as a non-malignant fistula between the duodenum and colon, with or without cecum-involvement, is an unusual complication of different gastrointestinal (GI) diseases 12. Case This is a case of a 28-year-old Filipino female who presented with periumbilical pain for five months, with associated anorexia, fever, and weight loss. Biopsy showed chronic granulomatous inflammation with caseation necrosis and Langhan’s type giant cells consistent with tuberculous etiology (Figure 6 and Figure 7). Category I Anti-TB treatment for six months was started and the service planned to repeat both colonoscopy and CT-scan after the initial round of anti-TB treatment. Conclusion Benign duodenocolic fistula in the form of extrapulmonary TB is a rare GI finding that is triggered by inflammatory processes. Proper management in this case was to treat the underlying TB infection which is endemic in the Philippines.
Oct 2020 DOI 10.14302/issn.2379-7835.ijn-20-3418
Isolation methods that employ readily-available inexpensive supplies on the open market, which are reliable, as well as economical, such as nucleic acid amplification techniques (NAAT) based on microfluidic technology in low-resource research settings (LRRS) that meets the ASSURED guidelines are essential to develop a noninvasive diagnostic colon cancer screen in stool using micro(mi)RNA molecules. A combination of a microfluidic-based MiRNA stool test with a reliable rolling circle amplification/detection method applied to the quantification of miRNA molecules, result in an affordable sensitive and specific isothermal method for the noninvasive quantitative detection of miRNAs in LRRS. Scientists and engineers have become interested in miRNAs, and they have intensified their efforts to apply emerging simple detection tools to the important bioanalytical challenge of quantifying these small 18-26 nt long molecules. Some of the proposed approaches incorporate novel material, such as simple centrifuges and methods based on microfluidic technology, while others utilize the interesting biological properties of these molecules, such as forming branched RCA structures, allowing for the detection of these biomarker molecules at an attomolar "aM" concentration level, using low cost extraction and isothermal amplification methods in LRRS. We have been interested in studying colorectal cancer (CRC) because it is the 3rd most common malignancy worldwide, and stool can be obtained noninvasively from the patients. We have focused in this research on colon cancer (CC) because it is more common in the USA than rectal cancer (RC). The innovation of our approach lies in the exploratory use of an affordable, quantitative miRNA profiling in noninvasive stool samples in LRRS, whose extracted fragile total RNA is stabilized shortly after excretion from stool by commercially available kits, so it does not ever fragment, followed by quantitative standardized analytical tests that are neither labor intensive, nor require expensive instrumentation, in order to develop apanel of novel miRNA genes for the noninvasive diagnostic screening of early left and right sporadic colon cancers, more economically, and with higher sensitivity and specificity than any other colon cancer screening test currently available on the market. To show the clinical sensitivity and specificity of the proposed quantitative miRNA test using simple methodologies in LRRS,the miRNA results are to be correlated with FOBT, colonoscopy, and pathology data. Standardization establishes test’s performance criteria (sample selection, optimal sample running conditions, preservation and storage), in order to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in low-resource laboratory settings worldwide.
Jun 2020 DOI 10.14302/issn.2379-7835.ijn-19-3123
Isolation methods that employ readily-available inexpensive supplies on the open market, which are reliable, as well as economical, such as nucleic acid amplification techniques (NAAT) based on microfluidic technology in low-resource research settings (LRRS) that meets the ASSURED guidelines are essential to develop a noninvasive diagnostic colon cancer screen in stool using micro(mi)RNA molecules. A combination of a microfluidic-based MiRNA stool test with a reliable rolling circle amplification/detection method applied to the quantification of miRNA molecules, result in an affordable sensitive and specific isothermal method for the noninvasive quantitative detection of miRNAs in LRRS. Scientists and engineers have become interested in miRNAs, and they have intensified their efforts to apply emerging simple detection tools to the important bioanalytical challenge of quantifying these small 18-26 nt long molecules. Some of the proposed approaches incorporate novel material, such as simple centrifuges and methods based on microfluidic technology, while others utilize the interesting biological properties of these molecules, such as forming branched RCA structures, allowing for the detection of these biomarker molecules at an attomolar "aM" concentration level, using low cost extraction and isothermal amplification methods in LRRS. We have been interested in studying colorectal cancer (CRC) because it is the 3rd most common malignancy worldwide, and stool can be obtained noninvasively from the patients. We have focused in this research on colon cancer (CC) because it is more common in the USA than rectal cancer (RC). The innovation of our approach lies in the exploratory use of an affordable, quantitative miRNA profiling in noninvasive stool samples in LRRS, whose extracted fragile total RNA is stabilized shortly after excretion from stool by commercially available kits, so it does not ever fragment, followed by quantitative standardized analytical tests that are neither labor intensive, nor require expensive instrumentation, in order to develop apanel of novel miRNA genes for the noninvasive diagnostic screening of early left and right sporadic colon cancers, more economically, and with higher sensitivity and specificity than any other colon cancer screening test currently available on the market. To show the clinical sensitivity and specificity of the proposed quantitative miRNA test using simple methodologies in LRRS,the miRNA results are to be correlated with FOBT, colonoscopy, and pathology data. Standardization establishes test’s performance criteria (sample selection, optimal sample running conditions, preservation and storage), in order to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in low-resource laboratory settings worldwide.
Feb 2019 DOI 10.14302/issn.2471-7061.jcrc-18-2526
There is currently no validated micro(mi)RNA diagnostic stool test to screen for colon cancer (CC) on the market because of the complexity of fecal density, vulnerability of stool to daily changes, and the presence of three sources of miRNAs in stool (cell-free from fecal homogenates, exsosomal miRNAs from fecal exosomes, and fecal colonocytes). To address these complexities, we have first carried out a microarray miRNA experiment, using Affymetrix GeneChip miRNA 2.0 Arrays, on immunocaptured and enriched stool colonocytes of 15 subjects (three healthy controls and twelve colon cancer patients [three TNM stage 0-1 (e.g., polyps◻ ³ 1 cm, villous or tubvillous, or with high grade dysplasia), three stage 2, three stage 3, and three stage 4 in triplicates to select a smaller panel of 14 preferentially expressed mature miRNAs associated with colon cancer (12 Up-Regulated, miR-19a, miR-20a, miR-21, miR-31, miR-34a, miR-96, miR-106a, miR-133a, miR-135b, miR-206, miR-224 and miR-302; and 2 Down-Regulated, miR-143 and miR-145). In a subsequent validation study carried out on total small RNA extracted by immunocapture, followed by RT that employed TaqMan® miRNA Reverse Transcription (RT) Kit and a Custom TaqMan RT Primer Pool, absolute quantification of miRNAs, in copies/µl, was measured using a chip-based Absolute QuantStudio 3D Digital PCR analysis. To ensure that we have chosen human and not bacterial small total RNA, we have carried out coextraction protocols with E. coli K1 strain RS18, compare Agilent electrophoretic patterns, and also sequenced random samples throughout this research using mRNA/miRNA sequencing. Our initial quantitative dPCR miRNA data presented herein showe that the quantitative changes in the expression of a few mature miRNA genes in stool, which are associated with right and left colon cancer, would provide for a more convenient, sensitive and specific diagnostic screening markers thatare more useful than those test markers currently available on the market, such as the low-sensitivity (<15%) fecal occult blood test (FOBT); result in better compliance; and is more economical than the invasive and expensive colonoscopy exam in colon cancer, which can be cured if that cancer is detected at the early TNM stages, and that becomes incurable and deadly if not diagnosed before metastasis. Initial test performance characteristics of the miRNA approach showed that the test has a high numerical predictive value in colon cancer. Moreover, underpinning of the miRNA markers as a function of total RNA showed that the test can numerically differentiate between control subjects and colon cancer patients, particularly at the early stages of that curable cancer. We propose to extend our initial research results to a larger prospective and randomized five-years nested case-control study, to validate the expression of the above 14 miRNAs, in stool of 180 individuals in an epidemiologically designed study, using (30 controls and 150 colon cancer patients (thirty precancerous polyps (stage 0-1), forty five stage 2, and seventy-five colon cancer stages 3 or 4). chosen randomly by an epidemiological method from 900 control and CC subjects to allow for an adequate time to collect the required 900 stool samples, as well as allowing for statistically valid analysis, standardized test conditions, and to provide a mean for determining the true sensitivity and specificity of a miRNA-screening approach in noninvasive human stool. Power-analysis has indicated that a total of 180 individuals, which will take us 5 years to enroll in testing, is an appropriate number of subjects to standardize and validate our proposed miRNA screening test. We may find out at the end of the proposed validation study in stool that fewer miRNAs, or even one miRNA, may suffice to serve as an efficient and a quantitative marker for the non-invasive diagnostic screening of colon cancer in human stool. The above approach when combined with bioinformatics analysis, to correlate miRNA seed data with our previously published messenger (m)RNA target data in stool, allows for a thorough mechanistic understanding of how miRNA genes regulate mRNA expression, and would offer a better comprehensive diagnostic screening test for the non-invasive early detection stage (0-1) of colon cancer. In order to show the clinical sensitivity and specificity of the proposed miRNA test, the absolute miRNA PCR values, in copies/µl, will be correlated with FOBT, colonoscopy, and pathology data. Standardization will establish test’s performance characteristics (sample selection, optimal sample running conditions, preservation and storage) to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in the World. Ultimately, a smaller number of selected validated miRNAs (<10) showing increased and reduced expression could suffice to give quantitative miRNAs colon cancer expression values, useful for the early diagnostic screening of that curable cancer.
Aug 2017 DOI 10.14302/issn.2471-7061.jcrc-17-1624
Background Despite the existence of the statutory early cancer detection program in Germany and the removal of financial barriers, which is frequently reported in the literature to be the main obstacle in screening, uptake of colorectal cancer screening remains quite low. The campaign for colorectal cancer screening in German companies reported in this article started in 2010. It was initiated because of the low compliance with opportunistic public colorectal cancer screening efforts. Its goal is to improve participation by offering an organized screening program using a simple test (FIT). Methods An offer for company employees is publicized through posters, company newsletters and the intranet. The difference between the positivity rates of those who returned the kits within 20 days and later than 20 days was assessed using the Z-test. The average time between a positive result and colonoscopy was estimated using the Poincaré plot method. The positive predictive values were calculated for carcinomas, advanced adenomas or any lesions. The sensitivity and specificity of immoCare-C published by Vogel et al. and Hundt et al. were used to derive the confidence intervals for the positive likelihood ratio (for carcinoma and any kind of adenoma). Results A total of 312,147 kits were returned and analyzed (return rate 70.2%). 5.6% gave a positive result. The PPV for cancer aged between 55 and 74 was 4.6% for men and women (95% CI: 2.38%-6.76% and 1.28%-7.99%, respectively), but 22% for men (95% CI: 17.93%-26.65%) and 8% for women (95%CI: 3.63%-12.26%) for advanced adenomas. The PPV for any lesion was higher for those with familial risk (49.3%) and 42.6% for those without familial risk (95% CI: 40.2%-45.0%), but with overlapping confidence intervals. Conclusions The reported sample is not representative. Although, offering CRC screening in companies may be an effective way of increasing uptake in the target population. Differences in the test performance between men and women need further evaluation.
Mar 2016 DOI 10.14302/issn.2471-7061.jcrc-15-899
Missed cancers have been reported at higher frequencies in the right colon despite optical colonoscopy screening. The purpose of this study was to determine if there are regional differences in haustral fold height between the ascending, transverse, and descending colon using CT colonography (CTC). 50 supine CTC datasets from 50 asymptomatic, adult patients were analyzed (NCI-CBIIT instance of the National Biomedical Imaging Archive). At least 5 consecutive, pairs of unobscured haustral folds in each colonic segment were necessary to be included in this study. Of an initial 201 patients, 151 were excluded due to suboptimal colonic distension, retained fluid, tortuosity, and diverticulosis. For each dataset, the heights of the non-dependent haustral folds were measured in the ascending, transverse, and descending colon on 2D multiplanar reformations. Differences in mean HFHs were assessed using a hierarchical generalized linear mixed model. A total of 2079 colonic folds were measured: 625 in the ascending colon (including the cecum), 687 in the transverse colon, and 767 in the descending colon. The mean number of folds measured per segment was 6.87 ± 2.11. Mean HFHs were significantly taller in the ascending colon (14.62 ± 5.47 mm) than in the transverse (9.49 ± 3.65mm) or descending (6.53 ± 3.12mm) colon; mean HFHs were also significantly taller in the transverse than the descending colon, (P<0.0001, for all comparisons). In conclusion, taller colonic haustral folds are present in the proximal colon and may contribute to more frequently missed lesions (e.g. polyps) in the right colon by conventional, optical colonoscopy.
Jan 2015 DOI 10.14302/issn.2471-7061.jcrc-13-375
Colorectal polyps were traditionally classified as hyperplastic or adenomatous polyps. Adenomatous polyps were thought to be the precursor lesions of most of the colorectal cancers, but later serrated lesions were recognized as precursors of nearly one-third of colorectal cancers. Serrated lesions are a distinct group of polyps with special morphologic and histologic properties and a different carcinogenesis pathway to colorectal cancers. They are pale, flat or depressed lesions which may result in failure of detection on colonoscopy. So the endoscopist should be aware of these lesions and should follow the patients according to the surveillance guidelines.