Providing Suggested Rules for Multiple Primary Cancer Recording, Coding and Registering in Population-based Cancer Registry.

BACKGROUND: Multiple primary cancers (MPC) present many coding difficulties, while a distinction should be made between new cases and those with metastasis and/or extension and recurrence of the primary ones. We aimed to reflect on the experiences and results of data quality control of the East Azerbaijan/Iran Population-Based Cancer Registry and present our suggested rules for reporting, recording and registering multiple primary cancer. METHODS: Comparability, validity, timeliness, and completeness of data assessment were performed. As a result, we created a consulting team including expert oncologists, pathologists, and gastroenterologists to discuss for multiple primary tumors recording, identifying, coding and registering. RESULTS: In case of confirmed Blood malignancies with definite BMB results, Brain and/or Bone involvements are always metastatic. In most cases of multiple cancers with the same morphological types, the earlier should be registered as primary tumor. In most of the synchronous multiple cancers, familial cancer syndromes should be considered and rules out. In case of two tumors diagnosed at the same time in colon and rectum, primary site should be detected by T stage or tumor sizes. In case of multiple tumors in Recto-sigmoid, Colon , and Rectum the earlier history of tumor should be considered as primary site. This rule was applied for Female Genital tumors, as earlier site is always the Primary cancer and other tumors should be registered as metastatic sites.  Conclusion: Given the complexity of coding MPCs, we suggested some additional rules for identifying, recording, coding, and registering multiple primary cancers in the context of the EA-PBCR program.

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran.

BACKGROUND: Colorectal cancer (CRC) is the third-most common cancer in Iran. The increasing incidence of CRC in the past three decades has made it a major public health burden in the country. This study aimed to determine any relationship of specific mutations in CRCs with clinicopathologic aspects and outcome of patients. MATERIALS AND METHODS: This study was conducted on 100 CRC patients by the case-only method. Polymerase chain-reaction products were analyzed by Sanger sequencing, and sequence results were compared with the significant KRAS and BRAF gene mutations in the My Cancer Genome database. Logistic regression models were used to detect associations of clinicopathologic characteristics with each of the mutations. Kaplan-Meier and Cox regression models were constructed to estimate overall survival in patients. RESULTS: A total of 26 subjects (26%) had heterozygote-mutant KRAS, and mutations were not detected in the amplified exon of BRAF in both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood of KRAS mutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood of KRAS mutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients with KRAS wild-type cancers, those with KRAS mutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44-9.68; log-rank P=0.003). CONCLUSION: Better understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease.

Characterization of Common Chromosomal Translocations and Their Frequencies in Acute Myeloid Leukemia Patients of Northwest Iran.

OBJECTIVE: Detection of chromosomal translocations has an important role in diagnosis and treatment of hematological disorders. We aimed to evaluate the 46 new cases of de novo acute myeloid leukemia (AML) patients for common translocations and to assess the effect of geographic and ethnic differences on their frequencies. MATERIALS AND METHODS: In this descriptive study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used on 46 fresh bone marrow or peripheral blood samples to detect translocations t (8; 21), t (15; 17), t (9; 11) and inv (16). Patients were classified using the French-American-British (FAB) criteria in to eight sub-groups (M0-M7). Immunophenotyping and biochemical test results of patients were compared with RT-PCR results. RESULTS: Our patients were relatively young with a mean age of 44 years. AML was relatively predominant in female patients (54.3%) and most of patients belonged to AML-M2. Translocation t (8; 21) had the highest frequency (13%) and t (15; 17) with 2.7% incidence was the second most frequent. CD19 as an immunophenotypic marker was at a relatively high frequency (50%) in cases with t (8; 21), and patients with this translocation had a specific immunophenotypic pattern of complete expression of CD45, CD38, CD34, CD33 and HLA-DR. CONCLUSION: Similarities and differences of results in Iran with different parts of the world can be explained with ethnic and geographic factors in characterizations of AML. Recognition of these factors especially in other comprehensive studies may aid better diagnosis and management of this disease.

Medical oncology, history and its future in Iran.

Systemic therapy is one of the cornerstones of cancer treatment. In 1972, following representations by American Society of Clinical Oncology (ASCO), the American Board of Internal Medicine (ABIM) recognized medical oncology as a new subspecialty of internal medicine. Subspecialty of Hematology and Medical Oncology was emerged in Iran in 1983. In the past, modern medical treatments and education were started in Dar Al-fonun school and then in Tehran University; now six universities in Iran are training in Subspecialty of Hematology and Medical Oncology. There are also ten active hematopoietic stem cell transplantation centers, thirty-one provincial medical schools use their specialized services. Future goals for Hematology and Medical Oncology in Iran include expansion and reinforcement of multidisciplinary teams across the country, early detection and prevention of cancer, providing educational program and conducting cancer researches. To achieve these goals, it is necessary to establish Cancer Hospitals in each province that link together through a network.

Molecular Analysis of IGH and Incomplete IGH D-J Clonality Gene Rearrangements in Hodgkin Lymphoma Malignancies.

BACKGROUND: We evaluated molecular clonality in immunoglobulin heavy chain (IGH) and incomplete IGH D-J genes for improvement of clinical diagnosis of Hodgkin's lymphoma (HL). We applied BIOMED-2 protocols in HL cases, which were previously approved by clonality detection in non-Hodgkin lymphoma (NHL) cases. METHODS: We investigated 50 consecutive FFPE samples of classical HL (cHL) patients to assess IGH and IGH D-J clonal gene rearrangements by multiplex PCR protocols, which were provided by the European Biomedicine and Health (BIOMED-2) Concerted Action Project BMH4-CT98-3936. RESULTS: In the present study, there was a monoclonality of 86% (43/50) including a clonality of 74% (37/50) for IGH and a clonality of 42% (21/50) in IGHD-J. In addition, a lack of clonality was detected in 14% (7/50) of cases. Frequent gene rearrangements were detected in framework (FR) III (54%) and FRII (20%), whereas no clonality was seen in FRI. Furthermore, a monoclonality of 28% and 14% was detected in the DH(1-6)-JH and DH(see symbol)-JH gene rearrangements, respectively. CONCLUSIONS: The present study suggests that the complete IGH and incomplete IGH D-J clonality gene rearrangement assays using BIOMED-2 protocols could be considered a valuable method for detection of clonal gene rearrangements, especially in HL cases.

Colorectal cancer in iran: molecular epidemiology and screening strategies.

Purpose. The increasing incidence of colorectal cancer (CRC) in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

Nucleostemin depletion induces post-g1 arrest apoptosis in chronic myelogenous leukemia k562 cells.

PURPOSE: Despite significant improvements in treatment of chronic myelogenous leukemia (CML), the emergence of leukemic stem cell (LSC) concept questioned efficacy of current therapeutical protocols. Remaining issue on CML includes finding and targeting of the key genes responsible for self-renewal and proliferation of LSCs. Nucleostemin (NS) is a new protein localized in the nucleolus of most stem cells and tumor cells which regulates their self-renewal and cell cycle progression. The aim of this study was to investigate effects of NS knocking down in K562 cell line as an in vitro model of CML. METHODS: NS gene silencing was performed using a specific small interfering RNA (NS-siRNA). The gene expression level of NS was evaluated by RT-PCR. The viability and growth rate of K562 cells were determined by trypan blue exclusion test. Cell cycle distribution of the cells was analyzed by flow cytometry. RESULTS: Our results showed that NS knocking down inhibited proliferation and viability of K562 cells in a time-dependent manner. Cell cycle studies revealed that NS depletion resulted in G(1) cell cycle arrest at short times of transfection (24 h) followed with apoptosis at longer times (48 and 72 h), suggest that post-G1 arrest apoptosis is occurred in K562 cells. CONCLUSION: Overall, these results point to essential role of NS in K562 cells, thus, this gene might be considered as a promising target for treatment of CML.

Prevalence of oral human papilloma virus in healthy individuals in East azerbaijan province of iran.

BACKGROUND: Human papilloma virus causes benign and malignant abnormalities in different part of the body. The link between high risk types of HPV and some anogenital and aerodigestive tract cancer is well established. Oral HPV infection plays a role in developing oropharyngeal squamous cell carcinoma. We studied the prevalence of oral HPV in healthy individuals and its relative risk factors. METHODS: Saliva samples of 114 healthy subjects were collected for HPV DNA analysis. Volunteers completed questionnaires and signed a written consent. For data analysis descriptive statistic, chi square test and odds ratio was used. RESULTS: The frequency of oral HPV in healthy individuals was 6.1 %(seven participant).The most frequent type was HPV-18 in five of them. HPV-6 and HPV-66 each was detected in one case. Relation of oral HPV positivity to demographic features and risk factors was not statistically significant. CONCLUSIONS: The prevalence of oral HPV infection in our community is the same as many other communities of developing countries, stressing that HPV-18 were the dominant type.

Successful management of total knee replacement in a high responder hemophilia patient with a history of inhibitor.

The development of inhibitors against administered clotting factors may render replacement therapy ineffective for some hemophilia patients. Such patients are therefore at the highest risk of developing arthropathy. Elective orthopedic surgery (EOS) in hemophilic patients having such inhibitors remains a rare, expensive, and difficult surgery, whose management represents a significant challenge. We report the case of a 35-year-old man with a severe form of hemophilia A (factor VIII < 1%), who was suffering from repetitive spontaneous hemarthrosis, especially in his knee joints that had consequently become more susceptible to bleeding. The patient had a history of high levels of factor VIII inhibitor (> 5.0 Bethesda Unit [BU]/ml) as shown by the factor VIII inhibitor assay; therefore, we began treatment with factor VIIa for his mild-to-moderate bleeding (90 µg/kg intravenous bolus injections). The interval between injections varied with the severity of the hemorrhage in each bleeding episode. The inhibitor level reduced to 3.1 BU/ml after three months, to 1.6 BU/ml after six months, and disappeared completely after one year of treatment. We administered factor VIII at a dose of 50 IU/kg every eight hours during the first three post-operative days, then continued administration with a dose of 40 IU/kg every 12 hours for another four days, and observed a very good response to treatment with no bleeding. Recombinant activated factor VII (rFVIIa) is not an inhibitor-removal strategy, but an inhibitor-bypassing product. However, in our patient, the treatment of mild-to-moderate bleeding with short-term use of rFVIIa and no exposure to factor VIII caused a gradual reduction in the inhibitor level over a period of 1 year.

Effect of vitamin e on uroepithelial cells and changes of urinary sediments in oncology hospital nursing personnel.

INTRODUCTION: Vitamin E is an important natural antioxidant, and its most common and biologically active form is α-tocopherol. The antiproliferative effects of alpha-tocopherol have been previously demonstrated. In this study we investigated the effects of vitamin E on urinary epithelial cells and urinary sediments of nursing from oncology hospital. MATERIAL AND METHODS: Sixty-two female nursing personnel from oncology hospital participated in the study. They received orally 200mg of vitamin E per day for two weeks. Also prior to vitamin E and after vitamin E administration, the uroepithelial cells counts and other components of urinary sediments were carried out. RESULTS: There were significant differences in the epithelial cells count and treatment with vitamin E causing significantly more number of epithelial cells and urinary sediments to be excreted in the urine. DISCUSSION: Vitamin E significantly plays an important role on the excretion of uroepithelial cells and urinary sediments. CONCLUSION: In conclusion we propose that use of vitamin E at nontoxic levels would significantly enhance its antioxidative properties, especially among individuals subjected to prophylaxis of occupational hazards.

The Relation between Awareness of Cancer Diagnosis and Spiritual Health among Cancer Patients.

INTRODUCTION: Disclosure of cancer diagnosis is one the main challenges in caring of patients with cancer since it may have negative effects on the spiritual health of patients. No study has ever been performed in Iran to investigate the relationship between awareness of cancer diagnosis and spiritual health in cancer patients. Therefore, the present study aimed to review the effects of awareness of cancer on spiritual health in patients with cancer. METHODS: This was a descriptive-comparative study conducted in Shahid Ghazi Tabatabaei University Hospital in 2009. The subjects included 150 patients aware of their cancer diagnosis and 150 unaware patients. The patients were selected through convenient sampling method. Using a questionnaire, the patient's spiritual health was assessed. Data analysis was conducted in SPSS17 using descriptive and inferential statistics. RESULTS: RESULTS showed the mean (SD) of spiritual health among aware and unaware patients to be 75.1 (3.8) and 75.4 (3.9), respectively. Statistically, there was no significant difference between the spiritual health of the two groups (p = 0.96). CONCLUSION: These findings showed that awareness of cancer diagnosis had no effects on spiritual health of patients. It is not surprising considering Iranian culture. However, confirmation of this finding requires further studies.

Quality of life in cancer patients and its related factors.

INTRODUCTION: Despite the importance of quality of life (QOL) in outcomes of cancer pa-tients, there have been a few Iranian studies investigating the Iranian patients' quality of life. The present study aimed to assess the cancer patients' QOL and its related factors. METHODS: This cross-sectional study conducted in Shahid Ghazi Tabatabaei Hospital affiliated to Tabriz University of Medical Sciences in 2009. The samples included 150 cancer patients aged more than 18 years who were aware of their own diagnosis. They were selected through convenient sampling method and European Organization for Research and Treatment of Cancer-Quality of life questionnaire (EORTC-QOL 30) were completed. RESULTS: Our findings showed that 44.1% of the patients had moderate QOL. QOL had a significant correlation with the level of family support (p = 0.002). CONCLUSION: Many of cancer patients have a moderate QOL. However, confirmation of such finding requires further investigations.

Upper gastrointestinal bleedings in patients with hereditary coagulation disorders in Northwest of Iran: prevalence of Helicobacter pylori infection.

OBJECTIVE: Upper gastrointestinal (UGI) bleeding is one of the most life-threatening complications, in up to 25% of persons with hemophilia (PWH). Recurrent bleeding is common and can be caused by the Helicobacter pylori infection. Our aim was to evaluate the role of H. pylori infection in UGI bleeding in PWH. MATERIAL AND METHODS: Ninety patients with hereditary bleeding disorders, 30 patients with (group A), and 60 patients without (group B) a history of UGI bleeding episodes were included. The prevalence of H. pylori infection was investigated by stool antigen test, and serum serologic tests including immunoglobulin G and anti-CagA. RESULTS: Among 90 patients (81 men, nine women, mean age 31.30 ± 10.72 years), 66 patients with hemophilia A, 10 patients with hemophilia B, six patients with Von Willebrand disease, five patients with platelet function disorders, and three patients with other factor deficiencies were evaluated. About 46.7% of patients in group A, and 23.3% of patients in group B were anti-CagA-positive (P=0.02), whereas 76.7% of patients in group A and 51.7% of patients in group B had H. pylori immunoglobulin G antibodies (P=0.02). H. pylori antigen in stool was positive in 76.7% in group A and 55% in group B (P=0.03). No statistically significant difference was found between type and severity of diseases and risk of UGI. CONCLUSION: H. pylori infection should be considered as an important cause of UGI bleeding in PWH. We would recommend stool antigen test as a new and noninvasive screening test for diagnosis of H. pylori infection in all patients with hereditary hemorrhagic disorders.

Hope in Iranian cancer patients.

BACKGROUND: Hope is an important factor in the recovery of cancer patients. Few Iranian studies investigated the level of hope in cancer patients. Therefore, the present study aimed to investigate the level of hope in Iranian cancer patients and the related factors. METHODS: In a descriptive correlational study, 150 cancer patients were selected by a consecutive sampling method. Hope in patients was measured by the Herth Hope Index. Data analysis was performed using descriptive and inferential statistics. RESULTS: Results indicated that 61.1% of the patients had high levels of hope, 35.4% had moderate levels of hope, and 3.5% had low levels of hope. Hope has a statistically significant relationship with family support, but it is not statistically associated with other patient characteristics. CONCLUSIONS: Many cancer patients had a high level of hope. However, further studies are recommended to investigate the relation between hope and patient characteristics.