ISSN: 2008-2258

Original Article

Aim: This study aims to identify the risk factors of death disease-related in patients with colon cancer in the presence of competing risks.

Background: The competing risk analysis is the effective method for identifying risk factors of death for diseases and the evidence related to death prognosis in patients with colon cancer in the country is rare.

Methods: In this historical cohort study, the information of 196 patients with colon cancer who were referred to Imam Khomeini clinic in Hamadan during the years of 2003 to 2017 were examined. In this study, death due to the progression of cancer was considered an interested cause and death related to other causes were considered as competing event. Predictors of death due to the progression of cancer were determined in the presence of competing risks. The cause-specific hazard regression model was used to determine the effect of covariates. Data were analyzed using R software vol 3.4.3 and survival packages.

Results: The mean (SD) age of patients was 57.1 (12.9) years and 52.6% were male. The results of the multivariate cause-specific hazard regression model showed that the patient's age at the time of cancer diagnosis, T stage, stage of the disease and the N stage had a significant effect on the hazard of death due to cancer progression (P <0.05).

Conclusion: In the presence of various causes of death, in order to identify the risk factors of each cause separately, using the cause-specific hazard model can have better support for clinical decisions compared to other models.

Keywords: Competing risk, Colon cancer, cause-specific risk, Death due to cancer progression

Estimating the treatment effect in patients with gastric cancer in the presence of Noncompliance

Malihe Safari , Hossein Mahjub, Habib Esmaeili , Sanambar Sadighi , Ghodratollah Roshanaei

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021

Background: In medical sciences, to estimate of treatment effect in the presence of Noncompliance simple and advance method is used. In this paper, the treatment effect was estimated in patients with gastric cancer using these methods in the presence of Noncompliance.

Methods: In this historical cohort study, 178 patients with gastric cancer underwent chemotherapy (surgery plus chemotherapy group) and 193 patients underwent surgery, and chemotherapy (chemotherapy alone group) who entered from 2003 to 2007 to the cancer institute of Imam Khomeini Hospital (Tehran) were surveyed. Demographic and clinical characteristics were extracted from patients' hospital records. The survival of patients was calculated from diagnosis to death or the end of the study. The treatment effect was estimated using three methods: treatment as a time-dependent covariate, IPCW, and Structural Nested Models using STATA and R software.

Results: Fifty-six patients (31.5%) undergoing chemotherapy and 69 patients (35.8%) undergo surgery-chemotherapy died by the end of the study. The hazard ratio in the group I compared to group II was estimated between 1.5 to 2.07 times based on the simple analysis method. Still, the modified hazard ratio was estimated to be 1.21 (95% CI: 1.11-1.32) based on SNM method. surgery plus chemotherapy is superior to chemotherapy alone, and it improves the OS of gastric cancer patients.

Conclusion: the survival in patients undergoing chemotherapy and surgery compared to chemotherapy alone improved. The results of our study suggest that we can estimate treatment effect be unbiasely using the appropriate method.

Keywords: Treatment effect, Noncompliance, time-dependent covariate, Inverse Probability of Censoring Weights, Structural Nested Model

The potential of endoscopic ultrasound sonography (EUS)-elastography in determination the stage of pancreatic tumour

Afsaneh Saffarian, Pegah Eslami, Arash Dooghaie Moghadam, Faezeh Almasi, Mohamad Amin Pourhoseingholi, Hamid Asadzadeh Aghdaei, Amir Sadeghi, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Background: Pancreatic cancer is numbered as one of the lethal malignancy with only 5% survival, worldwide. pancreatic lesions include wide ranges of diagnosis from benign to malignant forms. Biopsy and pathological study is the gold standard for differentiation of the malignant lesions and staging of these tumors. Recently, Endoscopic Ultrasound Sonography (EUS) elastography has been noticed as a non-invasive diagnosis modality. Nevertheless, no evidence is available about its potential to determine different stages of malignant tumors. Herein, we designed this study to evaluate the role of semi-quantitative EUS- elastography (strain ratio) in staging the malignant pancreatic lesions.

Method: In this prospective study, 81 adult patients with a confirmed diagnosis of the malignant pancreatic lesion in different clarified stages were included. All the diagnosis was confirmed after endoscopic ultrasound sonography via pathological investigation of surgical specimens or needle biopsies. The results of EUS-elastography based on tumor size (T staging), involved lymph nodes (N staging) and metastasis (M staging) compared with the  gold standard.

Results: the mean age of patients was 60.11±13.57 years old. The mean of SR elastography was 52.78±48.97. elastography could not significantly discriminate T stage, N stage, M stage of tumors (P=0.57, P=0.92, P=0.11). in addition, the spearman rank correlation coefficient between T staging, N staging, M staging with SR elastography were not significant (P=0.40, P=0.94, P=0.39).

Conclusion: The EUS-elastography as a non-invasive modality could not replace the gold standard in staging the tumors. But, it seems, EUS-elastography could differentiation benign lesions from malignant type. 

Keyword: Pancreatic Neoplasms, Elasticity Imaging Techniques, Neoplasm Staging


The association between food insulin index with odds of Non-Alcoholic Fatty Liver Disease (NAFLD) in adults: A Case-Control Study

Somaye Fathi, Mohammadhassan Sohouli, Appaji Rayi, Farshad Teymoori, Farzad Shidfar

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Aim we aimed to study the association between food insulin index and biochemical parameters with the odds of developing NAFLD in adult Iranians.

Background: Hyperinsulinemia may play an important role in the development of non-alcoholic fatty liver disease (NAFLD), due to the relationship between insulin response and body fat accumulation.

Methods: A case-control study of 169 NAFLD patients and 200 healthy adults aged 18-55 years were conducted. Dietary data were collected using a validated 168- items quantitative food frequency questionnaire (FFQ). Food insulin index (FII) was calculated by dividing the total insulin load by total energy intake (kcal / day). Total insulin load (ILoverall) was also calculated using a standard formula.

Results: Mean age of study participants was 43.9 ± 5.9 years. Patients with NAFLD were significantly associated with higher body mass index, levels of liver enzymes, triglyceride, low density lipoprotein-cholesterol (LDL), total cholesterol, and fasting blood sugar (FBS) compared to the healthy subjects. (P < 0.05) The highest tertiles of FII was associated with higher odds of NAFLD (OR=1.4, 95% CI:0.88-2.48, P for trend<0.001) and obesity (OR=2.33, 95% CI: 0.97-5.75) compared to the lowest tertiles. The potential confounders for the association were controlled.

Conclusions: We found that adherence to a diet with a high FII was associated with greater odds of NAFLD and overweight or obesity. Additional studies are required to better understand this association.

Key words: Insulin; Biochemical Processes; Obesity; Chronic Diseases; Non-alcoholic Fatty Liver Disease

Is Melatonin Associated with Pro-Inflammatory Cytokine Activity and Liver Fibrosis in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients?

Masoudreza Sohrabi, Ali Gholami, Bahareh Amirkalali, Mahsa Taherizadeh, Mahsa Kolahdoz, Fahimeh SafarnezhadTameshkel, Sheida Aghili, Marzieh Hajibaba, Farhad Zamani, Mohsen Nasiri Toosi, Hossein Keyvani

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


The associations between serum levels of melatonin and concentrations of tumor necrosis factor (TNF)-a and interleukin (IL)-6 were assessed among patients with different degrees of non-alcoholic fatty liver diseases.



In this cross-sectional study, adult patients diagnosed with fatty liver disease by Fibroscan evaluation were included if they met the inclusion/exclusion criteria for NAFLD. The participants were categorized into the three following groups: 1) fibrosis> 9.1KP and steatosis>290 dbm; 2) fibrosis: 6-9.0 KP and steatosis 240-285; and 3) fibrosis< 5.8 KP and steatosis<240 dbm. Post-fasting, 5 ml of venous blood was collected for laboratory assessment, and a questionnaire including demographic, anthropometric, laboratories and clinical data were completed.



A total 97 participants were included. The mean age was 42.21±11 years old. 59 patients (60.0%) were female. Melatonin levels, as well as pro-inflammatory cytokines levels, correlated with advancing fibrosis and steatosis in the univariate analysis. A significant association was observed between these cytokines and advancing fibrosis, severe steatosis levels and melatonin concentrations. Furthermore, in the multiple linear regression model, melatonin levels showed a significant association with these cytokines.



Melatonin may have protective effects on tissue injury during advancing liver fibrosis via cytokines modulation. Therefore, it can be considered as a potential therapeutic management strategy for NAFLD .


Key words: Fatty liver, Cytokine, Melatonin, Inflammation

Study of re-transplantation and prognosis in liver transplant center in Iran

Mohamad Javad Salimi, Ali Jafarian, Nasir Fakhar,, Alireza Ramandi, Mohamad Behzadi, Ali Moeni, Habib Dashti, Atabak Najafi, Reza Shariat M, Jalil Makarem, Abdolhamid Chavoshi Kh, Mohamad Behzadi

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Background: due to the problem of organ shortage and high demand of liver transplantation among patients, this problem has been exacerbated, thus providing more information on the causes of liver re-transplantation and its prognosis and other related issues to this procedure is of great importance. The aim of this study was to investigate the causes of liver re-transplantation in patients referred to Imam Khomeini Hospital Liver Transplantation Center and also the prognosis of this re-transplantation.

Methods: This study was conducted in 2018 as a historical cohort. In this study, the records of liver transplantation patients at Imam Khomeini Hospital Liver Transplantation Center between 2000 to 2016 and were studied. Required data were extracted from the records of patients undergoing liver transplantation. Patients' data were entered SPSS 20 software and analyzed.

Results: In this study 1030 patients with mean age of 43.15 ± 14.57 years were studied. There were 426 women (41.4%) and 604 men (58.6%). The number of primary transplants was 966 with a mean age of 43.19 ± 14.72 and the number of re-transplants 64 with a mean age of 42.56 ± 12.82. Significant differences were found between the two groups in terms of MELD and CHILD scores, cold ischemic time, total and direct bilirubin levels, liver function factors (ALT, AST, and alkaline phosphatase), hemoglobin, and WBC. There was no significant difference between the two groups in terms of age, sex and platelets (> 0.05). The mortality rate was 241 (23.39%) in all patients and the mortality rate was 206 (21.32%) and in liver transplant patients was 35 (54.68%). The mortality rate in the transplant group was statistically higher (> 0.001). Secondary is primary non-functional graft (PNF) (37.5%) with 1, 3- and 5-years survival rates of 82%, 81% and 70% in primary group and 59%, 43% and 32% in re-transplantation. There was a significant difference in survival between the two groups (P <0.05). Hemoglobin and alkaline phosphatase were predictors of survival rates in transplant patients.

Conclusion: The results of this study showed that survival rate in re-transplant patients was significantly lower than primary transplant and mortality rate in re-transplant patients was significantly higher.

Key words: liver re-transplant; prognosis; Survival


Cross-cultural adaptation, the validity, and reliability of the Wexner questionnaire in patients with functional constipation in an Iranian population

Fatemeh Majidirad, Mohammad Reza Hadian, Hossein Asl Soleimani, Shohreh Jalaie, Tannaz Ahadi, Roxana Bazaz Bebahani, Hossein Bagheri

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021

Aim: The present study aimed to cross-culturally adapt and assess the validity and reliability of the English version of the Wexner questionnaire into the Persian language in Iranian patients.  

Background: Constipation is one of the most common gastrointestinal disorder; therefore, it is necessary to utilize an index, both for the clinic and research studies.

Materials and methods: In the first phase, The English version of the Wexner questionnaire was translated into the Persian language. In the second phase, it was assessed for the evaluation of psychometric properties in 136 patients with functional constipation who refer to Gastrointestinal and Physical Medicine Clinics. Content validity was assessed by face validity. Construct validity was tested based on hypothesis testing and structural validity. Correlation of the total score of the Wexner questionnaire and Patient Assessment Constipation Quality Of Life (PAC-QOL) questionnaire was used for concurrent criterion validity. Internal consistency and test-retest reliability were calculated using Cronbach's α and intraclass correlation coefficient (ICC). Also, the floor/ceiling effect of the questionnaire was evaluated.

Results: The content validity was acceptable. The construct and concurrent criterion validity showed moderate correlation. The internal consistency and Intrarater reliability were moderate (0.51) and excellent (rp = 0.97, P-value<0.001), respectively. No floor/ceiling effect was seen.

Conclusion: The Persian version of the Wexner questionnaire showed good validity and reliability in Iranian patients and therefore could be applied in clinics as well as in research for Persian-speaking countries.

Keywords: Constipation, Validity, Reliability, Persian, Questionnaire

Cost-effectiveness analysis of two Routine therapeutic methods to Helicobacter pylori eradication: A Persian cohort-based study

Farhad Pourfarzi, Hamed Zandian, Abbas Yazdanbod Yazdanbod, Telma Zahirian moghadam

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Background: Because of the importance of Helicobacter pylori (H. pylori) eradication on gastric cancer prevalence and costs, economic analysis of the eradication methods is essential for the health systems.

Purpose of the study: This study aimed to analyze the cost-effectiveness of two routine therapeutic methods to H. pylori eradication in Iran.

Methods: We conducted a cross-sectional study on 7,496 participants with positive Hepadnaviridae (HPsAg) test results for H. pylori, where 6,163 of them were treated with Furazolidone (Group A), and 1,333 participants were treated with Clarithromycin (Group B). GP visits, medications, and HPsAg cost as direct costs and absence from work and transportation as indirect costs collected by the researcher-made questionnaire. Indirect costs calculated based on face-to-face interviews with 365 patients of the Persian Cohort Center. Successful eradication of H. pylori infection (negative HPsAg) defined as the effectiveness of the interventions. Incremental Cost-Effectiveness Ratio (ICER) used to compare the overall results.

Results: The total direct cost of H. pylori for groups A and B were estimated at 13.7 and 5.83 billion IRR, respectively. The highest and lowest percentages of total costs were the cost of diagnostic services and the time cost, respectively. There was a significant difference between the two groups in drug costs (p<0.001). The effect ratio for Groups A and B was 85.93% and 96.54%, respectively. Cost per effectiveness for Clarithromycin (CE=3,250,170 IRR) was higher than Furazolidone (CE=2,988,488 IRR), and ICER showed that there is a need for 5.1 Million IRR to eradication H. pylori per participant.

Conclusion: Base on the results, Furazolidone was cost-effectiveness than Clarithromycin for H. pylori treatment. Therefore, due to the high prevalence of H. pylori and the economic conditions of the health system in Iran, Furazolidone can be a cost-effective choice between the two conventional treatment methods with considering the results of further research and possible side effects.

Keywords: Cost-Effectiveness, Helicobacter Pylori, Eradication, Furazolidone, Clarithromycin

In vitro antifungal susceptibility pattern of Candida species isolated from gastroesophageal candidiasis

Rasoul Mohammadi, Mohsen Mirshekar, Mohammad Hassan Emami

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Aim: Determination of antifungal susceptibility profile of Candida species isolated from gastroesophageal lesions.

Background: Gastroesophageal candidiasis is a common infection among HIV/AIDS patients and who are taking PPI and H2RAs drugs. More than 20 Candida spp. can cause different types of mucocutaneous infections in humans. The present study was conducted to assess the antifungal susceptibility testing of clinical Candida spp. isolated from gastroesophageal lesions.

Patients and methods: Forty-eight clinical samples were collected from 60 patients underwent endoscopy. All isolates were identified by molecular techniques (PCR-RFLP). The profiles of the susceptibility of Candida spp. to seven antifungal agents including amphotericin B, fluconazole, itraconazole, luliconazole, voriconazole, posaconazole and caspofungin were evaluated using broth microdilution.

Results: The susceptibility profile of Candida isolates revealed 100% sensitivity to amphotericin B, caspofungin, and voriconazole; moreover, fluconazole (6.25%) and itraconazole (2.1%) resistant isolates were observed.

Conclusion: With regard to the increase of fluconazole-resistant Candida species, it is necessary to determine the in vitro antifungal susceptibility pattern of clinical isolates for the best management of infection and to prevent the emergence of drug resistant isolates.

Keywords: Antifungal susceptibility testing, Candida spp., Gastroesophageal

NF-κB and NLRP3 gene expression changes during warm hepatic ischemia-reperfusion in rats with and without silibinin

Setareh Zarpou , Hadis Mosavi , Abouzar Bagheri , Majid Malekzadeh Shafaroudi , Abbas Khonakdar-Tarsi

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Hepatic ischemia-reperfusion (I/R) is a common phenomenon in many clinical cases, including liver surgery and transplantation. Inflammatory mediators are vital contributors to the expansion of hepatic damages after I/R injury (I/RI), and therefore, targeting inflammation is a considerable candidate for the management of hepatic I/RI and its complications. This research examined silibinin's anti-inflammatory outcomes on the Nod-like receptor protein-3 (NLRP3) and NF-κB gene expression, which plays a notable role in inciting inflammatory pathways.

Thirty-two male Wistar rats were divided into four equal groups: 1) control (Vehicle) group underwent laparotomy and received normal saline. 2) In the SILI group, a laparotomy was performed, and 30 mg/kg silibinin was injected intraperitoneal (IP). 3) I/R group underwent I/R and received normal saline. 4) The I/R + SILI group encountered I/R after laparotomy and received silibinin. After one hour of ischemia and three hours of reperfusion, blood and liver tissue samples were assembled for future biochemical, histological, and gene expression studies.

In vivo analysis attested that serum AST and ALT activities were significantly lessened by silibinin in the SILI + I/R group (P <0.001). Silibinin ameliorated inflammatory liver tissue injuries, including neutrophil and macrophage infiltration, hepatocyte degeneration, cytoplasmic vacuolation, vascular endothelial damages, and sinusoid dilation observed in the I/R group. During I/R, the NLRP3 and NF-κB gene expression owned a significant increment compared to the control group (P <0.001), which could alleviate by silibinin (P <0.01).

The results declared that adjusting the expression of NLRP3 and NF-κB genes during I/R is probably one of the mechanisms of the anti-inflammatory effects of silibinin.

Keywords: Ischemia, NF-κB, NLRP3, Reperfusion, Silibinin.


Case Report

Autopsy Diagnosis of Leptomeningeal Carcinomatosis, The First Manifestation of Gastric Adenocarcinoma, A Rare Case report and review of the Literature

Bita Geramizadeh, Mehran Fereidooni, Alireza Dehghan, Kamran Bagheri-Lankarani

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021


Aim: To report an unusual presentation of an advanced gastric adenocarcinoma

Background: Leptomeningeal carcinomatosis is a rare event in gastric adenocarcinoma. It is much more uncommon as the primary manifestation in post-mortem evaluation of the cause of death in a patient manifested with headache and neurological signs and symptoms. Herein we will discuss our experience with a case of gastric adenocarcinoma who was diagnosed after death presenting with neurological signs and symptoms of leptomeningeal carcinomatosis.

Patients and methods: A 52-year-old gentleman presented with intractable headache and neck pain as well as vertigo. His physical examination showed only decreased deep tendon reflexes. He died after a short period of coma.

Results: Post-mortem evaluation showed numerous signet ring cells in the subarachnoid space as well as gastric malignant ulcer.

Conclusion: In patients with intractable headache with no identifiable cause, meningeal involvement and infiltration should be considered as the probable underlying cause. Radiologic findings are not significant however lumbar puncture can be diagnostic.

Key Words; Leptomeningeal carcinomatosis, Gastric adenocarcinoma, Autopsy

Gastric Hepatoid Adenocarcinoma with multiple liver metastasis. A case report

Mariano Quino-Florentini, Frank Garcia-Rojas, Pedro Guerra-Canchari, Gustavo Cerrillo-Sanchez

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021

Hepatoid adenocarcinoma is a poorly differentiated alpha-fetoprotein-producing (AFP) tumor, frequently located in the stomach, ovary, and pancreas. Presentation in the stomach has a high mortality rate due to late diagnosis, which offers the patient little therapeutic alternative. A 44-year-old woman from Lima, on February 22, 2019, entered the emergency department for pain in the right hypochondrium for 4 months, weight loss, nausea and asthenia. On physical examination, hepatomegaly presented with liver span of 17cm. Serology showed severe anemia and AFP of 49800. The tomography showed multiple hypodense lesions in the liver and the presence of nodes. Endoscopy showed Bormann III gastric malignancy. Gastric biopsy determined undifferentiated epithelial malignancy, the immunohistochemical mark (+) for AFP and PAS Diastase confirmed a hepatoid gastric adenocarcinoma. A rare variant of gastric adenocarcinoma is evident, which often mimics an HCC. In this case, multiple liver metastases are observed that differ from the diagnosis of HCC, so this variant must always be taken into account when a primary gastric tumor presents with hepatic metastases.


Keywords: Hepatoid Adenocarcinoma, metastases, liver

Acute appendicitis, A case report of hyper infection with Enterobius vermicularis

Hossein Hooshyar, Ebrahim Kazemi, Mohammad Jannati Dastgerdi

Gastroenterology and Hepatology from Bed to Bench, , 26 April 2021

Acute appendicitis is one of the most common causes of abdominal emergent surgical disease worldwide. Enterobius vermicularis, a human intestinal parasite, is reported to be associated with acute appendicitis.

We report a case of an 8-years old girl who was admitted to emergency unite with complaints of severe abdominal pain and was diagnosed as acute appendicitis. Microscopic pathological examination showed lymphoid follicle with prominent germinal centers and mantle zones within the appendix wall. Cross-sections of multiple female and male Enterobius vermicularis worms and a few number of  longitudinal sections of  E.vermicularis were seen.

  1. vermicularis is one of the most commons human parasitic infections, so the possibility of infection of the appendix with E. vermicularis should be considered in the differential diagnosis of agents of appendicitis.

Key words: Appendicitis, Parasite, Enterobius, Khoy