Background: Recent studies indicate the immune dysfunction in cancer patients in comparison with healthy individuals. The quality and quantity of this dysfunction are not equal in all patients even with similar cancer type. Aim: This study aims to correlate health locus of control (HLC) beliefs with CD4+ helper T (Thelper) cells, T regulatory (Treg) cells, NK cells, IL-1ß and TNF-a in breast cancer patients.

Patients and methods: The study included 30 early diagnostic breast cancer patients who responded to Form C of the MHLC questionnaire that assessed internal (IHLC), chance (CHLC), doctor (DHLC) and other person’s (OHLC) control of the patient’s health status. Peripheral blood samples were collected to analyze the numbers and phenotype of Thelper cells, Treg cells and NK cells by flow cytometry and to measure gene expression of IL-1ß and TNF-a with real time PCR.

Results: A significant positive correlation was found between IHLC with Thelper cells and NK cells. However, a significant inverse correlation was found between DHLC with NK, Thelper and Treg cells.

Conclusion: There is strong probability that the quality of immunity in cancer patients is related to their MHLC beliefs. Further research is recommended for studying whether MHLC beliefs of patients with other types of cancer can improve their immune responses and how beliefs control immune system.

Key words: Breast cancer; Thelper cells; Cytokines; locus of control; Immune; NK; Treg cells; IL1-ß; TNF-a.

12-18

19-25

Introduction: Breast cancer (BC) is a heterogenous disease and a major public health burden in Bahrain. Based on hormone receptor status (ER, PR, and HER2), BC can be divided into four molecular subtypes: Luminal A, Luminal B, HER2+, and Triple negative, each of which display distinct clinical behaviour.

Patients and Methods: This retrospective study included 216 patients diagnosed with BC between November 2017 and May 2019 at the Bahrain oncology centre. The clinicopathological characteristics (age, size of tumour, grade, lymph node involvement, metastasis) were examined, in addition to immunohistochemical markers (ER, PR, and HER2), and BRCA 1 and 2 status (when indicated). SPSS was used to evaluate the correlation between the molecular subtypes and different clinicopathological features.

Results: BC in Bahraini women was relatively of large size (68.5% larger than 20mm), with frequent metastasis to the lymph nodes (57.4%). The mean age at diagnosis was 51.8 years ±11.5, with invasive ductal carcinoma (IDC) being the most common histological type (90.3%). The most common molecular subtype was Luminal A (60.2%), followed respectively by luminal B (19%), triple negative (13.4%) and HER-2 (7.4%). Discussion: Significant differences were found between the subtypes regarding grade (p=0.001) and BRCA mutation status (0.001). Triple negative subtype was associated with highly-aggressive behaviour compared to the other subtypes. It presented at younger age, with high grade, large tumor size, and predominance to distant metastasis. It was also linked with positive BRCA mutations.

Conclusion: A significant proportion of Bahraini females with BC present with aggressive features (i.e. younger age, poorly differentiated tumors, and lymph node involvement). Expectedly this was associated with underlying aggressive molecular subtypes (namely TNBC). The aggressive properties of such molecular subtype mandate further molecular testing to identify more accurate prognostic and predictive targets for effective treatment and risk reduction strategies.

Keywords: Breast Cancer, Molecular subtypes, Bahrain, Triple negative breast cancer, BRCA mutation.

Introduction: Luminal B breast cancer is associated with a poor prognosis and resistance to hormone therapy. Studies have suggested that Ras-related protein 25 (RAB25), a member of Rab small GTPase family, is involved in breast cancer pathogenesis. Our aim in the present study is to analyze the association between RAB25 protein expression and clinical and pathological characteristics, and to investigate whether the expression of RAB25 was associated with a specific molecular subtype of breast cancer.

Materials and Methods: A retrospective study was conducted regarding female patients diagnosed with breast cancer; clinicopathologic data was obtained from medical reports. RAB25 expression was evaluated by immunohistochemistry in 57 primary breast cancer samples. The results were correlated with clinicopathologic variables and different breast cancer molecular subtypes.

Results: RAB25 expression was significantly associated with tumors expressing oestrogen receptor (P=0.03). A high significant difference was observed by analyzing RAB25 expression in various breast cancer subtypes (P=0.01). RAB25 expression was found in 66.7% of Luminal B breast tumors, considered as the most aggressive hormone dependent mammary tumors and was strongly associated with luminal breast cancer subtypes (p=0.004) but not with age, tumor size, SBR grade, axillary lymph node, or tumor stage.

Conclusion: RAB25 deregulated expression is most common in luminal B breast cancer tumors suggesting that RAB25 could be a potential therapeutic target for this molecular subtype.

Keywords: RAB25, Breast cancer, molecular subtypes, Luminal B, Therapeutic target

Introduction: Prostate cancer is one of the most common cancer among men in the world. Radical prostatectomy is the gold standard treatment for localized prostate cancer but advanced diseases are treated with hormonal therapy. Unfortunately, this treatment is not curative and approximately after 2 years, castration resistant prostate cancer occurs. In this study we aimed to investigate the terminology of castration resistant and refractory, hormone resistant and refractory articles on Web of Science database.

Materials and Methods: We searched the articles in the title section such as castration resistant prostate cancer, castration refractory prostate cancer, hormone resistant prostate cancer and hormone refractory prostate cancer between 1975 and 2018. Categories, publication years, document types, authors, countries, funding agencies and citation reports were recorded in 4 groups.

Results: There were 6733 articles in the system. Most of the articles (72.16%) were published as using castration resistant title. The United States of America and Italy were in the top 5 countries in 4 titles. Oncology and urology nephrology categories consisted more than 80% of the articles. Of these articles, only 1745 (26%) articles had funding agency. Discussion: Different terminology can be used in some diseases. One of these diseases is castration resistant prostate cancer which is referred to different terms such as castration refractory, hormone resistant and refractory. In this study we searched the literature and discussed the results.

Conclusion: Castration resistant prostate cancer is a serious health problem for clinicians and patients. If international associations, journals and authors use the same terminology, the articles can be published without different titles in the literature.

Keywords: prostate cancer, bibliometry, castration resistant, hormone

Background: Worldwide, the frequency of ALK rearrangement ranges between 3-6%, however its prevalence in the Middle Eastern population has not been reported. The aim of this study is to determine the frequency of the ALK rearrangement, as well as the clinico-pathologic characteristics of Lebanese patients with ALK-rearranged lung adenocarcinoma.

Methods: 152 patients diagnosed with non-squamous non-small cell lung carcinomas (NSCLC), at Hôtel-Dieu de France University Hospital between February 2014 and July 2016, were included in the study. ALK gene rearrangement expression was screened by immunohistochemistry (IHC) (D5F3 Clone). Positive cases were then sent for confirmation with Fluorescence in situ hybridization (FISH) technique.

Results: On immunohistochemistry, patients were distributed as following: score 0: n=108, score 1+: n=26, score 2+: n= 9, score 3+: n= 9. ALK gene rearrangement was detected in 6 out of 18 (2+ and 3+ score) tested patients by FISH technique. The presence of ALK rearrangement was significantly associated with the female gender (n=6, p=0.003) and with non-smoking status (n=4, p=0.0.18).

Conclusion: This study confirms that the prevalence of the ALK gene rearrangement in the Middle Eastern region is within the worldwide ranges and is almost exclusive to patients with adenocarcinoma subtype and tends to occur more frequently in women and non-smokers.

Keywords: epidemiology; ALK rearrangement; lung adenocarcinoma; Middle East; Lebanon

Introduction. BI-RADS in mammography screening is the guide to give a standardized terminology in mammary images. The BI-RADS 3 (uncertain cases) protocol requires anew mammography after six months. This matter of time usually generates much concern and anxiety in patients and in the Radiologists. The aim of this study is to show that using the test of micronuclei (MN) in exfoliated mucosa buccal cells a very early diagnosis is achieved.

Material and Methods. We performed an extensive search on Pub Med for “micronuclei in exfoliated buccal cells in breast cancer “and micronuclei in breast cancer”. We looked for the keywords in free text and with the cross-referencing method application. We experimentally got samples of buccal mucosa cells from twenty women BI-RADS 3 and twenty women BI-RADS 2. We fixed the samples with Papanicolaou staining. We registered the percentage of the cells containing MN in a total of 500 cells for each sample. The U Mann Whitney Calculator is the test for the statistical analysis of the results.

Results. Many studies showed that breast cancer produced MN both in exfoliated cells and in needle aspiration. Their score’s count was higher than compared to benign cases, while in the peripheral blood lymphocytes, the results for the MN test were not reproducible. In our preliminary study, the mean percentages of MN in buccal mucosa cells of BI-RADS 3 vs BI-RADS2 didn’t show a significant difference: p = 0.05. Two samples of BI-RADS 3 group had a much higher count of MN with a mean of 2.91 ±0.09, 2.88 ±0.08, respectively. This case required biopsy despite the in most of the cases of BI-RADS 3 investigated, the MN test confirmed their benignity.

Discussion. In literature, several studies have shown that the genetic damage in breast cancer cells results in MN increased production. Our research showed that in some cases of BI-RADS 3 there was a great increase in MN level. This fact happens in the patients who have taken oestrogens for many years. This therapy is definitely a strong risk factor for breast cancer development because the excesses of any type of hormones interacts with normal breast cell differentiation process. This BI-RADS 3 situation needs further investigation.

Conclusion. It’s interesting to apply the MN scoring in BI-RADS3 because in some cases this test can expect a cancer diagnosis by at least six months’ time because, in the other cases, test result can reassure both patient and Radiologists who will wait for the next following checkup with no anxiety.

Keywords: BIRADS, breast cancer, micronucleus

Introduction: Only a few studies (n=5) have focused on the importance of preoperative high white blood cell (WBC) count (leukocytosis) as a prognostic marker in patients with endometrial cancer (EC). Nevertheless, more related studies are needed to solidly corroborate these findings. To the best of our knowledge, no such study has been conducted in the Gulf region and Saudi Arabia in particular.

Methods: A retrospective cross-sectional study was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. The medical records of 130 patients with endometrioid-type EC were reviewed for clinico-pathological factors (that is, age, tumor stage, endometrioid grade, myometrial invasion depth, lymphovascular space involvement and recurrence) and survival outcomes. Survival outcomes included disease-free survival (DFS) and overall survival (OS). Leukocytosis was defined as a WBC count level >10 x 103 cells/uL. Chisquare test was used for univariate analysis of categorical data. Survival analyses of DFS and OS were calculated according to the Kaplan-Meier estimates method and compared by using two-tailed log-rank test. Univariate and multivariate analyses of survival were performed using Cox proportional hazards model. Statistical significance was regarded as a p value <0.05.

Results: The mean age was 59 ± 10.5 years (range: 36–99). The overall mean preoperative WBC count was 7.7 ± 2.4 x 103 cells/uL (range: 2.7–17 x 103). The frequency of preoperative leukocytosis was 18.5% (n=24). Patients with preoperative leukocytosis have statistically significant higher rates of advanced FIGO stage III–IV disease (p=0.007) and positive tumor recurrence (p=0.009) than patients with normal preoperative WBC count (chisquare test). Patients with preoperative leukocytosis have a higher statistically significant probability of developing recurrence than patients with preoperative normal WBC count (29.4 vs. 11.8%, p=0.008, log-rank test). Patients with preoperative leukocytosis have statistically significant lower mean DFS (58.3 ± 6.9 vs. 67.9 ± 2.3 months, p=0.015) and 5-year DFS rate (66.7 vs. 86.8%, p=0.015) than patients with normal preoperative WBC counts (log-rank test). However, there were no statistically significant differences between patients with preoperative leukocytosis and normal WBC counts in terms of mean OS (73.8 ± 4.5 vs. 79.3 ± 2.1, p=0.581) and 5-year OS rate (87.5 vs. 91.5%, p=0.581), respectively (log-rank test). Multivariate analyses using Cox proportional hazards model failed to significantly demonstrate preoperative WBC count as an independent prognostic factor of DFS and OS (log-rank test, p>0.05).

Conclusion: Preoperative leukocytosis is not rare in patients with endometrioid-type EC. Besides, preoperative leukocytosis is correlated with poor tumor FIGO stage, higher cumulative incidence of relapse and poor DFS in the univariate analysis. Our study suggests that preoperative leukocytosis may identify high-risk patients who may require more intensified therapy in terms of aggressive debulking and/or perioperative chemotherapy.

Keywords: preoperative, white blood cell, leukocytosis, endometrial cancer, Saudi Arabia

A cell is dying when there is no repair after damage. Indeed, the etiology of cancers associates with damaged or unrepaired cells. Cancer results from imbalance between cell’s oxidant and antioxidant defenses. This study aimed to review formation of cancer associated to oxidative stress. Tumorgenesis is caused by deregulation of the redox homeostasis by reactive oxygen species that stimulate the formation of tumor by starting an abnormal introduction of signaling nets. Proliferation accompanied by uncontrolled growth could lead to development of mass cancer cells. Kinases/phosphatases, transcription factors, reactive oxygen-nitrogen species and signal transduction are the most important cascades. The biology of tumor is affected by: 1) redox control through growth factor receptor signal, 2) superoxidase production due to small amount of oxygen, 3) infiltrating cytotoxic immune cells, 4) anticancer treatments, 5) repetitive ischemia-reperfusion cycles due to irregular blood supply and 6) inflammation.

Keywords: Oxidant; Anti-oxidant; Cancer; Bladder

A 5-year old boy presented with a picture of communicating hydrocele and was discovered to have an abdominoscrotal lymphangioma after undergoing hydrocele surgery. Upon initial presentation the lymphangioma was missed and the child underwent inguinal approach surgery for hydrocele. The lymphangioma was then noticed as an abdominal lump due to a rapid increase in size within 1 week following the hydrocele surgery. The sudden enlargement of the lymphangioma was due to intra-cystic hemorrhage post-operatively. The lymphangioma was then completely excised with no recurrence noted after 1 year of follow up. This is a rare case of a retroperitoneal, abdominoscrotal lymphangioma masquerading as a communicating hydrocele.

Keywords: Communicating Hydrocele, Abdominoscrotal lymphangioma, Scrotal Swelling

Chronic immunosuppression is known to cause an increased risk of cancers in organ transplant recipients leading to the rise in morbidity and mortality among these patients. Recent studies have observed that thyroid lesions are more frequently encountered in kidney transplant recipients.

A 45-year-old woman with history of chronic hypertension, kidney transplant and graft failure, was admitted for assessment for a second renal transplant and detected to have a thyroid nodule by ultrasound (US). A fine needle aspirate (FNA) on the nodule was reported as Hurthle cell neoplasm. Histopathology revealed a Hurthle cell adenoma with an incidental micro papillary carcinoma. On follow up a year later, US investigation revealed another nodule in the inferior pole of the remnant lobe of thyroid. FNA showed sheets of uniform small round cells arranged in micro follicles, intermixed with Hurthle-like cells with absence of colloid, raising the possibility of a parathyroid lesion. Biochemical tests, clinical history, cytomorphological, immunocytochemical and biochemical tests supported a parathyroid adenoma.

Advancements in diagnostic techniques and management strategies have not only improved survival rates in patients with chronic renal disease but have also identified an increasing number of multiple primary tumors in these patients. Thyroid lesions have cytomorphological similarities and may masquerade parathyroid neoplasms. Regular thyroid screening in post- transplant patients, meticulous pathological examination and parathormone assay are crucial in the early diagnosis, management and prevention of morbidity and mortality in these patients.

Keywords: Fine needle aspiration, kidney transplant, Hurthle cell neoplasm, parathyroid adenoma, micropapillary carcinoma

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government’s vision to reduce cancer mortality and provide high quality healthcare for its citizens.