GJO ISSUE NO. 24, MAY 2017
  Issue No. 24 - May 2017
6-9 Pattern of Karyotypic Aberrations in Pakistani Patients with De Novo Acute Myeloid Leukemia
  Syeda Alia Abbas, Sadia Sultan*, Sana Ashar, Syed Muhammad Irfan
Hematology Department, Liaquat National Hospital and Medical College, Karachi, Pakistan 
    Background: Acute myeloid leukemia (AML) is a malignant disease of the bone marrow in which karyotypic analysis is the most important diagnostic and prognostic tool for predicting remission rate, relapse and overall survival. This study was carried out to determine the frequency and type of cytogenetic aberrations in de novo acute myeloid leukemia in adults at a tertiary care hospital.

Materials and methods: This descriptive cross-sectional study was carried out in the Hematology Department, Liaquat National Hospital from November 2014 to April 2016.A total of 51cases were diagnosed with AML during the study period. Cytogenetic analysis was carried out by banding technique on bone marrow aspirate samples.

Results: The mean age of the study subject was 42.03±17.70 years. Frequency of karyotyping abnormalities was observed in 47% of cases, in which most frequently occurring cytogenetic abnormalities were those of good cytogenetics including t(15;17) and t(8;21), seen in 23.5% and 9.8% of cases respectively. Intermediate risk cytogenetics including Del 9q was seen in 1.96% of cases. However, poor risk cytogenetics including complex cytogenetics, t(11;q23) and del (13) were seen in 7.8%, 1.96% and 1.96% of cases respectively. Normal cytogenetics was seen in 27 (52.9%) patients.

Conclusion: Karyotyping is one of the most important diagnostic and prognostic tools and a maximum benefit could be attained through cytogenetic analysis. Cytogenetic aberrations in our series are more or less similar as reported at national level with preponderance of good risk cytogenetics in our setting.

Keywords: Acute myeloid leukemia, Cytogenetic abnormalities.
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2 10-14 Tinospora Cordifolia Induces Cell Cycle Arrest in Human Oral Squamous Cell Carcinoma Cells
    Parveen Bansal1*, Manzoor Ahmad Malik2, Satya N Das3, Jasbir Kaur4*
  1. University Centre of Excellence in Research, Baba Farid University of Health Sciences, Punjab, India.

  2. Cancer Diagnostic and Research Centre, Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India.

  3. Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.

  4. Department of Ocular Biochemistry, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

    Natural products with medicinal value are gradually gaining importance in clinical research due to their well-known property of no side effects as compared to drugs. Tinospora cordifolia (Guduchi) has been used for centuries in Ayurvedic system of medicine for treating various ailments including cancer. In present study, we found that the Tinospora cordifolia extracts (TCE) induced inhibition of proliferation of KB cells was associated with arrest of G0/G1-phase of cell cycle. The effectiveness of TCE in checking the growth of KB cells without altering the growth of normal peripheral blood mononuclear cells (PBMC) indicates that Tinospora cordifolia has differential effect on normal and malignant cells hence, it may have therapeutic potential in cancer.

Keywords: Tinospora cordifolia, cell cycle, antiproliferative, Oral squamous cell carcinoma.
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3 15-19 Detection Mutations of JAK2 exon 12 in Patients with JAK2 (V617F)-negative Myeloproliferative Disorders

S. Z. Makani1, N. Parsamanesh2, S. Mirzaahmadi1, M. Hashemi3, F. Shaveisi-Zadeh4, N. Mansouri4, M. Ghazi5, *A. Movafagh4

  1. Department of Biology, Zanjan Branch, Islamic Azad University, Zanjan, Iran
  2. Department of Molecular Medicine, faculty of Medicine, Birjand Medical University, Birjand, Iran.
  3. Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
  4. Department of Medical Genetics, School of Medicine, Cancer Research Center, Shohada Referral Hospital, Shahid Beheshti University of Medical Sciences, Tehran- Iran.
  5. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    Background: Mutations in exon 12 of JAK2 gene are detected as clonal markers in hematopoietic lineages in myeloproliferative disorders (MPNs). Our aim was, to study the relation between N542-E543del mutation of JAK2 gene and myeloproliferative neoplasms in V617Fnegative patients.

Patients and Methods: DNA specimen from 34 patients and 44 healthy controls were genotyped using ARMs- PCR method. We analyzed exon 12 JAK2 aberration in 34 myeloproliferative cases to be readily detected by both ARMS-PCR and DNA analysis regardless of whether peripheral blood or bone marrow cells was manipulated as the origin of RNA.

Results: In this case-control study, there was no significant difference in Pearson chi square analysis between the patients and control groups in genotype distribution of the frequency of single nucleotide polymorphism rs7869668 of JAK2 exon 12 (P > 0.05). Also, gene detection finding showed that the patients were negative of JAK2-V617F mutation.

Discussion and Conclusion: Present finding on a small number of patients diagnosed of various categories of MPDs revealed and needs more investigation and data for the prevalence and the incidence of the JAK2–V617F mutation. However, the clinical and genotyping of finding a disorder and non-significant correlation between patients and control group in this study in such a small fraction of the patients is unknown.

Keywords: Genotype; JAK2 V617F; Exon 12; Myeloproliferative Disorders
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4 20-23 Hepatocellular Carcinoma Peritoneal Metastasis: Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
    John Spiliotis, Georgios Nikolaou, Nikolaos Kopanakis, Dimitra Vassiliadou, Alexios Terra, Elias Efstathiou
1st Department of Surgical Oncology, Metaxa Cancer Hospital, Greece
    Introduction: Peritoneal dissemination of hepatocellular carcinoma (HCC) is a rare presentation with an incidence of 2-6%. The most common cause of peritoneal deposits is a ruptured HCC that results in tumor spillage into the peritoneal cavity. The overall incidence of spontaneous ruptures of HCC ranges from 5 to 15% and carries a high mortality rate of up to 50%. Other factors influencing peritoneal dissemination are the lymph node metastasis and the direct diaphragmatic invasion and there is no significant association with past history of FNAB, or percutaneous RFA or ethanol injection and lung or adrenal metastasis.

Clinical Study: We present our experience with 4 patients with localized peritoneal metastases from HCC controlled and managed with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The mean peritoneal cancer index (PCI) was 10.2. In two cases there is a history of rupture at the onset of diagnosis and in one case dissemination of peritoneal cavity after FNB procedure. All patients after CRS and HIPEC received Sorafenib.

Results: In our study the mean time of onset of peritoneal metastasis was 13.5 months from initial operation and the mean survival was 30 months. Our results are comparable with other studies.

Conclusion: Peritoneal metastasis of hepatocellular carcinoma is rare and the benefit of systemic chemotherapy is poor and from Sorafenib is not well described. Surgical resection of extrahepatic HCC metastasis remains challenging. However several case reports and a few case series have provided that surgical resection of HCC peritoneal implants may benefit. We believe from our experience in well-selected patients with peritoneal metastasis from HCC, cytoreductive surgery with HIPEC and Sorafenib may prolong survival compared to systemic chemotherapy alone.

Keywords: HIPEC, cytoreductive surgery, Hepatocellular carcinoma, peritoneal metastasis
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5 24-29 The Effect of Dose-Volume Parameters on Central Nervous System Relapse in Pediatric Patients with Acute Leukemia Receiving Prophylactic Cranial Irradiation

Zeliha Guzeloz1, Ayse Nur Demiral2, Fatma Eren3, Mehmet Adigul2, Ahmet Ergin Capar4, Handan Cakmakcı5, Sebnem Yilmaz6, Ozlem Tufekci6, Hale Oren6, Riza Çetingoz2

  1. Dept of Radiation Oncology, SBU Tepecik Training and Research Hospital, İzmir, Turkey.
  2. Dept of Radiation Oncology, Dokuz Eylül Univ Faculty of Medicine, İzmir, Turkey.
  3. Dept of Physical Med and Rehab, Bezmi Alem Univ Faculty of Medicine, İstanbul, Turkey.
  4. Dept of Radiology, SBU Tepecik Training and Research Hospital, İzmir, Turkey.
  5. Dept of Radiology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
  6. Dept of Pediatric Hematology, Dokuz Eylül Univ Faculty of Medicine, İzmir, Turkey
    Aim of the study: To investigate the effects of dosevolume parameters of brain parenchyma, optic nerves (ONs) and cribriform plate (CP), which were determined on central nervous system (CNS) control in pediatric leukemia patients who have undergone prophylactic cranial irradiation (PCI) at our department.

Patients and Methods: In the current study, the records of 14 patients were examined retrospectively. Along with the minimum and maximum doses for brain and CP, D95% (minimal dose received by the 95% volume of a structure) and V95% (percent volume of target receiving 95% of prescribed dose) could be obtained from the dose-volume histogram. Statistical analyses were conducted using the Mann Whitney test in SPSS-15.

Results: ALL/AML ratio was 9/5. CNS relapse was observed only in 2 patients. The minimum dose was 1249 (1100-1782) cGy, 1036 (547-1651) cGy, 856 (308-1460) cGy and 1234 (922-1727) cGy for brain parenchyma, right ON, left ON and CP, respectively. The value of D95%/D was 1.01 (1-1.06) and 0.99 (0.92- 1.06) for brain parenchyma and CP, respectively. V95% was 99.8 % (98.6%-100%) and 98.1% (80.5%-100%) for brain parenchyma and CP, respectively. The analyses revealed that none of the target tissue dose-volume parameters for PCI affected CNS relapse (p>0.05).

Conclusion: In our study; it was found that the dosevolume parameters of the brain, CP and ONs did not have any effect on CNS relapse. Along with the other clinical factors, the scarce number of patients included in the study might have concealed the effects of parameters related to RT.

Keywords: Prophylactic Cranial Irradiation (PCI), Acute Leukemia, Dose-volume Parameters, Central Nervous System, Relapse
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6 30-37 Long-term Results of Post-operative Pelvic Image guided Intensity Modulated Radiotherapy in Gynecological Malignancies

Rashi Agrawal1, Sowmiya Prithiviraj1, Dinesh Singh1, Vaishali Zamre2, Sandeep Agrawal1, Arun Kumar Goel2, Kanika Gupta2, Bala Subramanian1

    1 Dept. of Radiation Oncology, 2 Dept. of Surgical Oncology, Max Superspeciality Hospital, Ghaziabad, Delhi NCR, India
    Objective: To assess late clinical outcomes with image guided intensity modulated radiotherapy (IG- IMRT) in gynecological malignancies.

Patients and methods: We have been practicing IG IMRT for gynecological malignancies since January 2009. Here we are presenting our experience with this modern technique at median follow up of 38 months. During whole treatment bladder filling protocol was followed. Both target volumes and critical structures were contoured according to RTOG guidelines. Dose prescribed to clinical target volume (postop bed and nodal volume) was 50.4 Gy in 28 fractions. Cone beam CT (CBCT) scans were taken to quantify the status of target volume and normal structures.

Results: 80 patients were evaluated and analyzed who were treated from January 2009 to December 2014. Median age of our patients was 56.5 years. Out of eighty, forty four patients (55%) were of carcinoma endometrium and the rest 36 (45%) were of carcinoma cervix. None of our patients experienced late grade 3 or 4 bladder toxicity. Although late grade 3 and 4 bowel and rectal toxicity was experienced by single patient. 2.5% patients developed local recurrence, 5% patient developed nodal with distant metastases and 6.25% only distant metastases. Three of our patients developed lung cancer as second primary during follow up. 76.2% patients are alive with regular follow up.

Conclusions: Our study concluded that IG IMRT increases patient compliance and reduces long-term side effects in post-operative gynecological malignancies without compromising local-regional control, disease free survival and overall survival.

Keywords: Chronic toxicity, IMRT, Gynecological malignancy, Postoperative
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7 38-42 Epidemiology and Survival Analysis of Gastrointestinal Stromal Tumors in Lebanon: Real-life study from a Hospital tumor registry 2000-2015
    Elie El Rassy1, Fadi Nasr1, Tarek Assi1, Toni Ibrahim1, Nathalie Rassy1, Joseph Bou Jaoude2, Marcel Massoud3, Georges Chahine1
  1. Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
  2. Department of Gastroenterology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
  3. Department of Oncology, Notre-Dame des Secours University Hospital, Faculty of Medicine, Université Saint-Esprit de Kaslik, Beirut, Lebanon
    Background: We report, to our knowledge, one of the largest studies concerning gastrointestinal stromal tumors (GIST) in the Middle East. We also present a survival analysis of GIST in our 15-year real-life experience.

Methods: We studied demographic, epidemiologic and survival characteristics of 70 patients with confirmed GIST in a cross-sectional study between 2000 and 2015.

Results: The median age of our patients was 62 ±12.8 years (range, 25-84) with a male to female ratio of 1.7. The gastric and the small intestine GIST were the most frequent primary sites. The majority of our patients had localized disease at diagnosis (81.4%). Metastasis was limited to the abdominal cavity and lymph node spreading occurred in 14.3%. After a median follow up of 838 days (range 48-4309 days) with only two patients reported dead, two and five-year overall survival rates were 98% and 95% respectively. Median overall survival was not reached.

Conclusion: In the light of our results, molecular profiling of Lebanese patients with GIST would be of interest to detect the particularities responsible for the increased overall survival and lymph node spreading.

Keywords: GIST; Epidemiology; Middle East; Lebanon; Survival
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8 43-47 Giant Primary Sinonasal Mucosal Melanoma: A Rare Malignancy

Mehtab Alam, Mohd Aslam, Piyush Kant Singh, Shahab Farkhund Hashmi, Syed Abrar Hasan
Department of Otorhinolaryngology, J.N. Medical College, A.M.U, Aligarh, India

    It is extremely rare to find a case of primary sinonasal mucosal melanoma, which is more aggressive and have poorer outcome than its cutaneous counterpart. This tumour is refractory to the treatment which includes wide surgical excision with or without adjuvant postoperative radiotherapy. We are reporting a case of 60 year old female who presented with right sided nasal mass and facial deformity, in whom the diagnosis of mucosal melanoma was made on histopathological examination and confirmed by immunohistochemistry.

Keywords: Mucosal melanoma, Sinonasal, Immunohistochemistry
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9 48-50 Sarcomatoid Carcinoma of the Maxilla: A Case Report with Literature Review
    Lahcen Khalfi¹, Yassine Ziani², Mouna Kairouani³, Odry Agbessi¹, Mohammed Kamal Fiqhi¹, Alae Guerrouani²*, Karim El Khatib¹
  1. Department of Oral and Maxillofacial Surgery, Mohammed V Teaching Military Hospital, Rabat, Morocco.
  2. Department of Oral and Maxillofacial Surgery, Al Farabi Hospital, Oujda, Morocco.
  3. Department of Medical Oncology, Regional Center of Oncology, Oujda, Morocco
    Sarcomatoid carcinoma is a very rare malignant and aggressive tumor that can involve the maxillary sinus. We report the case of a 46 y/o male who presented a tumor of the right maxillary sinus with extension to the right nasal cavity. The diagnosis of sarcomatoid carcinoma was set by histology and immunohistochemistry. The patient received concomitant cisplatin based chemoradiotherapy with no response after 3 months of treatment. He died 6 months later. Through the present case and the review of literature we discuss all aspects of this entity: clinical presentation, differential diagnoses, pathology, treatment and prognosis.

Keywords: Carcinoma, spindle-cell, Maxillary neoplasms
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10 51-54 Neuroendocrine Carcinoma of Gall Bladder: A Rare Presentation with Review of Literature
    Amit Gupta1, Parvez Ahmed1, Prashant Durgapal2, Pooja Kala2, Shalinee Rao2, Rajesh Pasricha3, Sanjeev Misra4
    1 Dept. Of Surgery, 2 Dept. of Pathology, 3 Dept. of Radiotherapy, 4 Director of AIIMS Rishikesh,
All India Institute Of Medical Sciences, Rishikesh, Uttarkhand, India
    Neuroendocrine tumors are the rarest tumors of gallbladder. The most aggressive variant is neuroendocrine carcinoma which presents in about 0.5% of all gallbladder carcinomas and 0.2% of all neuroendocrine tumors. It seems possible that survival rates can be improved by utilizing wide surgical resection combined with chemotherapy. We report a case of neuroendocrine carcinoma of gall bladder in a 20-year old female patient. In present case, the etiology was not known as patient did not have cholelithiasis or any symptoms related to chronic inflammation. Our extensive search of indexed literature shows that our patient was the youngest patient with this disease so far.

Keywords: Gall bladder, Neuroendocrine carcinoma, cholecystectomy Corresponding
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11 55-60 Clear Cell Variant of Calcifying Epithelial Odontogenic Tumor: A Rare Clinical Entity
    Husain Sabir1*, Subhash Kumbhare2, Saurabh Redij3, Namrata Gajbhiye4

1 Raj Multispecialty Dental Clinic, Indore. (M.P), India. 2 Dept. of Oral Medicine & Radiology, 3 Dept. of Oral and Maxillofacial Surgery, 4 Dept. of Oral Pathology and Microbiology, Government Dental College & Hospital, Nagpur (M.S), India

    Calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic neoplasm of the jaws. Although clear cells have been reported in approximately 8% of cases of CEOT, the exact nature of these cells in clear cell calcifying epithelial odontogenic tumor (CCEOT) has not been elucidated. Presence of clear cells in CEOT may confer a more aggressive behavior to the lesion and a tendency for recurrence and metastatic spread. We report of a case of CCEOT in a 63 year old female patient which was first treated with enucleation; however recurrence prompted a segmental resection along with coronoid and condyle.

Keywords: Calcifying epithelial odontogenic tumor; clear cells; enucleation; biopsy;
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12 61-65 Hodgkin’s Lymphoma as a Multiloculated Lung Cavity Lesion
    Aisha M. Al-Osail1, Hind S. Al-Saif 2, Mashail M. Al-Hajri3, Hajer M. Al-Zuhair3, Deemah A. Al-Abdulhadi3, Emad M. Al-Osail3, Sarah M. Al-Hajri3

1 Department of Internal Medicine, 2 Department of Radiology, 3 Department of Internal Medicine,
Imam Abdulrahman Bin Faisal University, Prince Saud bin Fahd Street, Khobar, KSA

    Background: Pulmonary manifestation of Hodgkin’s lymphoma is common, and recently, single and/or multiple lung cavities with air-fluid levels has been reported as a primary manifestation of Hodgkin’s lymphoma. However, the unusual presentation of the lung cavity itself has not been previously reported for Hodgkin’s lymphoma, especially as the first presentation of the disease.

Case Presentation: We report a 16-year-old male who presented to the emergency department with chief complaints of fever, unintentional 10-kilogram weight loss, a productive cough and pulmonary cavity for investigation. The patient’s CT scan indicated multiloculated cavity lesions in the middle lobe with an air-fluid level and multiple enlarged mediastinal lymph nodes, which have not been previously reported as a primary presentation for Hodgkin’s lymphoma or in the histopathology of the nodular sclerosing type of classical Hodgkin’s lymphoma.

Conclusion: Pulmonary manifestation of Hodgkin’s lymphoma has already been reported and must be part of the differential diagnosis of lung cavity lesions, even if the likelihood is low based on previous reports, especially in younger individuals. Multiloculated lung cavities can be the first presentation of Hodgkin’s lymphoma.

Keywords: Hodgkin’s lymphoma; lung cavity; nodular sclerosing.
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13 66-69 Breast Adenoid Cystic Carcinoma: A Rare Case Report and Review of the Literature
  Lamiae EL Amarti1,2, Hanan Raiss1,2, Mohamed Layachi1,2, Salif Baldé1,2, Hamza Ettahri1,2, Ibrahim Elghissassi1,2, Hind Mrabti1,2, Hassan Errihani1,2
  1. Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco;
  2. Faculty of Medicine and Pharmacy, Mohammed V University, Souissi, Rabat, Morocco
    Background: Primary adenoid cystic carcinoma (ACC) of the breast is a rare subtype of invasive breast cancer. It has a particular interest because of its excellent prognosis conversely to other triple-negative breast cancers that are associated with poor prognosis. The place of chemotherapy and radiotherapy remains controversial and there is no consensus on optimal management of the ACC of the breast.

Case Report: A 50-year-old woman, presented with a palpable right breast lump. Core biopsy of the lump revealed an adenoid cystic carcinoma. A lumpectomy with axillary lymph node dissection was performed and completed by a mastectomy because of the positive surgical margins. The histopathological examination revealed an adenoid cystic carcinoma, with negative expression of hormone receptors and human epidermal growth factor receptor 2 HER2 and with no lymph node involvement. The patient underwent adjuvant sequential chemotherapy with anthracycline and taxane followed by radiotherapy. We discuss diagnosis, prognostic, and treatment options for ACC of the breast in light of existing literature.

Conclusion: Adenoid cystic carcinoma of the breast is a rare variant of triple negative breast cancer with excellent prognosis. Surgical treatment is the mainstay with no clear consensus for radiotherapy and chemotherapy.

Keywords: adenoid cystic carcinoma, breast, diagnostic, prognosis, treatment
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14 70-74 Industrial Pollutants and Nasopharyngeal Cancer: An Open Question
    Roberto Menicagli1, Gianni Bolla2, Laura Menicagli3, Anastassia Esseiridou3
  1. RomaBiomed Research Martiri Liberta ‘20060 Mediglia Italy.
  2. University Milan, Department of Science, Cliniche E Comunita, Italy
  3. IRSS Policlinico San Donato, University of Milan, Italy
    Introduction and Objectives: Nasopharyngeal Carcinoma represents 0.7% of the total cancer cases in the world with an ASR index of 1.7 and is widely associated with Epstein-Barr virus. It is not common in Italy (ASR index of 0.5) while in China (ASR 1.9), one third of the clinical cases are observed in Guangdong (ASR index 11.3). It is also quite common in Malaysia and Indonesia. The activation of the cancerogenesis process happens after the exposure to some environmental parameters that epidemiological studies have indicated with various dietary habits, mainly for salted fish consumption. The purpose of this work is to highlight such as exposure to compounds, such as formaldehyde, which is present in the different working conditions of these countries and may lead to the real cause to establish the carcinogenic process.

Materials and Methods: The most recent publications regarding the impact of various external factors on Pub Med, Google, TOXLINE, Chem Abstract, were analyzed with the radiological data that were found in Milan hospitals database.

Results: The relationship between food consumption and nasopharyngeal cancer are not clear and statistically insignificant in Indonesia. In Malaysia, the preparation of natural rubber for the use of formaldehyde is a dangerous environmental factor. The same exposure is a risk factor in Guangdong, where many workers are employed in the wood panel industry. Incidence of cancer in these Chinese ethnic groups decreases when they migrate to other countries. In the last 5 years, few cases were recorded in Italy, without any apparent change in ethnic environmental factors or HBV infection

Discussion: In the production of natural rubber, a lot of people are exposed to formaldehyde during the various steps of preparation and production such as stripping, drying and coagulation without observing proper environmental hygiene precautions. The same working conditions are present in industrial production of wood panels in Guangdong, China. The relationship between exposure to formaldehyde and nasopharyngeal cancer is demonstrated by the fact that epidemiological studies on the population of this Chinese district whose immigrant populations were not exposed to these pollutants, the appearance of these tumors decreases. Also an examination of our radiological data in Italy shows that in about one hundred sixty cases of nasopharyngeal cancer none of the patients were Indonesian or Chinese

Conclusion: The preliminary results of our study suggest that EPST-BARR virus could be a risk factor if associated with exposure to compounds such as formaldehyde which is present in industrial productions of countries like Indonesia, Malaysia, and China.

Keywords: nasopharyngeal cancer, natural rubber, wood panel, formaldehyde, migrants
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