Mitochondrial DNA Copy Number Variations and Serum Pepsinogen Levels for Risk Assessment in Gastric Cancer

Background: Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy. Methods: The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA. Results: The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups. Conclusion: The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.

Multiplex serology of Helicobacter pylori antigens in detection of current infection and atrophic gastritis - A simple and cost-efficient method.

INTRODUCTION: Helicobacter pylori express a large array of antigens, each of which is duly responsible for successful colonization and pathogenesis. Here, we have studied host serum antibody responses to four of its immunodominant antigens in association with the infection status and the resulting clinical outcomes. METHODS: For this purpose, four individual H. pylori proteins (UreB, CagA, Tip-α and HP0175) were produced in recombinant forms. Serum antibody responses of 246 (75 GC and 171 NUD) patients, against the above antigens, were evaluated by multiplex immunoblotting. The associations between the resulting data and the infection status, as well as clinical outcomes were evaluated using logistic regression models. RESULTS: Serum antibodies to all four recombinant antigens increased the chances of detecting screening ELISA-positive subjects, in an escalating dose-dependent manner, ranging from 2.6 (1.5-4.7) for HP0175 to 14.3 for UreB (4.3-50.7), exhibiting the lowest and highest odds ratios, respectively (PAdj ≤ 0.001), such that 98.2% of the subjects with antibodies to all four antigens, were also positive by the screening ELISA (P < 0.0001). Among the screening ELISA-positive subjects, the three antigens of CagA, Tip-α, and HP0175 were able to segregate current from past H. pylori infection (P < 0.05). Accordingly, subjects with antibodies to one or more antigen(s) were at 5.4 (95% CI: 1.8-16.4) folds increased chances of having current infection, as compared to triple negatives (PAdj = 0.003). In reference to the clinical outcomes, those with serum antibodies to CagA were more prevalent among gastric cancer, as compared to NUD patients (ORAdj: 5.4, 95% CI: 2.4-12.2, PAdj < 0.0001). When NUD patients were categorized according to their histopathologic status, multiple antigen analysis revealed that subjects with serum antibodies to one or more of the 3 current infection-positive antigens (CagA, Tip-α, and HP0175) were at 9.7 (95% CI: 2.1-44.9, P = 0.004) folds increased risk of atrophic gastritis, in reference to triple negatives. CONCLUSION: The non-invasive multiplex serology assay, presented here, was able to not only detect subjects with current H. pylori infection, it could also screen dyspeptic patients for the presence of gastric atrophy. This simple and cost-efficient method can supplement routine screening ELISAs, to increase the chances of detecting current infections as well as atrophic gastritis.

Travel Burden and Clinical Profile of Cancer Patients Admitted to the Cancer Institute of Iran in 2012.

BACKGROUND: Burden of cancer is increasing in developing countries, where healthcare infrastructures and resources are limited. Evaluating the pattern of care would provide evidence for planning and improvement of the situation. MATERIALS AND METHODS: We studied the pattern of residential place and clinical information of cancer patients who were admitted to the Cancer Institute of Iran from January 1, to May 31, 2012. RESULTS: We studied 1,705 consecutive cancer patients admitted to the Cancer Institute in the study period. The most common cancers were breast (29.2%), colorectal (9.0%), stomach (8.3%), head & neck (8.0%) and esophageal (3.8%) cancers. Radiotherapy was the main treatment (52.1%) followed by chemotherapy (43.8%) and surgery (29.1%). We found that 60% of the patients presented in the loco-regional or advanced stages. About 35% of patients travelled from other provinces mainly from Mazandaran (13.4%), Lorestan (10.6%), Zanjan (7.8%) and Ghazvin (6.6%). On average, the cancer patients travelled about 455 kilometers to receive care in the cancer institute. We found more than 38% patients who were referred from other provinces had an early stage tumor. CONCLUSION: Establishment of comprehensive cancer centers in different geographical regions and implementation of a proper referral system for advanced cancer patients is needed to improve the patient outcomes and mitigate the burden of travel of patients for cancer care.

Assessment of a Hospital Palliative Care Unit (HPCU) for Cancer Patients; A Conceptual Framework.

INTRODUCTION: The first hospital palliative care unit (HPCU) in Iran (FARS-HPCU) has been established in 2008 in the Cancer Institute, which is the largest referral cancer center in the country. We attempted to assess the performance of the HPCU based on a comprehensive conceptual framework. The main aim of this study was to develop a conceptual framework for assessment of the HPCU performances through designing a value chain in line with the goals and the main processes (core and support). MATERIALS AND METHODS: We collected data from a variety of sources, including international guidelines, international best practices, and expert opinions in the country and compared them with national policies and priorities. We also took into consideration the trend of the HPCU development in the Cancer Institute of Iran. Through benchmarking the gap area with the performance standards, some recommendations for better outcome are proposed. RESULTS: The framework for performance assessment consisted of 154 process indicators (PIs), based on which the main stakeholders of the HPCU (including staff, patients, and families) offered their scoring. The outcome revealed the state of the processes as well as the gaps. CONCLUSION: Despite a significant improvement in many processes and indicators, more development in the comprehensive and integrative aspects of FARS-HPCU performance is required. Consideration of all supportive and palliative requirements of the patients through interdisciplinary and collaborative approaches is recommended.

Priority Setting for Improvement of Cervical Cancer Prevention in Iran.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Organized cervical screening and vaccination against human papilloma virus (HPV) have been successful interventions for prevention of invasive cervical cancer (ICC). Because of cultural and religious considerations, ICC has low incidence in Iran and many other Muslim countries. There is no organized cervical screening in these countries. Therefore, ICC is usually diagnosed in advanced stages with poor prognosis in these countries. We performed a priority setting exercise and suggested priorities for prevention of ICC in this setting. METHODS: We invited experts and researchers to a workshop and asked them to list important suggestions for ICC prevention in Iran. After merging similar items and removing the duplicates, we asked the experts to rank the list of suggested items. We used a strategy grid and Go-zone analysis to determine final list of priorities for ICC prevention in Iran. RESULTS: From 26 final items suggested as priorities for prevention of ICC, the most important priorities were developing national guidelines for cervical screening and quality control protocol for patient follow-up and management of precancerous lesions. In addition, we emphasized considering insurance coverage for cervical screening, public awareness, and research priorities, and establishment of a cervical screening registry. CONCLUSION: A comprehensive approach and implementation of organized cervical screening program is necessary for prevention of ICC in Iran and other low incidence Muslim countries. Because of high cost for vaccination and low incidence of cervical cancer, we do not recommend HPV vaccination for the time being in Iran.

Situation analysis of the National Comprehensive Cancer Control Program (2013) in the I. R. of Iran; assessment and recommendations based on the IAEA imPACT mission.

INTRODUCTION: Iran was engaged in the Program of Action for Cancer Therapy (PACT) in 2012, and delegates from the International Atomic Energy Agency (IAEA), and the World Health Organization (WHO) evaluated the National Cancer Control Program (NCCP) status (the imPACT mission), based on which they provided recommendations for improvements of NCCP in the I.R. of Iran. We reported the results of this situational analysis and discussed the recommendations and their implication in the promotion of NCCP in the I.R. of Iran.  METHODS: International delegates visited the I.R. of Iran and evaluated different aspects and capacities of NCCP in Iran. In addition, a Farsi version of the WHO/IAEA self-assessment tool was completed by local experts and stakeholders, including experts from different departments of the Ministry of Health and Medical Education (MOHME) and representatives from the National Cancer Research Network (NCRN). Following these evaluations, the PACT office provided recommendations for improving the NCCP in Iran. Almost all the recommendations were endorsed by MOHME. RESULTS: The PACT program provided 31 recommendations for improvement of NCCP in Iran in six categories, including planning, cancer registration and information, prevention, early detection, diagnosis and treatment, and palliative care. The most important recommendation was to establish a strong, multi-sectoral NCCP committee and develop an updated national cancer control program. CONCLUSION: The imPACT mission report provided a comprehensive view about the NCCP status in Iran. An appropriate response to these recommendations and filing the observed gaps will improve the NCCP status in the I.R. of Iran.

Assessment of scientific thinking in basic science in the Iranian second national Olympiad.

BACKGROUND: To evaluate the scientific reasoning in basic science among undergraduate medical students, we established the National Medical Science Olympiad in Iran. In this Olympiad, the drawing of a concept map was used to evaluate a student's knowledge framework; students' ability in hypothesis generation and testing were also evaluated in four different steps. All medical students were invited to participate in this program. Finally, 133 undergraduate medical students with average grades ≥ 16/20 from 45 different medical schools in Iran were selected. The program took the form of four exams: drawing a concept map (Exam I), hypothesis generation (Exam II), choosing variables based on the hypothesis (Exam III), measuring scientific thought (Exam IV). The examinees were asked to complete all examination items in their own time without using textbooks, websites, or personal consultations. Data were presented as mean ± SE of each parameter. The correlation coefficient between students' scores in each exam with the total final score and average grade was calculated using the Spearman test. RESULTS: Out of a possible score of 200, the mean ± SE of each exam were as follows: 183.88 ± 5.590 for Exam I; 78.68 ± 9.168 for Exam II; 92.04 ± 2.503 for exam III; 106.13 ± 2.345 for Exam IV. The correlation of each exam score with the total final score was calculated, and there was a significant correlation between them (p < 0.001). The scatter plot of the data showed a linear correlation between the score for each exam and the total final score. This meant that students with a higher final score were able to perform better in each exam through having drawn up a meaningful concept map.The average grade was significantly correlated with the total final score (R = 0.770), (p < 0.001). There was also a significant correlation between each exam score and the average grade (p < 0.001). The highest correlation was observed between Exam I (R = 0.7708) and the average grade. This means students with higher average grades had better grades in each exam, especially in drawing the concept map. CONCLUSIONS: We hope that this competition will encourage medical schools to integrate theory and practice, analyze data, and read research articles. Our findings relate to a selected population, and our data may not be applicable to all medical students. Therefore, further studies are required to validate our results.

Cost of care for lung cancer in the first year after diagnosis in Iran.

OBJECTIVE: The aim of this study was to estimate the cost of lung cancer treatment in the first year after diagnosis in Iran. MATERIALS AND METHODS: Patients from two referral hospitals providing all lines of treatment to cancer patients in Tehran were sampled. The direct cost included the costs that patients and other payer' s (insurance, NGO's, or other source of payment services) paid for the services received since their first confirmed diagnosis of cancer for the duration of one year. Nine items of services were evaluated for each case with exact costs abstracted from patient's files. Using incidence of lung cancer and population figure of the country, total number of lung cancer was estimated. The total and itemized costs were estimated using an average per patients for each service. RESULTS: The average age at diagnosis was around 56 years and majority of cases were male. All patients were insured by major insurance companies. A total of 5,829 cases of lung cancer were estimated to occur in 2010. The average±standard deviation (sd) of duration of hospital stay was 11.9±9.7 days. Not all the patients received all lines of services: 86% received surgery, 36% radiotherapy; and 45% chemotherapy in the first year. Some 14% of cases utilized physiotherapy and 11.5% needed pre-treatment counseling. The grand total cost of treatment for the first year of services since diagnosis was estimated at 11,262,386 US dollars for the whole population of Iran in the year 2010. Among different services provided to the patients, surgery with annual cost of 3,178,725 US dollars constitute 28% of the total cost; radiotherapy and cost of paid for medication with an annual cost of 4,242,244 US dollars accounted for 38% of total costs. With 7.8% of Iranian GDP being consumed in health expenditure, the direct cost of lung cancer for the first year after diagnosis amounted to 4% of this figure. CONCLUSION: Our study, the first to estimate the direct cost of lung cancer in Iran, indicate how costly lung cancer is to the country. More comprehensive studies are needed to validate our results plus to assess other cost including indirect costs.

Cancer epidemiology and control in North-Western and Central Asia - past, present and future.

The North-Western and Central region of Asia stretches from Turkey through Armenia, Georgia and Azerbaijan, to Iran and Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Tadjikistan and Afghanistan. These countries in the main share Turkic, Iranian or Caucasus ethnicity and culture and can be considered as a regional entity for cooperation in control of cancer. The present review of cancer registry and other epidemiological data was undertaken to provide an evidence base for cancer control programs and pointers to possible research collaboration. The most prevalent cancer site in males is the lung in the Western part of the region and the stomach in most of Iran and Central Asia, followed by the oesophagus in the latter two. Bladder cancer is comparatively frequent throughout. In females breast cancer is number one, generally followed by gastric, oesophageal or cervical lesions. However, there are interesting differences between countries or regions, particularly regarding the stomach. General tendencies for increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer point to change in environmental influence over time. Variation in risk factors depends to some extent on the level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control, underlying the necessity for cooperation.