Gastric cancer after positive screening faecal occult blood testing and negative assessment

doi:10.1016/j.dld.2006.11.010

Digestive and Liver Disease

Volume 39, Issue 4, April 2007, Pages 321-326

https://doi.org/10.1016/j.dld.2006.11.010 Get rights and content

Abstract

Background

Gastric cancer may be suspected with otherwise unexplained positive faecal occult blood testing.

Aims

To assess the frequency of gastric cancer following positive faecal occult blood testing and negative colonoscopy.

Subjects

Age 40–74 cohort at first screening (1985–2001) with (a) faecal occult blood testing− (83,489), (b) faecal occult blood testing +/colonoscopy+ (2025), or faecal occult blood testing+/colonoscopy− (3555).

Methods

Gastric cancer incidence in faecal occult blood testing subsets, compared with expected standardized incidence rates.

Results

Gastric cancer risk was increased (standardized incidence rate = 146.7; 95% confidence interval: 105.8–203.4) in faecal occult blood testing+/colonoscopy− subjects. A four-fold excess incidence occurred during first year (observed cases = 10, standardized incidence rate = 408.3; 95% confidence interval: 219.7–758.8), irrespective of faecal occult blood testing type (guaiac, immunological). No excess risk occurred in faecal occult blood testing− (observed cases = 53, standardized incidence rate = 91.2; 95% confidence interval: 84.1–98.8) or in faecal occult blood testing+/colonoscopy+ subjects (observed cases = 2, standardized incidence rate = 101.9; 95% confidence interval: 25.5–407.4). Assuming a 100% 3-year study sensitivity for gastric cancer, faecal occult blood testing positive predictive value would be 0.4% (40–74 years) or 0.7% (≥60 years) in faecal occult blood testing+/colonoscopy− subjects.

Conclusions

Data suggest an association of faecal occult blood testing+/colonoscopy− and excess gastric cancer incidence in the following year. Due to low faecal occult blood testing+ positive predictive value, routine upper digestive tract endoscopy in these subjects is questionable.

Introduction

Screening for colorectal cancer (CRC), with faecal occult blood testing (FOBT) has been shown to be effective in reducing mortality from CRC [1], [2], [3], [4]. Although the positive predictive value (PPV) of immunochemical FOBT for colorectal neoplasm (cancer or adenoma) may be as high as 37% [5], no lesion is found in a substantial proportion of FOBT+ subjects. As FOBT+ might be caused by upper digestive tract bleeding (gastric cancer (GC) or other disease, such as esophageal cancer, ulcerative esophagitis, and gastric and duodenal ulcer), it may be argued whether this tract should be investigated in FOBT+ subjects with negative assessment of the colon.

A screening programme for CRC is ongoing since 1980s in Florence District. Detailed features of the programme have been already reported [5]. All residents aged 50–70 years are invited to undergo FOBT every other year. FOBT+ subjects are assessed by total colonoscopy, with double-contrast enema (DCE) being performed when colonoscopy is incomplete or refused [6]. Classic guaiac FOBT was employed until 1995 and was thereafter replaced by immunochemical FOBT (reversed passive haemagglutination until 2000, latex agglutination thereafter) [7], [8]. The effectiveness of the programme in reducing CRC mortality has been assessed by means of a case-control study [9].

The aim of the present study was to assess the frequency of GC in FOBT+ subjects with negative diagnostic assessment (henceforth referred to as DA−), and to evaluate whether it might be worthwhile to screen these subjects by upper digestive tract endoscopy.

Section snippets

Materials and methods

All subjects at their first screening visit during 1985–2001 were identified in our screening database. Subjects (a) aged <40 or >74 years, or (b) FOBT+ and assessed only by DCE, or (c) with GC detected before FOBT date (five cases) were excluded. The remaining cases were eligible for the study. FOBT+/DA− subjects were then compared with FOBT− and with FOBT+/DA+ subjects.

The number of GC expected in the study cohort was calculated by applying GC incidence rates (provided by the Tuscany Cancer

Results

Between January 1985 and December 2001, 5580 FOBT+ subjects underwent diagnostic assessment. Colonoscopy was complete in 3428 subjects (62.4%) and incomplete in 2075 (37.2%). For 77 subjects (0.1%) information on colonoscopy was missing. Incomplete colonoscopy was supplemented by DCE in 1699 cases (81.9%). It is worth noting that a substantial increase in colonoscopy completeness was observed over time: 37.3% (288/773), 61.1% (2093/3423) and 80.1% (1047/1307) during 1985–1990, 1991–1996 or

Discussion

The present study is based on a relatively large FOBT screening series, followed up by cancer registry, and thus allowing a reliable estimate of FOBT+ PPV for GC. The high rate of incomplete colonoscopy in the first period of the study might be of concern, as it might suggest a higher probability of false negative diagnostic assessment. This figure is probably overestimated as in the first period of the study missing information on the upper limit reached by colonoscopy was assumed as

Conflict of interest statement

None declared.

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Citation Excerpt :
There were no differences in the upper digestive cancer risk and related mortality between FIT positive and negative population [22]. In contrast, in an Italian study, the incidence of GC was shown to be increased in patients with positive FOBT or FIT and negative colonoscopy realized for CRC screening, when compared to the expected GC standardized incidence rates, with a four-fold excess incidence during the first year after colonoscopy [23]. In our study, the rate of upper digestive lesions found during systematic upper endoscopy did not differ between the patients with positive and negative results of CRC screening colonoscopy, suggesting that the screening of upper digestive lesions may be indicated in all the patients with positive FIT.
The French colorectal cancer screening program is based on a fecal immunochemical test, followed by colonoscopy in case of positivity. The benefit of adding a concomitant upper endoscopy to detect upper digestive lesions (precancerous or others) is still debated. Our aim was to evaluate the frequency of upper digestive lesions detected by upper endoscopy performed concomitantly with colonoscopy following a positive fecal immunochemical test, and their impact on the patients’ management (i.e., surveillance, medical treatment, endoscopic or surgical procedure).
Data of all the patients who consulted for a positive test between May 2016 and May 2019 in our center, and for whom concomitant upper endoscopy and colonoscopy were performed, were analyzed retrospectively. Patients with significant history of upper gastrointestinal diseases or with current gastrointestinal symptoms were excluded.
One hundred patients were included [median age (min–max): 62 (50–75), men 64%]. Macroscopic and/or microscopic upper digestive lesions were found in 58 of them (58%): Helicobacter pylori infection in 17 patients, gastric precancerous lesions in 9 patients (chronic atrophic gastritis with intestinal metaplasia, n = 8, low grade dysplasia, n = 1), Barrett's esophagus requiring surveillance in 4 patients, and 1 duodenal adenoma with low-grade dysplasia. In 44 patients (44%), the upper endoscopy findings had an impact on patients’ management, with no significant difference between the groups with positive (CRC or advanced adenoma)- or negative (any other lesions or normal) colonoscopy.
A systematic upper endoscopy combined with colonoscopy for positive fecal immunochemical test could represent an efficient strategy for upper digestive lesions screening in France. Further studies are necessary to confirm these results and to evaluate cost-effectiveness of this approach.
Risk of Oral and Upper Gastrointestinal Cancers in Persons With Positive Results From a Fecal Immunochemical Test in a Colorectal Cancer Screening Program
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Citation Excerpt :
A PPV for FOBT of 0.4% (14 of 3555 within 3 years after FOBT) for gastric cancer in FOBT positives with a negative colonoscopy was reported, resulting in a number needed to scope of 254. They only identified gastric cancers and did not select esophageal cancers or other proximal cancers.16 Rasmussen et al17 reported a significant difference in incidence between gastric and esophageal cancers between gFOBT positives and gFOBT negatives in a Danish population, but also reported a low PPV of 0.52% (within 2 years of a gFOBT) among persons with an negative colonoscopy.17
European guidelines recommend screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT), with follow-up colonoscopies for individuals with positive test results. However, more than half of participants with positive results from the FIT are not found to have advanced neoplasia in the colonoscopy examination. Fecal occult blood might also come from the upper gastrointestinal (GI) tract, so perhaps we should consider esophagogastroduodenoscopy (EGD), to detect upper GI cancers. We aimed to determine how many individuals are found to have oral or upper GI cancers (oral cavity, throat, esophageal, gastric, or small bowel cancer) within 3 years after a positive or negative result from a FIT in a CRC screening program.
We performed a retrospective analysis of data from a pilot study of 3 rounds of biennial FIT-based screening for CRC in 2 regions in the west of the Netherlands, from 2006 through October 2012. Participants who developed oral or upper GI cancers were identified through linkage with the National Cancer Registry. We classified these cancers into 3 groups: those that developed in individuals with a positive result from a FIT but negative findings from colonoscopy (no advanced neoplasia), those that developed in individuals with a positive result from a FIT and a positive finding from colonoscopy (advanced neoplasia), and those that developed in individuals with negative results from a FIT. We compared oral and upper GI cancer incidence among groups.
Among 16,165 screening participants, linkage identified 52 persons who developed an oral or upper GI cancer within 3 years after a FIT. We found no significant difference in incidence values between individuals with a positive vs a negative FIT result: 8 cancers developed in individuals with a positive result from a FIT (0.37%; 95% CI, 0.19–0.76) and 44 developed in individuals with a negative result from a FIT (0.31%; 95% CI, 0.23–0.42) (P = .65). Of the 8 individuals with a positive result from a FIT and an oral or upper GI cancer, 6 were diagnosed after negative findings from colonoscopy and 2 after positive findings from colonoscopy. We found that only 0.14% of all persons with a positive result from a FIT were diagnosed with a gastric or esophageal cancer within 3 years.
In a study of individuals in the Netherlands undergoing screening for CRC by FIT, we found fewer than 1% of patients with a positive result from the FIT to receive a diagnosis of upper GI cancers within 3 years. Routine EGD investigation of individuals with positive results from a FIT and negative findings from colonoscopy is therefore not recommended. TrialRegister.nl, Number: NTR5385.
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Previous studies have suggested that the immunochemical fecal occult blood test has superior specificity for detecting bleeding in the lower gastrointestinal tract even if bleeding occurs in the upper tract. We conducted a large population-based study involving asymptomatic adults in Taiwan, a population with prevalent upper gastrointestinal lesions, to confirm this claim.
We conducted a prospective cohort study involving asymptomatic people aged 18 years or more in Taiwan recruited to undergo an immunochemical fecal occult blood test, colonoscopy and esophagogastroduodenoscopy between August 2007 and July 2009. We compared the prevalence of lesions in the lower and upper gastrointestinal tracts between patients with positive and negative fecal test results. We also identified risk factors associated with a false-positive fecal test result.
Of the 2796 participants, 397 (14.2%) had a positive fecal test result. The sensitivity of the test for predicting lesions in the lower gastrointestinal tract was 24.3%, the specificity 89.0%, the positive predictive value 41.3%, the negative predictive value 78.7%, the positive likelihood ratio 2.22, the negative likelihood ratio 0.85 and the accuracy 73.4%. The prevalence of lesions in the lower gastrointestinal tract was higher among those with a positive fecal test result than among those with a negative result (41.3% v. 21.3%, p < 0.001). The prevalence of lesions in the upper gastrointestinal tract did not differ significantly between the two groups (20.7% v. 17.5%, p = 0.12). Almost all of the participants found to have colon cancer (27/28, 96.4%) had a positive fecal test result; in contrast, none of the three found to have esophageal or gastric cancer had a positive fecal test result (p < 0.001). Among those with a negative finding on colonoscopy, the risk factors associated with a false-positive fecal test result were use of antiplatelet drugs (adjusted odds ratio [OR] 2.46, 95% confidence interval [CI] 1.21–4.98) and a low hemoglobin concentration (adjusted OR 2.65, 95% CI 1.62–4.33).
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Alimentary tractGastric cancer after positive screening faecal occult blood testing and negative assessment

Abstract

Background

Aims

Subjects

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Conflict of interest statement

Lancet

Am J Med

Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota colon cancer control study

N Engl J Med

Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood

J Natl Cancer Inst

A randomized study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennal screening rounds

Gut

Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results

Eur J Cancer Prev

Role of double-contrast barium enema in colorectal cancer screening based on fecal occult blood

Tumori

Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing

J Med Screen

Screening for colorectal cancer by faecal occult blood test: comparison of immunochemical tests

J Med Screen

Alimentary tract
Gastric cancer after positive screening faecal occult blood testing and negative assessment