Arq Gastroenterol
ag
Arquivos de Gastroenterologia
Arq. Gastroenterol.
0004-2803
1678-4219
Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia e Outras Especialidades - IBEPEGE.
RESUMO
CONTEXTO:
Sangramento retal é o sintoma mais importante de neoplasia intestinal; portanto, testes para detecção de sangue oculto nas fezes são amplamente usados para rastreamento de lesões pré-neoplásicas e de câncer colorretal (CCR).
OBJETIVO:
Avaliar a acurácia do teste quantitativo OC-Sensor (Eiken Chemical, Tokyo, Japan) com o valor de corte de 10 µg Hb/g fezes (50 ng/mL) numa coorte de indivíduos que se submeteram à colonoscopia diagnóstica, e se mais de uma amostra coletada em dias consecutivos melhoraria a acurácia diagnóstica do teste.
MÉTODOS:
Pacientes (idade média 56,3±9,7 anos) que se submeteram à colonoscopia prospectivamente, randomicamente, receberam tubos de coleta: um (1-amostra FIT, FIT 1), ou dois (2-amostra FIT, FIT 2). Eles coletaram as amostras de fezes antes de iniciar o preparo da colonoscopia. As amostras foram analisadas pelo OC-Auto Micro 80 (Eiken Chemical, Tokyo, Japan). As performances do FIT 1 e do FIT 2 foram comparadas com os achados da colonoscopia.
RESULTADOS:
Entre 289 pacientes, CCR foi diagnosticado em 14 (4,8%), adenoma avançado em 37 (12,8%), adenoma precoce em 71 (24,6%) e sem anormalidades em 141 (48,8%). Para FIT 1, a sensibilidade para CCR foi 83,3% (95%IC 36,5-99,1%), para adenoma avançado foi 24% (95%IC 10,1-45,5%), com especificidade de 86,9% (95%IC 77,3-92,9%). Para FIT 2, a sensibilidade para CCR foi 75% (95%IC 35,6-95,5%), para adenoma avançado foi 50% (95%IC 22,3-77,7%), com especificidade de 92,9% (95%IC 82,2-97,7%). A razão de verossimilhança positiva foi 1,8 (95%IC 0,7-4,4 para FIT 1) e 7,1 (95%IC 2,4-21,4 para FIT 2) para adenoma avançado, e 6,4 (95%IC 3,3-12,3, para FIT 1) e 10,7 (95%IC 3,8-29,8, para FIT 2) para CCR. A razão de verossimilhança negativa foi 0,9 (95%IC 0,7-1, para FIT 1) e 0,5 (95%IC 0,3-0,9, para FIT 2) para adenoma avançado, e 0,2 (0,03-1,1, para FIT 1) e 0,3 (0,08-0,9, para FIT 2) para CCR. As diferenças de performance entre FIT 1 e FIT 2 não foram significantes. Entretanto, a comparação dos níveis de hemoglobina nas fezes dos pacientes de FIT 1 e FIT 2 mostraram que as diferenças entre sem pólipo e adenoma avançado e CCR foram significantes.
CONCLUSÃO:
A acurácia do OCR Sensor com valor de corte de 10 µg Hb/g de fezes foi comparável a outras publicações e a coleta de duas amostras melhorou a taxa de detecção de adenoma avançado, lesão pré-neoplásica, para prevenir CCR.
INTRODUCTION
In 2018 in Brazil 36,360 new cases of colorectal (CRC) cancer were diagnosed, being 17,380 in men and 18,980 in women, and 16,697 deaths caused by CRC, being 8,163 of men and 8,533 of women (https://www.inca.gov.br/tipos-de-cancer/cancer-de-intestino). Bowel symptoms of constipation, diarrhea or abdominal pain had no significant association with CRC or precancerous polyps, in contrast, rectal bleeding and weight loss were mostly associated with CRC, and only rectal bleeding was associated with precancerous polyps1. Thus, positive detection of fecal occult blood would be, mostly indicated, to select patients for colonoscopy1 for early detection of advanced adenoma to prevent CRC development2.
Initially, the tests were an indirect measure of blood on the stools, based on the colorimetric assay of peroxidase activity of the hemoglobin, named guaiac test, but also using “in-house” solution of toluidine. Presence of peroxidase activity in foods and the necessity of a diet at least three days before stool collection, and the small amount of bleeding by polyps (52.7-71.9 ng Hb/mL) and cancer (86.6 ng Hb/mL)3 restricted their use, due to a lack of sensitivity and specificity3-5. Although, guaiac-based fecal tests reduced mortality, detecting early neoplastic lesions, and if only guaiac test is available, is preferable to do the test for CRC screening than doing nothing6.
The development of fecal immunochemical tests (FITs) with polyclonal or monoclonal antibodies against human hemoglobin showed promising results with higher sensitivity and specificity than the chemical test3-7. FITs may be qualitative immunochromatographic with a visual reading, and pre-determined detection limit that varies from 25 ng/mL to 50 ng/mL, declared by the manufacturer, usually with similar performances4. However, other studies observed great variability, comparing the performance of six different qualitative FITs, when the sensitivity was highest, specificity was lowest, and vice versa2. Probably, due to the different detection limits that are fixed in the qualitative test.
Several brands of quantitative FITs that measures the hemoglobin concentration with preset threshold that stratifies the positive cases are available on the market. The most important advantage of quantitative tests is to adjust the threshold of hemoglobin concentration that defines positive tests. In fact, the comparison of nine different quantitative FITs showed that adjusting the cutoff would overcome the heterogeneity amongst them8. At preset cutoff 15µg hemoglobin/g feces, two quantitative FITs: FOB-Gold (Sentinel, Milan, Italy) and OC-Sensor (Eiken Chemical, Tokyo, Japan), had similar accuracy to detect advanced adenoma, precursor of CRC9. Another issue to be considered is the number of fecal samples collected. The collection of two samples in consecutive days improved the diagnostic outcome with no effect on attendance10. Although bleeding is the main symptom of advanced neoplasia1 and immunochemical test is far too superior to guaiac4,5, neoplasia may not bleed every day, then bleeding may be missed with one sample collection10.
Thus, the purpose of this study was to evaluate the accuracy of one quantitative test: OC-Sensor (Eiken Chemical, Tokyo, Japan) in a cohort of subjects that had to undergo diagnostic colonoscopy at cut-off 10 µg Hb/g feces, and if more than one sample collected in consecutive days would improve the diagnostic accuracy of the test.
METHODS
Study population
Patients that attended the Gastrointestinal Endoscopy Division from January 2015 to December 2016 to undergo colonoscopy for diagnostic purpose, were invited to participate. Patients randomly received one (1-sample FIT) or two (2-sample FIT) collection tubes and had to collect the stool sample before starting colonoscopy preparation of the same bowel movement. The two-sample collections were one sample per FIT of two bowel movements on consecutive days. Among 474 that were invited, 333 brought the stool samples the day that underwent colonoscopy, forty-four were excluded due to: colectomy (n=5), inadequate bowel preparation (n=4), incomplete colonoscopy (n=6), colon stenosis (n=2), and twenty-seven inflammatory bowel disease. 289 were eligible for the study, 172 one-sample FIT and 117 two-sample FIT (Figure 1). The mean age was 56.3±9.7 years and range of 27 to 77 years, 191 (66.1%) were women.
FIGURE 1
Flow diagram of the diagnostic accuracy of FIT for CRC screening.
Ethical statement
Ethics Committee of the Hospital approved this study protocol through http://plataformabrasil.saude.gov.br. Patients gave written informed consent to participate.
OCR FIT test
According to the manufacturer the sample collection tube may be stored at room temperature for 7 days. Patients were instructed to keep the sample collection tube at room temperature, and after delivering to the lab on the same day of colonoscopy, the samples were analyzed using the OC-Auto Micro 80 (Eiken Chemical, Tokyo, Japan). The calibration curve was performed every 15 days. The test was considered positive at ≥50 ng Hb/mL (10µg Hb/g feces), and for 2-sample FIT if one sample tested positive, was considered positive.
Colonoscopy
Colonoscopy was performed according to the routine of the Gastrointestinal Endoscopy Division. Patients were instructed to cleanse the colon with bisacodyl the day before the exam and 1 liter of oral 10% mannitol solution 4 hours before the exam. The quality of the bowel preparation was assessed using the Boston Preparation Score (BBPS) and a score of 6 or more was considered adequate preparation and the patient was excluded if the BBPS scale was <611. The colonoscopes used were high definition Olympus CF-H180 (Olympus Optical, Tokyo, Japan) and Fujinon EC 590 (Fujifilm Co., Tokyo, Japan). Sedation with intravenous midazolam, fentanyl and propofol was used for all the patients, and the dose was titrated according to each patient. After cecal intubation, the colonoscope was withdrawn, and the mucosa was carefully evaluated. The duration time of colonoscope withdrawal was longer than 6 minutes, regardless of the time of therapeutic procedures. All polyps were removed and sent for histological analysis. The polyp size measurement was based on opened biopsy forceps (7mm in diameter), and classified according to the size: <5 mm, 5-9 mm and ≥10 mm. The right-sided polyp was defined when its location was proximal to the splenic flexure and the left-sided polyp when distal to the splenic flexure.
Histological examination
Colon removed lesions were fixed in 10% formalin, stained with hematoxylin and eosin, and assessed by two pathologists for histological diagnosis. According to the WHO classification of tumours of the colon and rectum12, the biopsies were stratified as no polyp, serrated polyp (hyperplastic polyp, serrated adenoma), adenoma (tubular, tubulovillous, or villous), or adenocarcinoma. Dysplasia was defined as low grade or high grade. Early adenoma was defined as tubular with size <10 mm and low-grade dysplasia. Advanced adenoma was defined as either large (with size ≥10 mm), villous, tubulovillous (>25% villous) or high-grade dysplasia. Advanced neoplasia included advanced adenoma and adenocarcinoma.
Statistical analyses
The statistical analysis was performed with IBM SPSS 25 (Statistical Package for the Social Sciences) and Excel 2010® (Microsoft Office). Descriptive statistics characterized the findings of colonoscopy and the study patients. Sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios with 95% confidence interval (95%CI) were calculated using an online program (http://vassarstats.net/). The Kolmogorov-Smirnov test evaluated the normality of the variables distribution. The associations of 1-sample FIT (FIT 1), 2-sample FIT (FIT 2), and the higher value FIT of the group FIT 2 and the findings of colonoscopy were performed by Kruskal-Wallis test, and the significant values adjusted by Bonferroni correction for multiples tests. All the statistical tests considered two-sided α of 0.05 and 95% confidence interval. In the present study, G* Power version 3.1.9.4 (Franz Faul, Universität Kiel, Germany) was used to for post hoc power analysis. The effect size was calculated with the means and standard deviations between the no polyp group with either hyperplastic polyp, early adenoma, advanced adenoma, and CRC for FIT 1, FIT 2 and higher value FIT. The result of effect size was transferred to main window to calculate power (1- β error probability) for each one of the analysis of the study by means: Wilcoxon-Mann Whitney test (two groups). The input parameters were the effect size d, α=0.05, sample size of group 1 and sample size of group 2 to calculate power for each one of the analysis. Results are reported in accordance with the Standards for the Reporting of Diagnostic accuracy studies (STARD) checklist (2015)13.
RESULTS
Patients that were eligible for the study totalized the number of 289, with 172 in the 1-sample FIT and 117 in the 2-sample FIT group. The analysis of agreement between the results of 2-sample FIT showed that 94 (80.3%) patients had both FIT negative, 13 (11.1%) had both FIT positive and 10 (8.5%) had only one FIT positive, with a kappa index = 0.673 (substantial).The STARD flow diagram is depicted in Figure 1.
The endoscopic findings according to the size of the polypoid lesion, number of adenomas, location of polypoid lesion, and histological based diagnosis are depicted in Table 1. The comparisons according to the size and the number of polyps were not significant (Kruskal-Wallis test), Table 1.
TABLE 1
The findings of colonoscopy of 289 patients that entered the study.
Variables
Number
%
95%CI
Size of polyp (mm)
Non-polypoid lesion
157
54.3%
48.6-60%
<5
69
23.9%
19.2-29%
5-9
43
14.9%
11.1-19.3%
≥10
20
6.9%
4.4-10.3%
Number of adenomas
No adenoma
182
63.0%
57.3-68.4%
1-2
80
27.7%
22.8-33%
3 or more
27
9.3%
6.4-13.1%
Location of polyp
Left-sided
61
41.8%
34-49.9%
Right-sided
61
41.8%
34-49.9%
Bilateral
24
16.4%
11.1-23.1%
Histology
No polyp
141
48.8%
43.1-54.5%
Hyperplasic polyp
26
9.0%
6.1-12.7%
Early adenoma
71
24.6%
19.9-29.8%
Advanced adenoma
37
12.8%
9.3-17%
CRC
14
4.8%
2.8-7.8%
In the advanced adenoma, FIT 1 had a sensitivity of 24% (95%CI: 10.1-45.5%) and FIT 2 of 50% (95%CI: 22.3-77.7%) with positive predictive value of 15.6% (95%CI: 9.6-24%) and 14.5% (7.5-25.5%), respectively. The negative predictive value was 84.4% (95%CI: 75.9-90.3 for FIT 1 and 85.5% (95%CI: 74.5-92.5%) for FIT 2. The positive likelihood ratio of FIT 1 was 1.8 (0.7-4.4) and of FIT 2 was 7.1 (2.4-21.4). The negative likelihood ratio was 0.9 (95%CI: 0.7-1) and 0.5 (95%CI: 0.3-0.9) for FIT 1 and FIT 2, respectively (Table 2).
In the CRC, FIT 1 had a sensitivity of 83.3% (95%CI: 36.5-99.1%) and FIT 2 of 75% (95%CI: 35.6-95.5%) with positive predictive value of 17.8% (95%CI: 10.8-27.5%) and 15.4 (95%CI: 8-26.9%), respectively. The negative predictive value was 82.2% (95%CI: 72.4-89.2%) for FIT 1 and 84.6 (95%CI: 73-91.9%) for FIT 2. The positive likelihood ratio of FIT 1 was 6.4 (95%CI: 3.3-12.3) and of FIT 2 was 10.7 (95%CI: 3.8-29.8). The negative likelihood ratio was 0.2 (95%CI: 0.03-1.1) and 0.3 (95%CI: 0.08-0.9) for FIT 1 and FIT 2, respectively. The specificity was 86.9% (95%CI: 77.3-92.9%) and 92.9% (95%CI: 82.2-97.7%) for FIT 1 and FIT 2, respectively.
The performance of FIT 1 and FIT 2, considering advanced adenoma and CRC altogether as advanced neoplasia, is depicted in Table 2. The comparison of the performance of FIT 1 and FIT 2 to indicate advanced adenoma, advanced neoplasia and CRC were not significant (Table 2).
TABLE 2
The performance of FIT 1 and FIT2 (two samples, positive if either one was positive) for advanced adenoma, advanced neoplasia and CRC detection with 95% confidence interval.
Parameters
FIT 1
FIT 2
Sensitivity
Advanced adenoma
24% (10.1-45.5%)
50% (22.3-77.7%)
Advanced neoplasia
35.5% (19.8-54.6%)
60% (36.4-80%)
CRC
83.3% (36.5-99.1%)
75% (35.6-95.5%)
Specificity
86.9% (77.3-92.9%)
92.9% (82.2-97.7%)
PPV
Advanced adenoma
15.6% (9.6-24%)
14.5% (7.5-25.5%)
Advanced neoplasia
19.1% (12.6-27.7%)
20.8% (12.7-31.8%)
CRC
17.8% (10.8-27.5%)
15.4 (8-26.9%)
NPV
Advanced adenoma
84.4% (75.9-90.3%)
85.5% (74.5-92.5%)
Advanced neoplasia
80.9% (72.2-87.3%)
79.2% (68.1-87.3%)
CRC
82.2% (72.4-89.2%)
84.6 (73-91.9%)
+ Likelihood ratio
Advanced adenoma
1.8 (0.7-4.4)
7.1 (2.4-21.4)
Advanced neoplasia
2.7 (1.3-5.6)
8.6 (3.1-23.5)
CRC
6.4 (3.3-12.3)
10.7 (3.8-29.8)
Negative Likelihood ratio
Advanced adenoma
0.9 (0.7-1)
0.5 (0.3-0.9)
Advanced neoplasia
0.7 (0.6-1)
0.4 (0.2-0.7)
CRC
0.2 (0.03-1.1)
0.3 (0.08-0.9)
The comparison of the levels of hemoglobin in feces of patients of FIT 1 according to the colonoscopy findings showed that the differences between no polyp group and advanced adenoma and among CRC and all the other groups were significant (Figure 2).
FIGURE 2
The levels of hemoglobin in feces of the patients of FIT 1 according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
The comparison of the levels of hemoglobin in feces of patients of FIT 2 according to the colonoscopy findings showed that the differences between hyperplastic polyp and advanced adenoma, and among CRC, no polyp and hyperplastic polyp were significant (Figure 3).
FIGURE 3
The levels of hemoglobin in feces of the patients of FIT 2 according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
The comparison of the levels of hemoglobin in feces of patients of FIT 2, considering the higher value FIT, according to the colonoscopy findings showed that the differences among CRC and all the other groups were significant (Figure 4). The post hoc power analysis of FIT 1, FIT 2 and higher value FIT showed that power 1-β err probability was high (0.99, 0.94, 0.99, respectively) only for CRC.
FIGURE 4
The levels of hemoglobin in feces of the patients of higher value FIT according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
DISCUSSION
The importance of occult blood in stools, indicating the presence of a serious disorder in the gastrointestinal tract, usually cancer14, dates back to the beginning of the 20th century15. The chemical tests by guaiac and benzidine for occult blood detection considered the simplest among the other options had a relative specificity and sensitivity15. These assays depend upon the peroxidase like activity of heme of hemoglobin and hydrogen peroxide (the developer) to oxidize some chromogenic substances, yielding a color15. The addition of an enhancer to the developer to detect low levels of peroxidase improved the high-sensitive guaiac fecal occult blood tests; however, some immunochemical tests (FIT) had a better performance16.
The basis of FIT is the reaction of monoclonal or polyclonal antibodies against the globin molecule of human hemoglobin. The assays may be qualitative by lateral-flow immunochromatography2,4,5, or quantitative by immune-turbidimetry and ELISA8,9,17. In the qualitative test, a band of different intensities of color visually detected, resulting from the preset positive threshold designed by the manufacturer indicates two possible results: positive or negative4. Different from chemical tests15, FITs had no interference from diet and medications17; however, globin may degrade easier at high temperatures than heme18,19, turning out the winter the best season for CRC screening19.
In the light of that, Brazil is a tropical country with higher temperatures than the north continents; nonetheless, the qualitative FITs had similar performances and more sensitive than the chemical test, making qualitative FITs suitable for the clinical practice in spite of the weather4. In the present study, we sought to analyze the accuracy of a quantitative FIT (quantified by OC-Auto Micro 80), which principle is the immune reaction between hemoglobin and monoclonal anti-hemoglobin latex-adsorbed antibodies. The measure of optical absorbance of the turbid solution at 660 nm against a calibration curve indicating the concentration of hemoglobin19. The analysis was with predefined cut-off 10 µg Hb/g feces.
One of the advantages of the OC-Auto Micro 80 is the closed automated system, being the technique of choice at this time of SARS-CoV-2 threat. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in China at the end of 201920, spread worldwide, causing the COVID-19 pandemic disease with 257,405 confirmed deaths and 3,726,292 confirmed cases, involving 215 countries, areas or territories at this point (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). Although the infection is characterized by respiratory symptoms, indicating droplet transmission, several cases presented gastrointestinal symptoms, suggesting another possible route the fecal-oral transmission. Patients had positive rectal swabs even after nasopharyngeal tests were negative21. OC-Auto Micro 80 is safe for the lab personnel, as there is no risk of aerosol transmission from patients’ feces. The individual collects the stools in the sampling bottle, closes the bottle, delivers to the lab, a bar code is attached, and the closed sampling bottle is placed into the instrument where the needle of the probe perforates the sampling bottle, pipettes the sample, the reaction solutions, and after some minutes prints the result with the respective bar code.
The qualitative tests are less cumbersome, easier to handle, fast, and cheap; however, the samples of feces are opened inside the lab with the risk of aerosolization of the virus22, and contamination of the lab personnel. The comparison of FIT of several brands: qualitative and quantitative showed that the overall sensitivity was not much different among them, with the quantitative tests offering the advantage of positive threshold flexibility8,9,23. Another advantage of OCR-Auto Micro 80 in comparison to ELISA, is the possibility of placing the sampling bottle inside the equipment and analyzing as quickly as they are delivered to the lab.
The most important value of screening CRC is to detect advanced adenoma, rather than CRC itself. The analysis of the performance of OCR quantitative test at cut-off 10 µg Hb/g showed that collecting two samples improved the sensitivity to indicate advanced adenoma, although not significant that was different from previously described10. Otherwise, the high specificity and negative predictive value for both advanced adenoma and CRC indicated that collecting two samples would not increase the number of unnecessary colonoscopies.
In accordance with other authors24-27, most of the patients (48.8%; 95%CI: 43.1-54.5%) had no polyps or early (<10 mm) adenoma (24.6%; 95%CI: 19.9-29.8%). Taking into account the size of the polyp (≥10 mm), the prevalence in the present study (6.9%; 95%CI: 4.4-10.3%) was similar to that in non-Hispanic whites of the Eastern states in the US28. The prevalence of advanced adenoma in 12.8% (95%CI: 9.3-17%) was comparable to that described in Europeans of Amsterdam and Rotterdam regions25 and among colonoscopy-referral patients of a Cancer Hospital in Brazil26. However, the prevalence of CRC (4.8%; 95%CI: 2.8-7.8%) was higher than previous reported in asymptomatic individuals of The Netherlands (0.6%)25; nonetheless, was comparable to that described in symptomatic patients of mid-Sweden (5.4%)27, but half among colonoscopy-referral patients of a Cancer Hospital in Brazil (10.1%)26.
The more recent guideline of CRC surveillance29 proposes that screening to adults aged 50-79 should be based on the risk of CRC for the next 15 years, by answering the QCancer® calculator that takes into account age, gender, ethnicity, BMI, smoking, and medical and family history. Screening is suggested with one of the four options: FIT every year, FIT every two years, single sigmoidoscopy, or a single colonoscopy for individuals with risk of 3% or higher. Below 3% of risk, screening is not recommended based on benefits, harms, and burdens of screening.
The specificity of FIT in the present study (86.9% for one sample- FIT1 and 92.9% for two sample- FIT2) was similar (between 88-95%) to other reports2,8,16,23,25,30, except for the qualitative ColonView (Hb/Hp) with 65% specificity26, and the quantitative QuikRead go®FIT with 77%27. The sensitivity varied among the different tests and the colonoscopy findings, being higher for those with CRC than the ones with advanced adenoma, as adenoma bleeds less than CRC and does not bleed every day. For advanced adenoma the sensitivity varied from 18% with OC Sensor8, 25% ImmoCare-C2 to 33% automated ELISA23; however, with two sample FIT (FIT2) the sensitivity for advanced adenoma in this study increased from 24% (One-sample FIT) to 50% (two-sample FIT). For a developing country with a tropical weather, a lesion that bleeds less than CRC, and considering the simplicity of the test in relation to the colonoscopy, the sensitivity of collecting two consecutive samples is more reliable. The sensitivity for advanced neoplasia was from 15.1 % (OC FIT-CHEK)15, 21.8% (OC Sensor)8, 26.3% (InSure FIT)16, 35.2% (FOB Gold)30 and the present study for one-sample FIT, to 38% (OC- Sensor)25. However, the sensitivity for advanced neoplasia increased to 60% with two-sample FIT. The sensitivity for CRC was 68.8 % (OC Sensor)8, 88 % (OC Sensor)25, 92.3% (QuikRead go®FIT) one-sample FIT to 100% two-sample FIT27. In the present study two-sample FIT did not increase the sensitivity (75%), as with one-sample FIT for CRC was 83.3%.
The limitations of the study were the small number of the individuals with advanced adenoma, as the post hoc power analysis was high only for CRC and no assessment of symptoms and correlation with the findings of colonoscopy and OCR FIT- tests. Future study may evaluate a higher number of patients with advanced adenoma and symptoms to indicate intestinal neoplasia diagnosis.
CONCLUSION
In conclusion, the accuracy of OCR Sensor with 10 µg Hb/g feces cut-off was comparable to other reports and two-sample collection improved the detection rate of advanced adenoma, a pre neoplastic condition to prevent CRC incidence.
ACKNOWLEDGEMENTS
The authors thank Eiken Chemical, Tokyo, Japan for donating the kits for the study, Fujifilm for the support, the Department of Pathology (ICHC-FMUSP) for the histological diagnosis, Alex Jones Flores Cassenote of the Epidemiology and Statistics Group of the Department of Gastroenterology (FMUSP) for the statistical analysis, and Rodrigo Silva de Paula Rocha of the Endoscopy Division (HCFMUSP) for helping with the acquisition of data. The authors thank Prof. Venancio Avancini Ferreira Alves of the Department of Pathology (ICHC-FMUSP) for valuable comments and suggestions.
REFERENCES
1
1. Adelstein B-A, Macaskill P, Chan SF, Katelaris PH, Irwig L. Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review. BMC Gastroenterol. 2011;11:65. doi:10.1186/1471-230X-11-65.
Adelstein
B-A
Macaskill
P
Chan
SF
Katelaris
PH
Irwig
L
Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review
BMC Gastroenterol
2011
11
65
65
10.1186/1471-230X-11-65
2
2. Hundt S, Haug U, Brenner H. Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med. 2009;150:162-9.
Hundt
S
Haug
U
Brenner
H
Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection
Ann Intern Med
2009
150
162
169
3
3. Guittet L, Bouvier V, Mariotte N, Vallee JP, Levillain R, Tichet J, et al. Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location. Br J Cancer. 2009;100:1230-5.
Guittet
L
Bouvier
V
Mariotte
N
Vallee
JP
Levillain
R
Tichet
J
Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location
Br J Cancer
2009
100
1230
1235
4
4. Borges LV, Mattar R, Silva JMK, Silva ALW, Carrilho FJ, Hashimoto CL. Fecal occult blood: a comparison of chemical and immunochemical tests. Arq Gastroenterol. 2018;55:1-5.
Borges
LV
Mattar
R
Silva
JMK
Silva
ALW
Carrilho
FJ
Hashimoto
CL
Fecal occult blood: a comparison of chemical and immunochemical tests
Arq Gastroenterol
2018
55
1
5
5
5. Meklin J, Syrjänen K, Eskelinen M. Colorectal cancer screening with traditional and new-generation fecal immunochemical tests: a critical review of fecal occult blood tests. Anticancer Res. 2020;40:575-81.
Meklin
J
Syrjänen
K
Eskelinen
M
Colorectal cancer screening with traditional and new-generation fecal immunochemical tests: a critical review of fecal occult blood tests
Anticancer Res
2020
40
575
581
6
6. Young GP, Rabeneck L, Winawer SJ. The global paradigm shift in screening for colorectal cancer. Gastroenterology. 2019;156:843-51.
Young
GP
Rabeneck
L
Winawer
SJ
The global paradigm shift in screening for colorectal cancer
Gastroenterology
2019
156
843
851
7
7. Robertson DJ, Lee JK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US multi-society task force on colorectal cancer. Am J Gastroenterol. 2017;112:37-53.
Robertson
DJ
Lee
JK
Boland
CR
Dominitz
JA
Giardiello
FM
Johnson
DA
Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US multi-society task force on colorectal cancer
Am J Gastroenterol
2017
112
37
53
8
8. Gies A, Cuk K, Schrotz-King P, Brenner H. Direct comparison of diagnostic performance of 9 quantitative fecal immunochemical tests for colorectal cancer screening. Gastroenterology. 2018;154:93-104.
Gies
A
Cuk
K
Schrotz-King
P
Brenner
H
Direct comparison of diagnostic performance of 9 quantitative fecal immunochemical tests for colorectal cancer screening
Gastroenterology
2018
154
93
104
9
9. Wieten E, de Klerk CM, van der Steen A, Ramakers CR, Kuipers EJ, Hansen BE, et al. Equivalent accuracy of 2 quantitative fecal immunochemical tests in detecting advanced neoplasia in an organized colorectal cancer screening program. Gastroenterology. 2018;155:1392-9.
Wieten
E
de Klerk
CM
van der Steen
A
Ramakers
CR
Kuipers
EJ
Hansen
BE
Equivalent accuracy of 2 quantitative fecal immunochemical tests in detecting advanced neoplasia in an organized colorectal cancer screening program
Gastroenterology
2018
155
1392
1399
10
10. Van Roon AHC, Wilschut JA, Hol L, Van Ballegooijen M, Reijerink JCIY, Mannetje HT, et al. Diagnostic yield improves with collection of 2 samples in fecal immunochemical test screening without affecting attendance. Clin Gastroenterol Hepatol. 2011 9:333-9.
Van Roon
AHC
Wilschut
JA
Hol
L
Van Ballegooijen
M
Reijerink
JCIY
Mannetje
HT
Diagnostic yield improves with collection of 2 samples in fecal immunochemical test screening without affecting attendance
Clin Gastroenterol Hepatol
2011
9
333
339
11
11. Calderwood AH, Jacobson BC. Comprehensive validation of the Boston Bowel Preparation Scale. Gastrointest Endosc. 2010;72:686-92.
Calderwood
AH
Jacobson
BC
Comprehensive validation of the Boston Bowel Preparation Scale
Gastrointest Endosc
2010
72
686
692
12
12. Hamilton SR, Sekine S. Conventional colorectal adenoma. In: WHO classification of tumours editorial board. Digestive System Tumours. WHO Classification of Tumours. 5th ed; 2019.p.170-3.
Hamilton
SR
Sekine
S
Conventional colorectal adenoma
WHO classification of tumours editorial board. Digestive System Tumours. WHO Classification of Tumours
5th ed
2019
170
173
13
13. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin Chem. 2015;61:1446-52.
Bossuyt
PM
Reitsma
JB
Bruns
DE
Gatsonis
CA
Glasziou
PP
Irwig
L
STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies
Clin Chem
2015
61
1446
1452
14
14. Paul WD, Hamilton HE. The importance of occult blood in the stool. Am J Dig Dis. 1948; 15:23-26.
Paul
WD
Hamilton
HE
The importance of occult blood in the stool
Am J Dig Dis
1948
15
23
26
15
15. Irons GV Jr, Kirsner JB. Routine chemical tests of the stools for occult blood: an evaluation. Am J Med Sci. 1965;249:247-60.
Irons
GV
Jr
Kirsner
JB
Routine chemical tests of the stools for occult blood: an evaluation
Am J Med Sci
1965
249
247
260
16
16. Shapiro JA, Bobo JK, Church TR, Rex DK, Chovnick G, Thompson TD, et al. A comparison of fecal immunochemical and high-sensitivity guaiac tests for colorectal cancer screening. Am J Gastroenterol . 2017;112:1728-35.
Shapiro
JA
Bobo
JK
Church
TR
Rex
DK
Chovnick
G
Thompson
TD
A comparison of fecal immunochemical and high-sensitivity guaiac tests for colorectal cancer screening
Am J Gastroenterol
2017
112
1728
1735
17
17. Young GP, Symonds EL, Allison JE, Cole SP, Fraser CG, Halloran SP, et al. Advances in fecal occult blood tests: the FIT revolution. Dig Dis Sci. 2015;60:609-22.
Young
GP
Symonds
EL
Allison
JE
Cole
SP
Fraser
CG
Halloran
SP
Advances in fecal occult blood tests: the FIT revolution
Dig Dis Sci
2015
60
609
622
18
18. Catomeris P, Baxter NN, Boss SC, Paszat LP, Rabeneck L, Randell E, et al. Effect of temperature and time on fecal hemoglobin stability in 5 fecal immunochemical test methods and one guaiac method. Arch Pathol Lab Med. 2018;142:75-82.
Catomeris
P
Baxter
NN
Boss
SC
Paszat
LP
Rabeneck
L
Randell
E
Effect of temperature and time on fecal hemoglobin stability in 5 fecal immunochemical test methods and one guaiac method
Arch Pathol Lab Med
2018
142
75
82
19
19. Grazzini G, Ventura L, Zappa M, Ciatto S, Confortini M, Rapi S, et al. Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district. Gut. 2010;59:1511-5.
Grazzini
G
Ventura
L
Zappa
M
Ciatto
S
Confortini
M
Rapi
S
Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district
Gut
2010
59
1511
1515
20
20. Zhang N, Wang L, Deng X, Liang R, Su M, He C, et al. Recent advances in the detection of respiratory virus infection in humans. J Med Virol. 2020;92:408-17.
Zhang
N
Wang
L
Deng
X
Liang
R
Su
M
He
C
Recent advances in the detection of respiratory virus infection in humans
J Med Virol
2020
92
408
417
21
21. Hindson J. COVID-19: faecal-oral transmission? Nat Rev Gastroenterol Hepatol. 2020;17:259.
Hindson
J
COVID-19: faecal-oral transmission?
Nat Rev Gastroenterol Hepatol
2020
17
259
259
22
22. Liu Y, Ning Z, Chen Y, Guo M, Liu Y, Gali NK, et al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020. (https://doi.org/10.1038/s41586-020-2271-3).
Liu
Y
Ning
Z
Chen
Y
Guo
M
Liu
Y
Gali
NK
Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals
Nature
2020
https://doi.org/10.1038/s41586-020-2271-3
23
23. Haug U, Hundt S, Brenner H. Quantitative immunochemical fecal occult blood testing for colorectal adenoma detection: evaluation in the target population of screening and comparison with qualitative tests. Am J Gastroenterol . 2010;105:682-90.
Haug
U
Hundt
S
Brenner
H
Quantitative immunochemical fecal occult blood testing for colorectal adenoma detection: evaluation in the target population of screening and comparison with qualitative tests
Am J Gastroenterol
2010
105
682
690
24
24. Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. N Engl J Med. 2000;343:162-8.
Lieberman
DA
Weiss
DG
Bond
JH
Ahnen
DJ
Garewal
H
Chejfec
G
Use of colonoscopy to screen asymptomatic adults for colorectal cancer
N Engl J Med
2000
343
162
168
25
25. de Wijkerslooth TR, Stoop EM, Bossuyt PM, Meijer GA, van Ballegooijen M, van Roon AH, et al. Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol . 2012;107:1570-8.
de Wijkerslooth
TR
Stoop
EM
Bossuyt
PM
Meijer
GA
van Ballegooijen
M
van Roon
AH
Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia
Am J Gastroenterol
2012
107
1570
1578
26
26. Guimarães DP, Fregnani JH, Reis RM, Taveira LN, Scapulatempo-Neto C, Matsushita M, et al. Comparison of a new-generation fecal immunochemical test (FIT) with guaiac fecal occult blood test (gFOBT) in detecting colorectal neoplasia among colonoscopy-referral patients. Anticancer Res . 2019;39:261-9.
Guimarães
DP
Fregnani
JH
Reis
RM
Taveira
LN
Scapulatempo-Neto
C
Matsushita
M
Comparison of a new-generation fecal immunochemical test (FIT) with guaiac fecal occult blood test (gFOBT) in detecting colorectal neoplasia among colonoscopy-referral patients
Anticancer Res
2019
39
261
269
27
27. Tsapournas G, Hellström PM, Cao Y, Olsson LI. Diagnostic accuracy of a quantitative faecal immunochemical test vs. symptoms suspected for colorectal cancer in patients referred for colonoscopy. Scan J Gastroenterol. 2020 DOI: 10.1080/00365521.2019.1708965.
Tsapournas
G
Hellström
PM
Cao
Y
Olsson
LI
Diagnostic accuracy of a quantitative faecal immunochemical test vs. symptoms suspected for colorectal cancer in patients referred for colonoscopy
Scan J Gastroenterol
2020
10.1080/00365521.2019.1708965
28
28. Avalos DJ, Zuckerman MJ, Dwivedi A, Dodoo C, Satiya J, Castro FJ. Differences in prevalence of large polyps between Hispanic Americans from Mexican and non Mexican predominant States. Dig Dis Sci . 2019;64:232-40.
Avalos
DJ
Zuckerman
MJ
Dwivedi
A
Dodoo
C
Satiya
J
Castro
FJ
Differences in prevalence of large polyps between Hispanic Americans from Mexican and non Mexican predominant States
Dig Dis Sci
2019
64
232
240
29
29. Helsingen LM, Vandvik PO, Jodal HC, Agoritsas T, Lytvyn L, Anderson JC, et al. Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline. BMJ. 2019;367:l5515.
Helsingen
LM
Vandvik
PO
Jodal
HC
Agoritsas
T
Lytvyn
L
Anderson
JC
Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline
BMJ
2019
367
l5515
l5515
30
30. Brenner H, Werner S. Selecting a cut-off for colorectal cancer screening with a fecal immunochemical test. Clin Transl Gastroenterol. 2017;8:e111.
Brenner
H
Werner
S
Selecting a cut-off for colorectal cancer screening with a fecal immunochemical test
Clin Transl Gastroenterol
2017
8
e111
Disclosure of funding: no funding received
Autoria
Rejane MATTAR
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.
Declared conflict of interest of all authors: none
Authors’ contribution: PS: study design, kits donation management. SBM: study design, writing the research project, writing the article, patient inclusion, colonoscopy, collection of biopsy samples, data management. MKM: colonoscopy, collection of biopsy samples. JMKSE: OCR FIT performance. RM: writing the article, statistical analyses, OCR FIT performance, data management. EGHM and all the authors read and approved the final version of the manuscript.
SCIMAGO INSTITUTIONS RANKINGS
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.Universidade de São PauloBrasilSão Paulo, SP, Brasil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil.
FIGURE 2
The levels of hemoglobin in feces of the patients of FIT 1 according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
FIGURE 3
The levels of hemoglobin in feces of the patients of FIT 2 according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
FIGURE 4
The levels of hemoglobin in feces of the patients of higher value FIT according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
TABLE 2
The performance of FIT 1 and FIT2 (two samples, positive if either one was positive) for advanced adenoma, advanced neoplasia and CRC detection with 95% confidence interval.
imageFIGURE 1
Flow diagram of the diagnostic accuracy of FIT for CRC screening.
open_in_new
imageFIGURE 2
The levels of hemoglobin in feces of the patients of FIT 1 according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
open_in_new
imageFIGURE 3
The levels of hemoglobin in feces of the patients of FIT 2 according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
open_in_new
imageFIGURE 4
The levels of hemoglobin in feces of the patients of higher value FIT according to the colonoscopy findings. The boxes indicate 25-75% quartiles. The horizontal lines on the bottom of the figure indicate the comparisons of each group with one another that were significant (Kruskal-Wallis test).
open_in_new
table_chartTABLE 1
The findings of colonoscopy of 289 patients that entered the study.
Variables
Number
%
95%CI
Size of polyp (mm)
Non-polypoid lesion
157
54.3%
48.6-60%
<5
69
23.9%
19.2-29%
5-9
43
14.9%
11.1-19.3%
≥10
20
6.9%
4.4-10.3%
Number of adenomas
No adenoma
182
63.0%
57.3-68.4%
1-2
80
27.7%
22.8-33%
3 or more
27
9.3%
6.4-13.1%
Location of polyp
Left-sided
61
41.8%
34-49.9%
Right-sided
61
41.8%
34-49.9%
Bilateral
24
16.4%
11.1-23.1%
Histology
No polyp
141
48.8%
43.1-54.5%
Hyperplasic polyp
26
9.0%
6.1-12.7%
Early adenoma
71
24.6%
19.9-29.8%
Advanced adenoma
37
12.8%
9.3-17%
CRC
14
4.8%
2.8-7.8%
table_chartTABLE 2
The performance of FIT 1 and FIT2 (two samples, positive if either one was positive) for advanced adenoma, advanced neoplasia and CRC detection with 95% confidence interval.
Parameters
FIT 1
FIT 2
Sensitivity
Advanced adenoma
24% (10.1-45.5%)
50% (22.3-77.7%)
Advanced neoplasia
35.5% (19.8-54.6%)
60% (36.4-80%)
CRC
83.3% (36.5-99.1%)
75% (35.6-95.5%)
Specificity
86.9% (77.3-92.9%)
92.9% (82.2-97.7%)
PPV
Advanced adenoma
15.6% (9.6-24%)
14.5% (7.5-25.5%)
Advanced neoplasia
19.1% (12.6-27.7%)
20.8% (12.7-31.8%)
CRC
17.8% (10.8-27.5%)
15.4 (8-26.9%)
NPV
Advanced adenoma
84.4% (75.9-90.3%)
85.5% (74.5-92.5%)
Advanced neoplasia
80.9% (72.2-87.3%)
79.2% (68.1-87.3%)
CRC
82.2% (72.4-89.2%)
84.6 (73-91.9%)
+ Likelihood ratio
Advanced adenoma
1.8 (0.7-4.4)
7.1 (2.4-21.4)
Advanced neoplasia
2.7 (1.3-5.6)
8.6 (3.1-23.5)
CRC
6.4 (3.3-12.3)
10.7 (3.8-29.8)
Negative Likelihood ratio
Advanced adenoma
0.9 (0.7-1)
0.5 (0.3-0.9)
Advanced neoplasia
0.7 (0.6-1)
0.4 (0.2-0.7)
CRC
0.2 (0.03-1.1)
0.3 (0.08-0.9)
Como citar
MATTAR, Rejane et al. Acurácia diagnóstica de teste quantitativo imunoquímico fecal com uma amostra ou com duas amostras para detectar neoplasia intestinal. Arquivos de Gastroenterologia [online]. 2020, v. 57, n. 03 [Acessado 3 Abril 2025], pp. 316-322. Disponível em: <https://doi.org/10.1590/S0004-2803.202000000-58>. Epub 11 Set 2020. ISSN 1678-4219. https://doi.org/10.1590/S0004-2803.202000000-58.
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São Paulo -
SP -
Brazil E-mail: secretariaarqgastr@hospitaligesp.com.br
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