الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Differentiating between functional bowel disorders,
such as irritable bowel syndrome (IBS) and inflammatory
bowel disease (IBD), can often be difficult as they present
with similar symptoms. Noninvasive biomarkers in IBD are
being increasingly recognized as important, both at the initial
diagnosis and for monitoring disease activity. They also play
a valuable role in differentiating organic GI disease from
functional disorders by examining the entire GI tract.
Colorectal cancer (CRC) is a common and lethal
disease., CRC is one of the most common malignancies in
Egypt. The majority of CRC cases are preventable by early
detection in asymptomatic patients at a curable stage as it
might develop from variant processes like colorectal polyps
and inflammatory bowel disease (IBD).
Neoplastic polyps of the colon and rectum, namely
tubular and villous adenomas are precursor lesions of
colorectal cancer. Nearly 95% of sporadic colorectal cancers
develop from these adenomas. Early detection and removal
of an adenoma prior to malignant transformation may reduce
the risk of colorectal cancer.
The gold standard for the early detection of CRC is
colonoscopy. The selection of patients who should undergo
endoscopic or radiological procedures is one of the key
points of the diagnostic process of CRC, which should avoid
the abuse of invasive and expensive tests as well as the
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underestimation of potentially harmful diseases. The
diagnosis and management of CRC could be enhanced by the
discovery and validation of new candidate biomarkers, aimed
at facilitating early detection and/or patient stratification.
Plasma M2- pyruvate kinase (M2 - PK) plays an
important role in tumor metabolism and aerobic glycolysis
during tumor genesis. Plasma M2-PK is mainly tetrameric
with a high affinity for its substrate, phosphoenolpyruvate.
However, tumor cells usually express a dimeric form and
usually predominant in tumor cells by direct interaction with
various oncoproteins. Tumor M2-PK can be detected in
blood and fecal samples, most probably due to high
expression in tumor cells and release into the body fluids.
Blood tests are more convenient than fecal tests and can
achieve a higher compliance rate in the general population.
Serum M2 - PK among CRC patients was about 4 fold higher
than that among the normal. Serum M2-PK levels may be
useful in distinguishing malignant and benign lesions of the
colon and may provide insight in terms of survival.
The aim of this study is to evaluate the diagnostic value
of plasma M2-pyruvate kinase level in differentiating
functional colonic disorders (e.g: IBS) from organic colonic
disorders (e.g: IBD, colorectal polyps and colorectal cancer)
and to assess its use as screening tools for inflammatory bowel
disease, pre-malignant and malignant colorectal lesions.
This study was conducted on 80 patients who fulfilling
the designed inclusion criteria. The study was carried out from
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the inpatient unit and outpatient clinic of Gastroenterology and
Hepatology department at Ain Shams University Hospital and
El Galaa Military Hospital during the period from November
2017 to November 2019. Our study was conducted on 80
patients and divided into four groups:
group I: included 20 patients, with negative colonoscopic
examination that represent functional bowel disorders (IBS
group as a control group).
group II: included 20 patients with inflammatory bowel
diseases) consist of 18 patients with ulcerative colitis and
2 patient with colonic Crohn‘s disease(.
group III: included 20 patients with colorectal polyps)
consist of 31 patients with adenomatous polyp and 3
patients had non adenomatous polyp(
group IV: included 20 patients with colorectal cancer.
All the studied patients were subjected to: Full history
taking, thorough clinical examination, imaging, colonoscopy
and biopsies and routine laboratory investigations and
specific tumor marker; plasma M2-PK, CEA and CA19-9.
The current study revealed that there was highly
statistically significant difference between functional and
organic groups as regard FOBT as (P-value = 0.000).
Diagnostic performance of FOBT as a marker in
discrimination between functional and organic groups using
ROC curve which yielded sensitivity 51.7 %, specificity
100%, PPV 100% and NPV 69%. As regard stool analysis
there was highly statistically significant difference between
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functional and organic groups as regard stool analysis
especially WBCs and RBCs in stool which elevated in
organic more than functional colonic disorders as (P - value =
0.001). As regard CA 19-9 there was no statistically
significant difference between functional and organic groups
as regard CA19-9 as (P-value = 0.167).
The current study also, revealed that there was a highly
statistically significant difference between the functional and
organic groups as regard CEA as (P-value = 0.000). The
median value of CEA in functional group was 0.85 ng/mL
with IQR (0.7-1 ng/mL) while, in organic group its median
was 7ng/ml and with IQR (4.29-17.5 ng/mL). Also, ROC
curve showing the diagnostic performance of CEA as a marker
of discrimination between functional and organic groups.It
was found that the cut off value of CEA (> 1 ng /ml) yielded
sensitivity 98.33%, specificity 85%, PPV 95.2% and NPV
94.4%.
The present study showed that there was a highly
statistically significant difference between the functional and
organic groups as regard plasma M2-PK as (P-value = 0.000).
Average plasma M2-PK was ranged between (0.5 – 3
IU/mL) with Mean ± SD (1.34 ± 0.71 IU/mL) in functional
group and ranged between (1.9 – 29 IU/mL) with Mean ± SD
(10.72 ± 7.16 IU/mL) in organic group. The current study
showed that plasma M2 - PK can be used to differentiate
functional from organic colonic lesions at a cut-off point > 3
U/mL, with 93.33% sensitivity, 100% specificity, 100% PPV
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and 83.3% NPV. Also, The current study showed that plasma
M2-PK can be used to discriminate between benign
(colorectal polyp) and malignant colonic lesions (CRC) with
a cut-off level of > 12 U/ml, with 100% sensitivity, 100%
specificity, 100% PPV and 100% NPV.
In the present study there was a highly significant + ve
correlations between Plasma M2 PK level and CEA as (r =
0.787, p value = 0.000) and their combination can give
higher sensitivity and specificity.
In our study there was highly statically significant
difference as regard relation of plasma M2–PK to endoscopic
activity of ulcerative colitis as plasma M2-PK more elevated
in mayo1 & 2 & 3 (active disease) in comparison to Mayo 0
(normal or in active disease) as (P value =0.000).
In the current study there was highly statically
significant difference as regard relation of plasma M2-PK to
CRC histopathological severity as it more elevated in
Mucinous adenocarcinoma than non - Mucinous
adenocarcinoma as (P value=0.001). Also, there was statically
significant difference as regard relation of plasma M2-PK to
colorectal polyp histopathological severity as it elevated in
adenomatous polyp (villous > tubulovillous > tubular) more
than non-adenomatous polyp(hyperplastic polyp) as (P
value=0.025).
In the present study there was highly statically
significant difference as regard relation of plasma M2- PK to
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colorectal polyp grading risk as it more elevated in
adenomatous polyp (high risk adenoma > low risk adenoma)
than non - adenomatous polyp (hyperplastic polyp). Also,
There was highly statically significant difference as regard
relation of plasma M2-PK to CRC grading severity as it more
elevated in (poorly differentiated > moderately differentiated >
well differentiated colorectal cancer).
Overall, we conclude that no single test is currently
able to diagnose organic colonic disorders. Plasma M2-PK
can be used as an efficient primary screening test for organic
colonic disorders (IBD, colorectal polyps and CRC). It is
simpler and faster than a fecal test and cheaper, more
convenient, and safer than colonoscopy. It is a promising
non-invasive biomarker for organic colonic disorders early
detection. The data from the present study are consistent with
that Combined studies of different markers either fecal as
(FOBT) or blood as (CEA) are recommended with plasma
M2-PK to increase its efficacy in differentiation between
functional and organic colonic disorders.
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Conclusions
Plasma M2-PK can differentiate between functional
and organic colonic disorders as it is more elevated in
organic than functional colonic disorders. Also, it is
considered a promising rapid non invasive biomarker for
organic colonic disorders early detection and may be
considered as a marker for organic colonic disorders
screening to reduce unnecessary endoscopic investigations.
Also, Plasma M2-PK can discriminate between benign
(colorectal polyp) and malignant colonic lesions
(CRC).Moreover, plasma M2 - PK can differentiate between
active and in active IBD. Furthermore, plasma M2-PK can
evaluate grading risk of colorectal polyps and CRC as it
more elevated in adenomatous polyp (high risk adenoma >
low risk adenoma) than non - adenomatous polyp
(hyperplastic polyp) and also, it more elevated in (poorly
differentiated > moderately differentiated > well
differentiated CRC).