Crohn`s disease. Increasing trend in Saudi Arabia.

We attempted, through systematic review to explore the epidemiology and risk factors of Crohn's disease (CD) with special attention to the Kingdom of Saudi Arabia (KSA). We selected articles that contained population-based, epidemiological, and clinical character studies of CD. We collected data concerned with the prevalence, demographic features, and the possible etiology of CD that might explain its emergence in KSA. The prevalence of CD in Western countries ranged between 11-43/100,000 with flawless evidence of CD prevalence emerging in previously low incidence areas like Asia. Prevalence in KSA has markedly increased over the last 3 decades. Combined ileal and colonic involvement was the most frequently affected site. Diet, smoking, drugs, and westernization of life are assumed to contribute to the pathogenesis. There is convincing evidence of CD emerging in Asia, including KSA. Westernization of lifestyle and smoking is probably the major contributing factors. Genetic studies are warranted.

Emerging inflammatory bowel disease in saudi outpatients: a report of 693 cases.

BACKGROUND/AIM: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology and considered traditionally as a disease of the western world. Recently, rising trends have been observed in countries previously known to have a low prevalence and incidence. The aim of this study is to collect epidemiological data on IBD outpatients and to add data from the Kingdom of Saudi Arabia (KSA) to the available IBD literature. PATIENTS AND METHODS: The medical records of 693 Saudi patients with IBD over a period of 17 years, between 1993 and 2009, were reviewed. The demographic and clinical data and methods of diagnosis were retrieved. RESULTS: The total number of patients in this cohort was 693. It constituted 238 (34.3%) ulcerative colitis (UC) and 455 (65.7%) Crohn's disease (CD) patients. UC was steady throughout the years, whereas only 1.2 CD patients were diagnosed per year in the first 11 years, and 73.7 per year in the last six years. The median age of UC patients was 34 years, ranging from 10 to 80 years with a peak between 21 and 40 years and in CD it was 27 years, ranging from 11 to 73 years with a peak between 11 and 30 years. There was a male preponderance of 1.5:1 and 2:1, respectively. The rest of the data is discussed in this study. CONCLUSION: IBD is no longer a rare disease in KSA. UC is in a steady state, whereas CD is increasing significantly and far outnumbering UC.

Crohn's disease in a Saudi outpatient population: is it still rare?

BACKGROUND/AIM: To determine the epidemiology of Crohn's disease (CD) in an outpatient clinic and compare it with data previously reported from different centers in the Kingdom of Saudi Arabia and outside. MATERIALS AND METHODS: The medical records of all patients with CD seen in the clinic in the period from January 1993 through December 2007 were reviewed. The demographic, clinical data and methods of diagnosis were retrieved. RESULTS: Over a period of 15 years, we saw 133 Saudi patients with CD. They were predominantly young, with a median age of 26.2 years and male preponderance (2.3:1). The final diagnosis was established within 1 week of presentation in 47% of the patients. The leading symptoms were abdominal pain (88%), diarrhea (70%), bloating (61%), rectal bleeding (50%), weight loss (33%), constipation (24%) and perianal disease (23%). The diagnosis was established by endoscopy and histopathology. Ileocecal involvement was encountered in 40% of the patients. CONCLUSION: From the current study, it is obviously possible to diagnose a large proportion of patients with CD in a gastroenterology outpatient clinic. The data revealed a strikingly increased incidence of CD in a mainly young Saudi population in the past few years.

Severe acute pancreatitis: pathogenetic aspects and prognostic factors.

Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality.

Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals.

BACKGROUND/AIM: Previous studies on "Black seed" or "Black Cumin" Nigella sativa (NS) have reported a large number of pharmacological activities including its anti-ulcer potential. These studies employed either fixed oil, volatile oil components or different solvent extracts. In folkloric practices, NS seeds are taken as such, in the form of coarse dry powder or the powdered seeds are mixed with water. This study examines the effect of NS aqueous suspension on experimentally induced gastric ulcers and basal gastric secretion in rats to rationalize its use by herbal and Unani medicine practitioners. MATERIALS AND METHODS: The study was conducted at the Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Acute gastric ulceration was produced by various noxious chemicals (80% ethanol, 0.2 M NaOH, 25% NaCl and indomethacin) in Wistar albino rats. Anti-secretory studies were undertaken in a separate group of rats. Gastric wall mucus contents and non-protein sulfhydryl concentration were estimated, and gastric tissue was examined histopathologically. RESULTS: An aqueous suspension of Black seed significantly prevented gastric ulcer formation induced by necrotizing agents. It also significantly ameliorated the ulcer severity and basal gastric acid secretion in pylorus-ligated Shay rats. Moreover, the suspension significantly replenished the ethanol-induced depleted gastric wall mucus content levels and gastric mucosal non-protein sulfhydryl concentration. The anti-ulcer effect was further confirmed histopathologically. CONCLUSION: These findings validate the use of Black seed in gastropathies induced by necrotizing agents. The anti-ulcer effect of NS is possibly prostaglandin-mediated and/or through its antioxidant and anti-secretory activities.

Aqueous suspension of anise "Pimpinella anisum" protects rats against chemically induced gastric ulcers.

AIM: To substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise, "Pimpinella anisum L." on experimentally-induced gastric ulceration and secretion in rats. METHODS: Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol, 0.2 mol/L NaOH, 25% NaCl and indomethacin. Anti-secretory studies were undertaken using pylorus-ligated Shay rat technique. Levels of gastric non-protein sulfhydryls (NP-SH) and wall mucus were estimated and gastric tissue was also examined histologically. Anise aqueous suspension was used in two doses (250 and 500 mg/kg body weight) in all experiments. RESULTS: Anise significantly inhibited gastric mucosal damage induced by necrotizing agents and indomethacin. The anti-ulcer effect was further confirmed histologically. In pylorus-ligated Shay rats, anise suspension significantly reduced the basal gastric acid secretion, acidity and completely inhibited the rumenal ulceration. On the other hand, the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration. CONCLUSION: Anise aqueous suspension possesses significant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or through its anti-secretory and antioxidative properties.

Does Helicobacter pylori affect portal hypertensive gastropathy?

Helicobacter pylori (H. pylori) is a major etiological factor of peptic ulcer disease (PUD). It is supposed to be a risk factor for the more frequently encountered PUD in patients with liver cirrhosis. Several investigators have evaluated the effect of H. pylori on liver cirrhosis, portal hypertensive gastropathy (PHG) and encephalopathy with controversial results. Some reports have shown a higher seroprevalence and suggested a synergistic effect of H. pylori on liver cirrhosis and PHG. However, this increased prevalence is associated with a negative histology and is not influenced by the cause of cirrhosis, PHG, Child class or gender. Most studies have not found any correlation between H. pylori and PHG. In contrast, other studies have reported a markedly lower prevalence of H. pylori in cirrhotics with duodenal ulcer compared to controls. The aim of this article is to review the relationship between H. pylori infection and portal hypertensive gastropathy and the role of H. pylori eradication in cirrhotic patients.

Nonsteroidal, antiinflammatory drug-induced gastrointestinal injuries and related adverse reactions: epidemiology, pathogenesis and management.

A large proportion of the population all over the world consumes acetylsalicylic acid (ASA: aspirin) or other nonsteroidal, antiinflammatory drugs (NSAIDs). This is associated with a considerable morbidity and mortality. Elderly patients, patients with prior history of peptic ulcer disease (PUD) or its complications, those who require high doses of NSAIDs and those undergoing concomitant therapy with corticosteroids or anticoagulants, are at particularly high risk of developing gastroduodenal injuries and related adverse reactions. Gastroduodenal mucosal injuries induced by NSAIDs vary from subtle microscopic to gross macroscopic changes including ulcers. These injuries are induced by both topical and systemic actions of NSAIDs. Inhibition of gastroduodenal cyclooxygenase (COX) enzyme by NSAIDs is considered to be a major pathogenetic factor. Reactive oxygen species (ROS) appear also to play a significant role in the pathogenesis of mucosal injury. Withdrawal of NSAIDs is preferably the first therapeutic option; however, it is not feasible in the majority of patients. Therefore, several drugs including antisecretory drugs (ASDs-proton pump inhibitors and Histamine-2 receptor antagonists) and misoprostol, a prostaglandin analog are used for the prevention and treatment of NSAID-induced gastroduodenal injuries. Among ASDs, proton pump inhibitors (PPIs) are the most commonly used drugs. The antiulcerogenic effect of PPIs is similar to that of misoprostol and superior to standard doses of histamine-2 receptor antagonists (H2-RAs). The adverse effects of m, isoprostol such as diarrhea, abdominal pain, nausea, flatulence, headache, dyspepsia, vomiting, constipation, abortifacient and teratogenicity limit its general use. Aside from their antisecretory action, PPIs also possess an antioxidative effect. PPI maintenance is recommended in chronic NSAID treatment in those with an increased risk of complications and is more effective than Helicobacter pylori eradication. Low PPI dosage maintenance is as effective as a standard dosage regimen. The effect of H. pylori eradication remains controversial. It is advocated in naïve NSAID users, in chronic users with recent ulcer or ulcer complications and in those with an increased risk of ulcer and ulcer complications. In addition, some herbs have shown inhibition of gastric mucosal damage experimentally induced by necrotizing agents through their antisecretory and antioxidant properties.

Lipid peroxides in patients with inflammatory bowel disease.

BACKGROUND/AIMS: In this study, we aimed to determine the levels of malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to investigate its contribution to tissue injury in IBD. MATERIALS AND METHODS: Forty-two patients with IBD (24 cases of Crohn's disease and 18 cases of ulcerative colitis) and 38 matched healthy subjects (control group) were considered for study. MDA levels were quantified by the measurement of thiobarbituric acid reactive substances. RESULTS: Plasma MDA levels of Crohn's disease patients were significantly higher than the control group, but not higher than the ulcerative colitis patients. Plasma MDA levels of patients with ulcerative colitis were higher than the control group but not significant. CONCLUSION: Increased levels of plasma MDA in IBD is an important indication of oxidative stress. Patients with Crohn's disease are more susceptible to oxidative stress than patients with ulcerative colitis.

Gastritis in Saudi Arab children.

OBJECTIVE: Information on childhood gastritis in developing countries is rare; hence, the objective of this study is to report the pattern of this condition in Saudi Arab children. METHODS: Data analysis were carried out in all children <18 years of age who were referred for endoscopy at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from 1993 to 2002. Only children with histology-proven gastritis were included. RESULTS: One hundred and seventy-five patients out of 851, referred for the investigation of gastrointestinal symptoms, had histology-proven gastritis; whereas only 110/851 (13%) had endoscopic features of gastritis. Most of the children (96%) were Saudi nationals, the age ranged between 4 days to 18 years, and the male to female ratio was 0.4:1. The most common presentation of gastritis was abdominal pain in 42%, followed by combination of abdominal pain and vomiting in 20% and vomiting alone in 18% of the children. Rare but important presentations included refractory anemia, melena and halitosis. The prevalence of gastritis increased with age from 9% in children <5 years of age to 42% in adolescents 16-18 years of age. Likewise, the prevalence of Helicobacter pylori (H. pylori) gastritis increased from 47% in children <5, to 62% in the 6-15 year age group, and 69% in the 16-18 years old adolescents. Endoscopy was normal in 74/175 (42%) of histologic gastritis and the prevalence of H. pylori gastritis was the highest in cases of endoscopic nodularity (92%) CONCLUSION: Compared to findings from various parts of the world, this report document a similar clinical pattern, but high prevalence of H. pylori gastritis in Saudi Arab children.

Indications and yield of upper gastrointestinal endoscopy in children.

OBJECTIVE: Knowledge of the pattern of gastrointestinal tract (GIT) disorders detected by endoscopy is important for clinicians. The objective of this paper is to report on the indications and yield of endoscopy. METHODS: Retrospective analysis of data of all patients below 18 years of age who underwent upper GIT endoscopy from 1414 H (1993 G) through to 1424 H (2002 G) over a 10-year period at King Khaled University Hospital, Riyadh, Kingdom of Saudi Arabia. RESULTS: One thousand and fifteen upper GIT endoscopies were performed, of which 851 diagnostic procedures were performed on 851 children. The majority (96%) were Saudi nationals, the age range was between 4 days and 18-years, and the male to female ratio was 0.7: 1. The 2 most common indications were duodenal biopsy (29%) and abdominal pain (24%). The best diagnostic yield was in children presenting with ingestion of caustic substances, followed by hematemesis, and vomiting in 86%, 75% and 67%. The overall yield, however, was 43%. Finally, the most common diagnoses were gastritis and esophagitis occurring in 32% and 30% of the children. Age related variations are reported. CONCLUSION: The increasing practice of endoscopy in children resulted in the development of new indications such as endoscopic small bowel biopsy. The differences in indications and yield of endoscopy with age reflecting the varying pattern of diseases.

Biochemical and radiological predictors of malignant biliary strictures.

AIM: Differentiation of benign biliary strictures (BBS) from malignant biliary strictures (MBS) remains difficult despite improvement in imaging and endoscopic techniques. The aim of this study was to identify the clinical, biochemical and or radiological predictors of malignant biliary strictures. METHODS: We retrospectively reviewed all charts of patients who had biliary strictures (BS) on endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous cholangiography (PTC) in case of unsuccessful ERCP from March 1998 to August 2002. Patient characteristics, clinical features, biochemical, radiological and biopsy results were all recorded. Stricture etiology was determined based on cytology, biopsy or clinical follow-up. A receiver operator characteristic (ROC) curve was constructed to determine the optimal laboratory diagnostic criterion threshold in predicting MBS. RESULTS: One hundred twenty six patients with biliary strictures were enrolled, of which 72 were malignant. The mean age for BBS was 53 years compared to 62.4 years for MBS (P=0.0006). Distal bile duct stricture was mainly due to a malignant process 48.6% vs 9% (P=0.001). Alkaline phosphates and AST levels were more significantly elevated in MBS (P=0.0002). ROC curve showed that a bilirubin level of 84 micromol/L or more was the most predictive of MBS with a sensitivity of 98.6%, specificity of 59.3% and a positive likelihood ratio of 2.42 (95% CI=0.649-0.810). Proximal biliary dilatation was more frequently encountered in MBS compared to BBS, 73.8% vs 39.5% (P=0.0001). Majority of BBS (87%) and MBS (78%) were managed endoscopically. CONCLUSION: A serum bilirubin level of 84 micromol/L or greater is the best predictor of MBS. Older age, proximal biliary dilatation, higher levels of bilirubin, alkaline phosphatase, ALT and AST are all associated with MBS. ERCP is necessary to diagnose and treat benign and malignant biliary strictures.

Epidemiology and outcome of Crohn's disease in a teaching hospital in Riyadh.

AIM: To know the epidemiology and outcome of Crohn's disease at King Khalid University Hospital, Riyadh, Saudi Arabia and to compare the results from other world institutions. METHODS: A retrospective analysis of patients seen for 20 years (between 1983 and 2002). Individual case records were reviewed with regard to history, clinical, findings from colonoscopy, biopsies, small bowel enema, computerized tomography scan, treatment and outcome. RESULTS: Seventy-seven patients with Crohn's disease were revisited, 13% presented the disease in the first 10 years and 87% over the last 10 years. Thirty-three patients (42.9%) were males and 44 (57.1%) were females. Age ranged from 11-70 years (mean of 25.3+/-11.3 years). Ninety-two (92%) were Saudi. The mean duration of symptoms was 26+/-34.7 mo. The mean annual incidence of the disease over the first 10 years was 0.32:100,000 and 1.66:100,000 over the last 10 years with a total mean annual incidence of 0.94:100,000 over the last 20 years. The chief clinical features included abdominal pain, diarrhea, weight loss, anorexia, rectal bleeding and palpable mass. Colonoscopic findings were abnormal in 58 patients (76%) showing mostly ulcerations and inflammation of the colon. Eighty nine percent of patients showed nonspecific inflammation with chronic inflammatory cells and half of these patients revealed the presence of granulomas and granulations on bowel biopsies. Similarly, 69 (89%) of small bowel enema results revealed ulcerations (49%), narrowing of the bowel lumen (42%), mucosal thickening (35%) and cobblestone appearance (35%). CT scan showed abnormality in 68 (88%) of patients with features of thickened loops (66%) and lymphadenopathy (37%). Seventy-eight percent of patients had small and large bowel disease, 16% had small bowel involvement and only 6% had colitis alone. Of the total 55 (71%) patients treated with steroids at some point in their disease history, a satisfactory response to therapy was seen in 28 patients (51%) while 27 (49%) showed recurrences of the condition with mild to moderate symptoms of abdominal pain and diarrhea most of which were due to poor compliance to medication. Seven patients (33%) remained with active Crohn's disease. Nine (12%) patients underwent surgery with resections of some parts of bowel, 2 (2.5%) had steroid side effects, 6 (8%) with perianal Crohn's disease and five (6.5%) with fistulae. CONCLUSION: The epidemiological characteristics of Crohn's disease among Saudi patients are comparable to those reported from other parts of the world. However the incidence of Crohn's disease in our hospital increased over the last 10 years. The anatomic distribution of the disease is different from other world institutions with less isolated colonic affection.

Primary gastric lymphoma.

AIM: The purpose of this review is to describe the various aspects of primary gastric lymphoma and the treatment options currently available. METHODS: After a systematic search of Pubmed, Medscape and MDconsult, we reviewed and retrieved literature regarding gastric lymphoma. RESULTS: Primary gastric lymphoma is rare however, the incidence of this malignancy is increasing. Chronic gastritis secondary to Helicobacter pylori (H pylori) infection has been considered a major predisposing factor for MALT lymphoma. Immune histochemical marker studies and molecular biology utilizing polymerase chain reaction have facilitated appropriate diagnosis and abolished the need for diagnostic surgical resection. Advances in imaging techniques including Magnetic Resonance Imaging (MRI) and Endoscopic Ultrasonography (EUS) have helped evaluation of tumor extension and invasion. The clinical course and prognosis of this disease is dependent on histopathological sub-type and stage at the time of diagnosis. Controversy remains regarding the best treatment for early stages of this disease. Chemotherapy, surgery and combination have been studied and shared almost comparable results with survival rate of 70-90%. However, chemotherapy possesses the advantage of preserving gastric anatomy. Radiotherapy alone has been tried and showed good results. Stage IIIE, IVE disease treatment is solely by chemotherapy and surgical resection has been a remote consideration. CONCLUSION: We conclude that methods of diagnosis and staging of the primary gastric lymphoma have dramatically improved. The modalities of treatment are many and probably chemotherapy is superior because of high success rate, preservation of stomach and tolerable complications.

Esophageal ulceration complicating doxycycline therapy.

AIM: To report present state of iatrogenic drug-induced esophageal injury (DIEI) induced by medications in a private clinic. METHODS: Iatrogenic drug-induced esophageal injury (DIEI) induced by medications has been more frequently reported. In a private clinic we encountered 36 cases of esophageal ulcerations complicating doxycycline therapy in a mainly younger Saudi population (median age 29 years). RESULTS: The most frequent presenting symptoms were odynophagia, retrosternal burning pain and dysphagia (94 %, 75 % and 56 %, respectively). The diagnosis was according to medical history and confirmed by endoscopy in all patients. Beside withdrawal of doxycycline, when feasible, all patients were treated with a proton-pump inhibitor (PPI) and a prokinetic. Thirty patients who reported to the clinic after treatment were improved within 1-7 (median 1.7) days. CONCLUSION: Esophageal ulceration has to be suspected in younger patients with odynophagia, retrosternal burning pain and/or dysphagia during the treatment with doxycycline.

Malignant biliary strictures. Diagnosis and management.

OBJECTIVE: To identify the cause, methods of diagnosis and management of malignant biliary strictures in our institution and compare with studies from other communities. METHODS: From March 1998 through to August 2002, we reviewed 1000 files of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Gastroenterology unit, King Khalid University Hospital in Riyadh, Kingdom of Saudi Arabia for malignant biliary strictures (MBS). Clinical, laboratory data, method of diagnosis and management were recorded. RESULTS: Seventy-two patients (72/1000) with MBS were encountered. Forty one (57%) were males and 31 (43%) were females and the majority were Saudi nationals (82%). Jaundice and right upper quadrant pain were the most frequent symptoms in 84.7% and 52.8% of patients. Cholangiocarcinoma was present in 31 (43%) and pancreatic adenocarcinoma in 23 (31.9%) patients. Other malignancies found included gallbladder carcinoma in 5 patients (6.9%), ampullary carcinoma in 5 (6.9%), metastatic liver carcinoma in 4 patients (5.6%), hepatocellular carcinoma in 2 (2.8%) and lymphoma in 2 (2.8%). The diagnosis was entertained mainly by ERCP (93%). Endoscopic palliation was carried out in 77.8% of patients, percutaneous transhepatic drainage in 13.9% and surgery in 6 (8.3%). The mean survival was higher for the endoscopic compared to the percutaneous transhepatic and surgery groups (6.9 +/- 4.13, 4.27 +/- 4.29 and 3.67 +/- 2.65 months). CONCLUSION: In non-resectable tumors, ERCP is the optimal method of diagnosis and palliation of MBS.

Lack of association of coronary artery disease with H.pylori infection.

OBJECTIVE: It has been suggested from previous studies that there is an associated increased risk of coronary artery disease (CAD) in patients with Helicobacter pylori (H.pylori). However, others dispute this. We therefore evaluated this hypothesis in a group of patients with confirmed H.pylori infection. METHODS: A total of 158 patients with dyspeptic symptoms were evaluated by esophago-gastro-duodenoscopy (EGD) in King Khalid University Hospital in Riyadh, Kingdom of Saudi Arabia from May through to June 1997. Endoscopic biopsies and histology as well as culture and serology for H.pylori were obtained. In patients with confirmed H.pylori a further analysis was performed looking at associated (CAD) or known risk factors for CAD. RESULTS: Among the 158 patients who underwent EGD, 143 patients (90.5%) were found to have H.pylori either by culture, histology or serology, or both in a percentage of (31.5%) (77.6%) and (60.8%). There was no evidence of CAD in this group of patients based on history, electrocardiogram (ECG), echocardiography, ECG stress test, dypiridamole thallium scan or coronary angiography. Other known risk factors for CAD were cigarette smoking (12.6%), diabetes mellitus (10.5%), hypertension (1.4%) and hyperlipidemia (2.8%). CONCLUSION: Helicobacter pylori infection does not increase the risk of CAD, and should not be considered as an independent risk factor for CAD. Further, prospective large trial is needed to confirm our finding.