Gastroenterology and Hepatology from Bed to Bench

Over the past few decades, artificial intelligence (AI) has evolved dramatically and is believed to have a significant impact on all aspects of technology and daily life. The use of AI in the healthcare system has been rapidly growing, owing to the large amount of data. Various methods of AI including machine learning, deep learning and convolutional neural network (CNN) have been used in diagnostic imaging, which have helped physicians in the accurate diagnosis of diseases and determination of appropriate treatment for them. Using and collecting a huge number of digital images and medical records has led to the creation of big data over a time period. Currently, considerations regarding the diagnosis of various presentations in all endoscopic procedures and imaging findings are solely handled by endoscopists. Moreover, AI has shown to be highly effective in the field of gastroenterology in terms of diagnosis, prognosis, and image processing. Herein, this review aimed to discuss different aspects of AI use for early detection and treatment of gastroenterology diseases.

Keywords: Artificial intelligence, Deep learning, Polyp detection, Image processing, Computer-assisted, Colonoscopy.

(Please cite as: Rasouli P, Dooghaie Moghadam A, Aghajanpoor Pasha M, Asadzadeh Aghdaei H, Mehrvar A, Iravani Sh, et al. The role of artificial intelligence in colon polyps detection. Gastroenterol Hepatol Bed Bench 2020;13(3):191-199).

Aim: This study aimed at modeling the risk of local relapse and death from colorectal cancer after the first treatment and its related factors using multi-state models.

Background: In cancer studies modeling the course of disease regarding events which happen to patients is of great importance. By considering death as the final endpoint while incorporating the intermediate events, multi-state models have been developed.

Methods: This was a historical cohort study in which 235 patients with colorectal cancer, who referred to Omid Hospital in Mashhad between 2006 and 2011, were studied and followed up until 2017. The transition probabilities to death due to metastasis with or without experiencing local relapse and variables related to them were determined using the non-Markovian multi-state model in three states of disease, local relapse and death.

Results: The probability of not experiencing either of the events, just relapse and death in the first 5 years were 0.45, 0.09 and 0.46 respectively. If patients did not experience any event in the first year of treatment, the probability of relapse and death before the fifth year were 0.04 and 0.33 respectively and if they did experience relapse during this time, the probability of death by the fifth year was 0.62. The stage of cancer was associated with relapse and death, while ethnicity and history of addiction were related to death without relapse and BMI had a significant relationship with death after relapse (p<0.05).

Conclusion: Risk of death in patients with colorectal cancer depends on local relapse and the time between them.

Keywords: Non-Markovian Multi-State Model, Colorectal cancer, Local relapse, Death.

(Please cite as: Hajebi Khaniki S, Fakoor V, Shahid Sales S, Esmaily H, Heidarian Miri H. Risk of relapse and death from colorectal cancer and its’ related factors using non-Markovian Multi-State model. Gastroenterol Hepatol Bed Bench 2020;13(3):200-208).

Aim: The present study aimed at evaluating the demographic, pathological and clinical characteristics of patients with colon cancer and also the survival rate and its related factors.

Background: Cancer is the most important barrier to increasing life expectancy in the world. Furthermore, colon cancer is the fourth leading cause of cancer in Iran.

Methods: In this descriptive-analytical study, 219 patients with colon cancer were investigated. Data were analyzed through descriptive and univariate methods using R software. Kaplan-Meier survival analysis and log-rank test were used to evaluate the survival rate of the patients.

Results: In the present study, 25% of patients were below 50 years of age. A family history of cancer was positive in 30% of the patients. According to the clinical symptoms of the patients, rectorrhagia was higher in patients with sigmoid tumor site, abdominal pain was higher in patients with transverse and ascending tumor sites, and anemia was higher in patients with ascending and caecum tumor sites (p< 0.05). The mean life expectancy of the patients was 53.71±2.07 months. Three-year, five-year and seven-year survival rates were 70, 49, and 37 %, respectively.

Conclusion: Half of the patients were diagnosed at advanced stage and the mean survival time at advanced stage was approximately four years. One-third of the patients had local recurrence. It is recommended that patients refer to specialists at specified time intervals for timely diagnosis of the disease and prevention of its recurrence. Providing effective training for people in order for them to acquire more knowledge, and performing screening tests will lead to early diagnosis and lower mortality.

Keywords: Colon cancer, Demographic, Clinical, Pathology, Survival analysis.

(Please cite as: Rahimi E, Yazdani Charati J, Mohammad pour Tahamtan RA, Maleki I. Evaluation of demographic, pathologic, and clinical characteristics and overall survival of the patients with colon cancer in Northern Iran (Mazandaran Province) during 2012-2019. Gastroenterol Hepatol Bed Bench 2020;13(3):209-218).

Aim: To estimate the cost per patient for hepatocellular carcinoma in Greece, a setting that is currently facing financial constraints.

Background: Hepatocellular carcinoma patient management strategies are associated with significant costs. Despite this, patient level data on healthcare resource use and cost-of-illness analyses of hepatocellular carcinoma remain rather scarce in the international literature.

Methods: 123 patients diagnosed with hepatocellular carcinoma and followed in a specialised clinic of a tertiary hospital in Greece formed the basis of the analysis. Detailed resource use data were derived from the medical records of each patient. Data were recorded from the first encounter of the patient with the facility until a fatal endpoint or until the last day of follow up. Patients that were lost to follow-up were excluded from the analysis. Calculations follow a third-party payer perspective, according to official prices and tariffs.

Results: The average cost per patient was estimated at 12,119.1 Euros (SD: 14,670.3) (21,375.1 PPP USD) for the average follow-up period and 10,241.5 Euros (18,063.5 PPP USD) per year. Median costs per month of follow-up according to underlying disease were 1,218.1, 1,376.8, 1,521.3 and 686.9 Euros (2,148.4, 2,428.3, 2,683.2 and 1,211.5 PPP USD) for patients with alcoholic steatohepatitis, hepatitis B, hepatitis C and non-alcoholic fatty liver disease, respectively.

Conclusion: Hepatocellular carcinoma represents a heavy toll, both from the clinical as well as from the economic perspective, especially for a setting in “dire straits”. Interventions towards reducing the incidence and, subsequently, the cost of HCC are imperative.

Keywords: Cost-of-illness, Hepatocellular cancer, Economic evaluation.

(Please cite as: Athanasakis K, Pliarchopoulou F, Naoum V, Psarrakis C, Tziolos N, Marantos T, et al. A cost of illness analysis of hepatocellular carcinoma for the Greek healthcare setting. Gastroenterol Hepatol Bed Bench 2020;13(3):219-222).

Aim: The aim of the present study was to evaluate vitamin D levels, in correlation with age, body mass index (BMI), gender and ethnicity, in patients with gastrointestinal disorders (GID).

Background: Vitamin D deficiency (VDD) is a global health issue, affecting over 1 billion people. A great body of evidence has shown that it can lead to increased morbidity and mortality. Furthermore, latitude, sedentary lifestyle, limited sunlight exposure, ageing and the presence of comorbidities and chronic illnesses, places patients at an increased risk of VDD.

Methods: 305 consecutive patients, with GID, were assessed for vitamin D levels, using a two-step competitive binding immunoenzymatic assay. Patients were then classified as adequate (50-150nmol/l), insufficient (25-50nmol/l) and deficient (<25nmol/l).

Results: 62% of the investigated subjects had low vitamin D levels. From this group, 132 patients (43.3%) had insufficient vitamin D levels, 57 (18.7%) had deficient levels and 116 (38%) had adequate levels. Age was not significantly different in the 3 groups (p=0.29). Interestingly, vitamin D levels were significantly lower in men (39.23±23.62) compared to women (50.68±24.46) (p=0.0001). The BMI was significantly higher in patients with insufficient vitamin D levels. Being of Asian ethnicity had a positive influence on vitamin D levels (B=0.076) (p<0.0001). 71.4% of patients, with IBD, and 60% of patients, with abnormal liver function, had low vitamin D levels.

Conclusion: VDD has a high prevalence in patients with GID in particular IBD and liver disease in the United Kingdom. Routine vitamin D testing and supplementations in the case of deficiency and suboptimal level of vitamin D for patients with hepatobiliary, pancreatic, kidney, malabsorptive and restrictive diseases/surgeries is recommended.

Keywords: Vitamin D deficiency, 25-hydroxyvitamin D, Sunlight, demographics, IBD, Liver disease, Gastrointestinal disorders.

(Please cite as: Ahmad SJS, Ahmed AR, Ali J, Macfaul G, Johnson MW, Exadaktylos AK, et al. The correlation between vitamin D levels and demographics in patients with gastrointestinal disorders; a cross-sectional study. Gastroenterol Hepatol Bed Bench 2020;13(3):223-231).

Aim: The study aimed to find the best reading time for the best accuracy of RUT in optimal time to obtain faster results with lower false rates and consequently save time in commencing treatment of peptic ulcers.

Background: Rapid urease test is well known to be an accurate test for H.pylori detection in tissue biopsies.

Methods: Patients with GI problems referring to a university hospital in Tehran who underwent endoscopy and biopsy were entered  in the project and three samples of mucosal tissue were captured from the lesser curvature, the antrum and the body of stomach.

Results: We found 39.6% sensitivity and 95% specificity for the named test in the first 5 minutes as well as PPV = 95.5% and NPV = 37.3% while the accuracy was 54.79%. Except for the specificity which was constantly 95% in all RUT reading times, other diagnostic parameters increased as time went on. The PPV was also higher than 97% after 10 minutes. The highest values of sensitivity, specificity, PPV, NPV and accuracy were achieved after 12 hours including 88.7%, 95%, 97.9%, 76% and 90.41%, respectively.

Conclusion: To conclude, it seems that there are many different ideas with respect to the rapid urease test in H.pylori detection. However, the current study recommends reading the test optimally after 12 hours but it is suggested more multidisciplinary studies with bigger sample size be carried out to obtain better and more reliable results to be able to generalize in this regard.

Keywords: Helicobacter pylori, Rapid urease test (RUT), Diagnostic value, Pathophysiology.

(Please cite as: Eslaminejad A, Marashian SM, Aboutorabi M, Sadr M, Agah SH. Determination of optimal time for reading of rapid urease test diagnosis of Helicobacter pylori. Gastroenterol Hepatol Bed Bench 2020;13(3):232-237).

Aim: Determine the prevalence of enteric bacterial pathogens and their antimicrobial resistance among diarrheic children in Nairobi City, Kenya.

Background: Regardless of enteric bacterial pathogens being a major cause of gastroenteritis in children, their occurrence and antimicrobial resistance patterns reveals regional spatial and temporal variation.

Methods: In a cross-sectional study, a total of 374 children below five years presenting with diarrhea at Mbagathi County Hospital were recruited. Stool microbiology test was used to detect enteric bacterial infection. Antimicrobial resistance was determined using the disk diffusion method.

Results: Diarrheagenic E. coli (36.4%) was the leading species followed by Shigella (3.2%), Salmonella (2.4%), Campylobacter (1.6%), Yersinia (1.3%) and Aeromonas (1.1%) species. Escherichia coli pathotyping revealed that 20.9%, 4.0%, 10.2% and 0.5% of the study participants were infected with enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC) and enteroinvasive E. coli (EIEC) pure isolates while the prevalence of mixed pathotype infections was 0.3% for EAEC/EPEC/ETEC and 0.5% for EAEC/ETEC. Shigella sero-grouping revealed that 0.5%, 0.3%, 1.9%, and 0.5% were infected with Shigella boydii, Shigella dysentriae, Shigella flexneri and Shigella sonnei pure isolates. Shigella species and E. coli co-infection was detected in 2.4% of the children, specifically, 1.1% for EAEC/Shigella boydii, 0.5% for EAEC/Shigella dysentriae and 0.3% in each case of EAEC/Shigella sonnei, EPEC/Shigella flexneri and ETEC/Shigella flexneri co-infections. Most of the isolates were resistant to commonly prescribed antibiotics.

Conclusion: There was a high prevalence of enteric bacterial pathogens and co-infection alters epidemiological dynamics of bacterial diarrhea in children. Continuous antibiotic resistance surveillance is justified because the pathogens were highly resistant to commonly prescribed antimicrobials.

Keywords: Epidemiology; antimicrobial resistance; bacterial diarrhea.

(Please cite as: Kilongosi Webale M, Wanjala C, Guyah B, Shaviya N, Munyekenye GO, Lokamar Nyanga P, et al. Epidemiological patterns and antimicrobial resistance of bacterial diarrhea among children in Nairobi city,Kenya. Gastroenterol Hepatol Bed Bench 2020; 12(3):238-246).

Aim: The present study aims to evaluate the effects of antidiabetic and hepatoprotective of myricitrin in the aged mice induced by D-galactose (D-gal).

Background: Aging occurs during a person’s life; there has been no way to stop the aging process, but antioxidant and changing lifestyles can delay it.

Methods: In this experimental study, 72 female adult mice (weighing30–35g) were randomly divided into six groups: 1: control, 2: D-gal at 500mg/kg/d, 3-5: D-gal+ Myricitrin at 5, 10 and 20mg/kg/d 6: D-gal+ Vitamin E at 100mg/kg/d. Aging induced by D-gal for 45 days via intraperitoneal. Myricitrin and Vitamin E administrated orally by gavage for the last 28 days. The blood glucose, insulin level, β-cell function, insulin resistance, hepatic enzymes, lipid profile, and histology of the liver, and pancreas were evaluated.

Results: D-gal injection increased the glucose (p<0.001) and insulin levels (p<0.01) compared to control group. Myricitrin (p<0.01) and Vitamin E (p<0.001) increased insulin and decreased blood glucose levels compared to D-gal group. Myricitrin had a similar impact on insulin levels to vitamin E. Insulin resistance induced in the D-gal group (p<0.001). Myricitrin reduced insulin resistance and increased β-cell function (p<0.01) compared to D-gal group. D-gal elevated (p<0.01) cholesterol, LDL and triglyceride level, myricitrin (p<0.001), and Vitamin E (p<0.05) were reduced.

Conclusion: D-gal-induced aging causes the accumulation of RBCs, inflammation in the liver, and changes in the number and diameter of Langerhans islets in the pancreas. Myricitrin improved these D-gal effects. Myricitrin had the anti-diabetic and hepatoprotective effects on the aged mice induced by D-galactose.

Keywords: Myricitrin, Liver, Pancreas, D-galactose, Aging.

(Please cite as: Omidi M, Ahangarpour A, Khorsandi LS, Ramezani- AliAkbari F. The antidiabetic and hepatoprotective effects of myricitrin on aged mice with D-galactose Gastroenterol Hepatol Bed Bench 2020;13(3):247-253).

Aim: The present study aimed at investigating the necessity of preoperative liver function tests (LFTs) in patients with uncomplicated gallstone disease before laparoscopic cholecystectomy.

Background: Significant relationship between common bile duct (CBD) stones and acute cholecystitis is reported. There are contradictory reports about the effect of CBD stones on liver function tests in patients (LFTs).

Methods: In the current study, patients with symptomatic cholelithiasis who referred to hospitals during January 2015 and May 2016 were enrolled. Routine tests and ultrasonography were performed on all patients before surgery. Data were presented as means ± SD and qualitative variables as frequency (percentage) were considered. Statistical analyzes were performed with SPSS software.

Results: A consecutive series of 270 patients (58 males and 212 females) who referred for laparoscopic cholecystectomy were enrolled in this retrospective study. Pre- operative LFTs were normal in 249 patients (85%) and abnormal LFT was detected in 41 patients (15 %).

Conclusion: This study showed that 15 % of patients with cholelithiasis without dilated CBD had impaired LFTs.  Routine LFTs in preoperative evaluation of symptomatic cholelithiasis usually reveals normal findings and is not helpful in uncomplicated cholelithiasis.

Keywords: Liver function tests, Laparoscopic cholecystectomy, Cholelithiasis.

(Please cite as: Rezaei-Tavirani M, Abbasi MA, Bagaee M, Tizmaghz A, Khavanin-Zadeh M. Evaluation of preoperative liver function test efficacy in patient with symptomatic cholelithiasis. Gastroenterol Hepatol Bed Bench 2020;13(3):254-257).

Aim: The present study aims at teaching the right citation models in scientific publications by top authors from Iranian universities of medical sciences in 2017, considering the relationship between moral development and self-control variables and model of "citation to multi-authored papers" in these articles.

Background: Multi-authorship increases the amount of self-citation and also increases the likelihood of being cited by others.

Methods: This study is of the applied scientometrics and correlation (model presentation) studies type. The research population in the first part of this study includes all the authors who had an H-index of 10 or more in the scientific databases of 2017. The sample size at this stage was 110, selected by systematic random sampling. The collected data were analyzed using SPSS 16.0.

Results: The results of regression analysis based on the concurrent method indicated that the regression model is significant. The coefficient of determination is 0.096 and the F ratio is 5.650, which are significant at the level of p <0.001. In this regression model, the variables of the level of moral development (β = -5.801, p <0.001) and self-control (p < 0.001, β = -0.253) have significant predictive power and can be considered as predictors of behavioral modeling in citing "multi-authored papers".

Conclusion: Based on the results, teaching how to avoid blindly citing the "multi-authored papers", which is regarded as a kind of "citation deviation", can, to some extent, lead to strengthening citation indexes.

Keywords: Citation behavior, Self-Control, Moral development, Multi-authorship.

(Please cite as: Hosseini Ahangari Z, Hosseini Ahangari A. Teaching how to cite scientific articles: a study of citation deviation in citing "multi-authored papers" by top authors from Iranian universities of medical sciences in 2017. Gastroenterol Hepatol Bed Bench 2020;13(3):258-263).

Acute esophageal necrosis is a rare esophageal disease, typically characterized by the circumferential black appearance of the esophagus mucosa that usually affects the distal esophagus. It commonly affects the elderly man with multiple comorbidities. In medical literature, some cases have been reported about acute necrotizing esophagus, but according to our knowledge, no case has been reported about a patient with ischemic duodenum and esophagus. We describe the case of a 71-year-old man with an upper gastrointestinal bleeding and subsequently acute necrotizing esophagus and duodenum.

Angiosarcomas are soft-tissue neoplasms that originate from the vascular epithelium. The most commonly involved sites include the skin and subcutaneous tissues. In the GI tract, generally, angiosarcomas involve the spleen and liver, although locations in the small intestine and colon have been very occasionally reported. In the present study we report the unusual case of a man with duodenal epithelioid angiosarcoma, presenting with anemia and recurrent upper gastrointestinal bleeding, which was initially misdiagnosed as a Dieulafoy’s lesion. It is important to consider the diagnosis of gastrointestinal malignancy, including unusual neoplasms such as angiosarcomas, in the setting of anendoscopic appearance such as hemorrhagic nodule, purpuric mass and/or recurrent bleeding lesions that are persistent despite repeat interventions. In such cases, a biopsy should be considered to confirm the diagnosis.

Keywords: Duodenal, Angiosarcoma, Dieulafoy’s lesion.

(Please cite as: Amini A, Koury E, Vaezi Z, Melnick J, Su A, Chahla E. Duodenal angiosarcoma can misdiagnose as a Dieulafoy’s Lesion. Gastroenterol Hepatol Bed Bench 2020;13(3):268-271).

To The Editor

Shiha et al pose a contentious question in their recent article entitled “Diagnosing coeliac disease in the elderly: a United Kingdom cohort study” (1). They muse at the necessity for active case finding of coeliac disease in the elderly, implying that the burden of breaking nutritional habits may exceed the benefits of diagnosis.

While one may concede that the adage “scientia potentia est” may not always hold true, we are inclined to disagree with the authors in this instance. Bone health is an important consideration both in the elderly and in those with coeliac disease, independently. It follows that this should be of particular concern with respect to the elderly with coeliac disease. Regarding the authors reference to the need to establish the risks of not pursuing a diagnosis, we feel their suggestion belies a lack of appreciation for the potential to recognise and prevent bone related morbidity in such patients. An audit of patients within the catchment of our tertiary level hospital in the South-East of Ireland shows that such an under-appreciation may be widespread. The British Society of Gastroenterology guidelines on coeliac disease state that patients should undergo a vitamin D level check at diagnosis (2). On reviewing our laboratory records of patients with a positive IgA anti-tissue transglutaminase for over 18 months, from January 2018 to June 2019, we found that only 14.6% of patients had their vitamin D levels checked within 6 months of a first positive result.

Coeliac disease is associated with an increased risk of osteoporosis and fracture(3), and just 1 year of adhering to a gluten free diet in such patients has been shown to lead to an improvement in objective markers of bone mineral density(4). In light of this, we feel the need to express our respectful disagreement with the proposal to not seek out a diagnosis of coeliac disease in old age.Additionally, we should be reminding our clinician colleagues of its relationship with bone disease and to actively manage those patients who have multiple osteoporotic risk factors. This appears to be especially true in the case of coeliac disease given the poor compliance with guidelines in relation to vitamin D assessment in the cohort of patients within the catchment of our institution.  

To The Editor

We thank Dr. W.Shanahan and Dr. J.Shanahan for their interest in our study (1). In their letter, they have raised a few important points that we wish to clarify.

Firstly, they implied that we had a lack of appreciation for the recognition and prevention of bone-related morbidity in elderly Coeliac Disease (CD) patients. We respectfully disagree with their statement; throughout our paper, we repeatedly highlighted the importance of recognising such complications in this group of patients. Moreover, we reported that elderly CD patients had a significantly higher risk of osteopenia/osteoporosis compared to younger patients. In our practice, we routinely measure serum vitamin D, alkaline phosphatase and calcium levels for all CD patients and refer those older than 55 years or with known osteoporotic risk factors for bone density scans following the British Society of Gastroenterology guidelines. (2) A single centre audit, while valuable in improving local practices, should not be used to generalise poor adherence to national guidelines.

Secondly, we agree that CD is associated with an increased risk of osteoporosis and fractures. However, GFD adherence rarely reverses bone loss in adults. This is particularly evident in elderly patients with long-term exposure to gluten and established bone disease at the time of diagnosis (3, 4).  In our study, 57% of the osteopenic/osteoporotic elderly patients with CD were completely asymptomatic. Therefore, without strong evidence from randomised controlled trials or large prospective studies showing a clear benefit from adhering to a strict GFD over nutritional supplementation, only in this age group, we have to raise the question whether it is worthwhile breaking lifetime dietary habits in asymptomatic elderly patients.

Finally, should we be diagnosing Coeliac Disease in the elderly? The answer is probably yes. However, the majority of these elderley patients show little to no gastrointestinal symptoms and are often referred due to cancer or metabolic pathways with unexplained anaemia and bone loss. Hence, the diagnosis of CD may come as a shock to them. We feel that empowering elderly patients to adopt a GFD on an individual level based on the presence or absence of symptoms might be appropriate. Nonetheless, future research is needed to evaluate the alternatives to GFD and the other long-term risks of CD, such as malignancy and anaemia, before accepting such an approach.