فهرست مطالب کامران غفارزادگان

There are no data on familial aggregation of colorectal cancer (CRC) in northeastern Iran. The aim of this study was to determine the prevalence of early-onset CRC and patients suspected for hereditary non-polyposis colorectal cancer (HNPCC) based on the clinical criteria in this area.
Documents were collected from two hospitals in Mashhad regarding 326 inpatients during 2013-2015. Demographics, clinical, and tumor-related features were recorded. Interviews were done to identify cancer in the family up to second-degree relatives.
326 patients with CRC (48.5% male) were evaluated. The mean age at diagnosis was 55.44±14.85 years, with 91 patients (27.9%) below 45 years old. Eleven (3.4%) patients fulfilled the Amsterdam II criteria and 136 (41.7%) patients met at least one criterion of the revised Bethesda guideline. There was no difference between early- and late-onset CRC regarding the frequency of CRC in 1st degree relatives or tumor site (p=0.73, p =0.64). However, CRC in second-degree relatives and cases suspected for HNPCC were more common in early-onset of the disease (p =0.022, p =0.024). The patients who fulfilled the Amsterdam II criteria had lower mean age and higher frequency of proximal cancer (p =0.03, p =0.048).
As CRC is common in the young population and CRC clustering and patients suspected for HNPCC are also frequently encountered, measures should be taken to CRC screening policy and genetic studies in this area.

Interferon beta is one of the most common treatments to prevent relapses in multiple sclerosis. is hepatic injury is one of the major complications of Interferon beta but rarely can result in Autoimmune Hepatitis. Case report: This is a case report of a 18 years old lady, who received interferon beta for treatment of multiple sclerosis and presented by jaundice and maculopapular itchy skin lesion that was hospitalized in gastroenterology department. Liver biochemistry tests revealed acute hepatitis (alanine and aspartate aminotransferase elevation and hyperbilirubinemia).Other causes of acute hepatptis were excluded. Biopsy of Liver consistent with Autoimmune Hepatitis. Beta interferon was discontinued and oral steroid was started that led to complete resolution. This report has shown that particular attention must be paid side effects of beta interferon is necessary in the clinical practice.

P53 is mutated in more than 50% of solid tumors and has been changed in 30-40% of endometrial cancer which is the most common malignancy of the genital tract of women and this change is associated with papillary serous cell type and advanced stage and poor prognosis. In addition، the overexpression of BCL2 and tumor angiogenesis is important in the prognosis of patient. Therefore، this study was performed with aim to evaluate the expression of BCL2 and P53 and angiogenesis in endometrial cancer and its relationship with clinicopathological characteristics and the factors affecting the prognosis of disease.

In this retrospective longitudinal study which was performed during 2005-2014، 30 files of patients with endometrial cancer in three different hospitals (Imam Reza، Ghaem، Omid) were collected. The pathology samples were immunohistochemical staining in terms of Bcl2 and P53 markers and angiogenesis and the association of these markers with factors affecting the prognosis and recurrence of disease were investigated. Log rank، t-test and Chi-square tests were used to analyze the data and P.

P53 expression was positive in 9 cases of 10 patients (90%) with non-endometrial cancer and all patients (100%) were negative in terms of Bcl2 and angiogenesis was severe in 8 cases of 10 patients (80%) with non-endometrial cancer and in 6 cases of 20 patients (30%) with endometrial cancer. There was significant relation between tumor histology and tumor grade and stage of the disease and survival (P = 0. 002).

Since there is relationship between genetic markers with stage and grade of disease and also survival of the patients، it is better that the related block be evaluated in terms of these markers at the time of pathological diagnosis of endometrial cancer.

According to the epidemiological studies, manifestations of chronic inflammatory bowel diseases (IBD) are different in various parts of the world. Calprotectin, a complex of two S100A8 and S100A9 proteins, is one of the major mediators of inflammation in patients with inflammatory bowel disease. This study was aimed to investigate the genetic single nucleotide polymorphism (SNP) of calprotectin in ulcerative colitis and crohn’s disease patients and its association with the disease behaviors. One hundred and sixty six patients with inflammatory bowel disease (ulcerative colitis or crohn’s disease) were included in the study. A volume of 2 mL venous blood samples were collected and DNA samples purified. The target regions of calprotectin genes, including S100A8 (rs3806232) and S100A9 (rs3014866) were amplified by polymerase chain reaction (PCR) method. The relationship between polymorphism of calprotectin and age, sex, extension, flare, disease severity (according to the administered drugs), extra intestinal manifestations (arthritis, primary sclerosing cholangitis, eye and skin involvement), dysplasia, colon cancer and were evaluated. Analysis of data showed that CT genotype of S100A9 and TT genotype of S100A8 were the most common genotypes (P < 0.05). Majority of patients with arthritis showed CC genotype of S100A9 (P < 0.05). No significant differences were observed between the age, sex, incidence of extra intestinal manifestations and calprotectin genotype. TT genotype of S100A8 gene had a significant relationship with patients received the second-line drugs including corticosteroids and azathioprine (P < 0.05). Although, a significant association was not observed between patients with 1 to 2 flare in a year and calprotectin genotypes in our study, but 3 times annual flares were significantly more common in CC genotype of S100A9 gene than the other genotypes (P < 0.05). Our study results suggest genetic polymorphisms of calprotectin could affect IBD features including disease severity (based on the drugs needed to control the disease), extra intestinal manifestations (arthritis) and disease flare. This is, to our knowledge, the first investigation on the genetic polymorphisms of calprotectin in the inflammatory bowel diseases. Further investigation is really needed to confirm the role of calprotectin genotypes in the development of inflammatory bowel disease and their relationships with disease activity and features.

Ovarian cancer is often diagnosed at an advanced stage and evaluation of the various factors for early diagnosis of this cancer is highly valuable. This study was performed with the aim to evaluate the expression of HER-2/neu and P16 in epithelial ovarian tumors and its correlation with clinicopathologic variables. This descriptive-analytic and cross-sectional study was performed on 50 paraffin blocks of epithelial ovarian tumors obtained from the archives of pathology department of Mashhad Omid and Ghaem Hospitals during 2007 to 2013. After cutting the blocks، appropriate slides were prepared and immunohistochemical expression pattern of them، the slides were interpreted by an experienced pathologist. The study variables included patient''s age، disease stage، histological type of tumor، expression or non-expression of HER2-neu and P16 and survival of patients. The data related to the patients were extracted from the files available in department of Oncology، Ghaem Hospital. Data was analyzed using SPSS software (version 11. 5) and Kruskal-Wallis، Mann-Whitney، T-test and chi-square test. In this study، most common epithelial ovarian tumor was serous adenocarcinoma (64%). P16 was expressed in 32% of tumors، and its expression was associated with disease stage and overall survival of the patients (P = 0. 001، P = 0. 04). HER-2 was expressed in 28% of cases. Its expression was associated with histological type of tumor (P = 0. 03). But، no relation was observed between its expression and overall survival of the patients (P = 0. 07) and disease stage (P = 0. 70). With regard to significant relation of P16 expression with disease stage and overall survival of the patients، P16 expression is considered as a predictive factor of overall survival and disease stage. While، expression of HER-2 cannot be used as a prognostic factor of overall survival.

Hepatitis B and C infections have remained major global health burdens during the most recent century. The viral agents responsible for these diseases share common modes of transmission with human immunodeficiency virus (HIV) such as needle-sharing in IV drug abusers. Coinfection of hepatitis B or C with HIV increases the rate of progression of chronic liver disease. Given the lack of data in Iran, in particular Khorasan Razavi Province, with regards to this coinfection, the present study evaluates the frequency distribution of hepatitis B and C coinfection with HIV infection and their modes of transmission. This was a retrospective study based on available data at the Gastrointestinal and Liver Diseases Center, Emam Reza Hospital, Mashhad, Iran. We used questionnaires to collect demographic data from 749 patients infected with hepatitis B or C who refered to this clinic between 2005 and 2008. The available sera of these patients were tested for the coexistence of HIV infection with hepatitis B or C infections. The results were analyzed with SPSS version 16 software. From 749 patients infected with hepatitis B or C viruses, 650 were infected with hepatitis B (64.9% male and 35.1% female). There was no HIV antibody detected in any of the patients'' sera who had hepatitis B infection. Among the 106 patients with hepatitis C infection (84% male and 16% female), only one (0.9%) who was an IV drug abuser tested positive for HIV infection. Hepatitis B/hepatitis C coinfection was found in 7 (0.9%) patients. With regards to the risk factors of viral transmission among those with hepatitis B infection, the most common was a positive family history of hepatitis B (37.2%). Other risk factors in order of decreasing frequency included a history of venesection and tattooing (13.8%), transfusions (7.1%), IV drug abuse (2.6%), needle stick accidents (2.3%), and high-risk sexual activity (0.6%). In those with hepatitis C infection, a history of IV drug abuse was the most common risk factor (40.6%), followed by a history of transfusions (28.3%), venesection or tattooing (16%), surgery (13.2%), needle stick accidents (4.7%), hepatitis C infection in a family member (2.8%), and unsafe sexual contact (0.9%). There was a significant difference in the transmission risk factor ratio between hepatitis B and C patients (p=0.001, χ2=261/590) The most common risk factor for transmission of hepatitis B and C infections in patients who presented to Emam Reza Hospital, a referral center in Mashhad, was a positive family history of hepatitis B infection and IV drug abuse, respectively. The prevalence of HIV coinfection amongst patients with hepatitis B or C infections was low. However, further studies with larger populations are required.

The aim of this case report was to show how acommon oral condition, such as recurrent aphthous stomatitis, could be the only clinical sign leading to early diagnosis of celiac disease. Case Report: A recurrent oral ulcer was detected by a physician during examination of a 23-year-old young woman complaining of severe weakness and inability to intake foods orally. The patient was visited in oral medicine department and a major aphtous ulcer was diagnosed by an oral medicine specialist. An interesting finding was presence of gastrointestinal manifestations which exacerbated with oral ulcers. The patient was evaluated by gastroenterologist and diagnosis of celiac disease was established by laboratory findings and small intestine biopsy which showed a strong atrophy of the intestinal villi which confirmed diagnosis of celiac disease. After six months on a gluten-free diet, no evidence of oral ulcers was found. At the time of submission of this paper, the patient was in a good health status. Oral medicine specialist has a fundamental role in diagnosing syndromes associated with apthous ulcers. Appropriate referral by other health care providers can help in early diagnosis and prevent long term complications of celiac disease. However, the importance of investigating systemic anomalies in cases with aphtous ulcers should be emphasized.

Nodular regenerative hyperplasia is a rare cause of portal hypertension. Clinical findings are consist of complication of portal hypertension such as variceal bleeding. Histopathology is key of diagnosis. Case report: Patient was a 44 years old woman with a chief complaint of flank pain and easy bruising. She had a history of hematemesis many years ago. In physical examination، she had huge splenomegaly and ecchymoses on lower extrimities. Lab data are normal except for pancytopenia. In upper endoscopy، esophageal varices and portal hypertensive gastropathy were seen. Subsequently، she was found to have nodular regenerative hyperplasia on liver biopsy. Esophageal varices banded successfully and she was asymptomatic on Beta blocker after wards. Nodular regenerative hyperplasia should be considered in the differential diagnosis of any patient with portal hypertension without cirrhosis.

The improvement of knowledge in the field of molecular genetics and diagnostics of breast cancer can help us better to understand the biological process that leads a normal breast cell to be transformed into a malignant one with invasive and metastatic confidants. The aim of this study was to introduce the Relative Quantitative Real-time PCR technique based on sybr green dye for relative quantification of progesterone receptor A (PR-A) gene expression in normal and malignant neoplasia in human breast tissue. 20 malignant samples (Grad 2) and 10 normal samples of human breast tissue were collected before treatment and without contamination. After RNA extraction and cDNA synthesis, PR-A and GAPDH genes for measurement of relative quantification were amplified by Real-time PCR according to the standard method. The obtained Ct value were analyzed by SDS version 1.4 software, GLM program and T-test student procedure were performed in SAS version 9.1 software to determine statistical significance. PR-A gene can be expressed as in both normal and malignant breast tissue but expression of PR-A gene in malignant breast tissue was over expressed than normal cases (p≤0/05). The statistical significance difference test for comparing of PR-A gene expression in malignant breast tissue to the mean of normal samples showed an increased in 70 percent of samples. Also there was no significant correlation between over expression of PR-A gene and marital status and menopause (p ≤0.05). Furthermore, results indicated a linear correlation was between expression of PR-A gene and the age of cancer patients (p ≤0.05). PR-A gene can be used as a biomarker for prognosis, screening and diagnosis of malignant patients against normal persons at the beginning stages of breast cancer.

Colorectal cancer is one of the most common forms of cancer in the world. Amongseveral genetic events which have been documented in colorectal tumour progression, K-ras hashigh diagnostic value. Studies have shown that K-ras mutations are found in 20-50% of all coloncancers mostly in codons 12 and 13, and less frequently in codon 61.The aim of the present studyis to identify K-ras gene mutations in codon 13 in CRC patients among the East-North of IRAN, and toassess whether they are linked to the clinicopathological parameters. Tumorsamples were collected from a consecutive series of 54 patients undergone respective surgery for CRC.DNA was extracted from tumour and RFLP-PCR was applied for codon 13 mutation detection.The results reveal that 18.51% of the patients (10/54) have the mutation in the K-ras gene-codon 13. In the present study, K-ras mutations were significantly associated with CRC stage (P <0.05). No significant correlations were found between the mutations and sex, grade and tumor location.Conclution: The research shows that mutations in K-ras gene-codon 13 have a significant role in tumor type cell progression in CRC patients; therefore, screening for K-ras mutations appears to have a high prognostic value for evaluating of the risk of the tumor progression.

IntroductionCoeliac disease (CD) is an autoimmune enteropathy triggered by gluten. Several hepatic disorders have been described in association with coeliac disease. Nodular regenerative hyperplasia (NRH) of the liver is a rare disorder and is a cause of non-cirrhotic portal hypertension.Case reportA 22 y/o lady presented with portal hypertension, after all causes of chronic liver disease ruled out we checked for coeliac and it was positive. Liver biopsy was done and was compatible with nodular regenerative hyperplasia (NRH) of the liver. ConclusionAs far as we know this is one of the rare cases of nodular regenerative hyperplasia of the liver in a patient with coeliac. Only three cases have been reported until now and seems we should think about coeliac in any patient suffering from chronic liver disease with unknown cause.

Introduction & Chronic ulcer is a significant problem in patients referring to dermatologists and plastic surgeons. Diabetes delays or impairs wound healing. Fifteen percent of diabetic patients have lower extremities ulcer with high morbidity. Retinoic acid is a vitamin A derivative which has significant effect on cellular proliferation and connective tissue extra cellular proteins differentiation. Our purpose in this study was to observe the effects of tretinoin on wound healing. This study was a case-control study performed on 48 Wister male rats. The rats were made diabetic and then divided into two groups. We induced a full thickness wound on back of all rats. The wounds were treated with 0.1% tretinoin lotion once daily in the case group and with normal saline in the control group. Both groups were examined macroscopically and histological on the 5th, 10th, and 15th days. At last, the data was analyzed by ANOVA and t- student statistical tests. In the macroscopic evaluation on the 5th and 10th days, wounds that were tretinoin treated, healed more rapidly than that of the control (P=0.002, P=0.001), but on the 15th day, this effect was not significant (P=0.212). At the histological level on the 5th day an increase was observed in the granulation tissue, epidermal thickness and collagen density but it was not significant(P=0.417, P=0.999, P=0.470). On the 10th day, this increase was rather observable, but not significant (P=0.400, P=0.999, P=0.999). According to our findings, topical tretinoin treatment improves wound healing in diabetic ulcers.

IntroductionUlcerative colitis (UC) and Crohn’s disease (CD), collectively referred to as inflammatory bowel disease (IBD), present with different histology and cytokine profiles. While the precise mechanisms underlying the development of IBD are not known, sufficient data have been collected to suggest that it results from a complex interplay of genetic, environmental, and immunologic factors. An inappropriate mucosal immune response to normal intestinal constituents is a key feature, leading to an imbalance in local pro- and anti-inflammatory cytokines. Neutrophil and monocyte influx occurs with subsequent secretion of oxygen radicals and enzymes, leading to tissue damage. Case reportHere we report three patients with sever symptom of IBD after ovarian stimulation.ConclusionCytokine profile after ovarian stimulation may contribute to the altered intestinal permeability due to increase in systemic inflammatory cytokines and neutrophil or macrophage activation. In our hypothesis ovulation induction can induce inflammation in intestinal mucosa or exacerbate previous IBD by different cytokines.

Restrictive cardiomyopathy defined by increased ventricular wall stiffness and impaired LV filling and heart failure symptoms. This type of cardiomyopathy occurs with lower frequency relative to the dilated and hypertrophic cardiomyopathies. IRCM in 50% is idiopathic and in 50% is secondary to specific clinical disorders especially amyloidosis. Cardiac amyloidosis usually occurs during primary amyloidosis (AL type amyloidosis). Primary amyloidosis is often seen in people with multiple myelomacancer or in the in course of immunocytic dyscrasia. Disease process results from tissue deposition of proteins that have a unique secondary structure. Cardiac amyloidosis is an invariably progressive infiltrative cardiomyopathy that carries a grave prognosis we have presented a case of Cardiac amyloidosis which is a rare clinical disorder. Case report: The Present case was a 46 years old man who admitted for progressive dyspnea and congestive heart failure. Echocardiography revealed increased ventricular wall thickness with small size ventricles, enlarged atria, and a thickened intertribal septum and advanced diastolic dysfunction. Electrocardiography revealed low QRS voltage and normal sinus rhythm. Gingival Biopsy examined by congo Red staining and immunohistochemistry identified specific amyloid proteins. Pathology report confirmed amyloidosis. In patient complaining of progressive congestive heart failure and suspected to have restrictive cardiomyopathy, cardiac amyloidosis should be born in mind.

Renal involvement in systemic lupus erythematosus (SLE) is one of the most serious complications. Numerous reports have documented the unpredictable course of lupus nephritis and the role of renal biopsy in evaluation of individual patients. It is impossible to predict the types, severity and activity of renal lesions based only on combination of clinical and laboratory findings. The aim of this study was to evaluate the histological findings, activity and chronicity scores, and also assessing the correlation between histology and other laboratory findings in patients with lupus nephritis. This cross-sectional study was carried out on 40 patients with diagnosis of lupus nephritis at Ghaem Hospital in Mashhad during 2003 to 2006. Renal biopsy was performed for all patients and correlation between laboratory and serologic parameters and the histological findings were investigated. Data were analyzed using t-test, Chi square test, and Fischer exact test. Activity score was 9.02 in 34 patients with proteinuria and 6.33 in 6 patients without proteinuria (p=0.018). There was a significant correlation between the activity score and serum C4 levels (p=0.031). Also, a significant correlation was shown between fibrous crescent (one of the chronicity criteria on biopsy) and nephrotic syndrome (p=0.047). No significant correlation between activity and chronicity scores and other laboratory and serologic findings was found. Based on our data, no exact correlation between histological findings and laboratory data in lupus nephritis was demonstrated therefore, emphasis on important role of renal biopsy in evaluation of these patients is suggested.

Pyogenic Granuloma is a tumorlike lesion of oral cavity that is considered to be non-neoplastic in nature and arises in response to local irritation. Most studies show that this lesion is more common in women than men, possibly because of the vascular effects of female hormones. The purpose of this study was to evaluate the expression of estrogen and progesterone receptors in pyogenic granuloma in pregnant, non-pregnant women and men compared with normal mucosa by immunohistochemistry.

In this study, cross-sectional analytical 36 paraffin blocks of pyogenic granuloma samples (12 samples of pregnant women, 12 samples of non-pregnant women, 12 samples of men and 9 samples of normal mucosa) were obtained from O.M.F pathology department of Mashhad Dental School. 4 micron sections were prepared and stained by immunohistochemistry staining(Based on Dako factory instruction). After immunostaining, estrogen and progesterone receptors expression in three areas including epithelium, inflammatory and mesenchymal cells were evaluated. The data were analyzed by fisher's exact test.

After comparing the expression of estrogen receptors in epithelium(P=0.1), inflammatory cells(P=0.184), mesenchymal cells(P=0.316) in studied groups, no statistically differences were found. Expression of progesterone receptors was not seen in epithelium of any samples and it’s expression in inflammatory and mesenchymal cells was poor(P=0.19,P=0.547).

Although estrogen and progesterone receptor expression was observed in pyogenic granulomas of oral mucosa in pregnant, non pregnant women, men and normal mucosa, it did not seem to play an important role in pathogenesis of this lesion or these hormones may have put on effect by other mechanisms other than binding to specific receptors.

Adenocarcinoma of the stomach was the leading cause of cancer-related death worldwide through most of the 20th century. Usual presentations of gastric cancer include anorexia, epigastric pain or discomfort and weakness. Rarely, patients present with unusual clinical manifestations. In this article, we report two cases with uncommon presentations of gastric adenocarcinoma. The first patient was a 52-year-old male presented with testicular mass, and the second case was a 51- year-old female presenting with diffuse bone pain, petechiae and purpura on the skin of abdomen. In the first case, the initial pathologic specimen was provided from testicular mass (orchiectomy) and for the second case, bone marrow biopsy was done. The initial reports for these cases were seminoma and metastatic signet ring carcinoma, respectively. Chemotherapy was done for both.Gastric adenocarcinoma rarely presents with unusual clinical manifestations. Chemotherapy in one out of two cases showed good palliative results.

Breast cancer is one of the main causes of cancer fatality in women. Among Iranian females, it is the most common cancer which tends to affect younger ones. Molecular biomarkers such as steroid receptors, HER2/neu and p53 are valuable in evaluation the clinical course, prognosis and treatment decisions. However their prognostic role in Iranian patients has not been explained completely. The correlation of mentioned factors with survival of breast cancer has been assessed in this study. IHC staining for steroid hormone receptors, HER2/neu and p53 in 339 breast cancer patients diagnosed between 2000- 2006 was done. All cases were followed up to March 2007 and the significance of biomarker status for prognosis was analyzed. Of the 339 studied patients, 46.6%, 43.8%, 51.7% and 36.1% were positive for ER, PR, HER2/neu and p53 respectively. ER considerably correlated with PR (P = 0.000). There was a similar relation between HER2/neu and p53 (P = 0.041) as well HER2/neu and ER (P = 0.001). Survival analysis detected no correlation between molecular biomarkers and recurrence free survival. The presented pattern of prognostic role of these biomarkers is explained partly by demographic factors. Since no similar study has been conducted in this region, larger studies in the basis of demographic variables are suggested.

Prolactin exists in 3 different molecular forms, i.e., monomeric, big and at times big big (macroprolactine) in human serum. Macroprolactine is a complex of prolactine and IgG and may account for a significant proportion of idiopathic hyperprolactinemia. Its biological activity is considered low or absent, but it is measured by the common immunoassay method, thus can lead to expensive explorations and ineffective treatments. Conventionally the diagnosis of macroprolactinemia has been done by Gel Filtration Chromatography, which cannot be used routinely. Recently Poly Ethylene Glycol has been employed to precipitate macroprolactine, allowing its rapid detection, dependably and inexpensively. The objective of the present work is to assess the incidence of macroprolactinemia in patients with hyperprolactinemia, by its identification with PEG, and to establish the clinical (galactorrhea and oligomenorrhea) and radiological findings (sella MRI) of such a cohort. 50 patients with hyperprolactinemia were investigated for macroprolactine. Prolactine was measured before and after precipitation of macroprolactine by PEG, with recovery of <= 40% taken as indicating significant macrorprolactinemia. Macroprolactine was found in 14(28%) patients. In true hyperprolactinemic patients (36 patients) galactorrhea occurred in 59.4%, and oligomenorrhea occurred in 65.6% of patients, but in macroprolactinemic patients, galactorrhea occurred in 8.3% and oligomenorrhea occurred in 25% of patients. Also normal pituitary images were found in 41.2% of patients who had true hyperprolactinemia and in 85.7% of patients with macroprolactinemia.

Porokeratosis of Mibelli is a keratinization disorder due to cellular clones that show different degress of dysplasia. Sometimes, these lesions develop on the previously traumatized or burnt skin. Herein, a 24 – year- old female patient is presented with three facial skin lesions on her right cheek on a previous old scar due to cutaneous leishmaniasis is presented. The larger lesion was an erythematosquamous plaque with a well – defined hyperkeratotic margin and an atrophic center and two smaller erythematosquamous papules were located about 1.5 centimeter away from the main lesion. In the histopathologic evaluation of the skin biopsy of the patient, hyerkeratosis, irregular acanthosis and the characteristic column of parakeratotic cells (cornoid lamella) were evident. Considering clinical appearance of the lesion as well as the histopathologic findings, the patients was diagnosed as case of porokeratosis of Mibelli that was developed on an old scar due to cutaneous leishmaniasis.