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Stomach cancer is a serious threat to global health as it is the world's third leading cause of death from cancer. The major risk behind this disease is that it remains asymptomatic in the early stages. In this study, serum catenin-δ-1 (also known as δ-catenin), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were measured in 70 patients; 20 of which were diagnosed with gastric cancer, 20 with gastric ulcer and 30 with gastritis and also in 20 healthy volunteers as a control group. Infection with Helicobacter pylori was diagnosed by histology, rapid urease test (RUT) and serology, which included IgG and IgA antibodies. The results showed that there was a significant increase in the levels of serum δ-catenin in patients with gastric cancer compared to the control group as well as gastritis and gastric ulcer patients. A significant increase in the levels of δ-catenin was also seen in gastric ulcer and gastritis patients compared to the control group. In addition, a significant increase was seen in δ-catenin serum levels in patients with gastric cancer and gastric ulcer infected with H. pylori compared to the uninfected gastric cancer and gastric ulcer patients. A non-significant increase was observed in the levels of CEA and CA19-9 in all the patients compared to the control group. The results of the present study suggest that serum δ-catenin can serve as a potential marker for gastric cancer.
Mustafa K. Albayaty1*, Salma A. Abass2, Mohammed F. Al-Marjani3 and Safaa A. A. Razzak4
1Department of Forensic Evidence Techniques, College of Medical Techniques, Al-Farahidi University, Baghdad, Iraq.
2Department of Chemistry, College of Science, Mustansiriyah University, Baghdad, Iraq.
3Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq.
4Gastroenterology and Liver Diseases Hospital, Medical city, Baghdad, Iraq.
*e-mail :
(Received 25 March 2021, Revised 27 April 2021, Accepted 14 May 2021)
ABSTRACT : Stomach cancer is a serious threat to global health as it is the world’s third leading cause of death from cancer.
The major risk behind this disease is that it remains asymptomatic in the early stages. In this study, serum catenin-δδ
δ-1 (also
known as δδ
δ-catenin), carcinoembryonic antigen CEA and carbohydrate antigen 19-9 CA 19-9 were measured in 70 patients; 20
of which were diagnosed with gastric cancer, 20 with gastric ulcer and 30 with gastritis and also in 20 healthy volunteers as a
control group. Infection with Helicobacter pylori was diagnosed by histology, rapid urease test (RUT) and serology, which
included IgG and IgA antibodies. The results showed that there was a significant increase in the levels of serum δδ
δ-catenin in
patients with gastric cancer compared to the control group as well as gastritis and gastric ulcer patients. A significant increase
in the levels of δδ
δ-catenin was also seen in gastric ulcer and gastritis patients compared to the control group. In addition, a
significant increase was seen in δδ
δ-catenin serum levels in patients with gastric cancer and gastric ulcer infected with H. pylori
compared to the uninfected gastric cancer and gastric ulcer patients. A non-significant increase was observed in the levels of
CEA and CA 19-9 in all the patients compared to the control group. The results of the present study suggest that serum δδ
catenin can serve as a potential marker for gastric cancer.
Key words : δ-catenin, gastric cancer, gastric ulcer, gastritis, Helicobacter pylori.
How to cite : Mustafa K. Albayaty, Salma A. Abass, Mohammed F. Al-Marjani and Safaa A. A. Razzak (2021) Catenin-δ-1 as a
potential marker of gastric cancer in a sample of Iraqi patients with gastric diseases associated with Helicobacter pylori.
Biochem. Cell. Arch. 21, 1949-1954. DocID:
Gastric cancer is the world’s third-largest cause of
cancer death and a significant global threat to public
health (Takahiro et al, 2015; Ingrid et al, 2017). More
than 80 percent of the cases are due to H. pylori
infection. Furthermore, gastric carcinogenesis is
contributed also by diet, lifestyle, genetic, social, and other
factors (Magdalena et al, 2017). A very well-established
proposition states that stomach cancer starts the following
infection with H. pylori and proceeds through a stepwise
process of surface-related lesions (superficial then
atrophic gastritis followed by intestinal metaplasia and
dysplasia) (Lydia et al, 2010; Manuel et al, 2015).
The catenin-ä-1 (p120 catenin or ä-catenin) protein
was initially distinguished in a search for Src tyrosine
kinase substrates as a 120 kDa protein. It is externally
like â-catenin, in structure, since it is an individual belonging
to the armadillo (ARM) group of proteins, and also in
functions, since it attaches to cadherins at the AJs (Antonis
et al, 2013). δ-catenin is an auxiliary part of the CCC (E-
Cadherin/β-Catenin/α-Catenin), in addition, it inhibits the
endocytosis of essential cadherins through attachment
with the cytoplasmic juxta-membrane areas of E-cadherin
at a site, which covers their dileucine endocytic motif.
By covering this motif, δ-catenin inhibits the association
between the cytoplasmic tail of traditional cadherins and
Presenilin-1 and Hakai, thus inhibiting the endocytosis of
E-cadherin (Reynolds, 2007). In addition, ä-catenin enrolls
the short finishes of microtubules to the cadherin complex
prompting the development of the junctions. When δ-
catenin dislocates and separates from the complex of E-
cadherin, endocytosis of the membrane E-cadherin occurs
(Davis et al, 2003; Xiao et al, 2003; Hoshino et al, 2005).
Biochem. Cell. Arch. Vol. 21, Supplement 1, pp. 1949-1954, 2021 ISSN 0972-5075
DocID: eISSN 0976-1772
1950 Mustafa K. Albayaty et al
The endocytosed E-cadherins could either be broken down
or reprocessed to the plasma membrane (Hoshino et al,
2005; Balzac et al, 2005). Therefore, δ-catenin is a key
controller, which governs the rebalancing and construction
of E-cadherin into AJs (Stephanie et al, 2016; Qun et al,
2016; Diana et al, 2016; Ji et al, 2016). The dissociation
of ä-catenin from the cadherin-catenin complex, which
occurs during the carcinogenesis process or the damage
done to the cells lining the stomach in cases like gastritis
and gastric ulcer leads to the accumulation of δ-catenin
in the cytoplasm, this dislocated part of the δ-catenin is
believed to leak to the general circulation which enables
its measurement in the blood of the patients. Measurement
of ä-catenin might reflect the status or the integrity of
the cells adhesions in the stomach and thus might be useful
in the diagnosis of gastric cancer. In addition, it might
predict the risk of developing gastric cancer in gastritis
and gastric ulcer patients.
A total of 70 patients (36 males and 34 females) with
an age range of 18 – 74 and 14 – 85, respectively were
enrolled in this study with (20) healthy individuals (10
males and 10 females) with an age range of 22 – 41 and
18 – 47, respectively serving as the control group. The
patients enrolled in the present study were attending the
educational oncology hospital, medical city, Baghdad, the
endoscopy unit of gastroenterology and liver diseases
hospital, medical city, Baghdad, and the endoscopy unit
of Azadi Teaching Hospital, Duhok. This study was
approved by the Department of Chemistry, College of
Science, Al-Mustansiriyah University, Baghdad, Iraq, the
Iraqi Ministry of Health, and by the Research Ethics
Committee of Duhok Directorate General of Health,
Kurdistan Regional Government, Iraq. The study subjects
were divided into (3) groups according to their clinical
diagnosis; (20) patients with gastric cancer (12 males
and 8 females) with an age range of (37 – 74 and 59 – 85
respectively). (20) patients with gastric ulcer (10 males
and 10 females) with an age range of (19 – 60 and 14 –
60 respectively). (30) patients with gastritis (14 males
and 16 females) with an age range of (18 – 55 and 17 –
40 respectively).
Exclusion criteria
Cases were excluded from this study if one or more
of the following criteria were present; current or previous
chemotherapy, current or previous antibiotic or PPI
treatment, use of NSAID drugs, the presence of another
type of cancer, the presence of liver inflammation, or
other related liver diseases, gastrectomy and H. Pylori
infected volunteers.
Samples collection
Ten milliliters of blood were collected from each
patient and healthy control. Blood samples were
transferred into gel tubes and left for 15 – 30 minutes at
room temperature to clot. The blood samples were then
centrifuged and the obtained serum samples were stored
at -20ºC till assayed. In addition, biopsy samples were
also collected from the stomach of the patients by the
physicians performing the endoscopy for histology and
Histology and rapid urease test (RUT)
Histology was performed by specialized histologists
in the laboratories of each hospital from which the
biopsies were taken. RUT was performed in the
endoscopy unit during the endoscopy procedure. A biopsy
from the antrum was combined with a biopsy from the
corpus and was placed on the RUT cassette and covered.
After one hour, a color change (from yellow to pink)
indicated a positive test.
Biochemical analyses
Serum δ-catenin was measured by enzyme-linked
immunosorbent assay (ELISA) using the Human δ-
catenin Elisa Kit provided by (Shanghai Biological /
China) following the manufacturers directions. Anti-H.
pylori IgG and IgA antibodies were measures by (ELISA)
using Helicobacter IgG Elisa Kit and Helicobacter IgA
Elisa Kit provided by (Demeditec/ Germany) following
the manufacturers directions. CEA and CA 19-9 tumor
markers were measured by enzyme-linked fluorescent
assay (ELFA) using VIDAS CEA (S) and VIDAS CA
19-9 (199) kits provided by (Biomerieux/ France)
following the manufacturers directions.
Statistical analyses
Biochemical data were analyzed using SPSS
(statistical package for social sciences) version 25. T-
Test was used to calculate the mean ± standard deviation
(SD) and the p-value.
Diagnosis of H. pylori infection
The infection with H. pylori was diagnosed by
histology, RUT, IgA and IgG antibodies. Fifty (71.43%)
out of the seventy patients were positive for H. pylori
while all the healthy controls were negative for the
infection. Patients were considered positive if at least
two of the mentioned tests were positive. Tables 1 and 2
shows the status of the infection of each group in this
study and the results of each diagnostic method compared
with the others, respectively.
Catenin-δ-1 as a potential marker of gastric cancer in a sample of Iraqi patients 1951
Fifty patients (71.4%) were proved to be positive for
H. pylori infection by histology and RUT and as such,
they were considered to have a sensitivity and specificity
of (100 %). Histology was the first method to be used to
diagnose H. pylori and is considered the standard gold
method (Farzaneh et al, 2016; Ana et al, 2014). The RUT
operates on the principle that H. pylori produce huge
amounts of the urease enzyme that hydrolyses the host
urea producing ammonia, which can be detected by a
variety of indirect means (Choi et al, 2012; Moon et al,
2012). However, many factors affect histology and RUT
accuracy as diagnostic methods, such as size, the number
of biopsies, site of biopsies and methods of staining, proton
pump inhibitor (PPI), antibiotics, and the pathologist’s
experience, time-consuming, relatively costly, bleeding
(such as bleedings of peptic ulcers) (Ana et al, 2014),
gastrectomy (Tian et al, 2012; Yao-Kuang et al, 2015;
Saurabh et al, 2014; Amin, 2018). Several studies
concluded that, in addition to increasing the number of
biopsies, the collection of biopsies from different regions
of the stomach could result in a higher accuracy of RUT
(Farzaneh et al, 2016; Yao-Kuang et al, 2015; Amin,
2018). The low diagnosis cost, ease, and speed give the
RUT the upper hand over histology.
Fifty-nine patients (84.3%) were positive for the anti-
H. pylori IgG antibodies, while only eleven patients
(15.7%) were positive for the anti-H. pylori IgA
antibodies. The results of IgG showed only nine false-
positive cases and zero false-negative cases. In contrast,
IgA results showed thirty-nine false-negative cases and
zero false-positive cases. Accordingly, we concluded that
IgG showed better results in terms of sensitivity and
overall diagnostic accuracy. IgA results turned to be less
trustful and less reliable. Studies also showed that IgA
based serologic tests were much less useful and less
accurate in contrast to IgG based tests which showed
sensitivities up to (100%) and specificities of (58 – 97%)
supporting that IgG tests are more accurate and reliable
(Rosemary et al, 2009; Babak et al, 2013; Julian et al,
1990). High levels of IgG are seen in nearly all individuals
with H. pylori infection, but IgA levels exceed cut-off
values in only about two-thirds of cases (Pandya et al,
2014). Serological tests are generally relatively cheap,
performed quickly and, unlike invasive methods, cause
minimal discomfort to the patient (Priya et al, 2017).
Diagnosis of H. pylori with serology is not influenced by
gastric atrophy, ulcer bleedings, or PPI and antibiotics
(Yao-Kuang et al, 2015; Amin, 2018). Still, these tests
are not useful in evaluating eradication therapy because,
even after complete eradication, antibody levels remain
in the blood for extended periods (Yoshihisa et al, 2004).
These tests cannot differentiate active (current) infection
from past (inactive) infection, which makes these tests
unreliable in solely diagnosing H. pylori (Priya et al, 2017;
Best et al, 2018).
Serum levels of δδ
δ-catenin, CEA and CA 19-9
A significant increase in the levels of ä-catenin was
observed in the sera of patients diagnosed with gastric
ulcer (20.31 ± 0.94351) and gastritis (17.07 ± 0.8799)
compared to the control group (14.03 ± 1.47) (p < 0.001),
there was also a significant increase in the levels of δ-
catenin in sera of gastric cancer patients (28.34 ±
3.956823) in comparison to the controls as well as to the
gastric ulcer and gastritis groups. There was a small,
statistically non-significant increase in the levels of CEA
in the sera of gastric cancer patients (3.96 ± 1.93)
compared to the control group (2.98 ± 1.41) (p = 0.094)
as well as to the gastric ulcer (3.77 ± 1.64) and gastritis
patients (3.62 ± 1.42). A non-significant increase was
also seen in the levels of CA 19-9 in sera of patients
diagnosed with gastric cancer (17.68 ± 17.04) compared
to the control group (13.03 ± 8.35) (p = 0.313) as well as
to gastric ulcer (14.40 ± 9.13) and gastritis patients (13.94
± 7.74). Tables 3 and 4 shows the levels of ä-catenin,
CEA and CA 19-9 in patients’ groups and controls.
There was a large significant increase in the levels
of ä-catenin in sera of gastric cancer patients infected
Table 1 : Helicobacter pylori status of patients and control groups.
Groups H. pylori H. pylori
Positive Negative
N (%) N (%)
Gastric cancer 7 (35) 13 (65)
Total N = 20
Gastric ulcer 13 (65) 7 (35)
Total N = 20
Gastritis 30 (100) 0 (0)
Total N = 30
Control 0 (0) 20 (100)
Total N = 20
Table 2 : Results of Helicobacter pylori diagnostic methods.
Diagnostic method Positive cases Negative cases
N (%) N (%)
Patients N = 70 50 (71.4) 20 (28.6)
Histology 50 (71.4) 20 (28.6)
RUT 50 (71.4) 20 (28.6)
IgG 59 (84.3) 11 (15.7)
IgA 11 (15.7) 59 (84.3)
Control N = 20 0 (0) 20 (100)
IgG 0 (0) 20 (100)
IgA 0 (0) 20 (100)
1952 Mustafa K. Albayaty et al
with H. pylori (32.50 ± 0.99) compared to uninfected
gastric cancer patients (26.09 ± 3.03). There was also a
significant increase in ä-catenin levels in the sera of gastric
ulcer patients infected with H. pylori (20.91 ± 0.50)
compared to uninfected gastric ulcer patients (19.19 ±
0.37). There were no significant differences in the levels
of CEA and CA 19-9 tumor markers between H. pylori-
infected and H. pylori uninfected patients.
The significant segments of the adherens junctions
(AJs) proteins are E-Cadherin, β-Catenin and Catenin-
δ-1 (also known as p120 catenin). The AJs are confined
beneath the tight intersections (junctions) (TJs) and
playout numerous roles including stabilizing cell-cell
attachment, starting TJs gathering, adjusting cytoskeleton
modification, transcriptional regulation, and signaling
transduction Epithelial cells’ AJs contribute to maintaining
epithelial barrier integrity and loss of the AJs integrity
has been connected to tumor initiation and progression
(Junting et al, 2018). In the present study, all the study
subjects suffer from defects or damage in the cells lining
the stomach and these defects extend over different
degrees depending on the condition. Such defects are
thought to influence the cells’ adhesion and as such the
AJs complex. Furthermore, H. pylori stimulating the
proteolytic cleavage of the E-Cadherin extracellular
domain (David et al, 2012; Sandra et al, 2017). This
cleavage leads to the disassembly of the adheres junctions
complex and the subsequent accumulation of the β-
catenin and catenin-δ-1 in the cytoplasm (Nelson et al,
2004; Backert et al, 2017). This accumulated ä-catenin
might leak into the general circulation, which enables its
determination in the blood of the patients. This might give
a possible explanation for the findings of the current study
and might further explain the increased levels of this
protein in the patients infected with H. pylori, this also
may represent one of the possible mechanisms for the
influence of H. pylori on the pathogenesis of gastric
diseases. Based on these findings, elevated levels of δ-
catenin can be employed in the diagnosis of gastric cancer.
The elevated levels of ä-catenin in gastritis and gastric
ulcer patients might indicate the tendency and the possible
risk of developing gastric cancer in these patients.
Through intensive search in the literature, we could not
find a single study regarding serum levels of catenin-δ-1
in any diseases or disorders and this research would
represent the first study to describe its role in gastric-
related diseases.
The majority of studies demonstrate that CEA and
CA 19-9 markers are advantageous tools for metastasis
and recurrence of malignancies as well as for assessing
the effectiveness of chemotherapy and prognosis in
gastric malignant growth (Wang et al, 2014; Jing et al,
2013). However, CA 19-9 and CEA are not helpful for
the finding of early gastric malignancy (Feng et al, 2017).
Elevated concentrations of these markers are also seen
in different tumors and some nonmalignant conditions,
for example, gastritis, gastric ulcer, duodenitis, and
esophagitis (Ozgur, 2015; Xin et al, 2010; Cãtãlina et al,
2016). The consequences of certain investigations
question the advantage of CA 19-9 and CEA even as
monitoring or observing markers in gastric cancers (Polat
et al, 2014; Ohtsuka et al, 2008; Hasbahceci et al, 2018;
Junxiu et al, 2016). The results of the present study are
in accordance with the previous studies, the tumor
Table 3 : Levels of serum Catenin-ä-1, CEA and CA 19-9 in patients and control groups.
Parameters Gastric Cancer Gastric Ulcer Gastritis Control p-value p-value p-value
(A) (B) (C) (D) A vs D B vs D C vs D
Mean ± SD Mean ± SD Mean ± SD Mean ± SD
Catenin-ä-1 28.34 ± 3.956823 20.31 ± 0.94351 17.07 ± 0.8799 14.03 ± 1.47 0.000* 0.000* 0.000*
CEA (ng/mL) 3.96 ± 1.93 3.77 ± 1.64 3.62 ± 1.42 2.98 ± 1.41 0.094 0.135 0.147
CA 19-9 (U/mL) 17.68 ± 17.04 14.40 ± 9.13 13.94 ± 7.74 13.03 ± 8.35 0.313 0.642 0.708
*Significant at the level of (0.05).
Table 4 : Levels of serum Catenin-ä-1, CEA and CA 19-9 in patients’ groups.
Parameters Gastric Cancer Gastric Ulcer Gastritis p-value p-value p-value
(A) (B) (C) A vs B A vs C B vs C
Mean ± SD Mean ± SD Mean ± SD
Catenin-ä-1 28.34 ± 3.956823 20.31 ± 0.94351 17.07 ± 0.8799 0.000* 0.000* 0.000*
CEA (ng/mL) 3.96 ± 1.93 3.77 ± 1.64 3.62 ± 1.42 0.743 0.484 0.740
CA 19-9 (U/mL) 17.68 ± 17.04 14.40 ± 9.13 13.94 ± 7.74 0.464 0.308 0.852
*Significant at the level of (0.05).
Catenin-δ-1 as a potential marker of gastric cancer in a sample of Iraqi patients 1953
markers in this research were not useful nor reliable in
the diagnosis of gastric cancer.
Catenin-δ-1 may serve as a potential marker for the
diagnosis of gastric cancer and it may also serve as a
possible risk predictor for the development of gastric
cancer in gastritis and gastric ulcer patients. CEA and
CA 19-9 tumor markers are not adequate and reliable
tools for the diagnosis of gastric cancer. H. pylori
contribute to the damage of the adheren junctions that
link the stomach cells with each other.
This work was supported by the Department of
Chemistry and the Department of Biology, College of
Science at Mustansiriyah University, Baghdad, Iraq.
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Table 5 : Levels of serum Catenin-ä-1, CEA and CA 19-9 in H. Pylori infected patients.
Gastric Cancer (Mean ± SD) Gastric Ulcer (Mean ± SD)
Parameters p-value p-value
HP + HP - HP + HP -
Catenin-ä-1 (ng/mL) 32.50 ± 0.99 26.09 ± 3.03 0.000* 20.91 ± 0.50 19.19 ± 0.37 0.000*
CEA (ng/mL) 3.90 ± 1.02 3.99 ± 2.27 0.929 3.56 ± 1.18 4.15 ± 2.21 0.472
CA 19-9 (U/mL) 16.66 ± 11.73 18.14 ± 19.29 0.853 14.56 ± 9.45 14.07 ± 8.49 0.912
HP: H. pylori. *Significant at the level of (0.05).
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Helicobacter pylori (H . pylori) as gram-negative and spiral microorganism is responsible for colonization in the gastric microniche for more than 50% of world population. Recent studies have shown a critical role of H. pylori in the development of peptic ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. Over the past decade, there has been a sharp interest to use noninvasive tests in diagnosis of the H. pylori infection. During the years after discovery by Marshall and Warren, it has been frequently declared that the rapid urease test (RUT) is one of the cheapest and rapid diagnostic approaches used in detecting the infection. Although the specificity and sensitivity are durable for this test, clinical experiences had shown that the ideal results are only achieved only if we take biopsies from both corpus and antrum at the same time. Given the diagnosis of the H. pylori in clinical samples, gastroenterologists are facing a long list of various molecular and nonmolecular tests. We need more in-depth researches and investigations to correctly generalize rapid and accurate molecular tests determining both bacterial identity and antibiotic resistance profile.
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Purpose: Helicobacter pylori is one of the most prevalent infectious agents in the world which causes a variety of gastrointestinal diseases including gastritis, peptic ulcer and gastric carcinoma. The objective of this study was to comparatively evaluate invasive (rapid urease test and polymerase chain reaction) and non-invasive (enzyme-linked immunosorbent assay) tests in diagnosis of infection with cytotoxigenic H. pylori. Methods: Biopsy specimens and sera were collected from 105 patients with gastric disorders. The presence of H. pylori infection in gastric biopsies was evaluated by RUT and PCR methods using chemotaxis signal transduction protein gene (CSTP), Urea C and HP-16srRNA primers. Serum samples were used for the ELISA test. Detection of infection with cag A-positive strains was performed by PCR and cag A-IgG ELISA kit. Results: Patients with at least two out of three positive results were regarded as infected. The sensitivity, specificity, predictive value and accuracy of the three different methods were evaluated. Of the 105 gastric biopsies, H. pylori were positive in 51 patients (48.57%). The best sensitivity (92.16%) belonged to RUT. The sensitivities of other tests including PCR and ELISA test were 88.24% and 90.20%, respectively. PCR showed the best specificity (94.44%), and the specificities of the other tests including RUT and ELISA test, were 90.74 % and 61.11%, respectively. Furthermore, results of PCR and cag A-IgG ELISA showed high prevalence of cag A-positive strain in the study population. Conclusion: Based on our findings, serum ELISA is a rapid noninvasive test for screening of H. pylori infection in the absence of endoscopy indication. In addition, considering the high prevalence of cytotoxigenic H. pylori strains, cag A is suggested as a promising target for PCR and non- invasive ELISA tests for detection of infection with toxigenic strains.
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Background: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. Objectives: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. Search methods: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. Selection criteria: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. Data collection and analysis: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. Main results: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. Authors' conclusions: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.
Introduction To evaluate the impact of serum and peritoneal levels of tumour markers on peritoneal carcinomatosis and survival in gastric adenocarcinoma. Materials and methods Patients with gastric adenocarcinoma were evaluated with regard to serum and peritoneal carcinoembryonic antigen (CEA) and CA19-9. Numeric values and groupings based on serum and peritoneal cutoff values were used. Development of peritoneal carcinomatosis, including positive washing cytology, was regarded as main outcome. Gastric cancer outcomes as disease free and overall survival were analysed. Results There were 67 patients with a mean age of 60 ± 11 years. Positive peritoneal washing cytology was significantly associated with serum CA19-9 and high serum CA 19–9 group (P = 0.033 and P = 0.011, respectively). High peritoneal CEA was shown to be significantly associated with peritoneal carcinomatosis (P = 0.032). After a median follow up of 17 months, 48 patients (71.7%) were alive. Patients with peritoneal carcinomatosis showed significant poorer prognosis as shown by overall survival rate of 28.6%. Only serum CEA was significantly associated with lower disease free and overall survival (P = 0.002 and P = 0.001, respectively). Discussion and conclusion Serum CEA is shown to be significantly associated with poor prognosis for gastric cancer patients. Serum level of CA19-9 and high peritoneal CEA levels are significant predictors for positive peritoneal washing cytology and the development of peritoneal carcinomatosis, respectively. Therefore, the possible impact of serum and peritoneal tumor markers especially on the staging and prognosis of gastric cancer remains to be clarified by future studies.
Aim: This study assessed the Helicobacter pylori (H. pylori) serum antibody test as a diagnostic screening tool in symptomatic inner city children. Methods: This was a retrospective study of patients aged 1-18 years who were referred to our paediatric gastroenterology department from 2009-2013. We included all patients who had H. pylori serum antibodies and, or, faecal antigens who underwent esophagogastroduodenoscopy (EGD) for histology, with or without a gastric tissue rapid urease test. Results: A total of 395 patients had EGDs carried out to evaluate epigastric pain, heartburn and nausea or vomiting and their overall socioeconomic Z-score was -2.62. The histology was positive for H. pylori infection in 52/395 patients (13%), and epigastric pain was documented in 45 of these 52 patients (87%). Compared to histology, the serum H. pylori antibody test had a sensitivity of 88.4% and a specificity of 93.4%. The tissue rapid urease test and faecal antigen test had sensitivities of 89.3% and 55.6% and specificities of 89.9% and 98.9%, respectively. Conclusion: The serum H. pylori antibody test had high sensitivity and specificity and it was a good diagnostic screening tool in our study. Epigastric pain was strongly associated with a current H. pylori infection in our population. This article is protected by copyright. All rights reserved.