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Saudi Arabia

Cancer Statistics
Population in 2008: 25.2m
People newly diagnosed with cancer (excluding NMSC) / yr: 13,300
Age-standardised rate, incidence per 100,000 people/yr: 87.6
Risk of getting cancer before age 75:8.9%
People dying from cancer /yr: 8,900
Data from IARC GlobalCan (2008)
Saudi Arabia Cancer Organisations and Resources
Latest Research Publications Related to Saudi Arabia

Saudi Arabia Cancer Organisations and Resources (10 links)

Latest Research Publications Related to Saudi Arabia

Zekri J, Al-Shehri A, Mahrous M, et al.
Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes.
Genet Mol Res. 2017; 16(1) [PubMed] Related Publications
Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors. Most mutations were at codon 12 (89%) and were associated with metastasis [odds ratio (OR) = 1.38 (95%CI = 1.14-1.67] and occurrence of >40 µg/L carcinoembryonic antigen (CEA) [OR = 1.33 (1.1-1.74)] during diagnosis. Patients in stages I-III of the disease with wild-type K-ras tumors had a median relapse free survival (RFS) of 29 months in contrast to 22 months for those with the mutated K-ras tumor (P = 0.0357). In multivariate analysis, only the stage of the disease significantly predicted RFS (P = 0.001). Patients in stage IV of CRC with the wild-type K-ras tumor did not reach the median overall survival (OS), whereas patients with the mutated K-ras tumor survived for 23.5 months (P = 0.044). CEA level >40 µg/L (P = 0.004) and status of K-ras (P = 0.044) were independent predictors of OS. This is the largest study investigating K-ras mutations in patients with CRC in the Middle East. Mutations were associated with advanced stage of CRC, higher serum CEA, shorter RFS and OS.

Eldehna WM, Almahli H, Al-Ansary GH, et al.
Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.
J Enzyme Inhib Med Chem. 2017; 32(1):600-613 [PubMed] Related Publications
Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

Subash-Babu P, Alshammari GM, Ignacimuthu S, Alshatwi AA
Epoxy clerodane diterpene inhibits MCF-7 human breast cancer cell growth by regulating the expression of the functional apoptotic genes Cdkn2A, Rb1, mdm2 and p53.
Biomed Pharmacother. 2017; 87:388-396 [PubMed] Related Publications
Systematic analyses of plants that are used in traditional medicine may lead to the discovery of novel cytotoxic secondary metabolites. Diterpene possesses multiple bioactivities; here, epoxy clerodane diterpene (ECD) was isolated from Tinospora cordifolia (Willd.) stem and shown potential antiproliferative effect in MCF-7 human breast cancer cells. The antiproliferative effect of ECD on MCF-7 cells was systematically analyzed by cell and nuclear morphology, alterations in oxidative stress, and the expression of tumor suppressor and mitochondria-mediated apoptosis-related genes. We found that the IC50 value of ECD was 3.2μM at 24h and 2.4μM at 48h. We observed that the cytotoxicity of ECD was specific to MCF-7 cells, whereas ECD was nontoxic to normal Vero and V79 cells. ECD significantly triggered intracellular ROS generation even from the lower doses of 0.6 and 1.2μM; and it is relative to higher dose of 2.4μM. Further, we used 0.6μM, 1.2μM and 2.4μM as experimental doses to analyze the relative dose-dependent effects. Nuclear staining revealed that cells treated with the 2.4μM dose exhibited characteristic apoptotic morphological changes and that 46% of the cells were apoptotic and 4% were necrotic after 48h. ECD significantly increased the expression of mitochondria-dependent apoptotic pathway-related genes after 48h; we observed significantly (p≤0.05) increased expression of CYP1A, GPX, GSK3β and TNF-α and downregulated expression of NF-κB. ECD also increased the expression of tumor suppressor genes such as Cdkn2A, Rb1 and p53. In addition, we observed that ECD treatment significantly (p≤0.001) upregulated the expression of apoptotic genes such as Bax, cas-3, cas-8, cas-9 and p21 and downregulated the expression of BCL-2, mdm2 and PCNA. In conclusion, ECD regulates the expression of Cdkn2A, p53 and mdm2 and induces apoptosis via the mitochondrial pathway in MCF-7 human breast cancer cells.

Al-Alem F, Mattar RE, Fadl OA, et al.
Morbidity and mortality and predictors of outcome following hepatectomy at a Saudi tertiary care center.
Ann Saudi Med. 2016 Nov-Dec; 36(6):414-421 [PubMed] Related Publications
BACKGROUND: Hepatic resection is a major surgical procedure. Data on outcomes of hepatectomy in Saudi Arabia are scarce.
OBJECTIVE: To measure morbidity and mortality and assess predictors of outcome after hepatectomy.
DESIGN: Descriptive study.
SETTING: Tertiary care center in Saudi Arabia with well established hepatobiliary surgery unit.
PATIENTS AND METHODS: All patients undergoing liver resection in our institute during 2006-2014. Data were analyzed by Kaplan-Meier survival analysis.
MAIN OUTCOMES MEASURE(S): Postoperative morbidity and 90-day mortality. Secondary outcomes were risk factors associated with increased morbidity and mortality.
RESULTS: Data on 77 resections were collected; 56 patients (72.7%) had a malignant etiology, mainly colorectal liver metastases and hepatocellular carcinoma (45.5% and 14.3% respectively). Complications developed following 30 resections (39.0%), with the majority being Clavien grades I-III. In the univariate analysis, predicting factors were the total bilirubin level preoperatively, operative time, extent of resection (i.e., major resection), use of epidural anesthesia, and postoperative liver dysfunction. In the multivariate analysis, the Schindl liver dysfunction score showed the strongest correlation with the development of complications (P=.006). The 90-day postoperative mortality was 5.2% (4/77 patients); 3 patients fulfilled the 50:50 liver dysfunction criteria. Significant predictors were concurrent intra-abdominal surgery, postoperative liver dysfunction, and multiple complications.
CONCLUSION: Factors that predicted development of complications were elevated total bilirubin level preoperatively, operative time, extent of the resection, use of epidural anesthesia and a postoperative need for blood transfusion. Liver resection is a safe and feasible option at our center.
LIMITATIONS: The small number of indications for resection and consequent reduction in variety of risk factors limited ability to make inferences. Additionally, only a handful of cases were performed laparoscopically.

Aldiab A, Al Khayal KA, Al Obaid OA, et al.
Clinicopathological Features and Predictive Factors for Colorectal Cancer Outcome in the Kingdom of Saudi Arabia.
Oncology. 2017; 92(2):75-86 [PubMed] Related Publications
BACKGROUND/AIMS: Colorectal cancer (CRC) is the most frequent cancer and a leading cause of cancer death in the Kingdom of Saudi Arabia (KSA). To date, no nationwide screening programs have been adopted. This prospective, longitudinal study investigated factors influencing the outcome of CRC in Saudi patients.
METHODS: Patients completed a CRC awareness questionnaire. Colonoscopy, CT/MRI, histopathology of tumor biopsies, and KRAS and BRAF testing were performed. Patients were treated according to their stage. All patients were followed until the end of the study and 3- and 5-year survival was assessed.
RESULTS: Sixty percent of study patients with sporadic CRC presented with significantly advanced disease (stages III and IV) with or without metastases at entry. Patients showed low levels of awareness of the risk factors and signs of CRC. Patients presented at a median age of 50 years. Family history of CRC and ulcerative colitis were positive in 11 and 6% of patients, respectively. Stage III/IV tumors with distant metastases at enrollment, right-sided tumors, mucinous tumors, lymphovascular invasion, and KRAS (51%) or BRAF (28%) mutations predicted poor prognosis and survival.
CONCLUSION: CRC in KSA is usually diagnosed at advanced stages with metastases and KRAS/BRAF, and is associated with poor prognosis and short survival. Nationwide awareness campaigns and screening programs for CRC are critical for prevention, early detection and adequate management of CRC.

Abou-Al-Shaar H, Abd-El-Barr MM, Zaidi HA, et al.
Frontal dermoid cyst coexisting with suprasellar craniopharyngioma: a spectrum of ectodermally derived epithelial-lined cystic lesions?
Neurosurg Focus. 2016; 41(6):E16 [PubMed] Related Publications
There is a wide group of lesions that may exist in the sellar and suprasellar regions. Embryologically, there is varying evidence that many of these entities may in fact represent a continuum of pathology deriving from a common ectodermal origin. The authors report a case of a concomitant suprasellar craniopharyngioma invading the third ventricle with a concurrent frontal lobe cystic dermoid tumor. A 21-year-old man presented to the authors' service with a 3-day history of worsening headache, nausea, vomiting, and blurry vision. Magnetic resonance imaging depicted a right frontal lobe lesion associated with a separate suprasellar cystic lesion invading the third ventricle. The patient underwent a right pterional craniotomy for resection of both lesions. Gross-total resection of the right frontal lesion was achieved, and subtotal resection of the suprasellar lesion was accomplished with some residual tumor adherent to the walls of the third ventricle. Histopathological examination of the resected right frontal lesion documented a diagnosis of dermoid cyst and, for the suprasellar lesion, a diagnosis of adamantinomatous craniopharyngioma. The occurrence of craniopharyngioma with dermoid cyst has not been reported in the literature before. Such an association might indeed suggest the previously reported hypothesis that these lesions represent a spectrum of ectodermally derived epithelial-lined cystic lesions.

Naddaf S, Azzumeea F, Fahad Alzayed M
99mTc-DMSA Uptake in a Sister Mary Joseph's Nodule From Ovarian Cancer.
Clin Nucl Med. 2016; 41(12):993-994 [PubMed] Related Publications
A 50-year-old woman with ovarian cancer underwent Tc-DMSA scan to evaluate the functional status of the right hydronephrotic kidney. The images incidentally revealed a well-defined focus of mild radiotracer uptake at the midanterior abdominal wall, which correlated with a metastatic Sister Mary Joseph's nodule seen on CT performed a week earlier.

Alfayez M, Vishnubalaji R, Alajez NM
Runt-related Transcription Factor 1 (RUNX1T1) Suppresses Colorectal Cancer Cells Through Regulation of Cell Proliferation and Chemotherapeutic Drug Resistance.
Anticancer Res. 2016; 36(10):5257-5263 [PubMed] Related Publications
BACKGROUND/AIM: Altered expression of runt-related transcription factor 1 (RUNX1T1) has been observed in several human cancer types; however, the exact role for RUNX1T1 in colorectal cancer (CRC) remains unclear.
MATERIALS AND METHODS: The GSE21510 CRC and our previously published datasets were utilized in this study. Gene-expression profiling was conducted using the Agilent microarray platform, while data normalization and bioinformatics were conducted using GeneSpring software. AlamarBlue assay was used to assess cell viability in vitro.
RESULTS: The expression of RUNX1T1 was severely down-regulated in primary CRC and cell lines. Lentiviral-mediated re-expression of RUNX1T1 inhibited CRC cell growth, and global gene-expression analysis revealed the cell cycle, DNA replication, and DNA damage as the pathways most affected by RUNX1T1. Forced expression of RUNX1T1 induced a significant reduction in cellular proliferation and sensitized CRC cells to 5-flurouracil.
CONCLUSION: Our data revealed a novel role for RUNX1T1 as a tumor-suppressor gene in CRC through modulation of multiple cellular pathways.

Ekhzaimy A, Mujamammi A
Bilateral primary adrenal lymphoma with adrenal insufficiency.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Primary adrenal lymphoma is an extremely rare condition. We describe a case of bilateral adrenal lymphoma in a man aged 55 years who was admitted to our hospital. He had a 3-month history of left flank pain, nausea and vomiting with weight loss. A CT scan at a private hospital revealed bilateral large adrenal masses; the patient was referred to our centre based on these findings. He was evaluated for pheochromocytoma by an endocrinology team; however, all findings were negative. In addition, a cosyntropin stimulation test indicated adrenal insufficiency. A Trucut biopsy of the adrenal gland revealed diffuse large B-cell lymphoma of the adrenal glands, and the patient responded extremely well to chemotherapy.

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.

Korashy HM, Belali OM, Ansar MA, Alharbi NO
FoxO3a is Essential for the Antiproliferative and Apoptogenic Effects of Sunitinib in MDA-MB231 Cell Line.
Anticancer Res. 2016; 36(11):6097-6108 [PubMed] Related Publications
BACKGROUND: Sunitinib (SUN), a tyrosine kinase inhibitor, is a promising treatment for triple-negative breast cancer (TNBC), the most aggressive and fast-growing type of breast cancer. Yet, the protective effect of SUN against TNBC is poorly investigated and the role of Forkhead box type O (FOXO3a) transcription factor is still unknown.
MATERIALS AND METHODS: Cell proliferation was evaluated using the MTT assay. The mRNA and protein expression of apoptotic, oxidative stress and cell cycle genes were determined by real-time polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Percentage of the apoptotic cells were determined by flow cytometry. The role of FOXO3a was knock-downed using siRNA.
RESULTS: SUN caused suppression of MDA-MB231 cell growth associated with induction of apoptosis, cell cycle arrest, oxidative stress markers and FOXO3a gene. Importantly, silencing of FOXO3a mRNA using siRNA significantly rescued MDA-MB231 cells from SUN-induced cell-proliferative arrest.
CONCLUSION: SUN inhibits TNBC MDA-MB231 cell proliferation through activation of FOXO3a expression.

Bubendorf L, Büttner R, Al-Dayel F, et al.
Testing for ROS1 in non-small cell lung cancer: a review with recommendations.
Virchows Arch. 2016; 469(5):489-503 [PubMed] Free Access to Full Article Related Publications
Rearrangements of the ROS1 gene occur in 1-2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC. Consequently, focus on ROS1 testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed. ROS1 testing is often only considered after negative tests for EGFR mutation and ALK gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of ROS1 gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice, ROS1 fusion gene testing will be provided as part of the initial testing package.

Alsanad SM, Howard RL, Williamson EM
An assessment of the impact of herb-drug combinations used by cancer patients.
BMC Complement Altern Med. 2016; 16(1):393 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Herb/Dietary Supplements (HDS) are the most popular Complementary and Alternative Medicine (CAM) modality used by cancer patients and the only type which involves the ingestion of substances which may interfere with the efficacy and safety of conventional medicines. This study aimed to assess the level of use of HDS in cancer patients undergoing treatment in the UK, and their perceptions of their effects, using 127 case histories of patients who were taking HDS. Previous studies have evaluated the risks of interactions between HDS and conventional drugs on the basis on numbers of patient using HDSs, so our study aimed to further this exploration by examining the actual drug combinations taken by individual patients and their potential safety.
METHOD: Three hundred seventy-five cancer patients attending oncology departments and centres of palliative care at the Oxford University Hospitals Trust (OUH), Duchess of Kent House, Sobell House, and Nettlebed Hospice participated in a self-administered questionnaire survey about their HDS use with their prescribed medicines. The classification system of Stockley's Herbal Medicine's Interactions was adopted to assess the potential risk of herb-drug interactions for these patients.
RESULTS: 127/375 (34 %; 95 % CI 29, 39) consumed HDS, amounting to 101 different products. Most combinations were assessed as 'no interaction', 22 combinations were categorised as 'doubt about outcomes of use', 6 combinations as 'Potentially hazardous outcome', one combination as an interaction with 'Significant hazard', and one combination as an interaction of "Life-threatening outcome". Most patients did not report any adverse events.
CONCLUSION: Most of the patients sampled were not exposed to any significant risk of harm from interactions with conventional medicines, but it is not possible as yet to conclude that risks in general are over-estimated. The incidence of HDS use was also less than anticipated, and significantly less than reported in other areas, illustrating the problems when extrapolating results from one region (the UK), in one setting (NHS oncology) in where patterns of supplement use may be very different to those elsewhere.

Karam RA, Al Jiffry BO, Al Saeed M, et al.
DNA repair genes polymorphisms and risk of colorectal cancer in Saudi patients.
Arab J Gastroenterol. 2016; 17(3):117-120 [PubMed] Related Publications
BACKGROUND AND STUDY AIMS: Polymorphisms in the DNA repair genes may influence individual capacity to repair DNA damage, which may be associated with increased genetic instability and carcinogenesis. Our aim was to evaluate the relation of genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 (A399G), with colorectal cancer (CRC) susceptibility. We further investigated the potential effect of these DNA repair variants on clinicopathological parameters of CRC patients.
PATIENTS AND METHODS: Both XPD and XRCC1 polymorphisms were characterised in one hundred CRC patients and one hundred healthy controls who had no history of any malignancy by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and PCR with confronting two-pair primers (PCR-CTPP), using DNA from peripheral blood in a case control study.
RESULTS: Our results revealed that the frequencies of GG genotype of XRCC1 399 polymorphism were significantly higher in the CRC patients than in the normal individuals (p⩽0.03), and did not observe any association between the XPD Lys751Gln polymorphism and CRC risk. We found association between both XRCC1 A399G polymorphisms and histological grading of disease.
CONCLUSION: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to colorectal carcinoma.

Alhadheq AM, Purusottapatnam Shaik J, Alamri A, et al.
The Effect of Poly(ADP-ribose) Polymerase-1 Gene 3'Untranslated Region Polymorphism in Colorectal Cancer Risk among Saudi Cohort.
Dis Markers. 2016; 2016:8289293 [PubMed] Free Access to Full Article Related Publications
Background. DNA repair systems are essential for each cell to repair and maintain the genome integrity. Base excision repair pathway is one of the crucial pathways to maintain genome integrity and PARP-1 plays a key role in BER pathway. The purpose of this study is to evaluate the association between polymorphisms in PARP-1 3'untranslated region (3'UTR) SNP rs8679 and its expression in colorectal cancer. Methods. Genotyping and gene expression were performed using TaqMan assays. The effects of age, gender, and tumor location were evaluated in cases and controls regarding the genotyping results. Resulting data was analyzed using SPSS software. Results and Conclusions. Genotyping analysis for SNP rs8679 showed decreased susceptibility to colorectal cancer at heterozygous TC allele and at minor allele C. Further this protective association was also observed in younger age patients (≤57), in female patients, and also in patients with tumors located at colon and rectum. PARP-1 expression levels are significantly different in colorectal cancer compared to matched normal tissue. Our findings proved that the upregulation of PARP-1 is associated with tumor progression and poor prognosis in Saudi patients with colorectal cancer, suggesting that PARP-1 can be novel and valuable signatures for predicting the clinical outcome of patients with colorectal cancer.

Al-Qahtani AA, Al-Anazi MR, Al-Zoghaibi FA, et al.
 PARK2 polymorphisms predict disease progression in patients infected with hepatitis C virus.
Ann Hepatol. 2016 Nov-Dec 2016; 15(6):824-833 [PubMed] Related Publications
 Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases.
MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223.
RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020).
CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.

Seyam R, Khudair WA, Kattan SA, et al.
The impact of renal angiomyolipoma on estimated glomerular filtration rate in patients with tuberous sclerosis complex.
Ann Saudi Med. 2016 Sep-Oct; 36(5):356-363 [PubMed] Related Publications
BACKGROUND: There is a growing concern that renal impairment may develop in patients with renal angiomyolipomas (AMLs) associated with tuberous sclerosis complex (TSC) as a consequence of the disease itself and/or the interventions to mitigate the risk of hemorrhage.
OBJECTIVE: To assess the estimated glomerular filtration rate (eGFR) in patients with bilateral renal AMLs and the impact of tumor burden and intervention on renal function.
DESIGN: Retrospective study.
SETTING: Urology department of a tertiary care hospital.
PATIENTS AND METHODS: All adult patients (>=18 years of age) with TSC-associated renal AMLs seen from October 1998 to June 2015. We included only patients with bilateral tumors or solitary kidneys at the last follow-up.
MAIN OUTCOME MEASURES: The eGFR, renal volume, and number and type of interventions.
RESULTS: We identified 12 patients (median age 27.6, interquartile range 23.7-39.9 years), a median follow-up period of 1266 days (33-3133), and a median renal size of 454.7 mL (interquartile range 344.7-1016.9 on the right side; 558.1 mL, interquartile range 253.7-1001.4 on the left). In 11 (91.7%) patients, the eGFR was > 60 mL/min/1.77 m2. Six patients had three total nephrectomies, one had a contralateral partial nephrectomy, and seven had selective arterial embolizations. Intervention was associated with a significantly reduced eGFR. The renal size did not correlate with the eGFR.
CONCLUSIONS: TSC-associated renal AMLs may attain a large size but normal renal function is maintained in 92% of patients. Interventions to mitigate the risk of hemorrhage are associated with decreased renal function.
LIMITATIONS: The renal size was used as a surrogate for tumor size. Other limitations were the limited number of patients and lack of split renal function testing.

Aljabri KS, Bokhari SA, Assiri FY, et al.
The epidemiology of pituitary adenomas in a community-based hospital: a retrospective single center study in Saudi Arabia.
Ann Saudi Med. 2016 Sep-Oct; 36(5):341-345 [PubMed] Related Publications
BACKGROUND: Data on pituitary adenoma (PA) prevalence in Saudi Arabia are scarce.
OBJECTIVE: To estimate the epidemiology of PA in a well-defined population.
DESIGN: Retrospective analysis.
SETTING: Departments of Endocrinology and Radiology at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.
PATIENTS AND METHODS: Radiological and hormonal data of patients with pituitary adenoma by MRI were reviewed for the period January 2008 to December 2015.
MAIN OUTCOME MEASURES: Prevalence of PA and hormonal abnormalities.
RESULTS: Of 537 patients; 249 subjects (46.4%), 70 (28.1%) males and 179 (71.9%) females, were diagnosed to have PA with mean age 36.3 (14.1) years. Microadenoma and macroadenoma were seen in 171 (69%) and 78 (31%) subjects, respectively. Microadenomas were more prevalent than macroadenomas (68.7% vs. 31.3%). Microadenomas were significantly more prevalent in females, 131 (73.2 %) vs. 40 (57.1%) whereas macroadenomas were significantly more prevalent in males, 30 (42.9%) vs. 48 (26.8%) (P < .001 for both comparisons). Patients with microadenomas were significantly younger than patients with macroadenomas (P < .0001). Advanced age was significantly associated with a larger PA size (r=0.39, P < .0002). Three types of hyperfunctioning PA were seen: prolactinoma, somatotroph adenoma, and corticotroph adenoma. Five types of hypofunctioning PA were seen: panhypopituitarism, secondary hypogonadism, growth hormone deficiency, central hypothroidism and central adrenal insufficiency. Non-functioning PA were within normal laboratory hormonal values in 2% of cases.
CONCLUSION: Our study showed that the prevalence of PA was greater than previously reported. This increased prevalence may have important implications when prioritizing funding for research and treatment of PA.
LIMITATIONS: Clustering of cases within the study region might have affected estimates and limited study sample size.

Al-Mandeel HM, Sagr E, Sait K, et al.
Clinical Practice Guidelines on the Screening and Treatment of Precancerous Lesions for Cervical Cancer Prevention in Saudi Arabia.
Ann Saudi Med. 2016 Sep-Oct; 36(5):313-320 [PubMed] Related Publications
BACKGROUND: Cervical cancer is the third most common gynecological malignancy in Saudi women with an estimated incidence rate of 1.9 cases per 100 000 women-years. More than 40% of cervical cancer cases are diagnosed at advanced stages due to lack of a routine screening program in Saudi Arabia. Thus, national guidelines for routine screening and treatment of precancerous cervical lesions are needed.
METHODS: The Saudi Centre for Evidence-Based Healthcare invited a panel of local experts and partnered them with a team from McMaster University in Canada for methodological support, to develop national clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer. After the panel identified key clinical questions, the McMaster University working group updated existing systematic reviews that had been used for the 2013 WHO Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Recommendations were based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Those recommendations took into account the available evidence, patient values and preferences, and resource use in the Saudi context. The panel provided recommendations on two major issues: screening for precancerous lesions (cervical intraepithelial neoplasia 2 & 3) and treatment of those lesions to prevent cervical cancer in women who tested positive after screening.
CONCLUSIONS: The Saudi expert panel recommends using the HPV DNA test followed by colposcopy or cytology (Pap test) followed by colposcopy to screen for CIN2+ in women at risk of cervical cancer. The panel recommends cryotherapy or loop excision electrosurgery procedure (LEEP) over cold knife cone biopsy to treat women at risk of cervical cancer that tests positive for CIN2+. Universal screening for precancerous cervical dysplasia in women in Saudi Arabia is recommended using HPV testing and or cytology. Either cryotherapy or LEEP are preferred for treatment.
LIMITATIONS: National studies on cervical cancer screening modalities and treatment of precancerous cervical lesions, including HPV prevalence and its association with cervical cancer, are scarce.

Ali MR, Ibrahim IM, Ali HR, et al.
Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis.
Int J Nanomedicine. 2016; 11:4849-4863 [PubMed] Free Access to Full Article Related Publications
Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment.

Khalid EB, Ayman EE, Rahman H, et al.
Natural products against cancer angiogenesis.
Tumour Biol. 2016; 37(11):14513-14536 [PubMed] Related Publications
The process of angiogenesis is quite well-known nowadays. Some medicines and extracts affecting this process are already used routinely in supporting the conventional treatment of many diseases that are considered angiogenic such as cancer. However, we must be aware that the area of currently used drugs of this type is much narrower than the theoretical possibilities existing in therapeutic angiogenesis. Plant substances are a large and diverse group of compounds that are found naturally in fruits, vegetables, spices, and medicinal plants. They also have different anticancer properties. The aim of this literature review article is to present the current state of knowledge concerning the molecular targets of tumor angiogenesis and the active substances (polyphenols, alkaloids, phytohormones, carbohydrates, and terpenes) derived from natural sources, whose activity against cancer angiogenesis has been confirmed.

Elsamany S, Elemam O, Elmorsy S, et al.
Predictive Value of the Pattern of β-Catenin Expression for Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.
Asian Pac J Cancer Prev. 2016; 17(8):4089-93 [PubMed] Related Publications
PURPOSE: This study aimed to explore the association of β-catenin expression pattern with pathological response after neoadjuvant chemotherapy in breast cancer (BC) patients.
MATERIALS AND METHODS: In this retrospective exploratory study, data for 50 BC patients who received neoadjuvant chemotherapy were recorded. β-catenin expression in tumours was assessed using immunohistochemistry and classified as either membranous or cytoplasmic according to the pattern of staining. Distributions of different clinico-pathological parameters according to β-catenin expression were assessed using the Chi-square test. Logistic regression analysis was used to assess any relation of the pattern of β-catenin expression with the pathological response.
RESULTS: Cytoplasmic β-catenin expression was detected in 34% of BCs. Among our cases, 52% were hormonal receptor (HR)-positive, 24% were HER2-positive, 74% were clinical stage III and 74% received both anthracycline and taxane-based chemotherapy. Patients with cytoplasmic expression were more commonly younger than 40 years at diagnosis (cytoplasmic, 41.2% vs. no cytoplasmic expression, 12.1%, p=0.03). By doing t-test, cytoplasmic β-catenin expression was linked with a higher body mass index compared to membranous-only expression (mean± SD 33.0 ± 4.47 vs. 29.6 ±6.01, respectively, p=0.046). No significant associations were found between β-catenin expression and other parameters such as HR and HER2 status, or clinical stage. Complete pathological response (pCR) rate was twice as great in patients with membranous expression but without statistical signi cance (membranous- only, 33.3% vs. cytoplasmic, 17.6%, OR=2.3, 95% CI= 0.55-9.87, p=0.24).
CONCLUSIONS: This study suggests that cytoplasmic β-catenin expression may be linked with lower probability of achieving pCR after neoadjuvant chemotherapy. These data need to be validated in a larger cohort of patients.

Alhazzazi TY, Alghamdi FT
Head and Neck Cancer in Saudi Arabia: a Systematic Review.
Asian Pac J Cancer Prev. 2016; 17(8):4043-8 [PubMed] Related Publications
BACKGROUND: Head and neck cancer (HNC) is the ninth most common cancer worldwide, and has a poor 5-year survival rate averaging 50%, which has not changed for decades. A high prevalence of HNC has been reported in the southwestern region of Saudi Arabia, as compared to other areas of the country. However, data in regards to HNC are scattered and not well documented. Thus, the aim of this systematic review was to gather all available and updated important information regarding HNC in Saudi Arabia, and highlight the gaps of knowledge in our country with regard to this disease. In addition, suggestions of solutions to overcome the current status and improve our future standard of care to fight HNC are also highlighted.
MATERIALS AND METHODS: The electronic databases PubMed and Google Scholar using English-language literature were used for this systematic review, using specific inclusion and exclusion criteria and keywords. The search was performed in April 2016 and updated in June 2016.
RESULTS: Our search revealed twenty-one studies that fulfilled our inclusion and exclusion criteria and that were conducted in Saudi Arabia. These studies investigated different aspects of HNC, including prevalence, risk factors, biomarkers, and assessed knowledge and awareness of both public and practitioners with regard to HNC.
CONCLUSIONS: This review uncovered a big gap in our epidemiological data in cancer information in general, and head and neck cancer in particular. In addition, a lack of knowledge and awareness of both the public and health care practitioners hinders the early diagnosis of disease and negatively impact the prognosis, treatment and outcome. The Ministry of Health in Saudi Arabia should develop a more systematic way and adapt policies to gather cancer information in general, and head and neck cancer in particular, from all governmental and private sectors from all over the kingdom, and develop educational programs to raise the knowledge and awareness of HNC in the country.

Rai NP, Kumar P, Mustafa SM, et al.
Relation Between Periodontal Status and Pre-Cancerous Condition (Oral Lichen Planus): A Pilot Study.
Adv Clin Exp Med. 2016 Jul-Aug; 25(4):763-6 [PubMed] Related Publications
BACKGROUND: Oral lichen planus (OLP) is a common chronic mucocutaneous disease mostly seen in middle aged and elderly females. Oral lichen planus can occur in different oral sites such as gingiva, labial, buccal mucosa and on the tongue. And can have an indirect effect on initiating periodontitis.
OBJECTIVES: The purpose of the study was to evaluate the periodontal status of OLP patients and compare it with that of healthy controls. The presence of erosive lesions among gingival tissues makes oral hygiene procedures difficult to perform for obvious reasons. Plaque control and rigorous oral hygiene are primary requisites for the treatment of any oro-mucosal disease.
MATERIAL AND METHODS: Thirty patients with the erosive and reticular form of OLP as a study group and 30 healthy subjects as a control group were selected. The periodontal status of all subjects including gingival index (GI), Russell's periodontal index (PI) and bleeding on probing (BOP) were evaluated in both groups. Finally, the data was analyzed by a paired t-test using SPSS software v. 22.
RESULTS: The mean values of GI, PI and BOP were observed to be higher in the study group compared to the control group, and this was statistically significant (p < 0.05). The results shown are suggestive that periodontal status was poor in the study group as compared to the control group.
CONCLUSIONS: Further studies need to investigate periodontal status in oral lichen planus patients with larger sample size, and careful follow-up of these will assure an increase in the quality of life of these patients. The patient should be informed regarding the risk of periodontal problems in OLP and should be advised to have regular dental checkups to avoid a worsening of the conditio.

Al-Qahtani KH, Tunio MA, Asiri MA, et al.
Comparative clinicopathological and outcome analysis of differentiated thyroid cancer in Saudi patients aged below 60 years and above 60 years.
Clin Interv Aging. 2016; 11:1169-74 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: The aim of this study was to evaluate the treatment outcomes of differentiated thyroid cancer in Saudi patients aged above 60 years.
MATERIALS AND METHODS: Comparative analysis was performed in 252 patients aged 46-60 years (Group A) and 118 patients aged above 60 years (Group B), who had thyroidectomy, radioactive iodine-131, and thyroid-stimulating hormone suppression therapy between July 2000 and December 2012. Different clinicopathological features, treatment, complications, disease-free survival, and overall survival rates were compared.
RESULTS: Mean age of patients in Group A was 51.9 years (range: 46-60), and mean age of those in Group B was 68.6 years (range: 62-97). Group B patients had higher positive lymph nodes (43.2%), P=0.011. The frequency of extrathyroidal extension, multifocality, and lymphovascular space invasion was seen more in Group B than in Group A. Postsurgical complications (permanent hypoparathyroidism, bleeding, and wound infections) were also seen more in Group B (P=0.043, P=0.011, and P=0.021, respectively). Group B patients experienced more locoregional recurrences (11.0%, P=0.025); similarly, more distant metastases were observed in Group B (15.3%, P=0.003). The 10-year disease-free survival rates were 87.6% in Group A and 70.8% in Group B (P<0.0001).
CONCLUSION: Differentiated thyroid cancer in patients aged above 60 years are more aggressive biologically and associated with a worse prognosis, and the morbidity is significantly high as compared to patients aged below 60 years.

Al-Attas A, Assidi M, Al-Maghrabi J, et al.
Enhancement of Pathologist's Routine Practice: Reuse of DNA Extracted from Immunostained Formalin-fixed Paraffin-embedded (FFPE) Slides in Downstream Molecular Analysis of Cancer.
Cancer Genomics Proteomics. 2016 09-10; 13(5):399-406 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIM: To date, the conventional formalin-fixed, paraffin-embedded (FFPE) technique is the gold-standard for preserving histomorphology. Once FFPE tissues are stained, slides are routinely archived along with their blocks at biobanks/hospitals. However, the reuse of fixed and stained biospecimens as DNA source is not a common routine practice worldwide and, thus, indicates the need of studies to investigate the feasibility of extracting DNA from already immunohistochemistry (IHC) FFPE-stained slides and its possible reuse in subsequent downstream molecular analyses.
MATERIALS AND METHODS: FFPE IHC slides from colorectal cancer (CRC) patients were prepared and stored in the CEGMR Biobank. The workflow consists of digitalization of IHC stained slide's image, removing the slide cover-slip, crude dissection and DNA extraction. Following DNA quality assessment, mutation analysis of CTNNB1 and methylation profile of CDH1 were performed.
RESULTS: High-quality DNA was obtained allowing 60% concordance between CDH1 methylation and membranous E-cadherin expression pattern. Clean CTNNB1 DNA chromatograms with evenly-spaced peaks were observed.
CONCLUSION: This study is a proof of concept to recycle and reuse DNA from IHC stained slides with suitable concentration and integrity for further downstream molecular applications. These findings will enhance the pathologists' knowledge, attitudes and practices (KAP) towards the use of these biospecimens and support the implementation of this approach in clinical pathology practice. Therefore, the scientific community will benefit from the largest comprehensive database of human fully annotated FFPE biospecimens already available at their disposal in order to demystify the complexity and the heterogeneity of many challenging diseases and foster the transition towards precision medicine.

AlJohani B, AlMalik O, Anwar E, et al.
Impact of Surgery on Survival in Stage IV Breast Cancer.
Breast J. 2016; 22(6):678-682 [PubMed] Related Publications
We aimed to assess retrospectively the survival outcome in patients with stage IV breast cancer who underwent surgery. In a retrospective, nonrandomized study of stage IV breast cancer patients diagnosed in a single institution between 2000 and 2012, we assessed patient's survival in the context of baseline characteristics. A total 678 patients with metastatic breast cancer were included; 412 (60.77%) underwent surgery for the primary tumor (Surgery group), and 266 (39%) did not underwent surgery for the primary tumor (Nonsurgery group), with a median follow-up of 41 months. Patients in the Surgery group had longer survival (41 versus 27 months, p < 0.0029). The 5-year survival rate for Surgery group was 34% compared with 14% for the Nonsurgery group. A multivariate analysis revealed surgery (p = 0.0003), large tumor size (p = 0.0195), ER-positive (p < 0.0001), and metastasis at presentation (p = 0.0032) were prognostic variables. Loco-regional surgery does confer a survival advantage in stage IV breast cancer, however, selection bias cannot be excluded, a well-designed and powerful randomized, controlled trial would be valuable to answer whether surgery can improve survival.

Gautam S, Roy S, Ansari MN, et al.
DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention.
Breast Cancer. 2017; 24(2):180-190 [PubMed] Related Publications
Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.

Zakowski MF, Rekhtman N, Auger M, et al.
Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens.
Arch Pathol Lab Med. 2016; 140(10):1116-20 [PubMed] Related Publications
CONTEXT: -The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material.
OBJECTIVE: -To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non-small cell lung carcinoma using cytologic preparations.
DESIGN: -Nine cytopathologists from different institutions submitted cases of non-small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times.
RESULTS: -Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%).
CONCLUSION: -Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience.

Alomar SY, Mansour L, Abuderman A, et al.
β-Catenin accumulation and S33F mutation of CTNNB1 gene in colorectal cancer in Saudi Arabia.
Pol J Pathol. 2016; 67(2):156-62 [PubMed] Related Publications
Several risk factors associated with colorectal cancer (CRC) have been identified including β-catenin/CTNNB1 hotspot mutations. The levels of β-catenin within a cell are regulated via phosphorylation of the N terminus of β-catenin by GSK-3β. Thus far three serines (S33, 37, 45) and one threonine (T41) are considered to be the substrates for GSK-3β phosphorylation. In the present investigation an attempt was made to study the role of β-catenin mutations in exon-3 in 60 colorectal cancer patients from Kingdom of Saudi Arabia (KSA). The hot spot mutation region of β-catenin exon 3 was evaluated in matched tumor and normal tissues using PCR and direct sequencing. Sequencing of exon 3 of the CTNNB1 gene revealed an activating mutation (S33F) in one of the tumor samples as compared to the normal tissue from the same patient where there was no such mutation found. Immunohistochemical staining showed the accumulation of β-catenin protein both in cytoplasm and in the nuclei of cancer cells as compared to normal tissue.

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