Physical Activity among Colorectal Cancer Patients and Survivors in Egypt.

INTRODUCTION: Understanding physical activity (PA) levels is important when developing tertiary cancer prevention interventions, especially in Egypt where colorectal cancer (CRC) is more often diagnosed at later stages and at a younger age of onset (≤40 years). METHODS: We assessed PA levels among CRC patients and survivors in Alexandria, Egypt. All participants completed two self-reported PA assessments: Global Physical Activity Questionnaire (GPAQ) and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Participants could opt to wear an accelerometer for seven days. Results were compared against WHO recommendations of ≥150 minutes or ≥600 metabolic equivalents of tasks (METs) of moderate-to-vigorous PA weekly. RESULTS: Of 86 participants enrolled, all completed the surveys and 29 agreed to accelerometer use. Prevalence of meeting PA recommendations was 62.8% based on the GPAQ, 14.0% based on GLTEQ, and 41% based on accelerometer. Based on the GPAQ, very few respondents reported vigorous occupational, vigorous recreational, or moderate recreational activity (median = 0 with interquartile range [IQR] of 0 - 0 weekly minutes for all three) while most activity resulted from moderate occupational and transportation (median [IQR] of 60 [0-840] and 60 [0-187.5] weekly minutes, respectively). Participants meeting PA recommendations were less likely to be married (p = 0.043) according to GPAQ and more likely to be female (p=0.047) and early cancer stage (p=0.007) by GLTEQ. CONCLUSION: Non-leisure free-living PA is a major contributor to meeting PA recommendations while leisure-time PA is a potential target for future interventions that increase PA in this population.

Microbiome diversity in African American, European American, and Egyptian colorectal cancer patients.

Purpose: Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients. Patients and methods: CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA sequencing. Differential microbial abundance, diversity, and metabolic pathways were identified using linear discriminant analysis (LDA) effect size analyses. Additionally, we compared these profiles with our previously published microbiome data derived from Kenyan CRC patients. Results: Differential microbiome analysis of CRCs across all racial/ethnic groups showed dysbiosis. There were high abundances of Herbaspirillum and Staphylococcus in CRCs of Egyptians, Leptotrichia in CRCs of AAs, Flexspiria and Streptococcus in CRCs of EAs, and Akkermansia muciniphila and Prevotella nigrescens in CRCs of Kenyans (LDA score >4, adj. p-value <0.05). Functional analyses showed distinct microbial metabolic pathways in CRCs compared to normal tissues within the racial/ethnic groups. Egyptian CRCs, compared to normal tissues, showed lower l-methionine biosynthesis and higher galactose degradation pathways. Conclusions: Our findings showed altered mucosa-associated microbiome profiles of CRCs and their metabolic pathways across racial/ethnic groups. These findings provide a basis for future studies to link racial/ethnic microbiome differences with distinct clinical behaviors in CRC.

Comparable Efficacy of Submucosal Platelet-Rich Plasma and Combined Platelet-Rich Plasma Noncrosslinked Hyaluronic Acid Injections in Vulvovaginal Atrophy: A Cancer Survivorship Issue.

Background: Cancer survivors are often reluctant to discuss sexual complaints with their oncologists and treatment is frequently unsatisfactory due to paucity of controlled studies and inapplicability of vaginal estrogen. We aimed to evaluate efficacy and tolerability of platelet-rich plasma (PRP) injections alone or in combination with noncrosslinked hyaluronic acid compared with standard therapy with topical hyaluronic acid gel in the management of cancer therapy-induced or aggravated vulvovaginal atrophy. Materials and Methods: This prospective, parallel-group comparative study was conducted on 45 female patients with a history of cancer and complaining of symptoms of vulvovaginal atrophy either induced or aggravated by cancer treatment. Patients were randomly divided into three groups (A, B, and C). Group A patients received two submucosal vaginal PRP injections, group B patients received two similar injections of PRP combined with noncrosslinked hyaluronic acid, and group C received a topical vaginal hyaluronic acid gel applied three times weekly for 2 months. Main outcome measures were vulvovaginal atrophy symptom severity and vaginal health index (VHI) scores before treatment (v0), 1 month from baseline (v1), 2 months from baseline (v2), and 3 months after the last visit (v3). Results: Both groups A and B showed greater improvement of frequency of intercourse avoidance than group C. Group A showed greater improvement of dyspareunia than group C. Groups A and B demonstrated greater improvement of vaginal pH, fluid volume, and total VHI scores than group C. Short-term topical hyaluronic acid (HA) was not associated with any significant improvement of vaginal elasticity. Group B showed greater improvement of vaginal dryness and moisture scores than group C. Reported adverse events were injection-related pain in all patients of groups A and B and vaginal spotting in groups A and B. Conclusion: Both PRP and PRP-HA have comparable efficacy and patient-reported treatment satisfaction. PRP injections were better tolerated by patients than PRP-HA. Clinical trial registration number: NCT05782920.

Eligibility criteria to cisplatin in head and neck squamous cell carcinoma: Egyptian expert opinion.

Introduction: The use of cisplatin in clinical practice in the management of head and neck squamous cell carcinoma (HNSCC) is limited by its toxicity and acquired resistance, which makes the decision-making process of its prescription multifactorial. Methods: An Egyptian expert panel (comprising nine Egyptian oncologists) meeting was held after a comprehensive literature review on the use of cisplatin in HNSCC. The panel aimed to develop a consensus on evidence-based recommendations for receiving cisplatin in the chemoradiotherapy management of HNSCC in Egyptian clinical practice. Results: The panel indicated that an Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, creatinine clearance (CCR) < 50 ml/min, neuropathy grade ≥ 2, pre-existing hearing loss or tinnitus ≥2, hematological problems (platelets < 100,000/mm3, neutrophils < 1500/mm, and hemoglobin < 9 g/dl), and heart failure of New York Heart Association Classes III or IV (even if cardiovascular therapy is optimized); are all absolute contraindications to receiving cisplatin. On the other hand, relative contraindications to cisplatin according to the panel were an ECOG PS of 2, age more than 70 years, CCR between 50 and 60 ml/min, grade 1 neuropathy, grade 1 hearing loss, involuntary weight loss of ≥20% of body weight, Child-Pugh Scores B and C, previous induction chemotherapy, and heart failure of New York Heart Association Classes I or II with left ventricular ejection fraction ≤50%. The panel agreed that the socioeconomic status of patients should be considered when prescribing cisplatin to HNSCC patients. Conclusion: Our discussion resulted in a set of evidence-based recommendations for cisplatin eligibility criteria in patients of HNSCC in Egypt.

A signature of Prevotella copri and Faecalibacterium prausnitzii depletion, and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients.

Background: Colorectal cancer (CRC) is the fifth most diagnosed cancer in Sub-Saharan Africa. In Kenya, CRC incidence rates tripled from 1997 to 2017. In the Moi Teaching and Referral Hospital, Moi University, there has been an increase in CRC cases, notably for younger patients. A suggested pathobiology for this increase is gut microbiome dysbiosis. Since, for the Kenyan CRC patient population, microbiome studies are rare, there is a need for a better understanding of how microbiome dysbiosis influences CRC epidemiology in Kenya. In this single-center study, the focus was on profiling the gut microbiome of Kenyan CRC patients and healthy volunteers and evaluating associations between microbiome profiles and the age of CRC patients. Methods: The gut mucosa-associated microbiome of 18 CRC patients and 18 healthy controls were determined by 16S rRNA sequencing and analyzed for alpha and beta diversity, differential abundance, and microbial metabolic profiling. Results: Alpha diversity metrics showed no significant differences, but beta diversity metrics showed dissimilarities in the microbial communities between CRC patients and healthy controls. The most underrepresented species in the CRC group were Prevotella copri (P. copri) and Faecalibacterium prausnitzii (F. prausnitzii), although Bacteroides fragilis (B. fragilis) and Prevotella nigrescens were overrepresented (linear discriminant analysis, LDA score >2, P<0.05). Also, for CRC patients, significant metagenomic functional alterations were evident in microbial glutamate metabolic pathways (L-glutamate degradation VIII was enriched, and L-glutamate and L-glutamine biosynthesis were diminished) (P<0.05, log2 Fold Change >1). Moreover, the microbiome composition was different for patients under 40 years of age compared to older patients (LDA score >2, P<0.05). Conclusions: Microbiome and microbial metabolic profiles of CRC patients are different from those of healthy individuals. CRC microbiome dysbiosis, particularly P. copri and F. prausnitzii depletion and glutamate metabolic alterations, are evident in Kenyan CRC patients.

Evaluation of the Effect of Axillary Radiotherapy Dose and the Development of Lymphedema in Breast Cancer Patients.

Purpose: The present study is aiming to correlate different radiotherapy techniques, fractionations, and doses received by each axillary LN level and axillary vessels with the development of breast cancer-related lymphedema (BCRL). Methods and Materials: We retrospectively studied 181 female breast cancer patients who were diagnosed and treated by radiation therapy during the period from January 2012 to December 2017. The radiotherapy treatment plans were recalled from the archives. The axillary LN levels I, II, III, supraclavicular LN were contoured as well as axillary vessels. New dose volume histograms were generated to correlate between the radiotherapy dose t and the development of BCRL. Results: The study included 162 patients treated with a 3D radiotherapy technique and 19 treated with a 2D radiotherapy technique; 124 patients underwent MRM, while 57 patients underwent BCS; 117 patients were treated with a hypofractionated technique, while 64 patients were treated with a conventional radiotherapy technique. The cumulative incidence of BCRL after radiotherapy was 20.4%. There was a statistically significant relationship between the 2D radiotherapy technique compared with 3DCRT and development of lymphedema (55 vs. 16.6, respectively; p < 0.001). Patients who were treated with conventional radiotherapy had significantly higher rates of lymphedema (42.2%) compared with hypofractionated radiotherapy (8.5%) (p < 0.001). There was a non-significant relationship between mean radiotherapy dose to axillary levels or axillary vessels and development of lymphedema. Conclusion: Breast cancer radiotherapy with the 2D technique and conventional fractionation protocol might increase the risk of BCRL. No correlation was observed between radiotherapy dose to each axillary LN level, axillary vessels and BCRL.

Using Intervention Mapping to Develop a Theory-Based Intervention to Promote Colorectal Cancer Screening in Egypt.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates are increasing in Egypt. Because no national screening guidelines exist, developing an effective evidence-based screening intervention could lower rates by early detection of pre-cancerous and cancerous lesions and polyps. This paper describes the development of a CRC screening intervention in Alexandria, Egypt using Intervention Mapping (IM). MATERIALS AND METHODS: Between September 2019 and March 2020, the successive steps of the IM process were completed. Beginning with the needs assessment, we conducted a literature review, held focus groups with residents of Alexandria, and conducted interviews with local gastroenterologists and oncologists. Program objectives and target audience were determined before designing the program components and implementation plan. Using the PRECEDE-PROCEED theoretical model, predisposing, reinforcing, and enabling screening barriers were assessed. Finally, we developed a Standard Operating Procedures manual detailing aspects of the intervention and evaluation to serve as a model for an expanded screening program. RESULTS: The needs assessment, e.g., literature review, seven focus groups (N=61 participants) and interviews (N=17 participants), indicated that barriers among residents included CRC knowledge deficits, fear/anxiety regarding testing, high cost, and lack of accessibility. Physicians believed CRC testing should only be performed for high risk individuals. Findings from each step of the process informed successive steps. Our final intervention consisted of training components for medical students (Health Champions) who would deliver the intervention to patients in primary care waiting rooms, providing short descriptions of CRC risks and screening, educational brochures, and distributing vouchers for no-cost guaiac fecal occult blood test kits. Health Champions would then follow up with the patients, providing results and referrals for no-cost colonoscopy testing for those with abnormal results. CONCLUSION: Utilizing the IM steps successfully led to development of a theory-based CRC screening intervention for Egypt. Next steps include the implementation of a feasibility pilot intervention.

Risk of Developing Breast Reconstruction Complications: A Machine-Learning Nomogram for Individualized Risk Estimation with and without Postmastectomy Radiation Therapy.

BACKGROUND: The purpose of this study was to create a nomogram using machine learning models predicting risk of breast reconstruction complications with or without postmastectomy radiation therapy. METHODS: Between 1997 and 2017, 1617 breast cancer patients undergoing mastectomy and breast reconstruction were analyzed. Those with autologous, tissue expander/implant, and single-stage direct-to-implant reconstruction were included. Postmastectomy radiation therapy was delivered either with three-dimensional conformal photon or proton therapy. Complication endpoints were defined based on surgical reintervention operative notes as infection/necrosis requiring débridement. For implant-based patients, complications were defined as capsular contracture requiring capsulotomy and implant failure. For each complication endpoint, least absolute shrinkage and selection operator-penalized regression was used to select the subset of predictors associated with the smallest prediction error from 10-fold cross-validation. Nomograms were built using the least absolute shrinkage and selection operator-selected predictors, and internal validation using cross-validation was performed. RESULTS: Median follow-up was 6.6 years. Among 1617 patients, 23 percent underwent autologous reconstruction, 39 percent underwent direct-to-implant reconstruction, and 37 percent underwent tissue expander/implant reconstruction. Among 759 patients who received postmastectomy radiation therapy, 8.3 percent received proton-therapy to the chest wall and nodes and 43 percent received chest wall boost. Internal validation for each model showed an area under the receiver operating characteristic curve of 73 percent for infection, 75 percent for capsular contracture, 76 percent for absolute implant failure, and 68 percent for overall implant failure. Periareolar incisions and complete implant muscle coverage were found to be important predictors for infection and capsular contracture, respectively. In a multivariable analysis, we found that protons compared to no postmastectomy radiation therapy significantly increased capsular contracture risk (OR, 15.3; p < 0.001). This was higher than the effect of photons with electron boost versus no postmastectomy radiation therapy (OR, 2.5; p = 0.01). CONCLUSION: Using machine learning, these nomograms provided prediction of postmastectomy breast reconstruction complications with and without radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Highlighting Levels of Indoxyl Sulphate among Critically Ill Patients with Acute Nephrotoxicity; Correlations Between Indoxyl Sulphate Levels and Patients' Characteristics.

BACKGROUND: Many animal studies suggested that the uremic toxin indoxyl sulphate can add to renal damage following induced nephrotoxicity and this effect has not been proved in patients with such complication. METHODS: This is a prospective, case-control, and an observational study conducted on 74 critically ill patients with acute nephrotoxicity. It was designed to measure serum levels of indoxyl sulphate on the day of enrollment and over the course of their illness using high performance liquid chromatography (HPLC-UV) and to test the correlation between these levels and patient's demographics, clinical characteristics, physiological variables, and their outcomes. RESULTS: Critically ill patients with acute nephrotoxicity had significantly higher total (tIS) and free (fIS) indoxyl sulphate than healthy controls and significantly lower than patients with end-stage renal disease (ESRD). Although, no correlation was found between tIS or fIS and mortality, among survivors, tIS, fIS, creatinine and eGFR were independently associated with no renal recovery. CONCLUSION: Serum indoxyl sulphate levels were elevated in critically ill patients with acute nephrotoxicity. There is an association between high levels of indoxyl sulphate and no renal-recovery outcome among survivors of acute nephrotoxicity. Early removal of indoxyl sulphate from patients' blood may improve their outcomes.

LGR5, HES1 and ATOH1 in Young Rectal Cancer Patients in Egyptian.

OBJECTIVE: The study aimed to delineate the gene expression profile of LGR5, HES1 and ATOH1 in young Egyptian rectal cancer (RC) patients and investigate the correlation between expression profiles and clinical outcome. METHODS: The study was conducted on 30 young Egyptian RC patients. Expression study of LGR5, HES1 and ATOH1 were performed by quantitative PCR (QPCR) based on comparative Cq method after normalization to adjacent non tumor tissues and ACTB as a reference gene. Patients were followed up for assessment of response to neoadjuvant chemoradiotherapy (CRT) based on revised RECIST1.1. RESULT: The study detected overexpression of LGR5 and HES1 and down-regulation of ATOH1 in human RC tissues compared to non- tumor tissues. High expression of LGR5 was correlated with more depth of tumor invasion, lymph node (LN) metastasis, advanced cTNM stage and mesorectal fascia (MRF) involvement. More prominently, high LGR5 expression level was associated with poor response to CRT. LGR5 was suggested as unfavorable prognostic biomarker for RC. Conversely, HES1 and ATOH1 expression did not show significant association with most of the studied clinical criteria nor response to CRT. Still, HES1 and ATOH1 were significantly and inversely associated with presence of mucinous component. CONCLUSION: High LGR5 expression is indicative of poor prognosis among young Egyptian RC patients and is proposed as a predictive marker of resistance to neoadjuvant CRT. However, HES1 and ATOH1 expressions were not prognostic nor predictive of response to CRT. Overall, LGR5, HES1 and ATOH1 gene expression patterns among young onset RC patients, are in line with patterns encountered in older age groups.

Therapeutic strategies of recurrent glioblastoma and its molecular pathways 'Lock up the beast'.

Glioblastoma multiforme (GBM) has a poor prognosis-despite aggressive primary treatment composed of surgery, radiotherapy and chemotherapy, median survival is still around 15 months. It starts to grow again after a year of treatment and eventually nothing is effective at this stage. Recurrent GBM is one of the most disappointing fields for researchers in which their efforts have gained no benefit for patients. They were directed for a long time towards understanding the molecular basis that leads to the development of GBM. It is now known that GBM is a heterogeneous disease and resistance comes mainly from the regrowth of malignant cells after eradicating specific clones by targeted treatment. Epidermal growth factor receptor, platelet derived growth factor receptor, vascular endothelial growth factor receptor are known to be highly active in primary and recurrent GBM through different underlying pathways, despite this bevacizumab is the only Food and Drug Administration (FDA) approved drug for recurrent GBM. Immunotherapy is another important promising modality of treatment of GBM, after proper understanding of the microenvironment of the tumour and overcoming the reasons that historically stigmatise GBM as an 'immunologically cold tumour'. Radiotherapy can augment the effect of immunotherapy by different mechanisms. Also, dual immunotherapy which targets immune pathways at different stages and through different receptors further enhances immune stimulation against GBM. Delivery of pro-drugs to be activated at the tumour site and suicidal genes by gene therapy using different vectors shows promising results. Despite using neurotropic viral vectors specifically targeting glial cells (which are the cells of origin of GBM), no significant improvement of overall-survival has been seen as yet. Non-viral vectors 'polymeric and non-polymeric' show significant tumour shrinkage in pre-clinical trials and now at early-stage clinical trials. To this end, in this review, we aim to study the possible role of different molecular pathways that are involved in GBM's recurrence, we will also review the most relevant and recent clinical experience with targeted treatments and immunotherapies. We will discuss trials utilised tyrosine receptor kinase inhibitors, immunotherapy and gene therapy in recurrent GBM pointing to the causes of potential disappointing preliminary results of some of them. Additionally, we are suggesting a possible future treatment based on recent successful clinical data that could alter the outcome for GBM patients.

Psychological and Sexual Health During the COVID-19 Pandemic in Egypt: Are Women Suffering More?

INTRODUCTION: Psychological consequences of the COVID-19 pandemic include pandemic triggered feelings of fear, uncertainty, and anxiety added to the effects of restricting the population's activities in lockdown. AIM: We aimed to study the effect of COVID-19 pandemic on sexual satisfaction of females and males in Egypt and to evaluate possible predictive factors. METHODS: Married men and females in Egypt were invited to respond to an online questionnaire. The questionnaire addressed medical history, socioeconomic status, sexual performance satisfaction before and during the lockdown in addition to validated Arabic questionnaires for depression, sexual function in males and females, and sexual satisfaction (Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Female Sexual Function Index, International Index of Erectile Function-5, Index of Sexual Satisfaction, respectively). MAIN OUTCOME MEASURE: The main outcome measures were frequency of depression, anxiety, sexual dysfunction, and sexual satisfaction in males and females during COVID-19 lockdown. RESULTS: A total of 479 females and 217 males completed the questionnaire. Sexual satisfaction was significantly higher before (91.2%, 73.5%) than during lockdown (70.5%, 56.2%) in both males and females, respectively. During lockdown, significantly more males (70.5%) reported being satisfied with their sexual performance than females (56.2%) (P < .001). More than half of the male subjects (68.2%) had no erectile dysfunction while 97.3% females scored ≤26.5 on the Female Sexual Function Index scale suggestive of sexual difficulties. Sexual stress was significantly greater in females (70.8%) than males (63.1%). Educational level, occupation, anxiety, and erectile dysfunction were independently associated with sexual stress in males. Being a housewife or unemployed, husband's age >35 years, marriage duration of 5-10 years, anxiety, and female sexual dysfunction were predictors of sexual relation stress in females. CONCLUSION: COVID-19 pandemic was associated with lower sexual satisfaction in both genders. Females however suffered more anxiety and depression and thereby greater risk of sexual function difficulties and sexual dissatisfaction. Intervention strategies in order to lessen the suffering of affected individuals particularly after the pandemic are recommended. Omar SS, Dawood W, Eid N, et al. Psychological and Sexual Health During the COVID-19 Pandemic in Egypt: Are Women Suffering More. Sex Med 2021;9:100295.

Optimal breast reconstruction type for patients treated with neoadjuvant chemotherapy, mastectomy followed by radiation therapy.

PURPOSE: To explore the optimal type of breast reconstruction and the time interval to postmastectomy radiotherapy (PMRT) associated with lower complications in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: We reviewed the medical records of 300 patients who received neoadjuvant chemotherapy, mastectomy with breast reconstruction and PMRT at our institution from 2000 to 2017. Reconstruction types included autologous flaps (AR), single-stage-direct-to-implant and two-stages expander/implant (TE/I). The primary endpoint was the rate of reconstruction complications including infection, skin and fat necrosis. Subgroup analysis compared rates of capsular contracture, implant rupture, implant exposure and overall implant failure in single-stage-direct-to-implant to TE/I. The secondary endpoint was identifying the time interval between surgery with immediate implant-based reconstruction and PMRT associated with lower probability of implant failure. Logistic regression models, Kaplan-Meier estimates and Polynomial regression were used to assess endpoints. RESULTS: The median follow-up was 43.5 months. 29.3%, 28.3% and 42.4% of the cohort had AR, TE/I and single-stage-direct-to-implant D, respectively. The 5-year cumulative incidence rate of complications was 14.0%, 29.7% and 19.4% for AR, TE/I and single-stage-direct-to-implant, respectively (Log rank p = 0.02). Multivariate analysis showed significant association between TE/I and higher risk of infection (OR 8.1, p = 0.009) compared to AR, while single-stage-direct-to-implant and AR were comparable (OR 3.2, p = 0.2). On subgroup analysis, TE/I was significantly associated with higher rates of implant failure. The mean wait time to deliver PMRT after immediate reconstruction with no adjuvant chemotherapy was 8.4 and 10.7 weeks in single-stage-direct-to-implant and TE/I, respectively (p < 0.005). Delivering PMRT after 8 weeks of surgery yielded 10% probability of reconstruction failure in single-stage-direct-to-implant versus 40% in TE/I. CONCLUSION: In comparison to two stages reconstruction, single-stage-direct-to-implant following neoadjuvant chemotherapy has lower complications and offers timely delivery of PMRT.

Designing an Effective Colorectal Cancer Screening Program in Egypt: A Qualitative Study of Perceptions of Egyptian Primary Care Physicians and Specialists.

BACKGROUND: In Egypt more than one-third of colorectal cancer (CRC) cases occur in individuals aged 40 years and younger, and are diagnosed at advanced stages; currently, CRC screening is not done as a routine part of preventive care. To lay the foundation for the development of a CRC multilevel screening program in Egypt, this qualitative study aimed to explore the perspectives of Egyptian physicians. MATERIALS AND METHODS: The PRECEDE-PROCEED model, which focuses on predisposing (intrapersonal), reinforcing (interpersonal), and enabling (structural) factors inherent in health behaviors, served as our theoretical framework. Primary health care physicians, oncologists, and gastroenterologists practicing in Alexandria, Egypt, participated in 1 one-hour semistructured interview. Interviews were audio recorded, transcribed, translated into English, and analyzed by thematic analysis. RESULTS: Seventeen physicians participated (n = 8 specialists and n = 9 primary care physicians). Barriers to CRC screening included socioeconomic status, a lack of emphasis on prevention, fear, and cost (predisposing); a belief that only high risk patients should be screened and a lack of confidence in providers to perform and interpret screening tests appropriately (reinforcing); and cost, lack of availability of the tests, and inadequate training for laboratory technicians and providers (enabling). Potential facilitators included implementing a media campaign emphasizing early detection, curability and prevention (predisposing); educating physicians and eliciting physician engagement (reinforcing); and decreasing costs, making screening tests widely available, and providing well-trained providers (enabling). CONCLUSION: A CRC screening program is needed in Egypt, and to be successful it would likely need to address barriers at multiple levels. IMPLICATIONS FOR PRACTICE: In Egypt, colorectal screening is not a routine part of preventive care, and colorectal cancer is often diagnosed at an advanced stage in individuals aged 40 years or younger. Screening can prevent and detect colorectal cancer in its early stages, but before designing any screening program, understanding the context is important as cultural beliefs may impact the acceptability of screening methods. By exploring the perspectives of Egyptian physicians, this study found important insights into how screening program components should be considered in the Egyptian culture and lays the foundation for the development of a multilevel colorectal screening program in Egypt.

The Impact of Chest Wall Boost on Reconstruction Complications and Local Control in Patients Treated for Breast Cancer.

PURPOSE: Giving an additional radiation dose to the incision or chest wall has been a practice, but it has never been studied in a randomized setting, and it might lead to inferior cosmetic outcomes. This study aims to evaluate whether delivery of a chest wall boost (CWB) to the mastectomy scar or chest wall is independently associated with reconstruction complications and to assess its disease control efficacy in the setting of breast reconstruction. METHODS AND MATERIALS: We conducted a retrospective chart review of 746 patients with breast cancer who underwent mastectomy, breast reconstruction, and PMRT; all underwent treatment at our institution during 1997 to 2016. Various reconstruction techniques were used among this cohort including autologous reconstruction, single-stage direct-to-implant reconstruction, and 2-stage tissue expander implant. Cohorts were divided by administration of CWB. The primary objective was comparing the rate of reconstruction complications including skin necrosis, fat necrosis and infection between groups. Subgroup analysis for patients with implant-based reconstruction was performed to evaluate the effect of CWB on implant-related complications such as capsular contracture, implant exposure, and implant failure. The secondary objective was comparison of the cumulative incidence of local failure between groups overall and within clinically high-risk subgroups. RESULTS: The median follow-up was 5.2 years. Most clinicopathologic features were well balanced between the 379 (51%) patients who received CWB and the 367 (49%) who did not. On multivariate analysis, CWB was significantly associated with infection, skin necrosis, and implant exposure. For implant reconstruction patients, CWB independently increased risks of implant failure. CWB administration was not associated with local tumor control benefits, even in high-risk subgroups. CONCLUSIONS: Our findings suggest that omission of chest wall boost in postmastectomy radiation improves breast reconstruction outcomes without compromising local tumor control.

Site of Metastases as Prognostic Factors in Unselected Population of Stage IV Non-Small Cell Lung Cancer

Background: Advanced stage non-small cell lung cancer (NSCLC) is a heterogenous disease, yet, with the exception of targeted therapies, most guidelines recommended uniform treatment irrespective of tumor burden or sites of metastases and this may explain, in part, the wide range of responses to same lines of therapy. Aim of work: In this work we tried to explore the effect of metastatic sites in on overall survival (OS), in an unselected group of Non-small cell lung cancer patients who received different treatments line. Methods: A retrospective analysis was performed on patients with stage IV NSCLC who received systemic treatment at UAB Cancer Center (NCI designated comprehensive cancer center) between 2002 to 2012. The details of sites of metastases, systemic therapy and overall survival were recorded for each patient. Result: In 409 patients who received systemic treatment, there was statistically significant lower OS in those presenting with liver metastases (p<0.001), adrenal metastases (p=0.011) and metastases to abdominal lymph nodes (p=0.014). There was no statistically significance difference in OS in patient presenting with pleural metastases or effusion (p=0.908), metastases to heart or pericardium (p=0.654), metastases to bone (p=0.281), brain (p=0.717) or skin and subcutaneous tissue (p=0.642). Conclusion: Intra-abdominal metastases confer a particularly poor prognosis in stage IV NSCLC treated with systemic therapy and may identify patients in whom aggressive treatment beyond first line therapy is not appropriate.

Novel targeted therapies and immunotherapy for advanced thyroid cancers.

Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients' overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor's ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.

Natural Agents-Mediated Targeting of Histone Deacetylases.

In the past few years, basic and clinical scientists have witnessed landmark achievements in many research projects, such as those conducted by the US National Institutes of Health Roadmap Epigenomics Mapping Consortium, the International Human Epigenome Consortium, The Cancer Genome Atlas Network and the International Cancer Genome Consortium, which have provided near-complete resolution of epigenetic landscape in different diseases. Furthermore, genome sequencing of tumors has provided compelling evidence related to frequent existence of mutations in readers, erasers and writers of epigenome in different cancers. Histone acetylation is an intricate mechanism modulated by two opposing sets of enzymes and deeply studied as a key biological phenomenon in 1964 by Vincent Allfrey and colleagues. The research group suggested that this protein modification contributed substantially in transcriptional regulation. Subsequently, histone deacetylases (HDACs), histone acetyltransferases and acetyl-Lys-binding proteins were identified as transcriptional mediators, which further deepened our comprehension regarding biochemical modifications. Overwhelmingly increasing high-impact research is improving our understanding of this molecularly controlled mechanism; moreover, quantification and identification of lysine acetylation by mass spectrometry has added new layers of information. We partition this multi-component review into how both activity and expression of HDAC are targeted using natural agents. We also set spotlight on how oncogenic fusion proteins tactfully utilize HDAC-associated nano-machinery to modulate expression of different genes and how HDAC inhibitors regulate TRAIL-induced apoptosis in cancer cells. HDAC inhibitors have been reported to upregulate expression of TRAIL receptors and protect TRAIL from proteasomal degradation. Deeper understanding of HDAC biology will be useful for stratification and selection of patients who are responders, non-responders and poor-responders for HDACi therapy, and for the rational design of combination studies using HDACi.

Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies have been developed and being tested pre-clinically and clinically both as a single agent and in combinations. Of note, the monoclonal antibodies were not the only type of antibodies developed to target TRAIL receptors. Recent technology has brought forth several single chain variable domains (scFv) designs fused recombinantly to TRAIL as well. Also, it is becoming progressively more understandable that field of nanotechnology has revolutionized cancer diagnosis and therapy. The recent breakthroughs in materials science and protein engineering have helped considerably in strategically loading drugs into nanoparticles or conjugating drugs to their surface. In this review we aim to comprehensively highlight the molecular knowledge of TRAIL in the context of its pathway, receptors and resistance factors. We also aim to review the clinical trials that have been done using TRAIL based therapies and to review various scFv designs, the arsenal of nano-carriers and molecules available to selectively target tumor cells with TRAIL.