BACKGROUND: We describe a multidisciplinary approach for comprehensive care of amputees with concurrent targeted muscle reinnervation (TMR) at the time of amputation.
METHODS: Our TMR cohort was compared to a cross-sectional sample of unselected oncologic amputees not treated at our institution (N = 58). Patient-Reported Outcomes Measurement Information System (NRS, PROMIS) were used to assess postamputation pain.
RESULTS: Thirty-one patients underwent amputation with concurrent TMR during the study; 27 patients completed pain surveys; 15 had greater than 1 year follow-up (mean follow-up 14.7 months). Neuroma symptoms occurred significantly less frequently and with less intensity among the TMR cohort. Mean differences for PROMIS pain intensity, behavior, and interference for phantom limb pain (PLP) were 5.855 (95%CI 1.159-10.55; P = .015), 5.896 (95%CI 0.492-11.30; P = .033), and 7.435 (95%CI 1.797-13.07; P = .011) respectively, with lower scores for TMR cohort. For residual limb pain, PROMIS pain intensity, behavior, and interference mean differences were 5.477 (95%CI 0.528-10.42; P = .031), 6.195 (95%CI 0.705-11.69; P = .028), and 6.816 (95%CI 1.438-12.2; P = .014), respectively. Fifty-six percent took opioids before amputation compared to 22% at 1 year postoperatively.
CONCLUSIONS: Multidisciplinary care of amputees including concurrent amputation and TMR, multimodal postoperative pain management, amputee-centered rehabilitation, and peer support demonstrates reduced incidence and severity of neuroma and PLP.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide prospective registry study for surveying the treatment outcome of prostate cancer patients who have received a histopathological diagnosis. The study aims to clarify the clinical situation for prostate cancer in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo on December 2015, the second meeting in Seoul, Korea 2016, the third meeting in Chiang Mai, Thailand, on October 2017, the fourth meeting was held in Seoul, again on August 2018 with the participation of members and collaborators from 13 countries and regions. In the meeting, participating countries and regions presented the current status of data collection and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data cleaning and data up-dating which is the next step of the A-CaP study following the data collection phase between 2016 and 2018. There was specific difference in term of the patient characteristics, and initial treatment pattern among East Asia, Southeast Asia and Turkey, and Jordan. Finally, a close relationship between prevalence of PSA test and disease stage of the patients at diagnosis in Japan and Malaysia was discussed.

BACKGROUND: Alternative models of cancer follow-up care are needed to ameliorate pressure on services and better meet survivors' long-term needs. This paper reports an evaluation of a service improvement initiative for the follow-up care of prostate cancer patients based on remote monitoring and supported self-management.
METHODS: This multi-centred, historically controlled study compared patient reported outcomes of men experiencing the new Programme with men experiencing a traditional clinic appointment model of follow-up care, who were recruited in the period immediately prior to the introduction of the Programme. Data were collected by self-completed questionnaires, with follow up measurement at four and eight months post-baseline. The primary outcome was men's unmet survivorship needs, measured by the Cancer Survivors' Unmet Needs Survey. Secondary outcomes included cancer specific quality of life, psychological wellbeing and satisfaction with care. The analysis was intention to treat. Regression analyses were conducted for outcomes at each time point separately, controlling for pre-defined clinical and demographic variables. All outcome analyses are presented in the paper. Costs were compared between the two groups.
RESULTS: Six hundred and twenty-seven men (61%) were consented to take part in the study (293 in the Programme and 334 in the comparator group.) Regarding the primary measure of unmet survivorship needs, 25 of 26 comparisons favoured the Programme, of which 4 were statistically significant. For the secondary measures of activation for self-management, quality of life, psychological well-being and lifestyle, 20 of 32 comparisons favoured the Programme and 3 were statistically significant. There were 22 items on the satisfaction with care questionnaire and 13 were statistically significant. Per participant costs (British pounds, 2015) in the 8 month follow up period were slightly lower in the programme than in the comparator group (£289 versus £327). The Programme was acceptable to patients.
CONCLUSION: The Programme is shown to be broadly comparable to traditional follow-up care in all respects, adding to evidence of the viability of such models.

PURPOSE: Inflammatory reaction has been linked to bladder cancer. Diet, which drives systemic inflammation, may be considered a modifiable risk factor for bladder cancer. We examined the association of diet with pro-inflammatory potential and bladder cancer risk using the novel EDIP (empirical dietary inflammatory pattern) score comprising predefined food groups determining a pattern most predictive of plasma inflammatory markers.
MATERIALS AND METHODS: We followed a total of 172,802 women in the NHS (Nurses' Health Study) from 1984 to 2012 and the NHS II from 1991 to 2013 as well as 45,272 men in the HPFS (Health Professionals Follow-Up Study) from 1986 to 2012. Multivariable adjusted Cox regression models were used to estimate the RR and 95% CI of bladder cancer across EDIP score quintiles. We performed inverse variance weighted meta-analysis to pool estimates across cohorts stratified by smoking status.
RESULTS: During 4,872,188 person-years of observation 1,042 incident bladder cancer cases were identified. Overall, high EDIP scores reflecting dietary patterns with pro-inflammatory potential were not associated with a higher risk of bladder cancer (quintile 5 vs 1 pooled multivariable adjusted RR 0.92, 95% CI 0.75-1.12, p
CONCLUSIONS: We observed no association between diets with pro-inflammatory potential and bladder cancer risk. Although additional studies are needed to explore other nutritional pathways with the potential for bladder cancer prevention, our results suggest that diets associated with inflammation are not associated with bladder cancer risk.

OBJECTIVES: Breast cancer (BC) is the most common type of cancer worldwide. Globally, BC is rapidly becoming a major common health problem among women. This study aimed to evaluate the association between nutrient intake patterns and BC risk among Jordanian women.
METHODS: A total of 400 Jordanian women 20-65 years of age were recruited in this case-control study. Two hundred women recently diagnosed with BC were matched in age, income, and marital status to 200 BC-free women. A food frequency questionnaire was used to assess nutrient intake patterns.
RESULTS: In this study, 3 nutrient intake patterns were identified: a high vitamin C and β-carotene nutrient intake pattern; a high calcium, phosphorus, and vitamin D nutrient intake pattern; and a high-fat nutrient intake pattern. A significant increase in BC risk was associated with the high vitamin C and β-carotene nutrient pattern (the highest for the fourth quartile; odds ratio [OR], 5.42; 95% confidence interval [CI], 2.11 to 13.91; ptrend=0.001). In the high calcium, phosphorus, and vitamin D nutrient pattern, a significant inverse trend was detected for the risk of BC. The high-fat nutrient pattern showed a significant direct association with BC risk in the third (OR, 3.88; 95% CI, 1.58 to 9.51) and fourth (OR, 3.87; 95% CI, 1.53 to 9.77) quartiles (ptrend=0.001).
CONCLUSIONS: A significant increase in BC risk was detected for the high vitamin C and β-carotene nutrient intake pattern and the high-fat nutrient intake pattern. However, for the high calcium, phosphorus, and vitamin D nutrient intake pattern, a significant inverse trend was observed.

RATIONALE: Extraskeletal myxoid chondrosarcoma is a slow-growing soft tissue tumor of adults with a propensity for local recurrence and eventual metastasis. Only 17 pediatric and adolescent cases have been reported.
PATIENT CONCERNS: Here we present an 11-year-old boy with a 3-year history of a slowly growing painless left leg mass. Magnetic resonance imaging of the lesion revealed a subfascial well-circumscribed lesion with intramuscular extension in the medial gastrocnemius muscle of the left leg.
DIAGNOSES: He underwent wide local excision of the mass and the histomorphological and immunohistochemical findings were consistent with extraskeletal myxoid chondrosarcoma.
INTERVENTIONS: Possible radiotherapy was the further management plan.
OUTCOMES: He was in good condition with no evidence of recurrence at 6 months postsurgery.
LESSONS: Although pediatric cases of extraskeletal myxoid chondrosarcoma were reported to be aggressive, the tumor in this case demonstrated indolent behavior. Furthermore, the tumor in this case showed primitive round cell foci which adds to a previous study that especially reported this morphology in pediatric cases.

Methods to catalog and computationally assess the mutational landscape of proteins in human cancers are desirable. One approach is to adapt evolutionary or data-driven methods developed for predicting whether a single-nucleotide polymorphism (SNP) is deleterious to protein structure and function. In cases where understanding the mechanism of protein activation and regulation is desired, an alternative approach is to employ structure-based computational approaches to predict the effects of point mutations. Through a case study of mutations in kinase domains of three proteins, namely, the anaplastic lymphoma kinase (ALK) in pediatric neuroblastoma patients, serine/threonine-protein kinase B-Raf (BRAF) in melanoma patients, and erythroblastic oncogene B 2 (ErbB2 or HER2) in breast cancer patients, we compare the two approaches above. We find that the structure-based method is most appropriate for developing a binary classification of several different mutations, especially infrequently occurring ones, concerning the activation status of the given target protein. This approach is especially useful if the effects of mutations on the interactions of inhibitors with the target proteins are being sought. However, many patients will present with mutations spread across different target proteins, making structure-based models computationally demanding to implement and execute. In this situation, data-driven methods-including those based on machine learning techniques and evolutionary methods-are most appropriate for recognizing and illuminate mutational patterns. We show, however, that, in the present status of the field, the two methods have very different accuracies and confidence values, and hence, the optimal choice of their deployment is context-dependent.

BACKGROUND: Optimising breast cancer treatment remains a challenge. Resistance to therapy is a major problem in both ER- and ER+ breast cancer. Tumour recurrence after chemotherapy and/or targeted therapy leads to more aggressive tumours with enhanced metastatic ability. Self-renewing cancer stem cells (CSCs) have been implicated in treatment resistance, recurrence and the development of metastatic disease.
METHODS: In this study, we utilised in vitro, in vivo and ex vivo breast cancer models using ER+ MCF-7 and ER- MDA-MB-231 cells, as well as solid and metastatic breast cancer patient samples, to interrogate the effects of FKBPL and its peptide therapeutics on metastasis, endocrine therapy resistant CSCs and DLL4 and Notch4 expression. The effects of FKBPL overexpression or peptide treatment were assessed using a t-test or one-way ANOVA with Dunnett's multiple comparison test.
RESULTS: We demonstrated that FKBPL overexpression or treatment with FKBPL-based therapeutics (AD-01, pre-clinical peptide /ALM201, clinical peptide) inhibit i) CSCs in both ER+ and ER- breast cancer, ii) cancer metastasis in a triple negative breast cancer metastasis model and iii) endocrine therapy resistant CSCs in ER+ breast cancer, via modulation of the DLL4 and Notch4 protein and/or mRNA expression. AD-01 was effective at reducing triple negative MDA-MB-231 breast cancer cell migration (n ≥ 3, p < 0.05) and invasion (n ≥ 3, p < 0.001) and this was translated in vivo where AD-01 inhibited breast cancer metastasis in MDA-MB-231-lucD3H1 in vivo model (p < 0.05). In ER+ MCF-7 cells and primary breast tumour samples, we demonstrated that ALM201 inhibits endocrine therapy resistant mammospheres, representative of CSC content (n ≥ 3, p < 0.05). Whilst an in vivo limiting dilution assay, using SCID mice, demonstrated that ALM201 alone or in combination with tamoxifen was very effective at delaying tumour recurrence by 12 (p < 0.05) or 21 days (p < 0.001), respectively, by reducing the number of CSCs. The potential mechanism of action, in addition to CD44, involves downregulation of DLL4 and Notch4.
CONCLUSION: This study demonstrates, for the first time, the pre-clinical activity of novel systemic anti-cancer therapeutic peptides, ALM201 and AD-01, in the metastatic setting, and highlights their impact on endocrine therapy resistant CSCs; both areas of unmet clinical need.

After several years of discouraging results, immunotherapy finally becomes a powerful, clinically valid and approved treatment for numerous types of cancer. Immunotherapy involves treatment approaches that work in various ways; some boost the body's immune system while others help guide and direct the immune cells to attack cancer cells specifically. In this review article, we summarize the current cancer immunotherapy strategies; immune checkpoint blockade, adoptive cellular therapy, cancer vaccines, oncolytic viruses, and the monoclonal antibodies and discuss the recent progress and future trends of the combination therapies.

Objectives: There is no consensus regarding the surgical or immunosuppressive treatment of idiopathic granulomatous mastitis (IGM). This study aimed to introduce a clinical classification system for IGM that might facilitate its treatment and predict recurrence. Methods: We analyzed the management of 68 patients with IGM at (Princess Basma Teaching Hospital and King Abdulla University Hospital (1994-2016) to find out if distinct patterns of presentation exist according to the following parameters: presence of a painful or painless breast mass, local inflammation, abscess formation, communication to the skin, and extra-mammary manifestation. Results: We identified four distinct patterns of IGM: A: (13.23 %) A hard, painless breast mass. B: (52.94 %) A hard, painful breast mass with gross inflammation. C: (26.47 %) A breast abscess-like presentation. D: (7. 35 %) A subacute presentation with ulceration, sinus, or fistula formation. Erythema nodosum might complicate any of these patterns. Wide local excision in pattern A was curative with zero recurrence rate. The recurrence rates in patterns B and C were 22.20 % and 50.00 %. Patterns B, C, and D were treated by a combination of surgery and prednisolone. In keeping with this, recent literature is in favor of a wider use of immunosuppression especially in the presence of pus and extra-mammary findings. Conclusion: IGM could be classified into 4 distinct patterns according to the presenting signs and symptoms. These patterns correlated with treatment, recurrence rate, and the gross operative findings. This is the first step toward a classification for IGM. Multicenter and Meta-analysis studies are essential for a comprehensive prognostic classification. Treatment of IGM in any institution should be the responsibility of a multidisciplinary team.

Background: Globally, colorectal cancer (CRC) is ranked the third most common cancer among men and the second in women. The American Cancer Society recommends that starting from the age 50 years, both men and women should be screened for polyps and for early detection of CRC. In Jordan, CRC is the most common cancer among males and the second most common cancer among females. This study aims to assess the knowledge and practices of CRC early detection tests and the barriers and motivators of screening in Jordan. Methods: A semi-structured questionnaire and face-to-face interviews were conducted with 300 males and 300 females recruited using stratified clustered random sampling technique from four governorates in Jordan. The participants were aged 30 to 65 years, without a previous history of CRC. Descriptive and multivariate analyses were used to assess knowledge and practices of CRC early detection tests. Results: Overall, there were poor knowledge and practices of CRC early detection tests. Better knowledge and practices were significantly associated with previously consulting a doctor due to symptoms and worries from CRC, receiving a recommendation from a doctor to perform CRC testing, or having more knowledge about CRC signs and symptoms (p≤ 0.05). Conclusions: This study indicates that there is a need for raising awareness about CRC early detection tests in Jordan, especially among those aged 50 years and above, and those who have a family history of CRC. Additionally, it is important to educate and encourage physicians to recommend CRC screening to patients that are at higher risk of the disease.

Background: Breast cancer is the most common cancer affecting women worldwide. The purpose of this study was to generate an understanding of women’s perceptions of changes to their body image due to breast cancer treatment. Method: A phenomenological qualitative approach was taken and semi-structured interviews conducted with 20 women who underwent breast cancer treatment at a public hospital in Jordan. Results: Data were analyzed following Colaizzi’s methodology, yielding a core theme (“Broken things cannot be repaired”) and four subthemes: changes in physical wellbeing (“my body fall apart”), changes in emotional wellbeing (“broken heart”), changes in social wellbeing (“broken future”), and coping strategies (“repairing what has been broken”). Religion and family support were major factors helping the women cope with their condition. Conclusion: Nurses and other healthcare providers need to be aware of body image changes of women with breast cancer to initiate timely, and culturally sensitive nursing intervention and support. Therefore, nurses should support patients in finding their own sources of strength to facilitate their healing process.

PURPOSE: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated.
METHODS: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n = 7,022). Using age- and stage-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors.
RESULTS: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR = 1.37; 95% CI 1.10-1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR = 1.28; 95% CI 1.08-1.52, and HR = 1.26; 95% CI 1.04-1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS.
CONCLUSIONS: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients' survival.

The biologic and prognostic value of focal neuroendocrine differentiation (NED) in conventional prostate adenocarcinoma (PC) patients who undergo radical prostatectomy (RP) remains controversial. In this systematic review and meta-analysis, we assessed the association of focal NED in conventional PC with oncological outcomes after RP. A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on December 2018 to find relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We used a fixed-effect model to analyze the impact of focal NED in RP specimen on progression-free survival defined by biochemical recurrence (BCR). A total of 16 studies with the outcomes of disease progression and survival were eligible. No patient in these studies received androgen deprivation therapy prior to RP. Eleven studies found no significant correlation between focal NED and outcomes of interest, while five studies reported a significant association of focal NED assessed by immunohistochemical chromogranin A or serotonin staining with BCR or survival. Focal NED was associated with higher BCR rates after RP with a pooled HR of 1.39 (95% CI 1.07‒1.81) in five studies. No heterogeneity was reported in this analysis (I² = 21.7%,

The aim of this retrospective study was to analyze urinary bladder cancer cases that were diagnosed in Jordan University Hospital, Amman according to age, gender, grade and muscle invasion.There were 212(85.1%) male and 37(14.9%) female patients. Of them, 115(46.2%) patients were aged <65 years (range: 25-64 years), 128(51.4%) were aged 65-84 years, and 6(2.4%) were aged > 85 years. Analysis of transitional cell carcinoma cases revealed that 143(59.3%) of the cases were of low grade, while 98(40.7%) were of high grade. Of these cases, 199(82.6%) were superficial, whereas 42(17.4%) were muscle invasive at initial diagnosis. Of the high-grade tumour cases, 57 (58.2%) and 5(5.1%) were found in the age groups 65-84 and >84 years, respectively. Both the grade and the muscle-invasion status were not significantly associated with patient gender. Our study showed significant demographic changes in urinary bladder cancer in comparison to a previous study from northern Jordan.

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most important underlying causes for the development of hepatocellular carcinoma (HCC) worldwide. Determining the optimal approach for management of the viral infection and the HCC depends on the virus and the stage of the cancer. In patients with HCV-associated HCC, there are multiple reasons to first treat the HCC. Firstly, in case of a curable HCC, the urgency for HCC treatment is important to avoid progression during HCV treatment. Secondly, the presence of HCC itself appears to reduce the rates of sustained virological response (SVR) achieved with direct-acting antivirals (DAAs). And finally, the evidence does not support the concept of an increase in HCC recurrence due to DAAs, so a patient can safely be treated after HCC cure. For patients with very advanced HCC, the benefits of HCV therapy are questionable. In contrast, those who develop HCC in the setting of chronic HBV infection, treatment with nucleoside analogues (NAs) is recommended prior to treating HCC, to prevent further liver injury and reduce the risk for HCC recurrence. Ultimately, earlier diagnosis and treatment of HBV and HCV will hopefully reduce the incidence of HCC worldwide.

BACKGROUND AND AIM: Helicobacter pylori inhabits the gastric mucosa of humans and causes 89% of all gastric cancers. This is the first study of the seroprevalence, spatial distribution, and risk factors for H pylori in Jordan.
MATERIALS AND METHODS: This is a cross-sectional study of 460 healthy participants (aged between 15 and 81 years) proportionately sampled across each region of Jordan. Sera samples were tested for H pylori using Enzygnost
RESULTS: The results showed a high seroprevalence (88.6%; 95% confidence interval [CI]: 85.3-91.2) of H pylori in the study population. After adjusting for possible confounders, age, consumption of raw milk, and location of residence were significantly associated with seropositivity. Older participants aged 30-49 years had an 11% greater risk of seropositivity compared to participants aged 15-29 years. Participants who consume raw milk and dairy products have a 9% decreased risk in seropositivity (prevalence ratio = 0.92; 95% CI: 0.84-0.99) compared to those who do not consume these products.
CONCLUSION: This study reports a negative association between consumption of raw milk and seropositivity, and this is in line with several studies that report consumption of raw milk may be protective against H pylori. However, because of the risk of other serious pathogens associated with the consumption of raw dairy products, this study recommends pasteurization of raw milk. Future studies on the effect of fermented dairy products on H pylori colorization in gastric mucosa are recommended.

Lung cancer is the leading cause of cancer-related death. According to the American Cancer Society, there were an estimated 222,500 new cases of lung cancer and 155,870 deaths from lung cancer in the United States in 2017. Accurate localization in lung interventions is one of the keys to reducing the death rate from lung cancer. In this study, a total of 217 publications from 2006 to 2017 about designs of medical devices for localization in lung interventions were screened, shortlisted, and categorized by localization principle and reviewed for functionality. Each study was analyzed for engineering characteristics and clinical significance. Research regarding interventional imaging equipment, navigation systems, and surgical devices was reviewed, and both research prototypes and commercial products were discussed. Finally, the future directions and existing challenges were summarized, including real-time intra-procedure guidance, accuracy of localization, clinical application, clinical adoptability, and clinical regulatory issues.

BACKGROUND: Successful implementation of shared decision-making in clinical encounters is influenced by system, patient, and clinician factors that both facilitate and present barriers to patient-centered care. Little is known about which factors Jordanian physicians believe influence their ability to implement shared decision-making with cancer patients.
AIMS: To determine Jordanian physicians' perceived barriers and facilitators to patient participation in treatment decision-making.
SETTINGS AND DESIGN: A cross-sectional exploratory survey design was used in the study. A convenience sample of 86 Jordanian medical and radiation oncologists and surgeons was recruited.
MATERIALS AND METHODS: A valid measure of physicians' views of shared decision-making was slightly modified from its original English and used to collect data. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) for windows version 19.0 (SPSS, Inc., Chicago, IL, USA). Descriptive and inferential statistics were carried as appropriate.
RESULTS: Insufficient time to spend with the patient, patient expecting a certain treatment rather than a consultation, and the patient's family overriding the decision-making process were the most frequently reported barriers to patient participation in treatment decision-making. Physicians believed that patients trust in physicians and patient being accompanied at the consultation were important facilitators of patient participation in treatment decision-making.
CONCLUSIONS: Jordanian physicians perceive multiple barriers to patient participation in treatment decision-making. Patient-related difficulties (e.g., indecision), and system-related difficulties, in particular, patient's family influence on the decision-making process are more prevalent among Jordanian physicians compared to Western physicians.

Non-urothelial (NU) histologies represent less than 10% of bladder cancers, with squamous cell carcinoma (SCC) being the most common subtype (approximately 5%). Bladder SCCs are subdivided into Schistosoma-related or non-Schistosoma-related tumors, with the latter being the most frequent subtype in the western world. Typically, these patients have been excluded or under-represented in clinical trials and thus little is known about treatment efficacy in bladder SCC. To address this paucity of data, extrapolation from urothelial carcinoma (UC) trials can be performed but this approach has inherent limitations. In the era of precision medicine, efforts to characterize the genomic and molecular profiles of bladder tumors may yield evidence to support new targets for effective therapies. We reviewed the available data on biomarkers of bladder SCC and provide suggestions on how these may influence therapeutic testing and clinical trials in the future.

Introduction: Cranial meningiomas considered one of most frequently encountered primary intracranial tumors in our daily neurosurgical practice, represent about 36% of brain neoplasms.
Aim: In this cohort analysis, we investigated epidemiological features of brain meningiomas diagnosed at a single institution. Special highlighting has been dedicated to demographic features, foretelling radiological signs, and concomitant factors predictive of tumor atypia.
Material and Methods: This retrospective analysis was conducted by revising all medical registries of patients aged ≥18 years, with a diagnosis of brain meningioma treated at King Hussein Medical Center, patients were retrieved from the electronic hospital database during a 12-year period (2004 to 2015). Preoperative radiology reports were examined to confirm tumor site and size based on largest measured dimension. Level of resection was based on surgical operative reports and post-operative radiological imaging.
Results: A total of 665-patients operated for intracranial meningiomas were analyzed out of total 2047-patients operated for intracranial neoplasm during the same period. Demographic analysis showed; female to male ratio 2.4:1. Mean age 49.6-years. Average follow-up of 8.7 years. Tumor locations were classified as parasagittal (39.55%), convexity (27.52%), tentorial/ falx (6.17%), intraventricular (2.04%). Mean tumor size was 3,86 cm and tumor size was >4.5cm in (28. 07%) of cases. In this study we achieved gross total resection in (73.1%) of cases, subtotal resection in (22.6%). The majority of patients evolved favorably with respect to their neurological examination post-operatively, though a neurological deficit persisted in 64-cases and 16-cases developed a new neurological deficit. Ninety five cases developed recurrence during the observation period. Surgical mortality was reported in 11-cases in the immediate post-operative period and in 42-cases further cases during the observation period related to other causes.
Conclusion: Neurosurgery faces a large number of intracranial meningioma patients in daily practice. Because of its "benign" nature; the variability in management strategy, Neurosurgery is more and more challenged with the concern of intracranial meningioma treatment in the daily practice. Because of its "benign" nature; the variability in management strategy, research regarding the meningioma etiology and epidemiology has lagged behind that for more malignant intracranial neoplasms. These risk factors piloted a revitalization in the study of meningiomas.

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer.

Many food-derived phytochemicals and their derivatives represent a cornucopia of new anti-cancer compounds. Luteolin (3,4,5,7-tetrahydroxy flavone) is a flavonoid found in different plants such as vegetables, medicinal herbs, and fruits. It acts as an anticancer agent against various types of human malignancies such as lung, breast, glioblastoma, prostate, colon, and pancreatic cancers. It also blocks cancer development in vitro and in vivo by inhibition of proliferation of tumor cells, protection from carcinogenic stimuli, and activation of cell cycle arrest, and by inducing apoptosis through different signaling pathways. Luteolin can additionally reverse epithelial-mesenchymal transition (EMT) through a mechanism that involves cytoskeleton shrinkage, induction of the epithelial biomarker E-cadherin expression, and by down-regulation of the mesenchymal biomarkers N-cadherin, snail, and vimentin. Furthermore, luteolin increases levels of intracellular reactive oxygen species (ROS) by activation of lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells, and by activation of ER stress-associated proteins expressions, including phosphorylation of eIF2α, PERK, CHOP, ATF4, and cleaved-caspase 12. Accordingly, the present review article summarizes the progress of recent research on luteolin against several human cancers.

Dysregulation of epidermal growth factor receptor (EGFR)/human epidermal growth factor-2 (HER2) family is a hallmark of aggressive breast cancer. Small-molecule tyrosine kinase inhibitors are among the most effective cancer targeted treatments. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid lead from extra-virgin olive oil with documented anti-cancer activities via targeting mesenchymal epithelial transition factor (c-Met). Dysregulation of c-Met promotes aggressiveness to breast cancer-targeted therapies. Lapatinib (LP) is an FDA-approved dual EGFR/HER2 inhibitor for HER2-amplified breast cancer. HER2-Positive tumor cells can escape targeted therapies like LP effects by overexpressing c-Met. Combined OC-LP treatment is hypothesized to be mechanistically synergistic against HER2-overexpressing breast cancer. Combined sub-effective treatments of OC-LP resulted in synergistic anti-proliferative effects against the HER2-positive BT-474 and SK-BR-3 breast cancer cell lines, compared to OC or LP monotherapy. Antibody array and Western blot analysis showed that combined OC-LP treatment significantly inhibited EGFR, HER2, and c-Met receptor activation, as well as multiple downstream signaling proteins, compared to individual OC or LP treatment. OC-LP Combination significantly inhibited invasion and migration of breast cancer cells through reduced activation of focal adhesion kinase (FAK) and paxillin. Combined treatment of OC-10 mg/kg with LP-12.5 mg/kg suppressed more than 90% of BT-474 tumor cells growth in a nude mouse xenograft model, compared to individual OC or LP treatment. Activated c-Met, EGFR, HER2, and protein kinase B (AKT) were significantly suppressed in combination-treated mice tumors, compared to OC or LP monotherapy. This study reveals the OC future potential as combination therapy to sensitize HER2-overexpressing breast cancers and significantly reduce required doses of targeted HER family therapeutics.

BACKGROUND: Despite the recent progress in the development of anti-cancer drugs, the treatment of metastatic tumors is usually ineffective. The systemic inflammatory response performs key roles in different stages of the carcinogenesis process including metastasis. The high neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were found to be associated with poor survival rates in the majority of solid tumors. However, only a few studies were conducted to further investigate this association in patients with advanced gynecological cancers.
METHODS: Clinical data from 264 patients with FIGO stage III and IV gynecological (endometrial, ovarian and cervical) cancers treated at King Hussein Cancer Center (Amman-Jordan) from 2006 to 2012 were retrospectively reviewed. We examined the association between absolute neutrophil count (ANC), absolute monocyte count (AMC), MLR, PLR, and NLR with distant metastases, overall survival and event-free survival in gynecological cancers. For survival analysis, Receiver Operating Characteristic (ROC) curve analysis was operated to determine the optimal cutoff values.
RESULTS: Patients with high baseline NLR (≥4.1) had more baseline distant metastases than patients with low baseline NLR (< 4.1), (p-value 0.045). Patients with high baseline AMC (≥560) had more distant metastases in comparison to patients with low baseline AMC (< 560), (p-value 0.040). Furthermore, Patients with high baseline PLR (≥0.3) had more distant metastases in comparison to patients with low baseline PLR (< 0.3), (p-value 0.025). Additionally, patients with high baseline ANC (≥5700) had worse overall survival compared to the patients with low baseline ANC (< 5700), (p-value 0.015). Also, patients with high baseline AMC (≥490) had worse overall survival compared to the patients with low baseline AMC (< 490), (p-value 0.044).
CONCLUSION: Different hematologic markers obtained from a cheap test (CBC) could potentially be used to predict the presence of distant metastases thus used as prognostic indices in gynecological cancers.

Hereditary cancer disorders often provide an important window into novel mechanisms supporting tumor growth. Understanding these mechanisms thus represents a vital goal. Toward this goal, here we report a chemoproteomic map of fumarate, a covalent oncometabolite whose accumulation marks the genetic cancer syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). We applied a fumarate-competitive chemoproteomic probe in concert with LC-MS/MS to discover new cysteines sensitive to fumarate hydratase (FH) mutation in HLRCC cell models. Analysis of this dataset revealed an unexpected influence of local environment and pH on fumarate reactivity, and enabled the characterization of a novel FH-regulated cysteine residue that lies at a key protein-protein interface in the SWI-SNF tumor-suppressor complex. Our studies provide a powerful resource for understanding the covalent imprint of fumarate on the proteome and lay the foundation for future efforts to exploit this distinct aspect of oncometabolism for cancer diagnosis and therapy.

BACKGROUND: Indeterminate pulmonary nodules (IPNs) are common during initial evaluation of bladder cancer patients. Their significance is still unknown.
OBJECTIVE: Determine the significance of indeterminate pulmonary nodules, including their size and number, in muscle-invasive bladder cancer patients before definitive local therapy by surgery or chemo-radiotherapy.
DESIGN: Retrospective review, single-center descriptive study.
SETTINGS: A tertiary cancer center.
PATIENTS AND METHODS: We performed a retrospective review of patients who underwent definitive local therapy of bladder cancer by either radical cystectomy and lymph node dissection or with chemo-radiotherapy between January 1997 and December 2015. We identified patients with baseline CT scans done during staging work-up prior to definitive treatment. Patients with proven clinical metastasis at pre.sentation were excluded, while patients who had IPNs without features suggesting metastasis were included.
MAIN OUTCOME MEASURES: Disease-free survival and overall survival.
SAMPLE SIZE: 168 patients.
RESULTS: The median age of patients at diagnosis was 66 years; 92% were males and 56% were smokers. IPNs (3 cm or less) were present in 74 patients (44.0%). Median follow-up was 24 months. IPNs were associated with decreased disease-free survival while IPNs did not affect the overall survival (HR=1.9; 95% CI: 1.1-3.4); P=.01 and HR=1.5; 95% CI: 1.0-2.5); P=.07, respectively. In addition, nodules greater than 1 cm had reduced disease-free survival (HR=2.5; 95% CI: 1.1-5.9); P=.04. In the surgery group (n=126), the median number of lymph nodes excised was 14, with no association between lymph nodes status and the presence of IPNs (P=.08).
CONCLUSION: The presence of IPNs, especially nodules greater than 1 cm had a negative effect on disease-free survival. Tailored postoperative follow-up of these patients may impact disease outcomes.
LIMITATIONS: The retrospective nature, the lack of standardized preoperative imaging protocols, the lack of a central radiology review and the small number of patients.
CONFLICT OF INTEREST: None.

Screening mammography and evolving treatments have improved mortality over the last 25 years. However, breast cancer remains the second leading cause of cancer-related mortality for women in the United States. There are several contradictory recommendations regarding breast cancer screening. Familiarity with these recommendations will allow physicians to counsel their patients and ensure well-informed shared decision making.

AIM: To analyze the frozen section (FS) diagnostic accuracy in correlation with the final diagnosis of brain tumors.
MATERIAL AND METHODS: This retrospective study comprised all brain tumor cases with FS diagnosis and permanent section diagnosis in Jordan University Hospital from July 1, 2007 to December 31, 2017. Data were obtained by reviewing slides and reports from the histopathology archives. Statistical Package for the Social Science (SPSS) software v20 was used for analysis.
RESULTS: A total of 179 cases with frozen section and permanent section diagnoses were analyzed. Eighty-four (47%) patients were males and 95 (53%) females.The ages ranged from 1 to 85 years. Diagnostic accuracy of FS was 88.8%. Discrepancy was noted in 20 cases. Of the discrepancies, misclassification of tumor type was the most common category (12 cases, 60%), followed by grading mismatch (7 cases, 35%) and misdiagnosis of tumor versus non-tumor conditions (1 case, 5%). Patient age and gender were not significantly associated with the discrepancy between FS and final diagnosis.
CONCLUSION: Our results were comparable to international reports. However, more emphasis on diagnostic cytology in intraoperative consultation is required as an effective adjunct to frozen section to overcome limitations.

Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.