|
1
|
Zhou MJ, Singh G, Hwang JH, Ladabaum U. Risk of Proximal Gastrointestinal Cancer After Positive Fecal Immunochemical Test. Clin Gastroenterol Hepatol 2023; 21:3179-3181.e3. [PMID: 36464140 DOI: 10.1016/j.cgh.2022.11.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/22/2022] [Accepted: 11/22/2022] [Indexed: 12/03/2022]
Affiliation(s)
- Margaret J Zhou
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Gurkirpal Singh
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Institute of Clinical Outcomes Research and Education, Woodside, California
| | - Joo Ha Hwang
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Uri Ladabaum
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California.
| |
Collapse
|
|
2
|
Evaluation of Two Fecal Occult Blood Tests for Detecting Non-Perforating Abomasal Lesions in Cattle. Animals (Basel) 2020; 10:ani10122356. [PMID: 33317186 PMCID: PMC7763188 DOI: 10.3390/ani10122356] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/25/2020] [Accepted: 12/05/2020] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Abomasal lesions in dairy cattle are highly prevalent, but diagnosis of the non-penetrating lesions is a challenge. We performed one experiment to estimate the amount of blood detectable in feces using two different tests, one experiment to determine if hemoglobin is degraded in the rumen to find possible false-positive tests due to blood from extra gastrointestinal sources and subsequently an observational study to estimate the diagnostic properties of the test with the observed lower detection limit. The observational study included primarily dairy cattle at slaughter, where we could observe the actual lesions postmortem. The detection limits of the tests marketed as Hemo-Fec® and Hemoccult II® SENSA® were 1–2 mL blood/kg feces and 2–4.5 mL blood/kg feces, respectively. Hemoglobin was not degraded in ruminal fluid and could possibly bypass the rumen and be detected in feces. In the observational study, the Hemo-Fec® test had no diagnostic value in dairy cattle with superficial erosions, with scarring, and with <4 acute or chronic lesions. The test had diagnostic potential in cattle with ≥4 acute or chronic lesions, where the proportion of true positives exceeded the proportion of false-positive results. However, many false-positive reactions make the use of the test a challenge. Abstract Non-perforating abomasal lesions occur with a high prevalence in slaughtered dairy cattle. Ante mortem diagnosis is a challenge, but the presence of occult blood in feces is suggested as a diagnostic criterion. The lower detection limit of Hemo-Fec® (Med-Kjemi, Asker, Norway) and Hemoccult II® SENSA® (Beckman Coulter, Brea, California, USA) for fecal occult blood were estimated. The Hemo-Fec® and Hemoccult II® SENSA® could detect 1–2 mL and 2–4.5 mL of blood in 1000 g of feces, respectively. Therefore, the Hemo-Fec® test was selected to access hemoglobin degradation in the rumen to establish if blood from outside the gastrointestinal tract could result in false-positive tests and an observational study to estimate the diagnostic sensitivity and specificity. Rumen microbiota did not degrade hemoglobin in a 1% blood concentration in vitro during 48 h of fermentation. The Hemo-Fec® test was only able to detect cattle with ≥4 acute lesions (diagnostic sensitivity: 0.40 [95% confidence interval (95% CI): 0.32–0.48] and ≥4 chronic lesions (sensitivity: 0.44 [95% CI: 0.35–0.52]). The Hemo-Fec® test had no diagnostic potential to detect superficial erosions or scar tissue in abomasa. Furthermore, the specificity was 0.71 [95% CI: 0.68–0.75%], and a positive test is thus not equivalent with abomasal lesions in cattle.
Collapse
|
|
3
|
Cooper RE, Hutchinson EK, Izzi JM. Evaluation of the guaiac fecal occult blood test for detection of gastrointestinal bleeding in the rhesus macaque (Macaca mulatta). J Med Primatol 2020; 49:16-25. [PMID: 31674042 PMCID: PMC6972668 DOI: 10.1111/jmp.12446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 08/20/2019] [Accepted: 09/24/2019] [Indexed: 11/16/2022]
Abstract
BACKGROUND Gastrointestinal (GI) hemorrhage accompanies several common diseases of rhesus macaques (Macaca mulatta). Guaiac fecal occult blood testing (gFOBT) is a non-invasive means to detect such bleeding in several species; however, there are currently no data indicating reliability of this test to detect GI hemorrhage in macaques. METHODS We evaluated sensitivity and specificity of gFOBT to detect simulated and biopsy-associated bleeding in the stomach, duodenum, and colon of 15 rhesus macaques. Fecal samples were analyzed via gFOBT for 72 hours. RESULTS Guaiac fecal occult blood testing was more sensitive to detect lower vs upper GI bleeding; sensitivity was volume-dependent in the upper GI tract. Single-test specificity was 95.2%. Repeated fecal collections increased gFOBT sensitivity without affecting specificity. CONCLUSIONS Guaiac fecal occult blood testing is a useful screening test for both upper and lower GI bleeding in rhesus macaques. For highest sensitivity, gFOBT should be performed on three fecal samples collected 24 hours apart.
Collapse
Affiliation(s)
- Rachel Elizabeth Cooper
- Department of Molecular and Comparative PathobiologyJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Eric Kenneth Hutchinson
- Department of Molecular and Comparative PathobiologyJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Jessica Marie Izzi
- Department of Molecular and Comparative PathobiologyJohns Hopkins University School of MedicineBaltimoreMDUSA
| |
Collapse
|
|
4
|
Lawson A, Walton B. Monitoring side effects of long‐term NSAID use in dogs with chronic osteoarthritis. IN PRACTICE 2019. [DOI: 10.1136/inp.l1506] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
|
5
|
Abstract
Background Early detection of colorectal cancer decreases the risk of mortality. Faecal occult blood tests (FOBT) are recognised as a useful tool for colorectal cancer screening. These non-invasive, rapid, and easy-to-carry assays are very often used as a point-of-care test and for self-testing. On the market, there are various types of FOB tests available, including chemical and immunochromatographic tests, which are based on different detection methods and differ in their sensitivity and specificity. Conclusions Clinicians should be aware of the causes of false-negative and false-positive test results, which can vary depending on the test. Additionally, stool sampling bias may be a source of error and must be considered by the clinician. The current FOBT methods are subject to various interfering factors; items such as proper preparation of the patient prior to testing or the clinician’s knowledge of testing limitations are key in correct interpreting results. Novel technologies such as FOBT DNA tests, micro RNA tests, and biochips equipped with bacteria can indicate bleeding from the gastrointestinal tract and improve diagnostics process.
Collapse
|
|
6
|
Kim NH, Lee MY, Park JH, Park DI, Sohn CI, Choi K, Jung YS. A Combination of Fecal Immunochemical Test Results and Iron Deficiency Anemia for Detection of Advanced Colorectal Neoplasia in Asymptomatic Men. Yonsei Med J 2017; 58:910-917. [PMID: 28792133 PMCID: PMC5552644 DOI: 10.3349/ymj.2017.58.5.910] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 04/27/2017] [Accepted: 04/27/2017] [Indexed: 12/11/2022] Open
Abstract
PURPOSE A substantial proportion of patients with colorectal cancer (CRC) present with iron deficiency anemia (IDA), and fecal immunochemical test (FIT) has proven to be an effective method for detecting the majority of CRC cases. A combination strategy of FIT results and IDA may be useful for risk stratification for detecting advanced colorectal neoplasia (ACRN). We compared the prevalence of ACRN among four groups stratified by FIT results and the presence of IDA. MATERIALS AND METHODS A cross-sectional study was performed on asymptomatic male participants who underwent both FIT and colonoscopy between 2010 and 2014 as part of a comprehensive health screening program in Korea. RESULTS Of 17236 participants, 522 (3.0%) showed positive FIT results and 26 (0.2%) had IDA. The mean age of the study participants was 40.8 years. The participants were classified into four groups: positive FIT result/IDA (G1, n=7), positive FIT result/no IDA (G2, n=515), negative FIT result/IDA (G3, n=19), and negative FIT result/no IDA (G4, n=16695). The prevalences of ACRN in G1, G2, G3, and G4 were 28.6, 13.4, 5.3, and 1.5%, respectively (p<0.001) and those of CRC were 28.6, 1.6, 0.0, and 0.01%, respectively (p<0.001). Subjects with positive FIT results and IDA had an increased risk of ACRN and CRC in both group aged <50 and ≥50 years. CONCLUSION Subjects with positive FIT results and IDA had an increased risk of ACRN. Our results suggest that a combination strategy of FIT and IDA may be helpful in selecting and prioritizing asymptomatic men for colonoscopy.
Collapse
Affiliation(s)
- Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi Yeon Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Seoul, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyuyong Choi
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
| |
Collapse
|
|
7
|
Wu CW, Cao X, Berger CK, Foote PH, Mahoney DW, Simonson JA, Anderson BW, Yab TC, Taylor WR, Boardman LA, Kisiel JB, Ahlquist DA. Novel Approach to Fecal Occult Blood Testing by Assay of Erythrocyte-Specific microRNA Markers. Dig Dis Sci 2017; 62:1985-1994. [PMID: 28660489 PMCID: PMC6021130 DOI: 10.1007/s10620-017-4627-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 05/23/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Fecal occult blood testing (FOBT) has historically relied on methods to detect hemoglobin with no fundamental innovations in decades. AIM To examine microRNA (miRNA) as a new marker class for FOBT. METHODS Candidate miRNA markers were identified by small RNA sequencing of human whole blood compared to colorectal epithelia. Markers were tested in human blood cell subsets and blood from non-human species. We assessed assay linearity in blood spiking and marker stability in stool over incubation experiments. Levels of candidate erythrocyte markers were explored in stools from colorectal cancer (CRC) cases and controls. RESULTS Based on small RNA sequencing and validation RT-qPCR, expression level of each of the top blood-enriched markers (hsa-miR-144-3p, 144-5p, 451a, 486-5p, 363-3p, 20b-5p) could perfectly discriminate blood from colorectal epithelia. All six markers arose from and showed specificity to human erythrocytes. Marker levels increased linearly with erythrocyte concentration in saline or stool and demonstrated a broader dynamic range than did immunochemical test for hemoglobin. Degradation of markers occurred in stool but was reduced with preservative buffers. Erythrocyte marker candidates for stool testing were selected in an exploratory set of stools (20 CRC, 40 normal). Candidates were then further tested in a feasibility set (29 CRC, 31 advanced adenoma, and 115 normal); a miRNA panel (hsa-miR-451a, 144-5p, and 200b-3p as normalizer) yielded an AUC of 0.89 (95% CI 0.82-0.95, P < .0001) for CRC. CONCLUSIONS A novel miRNA-based approach accurately quantifies fecal blood levels over a broad, clinically relevant range.
Collapse
Affiliation(s)
- Chung Wah Wu
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Xiaoming Cao
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Calise K. Berger
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Patrick H. Foote
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Douglas W. Mahoney
- Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Julie A. Simonson
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Bradley W. Anderson
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Tracy C. Yab
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - William R. Taylor
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Lisa A. Boardman
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - John B. Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - David A. Ahlquist
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| |
Collapse
|
|
8
|
Kim NH, Park JH, Park DI, Sohn CI, Choi K, Jung YS. Are Hemorrhoids Associated with False-Positive Fecal Immunochemical Test Results? Yonsei Med J 2017; 58:150-157. [PMID: 27873508 PMCID: PMC5122631 DOI: 10.3349/ymj.2017.58.1.150] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/05/2016] [Accepted: 05/13/2016] [Indexed: 01/02/2023] Open
Abstract
PURPOSE False-positive (FP) results of fecal immunochemical tests (FITs) conducted in colorectal cancer (CRC) screening could lead to performing unnecessary colonoscopies. Hemorrhoids are a possible cause of FP FIT results; however, studies on this topic are extremely rare. We investigated whether hemorrhoids are associated with FP FIT results. MATERIALS AND METHODS A retrospective study was conducted at a university hospital in Korea from June 2013 to May 2015. Of the 34547 individuals who underwent FITs, 3946 aged ≥50 years who underwent colonoscopies were analyzed. Logistic regression analysis was performed to determine factors associated with FP FIT results. RESULTS Among 3946 participants, 704 (17.8%) showed positive FIT results and 1303 (33.0%) had hemorrhoids. Of the 704 participants with positive FIT results, 165 had advanced colorectal neoplasia (ACRN) and 539 had no ACRN (FP results). Of the 1303 participants with hemorrhoids, 291 showed FP results, of whom 81 showed FP results because of hemorrhoids only. Participants with hemorrhoids had a higher rate of FP results than those without hemorrhoids (291/1176, 24.7% vs. 248/2361, 10.5%; p<0.001). Additionally, the participants with hemorrhoids as the only abnormality had a higher rate of FP results than those experiencing no such abnormalities (81/531, 15.3% vs. 38/1173, 3.2%; p<0.001). In multivariate analysis, the presence of hemorrhoids was identified as an independent predictor of FP results (adjusted odds ratio, 2.76; 95% confidence interval, 2.24-3.40; p<0.001). CONCLUSION Hemorrhoids are significantly associated with FP FIT results. Their presence seemed to be a non-negligible contributor of FP results in FIT-based CRC screening programs.
Collapse
Affiliation(s)
- Nam Hee Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyuyong Choi
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
| |
Collapse
|
|
9
|
Young GP, St John DJB, Cole SR, Bielecki BE, Pizzey C, Sinatra MA, Polglase AL, Cadd B, Morcom J. Prescreening Evaluation of a Brush-Based Faecal Immunochemical Test for Haemoglobin. J Med Screen 2016; 10:123-8. [PMID: 14561263 DOI: 10.1177/096914130301000305] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES To undertake a prescreening evaluation of a new brush-based faecal immunochemical test for haemoglobin, relative to a traditional spatula-sampling immunochemical test. METHODS SETTING Patients aged between 24 and 90 years, scheduled to undergo diagnostic colonoscopy in two major urban hospitals, for a range of clinical indications. DESIGN Patients sampled three stools using a spatula for the reference FlexSure OBT test and two stools using a brush for the InSure test; order of sampling was randomised. Faecal haemoglobin was quantified by a modified InSure in a subset of patients to determine whether brush-sampling allowed discrimination between groups. MAIN OUTCOME MEASURES Sensitivity for cancer or adenoma; false-positive rate in normals. Faecal haemoglobin levels. Preference for sampling method. RESULTS InSure and FlexSure OBT did not differ in their sensitivities for cancer (27/36, 75% vs 29/36, 80.5%, respectively), adenomas >or= 10 mm (12/29, 41.4% vs 13/29, 44.8%) or adenomas <10 mm (each 8/56, 14.3%). Likewise, false-positive rates in normals were similar: 4/179 (2.2%) and 5/179 (2.8%) respectively (specificities of 97.8% and 97.2%, respectively). Levels of faecal haemoglobin were highest in those with cancers; those with adenomas had intermediate levels which were also significantly higher than those in normals. The brush sampling method was preferred by 38/46 (82.6%), while 4/46 (8.7%) preferred the spatula (p<0.00001). CONCLUSIONS InSure is as sensitive and specific as FlexSure OBT for faecal haemoglobin. The novel stool-sampling method of InSure allows discrimination between normals and classes of neoplasia, and is highly preferred. The brush-sampling faecal immunochemical test InSure should now be evaluated in a screening population.
Collapse
Affiliation(s)
- G P Young
- Department of Medicine, Flinders University of South Australia, Bedford Park, SA, Australia.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
|
|
11
|
Burbridge R, Teitelman M. Evaluation of the Guaiac-Positive Patient. GASTROINTESTINAL BLEEDING 2016:183-189. [DOI: 10.1007/978-3-319-40646-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
12
|
Ong B, Rockey DC. The syndrome of a large drop in hematocrit in hospitalized patients: clinical features and gastrointestinal bleeding outcomes. J Investig Med 2015; 62:963-7. [PMID: 25203151 DOI: 10.1097/jim.0000000000000109] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Hemoglobin/hematocrit decreases in hospitalized patients without evidence of obvious gastrointestinal (GI) bleeding are common and often attributed to GI lesions. We hypothesized that inpatients with hematocrit declines without clinically overt GI bleeding have distinct clinical features and hence aimed to evaluate this clinical syndrome. METHODS We evaluated consecutive GI consults for patients with a decrease (drop) in hematocrit. Patients with documented prior GI bleeding, melena, hematochezia, hematemesis, and melenemesis were excluded. Hematocrit drops were calculated from preconsult zenith and nadir values and identified as acute (within 7 days), intermediate (7-30 days), or remote (beyond 30 days) on the basis of the shortest time to a hematocrit drop of at least 6%. RESULTS We identified 101 patients having hematocrit drops without clinical evidence of GI bleeding. Seventy-six patients (75%) had an acute drop in hematocrit with a mean decline of 9.5%, whereas the 25 patients with an intermediate or remote drop in hematocrit had a mean decline of 12.5%. Endoscopic evaluation was performed in 55 patients. Five patients (5%) had a lesion consistent with GI bleeding; identified lesions included ischemic colitis, duodenal ulcer, esophageal varices, and postsphincterotomy ulcer. In the remaining 96 patients, a clinical explanation for the hematocrit drop was identified in 56 patients (58%), most commonly attributed to sepsis/shock, volume shifts, and postprocedure bleeding. CONCLUSIONS Hematocrit drops without visible GI bleeding were uncommonly caused by bleeding intestinal lesions, contrary to current dogma. Non-GI explanations for hematocrit drops were often identified, although the cause of hematocrit drop remained unexplained in many patients.
Collapse
Affiliation(s)
- Bryan Ong
- From the *Division of Digestive and Liver Diseases, and the Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Memorial Hospital, Dallas, TX; and †Department of Internal Medicine, Medical University of South Carolina, Charleston, SC
| | | |
Collapse
|
|
13
|
Phalguni A, Seaman H, Routh K, Halloran S, Simpson S. Tests detecting biomarkers for screening of colorectal cancer: What is on the horizon? GMS HEALTH TECHNOLOGY ASSESSMENT 2015; 11:Doc01. [PMID: 26131022 PMCID: PMC4466319 DOI: 10.3205/hta000122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Aim: To identify new and emerging screening tests for colorectal cancer (CRC) that involves detection of various biomarkers like blood, DNA and RNA in samples of faeces, tissue or blood. Current practice: Screening for CRC can be done by bowel visualisation techniques and tests that measure biomarkers. The Bowel Cancer Screening Programme (BCSP) in England uses a guaiac faecal occult blood test. Methods: The strategy was to search available literature, identify developers and contact them for relevant information. Advice from experts was sought on potential utility and likely impact of identified technologies on the BCSP. Results: Ninety-three companies and five research groups were contacted. Sixty-nine relevant tests were identified. Detailed information was available for 48 tests, of these 73% were CE marked and the remainder were considered as emerging. Forty-nine tests use immunochemical methods to detect occult blood in faeces. Eight, four and two tests detect biomarkers in a sample of blood, or exfoliated cells either shed in faeces or collected from rectal mucosa respectively. Six tests were grouped as ‘other tests’. Most of the identified tests are performed manually and give qualitative detection of biomarkers. Conclusion: Variation in test performance and characteristics was observed amongst the 69 identified tests. Automated, quantitative FIT with a variable cut off are the preferred approach in the BSCP. However the units used to report FITs results do not enable comparison across products. Tests detecting biomarkers other than occult blood are more specific to neoplasms but have limited sensitivity due to the heterogeneity of cancer. Research is ongoing to identify an optimal panel of biomarkers, simplifying and automating the test, and reducing the cost.
Collapse
Affiliation(s)
- Angaja Phalguni
- NIHR Horizon Scanning Research & Intelligence Centre, School of Health and Population Sciences, University of Birmingham, United Kingdom
| | - Helen Seaman
- University of Surrey, NHS Bowel Cancer Screening Southern Programme Hub, United Kingdom
| | - Kristina Routh
- NIHR Horizon Scanning Research & Intelligence Centre, School of Health and Population Sciences, University of Birmingham, United Kingdom
| | - Stephen Halloran
- University of Surrey, NHS Bowel Cancer Screening Southern Programme Hub, United Kingdom
| | - Sue Simpson
- NIHR Horizon Scanning Research & Intelligence Centre, School of Health and Population Sciences, University of Birmingham, United Kingdom
| |
Collapse
|
|
14
|
Kobayashi Y, Watabe H, Yamada A, Suzuki H, Hirata Y, Yamaji Y, Yoshida H, Koike K. Impact of fecal occult blood on obscure gastrointestinal bleeding: Observational study. World J Gastroenterol 2015; 21:326-332. [PMID: 25574108 PMCID: PMC4284352 DOI: 10.3748/wjg.v21.i1.326] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 08/08/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate the association between small bowel diseases (SBDs) and positive fecal occult blood test (FOBT) in patients with obscure gastrointestinal bleeding (OGIB).
METHODS: Between February 2008 and August 2013, 202 patients with OGIB who performed both capsule endoscopy (CE) and FOBT were enrolled (mean age; 63.6 ± 14.0 years, 118 males, 96 previous overt bleeding, 106 with occult bleeding). All patients underwent immunochemical FOBTs twice prior to CE. Three experienced endoscopists independently reviewed CE videos. All reviews and consensus meeting were conducted without any information on FOBT results. The prevalence of SBDs was compared between patients with positive and negative FOBT.
RESULTS: CE revealed SBDs in 72 patients (36%). FOBT was positive in 100 patients (50%) and negative in 102 (50%). The prevalence of SBDs was significantly higher in patients with positive FOBT than those with negative FOBT (46% vs 25%, P = 0.002). In particular, among patients with occult OGIB, the prevalence of SBDs was higher in positive FOBT group than negative FOBT group (45% vs 18%, P = 0.002). On the other hand, among patients with previous overt OGIB, there was no significant difference in the prevalence of SBDs between positive and negative FOBT group (47% vs 33%, P = 0.18). In disease specific analysis among patients with occult OGIB, the prevalence of ulcer and tumor were higher in positive FOBT group than negative FOBT group. In multivariate analysis, only positive FOBT was a predictive factors of SBDs in patients with OGIB (OR = 2.5, 95%CI: 1.4-4.6, P = 0.003). Furthermore, the trend was evident among patients with occult OGIB who underwent FOBT on the same day or a day before CE. The prevalence of SBDs in positive vs negative FOBT group were 54% vs 13% in patients with occult OGIB who underwent FOBT on the same day or the day before CE (P = 0.001), while there was no significant difference between positive and negative FOBT group in those who underwent FOBT two or more days before CE (43% vs 25%, P = 0.20).
CONCLUSION: The present study suggests that positive FOBT may be useful for predicting SBDs in patients with occult OGIB. Positive FOBT indicates higher likelihood of ulcers or tumors in patients with occult OGIB. Undergoing CE within a day after FOBT achieved a higher diagnostic yield for patients with occult OGIB.
Collapse
|
|
15
|
Abstract
GOALS To evaluate gastroenterologists' use of esophagogastroduodenoscopy (EGD) for positive fecal occult blood test (FOBT). BACKGROUND Colonoscopy is recommended when an FOBT performed for colorectal cancer screening is positive. Guidelines suggest no further evaluation if anemia and gastrointestinal (GI) symptoms are absent. METHODS Online surveys included 4 vignettes: positive FOBT in average-risk adults 50 years of age or older with/without iron-deficiency anemia and with/without upper GI symptoms. For each scenario, respondents were asked if they would perform colonoscopy only, EGD only, colonoscopy+EGD on same day, or colonoscopy followed by EGD on different day if colonoscopy was negative. RESULTS Surveys were returned by 778 (11%) of 7094 potential responders. In patients without anemia or upper GI symptoms, 65% performed colonoscopy only; 35% added EGD (9% same day, 25% different day). EGD was added in 91% with anemia, 96% with symptoms, and 100% with anemia+symptoms. In patients with positive FOBT alone (no symptoms or anemia), multivariate analysis revealed fear of litigation as the primary factor associated with adding EGD to colonoscopy (odds ratio=4.1; 95% confidence interval, 2.3-7.3). When EGD+colonoscopy were planned for positive FOBT, private practice was associated with performing EGD on a different day (odds ratio=6.3; 95% confidence interval, 2.9-13.5 for private versus academic setting). CONCLUSIONS One third of gastroenterologists perform EGD in addition to colonoscopy for a positive FOBT alone. Fear of litigation is the most important factor in deciding whether to add EGD to colonoscopy. When both procedures are planned, they are more likely to be performed on different days in a private practice setting than in an academic setting.
Collapse
|
|
16
|
Lee YC, Chiu HM, Chiang TH, Yen AMF, Chiu SYH, Chen SLS, Fann JCY, Yeh YP, Liao CS, Hu TH, Tu CH, Tseng PH, Chen CC, Chen MJ, Liou JM, Liao WC, Lai YP, Wang CP, Ko JY, Wang HP, Chiang H, Lin JT, Chen HH, Wu MS. Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions. BMJ Open 2013; 3:e003989. [PMID: 24176798 PMCID: PMC3816242 DOI: 10.1136/bmjopen-2013-003989] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 09/27/2013] [Accepted: 10/03/2013] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions. DESIGN Cross-sectional design. SETTING Hospital-based and community-based screening settings. PARTICIPANTS A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings. INTERVENTIONS Three types of stool tests with bidirectional endoscopy as the reference standard. OUTCOMES Sensitivity, specificity and positive and negative likelihood ratios. RESULTS For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values. CONCLUSIONS The H pylori stool antigen test is more accurate than the guaiac-based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection. TRIAL REGISTRATION NCT01341197 (ClinicalTrial.gov).
Collapse
Affiliation(s)
- Yi-Chia Lee
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Tsung-Hsien Chiang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Integrated Diagnostic and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
| | - Amy Ming-Fang Yen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sherry Yueh-Hsia Chiu
- Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan
| | - Sam Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jean Ching-Yuan Fann
- Department and Graduate Institute of Health Care Management, Kainan University, Tao-Yuan, Taiwan
| | - Yen-Po Yeh
- Changhua County Public Health Bureau, Changhua County, Taiwan
| | - Chao-Sheng Liao
- Division of Gastroenterology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Hung Tu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ping-Huei Tseng
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Jyh Chen
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Integrated Diagnostic and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Wei-Chih Liao
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Yo-Ping Lai
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chen-Ping Wang
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jenq-Yuh Ko
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hung Chiang
- Taipei Institute of Pathology, Taipei, Taiwan
| | - Jaw-Town Lin
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Department of Internal Medicine, E-Da Hospital, Kaohsiung County, Taiwan
| | - Hsiu-Hsi Chen
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
17
|
The impact of age, sex and socioeconomic deprivation on outcomes in a colorectal cancer screening programme. PLoS One 2013; 8:e66063. [PMID: 23776606 PMCID: PMC3680425 DOI: 10.1371/journal.pone.0066063] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2013] [Accepted: 05/03/2013] [Indexed: 12/29/2022] Open
Abstract
Background Population-based colorectal cancer screening has been shown to reduce cancer specific mortality and is used across the UK. Despite evidence that older age, male sex and deprivation are associated with an increased incidence of colorectal cancer, uptake of bowel cancer screening varies across demographic groups. The aim of this study was to assess the impact of age, sex and deprivation on outcomes throughout the screening process. Methods A prospectively maintained database, encompassing the first screening round of a faecal occult blood test screening programme in a single geographical area, was analysed. Results Overall, 395 096 individuals were invited to screening, 204 139 (52%) participated and 6 079 (3%) tested positive. Of the positive tests, 4 625 (76%) attended for colonoscopy and cancer was detected in 396 individuals (9%). Lower uptake of screening was associated with younger age, male sex and deprivation (all p<0.001). Only deprivation was associated with failure to proceed to colonoscopy following a positive test (p<0.001). Despite higher positivity rates in those that were more deprived (p<0.001), the likelihood of detecting cancer in those attending for colonoscopy was lower (8% most deprived vs 10% least deprived, p = 0.003). Conclusion Individuals who are deprived are less likely to participate in screening, less likely to undergo colonoscopy and less likely to have cancer identified as a result of a positive test. Therefore, this study suggests that strategies aimed at improving participation of deprived individuals in colorectal cancer screening should be directed at all stages of the screening process and not just uptake of the test.
Collapse
|
|
18
|
Abstract
AIM Advances in molecular technology have resulted in the discovery of many putative biomarkers relevant to colorectal cancer (CRC). METHOD Literature searches were performed on PubMed and EMBASE using the words 'colorectal cancer', AND 'biomarkers OR markers'. Biomarkers that are either currently in clinical use or have potential clinical use were identified. RESULTS Most potential markers are in the discovery phase waiting to undergo clinical validation. Hypermethylation of the plasma septin-9 gene shows promise as a nonstool-based screening tool. Hypermethylation of the DYPD gene (encodes the enzyme dihydropyrimidine dehydrogenase) and variation of the uridine diphosphate-glucuronosyltransferase 1A (UGT1A1) gene have predictive value for side effects and the efficacy of 5-fluoruracil and irinotecan, respectively. Mismatch repair protein immunohistochemistry is able to predict response to 5-fluorouracil, and the KRAS (Kirsten rat sarcoma viral oncogene) and B-RAF (v-RAF murine sarcoma viral oncogene homolog B1) somatic gene mutation status can predict the response to anti-epidermal growth factor receptor therapy. CONCLUSION Recent advances indicate that the widespread use of biomarkers may herald the next major advance in the diagnosis and management of CRC.
Collapse
Affiliation(s)
- K F Newton
- Department of General Surgery, Manchester Royal Infirmary Department of Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester University Hospitals Trust, Manchester, UK
| | | | | |
Collapse
|
|
19
|
Julka M, Cherukuri M, Lameh R. Screening for cancerous and precancerous conditions of the colon. Prim Care 2011; 38:449-68; viii. [PMID: 21872091 DOI: 10.1016/j.pop.2011.05.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Five points for the primary care physician: 1. Colorectal cancer (CRC) is the second leading cause of cancer-related death in both men and women in the United States. 2. Guidelines recommend initiating CRC screening in average-risk patients at age 50 years, but in African Americans at age 45 years. 3. It is preferred that an informed decision is made by the patient with the help of their clinician about the type of screening test based on the patient's personal preferences. 4. Patients with personal history of chronic ulcerative colitis and Crohn colitis have significant cancer risk 8 years after the onset of pancolitis or 12 to 15 years after the onset of left-sided colitis. Colonoscopy every 1 to 2 years should be performed, with biopsies for dysplasia. 5. Counseling to consider genetic testing and early screening recommendations for those with personal or family history of familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer.
Collapse
Affiliation(s)
- Manjula Julka
- Department of Family and Community Medicine, University of Texas Southwestern Medical Center at Dallas, 6263 Harry Hines Boulevard, Clinical Building 1, Forest Park Road Suite#651, Dallas, TX 75390-9165, USA.
| | | | | |
Collapse
|
|
20
|
Esophago-gastro-duodenoscopy is not indicated in patients with positive immunochemical test and nonexplanatory colonoscopy. Eur J Gastroenterol Hepatol 2010; 22:1431-4. [PMID: 20962660 DOI: 10.1097/meg.0b013e32834059ff] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Patients with positive fecal occult blood test and unrevealing colonoscopy are often advised to undergo esophago-gastro-duodenoscopy (EGD) to exclude a bleeding source in the upper gastrointestinal tract. In this study, we evaluated EGD findings in patients with positive immunochemical fecal occult blood test (I-FOBT) not explained by colonoscopy. METHODS Out of 1221 consecutive patients having total colonoscopy after preparing I-FOBT (OC-MICRO, with threshold of 75 or 100 ngHb/ml), we included only patients without colorectal cancer or advanced adenomatous polyp on colonoscopy, who also underwent EGD within 4 months of the fecal blood testing. Findings on EGD were classified as those lesions which are likely or unlikely to bleed. RESULTS EGD was performed in 160 patients after a negative colonoscopy. The procedure was performed 1.6 ± 1.4 months after the I-FOBT. Lesion with a bleeding potential was found in 24 patients (15%). In three (12.5%) and two (8.3%) of these patients I-FOBT was positive at the 75 and 100 ngHb/ml threshold, respectively. In 136 patients EGD was normal, and I-FOBT was similarly positive in 16 (11.7%) and 13 patients (9.5%), respectively. The mean fecal hemoglobin was also similar between the groups. CONCLUSION Immunological FOBT positivity was not correlated with the finding of lesions, which are likely to bleed on EGD. Thus, EGD is probably not indicated in patients with positive I-FOBT and unrevealing colonoscopy.
Collapse
|
|
21
|
Abstract
Occult gastrointestinal bleeding, defined as bleeding that is unknown to the patient, is the most common form of gastrointestinal bleeding and can be caused by virtually any lesion in the gastrointestinal tract. Patients with occult gastrointestinal bleeding include those with fecal occult blood and iron-deficiency anemia (IDA). In men and postmenopausal women, IDA should be considered to be the result of gastrointestinal bleeding until proven otherwise. Indeed, the possibility of gastrointestinal tract malignancy in these patients means that gastrointestinal evaluation is nearly always indicated. Obscure gastrointestinal bleeding is defined as obvious bleeding from a difficult to identify source and is always recurrent. This form of bleeding accounts for approximately 5% of all cases of clinically evident gastrointestinal bleeding and is most commonly caused by bleeding from the small intestine. Capsule endoscopy and deep enteroscopy have had a major impact on the way that patients with occult and, in particular, obscure bleeding are managed. In this Review the causes, diagnostic evaluation and treatment of occult and obscure gastrointestinal bleeding are discussed.
Collapse
|
|
22
|
|
|
23
|
Positive occult blood and negative colonoscopy--should we perform gastroscopy? CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 21:633-6. [PMID: 17948132 DOI: 10.1155/2007/713047] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
24
|
Wang X, Uzu T, Isshiki K, Kanasaki M, Hirata K, Soumura M, Nakazawa J, Kashiwagi A, Takaya K, Isono M, Nishimura M, Shikano T, Nishio T, Tomita K, Arimura T. Iron status and the use of non-steroidal anti-inflammatory drugs in hemodialysis patients. Ther Apher Dial 2007; 11:215-9. [PMID: 17498004 DOI: 10.1111/j.1744-9987.2007.00476.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
We examined whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) can affect the anemia and iron status of hemodialysis patients. We recruited patients from six dialysis centers who had undergone maintenance hemodialysis for at least four months. We examined the use of NSAIDs during the past three months based on their medical records and assigned the patients to three groups (group A, non-NSAID group; group B, aspirin group; and group C, non-aspirin NSAID group). Of the 446 patients, 95 (21.3%) were treated with aspirin and 103 (23.1%) were treated with non-aspirin NSAIDs. The serum iron level and transferrin saturation (TSAT) were significantly lower in group C patients than those in group A. However, the ratio of the patients who were administrated iron preparations during the past three months was significantly higher than that in the other two groups. The incidences of positive fecal occult blood tests did not differ substantially between the three groups. The ratios of the patients who were administrated recombinant human erythropoietin were the same between three groups. Using a multiple regression analysis, the administration of non-aspirin NSAIDs was identified as an independent factor for the decreased serum iron and the decreased TSAT levels. A multiple logistic regression analysis revealed that the patients using non-aspirin NSAIDs had an increased the requirement for iron preparation therapy (OR 2.03, 95% CI, 1.28-3.22). The use of non-aspirin NSAIDs may therefore increase the risk of the iron deficiency in patients undergoing hemodialysis.
Collapse
Affiliation(s)
- Xiaoxia Wang
- Department of Medicine, Shiga University of Medical Science, Shiga, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Lin SY, Shih SH, Wu DC, Lee YC, Wu CI, Lo LH, Shiea J. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the detection of hemoglobins as the protein biomarkers for fecal occult blood. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2007; 21:3311-6. [PMID: 17879387 DOI: 10.1002/rcm.3217] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
In this study, we discover that hemoglobins (Hb), highly water-soluble globular proteins that are the most predominant proteins detected by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry in blood, can be used as protein biomarkers for fecal occult blood (FOB). Hemoglobins were extracted from the feces with pure water and separated from the solids in feces through centrifugation. Singly charged molecular ions of Hb-related alpha chains (theoretical MW: 15 126) and beta chains (theoretical MW: 15 867) were detected by MALDI-TOF operated in linear mode using 4-hydroxy-alpha-cyanocinnamic acid (alpha-CHC) as the matrix (with a volumetric ratio of 1:1). The detection limit of FOB using this method is estimated to be lower than 0.1 microg blood per mg of feces, which is approximately 10 to 100 times lower than that of the conventional chemical approaches. The foods and dietary supplements that commonly interfere with the conventional chemical assays of FOB - such as animal blood food products and tablets containing iron and vitamin C - do not interfere with the detection of Hb biomarkers during MALDI-TOF analysis.
Collapse
Affiliation(s)
- Shu-Yao Lin
- Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
26
|
Scales CD, Fein S, Muir AJ, Rockey DC. Clinical utilization of digital rectal examination and fecal occult blood testing upon hospital admission. J Clin Gastroenterol 2006; 40:913-8. [PMID: 17063111 DOI: 10.1097/01.mcg.0000225674.14594.9f] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
GOALS The objective of our investigation was to examine the clinical utilization of digital rectal examination (DRE) and fecal occult blood testing (FOBT) at hospital admission. BACKGROUND DRE at the time of hospital admission is frequently accompanied by FOBT. However, the utility of DRE with FOBT in this setting is unknown. STUDY The study cohort comprised consecutive admissions to an internal medicine service over a 3-month period. Patient characteristics were compared for subjects by DRE performance and FOBT result. Follow-up endoscopic procedures within 1 year of admission were recorded. RESULTS Complete data were available for 806 of 832 patients (96.9%). Three hundred forty eight patients underwent DRE on admission (43.2%). Patients undergoing DRE/FOBT were older (mean age 60.4+/-18.4 y vs. 55.0+/-19.6 y, P<0.001). Patients with gastrointestinal (GI) bleeding symptoms (relative risk 11.2, 95% confidence interval 5.47-23.0) or a past history of GI bleeding (relative risk 2.98, 95% confidence interval 1.93-4.58) were more likely to undergo DRE/FOBT. Among 130 (37.4%) patients with a positive FOBT, 72 (51.6%) had no history of GI bleeding symptoms; these patients were substantially less likely to undergo follow-up examination(s) than patients with a positive FOBT and a history of GI bleeding symptoms (30.6% vs. 82.8%, P<0.001). CONCLUSIONS In this cohort, patients with a past history of GI disease or symptoms were more likely to undergo FOBT. Follow-up evaluation of positive FOBT in the absence of GI bleeding symptoms was very low. Low utilization and follow-up rates may limit the utility of admission DRE with FOBT for cancer screening.
Collapse
Affiliation(s)
- Charles D Scales
- Division of Gastroenterology, Department of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
| | | | | | | |
Collapse
|
|
27
|
Abstract
Colorectal cancer screening reduces mortality in individuals 50 years and older. Each of the screening tests currently available has advantages and limitations, and there is no consensus as to which test or combination of tests is best. What is clear, however, is that the rates of colorectal cancer screening remain low. This review summarizes the clinical evidence supporting colorectal cancer screening in the average risk population and in high risk groups, discusses the advantages and disadvantages of the available screening tests, outlines the currently recommended guidelines for screening based on risk category, and discusses new and emerging technologies for colorectal cancer screening.
Collapse
Affiliation(s)
- J P Heiken
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
| |
Collapse
|
|
28
|
Gibbons PM, Tell LA, Kass PH, Christopher MM. Evaluation of the sensitivity and specificity of four laboratory tests for detection of occult blood in cockatiel (Nymphicus hollandicus) excrement. Am J Vet Res 2006; 67:1326-32. [PMID: 16881843 DOI: 10.2460/ajvr.67.8.1326] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To compare sensitivity and specificity of cytologic examination and 3 chromogen tests for detection of occult blood in cockatiel (Nymphicus hollandicus) excrement. ANIMALS 20 adult cockatiels. PROCEDURES Pooled blood from birds was divided into whole blood and lysate aliquots. Excrement was mixed with each aliquot in vitro to yield 6 hemoglobin (Hb) concentrations (range, 0.375 to 12.0 mg of Hb/g of excrement). For the in vivo portion of the study, birds were serially gavaged with each aliquot separately at 5 doses of Hb (range, 2.5 to 40 mg/kg). Three chromogen tests and cytologic examination were used to test excrement samples for occult blood. Sensitivity, specificity, and observer agreement were calculated. RESULTS In vitro specificity ranged from 85%to 100% for the 3 chromogen tests and was 100% for cytologic examination. Sensitivity was 0% to 35% for cytologic examination and 100% for the 3 chromogen tests on samples containing >or= 1.5 mg of Hb/g of excrement. In vivo specificity was 100%, 90%, 65%, and 45% for cytologic examination and the 3 chromogen tests, respectively. Sensitivity was 0% to 5% for cytologic examination and >or= 75% for all 3 chromogen tests after birds received doses of Hb >or= 20 mg/kg. Observer agreement was lowest for cytologic examination. CONCLUSIONS AND CLINICAL RELEVANCE Chromogen tests were more useful than cytologic examination for detection of occult blood in cockatiel excrement. The best combination of sensitivity, specificity, and observer agreement was obtained by use of a chromogen test.
Collapse
Affiliation(s)
- Paul M Gibbons
- Companion Avian and Exotic Pet Medicine Service, Veterinary Medical Teaching Hospital, Davis, CA 95616, USA
| | | | | | | |
Collapse
|
|
29
|
Thalmann M, Sodeck GH, Kavouras S, Matalas A, Skenderi K, Yannikouris N, Domanovits H. Proton pump inhibition prevents gastrointestinal bleeding in ultramarathon runners: a randomised, double blinded, placebo controlled study. Br J Sports Med 2006; 40:359-62; discussion 362. [PMID: 16556794 PMCID: PMC2577540 DOI: 10.1136/bjsm.2005.024463] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Ultra-endurance running is emerging as a popular sport in Western industrialised countries. Gastrointestinal bleeding has been reported to be an adverse effect in these runners. OBJECTIVE To see if the oral administration of a proton pump inhibitor would reduce the incidence of gastrointestinal bleeding in an ultramarathon. METHODS In a randomised, double blinded, placebo controlled study, a prophylactic regimen of three days of an oral proton pump inhibitor (pantoprazole 20 mg) was tested in healthy athletes participating in the Spartathlon ultramarathon. The incidence of gastrointestinal bleeding was assessed by a stool guaiac test. RESULTS Results were obtained for 70 healthy volunteers. The data for 20 of 35 runners in the intervention group and 17 of 35 runners in the placebo group were entered into the final analysis. At the end of the ultramarathon, two subjects in the intervention group and 12 in the placebo group had positive stool guaiac tests (risk difference 0.86; 95% confidence interval 0.45 to 0.96; p = 0.001). CONCLUSION A short prophylactic regimen of oral proton pump inhibition can successfully decrease the incidence of gastrointestinal bleeding in participants in an ultramarathon.
Collapse
Affiliation(s)
- M Thalmann
- Department of Cardiothoracic Surgery, Lainz- Hospital, Vienna, Austria
| | | | | | | | | | | | | |
Collapse
|
|
30
|
Chiang C, Jeng J, Wang W, Jheng B, Hsu W, Chen B. A comparative study of three fecal occult blood tests in upper gastrointestinal bleeding. Kaohsiung J Med Sci 2006; 22:223-8. [PMID: 16793557 PMCID: PMC11917784 DOI: 10.1016/s1607-551x(09)70240-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2005] [Accepted: 03/22/2006] [Indexed: 12/23/2022] Open
Abstract
The purpose of this study was to evaluate the performance characteristics of three fecal occult blood tests (FOBTs): the chemical o-toluidine test, the immunochemical OC-Hemodia test, and the immunochromatographic Quick Chaser Occult Blood (QCOB) test, which detect human hemoglobin and transferrin simultaneously in cases of upper gastrointestinal (GI) bleeding. Included were 48 FOBT specimens in 48 consecutive admission cases of upper GI bleeding (endoscopy confirmed). We excluded those fecal specimens with an obvious tarry and bloody appearance. The QCOB test revealed the highest positive rates of 33/48 (68.8%), and significantly higher positive rates than that of the OC-Hemodia test and o-toluidine test (p < 0.025 and < 0.01, respectively). In the patient group with upper GI bleeding due to gastric and duodenal ulcers, the QCOB test had higher positive rates (68.6%) than did the o-toluidine test (34.3%) (p < 0.01). There was no fecal specimen that was positive for the o-toluidine test or OC-Hemodia test and was negative for the QCOB test. Our results reveal that the QCOB test has significantly higher positive rates of fecal occult blood than either the OC-Hemodia test or o-toluidine test. The QCOB test is better than the other two tests for detecting occult blood in patients with upper GI bleeding.
Collapse
Affiliation(s)
| | | | - Wen‐Ming Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaoshiung Medical University, Kaohsiung, Taiwan
| | | | - Wan‐Ting Hsu
- Department of Laboratory Medicine Kaohsiung, Taiwan
| | | |
Collapse
|
|
31
|
Abstract
Occult gastrointestinal bleeding commonly manifests as iron deficiency anemia or fecal occult blood. Iron deficiency anemia results from chronic occult gastrointestinal bleeding. Evaluation of asymptomatic patients who have iron deficiency anemia or fecal occult blood usually should begin with investigation of the colon. Colonoscopy is preferred, but flexible sigmoidoscopy plus air contrast barium enema, or computed tomographic colonography may be acceptable in certain circumstances. If evaluation of the colon does not reveal a bleeding site, evaluation of the upper gastrointestinal tract is mandatory in patients who have iron deficiency anemia, and this should be considered in those who have fecal occult blood. In patients who have gastrointestinal symptoms, evaluation of the portion of the gastrointestinal tract from which the symptoms is derived should be pursued initially. The role of small intestinal investigation is controversial, and this probably should be reserved for patients who have iron deficiency anemia and persistent gastrointestinal symptoms or those who fail to respond to appropriate therapy. Celiac sprue should be considered as a potential cause of iron deficiency anemia in all patients. The treatment and prognosis of patients who have iron deficiency anemia or fecal occult blood depends on the gastrointestinal tract abnormality(ies) identified. Those without identifiable bleeding sites generally respond to conservative management and have a favorable prognosis. On the other hand, the outlook is poorer for patients with refractory occult blood loss or those who have vascular ectasias. Both groups of patients are clinically challenging and require a focused and experienced team approach to diagnosis and therapy.
Collapse
Affiliation(s)
- Don C Rockey
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
| |
Collapse
|
|
32
|
Abstract
OBJECTIVES Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Endoscopic screening is now in favor and its use is increasing, but overall participation rates are poor. A substantial percentage of the population will likely continue to resist endoscopic screening. As such, a noninvasive biomarker for the early detection of CRC remains a priority. Herein, we (i) review the currently available noninvasive screening markers for the early detection of CRC, (ii) discuss newer markers that have undergone preliminary testing, and (iii) introduce and explain potentially promising markers of the future. METHODS The published literature on markers for early detection of CRC was identified using a MEDLINE/PubMed search with secondary review of cited publications. RESULTS Noninvasive testing for CRC is most advanced in testing for stool fecal occult blood, globin, or DNA mutations. Study of abnormal mucins has also been explored. Research for serum-based markers is just beginning and includes serum proteomics, nuclear matrix proteins, and serum DNA testing. CONCLUSIONS Serial guaiac-based fecal occult blood testing (FOBT) is simple, inexpensive, and proven effective at reducing mortality from CRC. Immunochemical fecal occult blood tests facilitate compliance and offer improved specificity, but at increased cost in comparison to FOBT. Fecal DNA testing may provide enhanced sensitivity for detection of CRC in comparison with FOBT, but its high cost limits its use for generalized screening. Rectal mucin testing requires additional evaluation to determine its sensitivity and specificity in comparison with guaiac-based FOBT. Serum tests, such as proteomics, nuclear matrix proteins, and serum DNA, are still in their infancy, but remain a hope for the future.
Collapse
Affiliation(s)
- Daniel L Ouyang
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | | | | | | |
Collapse
|
|
33
|
|
|
34
|
Ahlquist DA, Shuber AP. Stool screening for colorectal cancer: evolution from occult blood to molecular markers. Clin Chim Acta 2002; 315:157-68. [PMID: 11728417 DOI: 10.1016/s0009-8981(01)00712-4] [Citation(s) in RCA: 90] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. Participation rates for colorectal cancer screening remain low due, in part, to perceived discomfort, potential harm, and high costs with available tools. METHODS Stool testing, unlike other conventional screening approaches, is noninvasive and requires no cathartic preparation. However, widely used fecal blood tests yield frequent false-negative and false-positive results that lower screening effectiveness and raise program costs. There is a compelling biological rationale to target DNA alterations exfoliated from neoplasms into stool, and multiple DNA markers would need to be assayed because of the genetic heterogeneity of colorectal neoplasia. Early clinical studies with this multi-target DNA-based stool assay approach suggest high sensitivity for both colorectal cancer and premalignant adenomatous polyps while maintaining high specificity. CONCLUSIONS This apparently accurate and user-friendly new approach holds promise to improve the effectiveness, efficiency, and appeal of colorectal cancer screening. Large-scale clinical studies are clearly warranted to corroborate the early results.
Collapse
Affiliation(s)
- David A Ahlquist
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
| | | |
Collapse
|
|
35
|
Affiliation(s)
- H Strul
- Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
| | | |
Collapse
|
|
36
|
Harewood GC, McConnell JP, Harrington JJ, Mahoney DW, Ahlquist DA. Detection of occult upper gastrointestinal tract bleeding: performance differences in fecal occult blood tests. Mayo Clin Proc 2002; 77:23-8. [PMID: 11794453 DOI: 10.4065/77.1.23] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To compare rates of detection of occult upper gastrointestinal (GI) tract bleeding by guaiac (Hemoccult II [HO]), immunochemical (HemeSelect [HS]), and heme-porphyrin (HemoQuant [HQT]) fecal occult blood tests. PATIENTS, SUBJECTS, AND METHODS: In a cross-sectional study to detect native occult upper GI tract bleeding, single stools were collected from 56 patients with iron deficiency and a proven hemorrhagic GI tract lesion. In a longitudinal study to detect simulated occult upper GI tract bleeding, 3 stool samples were serially collected from 10 clinically normal subjects after ingestion of 5 and 15 mL of autologous blood. All stool samples were subjected to blinded fecal occult blood determinations with use of the 3 tests. RESULTS In the cross-sectional study, the HQT test detected 88% (37/42) of hemorrhagic upper GI tract lesions compared with 26% (11/42) detected by the HO test (P<.001) and 2% (1/42) by the HS test (P<.001). In the longitudinal study, all preingestion fecal occult blood test results were negative. After ingestion of 5 mL of blood, the HQT result became positive in 60% (6/10), and the HO and HS results remained negative (P=.03). After ingestion of 15 mL of blood, the HQT result became positive in all 10 cases, the HO result was positive in 6 (P=.12 vs HQT), and the HS result was positive in none (P=.002 vs HQT); all 3 stool samples collected after the 15-mL ingestion were positive in each of the 10 subjects by the HQT test but in only 1 subject by the HO test (P=.003). CONCLUSION The HQT test detects occult upper GI tract blood loss significantly more frequently than the HO or HS test.
Collapse
Affiliation(s)
- Gavin C Harewood
- Division of Gastroenterology and Hepatology and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA
| | | | | | | | | |
Collapse
|
|
37
|
Affiliation(s)
- S A Chamberlain
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | |
Collapse
|
|
38
|
Hunt RH, Bowen B, Mortensen ER, Simon TJ, James C, Cagliola A, Quan H, Bolognese JA. A randomized trial measuring fecal blood loss after treatment with rofecoxib, ibuprofen, or placebo in healthy subjects. Am J Med 2000; 109:201-6. [PMID: 10974182 DOI: 10.1016/s0002-9343(00)00470-8] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
PURPOSE Gastrointestinal microbleeding, as assessed by the measurement of (51)chromium-labeled red blood cells, is a marker of the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs. This study tested the hypotheses that cyclooxygenase-2 specific inhibition with rofecoxib would cause less fecal blood loss than a therapeutic dose of ibuprofen and would be equivalent to placebo. SUBJECTS AND METHODS In this randomized, double-blind group study, gastrointestinal blood loss was assessed by measurement of fecal (51)chromium radioactivity during a 1-week placebo baseline period and during 4 weeks of treatment with rofecoxib (25 mg or 50 mg once daily), ibuprofen (800 mg three times daily), or placebo in 67 healthy subjects. Gastrointestinal blood loss during treatment weeks 2 to 4 (versus the baseline period) was expressed as the geometric mean ratio of fecal radioactivity in weeks 2 to 4 compared with baseline. RESULTS Ibuprofen caused significantly (P <0.001) greater gastrointestinal blood loss (geometric mean ratio of 5.2, 95% confidence interval [CI]: 4.2 to 6.3) than the 25-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.1), the 50-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.0), or placebo (2.1, 95% CI: 1.8 to 2.5). In contrast, gastrointestinal blood loss with both doses of rofecoxib were equivalent to placebo by a predetermined clinical similarity bound. CONCLUSIONS In healthy subjects, treatment with rofecoxib, at 2 to 4 times the doses that are currently recommended for the treatment of patients with osteoarthritis, produced significantly less fecal blood loss than a therapeutic dose of ibuprofen and was equivalent to placebo.
Collapse
Affiliation(s)
- R H Hunt
- McMaster University, Hamilton, Ontario, Canada
| | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Zuckerman GR, Prakash C, Askin MP, Lewis BS. AGA technical review on the evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology 2000; 118:201-21. [PMID: 10611170 DOI: 10.1016/s0016-5085(00)70430-6] [Citation(s) in RCA: 321] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics committee. The paper was approved by the committee on May 16, 1999, and by the AGA governing board on July 18, 1999.
Collapse
Affiliation(s)
- G R Zuckerman
- Division of Gastroenterology Washington University School of Medicine St. Louis, Missouri, USA
| | | | | | | |
Collapse
|
|
40
|
Abstract
There are few randomized, prospective trials evaluating the optimal diagnostic and therapeutic strategies in the management of lower gastrointestinal bleeding. However, recent data suggest that urgent colonoscopy represents a safe and effective initial diagnostic approach. The role of tagged erythrocyte scintigraphy is yet to be defined, but it may be of utility as a screening test for visceral angiography. Colonoscopy and angiography both offer substantial therapeutic options but remain of unproved benefit from a treatment standpoint; surgery continues to play an important role in the management of lower gastrointestinal bleeding. Obscure gastrointestinal bleeding, which often presents as lower gastrointestinal bleeding, continues to be one of the most challenging diagnostic and therapeutic problems in gastroenterology. Occult gastrointestinal bleeding, often arising from the lower gastrointestinal tract, usually mandates gastrointestinal evaluation.
Collapse
Affiliation(s)
- R S Bloomfeld
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
| | | |
Collapse
|
|
41
|
Affiliation(s)
- D C Rockey
- Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA.
| |
Collapse
|