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Jordan

Cancer Statistics
Population in 2008: 6.1m
People newly diagnosed with cancer (excluding NMSC) / yr: 4,900
Age-standardised rate, incidence per 100,000 people/yr: 128.9
Risk of getting cancer before age 75:13.9%
People dying from cancer /yr: 3,400
Data from IARC GlobalCan (2008)
Jordan Cancer Organisations and Resources
Latest Research Publications Related to Jordan

Jordan Cancer Organisations and Resources (4 links)


Latest Research Publications Related to Jordan

Jordan KS, Mannle SE
An Unusual Case of Chest Pain in an Adolescent Male: Important Cues to Differential Diagnosis.
Adv Emerg Nurs J. 2017 Jan/Mar; 39(1):10-17 [PubMed] Related Publications
Chest pain is a common presenting symptom in the pediatric population, and in contrast to adults, the etiology is rarely cardiac or life-threatening. The majority of chest pain complaints in children and adolescents are benign and can be managed with reassurance and follow-up. The emergency care provider must obtain a comprehensive history and physical examination, as the differential diagnosis of pediatric chest pain is extensive and serious underlying organic pathology may be present. This article describes the case of an adolescent male with an unusual case of chest pain with a serious underlying medical condition. A systematic approach to the clinical decision-making process is discussed to identify those patients who may have a serious underlying organic cause. Information is also included to guide the provider in the identification of red flags for cardiac etiologies of chest pain and indications for a pediatric cardiology consultation.

Khandelwal A, Malhotra A, Jain M, et al.
The emerging role of long non-coding RNA in gallbladder cancer pathogenesis.
Biochimie. 2017; 132:152-160 [PubMed] Related Publications
Gallbladder cancer (GBC) is the most common and aggressive form of biliary tract carcinoma with an alarmingly low 5-year survival rate. Despite its high mortality rate, the underlying mechanisms of GBC pathogenesis are not completely understood. Recently, from a growing volume of literature, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression and appear to play vital roles in many human cancers. To date, a number of lncRNAs have been implicated in GBC, but their potential roles in GBC have not been systematically examined. Thus, in this review, we critically discuss the emerging roles of lncRNAs in GBC, and the pathways involved. Specifically, we note that some lncRNAs show greater expression in T1 and T2 tumor stages compared to T3 and T4 tumor stages and that their dysregulation leads to alterations in cell cycle progression and can cause an increase in GBC cell proliferation or apoptosis. In addition, some lncRNAs control the epithelial-mesenchymal transition process, while others take part in the regulation of ERK/MAPK and Ras cancer-associated signaling pathways. We also present their potential utility in diagnosis, prognosis, and/or treatment of GBC. The overall goal of this review is to stimulate interest in the role of lncRNAs in GBC, which may open new avenues in the determination of GBC pathogenesis and may lead to the development of new preventive and therapeutic strategies for GBC.

Tatarian T, Winter JM
Genetics of Pancreatic Cancer and Its Implications on Therapy.
Surg Clin North Am. 2016; 96(6):1207-1221 [PubMed] Related Publications
Over the past decade, emerging technologies have provided new insights into the genomic landscape of pancreatic ductal adenocarcinoma (PDA). In addition to the commonly recognized genetic drivers of pancreatic carcinogenesis (KRAS, CDKN2A, TP53, SMAD4), new genes and pathways have been implicated. However, these efforts have not identified any new high-frequency actionable mutations, limiting the success of mutation-targeted therapy in PDA. This article provides a report on the current landscape of pancreas cancer genetics and targeted therapeutics.

Sadeghi M, Ghoncheh M, Mohammadian-Hafshejani A, et al.
Incidence and Mortality of Testicular Cancer and Relationships with Development in Asia.
Asian Pac J Cancer Prev. 2016; 17(9):4251-4257 [PubMed] Related Publications
BACKGROUND: Testicular cancer is one of the most common cancers among young men between ages 20-34 in countries with high or very high levels of the Human Development Index (HDI). This study investigated the incidence and mortality of prostate cancer and the relationship with the HDI and its dimensions in Asia in 2012.
MATERIALS AND METHODS: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Standardized incidence and mortality rates of testicular cancer were calculated for Asian countries. Correlations between incidence and/ormortality rates, and the HDI and its components were assessed with the use of the correlation test, using SPSS software.
RESULTS: There was a total of 14902 incidences and 5832 death were recorded in Asian countries in 2012. Among the Asian countries, the five countries with the highest standardized incidence rates of testicular cancer were Israel, Georgia, Turkey, Lebanon and Kazakhstan and the five countries with the highest standardized mortality rates were Turkey, Georgia, Jordan, Cambodia and the Syrian Arab Republic. A positive correlation of 0.382 was observed between the standardized incidence rates of testicular cancer and the HDI (p=0.009). Also a negative correlation of 0.298 between the standardized mortality rate of testicular cancer and the Human Development Index was noted although this relation was statistically non-significant (p=0.052).
CONCLUSIONS: There is a positive correlation between HDI and the standardized incidence rate of testicular cancer and negative correlation with standardized mortality rate.

Alfawareh M, Alotaibi T, Labeeb A, Audat Z
A Symptomatic Case of Thoracic Vertebral Hemangioma Causing Lower Limb Spastic Paresis.
Am J Case Rep. 2016; 17:805-809 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Despite being the most common tumor of the spine, vertebral hemangioma is rarely symptomatic in adults. In fact, only 0.9-1.2% of all vertebral hemangiomas may be symptomatic. When hemangiomas occur in the thoracic vertebrae, they are more likely to be symptomatic due to the narrow vertebral canal dimensions that mandate more aggressive management prior to the onset of severe neurological sequelae. CASE REPORT An 18-year-old male presented to the emergency room with a one-month history of mild to moderate mid-thoracic back pain, radiating to both lower limbs. It was associated with both lower limb weakness and decreased sensation. There was no history of bowel or bladder incontinence. Neurological examination revealed lower limb weakness with power 3/5, exaggerated deep tendon reflexes, bilateral sustained clonus, impaired sensation below the umbilicus, spasticity, and a positive Babinski sign. A CT scan showed a diffuse body lesion at the 8th thoracic vertebra with coarse trabeculations, corduroy appearance, or jail-bar sign. The patient underwent decompression and fixation. Biopsy of permanent samples showed proliferation of blood vessels with dilated spaces and no malignant cells, consistent with hemangioma. Postoperatively, spasticity improved, and the patient regained normal power. CONCLUSIONS Symptomatic vertebral hemangiomas are rare but should be considered as a differential diagnosis. They can present with severe neurological symptoms. When managed appropriately, patients regain full motor and sensory function. Decompression resulted in quick relief of symptoms, which was followed by an extensive rehabilitation program.

Alsmady MM, Aladaileh MA, Al-Zaben K, et al.
Chylopericardium presenting as cardiac tamponade secondary to mediastinal lymphangioma.
Ann R Coll Surg Engl. 2016; 98(8):e154-e156 [PubMed] Related Publications
Mediastinal lymphangioma is a rare entity and chylopericardium is a rare form of pericardial effusion. We report a case of acute chylous cardiac tamponade due to a cervicomediastinal lymphangioma in a one-year-old boy. A chest x-ray revealed marked cardiac enlargement and echocardiography showed massive pericardial effusion. Emergency surgery was performed whereby a pericardial window was created, followed by excision of the lymphangioma.

Alaarg A, Jordan NY, Verhoef JJ, et al.
Docosahexaenoic acid liposomes for targeting chronic inflammatory diseases and cancer: an in vitro assessment.
Int J Nanomedicine. 2016; 11:5027-5040 [PubMed] Free Access to Full Article Related Publications
Inflammation, oxidative stress, and uncontrolled cell proliferation are common key features of chronic inflammatory diseases, such as atherosclerosis and cancer. ω3 polyunsaturated fatty acids (PUFAs; also known as omega3 fatty acids or fish oil) have beneficial effects against inflammation upon dietary consumption. However, these effects cannot be fully exploited unless diets are enriched with high concentrations of fish oil supplements over long periods of time. Here, a nanomedicine-based approach is presented for delivering effective levels of PUFAs to inflammatory cells. Nanoparticles are internalized by immune cells, and hence can adequately deliver bioactive lipids into these target cells. The ω3 FA docosahexaenoic acid was formulated into liposomes (ω-liposomes), and evaluated for anti-inflammatory effects in different types of immune cells. ω-Liposomes strongly inhibited the release of reactive oxygen species and reactive nitrogen species from human neutrophils and murine macrophages, and also inhibited the production of the proinflammatory cytokines TNFα and MCP1. Moreover, ω-liposomes inhibited tumor-cell proliferation when evaluated in FaDu head and neck squamous carcinoma and 4T1 breast cancer cells in in vitro cultures. We propose that ω-liposomes are a promising nanonutraceutical formulation for intravenous delivery of fish oil FAs, which may be beneficial in the treatment of inflammatory disorders and cancer.

Obed A, Jarrad A, Bashir A
First Left Hepatic Trisectionectomy Including Segment One with New Associated Liver Partition and Portal Vein Ligation with Staged Hepatectomy (ALPPS) Modification: How To Do It?
Am J Case Rep. 2016; 17:759-765 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Associated Liver Partition and Portal vein ligation with Staged hepatectomy (ALPPS) leads to rapid hepatic hypertrophy and decreases incidence of post-hepatectomy liver failure in patients with a marginal future liver remnant. Various procedural ALPPS modifications were previously described. Here, we present the first case of a new ALPPS modification, carrying out a left hepatic trisectionectomy with segment 1. CASE REPORT We present the case of a 36-year-old woman with locally advanced sigmoid adeno-carcinoma and extensive left liver metastases extending to segment V and VIII, who received state-of-the-art systemic conversion chemotherapy. Preoperative CT volumetric scan demonstrated a FLR/TLV (Future Liver Remnant/Total Liver Volume) of 22%. A left hepatic trisectionectomy procedure was conducted using our new ALPPS modification. Sufficient hepatic hypertrophy of FLR was reached with a volume increase of 100%. The period between the 2 stages was 7 days. The patient underwent left trisectionectomy and left colectomy with tumor-free margins. All dissected lymph nodes were tumor-negative. The surgical intra- and postoperative course was uneventful. Medically, the patient acquired an Acinetobacter infection, with severe sepsis and acute renal injury. After 3 dialysis sessions, the renal function recovered completely. Afterwards, the patient recovered slowly, and reintroduction ambulation and oral feeding was prolonged. Later on, the patient received Xeloda 1500 mg twice daily as adjuvant chemotherapy. CONCLUSIONS The new ALPPS modification leads to a sufficient hypertrophy of FRL within 1 week, allowing left hepatic trisectionectomy with tumor-free FRL. Despite the challenging complications, the new ALPPS modification might represent an alternative procedure for use when the classic ALPPS procedure is not applicable. Further studies are required.

Obed A, Bashir A, Jarrad A
Rapid Virological Response After Early Treatment with a Combined Therapy of Ledipasvir and Sofosbuvir in HCV Genotype 4 After Living Donor Liver Transplantation in a HCC Downstaged Patient: Case Report and Review of the Literature.
Am J Case Rep. 2016; 17:672-5 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Hepatitis C virus (HCV) genotype 4 (GT-4) is widespread in the Middle East, where it is responsible for the majority of HCV infections. It shows moderate treatment response rates when compared to other genotypes in the current era of interferon-based regimens. However, in the era of direct acting antiviral (DAA) drugs, its response is at least as good as observed for HCV genotypes 1-3. CASE REPORT We present a case of a 44-year-old patient with HCV cirrhosis. Since 2007, he has been treated for HCV infection with multiple ineffective regimens of interferon (INF) and ribavirin. A liver biopsy in 2010 revealed stage 5-6/6 indicating cirrhosis, which was later complicated by the occurrence of portal vein thrombosis and a large hepatocellular carcinoma (HCC) (maximum diameter 9 cm). The patient was successfully treated with sorafenib, transcatheter arterial chemoembolization (TACE), and radiofrequency ablation. After four TACE procedures, the patient's AFP (alpha-fetoprotein) decreased remarkably and almost normalized. The HCC disappeared radiologically as shown by triple phase CT, MRI with contrast, and PET-CT. He successfully underwent a living donor liver transplantation. Four weeks post liver transplantation he started treatment with sorafenib, and switched from tacrolimus to Rapamune (sirolimus) as immunosuppressant therapy. Ten weeks after liver transplantation, HCV treatment was introduced along with ledipasvir and sofosbuvir due to his increasing liver enzyme levels. A rapid viral response was achieved after 14 days. In total, the patient received 12 weeks of this treatment. CONCLUSIONS This case study might be of significance in informing early management and personalized treatment of patients with recurrent HCV GT-4 infections after liver transplantation, even in complex clinical surroundings.

Yaghan RJ, Dagher NM
Phase II Study of Compliance and Morbidity with 4 Cycles of Taxotere Followed by 4 of Doxorubicin-Cyclophosphamide for Adjuvant Treatment of Operable Breast Cancer Patients.
Asian Pac J Cancer Prev. 2016; 17(8):4031-5 [PubMed] Related Publications
BACKGROUND: In the adjuvant treatment of breast cancer, anthracycline and taxane based regimens can be used concomitantly or sequentially. The best order in the sequential regimens has yet to be well established. This study evaluated the feasibility of 4 cycles of adjuvant taxotere (100mg/m2) every 3 weeks followed by 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) every 3 weeks. The primary outcome was the safety profile. Secondary outcomes were disease free survival (DFS) and overall survival (OS).
MATERIALS AND METHODS: This non-randomized prospective phase II study was performed at Jordan University of Science and Technology and its affiliated King Abdulla Teaching Hospital between July 2009 and August 2010. Data collection was closed on May 31th, 2015, giving a median follow up period of 62 months. The study was approved by the institutional review board and written informed consent was obtained for each patient.
RESULTS: Fifty patients were enrolled. The median age was 53.1 years (range 34-76). One patient (2%) had stage I disease, 17 (34%) stage II, and 32 (64.0%) stage III. Forty-six patients were evaluable for efficacy analysis. The completion rate was 95.7%. No dose modifications were needed. The incidences of grade 3-4 neutropenia and febrile neutropenia were 14% and 10%. No grade 3-4 non-hematological adverse events were encountered. At a median follow up time of 62 months the OS and the DFS rates were 76.1% and 56.5%. Those for stages I and II combined were 100% and 75%.
CONCLUSIONS: Taxotere first followed by doxorubicin-cyclophosphamide appears a feasible regimen as evidenced by an acceptable completion rate, a satisfactory safety profile, and OS and DFS rates comparable to other studies.

Bodoor K, Jalboush SA, Matalka I, et al.
Heat Shock Protein Association with Clinico-Pathological Characteristics of Gastric Cancer in Jordan : HSP70 is Predictive of Poor Prognosis.
Asian Pac J Cancer Prev. 2016; 17(8):3929-37 [PubMed] Related Publications
Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N=87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced significantly and was also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our findings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

Abu Abeeleh M, Bani Hani A, Ghaith A, et al.
Aortopulmonary ectopic parathyroid gland and concurrent thymolipoma.
Asian Cardiovasc Thorac Ann. 2016; 24(8):822-824 [PubMed] Related Publications
Ectopic parathyroid adenomas are considered the main cause of primary hyperparathyroidism. However, concurrent parathyroid and thymic pathologies are rarely diagnosed in the same patient. A 47-year-old man with history of diabetes mellitus, hypertension, and myasthenia gravis presented with persistent hypercalcemia. Laboratory investigations, computed tomography, and technetium-99 m sestamibi scintigraphy revealed ectopic parathyroid glands, a mediastinal mass, and an enlarged thymus. The patient underwent thymectomy and mass excision via a median sternotomy. Histopathology was consistent with ectopic parathyroid adenoma and thymolipoma. The serum calcium and parathormone concentrations normalized within 48 hours after surgery.

Khraise WN, Allouh MZ, Hiasat MY, Said RS
Successful Management of Intraoperative Acute Bilateral Pulmonary Embolism in a High Grade Astrocytoma Patient.
Am J Case Rep. 2016; 17:632-6 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Intraoperative pulmonary embolism (PE) is a rare life-threatening complication in patients undergoing surgical intervention. Generally, cancer patients have a higher risk for developing this complication. Unfortunately, there is no standard procedure for its management. CASE REPORT We report the case of a 39-year-old woman with high-grade glioma in the right frontal lobe who was admitted to the surgical theater for craniotomy and excision of the tumor. During the general anesthesia procedure and just before inserting the central venous line, her end-tidal CO2 and O2 saturation dropped sharply. The anesthesiologist quickly responded with an aggressive resuscitation procedure that included aspiration through the central venous line, 100% O2, and IV administration of ephedrine 6 mg, colloid 500 mL, normal saline 500 mL, and heparin 5000 IU. The patient was extubated and remained in the supine position until she regained consciousness and her vital signs returned to normal. Subsequent radiological examination revealed a massive bilateral PE. A retrievable inferior vena cava (IVC) filter was inserted, and enoxaparin anticoagulant therapy was prescribed to stabilize the patient's condition. After 3 weeks, she underwent an uneventful craniotomy procedure and was discharged a week later under the enoxaparin therapy. CONCLUSIONS The successful management of intraoperative PE requires a quick, accurate diagnosis accompanied with an aggressive, fast response. Anesthesiologists are usually the ones who are held accountable for the diagnosis and early management of this complication. They must be aware of the possibility of such a complication and be ready to react properly and decisively in the operation theater.

Jordan NV, Bardia A, Wittner BS, et al.
HER2 expression identifies dynamic functional states within circulating breast cancer cells.
Nature. 2016; 537(7618):102-106 [PubMed] Free Access to Full Article Related Publications
Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER(+)/HER2(-) primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2(+) and HER2(-) subpopulations: HER2(+) circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2(-) circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2(+) and HER2(-) circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2(+) and HER2(-) circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2(+) state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2(-) phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance.

Evans A, Purdie CA, Jordan L, et al.
Stiffness at shear-wave elastography and patient presentation predicts upgrade at surgery following an ultrasound-guided core biopsy diagnosis of ductal carcinoma in situ.
Clin Radiol. 2016; 71(11):1156-9 [PubMed] Related Publications
AIM: The aim of this study is to establish predictors of invasion in lesions yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ (DCIS).
MATERIALS AND METHODS: Patients subjected to ultrasound-guided core biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold of 50 kPa was used for mean elasticity (Emean) to dichotomise the elasticity data between invasive and non-invasive masses. Data recorded included the mammographic and ultrasound features, the referral source, and grade of DCIS in the biopsy. The chi-square test was used to detect statistical significance.
RESULTS: Of 57 lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients with stiff lesions were more likely to have invasion than patients presenting through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33], p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors showed a relationship with invasion. Combining the two predictors of invasion improved risk stratification with symptomatic and stiff lesions having a risk of invasion of 67% (12 of 18) and soft lesions presenting at screening having only a 17% (2 of 12) risk of invasion (p=0.02).
CONCLUSION: Stiffness on SWE and the referral source of the patient are predictors of occult invasion in women with an ultrasound-guided core biopsy diagnosis of DCIS.

Obeidat N, Awidi A, Ababneh N, et al.
Frequency of epidermal growth factor receptor mutations in Jordanian lung adenocarcinoma patients at diagnosis.
J Cancer Res Ther. 2016 Apr-Jun; 12(2):616-9 [PubMed] Related Publications
BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) gene have been associated with tumor response to tyrosine kinase inhibitors (TKIs) and favorable outcome in patients with non-small-cell lung cancer (NSCLC). The activating mutations that confer sensitivity to EGFR TKIs are present in the TK domain of the EGFR gene. This study aims to report on the prevalence of EGFR mutations in NSCLC and non-squamous lung cancer patients at diagnosis, using genomic deoxyribonucleic acid (DNA) obtained from paraffin-embedded tissue samples.
MATERIALS AND METHODS: We collected formalin.fixed, paraffin.embedded. (FFPE) tissue samples from 166. cases of lungadenocarcinomas referring to Jordan University Hospital and King Hussein Cancer Center between 2007 and first half of 2013. None of the patients met the definition of never smoker defined as those who smoked less than 100 cigarettes in their lifetime. We evaluated EGFR mutations by nested polymerase chain reaction. (PCR) followed by direct sequencing of the EGFR kinase domain from exon 18 to 21.
RESULTS: Six different point mutations were detected in 24 patients (14.46%) of the study population. The resultant mutations were as follows: Ten patients have deletion in exon 19, sevenpatients have L858R, two patients have L861P, and one of each of the following: A735T, D770_N771 insY, L858P, L861Q, and G917C.
CONCLUSION: The present study revealed that the EGFR mutations rate in Jordanian patients with adenocarcinoma of the lung was higher than in African-American, and some white Caucasian patients, and was lower than in patients in East Asia, and other countries of South Asia.

Al-Gamal E, Long T
Health-related quality of life and its association with self-esteem and fatigue among children diagnosed with cancer.
J Clin Nurs. 2016; 25(21-22):3391-3399 [PubMed] Related Publications
AIMS AND OBJECTIVES: To identify the links between self-esteem, fatigue and health-related quality of life for children and young people during and following treatment for cancer.
BACKGROUND: Measures to minimise adverse outcomes for survivors of childhood cancer have been developed, but the crucial periods of returning to school and transition to adult life and adult services are not addressed so well. Screening of quality of life, fatigue and self-esteem in childhood cancer patients during and after treatment is important for optimising the nursing response and improving outcomes for children.
DESIGN: A cross-sectional, descriptive, correlational, comparative survey was designed.
METHODS: Validated measures of the attributes being studied were used. This study was conducted in private rooms on the ward and in the outpatient clinic of a major oncology hospital in Jordan in 2015. Seventy children aged 5-16 years were included. Ethical approval was secured.
RESULTS: The age range of the children was 5-16 years (Mean 10·17, SD 3·4 years). Thirty were girls and 40 were boys. The total quality of life scores ranged from 21-100 (M = 65·5; SD = 17·6). The total scores of fatigue range from 12·5-100 (M = 65·79; SD = 22·20). Children with a high level of fatigue experienced lower quality of life.
CONCLUSION: Continuing education centres at hospitals may find the results of this study helpful to provide professional updates and training events to enhance nurses' understanding of psychosocial distress responses and ability to intervene effectively within the multiprofessional effort.
RELEVANCE TO CLINICAL PRACTICE: The outcomes of this study may enhance the development of guidelines for routine assessment by nurses and others of these factors among children with cancer. The nursing role in ensuring holistic care and attention to the problems of most concern to patients could be strengthened.

Zayadeen AR, Abu-Yousef M, Berbaum K
JOURNAL CLUB: Retrospective Evaluation of Ultrasound Features of Thyroid Nodules to Assess Malignancy Risk: A Step Toward TIRADS.
AJR Am J Roentgenol. 2016; 207(3):460-9 [PubMed] Related Publications
OBJECTIVE: The aim of this retrospective study was to develop a thyroid nodule scoring system for malignancy potential to better select nodules for ultrasound (US)-guided fine needle aspiration (FNA).
MATERIALS AND METHODS: US-guided FNA was performed on 2375 thyroid nodules in successive patients. Cytologic or histopathologic confirmation of disease state in 2002 lesions showed that 148 were malignant. We developed an extended scoring system to provide more decision levels than standard scoring by including weak (macrocalcification, eggshell calcification, hypoechogenicity, solid consistency) as well as strong indicators of malignancy (microcalcification, hypoechogenicity, lobulated or ill-defined margins, taller-than-wide shape, suspicious lymph nodes) and by including contraindications (hyperechogenicity, comet-tail artifact, complete halo, cystic or microcystic). ROC analysis was used to compare detection accuracy and decision thresholds resulting from standard scoring using five major features with extended scoring.
RESULTS: Although an accuracy advantage was found for the extended scoring over standard scoring, we discount this finding because our scoring involved a preliminary analysis. However, the extended scoring offers more reporting options for certainty of malignancy: standard scoring gave four potential thresholds for reporting; extended scoring gave nine. The most useful of the additional thresholds captured nearly 88% of malignancies but resulted in only 28% of patients without malignancy undergoing biopsy.
CONCLUSION: Our extended Thyroid Imaging Reporting and Data System scoring provides more operating points to support treatment decisions. A simplified decision rule-biopsy every nodule with at least two weak features or one strong feature-preserves the most useful of the new decision thresholds from extended scoring.

Ruff P, Al-Sukhun S, Blanchard C, Shulman LN
Access to Cancer Therapeutics in Low- and Middle-Income Countries.
Am Soc Clin Oncol Educ Book. 2016; 35:58-65 [PubMed] Related Publications
Cancer is rapidly becoming a major health care problem, especially in developing countries, where 60% of the world's total new cases are diagnosed. The success of new antineoplastic medicines and modern radiation devices to cure a good proportion of patients with cancer and to alleviate the suffering of many more has been achieved at a dramatic cost. Therefore, it has become mandatory for health care authorities and pharmaceutical companies to cooperate to use and develop resources in an efficient manner to improve health care delivery to patients with cancer worldwide. Regulatory harmonization is an important key to overcome delays in the approval process, whether for antineoplastic and pain control medicines or for essential medical devices. More emphasis on the significant role of opiates in pain control among patients with cancer is needed to overcome the ingrained belief in their potential for addiction. The World Health Organization (WHO) serves an important role in guiding priorities for health care and efficiently allocating resources by providing essential medicine lists (EMLs) and device lists. However, the financial challenge for access to health care is multi-tiered and requires collaboration between key stakeholders including pharmaceutical industry, local national health authorities, WHO, and other nonprofit, patient-oriented organizations.

Al-Muqbel KM, Yaghan RJ
Effectiveness of 18F-FDG-PET/CT vs Bone Scintigraphy in Treatment Response Assessment of Bone Metastases in Breast Cancer.
Medicine (Baltimore). 2016; 95(21):e3753 [PubMed] Free Access to Full Article Related Publications
The aim of the study was to examine the effectiveness of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) versus bone scintigraphy (BS) in treatment response assessment of bone metastases in breast cancer.The medical records of breast cancer patients with metastatic bone disease were reviewed retrospectively in our hospital from the period of January 2003 until April 2014. We included in our study patients evaluated by BS and/or 18F-FDG-PET/CT. Group 1 included patients who underwent pre- and post-treatment BS. Group 2 included patients who underwent pre- and post-treatment 18F-FDG-PET/CT scans. Group 3 included patients who underwent pretreatment BS and post-treatment both modalities. Functional and structural bone changes were monitored on pre- and post-treatment scans.Group 1 included 71 patients, average age of 49.5 y (range 28-73 y). Post-treatment results were as follows: 34% stable disease, 43% progressed disease, 19% improved disease, 3% resolved disease, and 2% relapsed disease. Group 2 included 32 patients, average age 53.2 y (ranges between 37 and 78 y). Post-treatment results were as follows: 3% stable disease, 15% progressed disease, 15% improved disease, 53% resolved disease, and 14% relapsed disease. After treatment, the total symptomatic/imaging concordance rate was 51% in BS and 83% in 18F-FDG-PET/CT. Structurally, most patients with newly diagnosed metastatic bone disease had predominantly osteolytic lesions, which became mixed or osteoblastic after treatment as noted on CT images of responders. Group 3 included 8 patients, average age 48.9 y (ranges 32-64 y). Five patients had stable disease according to BS. 18F-FDG-PET/CT was concordant in 3/5 patients and discordant in 2/5 patients. Three patients had progressed disease on BS with concordant findings on 18F-FDG-PET/CT.18F-FDG-PET/CT was found a powerful tool in treatment response assessment of bone metastases in breast cancer and consistent with clinical status of the patients as it reflects tumor activity. BS is insufficient for response assessment of bone metastases as it reflects osteoblastic reaction of the bone against metastatic disease which increases as the disease responds to treatment.

Rejeeth C, Salem A
Novel luminescent silica nanoparticles (LSN): p53 gene delivery system in breast cancer in vitro and in vivo.
J Pharm Pharmacol. 2016; 68(3):305-15 [PubMed] Related Publications
OBJECTIVES: Mutations in the p53 tumor suppressor gene are one among the most common genetic abnormalities to be described in breast cancer. However, there are a few recant reports on non-viral vector-mediated p53 gene delivery in breast cancer.
METHODS: A new formulation of luminescent silica nanoparticles (LSNs) for gene delivery was produced by the two-step method with slight modification.
KEY FINDINGS: The pp53 plasmid constructs (p53-EGFP)/LSNs complexes were transfected into human breast cancer cell (MCF-7) and transfection efficiency was determined by FACS analysis. The gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis respectively. Further the growth inhibition through induced apoptosis with pp53-EGFP/LSNs complex were assessed by trypan blue exclusion assay and annexin V staining, respectively. Interestingly the in vivo biodistribution of plasmid DNA study revealed the occurrence was investigated by PCR and RT-PCR. The transfection efficiency of LSNs showed the highest transfection efficiency among the LSN formulation was higher than that of commercially available Lipofectin®. The LSNs-mediated transfection of the p53 gene resulted in efficient high level of wild-type p53 mRNA and protein expression levels in MCF-7 cells. Selected tissues were analyzed for any potential toxicity by histological analysis the efficient reestablishment of wild-type p53 function in breast cancer cells restored the p53 dependent apoptotic pathway.
CONCLUSIONS: Taken together, our results reveal that cationic LSN-mediated p53 gene delivery may have potential application as a non-viral vector-mediated breast cancer gene therapy due to its effective induction of apoptosis and tumor growth inhibition.

Al Hamal Z, Jordan M, Hachem RY, et al.
Mycobacterium arupense in Cancer Patients: An Emerging Infection or a Commensal Organism.
Medicine (Baltimore). 2016; 95(14):e2691 [PubMed] Free Access to Full Article Related Publications
Mycobacterium arupense is a slow-growing, nonchromogenic, acid-fast bacillus. Its clinical spectrum, epidemiology, and frequency of colonization versus true infection remain unknown. We evaluated the clinical significance of M arupense and positive cultures from cancer patients.We retrospectively reviewed records of all cancer patients treated at our institution between 2007 and 2014 to identify those who had positive cultures for M arupense. Mycobacterium arupense was identified by sequencing the 16S rRNA and hsp65 genes. A total of 53 patients had positive cultures, 100% of which were isolated from respiratory specimens. Of these, 7 patients met the American Thoracic Society/Infectious Diseases Society of America criteria for a definitive diagnosis of M arupense infection, 14 cases were considered to be probable infections, and 29 cases were considered to be possible infections. Of the included patients, 13 received therapy for M arupense infection and 40 did not.The outcomes of treated and untreated patients did not differ significantly. No relapses of M arupense infection. In addition, there were no M arupense-related deaths in either group.In cancer patients, M arupense appears to be mostly a commensal organism rather than a pathogen. Patients who did or did not receive treatment had similar outcomes. Validation of these findings in a larger prospective trial is warranted.

Tran LB, Bol A, Labar D, et al.
DW-MRI and (18) F-FLT PET for early assessment of response to radiation therapy associated with hypoxia-driven interventions. Preclinical studies using manipulation of oxygenation and/or dose escalation.
Contrast Media Mol Imaging. 2016 Mar-Apr; 11(2):115-21 [PubMed] Related Publications
Early markers of treatment response may help in the management of patients by predicting the outcome of a specific therapeutic intervention. Here, we studied the potential value of diffusion-weighted MRI (DW-MRI) and (18)F-fluorothymidine ((18)F-FLT), markers of cell death and cell proliferation respectively, to predict the response to irradiation. In addition, dose escalation and/or carbogen breathing were used to modulate the response to irradiation. The studies were performed on two hypoxic rat tumor models: rhabdomyosarcoma and 9L-glioma. The rats were imaged using MRI and PET before and two days after the treatment. In both tumor models, changes in ADC (apparent diffusion coefficient) and (18)F-FLT SUV (standardized uptake value) were significantly correlated with the tumor growth delay. For both tumor models, the ADC values increased in all irradiated groups two days after the treatment while they decreased in the untreated groups. At the same time, the uptake of (18)F-FLT increased in the untreated groups and decreased in all treated groups. Yet, ADC values were not sensitive enough to predict the added value of dose escalation or carbogen breathing in either model. Change in (18)F-FLT uptake was able to predict the higher tumor response when using increased dose of irradiation, but not when using a carbogen breathing challenge. Our results also emphasize that the magnitude of change in (18)F-FLT uptake was strongly dependent on the tumor model.

Sawair F, Hassona Y, Irwin C, et al.
p53, Cyclin D1, p21 (WAF1) and Ki-67 (MIB1) Expression at Invasive Tumour Fronts of Oral Squamous Cell Carcinomas and Development of Local Recurrence.
Asian Pac J Cancer Prev. 2016; 17(3):1243-9 [PubMed] Related Publications
BACKGROUND: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence.
MATERIALS AND METHODS: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables.
RESULTS: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value.
CONCLUSIONS: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

Aldaoud N, Joudeh A, Al-Momen S, et al.
Anaplastic Carcinoma Arising in a Mucinous Cystic Neoplasm Masquerading as Pancreatic Pseudocyst.
Diagn Cytopathol. 2016; 44(6):538-42 [PubMed] Related Publications
Mucinous cystic neoplasms (MCN) of the pancreas can vary from benign to premalignant and malignant. Preoperative diagnosis is essential to offer the patient appropriate treatment. Occasionally these cases may harbor anaplastic carcinoma while clinically masquerade as a pseudocyst. Here in, we report an unusual case of a 37-year old female presented with recurrent abdominal pain that was suspected clinically and by imaging studies to have a pseudocyst. EUS-FNA with internal drainage of the cyst was performed. Cytological evaluation of the cyst fluid showed numerous inflammatory cells composed mainly of many neutrophils admixed with macrophages reminiscent of the usual pseudocyst content but there were scattered rare dyscohesive malignant cells which were highly pleomorphic with multinucleation. Immunostains on the cell block showed immunoreactivity of these cells including the multinucleated cells for Cam 5.2 and AE1/AE3 and focally for Ber-Ep4, Moc -31, and CA19-9. The subsequent resection confirmed the presence of anaplastic (undifferentiated) carcinoma (AC) arising in a MCN of the pancreas. Diagn. Cytopathol. 2016;44:538-542. © 2016 Wiley Periodicals, Inc.

Jordan BC, Mock CD, Thilagavathi R, Selvam C
Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment.
Life Sci. 2016; 152:135-44 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
Primary prostate cancer, also known as prostate adenocarcinoma (PCa), is a devastating cancer in men worldwide. Europe and developing countries of Asia have fewer reported cases of prostate cancer compared to increasing cases in the United States with higher incidence in Black men. Risk factors associated with prostate cancer are aging, genetics, lifestyle, high body mass index as well as carcinogenic exposure to carbon-containing fuels, tobacco, and charbroiled meats. Hormone therapy and radical prostatectomy are commonly implemented treatments. The >20.000 prostate cancer deaths of 2013 suggest that there exists a need for enhanced chemopreventive and therapeutic agents for prostate cancer treatment. Fruits, vegetables, and red wines contain high levels of polyphenolic levels. Consumption of these products may provide chemoprevetion of PCa. Curcumin, the major compound from the turmeric rhizome Curcuma longa has long been used for medicinal purposes as an antiseptic and wound healing. This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models. The review will highlight the mechanisms of actions of curcumin in the signaling pathways of prostate cancer.

Evans A, Sim YT, Thomson K, et al.
Shear wave elastography of breast cancer: Sensitivity according to histological type in a large cohort.
Breast. 2016; 26:115-8 [PubMed] Related Publications
PURPOSE: To define the shear wave elastography (SWE) characteristics of breast cancer histological types by size in a large cohort.
METHODS: Consecutive patients with US visible masses underwent SWE. All those with confirmed invasive breast cancer were included in the study. Histologic type was ascertained from core biopsy and surgical resection specimens. For each type, mean and median values for Emean and Emax were ascertained. Commoner tumour types were further analysed by invasive size. The significance of differences was established using the Chi-square test.
RESULTS: 1137 tumours constituted the study group. The proportion of tumours with Emean below 50 kPa was higher in tubular cancers (23%) compared to ductal carcinomas of no specific type (DNST) (6%) (p < 0.001). Emax below 80 kPa was seen in 34% of tubular cancers compared to 16% of DNST (p < 0.002). Emean and Emax for lobular, mucinous, papillary and metaplastic cancers were not different from those of DNST. There were no significant differences in Emean or Emax between tumour types once broken down according to invasive size.
CONCLUSIONS: Most breast cancer histological types have similar SWE characteristics. The exception is tubular cancer which has significantly lower stiffness than other histologic types, accounted for largely by their small size.

Giannotti E, Vinnicombe S, Thomson K, et al.
Shear-wave elastography and greyscale assessment of palpable probably benign masses: is biopsy always required?
Br J Radiol. 2016; 89(1062):20150865 [PubMed] Article available free on PMC after 01/06/2017 Related Publications
OBJECTIVE: To establish if palpable breast masses with benign greyscale ultrasound features that are soft on shear-wave elastography (SWE) (mean stiffness <50 kPa) have a low enough likelihood of malignancy to negate the need for biopsy or follow-up.
METHODS: The study group comprised 694 lesions in 682 females (age range 17-95 years, mean age 56 years) presenting consecutively to our institution with palpable lesions corresponding to discrete masses at ultrasound. All underwent ultrasound, SWE and needle core biopsy. Static greyscale images were retrospectively assigned Breast Imaging Reporting and Data System (BI-RADS) scores by two readers blinded to the SWE and pathology findings, but aware of the patient's age. A mean stiffness of 50 kPa was used as the SWE cut-off for calling a lesion soft or stiff. Histological findings were used to establish ground truth.
RESULTS: No cancer had benign characteristics on both modalities. 466 (99.8%) of the 467 cancers were classified BI-RADS 4a or above. The one malignant lesion classified as BI-RADS 3 was stiff on SWE. 446 (96%) of the 467 malignancies were stiff on SWE. No cancer in females under 40 years had benign SWE features. 74 (32.6%) of the 227 benign lesions were BI-RADS 3 and soft on SWE; so, biopsy could potentially have been avoided in this group.
CONCLUSION: Lesions which appear benign on greyscale ultrasound and SWE do not require percutaneous biopsy or short-term follow-up, particularly in females under 40 years.
ADVANCES IN KNOWLEDGE: None of the cancers had benign characteristics on both greyscale ultrasound and SWE, and 32% of benign lesions were BI-RADS 3 and soft on SWE; lesions that are benign on both ultrasound and SWE may not require percutaneous biopsy or short-term follow-up.

Aapro M, Hesketh PJ, Jordan K, et al.
Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program.
Oncologist. 2016; 21(4):494-502 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
BACKGROUND: Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials.
MATERIALS AND METHODS: This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures.
RESULTS: Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare.
CONCLUSION: NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity.
IMPLICATIONS FOR PRACTICE: Supportive care for cancer should ideally be efficacious, convenient, and well-tolerated. There have been concerns about cardiac safety with current antiemetic prophylactic agents, namely dolasetron and ondansetron. This pooled safety analysis demonstrates that the new oral fixed combination therapy NEPA can be safely added to an antiemetic regimen without increased toxicity.

Martin TA, Jordan N, Davies EL, Jiang WG
Metastasis to Bone in Human Cancer Is Associated with Loss of Occludin Expression.
Anticancer Res. 2016; 36(3):1287-93 [PubMed] Related Publications
BACKGROUND: Occludin is an integral membrane protein localised at tight junctions (TJ). There is no consensus regarding its paramount role in TJ. In previous work we showed that occludin is aberrantly expressed in both human breast tissues and cancer cell lines. This study demonstrates a link to bone metastasis in human cancer.
MATERIALS AND METHODS: Primary breast tumours (n=124) and matched normal tissues (n=30) were processed for quantitative polymerase chain reaction (QPCR) analysis. A hammerhead ribozyme was constructed to create occludin knockdown cell lines, MDA-MB-231(ΔOcc) and PC-3(ΔOcc). The effect of human bone matrix extract (BME) was investigated using cell growth and electric cell impedance sensing (ECIS) technology to measure changes in attachment/migration. Trans-epithelial resistance (TER) was measured for assessing changes in TJ function. Cells used were MDA-MB-231, PC-3, CORL-23, SKMES-1 and A-549 human cancer cell lines.
RESULTS: Tumours from patients with bone metastasis had significantly lower occludin expression compared to those remaining alive/well (60.7±21 vs. 331±98, respectively, p=0.008). This was striking in ductal carcinomas, where patients alive/well had significantly higher occludin expression compared to those with bone metastasis (391±12.5 vs. 67.9±28, respectively, p=0.0014). ECIS demonstrated that MDA-MB-231(ΔOcc) showed reduced attachment to 5% BME compared to controls (84% vs. 100%) that prevented closure of wounded cell layers. Moreover, these cells had reduced growth on BME. In addition, BME changed the TER of a number of human cell lines and was able to effect changes in the growth of MDA-MB-241 and PC-3 cells, with greater effect on knockdown cells.
CONCLUSION: This is the first study to demonstrate that occludin expression has a clear relationship with bone metastasis in human cancer. The discrepancy between this and the in vitro data indicating a reduction in migration/growth rate of occludin knockdown indicates that loss of occludin leads to complex changes in human cancer cell phenotype.

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