Esophagitis may not be a major precursor lesion for esophageal squamous cell carcinoma in a high incidence area in north-eastern Iran

Esophageal squamous cell carcinoma [ESCC] is usually detected in advanced stages resulting in a very poor prognosis. Early diagnosis needs identification of clinically releveant precancerous lesions which could become the target of screening and early treatment. Our aim was to check whether esophagitis could serve as a relevant histological precursor of ESCC in Northern Iran. During 2001-2005, all adult patients who were referred to Atrak clinic for upper gastrointestinal endoscopy and biopsy were enrolled. Atrak clinic is a major center for upper gastrointestinal cancer research in eastern Golestan. All subjects had been complaining of upper GI symptoms and were under further investigation to rule out cancer. Biopsies from the endoscopically normal mid-esophagus and also just above the esophago-gastric junction were obtained in all subjects whose esophagus appeared normal during endoscopy and from endoscopically normal appearing mucosa at the proximal vicinity of any detected mass. Microscopic examinations for the verification of the presence or absence of esophagitis was performed by independent histological examination of the samples by two pathologists. All the discrepant diagnoses were resolved in joint diagnostic sessions. During the study period 836 patients were enrolled including 419 non cancer patients [endoscopy clinic controls], 387 cancer patients, and 30 subjects with clinical diagnosis of malignancy referred for histological reconfirmation of diagnosis by repeated biopsy. Mild or marked mid-esophagitis was diagnosed in 39 [9.3%], 47 [12.5%] and 12 [40%] of endoscopy clinic controls, cancer patients and those who were suspicious for upper gastrointestinal malignancies. Our observation does not show evidence for esophagitis to be a predisposing factor for ESCC in Gonbad region In North Eastern Iran

Histopathological study of chronic hepatitis B: a comparative study of Ishak and METAVIR scoring systems

Ishak and METAVIR scoring systems are among the most commonly used histopathological systems to evaluate chronic hepatitis. To assess the level of agreement between these two scoring systems in patients with chronic hepatitis B. Liver biopsy samples taken from 92 patients with chronic hepatitis B were considered as the training set; 57 more biopsy specimens were used as the validation set. In the training set, grade of necroinflammation and stage of fibrosis for each liver biopsy specimen were determined by two expert liver pathologists using both Ishak and METAVIR systems. Inter-observer variability between the two pathologists was evaluated. Biopsy specimens of the validation set were seen and scored by a third expert pathologist. In the training set, criteria were developed to categorize Ishak grading and staging systems separately to best fit with the METAVIR scoring system. The criteria found in the training set, was then tested in the validation set. The level of agreement between the two scoring systems was assessed by weighted kappa statistics. For the training set, agreement between the two pathologists was excellent. Using our proposed criteria in the training set, there was excellent level of agreement in grading [Kappa = 0.89] and staging [Kappa = 0.99] between Ishak and METAVIR systems. In the validation set, the criteria led to substantial correlation [Kappa = 0.61] in grading, and excellent correlation [Kappa = 0.94] in staging between the two systems. Using our proposed criteria, excellent or at least substantial concordance between Ishak and METAVIR scoring systems can be achieved for the degree of both necro-inflammatory changes and fibrosis

[Effect of oral vanadyl sulphate on ultrastructure of pancreatic islets beta cells in streptozotocin-induced diabetic rats]

Considering insulin like effects of vanadium salts, these compounds have been evaluated as a therapeutic agent for treatment of diabetes mellitus in the experimental models of the disease in animals. This study was performed to study the ultrastructrure of islet beta cells in streptozotocin [STZ]- induced diabetes in rats after treatment with vanadyl sulfate [VS]. diabetes was induced in male Wistar rats by intravenous injection of 40 mg/kg STZ. Equal volume of normal saline was injected via lateral tail vein in sham animals. Seven days after injection animals in both groups were divided into treated and control groups. VS was added to the drinking water of the diabetic treated [DT] and Sham treated [NT] animals with a concentration of 0.5 mg/ml for one week and 1mg/ml up to three months. Untreated diabetic [DC] and sham rats [NC] received tap water during this period. Two months later all animals were killed. Langerhans islets were isolated from exocrine parts by use of collagen digestion, and were fixed in glutaraldehyde. Ultrastructure of islet beta cells were studied by means of transmission electron microscope. VS treatment led to amelioration of the symptoms of diabetes including hyperglycemia and polydepsia in DT rats. DC rats remained diabetic during the period of study. No significant changes were observed in plasma glucose and fluid intake of NT animals. Ultrastructural studies of islet beta cells of DT rats showed normal cells with normal chromatin distribution, well-developed rough endoplasmic reticulum, increased cytoplasmic granules and no clear sign of cell injury. Lymphocytic infiltration was not detected in langerhans islets of DT group. Nuclear pyknosis, cytoplasmic vacuolization, lymphocytic infiltration and signs of cell death such as cell necrosis were found in the islets of beta cells of DC rats. Cytoplasm of islets beta cells of NT rats were more granular in comparison to NC rats. Considering the results of this study we concluded that amelioration of diabetes signs in VS treated STZ induced diabetic rats are accompanied by preservation of islets beta cells ultrastructure

[Determination of the normal range of the number of intraepithelial lymphocytes in the duodenal mucosa of healthy Iranian individuals]

An increase in the number of intraepithelial lymphocytes [IEL] in the duodenal mucosa is an important criterion for the histological diagnosis of celiac disease [CD]. We determined the normal range for intraepithelial lymphocytes [IEL] in the second part of duodenum in healthy Iranian population. Four biopsy samples of the endoscopically normal appearing mucosa at the second part of duodenum were obtained from 50 individuals referred to Shariati hospitals [48 for epigastric pain, 2 for esophageal varices]. They had no sign, symptoms and evidence for malabsorption or small intestinal disorders in history, physical examination, Laboratory tests and IgA anti tissue transglutaminase [t.T.G]. Four-micrometer thick sections were stained with Hematoxillineosine [H and E] and immunohistochemistry [IHC] for leukocyte common antigen [LCA]. At least 500-600 cells from the tip and body of villi were counted separately and the number of IEL was given as mean/ 100 epithelial cells. The mean for IEL count in total villi in IHC method was 21/100 [23/100 in tip, 21/100 in body, p = 0.058] and 19/100 in H and E method [19/100 in tip, 18/100 in body, p =0.035] [p = 0.006]. Considering total villi, the normal upper limit [Mean+2SD] was calculated to be 35/100 in IHC and 34/100 in H and E stained sections and normal upper limit of confidence interval [the 95 percentile] was 39/100 in IHC and 37/100 in H and E stained sections. The villus height to crypt depth ratio was 3/94 in average. Respectively in IHC and H and E methods, the amounts equal or less than 35/100 and 34/100 are considered as normal., values between 35-39/100 and 34-37/100 as border line and counts more than 39/100 and 37/100 represent a pathology. Although the difference between two staining methods was statistically significant, considering cost effectiveness, we recommend H and E staining for routine clinical practice

[Case report: calcified pancreatic tumor in a 41 year-old male]

Endocrine tumors of the pancreas [Islet-cell tumors] are rare with neuroendocrine origin. The patient was a 41- year- old man, admitted with chief complains of epigastric mass feeling, dull abdominal pain, lack of appetite and weight loss up to 2-3 kg since 6 months ago. In physical examination, a mass was detected in epigaster and left upper quadrant [LUQ]. In abdominal x-ray, a calcified mass was seen in LUQ. For better evaluation, abdominal CT was performed in which, a large calcified mass in pancreas tail was reported. Finally, by means of immunohistochemical markers, the neuroendocrine carcinoma of the pancreas was confirmed. In spite of the rareness of calcification in these tumors, it is also necessary to consider malignancies when encountering a large calcified mass in pancreas

[Familial risks of esophageal cancer in the Caspian Littoral of Iran]

In northeastern Iran there is an area of high incidence of esophageal cancer which is populated by residents of Turkmen ancestry. Several environmental risk factors for esophageal cancer have been proposed, but the roles of familial and genetic factors have not been studied extensively in the Turkmen population. We evaluated the importance of familial risk factors for esophageal cancer by performing a case-control study of 167 cases of esophageal squamous cell carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the cases and controls were constructed, which documented all cancers in first- and seconddegree relatives. The actuarial risk of cancer was then estimated in 2097 first-degree relatives of cases and 2783 first-degree relatives of the controls. A hazard ratio was constructed, based on a comparison of the two cumulative incidence curves. The risk to age 75 of esophageal cancer in the first-degree relatives of Turkmen patients with esophageal cancer was 34%, versus 14% for the first-degree relatives of the controls [hazard ratio = 2.3; p = 3 x 10[-8]]. 9.6% of the cases reported that their parents were related, versus 2.5% of the controls [odds ratio = 4.1; p -value = 0.006]. Familial factors are important in the etiology of esophageal cancer among the Turkmen residents of Iran. The hazard ratio of 2.3 for cancer among first-degree relatives is consistent with an important contribution of heritable factors. It will be of interest to perform marker studies to establish which genes are responsible

[Familial risks of esophageal cancer in the caspian littoral of Iran]

In northeastern Iran there is an area of high incidence of esophageal cancer which is populated by residents of Turkmen ancestry. Several environmental risk factors for esophageal cancer have been proposed, but the roles of familial and genetic factors have not been studied extensively in the Turkmen population. We evaluated the importance of familial risk factors for esophageal cancer by performing a case-control study of 167 cases of esophageal squamous cell carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the cases and controls were constructed, which documented all cancers in first- and second degree relatives. The actuarial risk of cancer was then estimated in 2097 first-degree relatives of cases and 2783 first-degree relatives of the controls. A hazard ratio was constructed, based on a comparison of the two cumulative incidence curves. The risk to age 75 of esophageal cancer in the first-degree relatives of Turkmen patients with esophageal cancer was 34%, versus 14% for the first-degree relatives of the controls [hazard ratio = 2.3; p = 3 x 10[-8]]. 9.6% of the cases reported that their parents were related, versus 2.5% of the controls [odds ratio = 4.1; p -value = 0.006]. Familial factors are important in the etiology of esophageal cancer among the Turkmen residents of Iran. The hazard ratio of 2.3 for cancer among first-degree relatives is consistent with an important contribution of heritable factors. It will be of interest to perform marker studies to establish which genes are responsible

[Ecologic study of serum selenium and upper gastrointestinal cancers in Iran]

Both observational and experimental studies have shown that higher selenium status reduces the risk of upper gastrointestinal cancers in selenium deficient populations. Recent cancer registry data have shown very different rates of esophageal cancer [EC] and gastric cancer [GC] in four provinces of Iran, namely Ardabil, Mazandaran, Golestan, and Kerman. The aim of this study was to have a preliminary assessment of the hypothesis that high rates of EC in Golestan and high rates of GC in Ardabil may be partly attributable to selenium deficiency. We measured serum selenium in 300 healthy adults from Ardabil [n=100], Mazandaran [n=50], Golestan [n=100], and Kerman [n=50], using inductively coupled plasma, with dynamic reaction cell, mass spectrometry [ICP-DRC-MS] at the US Centers for Disease Control [Atlanta, Georgia]. The median serum selenium concentrations were very different in the four provinces. The medians [IQR] for selenium in Ardabil, Mazandaran, Golestan, and Kerman were 82 [75-94], 123 [111-132], 155 [141-173], and 119 [110 -128] micro g/L, respectively [p<0.001]. The results of linear regression showed that the province variable, by itself, explained 76% of the variance in log selenium [r2=0.76]. The proportion of the populations with a serum selenium more than 90 micro g/L [the concentration at which serum selenoproteins are saturated] was 100% in Golestan, Kerman, and Mazandaran but only 29% in Ardabil. Our findings suggest that selenium deficiency is not a major contributor to the high incidence of EC seen in northeastern Iran, but it may play a role in the high incidence of GC in Ardabil province

[Prevalence of Celiac disease in north of Iran: Screening of an adult population in Sari]

Background and Objective: studies about the prevalence of Celiac disease [CD] in western Asian countries are scarce and there is only one study on the prevalence of CD in healthy blood donors in Iran. The aim of this study is to determine the prevalence of CD in general population of the city of Sari in north of Iran

Materials and Methods: this was a descriptive study and the blood samples were obtained from 1438 person from general population [686 males, 752 females: Mean age 35.5 range 18-66 year] of the Sari which were selected by stratified randomized sampling method during 2003. Total serum IgA was measured in all and IgA-deficient cases were excluded. From this study all cases were analyzed for IgA tissue transglutaminase antibody [Human recombinant tTG]. All persons who had a positive serology for tTG-Ab underwent small intestinal biopsy. The biopsy samples were classified according to modified Marsh criteria

Results: all of the samples had normal total IgA. 13 cases showed positive IgA-tTG Ab [6 males and 7 females, mean age 37.5 yrs]. All subjects with positive serology except one of them were found to have small bowel biopsies compatible with gluten sensitive enteropathy. One of 13 had Marsh 0, 8/13 Marsh I, 3/13 Marsh II and 1/13 showed Marsh IIIa lesion

Conclusion: the minimum prevalence of gluten-sensitivity among general population in north of Iran is 1/120. This data confirms our study on healthy blood donors, which has published previously and is like of prevalence of Celiac disease in western countries. So Celiac disease is not a rare disease as it thought before in this area

Histological and immunohistochemical study of pancreatic islet beta cells of diabetic rats treated with oral vanadyl sulphate

Vanadium salts have been suggested as a possible therapeutic agent for the treatment of diabetes. The aim of the present study was to clarify histological and immunohistochemical changes that occur in the pancreatic [beta] cells of vanadyl sulphate [VS]-treated streptozotocin [STZ] induced diabetic rats. Male Wistar rats were made diabetic by injecting a single intravenous dose of STZ [40 mg/kg] and were divided into two groups seven days after STZ injection. In the first group VS was administered via drinking water at a concentration of 1 mg/mL and treatment was maintained until normoglycemia appeared [DT]. A second group of diabetic animals received distilled water for the same period and were considered as control diabetic [DC]. One group of animals [NC] was injected intravenously with the same amount of vehicle as the diabetic rats and was considered as non-diabetic control. VS treatment was accompanied by amelioration of the signs of diabetes in DT rats while DC animals remained diabetic during this period. Hemotoxylin - Eosin stained pancreatic sections of DC rats showed a decrease in the number and size of islets and a disruption in their architecture. In DT rats the histological appearance of the islets was normal, their shape and size being within normal limits. In horseradish peroxidase procedure [using guinea pig antiserum to insulin as primary antibody] performed on pancreatic islet paraffin sections of rats, insulin immunoreactivity was found in the majority of the islets in DT rats while in the islets of DC rats immunoreactivity was rare. The results of this study indicated that amelioration of diabetes in vanadyl sulphate treated diabetic rats was accompanied with well preservation of islet structure and insulin immunoreactivity

Gastric strongyloidiasis

Involvement of the gastric antral mucosa by Strongyloides stercoralis is reported in a 55-year-old female with adult onset diabetes mellitus. Her symptoms were dyspepsia and non-specific epigastric pain. Observation of the larvae of this parasitic helminth in sites other than the small intestinal mucosa has been previously reported in disseminated forms, in patients with underlying disabling disease or immunosuppression. Few reports are available on the infestation of the gastric mucosa. Involvement of this anatomic site may be attributed to achlorhydria and/or her diabetes mellitus. It is concluded that S. stercoralis infection should be considered as a potential cause of upper gastrointestinal symptoms in tropical and sub-tropical areas