Mohammad H. Derakhshan

Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran

Background/Aims: Ardabil Province, in northwestern Iran, has the highest rate of gastric (predominantly cardia) adenocarcinoma in Iran. This study aimed to investigate the feasibility of endoscopic screening and to look for associated Helicobacter pylori infection and gastric precancerous lesions. Methods: One thousand one hundred and five adult volunteers, residents of Ardabil and Meshkinshahr, districts, 40 years old and above were selected and invited by a simple random household canvass in rural and urban locations. Informed consents were obtained and upper gastrointestinal video endoscopy was performed to biopsy all visible lesions and standard sites in the antrum, corpus, and cardia Results: One thousand and eleven of the invited individuals agreed to participate, including 494 men and 517 women, with a mean (SD) age of 53.32 (10.39) years. Endoscopy was well tolerated by all subjects; 96.7% of antral and 80.7% of cardia mucosal biopsies were satisfactory. The urease test or histology for H pylori was positive in at least 89.2% of subjects. Histological evidence of mucosal atrophy was seen in 39.3% of antral and 21.9% of cardia samples. Chronic gastritis with or without activity, reactive atypia of glandular epithelium, intestinal metaplasia, dysplasia, and cancer were found in 95.1%, 38.0%, 8.7%, 0.2%, and 0.3% of antral and 85.3%, 22.9%, 3.8%, 0.3%, and 0.1% of cardiac biopsies, respectively. Conclusion: Endoscopic screening for upper gastrointestinal diseases was feasible and well tolerated in Ardabil, Iran. Most subjects showed H pylori infection. Atrophic gastritis, reactive atypia, and intestinal metaplasia were common in antrum, corpus, and cardia subsites.

Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach. Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin. Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II <2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer.

Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females

Background and aims: Upper gastrointestinal adenocarcinomas show an unexplained male predominance that is more apparent in oesophagus than stomach and in intestinal than diffuse histological subtype. We have conducted a population-based study to determine whether the gender phenomenon is primarily related to the anatomical site or the histological subtype. Method and materials: Of 3270 gastric and oesophageal cancers recorded in the West of Scotland Cancer Registry, 1998–2002, 812 were randomly selected for detailed analysis. The Lauren histological subtype of adenocarcinoma was determined by reviewing 1204 original reports and 3241 biopsies. Results: Analysis included 405 non-cardia cancers, 173 cardia cancers and 209 oesophageal adenocarcinomas. Crude incidence rate of intestinal subtype was higher in males (23.86/100 000 person-years) versus females (9.00/100 000 person-years), giving a male/female (M/F) ratio of 2.65 whereas diffuse subtype was similar for both genders (5.58 vs 5.20/100 000 person-years) yielding M/F of 1.07. The M/F ratios for oesophageal, cardia and non-cardia gastric cancer were 3.5, 2.0 and 1.6, respectively. Multiple logistic regression indicated that the odds of male gender was related to the histological subtype rather than anatomical location (odds ratio 2.6, 95% confidence interval 1.78 to 3.9). Curve fitting of the age-specific incidence of intestinal subtype indicated that similar functions describe the rise in incidence with age in males and in females. However, the age-specific incidence of female intestinal subtype was delayed by 17.3 years. The M/F ratio of intestinal subtype was 3.41 at age <50 years, peaked at 7.86 at age 50–59 years and then showed a progressive decrease after 50–60 years of age. Conclusion: Male predominance of upper gastrointestinal adenocarcinoma is related to the intestinal histological subtype rather than tumour location and is due to marked delayed development of this subtype in females prior to 50–60 years of age.

Central Obesity in Asymptomatic Volunteers Is Associated With Increased Intrasphincteric Acid Reflux and Lengthening of the Cardiac Mucosa

BACKGROUND & AIMS In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma. METHODS We performed a study of 24 healthy, Helicobacter pylori-negative volunteers with a small WC and 27 with a large WC. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. RESULTS The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). CONCLUSIONS Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.

High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran

Background: In the West, the subsite incidence of gastric cancer has changed in recent decades, with cancer of the cardia increasing in incidence and that of the more distal stomach decreasing. NW Iran has a very high incidence of upper gastrointestinal cancer and we have examined the anatomical site specific incidence in this geographical region. Method and materials: Of 33 718 patients who visited our clinic from March 2000 to Jan 2003, 3119 (9.3%) with persistent upper gastrointestinal symptoms underwent upper gastrointestinal fibreoptic endoscopy. Exact tumour site, subsite, and axial view were determined. Demographic data including age, sex, and place of residence were assessed. Using matched data from the cancer registry and endoscopic survey, age standardised rates (ASR) for all subsites were calculated. Results: Upper gastrointestinal cancer was diagnosed histologically in 499 patients (16.0%). The most frequent site was the gastric cardia (126 (25.3%)) followed by the oesophageal body (90 (18.0%)), antrum (82 (16.4%)), corpus (74 (14.8%)), distal oesophagus (57 (11.4%)), gastro-oesophageal junction (47 (9.4%)), and proximal oesophagus (22 (4.4%)). From axial views of the cardia, 51.4% and 6.8% of tumours were found to originate from the lesser and greater curve, respectively. ASR for gastric cancer were 51.2 in males and 15.4 in females. Cardia cancer with ASR of 26.4 in males and 8.6 in females was the major component of gastric cancer. Conclusion: NW Iran is a geographical region with a very high incidence of cardia cancer and with the great majority originating from the right side of the cardia. This suggests a locally acting luminal carcinogen. Studying the aetiology of this cancer in NW Iran is likely to increase our understanding of the rising incidence of this cancer throughout the Western world.

Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected with Helicobacter pylori.

Background: Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion. Aim: To study the association between the pattern of H pylori gastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease. Methods and materials: Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy and H pylori infection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO. Results: Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R2 = 0.62). Conclusion: Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected with H pylori.

Sociocultural and Dietary Practices Among Malay Subjects in the North-Eastern Region of Peninsular Malaysia: A Region of Low Prevalence of Helicobacter pylori Infection

Background and Aim:  The prevalence of Helicobacter pylori infection is exceptionally low among the Malays in the north‐eastern region of Peninsular Malaysia. The reasons are unknown. Our aim was to compare environmental factors that differed in relation to H. pylori prevalence among Malays born and residing in Kelantan.

Mechanism of association between BMI and dysfunction of the gastro-oesophageal barrier in patients with normal endoscopy

Introduction The association between body mass index (BMI) and gastro-oesophageal pressure gradient (GOPG) is incompletely understood. We examined the association between BMI and gastro-oesophageal (GO) barrier function and the effect of mechanically increasing intra-abdominal pressure on GO physiology. Methods (A) 103 dyspeptic patients with normal endoscopy underwent 24 h pH-metry and upper gastrointestinal manometry. Relationships between BMI and acid reflux, intragastric pressure (IGP), GOPG and lower oesophageal sphincter (LOS) pressure were calculated using bivariate correlations. (B) In 18 healthy volunteers, the effects of increasing IGP by abdominal belt on GO manometry were studied. Results (A) There was a linear correlation between BMI and oesophageal acid exposure in erect (R=0.35, p<0.001) and supine (R=0.40, p<0.001) positions. BMI was strongly associated with IGP (inspiration: R=0.66, p<0.001; expiration: R=0.78, p<0.001) and inspiratory GOPG (R=0.50, p<0.001). There were a positive correlation between BMI and inspiratory LOS pressure relative to atmospheric pressure (R=0.29, p=0.016) and a negative correlation with LOS pressure relative to IGP on expiration (R=−0.25, p=0.018). Logistic regression models using all significant manometric variables and relevant interactions revealed marked decline in the magnitude and significance of relationship between BMI and oesophageal acid exposure in supine (from OR 1.12 (95% CI 1.03 to 1.22), p=0.009, to 1.00 (0.86 to 1.17), p=0.999) and upright positions (from 1.11 (1.02 to 1.20), p=0.020, to 1.03 (0.89 to 1.18), p=0.717). (B) Application of the constricting abdominal belt produced similar manometric changes to those associated with increased BMI. However, the belt did not reproduce the reduced LOS pressure relative to IGP. Conclusion The association between reflux and BMI may be largely explained by effects of increased intra-abdominal pressure. However, the reduced LOS pressure associated with BMI may be mediated by another mechanism or effects of chronic rather than acute elevation of intra-abdominal pressure.

Microscopic enteritis: Bucharest consensus

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women

BACKGROUND Adenocarcinomas of the upper gastrointestinal tract (UGI) show remarkable male predominance. As smoking is a well-established risk factor, we investigated the role of tobacco smoking in the male predominance of UGI adenocarcinomas in the United States NIH-AARP Diet and Health Study. METHOD A questionnaire was completed by 281,422 men and 186,133 women in 1995-1996 who were followed until 31st December 2003. Incident UGI adenocarcinomas were identified by linkage to state cancer registries. We present age-standardised cancer incidence rates per 100,000-person years and male/female ratios (M/F) calculated from age-adjusted Cox proportional hazards models, both with 95% confidence intervals (CI). RESULTS After 2013,142-person years follow-up, 338 adenocarcinomas of the oesophagus, 261 of gastric cardia and 222 of gastric non-cardia occurred in men. In women, 23 tumours of oesophagus, 36 of gastric cardia and 88 of gastric non-cardia occurred in 1351,958-person years follow-up. The age-standardised incidence rate of all adenocarcinoma sites was 40.5 (37.8-43.3) and 11.0 (9.2-12.8) in men and women, respectively. Among smokers, the M/F of all UGI adenocarcinomas was 3.4 (2.7-4.1), with a M/F of 7.3 (4.6-11.7) for tumours in oesophagus, 3.7 (2.5-5.4) for gastric cardia and 1.7 (1.2-2.3) for gastric non-cardia. In non-smokers, M/F ratios were 14.2 (5.1-39.5) for oesophagus, 6.1 (2.6-14.7) for gastric cardia and 1.3 (0.8-2.0) for gastric non-cardia. The overall M/F ratio was 3.0 (2.2-4.3). CONCLUSION The male predominance was similar in smokers and non-smokers for these cancer sites. These results suggest that the male predominance of upper GI adenocarcinomas cannot be explained by differences in smoking histories.