Gastroenterology and Hepatology from Bed to Bench

Aim: The aim of this systematic review was to determine if the human colon, through the lower gut-liver axis, drives PSC activity by assessing the progression of the disease in patients with and without colectomy for colonic disease.

Background: The gut-liver axis is involved in the pathogenesis of liver disease. Abnormal immune-mediated responses to intestinal

microbiome are implicated in primary sclerosing cholangitis (PSC) however the mechanisms remain poorly understood. Currently, no
single animal model recapitulates all attributes of PSC in humans and this limits further studies of gut-liver interactions.
Methods: A systematic search of PubMed, Medline, and Scopus was performed for articles that contained the terms “colectomy” or
“bowel resection” AND “primary sclerosing cholangitis” up to 15th April 2018. Articles were reviewed by 2 reviewers and raw data
collated. A Forest plot was used to illustrate the effect of colectomy on subsequent liver transplantation for PSC. Linear regression was
used to estimate mortality risk.
Results: Colectomy appeared to have no effect on PSC progression, although high-quality studies were lacking. Rates of liver
transplantation or transjugular intrahepatic portosystemic shunt for PSC were not affected by colectomy (OR 0.59, 95% CI 0.14 - 2.53,
p=0.48). Mortality risk following colectomy in patients with PSC is 2.11% per year (95% CI 0.03% - 4.18%, p=0.032, R2 = 0.722).
Conclusion: Current evidence is limited but suggests colectomy does not affect the progression of PSC in patients with colonic disease.
Pathogenic micro-organisms or antigens that drive PSC may not be limited to the lower gut.
Keywords: Primary sclerosing cholangitis, Inflammatory bowel disease, Colectomy, Procto-colectomy.
(Please cite as: Ong J, Bath MF, Swift C, Al-Naeeb Y. Does colectomy affect the progression of primary sclerosing
cholangitis? A systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench 2018;11(4):277-283).

Cancers of the gastrointestinal (GI) track are a serious global health problem. The human GI tract is home to trillions of
microorganisms that known as gut microbiota and have established a symbiotic relationship with the host. The human intestinal
microbiota plays an important role in the development of the gut immune system, metabolism, nutrition absorption, production of
short-chain fatty acids and essential vitamins, resistance to pathogenic microorganisms, and modulates a normal immunological
response. Microbiota imbalance has been involved in many disorders including inflammatory bowel disease, obesity, asthma,
psychiatric illnesses, and cancers. Oral administration of probiotics seems to play a protective role against cancer development as a
kind of functional foods. Moreover, clinical application of probiotics has shown that some probiotic strains can reduce the incidence
of post-operative inflammation in cancer patients. In the present narrative review, we carried out update knowledge on probiotic
effects and underlying mechanism to GI cancers. Currently, it is accept that most commercial probiotic products are generally safe
and can used as a supplement for cancer prevention and treatment. Nevertheless, well-designed, randomized, double blind, placebocontrolled
human studies are required to gain the acceptance of the potential probiotics as an alternative therapy for cancer control..
Keywords: Probiotic, Prebiotics, Gastrointestinal cancer, Gut microbiota.
(Please cite as: Javanmard A, Ashtari S, Sabet B, Davoodi SH, Rostami-Nejad M, Akbari ME, et al. Probiotics and
their role in gastrointestinal cancers prevention and treatment; an overview. Gastroenterol Hepatol Bed Bench
2018;11(4):284-295).

Aim: In this study we tried to find out the accuracy of biliary tract brushing cytology in our center as the largest referral center in the
south of Iran.
Background: Common bile duct brushing cytology has been introduced as the method of choice for the diagnosis of
pancreaticobiliary malignancies. However, there have been controversial reports about the sensitivity, specificity and overall accuracy
of this method in the English literature.
Methods: During the study period (2012-2016) there has been 166 cases of common bile duct brushing cytology taken during
endoscopic retrograde cholangiopancreatography (ERCP). One case has been excluded because of inadequate number of cells in the
cytology smear. All the smears have been stained by routine cytologic stains and screened by cytotechnologists and diagnosed by
expert cytopathologist. Final diagnosis by biopsy has been considered as the gold standard.
Results: According to the final histologic diagnosis as the gold standard, there were 22 false negative and 7 false positive cases. All of
the false positive cases have been suspected cases in the background of primary sclerosing cholangitis. The most common final
diagnosis of false negative cytologic diagnoses has been intrahepatic cholangiocarcinoma in which no malignant cell has been
identified in the presence of adequate number of normal ductal epithelial cells.
Conclusion: Common bile duct brushing cytology is the method of choice for the diagnosis of pancreaticobiliary tract malignancies;
however, having high specificity (90%), the sensitivity is low (56%). Cytologic diagnosis of biliary tract malignancies should be
made with caution in the patients with primary sclerosing cholangitis. Also it is important to know that high false negative rate is
present in common bile duct brushing cytology especially in the cases of intrahepatic cholangiocarcinoma without extension into
extrahepatic ducts.
Keywords: Brush cytology, Common bile duct
(Please cite as: Geramizadeh B, Moughali M, Shahim-Aein A, Memari S, Ghetmiri Z, Taghavi A, et al. False
negative and false positive rates in common bile duct brushing cytology, a single center experience.
Gastroenterol Hepatol Bed Bench 2018;11(4):296-300).

Aim: Is Karnofsky Performance Status (KPS) a predictor of 3 month post discharge mortality in cirrhotic patients?
Background: Cirrhotic patients often experience an abrupt decline in their health, which often leads to frequent hospitalization and
can cause morbidity and mortality. Various models are currently used to predict mortality in cirrhotics however these have their
limitations. The Karnofsky Performance Status (KPS) being one of the oldest performance status scales, is a health care provider–
administered assessment that has been validated to predict mortality across the elderly and in the chronic disease populations.
Methods: We used the KPS performance status scale to envisage short-term mortality in cirrhotic and HCC patients who survive to
be discharged from hospital.
Results: Our study showed that KPS one week post-discharge, child pugh score, hospital stay, international normalized ratio, serum
albumin, total bilirubin and serum creatinine showed statistical significance on univariate analysis. On multivariate analysis, KPS was
found to be statistical significant predictor of 3-month mortality.
Conclusion: Hence KPS can be utilized to identify cirrhotic patients at risk of 3-month post discharge mortality.
Keywords: Karnofsky Performance Status (KPS), Cirrhosis, 3 months mortality
(Please cite as: Khalid MA, Achakzai IK, Ahmed Khan S, Majid Z, Hanif FM, Iqbal J, et al. The use of Karnofsky
Performance Status (KPS) as a predictor of 3 month post discharge mortality in cirrhotic patients Gastroenterol
Hepatol Bed Bench 2018;11(4):301-305).
Introduction
1 Hospitalization is a marker of poor outcomes
including readmission and death. Patients with cirrhosis
experience abrupt deterioration in their health that leads
to repeated hospitalizations along with increased
morbidity and mortality (1-3). Currently, the models
used to predict mortality in cirrhotics are liver-specific
and kidney-specific prognostic indicators such as the
Model for End-Stage Liver Disease (MELD) score (4).
However the MELD score has several limitations (5-7)
one of them being its lack of ability to account for an
individual’s performance status.
It is now a well-known fact that performance status and
the linked concept of infirmity are strong predictors of
Received: 29

Aim: The aim of this study was to compare general and stoma specific short term complications in patients having stoma surgery in
either an emergency or elective setting during their index hospital stay. It also compares the complications specific to a stoma carried
out by surgeons with or without a specialist interest in colorectal surgery.
Background: The stoma created in emergency surgery has a high short and long term complication rate. Emergency stomas where
the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely
affect a patient’s quality of life.
Methods: We retrospectively analysed data for all non-urological stomas created over the last three years in our institute. This
covered the period from January 2014 to January 2017. The stoma care department kept a full database record of all patients. Besides
demography we analysed the type of stoma i.e. colostomy or ileostomy, indications for the stoma, most common operation, length of
stay (LOS) and short term complications based on the Clavien-Dindo classification. We also analysed the perioperative stoma related
complications within the emergency cohort.
Results: A total of 199 patients had new ostomies created during the three-year period. Four patients died during the inpatient stay
and were excluded from the analysis. The total number of stomas created in the emergency cohort was 60 and 135 stomas were
elective procedures. The male to female ratio was 1:1.01. The average age for the emergency cohort was 6 years older than for the
elective cohort. There was a statistically significant difference in length of stay between the two cohorts (T Test P Value =.02). There
was a higher number of elective patients discharged in the first week compared to the emergency surgery patients. The rate of grade 3
or 4 complications was higher in the emergency cohort of patients. The rate of grade 3 or 4 complications was also much higher in
patients operated by surgeons who did not have a specialist interest in colorectal surgery. The majority of grade 3 complications seen
in the emergency surgery cohort and operated on by non-colorectal specialists (NCS) were stoma related, i.e retraction, necrosis and
prolapse.
Conclusion: Emergency surgery procedures are frequently bowel related. Emergency stoma surgery should not be taken as trivial
procedure, non-colorectal surgeons should take advice and assistance from specialist colorectal surgeons for bowel related cases,
particularly when a stoma is involved
Keywords: Stoma, Colostomy, Non-colorectal surgeons, Hartman’s operation.
(Please cite as: Qureshi A, Cunningham J, Hemandas A. Emergency stomas; should non-colorectal surgeons be
doing it?. Gastroenterol Hepatol Bed Bench 2018;11(4):306-312).

Aim: The present study is aimed to investigate the effect of red sugar on functional constipation in children compared to figs syrup.
Background: Treatment of constipation in childhood improves gastrointestinal function in the future and regular bowel habit. Red
sugar is an effective ingredient in the treatment of constipation. Figs syrup is the other common natural substance used to treat
constipation in children. Conducted studies on these two substances and similar herbal substances have shown their beneficial effects,
but in a conducted study, it is reported that the effect of fig syrup is less than the chemical material.
Methods: This Randomized Controlled Trial (RCT) Study was done in 2016. First, by performing an examination and filling out the
identifying form of the patient's health status, mothers respond to the designed questionnaire. 30 children with constipation were
treated with the usual drug, fig syrup, and 30 other children received red sugar. After a 4-week treatment period, the examination was
conducted again and the questionnaire was filled out again. The changes following the intervention were measured and the status
before and after treatment were compared as well. The analyses were performed using SPSS 20 (SPSS for Windows, SPSS Inc.,
Chicago, IL, USA).
Results: In this study, there was no significant difference between effects of red sugar and fig syrup in terms of the frequency of fecal
excretion, and pain at the time of excretion (p = 0.264). However, the fig syrup was more effective in reducing the anorexia (p <
0.001) and abdominal pain compared with fig syrup (p < 0.001). Also fig syrup was more effective in inducing diarrhea (p = 0.019).
Conclusion: In general, treatment by red sugar has been effective in improving the functional characteristics of constipation in
children; and did not show any complication and toxic effects. It is easily accessible at affordable prices to resolve childhood
constipation.
Keywords: Constipation, Children, Traditional medicine, Iran.
(Please cite as: Tajik P, Goudarzian AH, Shadnoush M, Bagheri B. Effect of red sugar on functional constipation
in children compared to figs syrup; a randomized controlled trial study. Gastroenterol Hepatol Bed Bench
2018;11(4):313-318).

Aim: To investigate whether aggressive hydration can increase the efficacy of prophylactic non-steroid anti-inflammatory drugs
(NSAIDs) in prevention of post-ERCP pancreatitis.
Background: NSAIDs are recommended for the prevention of PEP; however, whether aggressive hydration can have additional
benefits in this regard is not known.
Methods: Patients candidate for ERCP received either pre-procedural rectal diclofenac (100 mg) alone (n = 112) or in combination
with aggressive hydration by lactate ringer’s (n = 107) as prophylactic method. PEP was defined based on increase in serum levels of
pancreatic enzymes (from baseline to 24 hours following the procedure) accompanied with symptoms.
Results: PEP was occurred in 3 patients in the diclofenac only group and in 1 patient in the diclofenac + hydration group with no
significant difference (2.7% vs. 0.9%, P = 0.622). Serum amylase levels decreased over time in the diclofenac + hydration group but
not in the diclofenac only group. Also, serum lipase levels decreased more rapidly over time in the diclofenac + hydration group
compared to the diclofenac only group.
Conclusion: Combination prophylactic therapy with NSAIDs plus aggressive hydration does not seem to have additional clinically
important benefits in preventing PEP. Studies with larger sample of patients are required in this regard.
Keywords: Pancreatitis, Endoscopic retrograde cholangiopancreatography, Prevention, Inflammation, Diclofenac, Aggressive
hydration.
(Please cite as: Hajalikhani M, Emami MH, Khodadoostan M, Shavakhi A, Rezaei M, Soluki R. Combination of
diclofenac and aggressive hydration for the prevention of post-ERCP pancreatitis. Gastroenterol Hepatol Bed
Bench 2018;11(4):319-324).

Aim: To assess NT-proBNP as a biomarker for hyperdynamic circulation in decompensated cirrhosis.
Background: Hyperdynamic circulation is common in decompensated cirrhosis. The previous studies reveal that N-terminal-proBNP
(NT-proBNP) is elevated in cirrhosis.
Methods: A prospective study involved 47 patients with decompensated cirrhosis. All of them underwent echocardiography with
simultaneous measurement of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated. The
concentration of NT-proBNP in blood was measured with enzyme-linked immunosorbent assay.
Results: In patients with decompensated cirrhosis, the concentration of NT-proBNP in blood directly correlated with end-diastolic
volume (r=0.482; p<0.001), stroke volume (r= 0.566; p<0.001), cardiac output (r=0.556; p<0.001), volume of the left atrium
(r=0.292; p=0.047), and inversely correlated with systemic vascular resistance (r=-0.538; p<0.001). There was no significant
correlation between NT-proBNP and ejection fraction (p=0.083). Patients with hyperdynamic circulation have higher concentration of
NT-proBNP (152÷476 pg/ml vs. 31÷133 pg/ml, p<0.001) regardless of the presence of diastolic dysfunction (p=0.222). According to
ROC analysis, the best cut-off values for detection of hyperdynamic circulation in decompensated cirrhosis are considered to be 170.0
pg/ml of blood NT-proBNP, showing sensitivity and specificity of 72.0 and 86.4%, respectively. The positive and negative predictive
value are 86.4% and 73.1%, AUC = 0.829 (0.709-0.949).
Conclusion: NT-proBNP may serve as a non-invasive biomarker for hyperdynamic circulation in decompensated cirrhosis.
Keywords: Blood circulation, Liver cirrhosis, Biomarkers, Natriuretic peptide, Brain.
(Please cite as: Maslennikov R, Driga A, Ivashkin K, Ivashkin V. NT-proBNP as a biomarker for hyperdynamic
circulation in decompensated cirrhosis. Gastroenterol Hepatol Bed Bench 2018;11(4):325-332).

Aim: In this research, we designed a direct Enzyme Linked Immunoassay method to detect Helicobacter pylori antigens in stool
specimens.
Background: Helicobacter pylori infection as the worldwide problem is related to many gastrointestinal disorders such as gastritis,
gastric cancer, non-ulcer disease, peptic ulcer disease and duodenal ulcer.
Methods: We produced and purified recombinant CagA and NapA antigens in Escherichia coli and extracted their antibodies from a
panel of positive sera specimens. We designed a novel enzyme linked immunoassay direct method in combination with the whole cell
for the qualitative and quantitative detection of Helicobacter pylori antigens in human stool. Assay performance was evaluated by
histopathology staining and urease activity.
Results: The sensitivity and specificity of assay was determined as 91.7 [95% confidence interval: 89.3–95.6%] and 93.1% [95% CI:
91.2–96.4%], respectively. Novel ELISA exhibits enhanced sensitivity and specificity of Helicobacter pylori detection in comparison
with another commercially available kit.
Conclusion: Combination of the recombinant antigens and whole cell of Helicobacter pylori in immunoassay designing is a new
approach about early diagnosis, treatment and fallowing up of the Helicobacter pylori infected patients, especially in peptic cancer
cases.
Keywords: CagA protein, Helicobacter pylori, Neutrophil activating protein A, Enzyme-linked immunosorbent assay.
(Please cite as: Kamarehei F, Khabiri AR, Saeedi Jam M, Soleimani M, Alikhani MY. Designing a novel ELISA
method based on CagA, NapA recombinant antigens to increase sensitivity and specificity of Helicobacter pylori
whole cell antigen detection. Gastroenterol Hepatol Bed Bench 2018;11(4):333-342).

Aim: In this study the significant differentially expressed genes (DEGs) related to gastric cancer (GC) and chronic gastritis were
screened to introduce common and distinctive genes between the two diseases.
Background: Diagnosis of gastric cancer as a mortal disease and chronic gastritis the stomach disorder which can be considered as
risk factor of GCs required safe and effective molecular biomarkers.
Methods: Microarray profiles were downloaded from Gene Expression Omnibus (GEO) and analyzed via GEO2R. The candidate
DEGs plus relevant genes from STRING database were interacted by Cytoscape software version 3.6.0 the central nodes were
determined and analyzed.
Results: JUN, GAPDH, FOS, TP53, PRDM10, VEGFA, and CREB1 as central nodes and TFF1 and ERG1 as the top changed
expressed genes were determined as critical nodes related to gastric cancer. GAPDH, PRDM10, TP53, JUN, AKT1, EGFR, MAPK1,
EGF, DECR1, and MYC were identified as common remarkable genes between GC and chronic gastritis.
Conclusion: Identification of distinctive and common genes between GC and chronic gastritis can be useful in the early stage
detection of disease and reducing risk of GCs.
Keywords: Chronic gastritis, Gene ontology, Biomarkers, Gastric cancer.
(Please cite as: Mansouri V, Rezaei Tavirani S, Zadeh-Esmaeel MM, Rostami-Nejad M, Rezaei-Tavirani M.
Comparative study of gastric cancer and chronic gastritis via network analysis. Gastroenterol Hepatol Bed
Bench 2018;11:343-351).

Aim: The aim of the present study was to simultaneously investigate parasitic contamination of treated wastewater and downstream
vegetable farms that are irrigated with treated sewage, during a year.
Background: (Oo) Cysts and eggs of parasites are resistant to most of routine wastewater treatment process. Irrigation of vegetables
farms with either treated wastewater or illegally use of raw wastewaters enhances the risk of contamination with enteric pathogens.
Methods: The treated wastewater samples were taken after chlorination from a wastewater treatment plant located at the south of
Tehran. In addition, 60 vegetable samples (5 samples from each farm) were collected from the selected downstream farms that
routinely used treated wastewater for irrigation of crops. Parasitological tests were performed using Ziehl–Neelsen, conventional
lugol’s iodine staining and direct microscopical examination.
Results: Parasites including free living larvae, eggs of Toxoascaris leonina, egg of Toxocara sp. Trichuris sp, Trichostrongylus sp
and amoeboid trophozoite were seen in 5/12 (41.7%) of vegetable samples gathered during a year. There was no statistically
significant correlation between the season and parasitic contamination of the vegetables (P= 1). Furthermore, parasitic contamination
was observed in 7/12 (53.8%) of treated wastewater samples. The correlation between season and parasitic contamination of treated
wastewater was evaluated that the results showed a higher contamination of treated wastewater in spring and autumn (P<0.05).
Fisher’s exact test also showed that there was no significant correlation between parasitic contaminations of vegetable samples and
treated wastewater according to seasonal change.
Conclusion: The results showed parasites in both treated wastewater plant and downstream crops farms that suggests the public
health importance of the quality of water resources that routinely used for irrigation of vegetable farms.
Keywords: Treated wastewaters, Vegetable farms, Irrigation, Parasitic contamination, Iran.
(Please cite as: Javanmard E, Mirjalali H, Niyyati M, Sharifdini M, Jalilzadeh E, Seyed Tabaei SJ, et al. Small-scale
risk assessment of transmission of parasites from wastewater treatment plant to downstream vegetable farms.
Gastroenterol Hepatol Bed Bench 2018;11(4):352-358).

Simple renal cysts are one of the most common lesions in elderly. These cysts are usually asymptomatic but when the size of these
cysts increase, we would see symptoms such as hypertension, hematuria, flank pain or urinary obstruction. In this study, we explore a
case of small bowel obstruction that presented with nausea, repeated vomiting that causes hematemesis, and a submucosal obstructive
lesion that was seen in Esophagogastroduodenoscopy (EGD). After endoscopic ultrasound (EUS) evaluation, we detected a large
simple renal cyst and approved our diagnosis with CT scan. We planned a medical treatment for this patient that consist consuming
small size meals, 5 to 6 times a day, and high calorie liquids in small volumes. We conclude that simple renal cyst can be one of the
cause of extrinsic intestinal obstruction and EUS is affective for differentiation of intrinsic submucosal lesion from extrinsic
compression.
Keywords: Intestinal obstruction, Renal cyst, Endoscopic ultrasound.
(Please cite as: Sadeghi A, Shahrbaf MA, Asadzadeh Aghdaei H, Esmaeilinejad K, Zali MR. A rare presentation of
simple renal cyst: gastrointestinal obstruction. Gastroenterol Hepatol Bed Bench 2018;11(4):359-362).

Aim: To assess NT-proBNP as a biomarker for hyperdynamic circulation in decompensated cirrhosis.
Background: Hyperdynamic circulation is common in decompensated cirrhosis. The previous studies reveal that N-terminal-proBNP
(NT-proBNP) is elevated in cirrhosis.
Methods: A prospective study involved 47 patients with decompensated cirrhosis. All of them underwent echocardiography with
simultaneous measurement of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated. The
concentration of NT-proBNP in blood was measured with enzyme-linked immunosorbent assay.
Results: In patients with decompensated cirrhosis, the concentration of NT-proBNP in blood directly correlated with end-diastolic
volume (r=0.482; p<0.001), stroke volume (r= 0.566; p<0.001), cardiac output (r=0.556; p<0.001), volume of the left atrium
(r=0.292; p=0.047), and inversely correlated with systemic vascular resistance (r=-0.538; p<0.001). There was no significant
correlation between NT-proBNP and ejection fraction (p=0.083). Patients with hyperdynamic circulation have higher concentration of
NT-proBNP (152÷476 pg/ml vs. 31÷133 pg/ml, p<0.001) regardless of the presence of diastolic dysfunction (p=0.222). According to
ROC analysis, the best cut-off values for detection of hyperdynamic circulation in decompensated cirrhosis are considered to be 170.0
pg/ml of blood NT-proBNP, showing sensitivity and specificity of 72.0 and 86.4%, respectively. The positive and negative predictive
value are 86.4% and 73.1%, AUC = 0.829 (0.709-0.949).
Conclusion: NT-proBNP may serve as a non-invasive biomarker for hyperdynamic circulation in decompensated cirrhosis.
Keywords: Blood circulation, Liver cirrhosis, Biomarkers, Natriuretic peptide, Brain.
(Please cite as: Maslennikov R, Driga A, Ivashkin K, Ivashkin V. NT-proBNP as a biomarker for hyperdynamic
circulation in decompensated cirrhosis. Gastroenterol Hepatol Bed Bench 2018;11(4):325-332).