Kassem, A. M., "A note from the Editor's desk: Arab Journal of Gastroenterology in Thomson Reuters.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 16, issue 3-4, pp. iv, 2015 Sep-Dec.
Abdel-Aziz, H., M. Schneider, W. Neuhuber, A. M. Kassem, S. Khailah, J. Müller, H. G. E. deen, A. Khairy, M. T. Khayyal, A. Shcherbakova, et al., "GPR84 and TREM-1 signaling contribute to the pathogenesis of reflux esophagitis.", Molecular medicine (Cambridge, Mass.), 2015 Nov 24. Abstract

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a non-uniform etiology. Thus the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients.To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced sub-chronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cellline HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein coupled receptor (GPR) 84 in human tissue.Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known pro-inflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was up-regulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly up-regulated in patients with grade B reflux esophagitis.The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

Abdelhafez, M., V. Phillip, A. Hapfelmeier, M. Elnegouly, A. Poszler, K. Strobel, P. Born, M. Dollhopf, A. M. Kassem, L. Calavrezos, et al., "Cap Assisted Upper Endoscopy for Examination of the Major Duodenal Papilla: A Randomized, Blinded, Controlled Crossover Study (CAPPA Study).", The American journal of gastroenterology, 2017 Mar 14. Abstract

OBJECTIVE: Examination of major duodenal papilla (MDP) by standard forward-viewing esophagogastroduodenoscopy (S-EGD) is limited. Cap assisted esophagogastroduodenoscopy (CA-EGD) utilizes a cap fitted to the tip of the endoscope that can depress the mucosal folds and thus might improve visualization of MDP. The aim of this study was to compare CA-EGD to S-EGD for complete examination of the MDP.

METHODS: Prospective, randomized, blinded, controlled crossover study. Subjects scheduled for elective EGD were randomized to undergo S-EGD (group A) or CA-EGD (group B) before undergoing a second examination by the alternate method. Images of the MDP were evaluated by three blinded multicenter-experts. Our primary outcome measure was complete examination of the papilla. Secondary outcome measures were duration and overall diagnostic yield.

RESULTS: A total of 101 patients were randomized and completed the study. Complete examination of MDP was achieved in 98 patients using CA-EGD compared to 24 patients using S-EGD (97 vs. 24%, P<0.001). Median duration from intubation of the esophagus until localization of the MDP was shorter with CA-EGD (46. vs. 96 s., P<0.001). In group A, 11 extra lesions and 12 additional incidental findings were detected by secondary CA-EGD, whereas neither were detected by secondary S-EGD in group B (22 vs. 0% and 24 vs. 0%, P<0.001 and P<0.001).

CONCLUSION: CA-EGD enabled complete examination of MDP in almost all cases compared to a low success rate of S-EGD. CA-EGD detected a significant amount of lesions and incidental findings when added to S-EGD. CA-EGD is a safe and effective method for examination of MDP.Am J Gastroenterol advance online publication, 14 March 2017; doi:10.1038/ajg.2017.47.

Meguid, K. A., Reflux, , 2016.
El-Serafy, M., A. - M. Kassem, A. Alansary, A. Omar, A. Yosry, G. Esmat, R. Kamel, S. Refaat, W. Doss, N. Zayed, et al., "Quality of life of Egyptian donors after living-related liver transplantation.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 10, issue 1, pp. 21-4, 2009 Mar. Abstract

BACKGROUND AND STUDY AIM: Quality of life after liver donation must remain a primary outcome measure when we consider the utility of living donor liver transplants. In making clinical decisions on the use of transplantation for chronic liver diseases, consideration should be given to the key factors likely to affect subsequent health related quality of life. It would be beneficial for donors, if factors predicting good quality of life are identified. The aim of this study was to assess the health related quality of life changes experienced by donors following living related liver transplantation using the Short Form 36 (SF-36) questionnaire.

PATIENTS AND METHODS: Between August 2001 and December 2006, 125 adults received liver grafts from living donors at Dar Al-Fouad Hospital, Cairo, Egypt. The SF-36v2 questionnaire was applied to 30 donors after at least 6 months following donation and maximally 4 years after donation (mean±STD:3.28±1.56 years). Furthermore, 30 healthy volunteers were taken as a control group.

RESULTS: None of the donors required re-surgery and no deaths were reported. Only 4 (13.3%) donors experienced minor complications, which did not affect their quality of life and had no long term effects. No significant difference was found between donors and control group when means of the Physical and Mental Component Summary were compared. The physical functioning domain was the only domain of health which showed a statistically significant difference between both groups.

CONCLUSION: Health related quality of life of donors was not compromised after full recovery. All donors had good recovery and returned to regular activities within 2-4 months post donation.

Abouzeid, H. E., A. M. Kassem, A. H. A. Wahab, H. A. El-mezayen, H. Sharad, and S. Abdel Rahman, "Promoter hypermethylation of RASSF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors.", Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, vol. 32, issue 5, pp. 845-52, 2011 Oct. Abstract

Hypermethylation at the promoter region is an important epigenetic mechanism underlying the inactivation of tumor suppressor genes and frequently occurs as an early event in the development of different types of cancer including colorectal carcinoma (CRC). The aim of the present study is the detection of methylation status for some tumor suppressor genes including RASSF1A, MGMT, and HIC-1 in both cancerous and precancerous lesions of colorectal mucosa to evaluate the possibility of developing epigenetic biomarker for early detection of Egyptian CRC. Tissue biopsy was collected from 72 patients (36 CRC, 17 adenomatous polyps, and 19 ulcerative colitis), and in addition, adjacent normal-appearing tissues were collected as control. Promoter hypermethylation status for RSSAF1A, MGMT, and HIC-1 genes was detected after isolation of genomic DNA from the tissues samples using methylation-specific PCR technique. High frequency of methylation at MGMT, RASSFA, and HIC-1 was detected in CRC patients (25%, 47.2%, and 41.7% respectively). The highest methylation detected in adenomatous polyps patients was in MGMT gene (47.1%) followed by 35.3% for HIC-1 and only 5.9% for RASSF1A gene. HIC-1 gene exhibited highest frequency of methylation in ulcerative colitis patients (57.8%) whereas it was 26.3% for both RASSF1A and MGMT genes. A nonsignificant association was recorded between the methylation status in different genes examined with the clinicopathological factors except the association between methylation at RASSF1A gene with gender (p=0.005), and it was significant. In conclusion, aberrant hypermethylation at promoter region of RASSFA, MGMT, and HIC-1 genes is involved in Egyptian CRCs. Hypermethylation of MGMT and HIC-1 genes plays an important role in the initiation of disease especially ulcerative colitis-carcinoma pathway.

Mostafa, M. S., E. A. El-Seidi, A. M. Kassem, M. A. Shemis, M. Saber, and M. N. Michael, "Detection of ascitic fluid infections in patients with liver cirrhosis and ascites.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 12, issue 1, pp. 20-4, 2011 Mar. Abstract

BACKGROUND AND STUDY AIMS: Ascitic fluid infections (AFIs) are the frequent complications of advanced liver disease. Bacterial translocation is considered a key step in the pathogenesis of gut-derived bacterial infections; mainly spontaneous bacterial peritonitis (SBP) in cirrhotic patients. Bacterial DNA (bactDNA) in ascitic fluid and serum has been suggested as a surrogate marker for bacterial translocation. We attempted at the isolation and identification of bacteria in ascitic fluid in cirrhotic patients and the assessment of polymerase chain reaction (PCR) in ascitic fluid and serum.

PATIENTS AND METHODS: Fifty cirrhotic patients having ascites with no signs of infection were included. Ascitic fluid cultures were obtained from patients. Ascitic fluid and serum were subjected to DNA extraction and PCR for the universal amplification of a region of the 16S ribosomal RNA (16S rRNA) gene to detect bactDNA.

RESULTS: Bacteria were isolated from 9 (18%) of the ascitic fluid samples, and were mainly Gram-positive bacteria. BactDNA was detected simultaneously in the ascitic fluid and serum of 17 (34%) patients and in the ascitic fluid of only 2 patients. In a single patient with positive ascitic fluid culture no bactDNA was detected in ascitic fluid or serum. By considering AFIs as a positive ascitic fluid culture and/or the presence of bactDNA in the ascitic fluid and/or serum, ascitic fluid culture could detect 9 out of 20 patients with AFIs (45%), PCR of ascitic fluid could detect 19 out of 20 (95%) while PCR of serum could detect 17 out of 20 (85%). In 10 patients with culture negative non-neutrocytic ascites (CNNNA) bactDNA could be detected in serum and ascitic fluid.

CONCLUSION: AFI can be caused by Gram positive as well as Gram negative organisms. A substantial percentage of cases with CNNNA show bactDNA in serum and ascitic fluid. PCR of ascitic fluid should, therefore, be used in the diagnostic workup of suspected cases of ascitic fluid infections.

Wahab, A. H. A. A., A. M. Kassem, S. Matter, A. N. F. El Deen, A. S. Helmy, M. M. Ismaeil, and M. S. Zakaria, "Role of KLF6 tumor suppressor gene mutations in the development of colorectal carcinoma in an Egyptian population.", Hepato-gastroenterology, vol. 57, issue 104, pp. 1405-10, 2010 Nov-Dec. Abstract

BACKGROUND/AIMS: Colorectal cancer is one of the common cancers of the gastrointestinal tract in Egypt. It is characterized by a relatively earlier onset compared to that in the western world. Studying genetic alterations involved in colorectal cancer progression may help in identifying molecular biomarkers that can be used for early detection.

METHODOLOGY: We analyzed DNA isolated from 83 cases including 38 colorectal carcinomas, 23 polyps (16 of which were adenomatous) and 22 cases with inflammatory bowel disease (IBD). Mutations at KLF6 tumor suppressor gene (exon 1-4) were examined by PCR-SSCP silver staining technique followed by direct sequencing. 10p15 LOH was analyzed using KLF6 M1, KLF6 M2 and KLF6 M4 markers by microsatellite assay.

RESULTS: KLF6 mutations were found in 45%, 27% and 26% of colorectal carcinoma, ulcerative colitis and polyp cases, respectively. Most of the mutations detected were located at exon 2. The majority of mutations found in KLF6 were missense mutation and their type and locations were different from those previously described in the western population. The frequencies of LOH at the three markers examined were 29%, 36%, and 52% for colorectal carcinomas, IBD, and polyp cases, respectively. LOH was detected in mutant KLF6 as well as wild type. No significant association was found between genetic alterations examined with different clinicopathological factors.

CONCLUSIONS: Our data highlights for the first time an association of KLF6 gene in colorectal cancer in an Egyptian population. Detecting mutational sites different from those in western population is a characteristic feature in our study which may be related to environmental and/or genetic factors that have to be further identified.

Kassem, A. M., N. El-Guendy, M. Tantawy, H. Abdelhady, A. El-Ghor, and A. H. A. Wahab, "Mutational hotspots in the mitochondrial D-loop region of cancerous and precancerous colorectal lesions in Egyptian patients.", DNA and cell biology, vol. 30, issue 11, pp. 899-906, 2011 Nov. Abstract

Mutations in the mitochondrial genome (mtDNA) are associated with different types of cancer, specifically colorectal cancer (CRC). However, few studies have been performed on precancerous lesions, such as ulcerative colitis (UC) lesions and adenomatous polyps (AP). The aim of this study was to identify mtDNA mutations in the cancerous and precancerous lesions of Egyptian patients. An analysis of the mutations found in six regions of the mtDNA genome (ND1, ND5, COI, tRNAser, D-loop 1, and 2) in 80 Egyptian patients (40 CRC, 20 UC, and 20 AP) was performed using polymerase chain reaction-single-strand conformational polymorphism techniques and followed up by direct sequencing. The overall incidence of mutations was 25%, 25%, and 35% in CRC, UC, and AP cases, respectively. Although there was no common mutation pattern within each group, a large number of mutations were detected in the D-loop region in all of the groups. Some mutations (e.g., T414G) were detected repeatedly in precancerous (UC and AP) and cancerous lesions. Mutations detected in patients with CRC were predominantly found in the ND1 gene (40%). Our preliminary study suggests that Egyptian patients with CRC have a large number of mtDNA mutations, especially in the D-loop region, which have not been previously reported. Mutations in the mtDNA of precancerous lesions (i.e., AP and UC) may contribute to transformation events that lead to CRC.

Mulder, C. J. J., G. Bouma, S. W. van der Merwe, and A. M. Kassem, "Building up a research pipeline in gastroenterology.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 12, issue 2, pp. 55-7, 2011 Jun. Abstract