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Lebanon

Cancer Statistics
Population in 2008: 4.2m
People newly diagnosed with cancer (excluding NMSC) / yr: 7,100
Age-standardised rate, incidence per 100,000 people/yr: 169.6
Risk of getting cancer before age 75:17.5%
People dying from cancer /yr: 4,900
Data from IARC GlobalCan (2008)
Lebanon Cancer Organisations and Resources
Latest Research Publications Related to Lebanon

Lebanon Cancer Organisations and Resources (6 links)


Latest Research Publications Related to Lebanon

Rafei H, El-Bahesh E, Finianos A, et al.
Immune-based Therapies for Non-small Cell Lung Cancer.
Anticancer Res. 2017; 37(2):377-387 [PubMed] Related Publications
Lung cancer is the leading cause of cancer-related death worldwide. Treatment of non-small cell lung cancer has evolved tremendously over the past decade. Specifically, immune checkpoint inhibitors have become an increasingly interesting target of pharmacological blockade. These immune inhibitors have shown promising results in front-line therapy and after failure of multiple lines, as well as in monotherapy and combination with other therapies. Vaccination in non-small cell lung cancer is also an emerging field of research that holds promising results for the future of immunotherapy in non-small cell lung cancer. This review presents a concise update on the most recent data regarding the role of checkpoint inhibitors as well as vaccination in non-small cell lung cancer.

Shebaby WN, Mroueh MA, Boukamp P, et al.
Wild carrot pentane-based fractions suppress proliferation of human HaCaT keratinocytes and protect against chemically-induced skin cancer.
BMC Complement Altern Med. 2017; 17(1):36 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous studies in our laboratory showed that the Lebanese Daucus carota ssp. carota (wild carrot) oil extract possesses in vitro and in vivo anticancer activities. The present study aims to examine the cytotoxic effect of Daucus carota oil fractions on human epidermal keratinocytes and evaluate the chemopreventive activity of the pentane diethyl ether fraction on DMBA/TPA induced skin carcinogenesis in mice.
METHODS: Wild carrot oil extract was chromatographed to yield four fractions (F1, 100% pentane; F2, 50:50 pentane:diethyl ether; F3, 100% diethyl ether; F4 93:7 chloroform:methanol). The cytotoxic effect of fractions (10, 25, 50 and 100 μg/mL) was tested on human epidermal keratinocytes (non-tumorigenic HaCaT cells and tumorigenic HaCaT-ras variants) using WST a ssay. Cell cycle phase distribution of tumorigenic HaCaT-ras variants was determined by flow cytometry post-treatment with F2 fraction. Apoptosis related proteins were also assessed using western blot. The antitumor activity of F2 fraction was also evaluated using a DMBA/TPA induced skin carcinoma in Balb/c mice.
RESULTS: All fractions exhibited significant cytotoxicity, with HaCaT cells being 2.4-3 times less sensitive than HaCaT-ras A5 (benign tumorigenic), and HaCaT-ras II4 (malignant) cells. GC-MS analysis revealed the presence of a major compound (around 60%) in the pentane/diethylether fraction (F2), identified as 2-himachalen-6-ol. Treatment of HaCaT-ras A5 and HaCaT-ras II4 cells with F2 fraction resulted in the accumulation of cells in the sub-G1 apoptotic phase and decreased the population of cells in the S and G2/M phases. Additionally, F2 fraction treatment caused an up-regulation of the expression of pro-apoptotic (Bax) and down-regulation of the expression of anti-apoptotic (Bcl2) proteins. A decrease in the phosphorylation of AKT and ERK was also observed. Intraperitoneal treatment with F2 fraction (50 or 200 mg/kg) in the DMBA/TPA skin carcinogenesis mouse model showed a significant inhibition of papilloma incidence (mice with papilloma), yield (number of papilloma/mouse) and volume (tumor relative size) at weeks 15, 18 and 21.
CONCLUSION: The present data reveal that F2 fraction has a remarkable antitumor activity against DMBA/TPA-induced skin carcinogenesis, an effect that may be mediated through inhibition of the MAPK/ERK and PI3K/AKT pathways.

Yan S, Holderness BM, Li Z, et al.
Epithelial-Mesenchymal Expression Phenotype of Primary Melanoma and Matched Metastases and Relationship with Overall Survival.
Anticancer Res. 2016; 36(12):6449-6456 [PubMed] Related Publications
E-Cadherin and N-cadherin are important components of epithelial-mesenchymal transition (EMT). The majority of studies on EMT in melanoma have been performed with cultured cell lines or pooled melanoma samples. The goal of our study was to evaluate the expression of E-cadherin and N-cadherin in matched tissue samples from primary and metastatic sites of melanoma and to determine the correlation with survival outcome. We analyzed tissues from 42 melanoma primary lesions and their corresponding metastases, as well as 53 benign nevi, for expression levels of E-cadherin and N-cadherin using immunohistochemical methods. There were heterogenous expression patterns of E- and N-cadherin in both primary and metastatic melanomas. Overall, metastatic tumor showed a decrease in E-cadherin expression and an increase in N-cadherin expression compared to the primary tumor, although the difference did not reach statistical significance (p=0.24 and 0.28 respectively). A switch of membranous expression from E-cadherin to N-cadherin from primary to metastatic melanoma was seen in eight patients (19%). Aberrant E-cadherin expression (defined as negative to weak membranous E-cadherin or positive nuclear E-cadherin expression) was more frequently observed in metastatic than in primary melanomas (p=0.03). Multivariate analysis showed that absence of N-cadherin expression in primary melanomas and the presence of aberrant E-cadherin expression in primary melanomas and metastatic melanomas was associated with a significantly worse overall survival. Our data support the importance of E-cadherin and N-cadherin proteins in melanoma progression and patient survival.

Olofson AM, Loo EY, Hill PA, Liu X
Plasmablastic lymphoma mimicking carcinomatosis: A case report and review of the literature.
Diagn Cytopathol. 2017; 45(3):243-246 [PubMed] Related Publications
First identified as a distinct disease entity in HIV-positive patients, plasmablastic lymphoma is a rare aggressive disease which arises predominantly in men and is associated with immunodeficiency of all causes. Although its exact etiology is poorly understood, Epstein-Barr virus infection and MYC gene aberrations have been implicated in its development in both HIV-positive and HIV-negative patients. The disease typically involves extranodal sites with a predilection for the oral cavity but may occur in other locations. Here we present a case of plasmablastic lymphoma diffusely involving the omentum and peritoneal cavity of an immunocompetent woman, clinically mimicking an ovarian carcinomatosis. To the best of our knowledge, this is the first case in which plasmablastic lymphoma has presented as peritoneal lymphomatosis. Diagn. Cytopathol. 2017;45:243-246. © 2016 Wiley Periodicals, Inc.

Welch HG, Prorok PC, O'Malley AJ, Kramer BS
Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness.
N Engl J Med. 2016; 375(15):1438-1447 [PubMed] Related Publications
Background The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002). Results After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality. Conclusions Although the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.

Gardner JA, Peterson JD, Turner SA, et al.
Detection of CALR Mutation in Clonal and Nonclonal Hematologic Diseases Using Fragment Analysis and Next-Generation Sequencing.
Am J Clin Pathol. 2016; 146(4):448-55 [PubMed] Related Publications
OBJECTIVES: To describe three methods used to screen for frameshift mutations in exon 9 of the CALR gene.
METHODS: Genomic DNA from 47 patients was extracted from peripheral blood and bone marrow using the EZ1 DNA Blood Kit (Qiagen, Valencia, CA) and quantified by the Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen, San Diego, CA). After clinical history, cytogenetics, and molecular tests, patients were diagnosed with either clonal or nonclonal hematologic diseases. CALR screening was primarily performed using fragment analysis polymerase chain reaction, then next-generation sequencing and Sanger sequencing.
RESULTS: Among the 18 patients diagnosed with clonal diseases, one had acute myeloid leukemia (positive for trisomy 8), and 17 had myeloproliferative neoplasms (MPNs), including chronic myeloid leukemia (CML), essential thrombocythemia (ET), primary myelofibrosis (PMF), and polycythemia vera (PV). Patients with CML were positive for the BCR-ABL1 fusion. Ten patients were positive for JAK2 (PMF, n = 1; ET, n = 2; PV, n = 7), and three were CALR positive (ET, n = 1; PMF, n = 2). Patients diagnosed with a nonclonal disease were negative for JAK2, BCR-ABL, and CALR mutations.
CONCLUSIONS: Screening for CALR mutations is essential in BCR-ABL-negative MPNs since it not only provides valuable diagnostic and prognostic information but also identifies potential treatment targets. Since this study describes the importance of screening for known and novel biomarkers, we described in detail three methods that could be easily integrated into a clinical laboratory.

Kattan J, Eid R, Kourie HR, et al.
Mesotheliomas in Lebanon: Witnessing a Change in Epidemiology.
Asian Pac J Cancer Prev. 2016; 17(8):4169-73 [PubMed] Related Publications
BACKGROUND: Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001.
MATERIALS AND METHODS: Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families.
RESULTS: A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care.
CONCLUSIONS: Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.

Yacoubian A, Dargham RA, Khauli RB, Bachir BG
Overview of Dietary Supplements in Prostate Cancer.
Curr Urol Rep. 2016; 17(11):78 [PubMed] Related Publications
Prostate cancer is a key health concern for men with its etiology still under investigation. Recently, the role of dietary supplements has been noted to have a major inhibitory effect on prostate cancer and numerous studies have been conducted in this regard. This review provides a summary on numerous recent studies conducted in this field. Some of the studies reviewed revealed a protective role for supplements, and others showed no correlation while some even had an adverse effect. The mechanism of how these supplements act on the prostate is still not clear. Further studies are warranted especially for supplements that have been shown to have a potential inhibitory role in prostate cancer.

Elias F, Khuri FR, Adib SM, et al.
Financial Burden of Cancer Drug Treatment in Lebanon.
Asian Pac J Cancer Prev. 2016; 17(7):3173-7 [PubMed] Related Publications
BACKGROUND: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total caseload. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon.
MATERIALS AND METHODS: Using utilization and spending data accumulated at MOPH during 20082013, the cost to the public budget of cancer drugs was assessed per case and per drug type.
RESULTS: The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and NonHodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years.
CONCLUSIONS: Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

Nguyen NP, Nguyen LM, Thomas S, et al.
Oral sex and oropharyngeal cancer: The role of the primary care physicians.
Medicine (Baltimore). 2016; 95(28):e4228 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: We aimed to study the prevalence of oral sex and its possible association with human papillomavirus (HPV) 16 infection in the development of oropharyngeal cancer in the US population for possible prevention.
METHODS: We conduct a systemic review on the prevalence of oral sex among Americans among different age groups, the prevalence of HPV 16 infection reported in oropharyngeal cancer, and correlation between oral sex and oropharyngeal cancer.
RESULTS: Oral sex is prevalent among adolescents and sexually active adults. Sixty percent of oropharyngeal cancer reported in the United States is associated with HPV 16 infections. Individuals who practiced oral sex with multiple partners are at risk for developing oropharyngeal cancer and need to be informed about practicing safe sex or getting vaccination.
CONCLUSION: Family physicians will play a key role in prevention and educating the public about the risk of oral sex.

Karouni M, Kurban M, Abbas O
Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma.
Arch Dermatol Res. 2016; 308(7):487-92 [PubMed] Related Publications
Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.

Kang R, Goodney PP, Wong SL
Importance of cost-effectiveness and value in cancer care and healthcare policy.
J Surg Oncol. 2016; 114(3):275-80 [PubMed] Free Access to Full Article Related Publications
The cost of cancer care has increased by five fold over the last three decades. As our healthcare system shifts from volume to value, greater scrutiny of interventions with clinical equipoise is required. Traditionally, QALYs and ICER have served as surrogate markers for value. However, this approach fails to incorporate all stakeholders' viewpoints. Prostate cancer, low risk DCIS, and thyroid cancer are used as a framework to discuss value and cost-effectiveness. J. Surg. Oncol. 2016;114:275-280. © 2016 Wiley Periodicals, Inc.

Nicolas G, Kfoury T, Shimlati R, et al.
Incidental Finding and Management of Mesenteric Fibromatosis.
Am J Case Rep. 2016; 17:389-94 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Mesenteric fibromatosis, also known as mesenteric desmoids, is part of the clinical-pathologic spectrum of deep fibromatosis, which encompasses a group of benign fibro-proliferative processes that are locally aggressive and have the capacity to infiltrate or recur without metastasis.
CASE REPORT: Case of a 45-year-old man, with a history of hypertension and lung fibrosis, presenting for a left abdominal mass, which was found incidentally during his lung fibrosis imaging. He complained of constipation due to pressure upon his bowel leading to difficulty in defecation.
CONCLUSIONS: Although there are many overlapping criteria between gastrointestinal stromal tumors and mesenteric fibromatosis, making it difficult to discriminate between the two, there are differences that are unique to mesenteric fibromatosis that should be noticed during the diagnosis. In this case, mesenteric fibromatosis was unusual as it is not associated with Gardner's syndrome, desmoid tumors, nor familial adenomatous polyposis, but was an incidental finding.

Yan S, Coffing BN, Li Z, et al.
Diagnostic and Prognostic Value of ProEx C and GLUT1 in Melanocytic Lesions.
Anticancer Res. 2016; 36(6):2871-80 [PubMed] Related Publications
BACKGROUND: Melanoma is one of the most aggressive types of skin cancer. The purpose of this study was to evaluate the use of two biomarkers, ProEx C and glucose transporter isoform 1 (GLUT1), in the diagnosis and prognostication of melanoma.
MATERIALS AND METHODS: We analyzed 129 melanomas and 59 benign nevi in a tissue microarray using immunohistochemical method with antibodies to topoisomerase IIα (TOP2A) and minichromosome maintenance complex component 2 (MCM2) using ProEx C and to GLUT1.
RESULTS: The average proliferative index by ProEx C immunostain was significantly higher in melanomas (37.5%) compared to benign nevi (1.9%) as was the expression of GLUT1 (p<0.0001 respectively). Dermal mitosis was found to correlate positively with both ProEx C and GLUT1 (p=0.003 and p<0.001, respectively). Ulceration and tumor thickness positively correlated with GLUT1 expression (p=0.013 and p=0.033, respectively), but not with ProEx C staining. There was a significant association between increasing ProEx C index and stronger expression of GLUT1 (p<0.001). Kaplan-Meier disease-specific survival analyses indicated that patients whose melanoma exhibited expression of GLUT1 had a significantly lower rate of disease-specific survival than patients whose melanoma did not (p=0.039). However, staining by ProEx C did not show a prognostic significance in disease-specific survival.
CONCLUSION: ProEx C and GLUT1 are potentially useful markers in differentiation of melanoma from nevi. Absence of GLUT1 expression in patients with primary melanoma predicts better survival.

Kourie HR, Ghorra C, Rassy M, et al.
Digestive Neuroendocrine Tumor Distribution and Characteristics According to the 2010 WHO Classification: a Single Institution Experience in Lebanon.
Asian Pac J Cancer Prev. 2016; 17(5):2679-81 [PubMed] Related Publications
BACKGROUND: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in the gastrointestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP-NENs in a Lebanese population.
MATERIALS AND METHODS: This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site.
RESULTS: A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP-NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC).
CONCLUSIONS: This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports.

Kesrouani C, Ghorra C, Rassy M, et al.
Distribution and Characteristics of Pulmonary Neuroendocrine Tumors: Single Institution Experience in Lebanon.
Asian Pac J Cancer Prev. 2016; 17(5):2579-81 [PubMed] Related Publications
BACKGROUND: Neuroendocrine tumors represent 20% of primary lung neoplasms in some registries. According to the WHO classification of 2004, reconsidered for 2015, these lung tumors are divided into 4 groups: typical and atypical carcinoid, small cell and large cell neuroendocrine carcinomas. We report in this paper, for the first time in Lebanon, the distribution and the population characteristics of these tumors.
MATERIALS AND METHODS: This descriptive retrospective study concerned all the pulmonary neuroendocrine tumors (NET) with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, with attention to features like age, gender and subgroup.
RESULTS: Of 194 patients with pulmonary NET, 12.4% were typical carcinoid tumors, 3.6% atypical carcinoid, 66.5% small cell lung cancer, 7.7% combined small cell carcinomas and 9.8% large cell neuroendocrine tumors. The mean ages of patients were respectively 51.2 years in typical carcinoid, 64 years in atypical carcinoid, 64.2 years in small cell lung cancers, 67.2 in combined small cell lung cancer and 66.9 in large cells neuroendocrine tumors. The M/F sex ratios were respectively 0.3, 1.3, 1.4, 2.7 and 2.2.
CONCLUSIONS: The characteristics of lung neuroendocrine tumors in our Lebanese institution are comparable to those reported in the literature.

Saad A, Der-Nigoghossian CA, Njeim R, et al.
Prescription Errors with Chemotherapy: Quality Improvement through Standardized Order Templates.
Asian Pac J Cancer Prev. 2016; 17(4):2329-36 [PubMed] Related Publications
BACKGROUND: Despite the existence of established guidelines advocating the use and value of chemotherapy order templates, chemotherapy orders are still handwritten in many hospitals in Lebanon. This manuscript describes the implementation of standardized chemotherapy order templates (COT) in a Lebanese tertiary teaching hospital through multiple steps.
INITIAL ASSESSMENT: An initial assessment was conducted through a retrospective appraisal of completeness of handwritten chemotherapy orders for 100 adult patients to serve as a baseline for the project and identify parameters that might afford improvement.
CHOICE OF SOLUTION: Development of over 300 standardized pre-printed COTs based on the National Comprehensive Cancer Network templates and adapted to the practice culture and patient population.
IMPLEMENTATION: The COTs were implemented, using Kotter's 8-step model for leading change, by engaging health care providers, and identifying and removing barriers.
EVALUATION: Assessment of physicians' compliance with the new practice (122 orders assessed) was completed through two phases and allowed for the identification of areas of improvement.
LESSONS LEARNED: Overall, COT implementation showed an average improvement in order completion from 49.5% (handwritten orders) to 77.6% (phase 1-COT) to 87.6% (phase 2-COT) reflecting an increase of 38.1% between baseline and phase 2 and demonstrating that chemotherapy orders completeness was improved by pre-printed COT. As many of the hospitals in Lebanon are moving towards standardized COTs and computerized physician order entry (CPOE) in the next few years, this study provides a prototype for the successful implementation of COT and demonstrates their role in promoting quality improvement of cancer care.

Assi T, Nasr F, Rassy EE, et al.
Characteristics of Incident Testicular Cancer in Lebanon - 1990-2015 Single Institutional Experience.
Asian Pac J Cancer Prev. 2016; 17(4):1899-902 [PubMed] Related Publications
BACKGROUND: Despite the fact that testicular cancer is a major health issue with its increasing incidence, very few studies have described its characteristics in the Middle East, particularly in Lebanon.
MATERIALS AND METHODS: We report in this paper a retrospective pilot study of the characteristics of testicular cancer in Lebanon. The demographic, epidemiologic and survival characteristics of 178 patients diagnosed between 1990 and 2015 at an oncology clinic affiliated to Hotel Dieu de France Hospital were analyzed.
RESULTS: The mean age at diagnosis was 32 ±10 years. The most prevalent testicular tumor was the germ cell type (GCT) (95.2%) of which non-seminomatous tumors (NST) were the commonest (64.7%). Most of our patients were diagnosed at an early stage. Lymph node spread affected most commonly the retroperitoneal region and distant visceral metastases occurred in 14.6%. All patients underwent orchiectomy with 67% receiving adjuvant treatment, mainly chemotherapy. After a median follow up of 2,248 days (75.9 months) 16 patients were reported dead. Two, five and ten-year overall survival rates were 96%, 94% and 89% respectively. The median overall survival rate was not reached.
CONCLUSIONS: Despite being part of the developing world, demographic, epidemiologic and survival analyses of testicular cancer reported in our study are in line with those reported from developed countries and would allow us to extrapolate management plans from these populations.

Abi Nader E, Kourie HR, Ghosn M, et al.
Informational Needs of Women with Breast Cancer Treated with Chemotherapy.
Asian Pac J Cancer Prev. 2016; 17(4):1797-800 [PubMed] Related Publications
BACKGROUND: Research in the field of informational needs of breast cancer patients is scarce. In the few published articles, these needs were usually not satisfied. The main objective of this study was to evaluate satisfaction regarding informational needs in women with breast cancer. The long-term goal was to guide physician-patient communication to meet these needs.
MATERIALS AND METHODS: A survey with 21 questions was completed by 84 female patients receiving chemotherapy in a one-day hospital in Beirut, Lebanon. All patients were aware of their disease and agreed to participate in the survey.
RESULTS: The doctor was the major source of information for patients followed by media (radio and television). The level of knowledge of patients concerning their disease was proportional to the number of information sources. Women aged younger than 45 years, diagnosed during the last three months before the survey and certified from high school were less satisfied with information given by the oncologist. The missing information was in relation with the steps of the treatment after the chemotherapy regimen, the risk of a family member (sisters and daughters) of developing the disease and management of lymphedema.
CONCLUSIONS: This study generated a scale for the degree of satisfaction of information received by women with breast cancer from their oncologist. The physician can use this scale to improve his or her skills of communication to patients and diminish their level of fear and anxiety.

Lole Harris BH, Walsh JL, Nazir SA
Wünderlich ist nicht so Wunderbar: Bilateral Angiomyolipomas and Wünderlich Syndrome Requiring Emergency Embolization in a Patient without Tuberous Sclerosis.
Ann Vasc Surg. 2016; 34:270.e7-270.e11 [PubMed] Related Publications
Bilateral renal angiomyolipomata are rare and usually associated with tuberous sclerosis. Renal angiomyolipomata can rupture spontaneously giving rise to (potentially catastrophic) retroperitoneal hemorrhage (Wünderlich syndrome). We present a very rare case of bilateral renal angiomyolipomata in an individual without tuberous sclerosis, presenting with life-threatening hemorrhage. The patient had emergency embolization of the bleeding angiomyolipoma and received elective embolization of a contralateral lesion. A follow-up brain magnetic resonance imaging showed no tubers but revealed a pituitary adenoma of uncertain significance.

Jurca G, Addam O, Aksac A, et al.
Integrating text mining, data mining, and network analysis for identifying genetic breast cancer trends.
BMC Res Notes. 2016; 9:236 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Breast cancer is a serious disease which affects many women and may lead to death. It has received considerable attention from the research community. Thus, biomedical researchers aim to find genetic biomarkers indicative of the disease. Novel biomarkers can be elucidated from the existing literature. However, the vast amount of scientific publications on breast cancer make this a daunting task. This paper presents a framework which investigates existing literature data for informative discoveries. It integrates text mining and social network analysis in order to identify new potential biomarkers for breast cancer.
RESULTS: We utilized PubMed for the testing. We investigated gene-gene interactions, as well as novel interactions such as gene-year, gene-country, and abstract-country to find out how the discoveries varied over time and how overlapping/diverse are the discoveries and the interest of various research groups in different countries.
CONCLUSIONS: Interesting trends have been identified and discussed, e.g., different genes are highlighted in relationship to different countries though the various genes were found to share functionality. Some text analysis based results have been validated against results from other tools that predict gene-gene relations and gene functions.

Farhat F, Kattan JG, Ghosn M
Oral vinorelbine in combination with trastuzumab as a first-line therapy of metastatic or locally advanced HER2-positive breast cancer.
Cancer Chemother Pharmacol. 2016; 77(5):1069-77 [PubMed] Related Publications
PURPOSE: Vinorelbine-trastuzumab combination proved to be an effective first-line treatment for patients with locally advanced or metastatic breast cancer (MBC). Oral chemotherapy represents a step forward in MBC management. To improve patients' comfort using the oral form of vinorelbine, we conducted a multicenter phase II study to investigate the efficacy and safety of the oral vinorelbine-trastuzumab combination in women with MBC with human epidermal growth factor receptor 2 (HER2) overexpression.
METHODS: Main eligibility criteria: HER2-positive disease, no adjuvant chemotherapy within the last 6 months and no prior chemotherapy for MBC. Patients were treated with oral vinorelbine 80 mg/m(2) D1, D8, D15 (following first 3 administrations at 60 mg/m(2) during the first cycle) for a total of 8 cycles (1 cycle = 3 weeks), in combination with trastuzumab 6 mg/kg on D1 (loading dose: 8 mg/kg) every 3 weeks or 4 mg/kg (loading dose: 6 mg/kg) weekly. Response was evaluated every 2 cycles using RECIST 1.0.
PRIMARY ENDPOINT: objective response rate (ORR); secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: In the full population (n = 26), median age was 50.7 years and median WHO PS 0. Median disease-free interval was 50.7 months [95 % CI (43.6-57.9)]. In the evaluable patients population, ORR was 56 % [95 % CI (34.9-75.6)], including 3 complete responses (12 %) and 11 partial (44 %); 8 (32 %) patients had stable disease resulting in a clinical benefit (or disease control) rate of 88 % [95 % CI (68.8-97.5)]. Median DOR was 7.1 months [95 % CI (3.9-10.2)], median PFS 6.7 months (95 % CI 3.5-10), and median OS 27.9 months (95 % CI 17.4-38.3). Treatment was generally well tolerated with main observed grade 3/4 hematological toxicities being neutropenia (46 %) and anemia (4 %). Grade 3-4 nausea-vomiting were observed in 11.5 % of patients.
CONCLUSIONS: Our results confirm the efficacy of oral vinorelbine-trastuzumab combination as a first-line treatment in HER2-positive locally advanced or MBC patients with an acceptable safety profile. Oral vinorelbine-trastuzumab optimizes the convenience of this chemotherapy regimen, especially for patients receiving trastuzumab every 3 weeks.

Kheir WJ, Tetzlaff MT, Pfeiffer ML, et al.
Epithelial, non-melanocytic and melanocytic proliferations of the ocular surface.
Semin Diagn Pathol. 2016; 33(3):122-32 [PubMed] Related Publications
Ocular surface tumors are commonly encountered by ophthalmologists and ophthalmic pathologists. These tumors have varied clinical manifestations. In this article, we discuss the most commonly encountered non-melanocytic and melanocytic ocular surface tumors, with emphasis on their common clinical features, morphologic patterns, and prognostic factors.

Temraz S, Mukherji D, Shamseddine A
Dual targeting of HER3 and EGFR in colorectal tumors might overcome anti-EGFR resistance.
Crit Rev Oncol Hematol. 2016; 101:151-7 [PubMed] Related Publications
Multiple genetic alterations have been associated with resistance to anti-EGFR therapy in metastatic colorectal cancer (CRC) patients. Research has been mainly focused on driver mutations in KRAS, NRAS, BRAF and PI3K. However, recent evidence suggests a crucial role for non-genetic mechanisms in conferring resistance to anti-EGFR therapy. Specifically, the HER3 receptor is capable of heterodimerizing with multiple EGFR family members resulting in downstream activation of the PI3K and MAPK pathways. Monoclonal antibodies targeted against the HER3 receptor are being investigated in clinical trials; however, preliminary data has shown limited clinical activity. Thus, given the relevance of the HER3 receptor in activating downstream effector pathways and in conferring resistance to anti-EGFR therapy, the therapeutic targeting of HER3 in combination with primary drivers of the tumor is also being investigated. Here, we review the role of HER3 as a promoter of clinical resistance to EGFR therapy and discuss therapeutic approaches that could potentially overcome this resistance.

Ghosn M, Tabchi S, Kourie HR, Tehfe M
Metastatic gastric cancer treatment: Second line and beyond.
World J Gastroenterol. 2016; 22(11):3069-77 [PubMed] Free Access to Full Article Related Publications
Advanced gastric cancer (aGC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve survival and tumor related symptoms in the frontline setting, second-line therapy (SLT) is subject to much debate in the scientific community, mainly because of the debilitating effects of GC, which would impede the administration of cytotoxic therapy. Recent data has provided sufficient evidence for the safe use of SLT in patients with an adequate performance status. Taxanes, Irinotecan and even some Fluoropyrimidine analogs were found to provide a survival advantage in this subset of patients. Most importantly, quality of life measures were also improved through the use of adequate therapy. Even more pertinent were the findings involving antiangiogenic agents, which would add measurable improvements without significantly jeopardizing the patients' well-being. Further lines of therapy are cause for much more debate nowadays, but specific targeted agents have shown considerable promise in this context. We herein review noteworthy published data involving the use of additional lines of the therapy after failure of standard frontline therapies in patients with aGC.

David SP, Wang A, Kapphahn K, et al.
Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.
EBioMedicine. 2016; 4:153-61 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.
METHODS: We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).
FINDINGS: Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(-5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans.
INTERPRETATION: These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

Nassar L, Issa G, Farah Z, et al.
Predictors of Malignancy in Hyperechoic Breast Lesions.
J Ultrasound Med. 2016; 35(4):783-90 [PubMed] Related Publications
OBJECTIVES: Hyperechogenicity has been strongly associated with benign breast lesions. Although it is correct in most cases, hyperechogenicity must not always be considered synonymous with benignancy, as hyperechoic breast cancers do occur. The purpose of this study was to review clinical and imaging characteristics of hyperechoic breast lesions, looking for features associated with malignancy.
METHODS: Institutional Review Board approval was granted for this research. A total of 19,417 sonographic examinations were performed between January 2009 and June 2013. Among these, hyperechoic lesions with histologic diagnoses, stability on long-term followup, or characteristic imaging appearances were included in the study. The patients' clinical charts, mammograms, and sonograms were reviewed. The clinical and imaging features were recorded, and the data was analyzed by the χ(2) test, Fisher exact test, and independent-samples t test, looking for statistically significant predictors of malignancy.
RESULTS: Among the 19,417 scans, 42 patients (0.2%) with 44 hyperechoic lesions were identified. Twenty-six lesions fulfilling the inclusion criteria were included in the study: 5 malignancies (3 invasive ductal carcinomas, 1 invasive lobular carcinoma, and 1 invasive mucinous cancer) and 21 benign lesions. An irregular shape, a nonparallel orientation, and noncircumscribed margins were significantly associated with the risk of malignancy (P = .002, .02, and .01, respectively).
CONCLUSIONS: A hyperechoic breast lesion must not always be assumed to be benign. Instead, a full sonographic assessment according to the American College of Radiology Breast Imaging Reporting and Data System descriptors is needed for correct characterization and avoidance of misdiagnosis.

Iskandarani A, Bhat AA, Siveen KS, et al.
Bortezomib-mediated downregulation of S-phase kinase protein-2 (SKP2) causes apoptotic cell death in chronic myelogenous leukemia cells.
J Transl Med. 2016; 14:69 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Proteasome inhibitors are attractive cancer therapeutic agents because they can regulate apoptosis-related proteins. Bortezomib also known as Velcade(®), a proteasome inhibitor that has been approved by the food and drug administration for treatment of patients with multiple myeloma, and many clinical trials are ongoing to examine to the efficacy of bortezomib for the treatment of other malignancies. Bortezomib has been shown to induce apoptosis and inhibit cell growth of many cancer cells. In current study, we determine whether bortezomib induces cell death/apoptosis in CML.
METHODS: Cell viability was measured using MTT assays. Apoptosis was measured by annexin V/PI dual staining and DNA fragmentation assays. Immunoblotting was performed to examine the expression of proteins. Colony assays were performed using methylcellulose.
RESULTS: Treatment of CML cells with bortezomib results in downregulation of S-phase kinase protein 2 (SKP2) and concomitant stabilization of the expression of p27Kip1. Furthermore, knockdown of SKP2 with small interference RNA specific for SKP2 caused accumulation of p27Kip1. CML cells exposed to bortezomib leads to conformational changes in Bax protein, resulting in loss of mitochondrial membrane potential and leakage of cytochrome c to the cytosol. In the cytosol, cytochrome c causes sequential activation of caspase-9, caspase-3, PARP cleavage and apoptosis. Pretreatment of CML cells with a universal inhibitor of caspases, z-VAD-fmk, prevents bortezomib-mediated apoptosis. Our data also demonstrated that bortezomib treatment of CML downregulates the expression of inhibitor of apoptosis proteins. Finally, inhibition of proteasome pathways by bortezomib suppresses colony formation ability of CML cells.
CONCLUSIONS: Altogether, these findings suggest that bortezomib suppresses the cell proliferation via induction of apoptosis in CML cells by downregulation of SKP2 with concomitant accumulation of p27Kip1, suggesting that proteasomal pathway may form novel therapeutic targets for better management of CML.

Thompson KD, Connor SJ, Walls DM, et al.
Patients with Ulcerative Colitis Are More Concerned About Complications of Their Disease than Side Effects of Medications.
Inflamm Bowel Dis. 2016; 22(4):940-7 [PubMed] Related Publications
BACKGROUND: Patients with ulcerative colitis (UC) are often fearful about medication side effects and how the disease will affect their future. Our aim was to better understand what aspects of UC, and UC management, are most concerning to patients, and how they would like to be informed about treatment options.
METHODS: A Web-based survey was sent to UC patients throughout the United States and Australia. In addition to standard closed-response questions, audio clips were embedded in the survey and respondents showed their strength of agreement or disagreement using moment-to-moment affect-trace methodology. Standard quantitative analysis was used for the survey results, and cluster analysis was performed on the affect-trace responses.
RESULTS: A total of 460 patients with UC (370 patients from the United States and 90 patients from Australia) responded to the survey. Of them, 53% of the respondents were women, with a mean age of 49 (range 19-81) years. Most patients (87%) wanted to share treatment decision making with their doctors. The majority, 98%, wanted more than just a basic understanding of their disease. Patients were most concerned about the risk of colorectal cancer (37%), and the possible need for an ileostomy (29%). Only 14% of patients indicated that side effects from medications were their biggest concern. On affect-trace analysis, the most divergence in opinion centered on the appropriate timing for colectomy.
CONCLUSIONS: To facilitate informed treatment decisions for UC patients, in addition to reviewing the benefits and risks of medications, it is also important to discuss the best strategies for decreasing the risk of colectomy and colorectal cancer.

Valdés PA, Roberts DW, Lu FK, Golby A
Optical technologies for intraoperative neurosurgical guidance.
Neurosurg Focus. 2016; 40(3):E8 [PubMed] Free Access to Full Article Related Publications
Biomedical optics is a broadly interdisciplinary field at the interface of optical engineering, biophysics, computer science, medicine, biology, and chemistry, helping us understand light-tissue interactions to create applications with diagnostic and therapeutic value in medicine. Implementation of biomedical optics tools and principles has had a notable scientific and clinical resurgence in recent years in the neurosurgical community. This is in great part due to work in fluorescence-guided surgery of brain tumors leading to reports of significant improvement in maximizing the rates of gross-total resection. Multiple additional optical technologies have been implemented clinically, including diffuse reflectance spectroscopy and imaging, optical coherence tomography, Raman spectroscopy and imaging, and advanced quantitative methods, including quantitative fluorescence and lifetime imaging. Here we present a clinically relevant and technologically informed overview and discussion of some of the major clinical implementations of optical technologies as intraoperative guidance tools in neurosurgery.

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