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Lung cancer is the second most common cancer worldwide and the leading cause of death among cancers. The progressive approvals of immunotherapy as first-line treatment options have helped improve cancer prognosis. However, longer follow-up has confirmed the possibility of acquired resistance to immune checkpoint inhibitors (ICIs) which can lead to late relapses. Chemotherapy can act as a priming therapy to increase a tumor’s response to immunotherapy. We aim through this review to explain the mechanism behind ICI resistance and the value of chemotherapy in escaping this resistance. Finally, all US FDA approvals regarding the management of metastatic non-small-cell lung cancer using a combination of ICIs and chemotherapy are summarized.

IntroductionBladder cancer (BC) is a highly prevalent malignancy worldwide and particularly in Lebanon. Several studies have reported genetic risk factors in GSTM1 and NAT2, as well as many modifiable and non-modifiable risk factors, associated with BC.MethodsThis is a retrospective study that includes 51 Lebanese patients with BC. Peripheral blood samples were collected from patients and DNA extraction was performed using the standard salting-out method. Whole exome sequencing (WES) was performed and was followed by a thorough analysis of GSTM1, NAT2 and a panel of 127 genes known to be implicated in different hereditary cancers, for the detection of pathogenic germline mutations in the studied individuals.ResultsOur cohort included 42 men (82.4%) and 9 women (17.6%), with a mean age at diagnosis equal to 67 years. Of all participants, 10.8% had a family member diagnosed with BC and 17.3% with other cancer types. Our WES analysis allowed the detection of a high-risk variant found in APC (rs1801155) and a variant in BRIP1 (rs28903098) that are frequent in our cohort and more prevalent in our Lebanese in-house database compared to other international databases. Furthermore, two actionable variants, one in PALB2 (rs864622498) and another in ERCC2 (rs121913016) were detected in 2 different individuals from our cohort, paving the way to personalized therapies in these patients. A variant in NAT2 (rs1799931), shown to be associated with BC in other populations, was detected in 4 patients from our cohort.ConclusionThis is the first study in Lebanon and one of very few international studies carried out by NGS in patients with BC. Further studies in larger cohorts are required to confirm our findings in the Lebanese population.

The evolution of precision medicine in the field of oncology has led to a radical change in the course of malignancies. PARP inhibitors are drugs that block the activity of the PARP enzyme responsible for base excision repair and have shown significant positive response when used for tumors lacking homologous recombination, namely high efficacy among BRCA-mutated tumors. Since 2014, when olaparib received an accelerated US FDA approval in ovarian cancer, we witnessed many other FDA approvals for olaparib, rucaparib, niraparib and talazoparib. Additionally, many Phase I, II and III trials were published presenting revolutionizing results. Other ongoing trials combined PARP inhibitors with checkpoint inhibitors. We aimed in this review to state the FDA approvals for PARP inhibitors in breast, ovarian, fallopian tube and primary peritoneal cancers, report the major published trials in high impact medical journals, and mention the ongoing trials combining these drugs with checkpoint inhibitors.

The use of immune checkpoint inhibitors has been approved in the advanced and metastatic setting for many types of solid tumors. Nonetheless, their role in the adjuvant setting is limited to the treatment of surgically resected melanoma. Ipilimumab was the first immune checkpoint inhibitor approved for this indication, followed by nivolumab and pembrolizumab. Many ongoing trials are evaluating these molecules in the postoperative setting, alone or in combination with other therapies. Preliminary results are promising regarding the treatment of other cutaneous tumors, lung cancers, head and neck squamous cell carcinomas, bladder cancer and renal cell carcinomas. Some data assessing their use for the adjuvant treatment of esophageal, colorectal, ovarian cancer and other solid tumors are similarly emerging.

As a developing country, Lebanon lacks adequate awareness about Human papillomavirus (HPV) among its population, whether working in the medical field or not. Lebanon is traditionally considered conservative with a low incidence of sexually transmitted infections in general, but recently the incidence of HPV infections has significantly increased. The present cross-sectional study aims to evaluate the level of awareness on HPV and the attitude toward HPV vaccine among Lebanese medical students in a self-administered questionnaire-based survey. A total of 1009 answers were collected and analyzed from a population of about 3000 Lebanese medical students. Our study revealed a significant lack of knowledge and awareness on HPV among medical students in Lebanon, with a strikingly low vaccination rate (16.4%) due to many barriers. Education initiatives in medical schools remain crucial to raise awareness on HPV and promote HPV vaccination, especially among medical students, who represent the country's future healthcare providers and policymakers.

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy.

Stage III non-small cell lung cancer is a border line stage between localized and metastatic disease. PDL-1 is gaining an important role in the therapeutic arsenal of lung cancer, the most frequent cancer worldwide. We report for the first time a negativation of PDL-1 status in 2 cases of stage IIIA NSCLC with conversion to operable disease after using immunotherapy. The first patient was a 59-year old female diagnosed incidentally to have stage IIIA inoperable NSCLC that was treated with combination chemo-immunotherapy, and converted to operable disease with a negative PD-L1 in the postoperative setting. The second case is that of a 56-year old male that also had an inoperable stage IIIA NSCLC treated with chemotherapy first line followed by pembrolizumab at progression, then operated after surgical conversion, with negative PD-L1 postoperatively. In front of these findings, further work should be done to elucidate if the reverse of the PDL-1 status and the conversion to operability were due to the use of immunotherapy or to an incidental finding. If confirmed, it may have a therapeutic impact.

Metastatic colorectal cancer is the second most common cause of cancer death. Standard chemotherapy in combination with targeted therapies represent the backbone for the treatment of advanced disease. However, options are limited for patients progressing on these regimens. Genetic testing can offer patients the opportunity to benefit from novel therapies, namely immune checkpoint inhibitors in microsatellite instability-positive tumors. HER2 overexpression has recently emerged as a potentially targetable tumor marker in colorectal cancer (CRC). Despite the absence of approvals for anti-HER2 therapies in CRC, many agents such as trastuzumab and pertuzumab were tested and demonstrated significant antitumor activity, even in heavily pretreated patients. Early trials are also evaluating lapatinib, T-DM1, tucatinib and other anti-HER2 agents in patients with metastatic CRC, with promising results.

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to a worldwide medical crisis, affecting mostly immunocompromised patients, such as cancer patients. Various cancer societies have issued recommendations regarding patients care, but few studies addressed the perception of cancer patients regarding this pandemic. Objective The aim of the study was to assess the perception of cancer patients regarding their health risks during this pandemic and the preventive measures taken. Materials and methods An anonymous survey was conducted among cancer patients presenting for their treatment, during 10 consecutive working days, at the one-day clinic of Hotel-Dieu de France University hospital in Beirut. We evaluated their state of disease, comorbidities, precautions taken, and their concerns regarding the virus spread. Results A total of 216 patients responded with a mean age of 60 years. The majority had a good performance status (performance status = 0-1 in 79.6%), 51.4% had metastatic disease, and chemotherapy was the main therapy used (65.7%). A total of 52.3% of patients considered themselves to be at increased risk of contracting the virus. A total of 55.1% were more worried about the coronavirus rather than their disease. The priority was for the treatment of their cancer in 47.7% of the total patients studied. Of note, only 2.8% of planned one-day clinic reservations were canceled or postponed to avoid COVID-19 exposure. Conclusions Although cancer is a disease with a high mortality rate, many patients are more concerned about the actual pandemic rather than their disease. Nevertheless, the absenteeism from their treatment sessions during the COVID-19 atmosphere was minimal.

Background: In the light of the COVID-19 pandemic, the role of health care providers is essential to maintain the functioning of the health care system. Physicians accept a primary ethical duty to place the wellbeing and health of their patients above their own welfares. However, does the duty to patient well-being have any limit? Two ethical concerns are debated: public health’s ethical principles and medical ethics values. We aimed in this study to assess Lebanese physicians’ attitudes, practice and ethical considerations when treating their patients during the COVID-19 pandemic.Materials and methods: It’s a cross-sectional study conducted in March 2020 among a random sample of Lebanese physicians, using a questionnaire based mainly on a five-point Likert numerical scale to make the answers more reliable and valid. The questionnaire focused on the medical practice during the pandemic and the ethical considerations in public health and in medical practice. It also evaluates the physicians’ point of view toward the management of the pandemic in Lebanon. Results: A total of 318 physicians responded, with a mean age of 40 years. Five doctors of the total were affected by the COVID-19 infection (1.6%). 51.4% of medical specialists considered themselves to be at a higher risk of contracting the infection, while 52.3% of surgeons stated that they were at a lower risk. Doctors were neutral regarding treating patients according to any priority and discontinuing the ventilation of any patient with bad prognosis. The majority of doctors disagreed regarding the respect of the patient’s autonomy in refusing COVID-19 treatment with a mean score of 1.7/5. Finally, doctors expressed a neutral opinion regarding the ability of the country to manage such a pandemic with a mean score of 3.1/5. Conclusion: Although physicians recognize that they are at high risk of contracting COVID-19, they assume their responsibilities and their duty to treat, and they were neutral against any prioritization in treatment approach. However, applying the four ethical principles (autonomy, beneficence, non-maleficence and justice) may become challenging. Hence, more medical and ethical recommendations are required to guide physicians during this pandemic.

Aim: Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. Methods: We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. Results: 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). Conclusion: Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.

Aim: As no meta-analyses have evaluated tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma (RCC), the aim was to evaluate the benefit of sunitinib and pazopanib in the adjuvant setting. Methods: This meta-analysis included all Phase III randomized controlled trials evaluating adjuvant sunitinib and pazopanib in high-risk RCC. Primary outcome was the comparison of disease-free survival (DFS) between tyrosine kinase inhibitors and placebo. Results: There was a tendency for significant overall effect of both sunitinib and pazopanib on DFS (hazard ratio: 0.85; 95% confidence interval: 0.72–1.01; p = 0.06). There was no significant difference between the effect of sunitinib and pazopanib on DFS (p = 0.51; I2 = 0%). Conclusion: Pazopanib and sunitinib could prolong DFS in the adjuvant treatment of high-risk RCC and seem equally effective in this setting.

Driving molecular mutations such as rearrangement of ALK and EGFR mutation is present in 5–10% of non-small-cell lung cancer. Tyrosine kinase inhibitors have shown good efficacy and thus become the standard of care. However, tumors have developed several resistance mechanisms against tyrosine kinase inhibitors, including transformation to small-cell lung carcinoma (SCLC). Transformation to SCLC after administration of anti-EGFR in EGFR-mutated adenocarcinoma has been well documented. Similarly, it appears that the same transformation happens in ALK-rearranged adenocarcinoma after the use of anti-ALK. In fact, to date eight cases have been reported in the literature. We aimed in this paper to focus on the characteristics, prognosis and treatment of these transformed SCLC.

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months. The EXTREME protocol is commonly used in first-line setting. Recently, pembrolizumab, an anti-programmed death-1 agent, has been approved by the US Food and Drug Administration for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy. It demonstrated a durable objective response rate with a good safety profile and quality of life. Many ongoing trials are evaluating the use of pembrolizumab for the treatment of HNSCC in various indications such as adjuvant and neoadjuvant setting, maintenance and recurrent disease, alone or in combination with chemotherapy, radiation and targeted therapy. Finding those biomarkers predictive of response to immune checkpoints inhibitors has been a major concern. However, markers have been identified, such as PD-L1 expression, human papilloma virus infection, interferon-γ signature score, microsatellite instability and neoantigen production.

Aim: This study assessed the efficacy of anti-PD-1/PD-L1 agents in real life when used in second line or beyond. Materials & methods: Patients with advanced non-small-cell lung cancer progressing after standard chemotherapy and receiving immunotherapy in the second line or beyond were included. Results: One hundred and ten patients were included with PD-L1 expression above 50%, between 1–49 and

Testicular germ cell tumors are chemosensitive with very high cure-rates even in the metastatic setting. However, patients with platinum-refractory and relapsing tumors after autologous stem cell transplant have very poor outcomes despite salvage treatments, and with no effective alternative therapies. Immunotherapy, notably with PD-1 inhibitors, has proven to be very effective in treating various solid tumors. This review summarizes the experience with anti-PD-1 agents (pembrolizumab, nivolumab) in the treatment of testicular germ cell tumor relapsing after multiple lines of treatment, and exposes future trials evaluating newer checkpoint inhibitors in this setting.

Introduction Medical hypnosis has received an increasing attention during the past decades. Various applications of hypnosis can be incorporated into the oncology field. This study aims to assess the knowledge of Lebanese medical oncologists on the use of hypnosis in the management of cancer patients. Material and methods An anonymous questionnaire was sent to all Lebanese medical oncologists to assess their knowledge, opinion and understanding of hypnosis and its use in oncology, as well as the obstacles facing its application in Lebanon. Results Hundred and three Lebanese medical oncologists responded to the survey, with a response rate of 65%. The findings revealed that most oncologists had little or no knowledge about hypnosis, but recommended it due to the benefits they believed it provided for the patients in improving chronic pain, invasive procedures, chemotherapy-induced nausea and anxiety. Around 40% of participants were interested in receiving a training in hypnosis. Lebanese oncologists also described many obstacles to the practice of hypnosis, mainly the lack of training for this technique and the lack of financial resources. Conclusion Despite all obstacles, the majority of Lebanese oncologists would recommend hypnosis to their patients in order to improve their quality of life.

Aim: This study aims to recognize the distribution of different seizures etiologies in cancer patients, the most common primary tumors responsible for brain metastases, the most epileptogenic primary tumors and the therapeutic modalities. Methods: A retrospective study was conducted at Hotel-Dieu de France Hospital targeting patients admitted to hematology–oncology department between 2005 and 2016 who presented a seizure. Results: Of the 153 included patients, mean age was 57 years (standard deviation = 16 years) and a male predominance (66%). The majority of seizures were due to a primary tumor (49%) or brain metastases (32%). Other reversible (metabolic and drug) or nonreversible causes (carcinomatous meningitis, radiation and cardiovascular complications) formed the remaining causes. Regarding antiepileptic treatments, sodium valproate was mostly used, followed by levetiracetam and phenytoin. Conclusion: Numerous reversible causes are involved in the onset of epileptic seizures, including metabolic disorders, antibiotics and chemotherapies.

According to the latest data of the World Cancer Research Fund International (2012), Lebanon has the second highest age-standardized incidence rate of bladder cancer worldwide, both for "men" and "both-sexes" categories. This study was designed to assess bladder cancer knowledge among the Lebanese population. Between November 2017 and January 2018, a cross-sectional study was directed, including patients and visitors of one of the largest university hospitals in the capital Beirut. A face-to-face questionnaire evaluated knowledge regarding, among others, the most important risk factor for bladder cancer and the most frequent revealing symptom. This survey also obtained information regarding smoking habits. A total of 701 participants completed the survey. A total of 49.1% were younger than 50 years, 56.3% were male, 56.6% had a college degree and 54.4% were ever smokers. Two-hundred and thirty-two (33.1%) of the 701 surveyed individuals have never heard about bladder cancer. 157 (33.5%) of the 469 individuals who have heard about bladder cancer were unaware that bladder cancer is different from prostate cancer. Overall, 312 (44.5%) individuals have heard about bladder cancer and knew that it is different from prostate cancer. Of these 312 subjects, 94 (30.1%) knew that tobacco smoking was the most important risk factor for bladder cancer, 166 (53.2%) associated blood in the urine with the most frequent revealing symptom of this disease and 66 (21.2%) considered that bladder cancer is frequent in Lebanon compared to other cancers. This study suggests the lack of knowledge of the Lebanese population towards bladder cancer, including its association with tobacco.

Breast cancer is the most common malignancy among women worldwide and the leading cause of cancer death in many countries (1). In around 20% to 25% of breast cancer cases, there is an overexpression of HER2 or an amplification of its gene (HER2-positive subtype); HER2 is a transmembrane receptor implicated in tumor replication, invasion and dissemination (2). HER2-positive breast cancer is characterized by a worse prognosis, aggressive disease, higher mitotic index, worse nuclear grade and lymph nodes positivity (3).

BACKGROUND Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (WandW) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W and W strategy in Lebanese CLL patients. MATERIALS AND METHODS A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W and W strategy, different chemotherapeutic regimens and the indications for treatment. RESULTS Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was 39885/mm3 [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was 191255/mm3 [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W and W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W and W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade. CONCLUSIONS This retrospective review of CLL clinical practice showed an important implementation of the W and W strategy with a long duration, especially in early stage cases with low RAI or Binet scores.

e13045 Background: Hereditary breast (BC) and ovarian cancer (OC) genetic alterations are considered the most prevalent among familial cancer. To date, four studies have exposed the mutations related to hereditary BC predisposition in the Lebanese population , with percentage of BRCA-related pathogenic mutations ranging between 5 % and 15 %. Methods: Between 2017 and 2019, 117 patients with high risk hereditary breast and ovarian cancer were referred to undergo the testing at the Unité de Génétique médicale (UGM) of Saint-Joseph University of Beirut, Lebanon. The sequencing was accomplished by using the 21-panel Next-Generation Sequencing (NGS) method for all of our patients, to which we also added the MLPA technique followed by the Sanger sequencing for validation whenever a genetic alteration was found. Results: From 117 Lebanese women with high-risk hereditary breast and ovarian cancer predisposition, 19 pathogenic mutations were identified in this study: 11 BRCA1, 1 BRCA2, 2 PALB2, 1 ATM, 1 CDH1, 1 MSH6, 1 RAD51C, and 1 BRIP1. Among those, 13 patients had BC, one had OC and five were healthy individuals. Five similar mutations were found within the BRCA1 gene, the p.C44F mutation, accounting for 45.4 %, thus suggesting a founder effect. Average age at diagnosis in the BC patients carrying a mutation was 41 years and 38.5% had a triple negative BC. Conclusions: The overall pathogenic mutation rate was equal to 16.2% while the BRCA deleterious mutation rate was 10.3% lower to those reported in the literature. The p.C44F mutation appeared five times suggesting a founder effect. [Table: see text]

e13544 Background: Lesions of the central nervous system (CNS) are a heterogeneous group of tumoral and non-tumoral lesions, benign or malignant, primary or metastatic. The overall incidence rate of all brain tumors is estimated to be 10.82 per 100 000 person-years. There is no data in Lebanon characterizing the CNS lesions. The aim of our study is to report the epidemiologic and histologic characteristics of these lesions in a Lebanese tertiary center. Methods: This is a retrospective study evaluating the characteristics of the CNS lesions diagnosed in 20 years (from January 1998 to June 2017) in the pathology laboratory of Hôtel Dieu de France, Saint Joseph University hospital of Beirut, Lebanon. The data were extracted from the computerized records of the laboratory. Different variables were evaluated, from the samples types and epidemiologic characteristics, to the revealing symptoms and the histologic subtypes. Statistical analysis was performed using SPSS 24.0. Results: 2025 tumoral lesions over 20 years were interpreted. 25.4% of the samples were obtained by biopsy, 65% by surgical resection, 3.7% were cerebral spinal fluid and 5.9% were undetermined. 52.2% of the patients were men and 47.8% were women with a median age of 50 years, from 0 to 89 years. The most frequent revealing symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of the CNS tumors were primary and 9.3% were metastatic. Lung (35.6%) and breast (16.5 %) were the two most frequent primaries of the metastatic lesions. 46.2% of primary CNS tumors were glial, 42.5% non-glial, 3.5% mixed neuroglial and 6.4% mesenchymal. The two most frequent glial tumors were astrocytic (56.4%) and oligodendroglial (17.9%) tumors, while the most frequent non-glial tumors were meningeal tumors (58%) and cranial nerve and paraspinal tumors (16.3%). Conclusions: The histological and epidemiological characteristics of brain tumors in Lebanon are consistent in many features with what is known in the literature, but the Lebanese population differs by a younger age of onset, a lower rate of meningiomas, and a higher rate of gliomas.

e15141 Background: In terms of frequency, colorectal cancer (CRC) is the 3rd cancer in Lebanon with 1093 incidences registered in 2015. To this date not a single screening campaign has been organized in the country. Fecal immunochemical test (FIT) is an advised screening technique. We found it useful to organize a screening campaign using FIT to determine the prevalence of CRC in a population of 3000 healthy Lebanese allowing the extraction of useful data. Methods: 3000 tubes were distributed to Lebanese adults (45-80 years old) at average risk of developing CRC, followed by explanations. FIT analysis was done at the medical genetics unit (UGM) of Saint-Joseph University and patients with positive FIT were asked to undergo further investigations. Results: Out of the 3000 distributed tests, 705 were returned (23.5%) with 459 fully analyzable. The age median was 56 (45-80). Sex ratio F/M 2.3. Out of the 459 patients, 278 (60.5%) showed 0ng/ml, 137 (29.8%) showed 1-79ng/ml, 3 (0.6%) showed 80-99ng/ml (intermediate risk values), 33 (7.1%) showed 100-800ng/ml considered as a positive value and finally 8 (1.7%) showed over range values. Among the 44 positive patients we contacted 41. Out of the 8 (18%) colonoscopies results received: 5 showed hemorrhoids leading to false positive, 1 ulcerative ileitis, 1 tubular adenomas and 1 carcinoma. Conclusions: While it was hard for us to quantify people for whom a free FIT was proposed, the low restitution rate among those who took the test shows the necessity of national screening and sensitization campaigns.

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.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.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.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.

Homeobox genes are expressed in stage-, region-, and tissue-specific patterns during embryonic development of the mouse. In order to study cis-acting regulatory elements of murine homeobox genes, transgenic mouse embryos were generated which contained the LacZ reporter gene under the control of different fragments from the murine Hoxb6 gene. A 2 kb limb/LPM (lateral plate mesoderm) enhancer region was identified which reproduced several aspects of the endogenous Hoxb6 gene expression pattern in the mesenchyme of the developing limb buds and the ventro-lateral body region. Both tissues represent derivatives of the lateral plate mesoderm. In order to describe proteins interacting with specific DNA sequences in the limb/LPM enhancer, electro mobility shift assays were performed using nuclear extracts prepared from embryonic tissues. Several specific DNA-protein complexes could be detected, suggesting that these DNA-protein interactions are important for the regulation of Hoxb6 gene expression.

To characterize cis-acting regulatory elements of the murine homeobox gene, Hox-2.2, transgenic mouse lines were generated that contained the LacZ reporter gene under the control of different fragments from the presumptive Hox-2.2 promoter. A promoter region of 3600 base pairs (bp) was identified, which reproducibly directed reporter gene expression into specific regions of developing mouse embryos. At 8.5 days postcoitum (p.c.) reporter gene activity was detected in posterior regions of the lateral mesoderm and, in subsequent developmental stages, expression of the LacZ gene was restricted to specific regions of the developing limb buds and the mesenchyme of the ventrolateral body region. This pattern of Hox-2.2-LacZ expression was found in all transgenic embryos that have been generated with the 3.6 kb promoter fragment (two founder embryos and embryos from five transgenic lines). In addition, embryos from two transgenic mouse lines expressed the reporter gene at low levels in the developing central nervous system (CNS). Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs.