Expression of the signal transducer and activator of transcription factor 3
and Janus kinase 3 in colorectal carcinomas, colonic adenomas and
ulcerative colitis
Mohamed M Shareef1, Maha M Shamlola1, Asem A El Fert2, Mohamed El Sawaf3,
And Hanan H Soliman2
Departments Of Pathology, Tropical, and Surgery , Tanta University
Abstract :
Background and study aims: Despite the growing understanding of the involvement
of protooncogenes and tumour suppressor genes in the oncogenesis of CRC, the
exact biological and molecular mechanisms underpinning this process remain
poorly understood. The signal transducer and activator of transcription (STAT3)
has been implicated in the regulation of growth and malignant transformation.
Accumulating
evidences have come to indicate that abnormalities in the Janus kinase
(JAK)/STAT pathway are involved in oncogenesis of several cancers. The aim of
this study was to investigate the expression of JAK3 and STAT3 in both normal
and activated forms by immunohistochemistry in adenomas of the colon, ulcerative
colitis and CRC compared to normal colonic mucosa.
Patients and methods: Tissues from 30 cases with primary CRC and seven cases
with ulcerative colitis (UC), removed by colectomy, were included. In addition,
tissues from 10 colonic adenomas, 15 CRC and eight cases with UC, obtained by
endoscopic biopsies, were examined histopathologically. Immunohistochemical
evaluation of STAT3, p-STAT3, JAK3 and p-JAK3 expression in tissue sections
was completed.
Statistical analysis and correlation of data were then performed.
Results: Normal colonic mucosa showed expression of STAT3 only.
Immunoreactivity of p-JAK3 increased significantly (p < 0.05) and correlated with
the degree of dysplasia in colonic adenomas. Immunoreactivity of p-STAT3
increased significantly (p < 0.05) and correlated with the degree of dysplasia in
cases with UC. In CRC a significant positive correlation was found between pSTAT3 expression and grading, STAT3, JAK3 and p-JAK3 and TNM or Dukes’
staging, and p-STAT3 and nodal status excluding distant metastasis (p < 0.05).
Conclusion: JAK3 and STAT3, and particularly their activated forms, were found
to correlate significantly
with the degree of dysplasia in adenomas and UC, indicating their potential role in
colorectal carcinogenesis. They also correlate with anaplasia and invasion,
suggesting a definitive role in progression of CRC.
Probiotic Lactobacilus Casei (L.Casei) Can Support Intestinal
Barrier through Immune Modulation in Experimental
Cirrhosis
Hanan H. Soliman1, Abdel-Razek A. Sheta2 & Omayma K. Afifi3
Departments of Tropical medicine & infectious diseases1, Anatomy2 & Histology3, Faculty of
medicine, Tanta University, Egypt
ABSTRACT
Background/Aim: Liver cirrhosis induces intestinal mucosal barrier dysfunction and impairs
mucosal defenses against luminal bacteria. This work aims to study the histological changes
in the intestine of cirrhotic rats and to determine the ability of probiotic lactobacilus casei
(L.casei) to immune-modulate or prevent cirrhosis-induced intestinal changes.
Patients & Methods: Twenty seven adult rats were used in this study and classified into, 9
control, 9 injected with Ccl4 to induce cirrhosis and 9 animals received L.casei in addition to
Ccl4. Sera from all animals were tested for TNF-α and INF-γ, and intestinal segments were
examined histologically by light and electron microscopes.
Results: In cirrhotic rats, TNF-α increased significantly while INF-γ showed non-significant
increase compared to control. Histologically, intestinal mucosa showed degenerated lining
epithelium and submucosal thickening. The intestinal wall appeared thin and atrophied in
severely affected animals with complete damage of the lining epithelium. PAS stained
sections showed apparently decreased goblet cells number and reactivity of the brush border.
Ultrastructurally, enterocytes showed degenerated microvilli, wide intercellular spaces,
dilated rER, swollen mitochondria, small irregular nuclei and many secondary lysosomes. In
group III, TNF-α increased non-significantly, while IFN-γ showed a significant increase.
Histologically, apparent normal villi with intact lining epithelium were noticed except few
areas that were slightly affected. The brush border and goblet cells maintain their normal
PAS-positive reaction. Ultrastructurally, Except for mild rER dilatation, most of enterocytes
organelles appeared normal.
Conclusion: L.casei is a good probiotic in preventing intestinal mucosal damage associating
cirrhosis. These effects may be mediated by immunomodulation through TNF-α and IFN-γ.
Key words: cirrhosis, intestinal barrier, probiotic, L.casei
Corresponding Author: Hanan H. Soliman M.D. Department of Tropical Medicine, Faculty of
Medicine, Tanta University, Egypt. E-mail: hanansol@gmail.com
The Impact of H. pylori Eradication on Response to
Oral Iron Therapy in Patients with Iron Deficiency
Anemia
1Nesreen A Kotb, 1Mohamed M Bedewy, 2Hanan H Soliman, 3 Hala
M Nagy, 4 Eman A Hasby
Departments of 1Internal Medicine, 2 Tropical and Infectious Disease, 3 Clinical
Pathology and 4Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
Abstract
Infection with Helicobacter pylori has been associated with Iron
deficiency anemia (IDA). We assessed the effect of eradication of H.
pylori infection on response to oral iron treatment. Twenty patients
with IDA of no obvious cause, unresponsive to oral iron therapy with
positive gastric biopsy for H. pylori infection received sequential
eradication therapy for 10 days followed by oral iron therapy.
Treated patients were followed up at 6 weeks and 12 weeks post
eradication to assess dynamic changes in hemoglobin, serum ferritin
and transferrin saturation. While 65% of anemic H. pylori infected
cases had pangastritis, 35% had antral gastritis. In the antrum
severe and moderate gastritis were found in 40% and 45% of cases,
respectively. Hemoglobin and serum ferritin level correlated
inversely with grade of gastritis (P <0.001). Improvement in
hematological parameters and serum iron profile was observed 6
weeks and 12 weeks post successful H.pylori eradication oral iron
therapy.
In conclusion, eradication of H. pylori infection enhances the
response to oral iron supplementation in patients with refractory
IDA. Screening and eradication of H. pylori should be a standard
procedure for patients with IDA.
Assessment of the Role of L-Carnitine in Improving Hepatic
Encephalopathy Using MR Spectroscopy
Hanan H. Soliman1, Dina H. Ziada1, Mohamed Hefeda2, Manal Hamisa2 and
Samy A. Khodeir3
Tropical Medicine and Infectious Diseases1, Radiology2, Internal Medicine3, Departments, Faculty of
Medicine Tanta University-Egypt
Abstract:
Background and aim: Hepatic encephalopathy (HE) is related to the presence of
abnormal cerebral metabolites. MR Spectroscopy (MRS) can demonstrate the neurometabolite changes associated with therapy .The aim of this study was to evaluate the
influence of L-carnitine on mental conditions, serum ammonia and neurometabolite
levels in patients with HE using MRS.
Patients and methods: Ten control subjects and 54 patients with grades II to III HE,
were randomized into (GI) receiving lactulose 30ml/t.d.s as standard therapy and
(GII) receiving L-Carnitine 350mg t.d.s in addition to the lactulose. Clinical
assessment, fasting serum ammonia levels, and measurement of neurometabolite
levels using proton MRS were recorded and compared at base line and after one
week.
Results: After one week, 25% of HE patients were reversed in group I versus 42.3%
in group II. Fasting ammonia levels were significantly decreased in both groups
compared to pretreatment levels and significantly lower in the L-carnitine and
lactulose treated group compared to the lactulose group(P=0.041). Neurometabolites
mI/Cre, Cho/Cre, Gx/Cre, and (Cho+mI)/Gx ratios were significantly improved in
both groups compared to pre treatment levels, but the L Carnitine added group(II),
showed a significant increase in mI/Cre, and (Cho+mI)/Glx ratios and decrease in
Glx/Cre ratio in comparison to the lactulose group(p=0.002-p=0.003-p=0.002
respectively).
Conclusion: Adding L Carnitine to lactulose for treatment of hepatic encephalopathy
hastened the clinical improvement and was associated with significant improvements
in serum ammonia and neurometabolites specially mI/Cre, and (Cho+ mI)/Glx and
Glx/Cre ratios.
Key words: Hepatic encephalopathy, Neurometabolites, Magnetic Resonance
Spectroscopy, L-Carnitine.
Abbreviations: (HE) hepatic encephalopathy, (MRS) Magnetic Resonance
Spectroscopy, (Cho) Choline, (Cre) creatine, (NAA) N-acetylaspartate,
(Glx)glutamine+glutamate, and(mI) myo-inositol
Comparison of Partial Splenic embolisation versus Splenic
Irradiation as Treatment of Hypersplenism in Advanced
Cirrhosis
Dina H. Ziada, Hanan H. Soliman, Amr Al-Badery*, Nehal El Mashd**
Tropical Medicine and Infectious Diseases, Radiology *, Oncology and Nuclear
Medicine**Departments- Tanta University-Egypt.
Abstract:
Hypersplenism in advanced cirrhotic patient is a conflicting issue as surgical
splenectomy carries high perioperative morbidity and mortality rates. Partial splenic
embolization (PSE) and low dose splenic irradiation (LDSI) are alternative procedures
available in Egypt. The aim of this prospective controlled study was to compare (PSE)
versus (LDSI) for ablation of spleen as treatment of hypersplenism in advanced
cirrhosis.
Patients and methods: Seventy one cirrhotic patients suffering hypersplenism
underwent abdominal ultrasonography, liver functions, INR and bone marrow
examination to confirm the diagnosis. They were enrolled in 3 groups. Group
(I):26patients treated by (LDSI), Group (II):25patients treated by (PSE) and
GroupIII:20 patients received conventional therapy as control group then we followed
up these patients for 6months.
Results: LDSI group showed steady progressive increase in all CBC elements. A
significant increase in platelets started by week 2 While that of Hb and WBCs started
by first month. While these increases started by the first week in PSE group which
reached its peak in second week then gradually decreased but still significantly higher
than pre treatment and control levels. Both procedures were well tolerated by the
patients but more complications were reported with PSE. Both LDSI and PSE didn't
affect liver functions.
Conclusion: Both LDSI and PSE are safe and effective in treating hypersplenism in
decompensated cirrhosis. They induce improvement of cytopenia and splenomegaly.
The rapid onset and higher efficacy of PSE should be weighed against the wide safety
and moderate efficacy of Splenic irradiation.
Keywords: hypersplenism, advanced cirrhosis, Partial splenic embolization (PSE)
and low dose splenic irradiation (LDSI).
Leukocyte esterase and nitrate strip as a bedside test to
diagnose Spontaneous Bacterial Peritonitis in Egyptian
cirrhotic patients
Hanan H. Soliman, Dina H. Ziada, and Naglaa Ghoneim*
Tropical Medicine and Infectious Diseases, and microbiology* Departments- Tanta
University-Egypt
.
ABSTRACT:
Background and aim: Rapid diagnosis of Spontaneous Bacterial Peritonitis (SBP)
is essential to reduce its mortality. The aim of this study was to evaluate the
usefulness of Leukocyte esterase tests either alone or combined with nitrate tests in
same dipstick as a bedside tool for diagnosis of SBP in Egyptian cirrhotic patients
Patients and methods: Two hundred consecutive ascitic fluid samples were collected
from 103 cirrhotic patients. Chylus, Bloody, serosangounus or bile stained samples
were excluded. ,The routine and bacteriologic examination of ascitic samples were
performed and ascitic sample tested using dipstick (Urocolor Test™ SD Standard
diagnostics, Inc, Korea) for granulocyte esterase and nitrates designed for urine
analysis. The procedure was the same as what the manufacturer described for urine.
Results: By comparing the results of the routine and bacteriologic examination of
ascitic and dipstick test, Leucocytic esterase (LE) test had sensitivity (sens.),
specificity (sp.), positive predictive value(PPV), and negative predictive value(NPV)
of 93.6%, 98.7% , 95.7%, and 98.7% respectively at colorimetric level 2+ ; and
74.5%, 99.3%, 97.2%, and 92.2% respectively at colorimetric level 3+. The nitrite test
had sens., sp., PPV, and NPV of 12.7%, 85.6%, 21.4%, and 85.6% respectively.
While combining both testes reveilles; 11%, 98.7%, 71%, and 78.2% respectively. LE
test was superior to nitrite test in diagnosis of SBP
Conclusion: Leukocyte esterase is more reliable than nitrate test in diagnosis of SBP.
Uriscan SD dipstick test is better to be interpreted at colorimetric +2 which has high
NPV(98.7%) allow to rollout the diagnosis of SBP in most cases. Uriscan SD
dipstick test is rapid, cheap, and available everywhere, so it can be used as bedside
test to screen SBP in Egyptian cirrhotic patients.
Key words: Leukocyte esterase, nitrate test, Spontaneous Bacterial Peritonitis