Correlation of Minichromosome Maintenance Protein 6 Expression Rate and Clinical Outcome in Patients With Hodgkin's Lymphoma.

Minichromosome maintenance complex component 6 (MCM-6) is one of the six proteins of the MCM family, which are involved in the initiation of DNA replication, represents a marker of proliferating cells. The goal of this study was to evaluate the prognostic relevance of the neoplastic cell proliferation rate in patients with Hodgkin's lymphoma (HL). We evaluated the formalin-fixed paraffin-embedded lymph node biopsy specimens from 55 patients by using monoclonal antibody against MCM-6 and compared these findings with clinical data and treatment outcome. Median of MCM-6 expression was 85% (range: 35%-99%). In multivariate analysis, MCM-6 expression, B symptoms, and age were not statistically significant predictor for relapse in contrary to response (P=.001) and stage of disease (P=.048). Patients with lower MCM-6 expression rates showed higher relapse rate and lower disease-free survival (DFS). Meanwhile, patients with MCM-6 expression less than 85% showed shorter DFS (P=.031). We hypothesize that in group of patients with lower MCM-6 expression rate, a larger proportion of proliferating malignant cells are arrested in the very early phase of mitosis, in comparison to the group of patients with higher MCM-6 expression, and this could imply a shorter and probably higher relapse rate in the former group.

An Overview of Asbestos and Malignant Pleural Mesothelioma: An Iranian Perspective

Asbestos refers to a group of minerals that appears naturally in the environment as bundles of fibers. The incidence rate of asbestos-related diseases has considerably increased as well as the amount of asbestos utilization in few countries. Malignant pleural mesothelioma (MPM) is a rare type of aggressive and life threatening neoplasm which arise from various serous surfaces: pleura, peritoneum, tunica vaginalis and pericardium. The first case of MPM was reported in 1947. MPM etiologically is associated to the exposure of asbestos fibers. This form of malignancy is difficult to diagnose in paraclinical work-ups because mesothelioma could occur within 10-20 years of the first-time exposure to asbestos. The burden of MPM is not yet to be wholly understood. The toxic side effects of asbestos on environment and people compelled the European countries to accept the French view upon this matter. However, this approach has not been accepted by some developing countries. This review provides a brief points and facts in relation to MPM and asbestos in Iran.

Analysis of Cisplatin-Induced Ototoxicity Risk Factors in Iranian Patients with Solid Tumors: a Cohort, Prospective and Single Institute Study

Background: Cisplatin has been associated with irreversible hearing damage. Up to now, there is no therapeutic intervention showing benefit in preventing Cisplatin-induced ototoxicity. The aim of this study was to determine risk factors contributing to hearing impairment after cisplatin administration in Iranian patients. Methods: Hearing thresholds of 124 patients before and after cisplatin administration were assessed with reference to pure-tone audiometry averages at several frequencies from 2006 to 2010. Mean values were calculated at each tested frequency in each ear at baseline and subsequent follow-up audiometry. Hearing impairment was assessed with the Münster score. Results: The mean age at diagnosis and the median cumulative Cisplatin dose were 47.3 years and 453.8 milligrams, respectively. Bilateral hearing loss, mostly of grade 1, and tinnitus were detected in 26% and 3.2% of patients. Logistic regression analysis showed that a high cumulative dose of cisplatin was the most important risk factor for developing hearing damage (P=0.034). The most significant changes in the status of the auditory system and the most severe threshold shift from base line (35 dB) were observed at a frequency of 8 kHz. Also, patients who received higher individual doses of Cisplatin showed significantly more tinnitus (P=0.002). Conclusions: The results are testament to benefits of routine audiometric monitoring program during cisplatin-based chemotherapy. Further research should be performed to understand other risk factors, such as genetic predictors of Cisplatin-induced ototoxicity.

Prospective Randomized Phase II Parallel Study of Vinorelbine Maintenance Therapy versus Best Supportive Care in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Maintenance strategy has been used to improve survival in non-small cell lung cancer (NSCLC). We investigated whether switch maintenance therapy with vinorelbine improved progression free survival (PFS) after first-line chemotherapy with gemcitabine plus carboplatin. MATERIALS AND METHODS: In this single blind, parallel, phase 2, randomized trial, patients with NSCLC pathology, age >18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2, and advanced stage (IIIB and IV) were treated with up to 6 cycles of gemcitabine 1250 mg/m2 (day 1 and 8) plus carboplatin AUC 5 (day 1) every 3 weeks. Patients who did not show progression after first-line chemotherapy were randomly assigned to receive switch maintenance with vinorelbine (25 mg/m2, day 1, 15) or the best supportive care until disease progression. RESULTS: A total of 100 patients were registered, of whom 34 had a non-progressive response to first-line chemotherapy and randomly received maintenance vinorelbine (n=19) or best supportive care (n=15). The hazard ratio of PFS in the vinorelbine group relative to the best supportive care group was 1.097 (95% confidence interval = 0.479-2.510; P-value =0.827). There was no significant difference between the overall survival for the two groups (P=0.068). CONCLUSION: Switch maintenance strategies are beneficial, but defining the right candidates for treatment is a problem. Moreover, the trial designs do not always reflect the real-world considerations. Switch maintenance therapy with vinorelbine, though had tolerable toxicity, did not improve PFS in patients with NSCLC. Therefore, other agents should be considered in this setting.

Clinicopathological Characteristics of Iranian Patients with Lung Cancer: a Single Institute Experience.

BACKGROUND: Lung cancer has long been a leading cause of cancer related death in both women and men worldwide. The focus of this study was to review clinicopathological features of Iranian patients diagnosed with lung cancer. MATERIALS AND METHODS: Clinicopathological data of 1353 primary lung cancer patients diagnosed during 17 years (1997-2014) in the "National Institute of Tuberculosis and Lung Disease" (NRITLD), Tehran, Iran, were retrospectively reviewed. RESULTS: The median age of patients was 60 (mean: 58.95 years, range: 16- 99) and adenocarcinoma was the most prevalent pathology (45.2%). Male/female ratio was 3.22 and 57.2% of patients were smokers (men 70.3%, women 15%). The majority (85.3%) were referred in advanced stages (stage IIIB and IV). CONCLUSIONS: Although some of our findings are in concordance with other studies in lung cancer there are some discrepancies particularly in terms of smoking status and median age of Iranian patients. Further clinical and epidemiological studies are warranted to elucidate etiologic and factors other than smoking contributing to development of lung cancer, such as environmental exposures or genetic predisposition.

Bilateral Lymphoblastic Lymphoma of Breast Mimicking Inflammatory Breast Cancer: A Case Report and Review of Literature.

We report a 45 year-old woman who had bilateral breast masses with extradural involvement. Pathologic report revealed malignant high-grade lymphoblastic lymphoma. Systemic chemotherapy was performed but 3 months later, lesions indicating relapse in bone and breast re-appeared. She received salvage chemotherapy, but 4 months after that she was expired.

Clinicopathologic and survival characteristics of malignant pleural mesothelioma registered in hospital cancer registry.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal thoracic tumor, which in the majority of patients is caused by prolonged exposure to asbestos fibers. We aimed at presenting clinicopathological and treatment outcomes of 60 patients of MPM registered in our hospital cancer registry. MATERIALS AND METHODS: Demographic characteristics of patients, exposure to asbestos, smoking habit, their clinicopathologic characteristics and survival analysis were described. RESULTS: Sixty patients had MPM. Forty patients (66.7%) were men. The mean age of patients was 55.8±11 years. Chest pain and dyspnea were the most prevalent symptoms (31.7%, and 30%, respectively). Thirty-six (61.7%) patients reported asbestos exposure. The median survival and Progression free survival (PFS) were 10.5 months (0.95CI=9.22-11.78) and 7.57 months (0.95CI=5.68-9.45), respectively. In multivariate analysis, exposure to asbestos and epithelioid subtype significantly extended the survival time. Bilateral involvement, high blood level of LDH and platelet count ≥400,000 significantly shortened the overall survival. CONCLUSION: MPM is still an important health problem in Iran. Given the aforementioned results, developing a national program to eliminate asbestos-related diseases according to the world health organization (WHO) recommendation is necessary.

Nutrition and lung cancer: a case control study in Iran.

BACKGROUND: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. METHOD: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. RESULT: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). CONCLUSION: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran.

Comparing docetaxel plus Cisplatin with Paclitaxel plus Carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: a single institute study.

The backbone of treatment in advanced non-small cell lung cancer is platinum-based doublet chemotherapy. We intended to compare the effectiveness of two commonly used regimens in real world practice. This single institute, parallel comparative post marketing study included 100 patients with chemo-naïve advanced (stage IIIB, IV) non-small cell lung cancer and Eastern Cooperative Oncology Group performance status of 0 to 2. They were randomly assigned by stratified blocks to receive Docetaxel/Cisplatin (DC, n=50) on day 1 or Paclitaxel/Carboplatin AUC 5 (PC, n=50) on day 1, every 3 weeks for up to six cycles. Primary end point was progression free survival (PFS); secondary end points were objective response rate, overall survival (OS) and toxicity. The administered dosage could be modified according to clinician's discretion for each individual patient. PFS was similar between DC and PC arms (4.5 ± 0.3 v 4.6 ± 1.8 months, respectively; HR= 1.337; 95% CI: 0.874 to 2.046, P = 0.181). Although median overall survival for DC arm was longer (17.2 ± 4.4 m) than PC arm (10.6 ± 0.7 m) but was not statistically significant (P = 0.300). The 1-year survival rates were in favor of DC arm (53.1% v 37.9%). Objective response rates were similar in both groups. In our study, hematologic toxicity and neuropathy were more frequent in DC and PC arms, respectively. In our study two commonly used regimens of DC and PC showed statistically similar outcomes in terms of PFS and OS, albeit numerically results of OS and 1-year survival were in favor of DC arm.

Gorham's Disease With Chest Wall Involvement: A Case Report and a Review of the Literature.

INTRODUCTION: Gorham's disease is a rare disorder characterized by osteolysis and abnormal vascular growth within bones. Diagnosis of Gorham's disease is often delayed and for accurate and early diagnosis high clinical suspicion is crucial. No specific treatment is available. Management options include surgery, radiation therapy and medical therapy. We aimed to present the first case of Gorham's disease with chest wall involvement in Iran. By review of the literature we discussed important issues of this rare disease including clinical findings, diagnosis and treatment options. CASE PRESENTATION: We present a 48-year-old man with a history of dyspnea following a blunt chest trauma who was admitted to our clinic several times due to reaccumulation of pleural fluid and chylothorax. Gorham's disease was finally established according to clinical manifestations and radiological findings including massive osteolysis in his left ribs and also histological examination. DISCUSSION: According to review of the literature and considering all treatment modalities the patients was successfully treated with a combination of radiotherapy, pamidronate and thalidomide. We suggest that this disease should be considered among differential diagnoses of patients with chest pain, pleural effusion and/or chylothorax with an unknown reason and more importantly history of chest trauma. In suspected cases, it is essential to examine biopsy specimens of the bone adjacent to the inflammated tissues in order to confirm diagnosis.

Relationship between XPD Lys 751 Gln polymorphism and colorectal cancer risk: a case-control study in a population-based study.

AIM: In our study, we analyzed the allelic frequency of XPD Lys751Gln polymorphism of the XPD gene and the correlation between its variant alleles with colorectal cancer in patients and control groups. BACKGROUND: Human cells are routinely exposed to mutagenic and carcinogenic aromatic amines via smoking, pollution areas and other sources. These chemicals can form DNA adducts in vivo and thus lead to DNA damage. Amongst the known genetic polymorphisms of the DNA-repair genes the xeroderma pigmentosum group D (XPD, also known as ERCC2) has been the most extensively studied most commonly. PATIENTS AND METHODS: This study has examined the relationship between the XPD Lys 751 Gln polymorphism and colorectal cancer in 88 patients and their 88 age and sex-matched controls. Genomic DNA from peripheral whole blood was extracted using Miller method to determine the genotype of subjects with RFLP-PCR analysis. RESULTS: This study shows cancer patients have more of the heterozygous genotype (XPD Lys 751 Gln) compared to control group. However the results are not statistically significant. Furthermore, colorectal cancer was less common in individuals with recessive homozygous genotype (P< 0.0001). CONCLUSION: This study suggests that individuals with heterozygous polymorphism (Lys/Gln) may have an increased susceptibility to colorectal cancer compared to other polymorphisms (Lys/Lys and Gln/Gln).

Relationship between angiogenic squamous dysplasia and bronchogenic carcinoma in patients undergoing white light bronchoscopy.

OBJECTIVE: To better understand the characteristic morphology of angiogenic squamous dysplasia (ASD) and its association with different types of common bronchogenic carcinomas using routine white light bronchoscopy. METHODS: Using a case-control design, 186 formalin-fixed paraffin-embedded blocks of bronchial tissue (136 cases, 50 controls) obtained from patients who underwent routine nonfluorescence bronchoscopy between 2004 and 2005 were studied. RESULTS: ASD occurred at a higher frequency in patients with neoplastic lesions compared with those without neoplastic lesions (28 of 136 versus one of 50). ASD was also more prevalent in patients with squamous cell carcinoma compared with other neoplasms. Seventy six per cent of the ASD patients (22 of 29) smoked cigarettes. The morphology of ASD on hematoxylin and eosin- and CD31-stained sections was characterized by prominent microvasculature and capillary projections closely juxtaposed to variable degrees of dysplasia in all of the bronchogenic carcinoma specimens, and to metaplasia in one case in the control group. CONCLUSION: ASD is a unique morphological entity that should be considered by pathologists even on bronchoscopic biopsies from patients who undergo white light bronchoscopy. The presence of ASD may represent a risk biomarker of bronchogenic carcinoma in screening programs and in chemoprevention of lung cancer.

Characterization of melanoma-associated antigen-a genes family differential expression in non-small-cell lung cancers.

BACKGROUND: The melanoma-associated antigen (MAGE) genes families are found in different cancers, including non-small-cell lung cancers. These genes are silent in normal tissues, except for the testis. The goal of this study was to investigate the differentially expressed profile of the different MAGE genes subclass in non-small-cell lung cancer (NSCLC) tumoral tissue. METHODS: Formalin-fixed paraffin embedded NSCLC resected tissues were collected from 31 patients hospitalized in our referral hospital, and 29 patients were diagnosed with either squamous cell carcinoma (SCC) or adenocarcinoma (ADC). We used a nested reverse transcriptase-polymerase chain reaction, which comprised independent amplification of MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12, to detect expression frequency of the MAGE-A family in lung tissue biopsies at both tumoral and nontumoral parts of patients' tissues. RESULTS: From 29 patients with diagnosis of either SCC (n = 16) or ADCs (n = 13), 58 samples were prepared. From 58 blocks sampled for this experiment, 37 tumoral tissue samples and 22 nontumoral tissue samples expressed at least one of the MAGE-A genes. MAGE-A4 gene had the highest incidence among all MAGE-A genes in both tumoral and nontumoral gens. In SCC and ADCs, the data showed expression of at least one of the MAGE-A genes in 59.4% and 69.2% of tumoral and nontumoral tissues, respectively. CONCLUSION: The detection of the MAGE-A genes expression could be a molecular tumor marker for early diagnosis and potential targets for active immunotherapy in NSCLC, particularly in ADCs and SCC. Besides, the frequency of different subtypes of MAGE genes may vary in different regions of world.

Evaluating the effect of zingiber officinalis on nausea and vomiting in patients receiving Cisplatin based regimens.

Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study.

Modification and implementation of NCCN guidelines on non-small cell lung cancer in the Middle East and North Africa region.

A lung cancer committee from the Middle East and North Africa (MENA) region was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Non-Small Cell Lung Cancer to create a platform for standard care in the region. The committee comprised different experts in thoracic oncology from the region, including the disciplines of medical and clinical oncology, radiation oncology, thoracic surgery, pulmonary medicine, radiology, and pathology. The committee reviewed version 2 of the 2009 NCCN Guidelines on Non-Small Cell Lung Cancer and identified recommendations requiring modification for the region using published evidence and relevant experience. These suggested modifications were discussed among the group and with a United States-based NCCN expert for approval. The recommended modifications, with justification and references, were categorized based on the NCCN Guidelines flow. This article describes these recommended modifications. The process of adapting the first NCCN-based guidelines in the region is a step toward helping to improve lung cancer care in the region and encouraging networking and collaboration.

Environmental risk factors for lung cancer in Iran: a case-control study.

BACKGROUND: Lung cancer remains the leading cause of cancer death in the world. In Iran, lung cancer is one of the five leading tumours and its incidence has been increasing steadily in both men and women. There is a paucity of data from Iran on risk factors for lung cancer. We evaluated environmental risk factors for lung cancer in a case-control study in five hospitals of Tehran. METHODS: Between October 2002 and October 2005, 242 (178 male, 64 female) patients with histologically confirmed lung cancer and two controls for each patient (242 hospital controls and 242 visiting healthy controls) matched for age, sex and place of residence were interviewed using a structured questionnaire on potential risk factors for lung cancer, including environmental and occupational exposures. Associations between risk factors and lung cancer were assessed using conditional logistic regression. RESULTS: Smokers were 66.5% of all cases (85.4% of men and 14.1% of women) and smoking was the strongest correlate of lung cancer in multivariate analysis [odds ratio (OR) 5.4, 95% confidence interval (CI) 3.2-8.9]. Occupational exposures to inorganic dusts (OR 4.2, 95% CI 2.8-6.7), chemical compounds (OR = 3.4, 95% CI 2.1-5.6) and heavy metals (OR 3.0, 95% CI 1.3-7.0) were also independent risk factors for lung cancer. CONCLUSIONS: In our study, smoking was the principal risk factor for lung cancer. However, preventable exposures in the environment, including occupational settings, should not be ignored.

High expression of minichromosome maintenance protein 6 in classic Hodgkin's lymphoma points to a cell cycle arrest in G1 phase.

BACKGROUND: Minichromosome maintenance protein 6 (MCM6) is one of the six proteins of minichromosome maintenance family that are involved in the initiation of DNA replication and thus represent a marker for proliferating cells. The aim of this study was to determine the proliferation characteristics of neoplastic cells in patients with classic Hodgkin's lymphoma. METHODS: Paraffin-embedded blocks of lymph node, mediastinal, subcutaneous chest wall, and lung mass biopsies of 55 patients with classic Hodgkin's lymphoma were immunostained by the proliferation-associated monoclonal antibodies; Ki-S5 (Ki-67 antigen) and Ki-MCM6 (MCM6 antigen). RESULTS: High MCM6 antigen expression was a striking feature of Hodgkin's and Reed-Sternberg cells (median: 85%, range: 35 - 99%) in comparison with lower Ki-67 expression (median: 63.5%, range: 1 - 98%, P<0.001). This indicates that MCM6 is already expressed in the early G1 phase, a cell cycle fraction that is not covered by antibodies specific to the Ki-67 antigen. The proliferation rates were determined by two markers, independent of histologic subtype, stage, presence of B symptoms, and size. CONCLUSION: These data show that a subset of Reed-Sternberg and Hodgkin's cells is arrested in the early G1 phase and the MCM6-positive cells do not necessarily represent the real proliferating compartment of Hodgkin's lymphoma. Clinical relevance of this marker in patients with Hodgkin's lymphoma should be investigated.

Generalized neutrophilic dermatosis: a rare presentation of myelodysplastic syndrome.

We present a 30-year-old man admitted with generalized cutaneous lesions, fever and cough. Examination of skin biopsies of a papular lesion revealed dense neutrophilic infiltration of the upper dermis, so these lesions were diagnosed as neutrophilic dermatosis. Peripheral blood examination and bone marrow findings confirmed the diagnosis of myelodysplastic syndrome with excess blasts. The cutaneous lesions improved after administration of corticosteroid and follow-up bone marrow examination revealed a normocellular marrow. One year later he referred with acute myelogenous leukemia (AML-M0). Unfortunately, he did not respond to treatment and died a few months later due to disease progression.