Esophageal cancer: a twenty-four-year experience at a tertiary care center with an evaluation of the prognostic significance of the neutrophil-lymphocyte ratio.

BACKGROUND: A high neutrophil-lymphocyte ratio (NLR) may be associated with worse survival in esophageal cancer (EC). Our aims were to describe the demographic and clinical data of EC in a tertiary referral center in Lebanon and to determine the prognostic value of NLR. METHODS: A retrospective cohort study based on chart review of patients diagnosed with EC was conducted at the American University of Beirut Medical Center (AUBMC). The demographic characteristics, clinical presentation and outcomes were described and compared between squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). Data about esophageal cancer incidence were obtained from the National Cancer Registry, the Ministry of Public Health and GLOBOCAN 2020. Cox regression analysis was performed to determine whether the NLR is an independent predictor of survival, using variables based on clinical knowledge and previously established data. RESULTS: 110 patients were diagnosed with EC, which was the least common among other gastrointestinal malignancies. Our follow up rates reached 86.4%. The median survival was 9 months (IQR 3-25.5.) and was comparable between ESCC (median of 7 months, IQR 2-25) and EAC (median of 9 months, IQR 3-26.3), p = 0.803. Advanced stage was associated with a worse prognosis (p = 0.037). The mean NLR(±SD) was 5.20 ± 6.8, with no significant difference between EAC and ESCC (4.5 ± 3.4 vs. 5.9 ± 9.2, p = 0.420) or between early or advanced stages (5.4 ± 8.1 vs. 4.7 ± 6.8, p = 0.732). The area under the curve for the NLR was 0.560 (95% CI: 0.374-0.746, p = 0.488). After adjusting for age, gender, TNM staging and grading, cox regression analysis showed that an increased NLR was a significant predictor of mortality, with an adjusted hazard ratio of 1.095 (p = 0.011). CONCLUSION: EC is quite uncommon in Lebanon despite a high prevalence of smoking and obesity. Advanced stage and high NLR were associated with a negative prognostic value.

Allocation of authorship and patient enrollment among global clinical trials in oncology.

BACKGROUND: Oncology randomized controlled trials (RCTs) are increasingly global in scope. Whether authorship is equitably shared between investigators from high-income countries (HIC) and low-middle/upper-middle incomes countries (LMIC/UMIC) is not well described. The authors conducted this study to understand the allocation of authorship and patient enrollment across all oncology RCTs conducted globally. METHODS: A cross-sectional retrospective cohort study of phase 3 RCTs (published 2014-2017) that were led by investigators in HIC and recruited patients in LMIC/UMIC. FINDINGS: During 2014-2017, 694 oncology RCTs were published; 636 (92%) were led by investigators from HIC. Among these HIC-led trials, 186 (29%) enrolled patients in LMIC/UMIC. One-third (33%, 62 of 186) of RCTs had no authors from LMIC/UMIC. Forty percent (74 of 186) of RCTs reported patient enrollment by country; in 50% (37 of 74) of these trials, LMIC/UMIC contributed <15% of patients. The relationship between enrollment and authorship proportion is very strong and is comparable between LMIC/UMIC and HIC (Spearman's ρ LMIC/UMIC 0.824, p < .001; HIC 0.823, p < .001). Among the 74 trials that report country enrollment, 34% (25 of 74) have no authors from LMIC/UMIC. CONCLUSIONS: Among trials that enroll patients in HIC and LMIC/UMIC, authorship appears to be proportional to patient enrollment. This finding is limited by the fact that more than half of RCTs do not report enrollment by country. Moreover, there are important outliers as a significant proportion of RCTs had no authors from LMIC/UMIC despite enrolling patients in these countries. The findings in this study reflect a complex global RCT ecosystem that still underserves cancer control outside high-income settings.

The Impact of an Educational Video in Arabic Language on Patients' Knowledge and Attitudes Towards Genetic Testing for Cancer Therapy.

Rapid advances in cancer genetics are paving the way towards personalized cancer management, and genetic testing is now an important decision-making tool. Despite the advantages, genetic testing adds a layer of complexity in the management which is difficult to communicate with patients. The variability health literacy among patients may restrict their engagement in genetic procedures. Improving the language and presentation of genomic concepts can influence patients' risk assessment and willingness to undergo testing. The study aimed to compare the knowledge and attitudes of cancer patients presenting to oncology clinics at The American University of Beirut Medical Center before and after watching a short educational video that clarifies the concepts of genetic mutations, genetic testing technique, and its purposes.Twenty-nine adult patients presenting to the oncology clinics and due to receive somatic or germline genetic testing filled a questionnaire which assesses their knowledge and attitudes before and after the educational video was played. The majority of patients had poor baseline knowledge before the intervention. After watching the video, the percentage of patients with poor knowledge decreased to a minimum of 3.4% and a maximum of 39% for each concept. Mean score for attitude questions also increased significantly. Effective patient education and counseling programs in the patients' native language prior to genetic testing can increase knowledge, decrease hesitancy, and improve clinical decision making. A short educational video is an example of a simple intervention towards an inclusive approach in patient care all over the world.

The impact of young age (< 40 years) on the outcome of a cohort of patients with primary non-metastatic breast cancer: analysis of 10-year survival of a prospective study.

BACKGROUND: The role of young age (< 40 years) at diagnosis as an independent risk factor for adverse outcomes in female patients with breast cancer has been highlighted in several studies. In this prospective study, we assessed the difference in 10-year survival between two groups of patients diagnosed with non-metastatic breast cancer based on an age cutoff of 40 years. We also assessed the impact of factors including tumor characteristics, molecular markers and immunohistochemical markers on survival outcomes, highlighting the interaction of those variables with age. METHODS: A total of 119 female patients with newly diagnosed non-metastatic breast cancer were recruited at the American University of Beirut Medical Center (AUBMC) between July 2011 and May 2014. Patients were recruited and divided into 2 age groups (< 40 and ≥ 40 years). In addition to clinical characteristics, we assessed immunohistochemistry including estrogen, progesterone and HER2 receptors, p53, cyclin B1, vascular endothelial growth factor receptor (VEGFR), and ki-67. Germline BRCA mutations were also performed on peripheral blood samples. Patient and tumor characteristics were compared between the age groups. 10-year overall survival (OS) and disease-free survival (DFS) were estimated accordingly. Cox regression analysis was performed in order to assess the effect of the different variables on clinical outcomes. RESULTS: After a median Follow-up of 96 (13-122) months, the estimated 10-year OS was 98.6% for patients ≥40 as compared to 77.6% in patients < 40 (p = 0.001). A similar trend was found for 10-year DFS reaching 90% for patients ≥40 and 70.4% for those < 40 (p = 0.004). On multivariate analysis for DFS and OS, only younger age (< 40 years), higher stage and triple negative phenotype among other parameters assessed significantly affected the outcome in this cohort. CONCLUSION: This prospective study confirms the association between younger age and adverse survival outcomes in patients with non-metastatic breast cancer. Future studies of the whole genome sequences may reveal the genomic basis underlying the clinical differences we have observed.

A phase II single arm study of Nivolumab with stereotactic Ablative radiation Therapy after induction chemotherapy in CHOlangiocarcinoma (NATCHO).

BACKGROUND: Intrahepatic cholangiocarcinoma (CCA) is amongst the most common primary liver tumors worldwide. CCA carries a bad prognosis prompting research to establish new treatment modalities other than surgery and the current chemotherapeutic regimens adopted. Hence, this trial explores a new therapeutic approach, to combine stereotactic body radiation therapy (SBRT) and immunotherapy (Nivolumab), and asses its clinical benefit and safety profile after induction chemotherapy in CCA. METHODOLOGY: This is a Phase II open-label, single-arm, multicenter study that investigates Nivolumab (PD-1 inhibitor) treatment at Day 1 followed by SBRT (30 Gy in 3 to 5 fractions) at Day 8, then monthly Nivolumab in 40 patients with non-resectable locally advanced, metastatic or recurrent intrahepatic or extrahepatic CCA. Eligible patients were those above 18 years of age with a pathologically and radiologically confirmed diagnosis of non-resectable locally advanced or metastatic or recurrent intrahepatic or extrahepatic CCA, following 4 cycles of cisplatin-based chemotherapy with an estimated life expectancy of more than 3 months, among other criteria. The primary endpoint is the progression free survival (PFS) rate at 8 months and disease control rate (DCR). The secondary endpoints are overall survival (OS), tumor response rate (TRR), duration of response, evaluation of biomarkers: CD3 + , CD4 + and CD8 + T cell infiltration, as well as any change in the PD-L1 expression through percutaneous core biopsy when compared with the baseline biopsy following 1 cycle of Nivolumab and SBRT. DISCUSSION: SRBT alone showed promising results in the literature by both inducing the immune system locally and having abscopal effects on distant metastases. Moreover, given the prevalence of PD-L1 in solid tumors, targeting it or its receptor has become the mainstay of novel immunotherapeutic drugs use. A combination of both has never been explored in the scope of CCA and that is the aim of this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04648319 , April 20, 2018.

Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT.

BACKGROUND: A nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA. METHODS: Between 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan-Meier methods and predictors of outcomes using multi-variable cox regression model. RESULTS: In the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972-9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference. CONCLUSION: In HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.

Teaching critical appraisal to large classes of undergraduate medical students using team-based learning versus group discussions: a randomized controlled trial.

BACKGROUND: Evidence on the effectiveness of team-based learning in teaching critical appraisal to large classes of preclinical medical students is scarce. This study investigated whether team-based learning is effective in teaching critical appraisal to large classes of preclinical medical students. METHODS: Between April 2018 and May 2019, 107 first-year medical students were randomly allocated to receive instruction in critical appraisal using team-based learning or traditional group discussions as teaching methods. The primary outcome was students' performance on the Berlin Questionnaire administered at the end of second year. RESULTS: Students' mean (SD) age was 22.0 (0.7) years. Baseline characteristics of the two groups were similar (all p values > 0.05). The mean (SD) Berlin scores of both groups were 80.4 (11.6) and 80.1 (12.1) for team-based learning and group discussions, respectively. Multivariate stepwise linear regression analysis revealed that the student's academic achievement in medical school was the sole predictor of performance on the Berlin Questionnaire (ß = 1.079, p < 0.001), adjusting for gender, Medical College Admission Test score, student's self-reported preferred teaching method, rank upon admission to medical school, score on the Epidemiology and Biostatistics course, and teaching method (team-based learning versus group discussions). CONCLUSIONS: Team-based learning and group discussions were equally effective instructional strategies to teach critical appraisal to large classes of undergraduate medical students. Replication of our findings is needed in other educational settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15430424 , retrospectively registered on December 30, 2021.

Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome.

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges.

The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host's immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.

The economic burden of cancer care for Syrian refugees: a population-based modelling study.

BACKGROUND: Cancer represents a substantial health burden for refugees and host countries. However, no reliable data on the costs of cancer care for refugees are available, which limits the planning of official development assistance in humanitarian settings. We aimed to model the direct costs of cancer care among Syrian refugee populations residing in Jordan, Lebanon, and Turkey. METHODS: In this population-based modelling study, direct cost per capita and per incident case for cancer care were estimated using generalised linear models, informed by a representative dataset of cancer costs drawn from 27 EU countries. A range of regression specifications were tested, in which cancer costs were modelled using different independent variables: gross domestic product (GDP) per capita, crude or age-standardised incidence, crude or age-standardised mortality, and total host country population size. Models were compared using the Akaike information criterion. Total cancer care costs for Syrian refugees in Jordan, Lebanon, and Turkey were calculated by multiplying the estimated direct cancer care costs (per capita) by the total number of Syrian refugees, or by multiplying the estimated direct cancer costs (per incident case [crude or age-standardised]) by the number of incident cancer cases in Syrian refugee populations. All costs are expressed in 2017 euros (€). FINDINGS: Total cancer care costs for all 4·74 million Syrian refugees in Jordan, Lebanon, and Turkey in 2017 were estimated to be €140·23 million using the cost per capita approach, €79·02 million using the age-standardised incidence approach, and €33·68 million using the crude incidence approach. Under the lowest estimation, and with GDP and total country population as model predictors, the financial burden of cancer care was highest for Turkey (€25·18 million), followed by Lebanon (€6·40 million), and then Jordan (€2·09 million). INTERPRETATION: Cancer among the Syrian refugee population represents a substantial financial burden for host countries and humanitarian agencies, such as the UN Refugee Agency. New ways to provide financial assistance need to be found and must be coupled with clear, prioritised pathways and models of care for refugees with cancer. FUNDING: UK Research and Innovation Global Challenges Research Fund: Research for Health in Conflict-Middle East and North Africa region (R4HC-MENA).

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma.

BACKGROUND: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations.

PURPOSE: Prostate cancer care in the Middle East is highly variable and access to specialist multidisciplinary management is limited. Academic tertiary referral centers offer cutting-edge diagnosis and treatment; however, in many parts of the region, patients are managed by non-specialists with limited resources. Due to many factors including lack of awareness and lack of prostate-specific antigen (PSA) screening, a high percentage of men present with locally advanced and metastatic prostate cancer at diagnosis. The aim of these recommendations is to assist clinicians in managing patients with different levels of access to diagnostic and treatment modalities. METHODS: The first Advanced Prostate Cancer Consensus Conference (APCCC) satellite meeting for the Middle East was held in Beirut, Lebanon, November 2017. During this meeting a consortium of urologists, medical oncologists, radiation oncologist and imaging specialists practicing in Lebanon, Syria, Iraq, Kuwait and Saudi Arabia voted on a selection of consensus questions. An additional workshop to formulate resource-stratified consensus recommendations was held in March 2019. RESULTS: Variations in practice based on available resources have been proposed to form resource-stratified recommendations for imaging at diagnosis, initial management of localized prostate cancer requiring therapy, treatment of castration-sensitive/naïve advanced prostate cancer and treatment of castration-resistant prostate cancer. CONCLUSION: This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources.

The Crosstalk between Microbiome and Immune Response in Gastric Cancer.

Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host's immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk between the gut microbiome and immune response in gastric cancer.

Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

BRCA mutations in a cohort of Iraqi patients presenting to a tertiary referral center.

BACKGROUND: Unique pathogenic mutations in BRCA1 and 2 genes have been reported in different populations of patients originating from the Middle East region. Limited data are available for the Iraqi population. For many reasons a large number of Iraqi patients present to Lebanon for medical care. This is the first report of BRCA full gene sequencing conducted in a cohort of high-risk patients originating from Iraq. METHODS: This is a retrospective review of Iraqi patients diagnosed with breast or ovarian cancer referred for BRCA mutation testing at the American University of Beirut from January 2012 to October 2018. RESULTS: Of the 42 Iraqi women who underwent genetic testing at our institution, 3 BRCA pathogenic variants were found. Two mutations in BRCA1 c.224_227delAAAG and c.5431C > T and one mutation in BRCA2 c.5576_5579delTTAA were identified. Three other patients had sequence changes considered as variants of undetermined significance. CONCLUSION: In this cohort of high-risk patients, one out of the three pathogenic BRCA variants detected has not previously been reported in the Middle Eastern population. Further studies are required to delineate the spectrum of BRCA mutations in the Iraqi population.

The unveiling of a new risk factor associated with bladder cancer in Lebanon.

BACKGROUND: No accurate evaluation of smoking and water pollution on bladder cancer has been conducted in the Lebanese population. Our aim is to examine the significance of smoking and one of the main water pollutants Trihalomethanes (THM) on bladder cancer risk. METHODS: Population Attributable Fraction (PAF) was used to quantify the contribution of the risk factors smoking and THMs on bladder cancer in Lebanon. To calculate PAF for each risk factor, we used the proportion of the population exposed and the relative risk for each risk factor. Relative risks for each risk factor were obtained from published meta-analyses. The population at risk values were obtained from a report on chronic disease risk factor surveillance in Lebanon which was conducted by the World Health Organization between 2008 and 2009 and a national study by Semerjian et al. that conducted a multipathway exposure assessment of selected public drinking waters of Lebanon for the risk factors smoking and THMs, respectively. RESULTS: Bladder cancer cases that were the result of smoking in Lebanon among males and females are 33.4 and 18.6%, respectively. Cases attributed to mid-term exposure to THM contamination of drinking water is estimated at 8.6%. CONCLUSION: This paper further highlights the negative impact of smoking on bladder cancer risk and adds an overlooked and often underestimated risk that THMs have on this type of cancer. Thus, it is imperative that a national based study which assesses THM exposure by gender and smoking status be implemented to determine the real risk behind this byproduct.

BRCA mutation screening and patterns among high-risk Lebanese subjects.

BACKGROUND: Previous studies have suggested that the prevalence of BRCA1 and 2 mutations in the Lebanese population is low despite the observation that the median age of breast cancer diagnosis is significantly lower than European and North American populations. We aimed at reviewing the rates and patterns of BRCA1/2 mutations found in individuals referred to the medical genetics unit at the American University of Beirut. We also evaluated the performance of clinical prediction tools. METHODS: We retrospectively reviewed the cases of all individuals undergoing BRCA mutation testing from April 2011 to May 2016. To put our findings in to context, we conducted a literature review of the most recently published data from the region. RESULTS: Two-hundred eighty one individuals were referred for testing. The prevalence of mutated BRCA1 or 2 genes were 6 and 1.4% respectively. Three mutations accounted for 54% of the pathogenic mutations found. The BRCA1 c.131G > T mutation was found among 5/17 (29%) unrelated subjects with BRCA1 mutation and is unique to the Lebanese and Palestinian populations. For patients tested between 2014 and 2016, all patients positive for mutations fit the NCCN guidelines for BRCA mutation screening. The Manchester Score failed to predict pathogenic mutations. CONCLUSION: The BRCA1 c.131G > T mutation can be considered a founder mutation in the Lebanese population detected among 5/17 (29%) of individuals diagnosed with a mutation in BRCA1 and among 7/269 families in this cohort. On review of recently published data regarding the landscape of BRCA mutations in the Middle East and North Africa, each region appears to have a unique spectrum of mutations.

Pancreaticoduodenectomy in the Middle East: Achieving optimal results through specialization and standardization.

BACKGROUND: Pancreaticoduodenectomy is a challenging surgical intervention that remains the cornerstone in the treatment of localized peri­ampullary pathologies. The concept of treatment standardization has been well-established in many high-volume centers in the world. Here, we present our experience in pancreaticoduodenectomy from 1994 to 2015. METHODS: We performed a retrospective review of the medical charts of patients who underwent pancreaticoduodenectomy at our institution. Data was entered to SPSS statistical software and analyzed. The Mann-Whitney U and Fisher's exact tests were used to report statistical differences between groups. RESULTS: Of the 370 patients who underwent pacreaticoduodenectomy, 300 were analyzed. The 1-, 3-, 5- and 10-year survival rates were 85%, 35%, 15%, and 7%, respectively with a 30-day mortality rate of 5.0% (15 patients). The median age of the patients was 61 (13-84) years, with 193 (64.3%) males and 107 (35.7%) females. The median operative time was 300 (130-570) min. The median postoperative length of hospital stay was 12 (5-76) days. Thirty-two patients required re-laparotomies; 10 for pancreatic leak, 7 for biliary leak and 15 for control of bleeding. Seventy-five (25.0%) patients developed pancreatic fistulae. Delayed gastric emptying was present in 31 (10.3%) patients. A significant improvement in surgical outcome was observed in cases done after 2008 which indicates the important role of specialized team in surgical management. CONCLUSIONS: The number of patients undergoing pancreaticoduodenectomy has been increasing annually over the past twenty-two years in our institution with results comparable to published series from high-volume centers. Through standardization of surgical techniques and perioperative management carried out by a specialist team, our results continue to improve despite the increasing complexity of cases referred to our unit.

Gut Microbiome: A Promising Biomarker for Immunotherapy in Colorectal Cancer.

Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.