Complete Content of this Issue and Cover Content 2 0 0 2015/10/28 1394/8/6 2015/10/28 1394/8/6 ## ##

A prospective Crossover Triple-blind Controlled Trial on the Safety and Efficacy of Iranian Recombinant FVIII (Safacto) versus Plasma Derived FVIII A pilot study 2 2 Background: Considering the increasing number of patients with hemophilia and infrastructure requirements for a comprehensive approach, development of a recombinant factor has become a milestone. The objective of this study was to assess the safety, efﬁcacy and non inferiority of Safacto (Recombinant factor VIII) compared with plasma-derived factor in the treatment of hemophilia A. Methods: 10 patients with severe hemophilia A were enrolled in this study. Each patient was treated by a 40-50 IU/kg infusion of either plasma derived or recombinant factor VIII after initiation of each of 4 consecutive hemarthrosis episodes in a triple-blind prospective crossover permuted block randomizing method. Clinical efficacy scale score and in vivo recovery of factor VIII was assessed in each of the treated bleeding episodes. Any adverse event was also recorded. Results: The mean±SD level of factor VIII in the plasma versus recombinant groups was 111.5±39 and 115±39, respectively without any significant difference. Response scaling method which assessed pain and range of motion revealed equalized scores along with in vivo recovery, hence treatment success rate was comparable in both groups. One non-recurring, mild skin rash reaction occurred simultaneous with the administration of plasma derived factor. Conclusion: Safacto (r-FVIII) is safe and effective and non-inferior to plasma derived factor VIII in the treatment of hemophilia A related bleeding events. 171 174 2015/10/282015/09/9 1394/6/18 P Eshghi P Eshghi H Abolghasemi H Abolghasemi F Malek F Malek M Naderi M Naderi Y Panahi Y Panahi B Habibpanah B Habibpanah E Fatohlahzadeh E Fatohlahzadeh F Gorji F Gorji Hemophilia A Plasma derived factor VIII Recombinant factor Safacto ## ##

Is There any Association between Thyroid Autoimmunity and Breast Cancer? آیا بین اتوایمیونیتی تیروئید و سرطان پستان همراهی وجود دارد؟ 2 2 Background: The relationship between thyroid autoimmunity and breast cancer is a challenging subject. We aimed to investigate this association in women with breast cancer. Methods: In this descriptive study, 41 women with newly diagnosed breast cancer before receiving any pharmacologic treatment and 38 healthy age-matched women were enrolled. Anti TPO Ab (anti-thyroid peroxidase antibodies), FT4 (free thyroxine), T3 (triiodothyronine) and TSH (thyroid-stimulating hormone) were measured in both groups. Results: The mean±SD ages in patients with breast cancer and the control group were 41.71±1.73 and 40.03±1.74 years, respectively (P=0.496). There was no statistically significant difference between the mean values of FT4 and T3 in patients with breast cancer (P=0.447) and the control group (P=0.534). The mean TSH level in patients with breast cancer was 4.9±1.7 µIU/ml which was significantly higher than healthy women (1.79±0.15 µIU/ml, P=0.004). The frequency rate of the increased Anti TPO Ab levels (higher than 35 IU/ml) in women with breast cancer was 22% which was significantly higher than the control group (%0, P=0.002), while no statistically significant difference was found between the mean Anti TPO Ab levels between the two groups (61.07±29.73 versus 9.78±0.78, P=0.21). Four cases of subclinical and/or overt hypothyroidism were found in women with breast cancer. Conclusion: Based on our findings breast cancer patients have higher rates of thyroid autoimmunity. Measurement of FT4 and T3 in all women with breast cancer is not recommended but measurement of TSH and Anti TPO Ab levels seem reasonable. 175 178 2015/10/282015/09/92015/10/4 1394/7/12 ندا ولی زاده N Valizadeh Maternal and Childhood Obesity Research Center nvalizadeh2008@gmail.com عذرا دلپاک A Delpak Urmia University Of Medical Sciences adelpak@gmail.com علی عیشی اسکوئی A Eishi Oskuie Urmia University Of Medical Sciences eishi@umsu.ac.ir نسیم ولی زاده N Valizadeh Tehran University Of Medical Sciences nsedaha0@gmail.com Breast cancer Thyroid autoimmunity Thyroid function test ## ##

The Influence of Fetal Hemoglobin on Clinical and Hematological Variables of Children and Adolescents with Sickle Cell Anemia in Basra, Southern Iraq 2 2 Background: There are many parameters that modulate the severity of sickle cell anemia. Fetal hemoglobin (Hb F) is one of these major variables. However, its effect is clinically inconsistent. We conducted a descriptive study to assess the influence of Hb F on clinical events and hematological variables in patients with sickle cell anemia. Methods: 151 patients with sickle cell anemia with a stable condition, aged 1-18 years, were recruited from March through November 2010. The results of complete blood count and Hb F level and various clinical variables were recorded. Results: Of the 151 patients, the Hb F was more than 20%, 10-20%, and less than 10% in 77 (51%), 60 (39.7%), and 14 (9.3%) patients. A significant negative association was reported between Hb F level and frequency of painful crisis (95% CI=0.05-0.96, OR=0.22), acute chest syndrome (95% CI=0.01-0.43, OR=0.07) and frequency of hospitalizations (95% CI=0.03-0.85, OR=0.11). There was a significant positive association between hemoglobin level (95% CI=2.14-27.17, OR=7.63) and splenomegaly (95% CI=1.37-57.4, OR=12.88) with Hb F level. Conclusion: In children and adolescents with sickle cell anemia, the higher the Hb F levels, the lesser clinical complications of the disease would be. Therefore, patients with low Hb F need close follow-up and monitoring since early age to detect complications as early as possible and consider use of disease modifying agents. 179 183 2015/10/282015/09/92015/10/42015/10/6 1394/7/14 AK Badr AK Badr MK Hassan MK Hassan Sickle cell anemia Fetal hemoglobin Clinical severity Complications ## ##

Analysis of Expression Of SIRT1 Gene In Patients With Chronic Myeloid Leukemia Resistant To Imatinib Mesylate افزایش بیان ژن SIRT1 در بیماران لوسمی میلوئید مزمن مقاوم به داروی ایماتینیب 2 1 سابقه وهدف: لوسمی میلوئید مزمن یک بیماری میلوپرلیفراتیو کلونال میباشد که با فیوژن bcr-abl تشخیص داده میشود. با ظهور مهارکنندهای تیروزین کیناز مثل ایماتینیب پیشرفتهای مهمی در درمان این بیماری صورت گرفته است. اما وجود مقاومت دارویی بر علیه این دارو ، یک مانع در درمان لوسمی میلوئید مزمن محسوب میشود.) Sirt1سیرتونین یک ( عملکرد داستیلاز دارد و در بسیاری از سرطانها دارای افزایش بیان می باشد.این تحقیق به منظورتعیین ارتباط بین بیان ژن sirt1 و مقاومت دارویی بر علیه داروی ایمانیتیب انجام شد.هدف از پژوهش نشان دادن این موضوع بوده است که سیرتونین یک ممکن است در ایجاد مقاومت دارویی در بیماران لوسمی میلوئید مزمن تحت درمان با داروی ایمانیتیب نقش داشته باشد. روش بررسی: این مطالعه به صورت بنیادی کاربردی بر روی 48 بیمار با لوسمی میلوئید مزمن که به بیمارستان دکتر شریعتی مراجعه کرده بودند انجام شد. نمونه خون وریدی بیماران جمع اوری و RNA بیماران استخراج شد . بعد از این مرحله cDNA بیماران مورد سنتز قرار گرفت. بررسی بیان ژن sirt1 و آنالیز بیان این ژن با روش real-time PCR انجام شد. یافته ها: در این مطالعه 48 بیمار 15 تا 64 سال و با میانگین 40 سال مورد مطالعه قرار گرفتند. در این بین 59 درصد مرد و 41 درصد زن بودند. میانگین بیان BCR-ABL در بیماران مقاوم به دارو حداقل یک درصد و حداکثر 57 درصد بدست آمد. بررسی میزان دلتا سی تی برای ژن sirt1 در بیمارانی که به داروی ایماتیتیب ، مقاوم به دارو بودند در مقایسه با بیمارانی که به این دارو حساس بودند پایین تر بود )05/0P<). نتیجه گیری: به نظر میرسد که بیان ژن sirt1در بیماران مقاوم به داروی ایماتینیب افزایش نشان میدهد و به طور با معنایی این تفاوت بیشتر است . 2 Background: Chronic myeloid leukemia is a clonal myeloproliferative disease which is characterized by bcr/abl translocation. With the emergence of tyrosine kinase inhibitors such as imatinib mesylate, significant improvement has been made in treatment of this disease. However, drug resistance against this medicine is still an obstacle. SIRT1 is a gene with deacetylase activity which has been detected to have increased expression in many cancers. We aimed to determine if SIRT1expression could play a role in the emergence of drug resistance in patients with chronic myeloid leukemia being treated with imatinib mesylate. Methods: 48 patients with chronic myeloid leukemia referred to Dr. Shariati Hospital, Tehran, Iran, were studied. A venous blood sample of patients was collected, RNA was extracted and then cDNA were synthesized. SIRT1 gene expression was done by real-time PCR. The ratio of SIRT1 expression to ABL control gene was calculated. After calculation of CT for target gene and control gene, ;DeltaCT was calculated. The results of SIRT1 expression levels in patients with chronic phase of CML were compared with that of the control group. Results: 48 patients with chronic myeloid leukemia aged 15-64 years (mean: 40 years) were enrolled. 59% of the participants were men. The highest and lowest mean BCR-ABL expressions in drug-resistant patients were 1% and 57%, respectively. The results of analyzing the value of ;DeltaCT for SIRT1 gene revealed that patients who were drug-resistant to imatinib mesylate had a lower value of ;DeltaCT for SIRT1 than those who were not drug-resistant (P<0.05). Conclusion: SIRT1 gene expression in patients resistant to imatinib mesylate was significantly higher than patients who were not drug-resistant. 184 190 2015/10/282015/09/92015/10/42015/10/62015/10/12 1394/7/20 صادق عباسیان S Abbasian Tehran University of Medical Sciences a.ghotaslou@gmail.com عباس قوطاسلو A Ghotaslou Tehran University of Medical Sciences a.ghotaslou@gmail.com علی قاسمی A Ghasemi Tehran University of Medicaaal Sciences a.ghotaslou@gmail.com فاطمه ناد علی F Nadali Tehran University of Medical Sciences a.ghotaslou@gmail.com CML Gene expression SIRT1 gene Drug resistance Imatinib mesylate بیان ژن SIRT1 مقاومت دارویی داروی ایماتینیب ## ##

The Survey of Effective Agents on Factor VIII and IX Inhibitors in Patients with Hemophilia A and B in Kermanshah Province بررسی عوامل موثر بر فاکتورهای 9 و10 د ر بیماران هموفیلی در استان کرمانشاه 2 2 Background: Hemophilia is the most frequent severe hereditary hemorrhagic disease due to deficiency of coagulation factors VIII (Hemophilia A) or IX (Hemophilia B) in plasma. We aimed to identify patients with hemophilia in Kermanshah, Iran and assess the incidence of inhibitors in this population and its associated factors. Methods: This study was conducted on patients with hemophilia A and B admitted in hospitals of Kermanshah city, referred to coagulation laboratory of Kermanshah blood transfusion organization. Variables including age, sex, family history of the patients in terms of history of hemophilia and inhibitor formation, development of inhibitor in patients, age at starting the treatment, blood group, severity of hemophilia, average of factors received per month and liver disease were assessed in patients. Results: Of 123 patients with hemophilia A, 119 (96.7%) were men. The mean±SD age of patients with hemophilia A was 25.9±15.74 years. Only five men had developed factor VIII inhibitor. Of 25 patients with hemophilia B, 24 (96%) were men with a mean±SD age of 21.7±15.71 years. Factor IX inhibitor was not detected in any patient. There was no association between incidence of inhibitors and age at the onset of the treatment, family history of hemophilia, blood group, severity of hemophilia, average of received factor per month and liver disease. However, a positive association between incidence of inhibitors and family history of inhibitors was found (P<0.05). Conclusion: Association between family history of inhibitor and incidence of inhibitor formation in hemophilic patients was a new finding. Therefore this outcome and genetic evaluation of these for finding relevant mutations should be considered. 191 194 2015/10/282015/08/12 1394/5/21 2015/10/282015/09/92015/10/42015/10/62015/10/122015/10/17 1394/7/25 M Payandeh M Payandeh Department of Hematology and Medical Oncology, Kermanshah University of Medical Sciences, Kermanshah, Iran md.payandeh@yahoo.com N Amirifard N Amirifard E Sadeghi E Sadeghi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran sadeghi_mkn@yahoo.com M Sadeghi M Sadeghi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran sadeghi_mbrc@yahoo.com M Choubsaz M Choubsaz F Noor Mohammadi Far F Noor Mohammadi Far Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran Factor VIII Factor IX Hemophilia A Hemophilia B Inhibitorو Predisposing factor Genetic mutation Severity of disease ## ##

Neuroendocrine Carcinoma of the Stomach A Case Report Neuroendocrine Carcinoma, Mitotic Index, Immunohistochemistry, Stomach 2 1 Gastric neuroendocrine carcinomas are rare and have a poor prognosis. The present case concerns with a 55 year old female who presented with complaints of recurrent vomiting on and off, hematemesis and weight loss and history of lumbar stenosis. Esophagogastroduedenostomy (EGD) showed a large ulcerated growth in the antrum. Computed tomography abdomen revealed an ill defined soft tissue density in the gastric antrum, a partial gastrectomy was performed. Microscopic evaluation revealed a neuroendocrine neoplasm. Immunohistochemically positive for Chromogranin A and Non Specific Enolase (NSE). A diagnosis of Neuroendocrine carcinoma of the stomach was given based on recent WHO classification of Neuroendocrine carcinoma of the stomach and on mitotic index with reference to grading scale 2 Gastric neuroendocrine carcinoma is a rare tumor which has a poor prognosis. Herein, we present a 55-year-old woman who presented with complaints of recurrent vomiting, hematemesis and weight loss. Endoscopic examination showed a large ulcerated mass in the antrum. Microscopic evaluation of the specimen taken through biopsy was compatible with a small round cell tumor. However, definitive histopathological diagnosis was made after surgical resection which revealed a neuroendocrine neoplasm immunohistochemically positive for Chromogranin A and Neuron specific enolase. As a result a diagnosis of neuroendocrine carcinoma of stomach was made for the patient. 195 197 2015/10/282015/09/92015/10/42015/10/62015/10/122015/10/172015/10/18 1394/7/26 R Akhter R Akhter MS Khuroo MS Khuroo ZA Dar ZA Dar N Qayoom N Qayoom N Bhat N Bhat ## ##

Autoimmune Lymphoproliferative Syndrome Misdiagnosed as Hemophagocytic Lymphohistiocytosis A Case Report تشخیص اشتباه ALPS به عنوان HLH در یک کیس 2 2 Autoimmune lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of apoptosis. It usually presents with chronic lymphadenopathy, splenomegaly, and symptomatic cytopenia in a child. Herein, we report a 14-year-old boy with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis who was treated before ALPS was diagnosed for the patient. This case should alert pediatricians to consider ALPS in differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenia. 198 200 2015/10/282015/09/92015/10/42015/10/62015/10/122015/10/172015/10/182015/10/12 1394/7/20 H Abolghasemi H Abolghasemi Department of Pediatrics , Baqiyatallah University of Medical Sciences, Tehran, IR Iran h.abolghasemi@ibto.ir E Shahverdi E Shahverdi Students’ Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, IR Iran shahverdi_ehsan@yahoo.com F Dolatimehr F Dolatimehr Students’ Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, IR Iran fardin.dolatimehr@gmail.com R Mehdi Oghli R Mehdi Oghli Students’ Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, IR Iran esn.sh1387@yahoo.com Autoimmune lymphoproliferative Syndrome Hemophagocytic lymphohistiocytosis Cytopenia Splenomegaly Lymphadenopathy ## ##

Is Colorectal Cancer an Unusual Malignancy among Iranian Children? کانسرکولورکتال کودکان 2 2 Dear Editors: Adenocarcinoma of colon and rectum is the second most common cancer of the gastrointestinal (GI) tract in children. The development of carcinoma of colon in general appears to be associated with several predisposing factors such as familial polyposis, hereditary non-polyposis syndromes, ulcerative colitis, previous ureterosigmoidostomy or radiation therapy and dietary factors (high fat or low fiber diets) 1. Here we report three adolescents with colorectal cancer referring to Amir Oncology Hospital, Shiraz, southern Iran, presenting with various signs and symptoms including acute abdominal pain, painless rectorrhagia, and refractory iron deficiency anemia. They did not have any known predisposing risk factor. Patient 1 was a 14-year-old girl presented with acute abdomen. Abdominal sonography showed a target-like lesion on the thickened segmental bowel wall with a protrusion of the serosa which was surrounded by localized ascites in the lower abdomen. She was found to have a right-sided colon cancer at laparotomy. Histology showed stage 4 Duck. She was diagnosed to have a brain metastasis. Patient 2 was a 16 year-old boy presented with refractory iron deficiency anemia due to metastatic colorectal cancer without any underlying disease in the GI tract. The patient was treated by large amounts of iron supplement and was referred for evaluation of refractory iron deficiency anemia. Patient 3 was a 12 year-old girl presented with painless rectorrhagia without any abdominal complaints. Colonoscopic study revealed typical colon lesions in sigmoid, descending the colon and rectum. Family history was unremarkable for adenomatous polyps. Symptoms of colon cancer in children are nonspecific and include chronic persistent abdominal pain (90%), emesis, bowel habit changes, weight loss (77%), occult blood in the stool with chronic anemia (60%), tenesmus,2 and a palpable abdominal mass. Therefore early diagnosis of patients without predisposing factors is associated with better outcome and prevention of advanced stages and increased rate of successful treatment modalities such as adjuvant chemotherapy after primary surgery. Although this tumor is rare in children, physicians should be alert about the cardinal signs and symptoms and to improve patient’s outcome a high index of suspicion should be kept in mind. Likewise, infrequent signs and symptoms such as acute abdomen or refractory iron deficiency should increase suspicion. Primary diagnostic modalities such as fecal occult blood, complete blood count, abdominal ultrasound and/or invasive procedures such as colonoscopy should be carefully performed in children presenting with red flags for colon cancer including lower GI bleeding, acute abdomen, or iron deficiency anemia. Moreover, monitoring of carcinoembryonic antigen (CEA) levels is recommended during postoperative follow-up in pediatric colon cancers similar to adults 3. Another approach for early detection of this cancer in absence of red flags is routine screening in children predisposed to colorectal cancer as a way to increase overall prognosis. Stools may be tested or a barium enema, colonoscopy, sigmoidoscopy or virtual colonoscopy may be performed. Regardless of any test, a laboratory analysis of tissue ultimately determines existence of tumor. Therefore, cell biopsy, fluid or tissue in the colon needs to be examined to determine presence of tumor. 201 202 2015/10/282015/09/92015/10/42015/10/62015/10/122015/10/172015/10/182015/10/122015/09/9 1394/6/18 M Karimi M Karimi M Shahriari M Shahriari بابک عبدالکریمی B Abdolkarimi pediatric hematology oncology fellowship b.abdolkarimi@yahoo.com M Mokhtari M Mokhtari ## ##