Aim: Brucea Javanica oil emulsion (BJOE) has already been commercialized to treat various malignancies. The authors verified BJOE for its therapeutic effects on rhabdomyosarcoma (R1) in rats using magnetic resonance imaging (MRI), microangiography and histopathology.

Methods: Rats were implanted with R1 in both flanks and subjected to intratumoral injections of BJOE or normal saline on day 0 and 7 for intra-individual comparisons. Therapeutic responses were compared between treated and control tumors at a 3.0 T MRI on day 0, 7 and 14 using T2-, T1-, and diffusion-weighted imaging that generated apparent diffusion coefficient (ADC) with b values of 0, 50, 100, 150, 400, 600, 800 and 1,000 s/mm². Volumes of necrotic and viable tumors were measured and verified with histopathology and tumor vascularity was quantified on microangiography.

Results: After BJOE administration, tumor growth slowed down with increased intratumoral necrosis (P < 0.05) and reducedtumoral blood flow (P < 0.05). ADC maps differentiated viable and necrotic tumor components. Microangiography and histopathology supported MRI findings.

Conclusion: Local BJOE injection created necrosis, reduced the growth and lowered vessel density in rat R1 tumors. MRI allowed monitoring tumor growth and quantifying therapeutic responses. As a non-invasive and contrast-agent-free technique, ADC maps helped distinguish the necrotic from viable tumor tissues.

Aim: Cetuximab was administered weekly in registration clinical trials. Biweekly administration is more convenient when combining cetuximab with biweekly chemotherapy in patients with metastatic colorectal cancer (mCRC). The aim of this study is to evaluate safety and efficacy of biweekly cetuximab at a dose of 500 mg/m² with chemotherapy in routine clinical practice.

Methods: Clinical data of 19 consecutive patients with K-RAS wild type mCRC who received biweekly cetuximab with biweekly fluropyrimidine based chemotherapy were reviewed. Toxicity assessment was limited to the first 6 cycles of treatment. Best tumor response was assessed by an independent radiologist.

Results: Median age was 59 (24-74) years. Cetuximab was administered in first, second and third line settings in 7, 9 and 3 patients respectively. Grade I/II cetuximab specific adverse events (AEs) were skin rash (47.3%), diarrhea (21%), infusion reactions (10.5%), Hypomagnesaemia (10.5%) and nail disorders (5%). Grade III AEs were skin rash (10.5%) and diarrhea (5.3%). There was no grade IV AEs. There were no complete responders. Partial response was achieved in 8 (42.1%) and stable disease in 6 (31.5%) patients.

Conclusion: This small but real life experience shows that biweekly cetuximab with chemotherapy is safe and effective. The frequency of AEs compares favorably to weekly administration reported in the literature. These finding add to the relatively limited available data on biweekly administration to support its adoption in routine clinical practice.

Schistosomiasis is one of the most prevalent neglected tropical diseases, remains a serious public health problem in many developing countries in the tropics and subtropics and its pathogenesis depends on the parasite-host interaction. Periportal fibrosis of schistosomiasis complicated by portal hypertension results from increased intrahepatic vascular resistance and blood flow through the portal venous system. This leads to portosystemic collateral variceal veins formation which dilates until they finally rupture and bleed due to progressive rising in the portal venous pressure. The clinical impact of esophagogastric varices is critical due to the rebleeding rate of esophageal varices remains high within two years after cessation of acute bleeding from medium or large varices. In the present review, we will discuss hepatosplenic schistosomiasis and oesophagogastric varices pathophysiology and review the current surgical outcomes of distal splenorenal shunt or liver transplantation in schistosomal refractory variceal bleeding.

This article aims to review the role of immunotherapy in tumors of the head and neck, focusing primarily on US Food and Drug Administration (FDA) approved checkpoint inhibitors in squamous cell histology. The data showing superiority of checkpoint inhibitors over cytotoxic chemotherapy that led to FDA approval of two agents (Keytruda^® Merck and Opdivo^® Bristol-Myers-Squibb) in the recurrent and metastatic setting will be reviewed in detail, as well as summaries of ongoing trials for checkpoint inhibitor and combination therapies in both the curative and metastatic settings. Upcoming positive data regarding immunotherapy use and other innovative immune based therapies in rare histologies such as nasopharyngeal carcinoma and salivary gland tumors will also be reviewed. Additionally, data regarding management of immunotherapy side effects will be discussed and a brief review of recently published guidelines will be provided. Lastly, we will address risks to special patient populations that need further study.

Plant-based nutrition has been shown to protect against the 15 leading causes of death in the world, including many cancers, and may offer benefits as a disease modifying tool to improve the management and treatment of these conditions. Results on the effects of plant-based nutrition on breast, prostate, colorectal and gastrointestinal cancers have been the most extensively studied, and thus have the most published supporting evidence thus far. Whole foods plant-based diets have shown to significantly protect against these cancers, as well as additional cancers and other chronic disease states. Nutritional interventions in the prevention of various cancers offer a significant benefit to currently used medical therapies, and should be employed more often as an adjunct to first-line medical therapy. Although the effects of diet are becoming more well-known and the role of diet and lifestyle factors in health and disease is gaining more attention and emphasis, the benefits or detriments are still underestimated and undervalued.

Aim: The aim of the study was to evaluate knowledge, awareness, and practice related to forensic odontology among dental surgeons in Bhubaneswar, East India.

Methods: A blind cross-sectional study, using a questionnaire with close-ended questions, was carried out. Interns were included to assess their knowledge and practice (related to dental record keeping) while in an institutional setting. In addition, dentists with Bachelor of Dental Surgery (BDS) and Master of Dental Surgery (MDS) qualifications (irrespective of their specialty) were assessed, which included purely private practitioners, purely academicians (dental surgeons teaching in dental colleges), and academicians-cum-practitioners.

Results: The total forensic odontology knowledge, awareness, and practice score (based on summing all the positive responses -- for all the relevant questions -- and calculating the percentage) was 80%, 76%, and 84% for the MDS, BDS, and intern group, respectively.

Conclusion: This study is the first of its kind to be undertaken in East India. The results show that there is an adequate level of knowledge and awareness regarding forensic odontology in all the groups investigated. Overall, the three groups also had adequate levels of good practice related to dental record keeping. However, regarding individual questions, there were some instances among the groups of inadequate levels of good practice.

Aim: Cetuximab was administered weekly in registration clinical trials. Biweekly administration is more convenient when combining cetuximab with biweekly chemotherapy in patients with metastatic colorectal cancer (mCRC). The aim of this study is to evaluate safety and efficacy of biweekly cetuximab at a dose of 500 mg/m² with chemotherapy in routine clinical practice.

Methods: Clinical data of 19 consecutive patients with K-RAS wild type mCRC who received biweekly cetuximab with biweekly fluropyrimidine based chemotherapy were reviewed. Toxicity assessment was limited to the first 6 cycles of treatment. Best tumor response was assessed by an independent radiologist.

Results: Median age was 59 (24-74) years. Cetuximab was administered in first, second and third line settings in 7, 9 and 3 patients respectively. Grade I/II cetuximab specific adverse events (AEs) were skin rash (47.3%), diarrhea (21%), infusion reactions (10.5%), Hypomagnesaemia (10.5%) and nail disorders (5%). Grade III AEs were skin rash (10.5%) and diarrhea (5.3%). There was no grade IV AEs. There were no complete responders. Partial response was achieved in 8 (42.1%) and stable disease in 6 (31.5%) patients.

Conclusion: This small but real life experience shows that biweekly cetuximab with chemotherapy is safe and effective. The frequency of AEs compares favorably to weekly administration reported in the literature. These finding add to the relatively limited available data on biweekly administration to support its adoption in routine clinical practice.

Aim: The aim of the study was to evaluate knowledge, awareness, and practice related to forensic odontology among dental surgeons in Bhubaneswar, East India.

Methods: A blind cross-sectional study, using a questionnaire with close-ended questions, was carried out. Interns were included to assess their knowledge and practice (related to dental record keeping) while in an institutional setting. In addition, dentists with Bachelor of Dental Surgery (BDS) and Master of Dental Surgery (MDS) qualifications (irrespective of their specialty) were assessed, which included purely private practitioners, purely academicians (dental surgeons teaching in dental colleges), and academicians-cum-practitioners.

Results: The total forensic odontology knowledge, awareness, and practice score (based on summing all the positive responses -- for all the relevant questions -- and calculating the percentage) was 80%, 76%, and 84% for the MDS, BDS, and intern group, respectively.

Conclusion: This study is the first of its kind to be undertaken in East India. The results show that there is an adequate level of knowledge and awareness regarding forensic odontology in all the groups investigated. Overall, the three groups also had adequate levels of good practice related to dental record keeping. However, regarding individual questions, there were some instances among the groups of inadequate levels of good practice.

Embryonic and larval Danio rerio (zebrafish) is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features high genetic homology to mammals, robust, phenotypes, high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN and TALEN make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies employing zebrafish as experimental model, comparing it with other in vivo and in vitro models, presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity and efficacy in order to facilitate more extensive, easy and comprehensive knowledge of new generation drugs.

Plant-based nutrition has been shown to protect against the 15 leading causes of death in the world, including many cancers, and may offer benefits as a disease modifying tool to improve the management and treatment of these conditions. Results on the effects of plant-based nutrition on breast, prostate, colorectal and gastrointestinal cancers have been the most extensively studied, and thus have the most published supporting evidence thus far. Whole foods plant-based diets have shown to significantly protect against these cancers, as well as additional cancers and other chronic disease states. Nutritional interventions in the prevention of various cancers offer a significant benefit to currently used medical therapies, and should be employed more often as an adjunct to first-line medical therapy. Although the effects of diet are becoming more well-known and the role of diet and lifestyle factors in health and disease is gaining more attention and emphasis, the benefits or detriments are still underestimated and undervalued.

Aim: Colorectal cancer (CRC) remains a disease with poor prognosis and limited overall 5-year survival rate, which highlights a clear clinical need for novel treatment strategies. The stromal cancer-associated fibroblasts (CAFs) strongly dictate the metastatic potential of CRC and hence warrant investigation for clinical outcome.

Methods: The authors established primary cultures of CAFs from metastatic CRC patients and performed cellular characterization using phase contrast microscopy and histological staining followed by light microscopy. The isolated CAFs were further explored for the molecular characterization of genes which promote the process of metastasis.

Results: The stromal CAFs maintain their fibroblastic phenotype in vitro and manifested high proliferation potential. To explore the gene expression profile, total RNA was isolated from the primary culture of CAFs and qualitative RT-PCR was performed. The cultured CAFs exhibited gene signatures associated with cancer stemness, epithelial to mesenchymal transition induction and inflammatory cytokines/chemokines favoring metastasis. These genes play a pivotal role in chemotherapy resistance and are also associated with poor prognosis in CRC.

Conclusion: This study further delineates the role of CAFs as a part of the “corrupted” stromal cells within the tumor microenvironment in establishing and orchestrating the metastatic fate of CRC. The gene expression profile clearly indicates that CAFs represent a potential target for improved therapy of CRC.

Managing advanced non-small cell lung cancer has become far more complex than in the past. This in part is due to the fact that advances in molecular oncology allow for far more refined and effective treatment options for many lung cancer patients. One of the first advances was the identification of various biomarkers that are increasingly being tested for, even as a broad panel, that include some targets that we have been hearing about for a few years and others that are still emerging. Some of the most common biomarkers include epidermal growth factor receptor (EGFR) as well as anaplastic lymphoma kinase (ALK). Also, despite the fact that we have known about Kirsten rat sarcoma for decades, therapies targeting this molecule has been more elusive. In addition, other potentially useful therapeutic targets are constantly emerging and incorporated in the National Comprehensive Cancer Network guidelines. Several of these have phase 2 (or beyond) data that have been compelling enough to lead to them being considered beyond EGFR, ALK, and c-ros oncogene 1. Emerging clinical trial data for patients with EGFR-sensitizing mutations and ALK rearrangements, showed that tyrosine kinase inhibitors offer superior progression free survival and response rates over standard chemotherapy.

Embryonic and larval Danio rerio (zebrafish) is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features high genetic homology to mammals, robust, phenotypes, high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN and TALEN make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies employing zebrafish as experimental model, comparing it with other in vivo and in vitro models, presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity and efficacy in order to facilitate more extensive, easy and comprehensive knowledge of new generation drugs.

Plant-based nutrition has been shown to protect against the 15 leading causes of death in the world, including many cancers, and may offer benefits as a disease modifying tool to improve the management and treatment of these conditions. Results on the effects of plant-based nutrition on breast, prostate, colorectal and gastrointestinal cancers have been the most extensively studied, and thus have the most published supporting evidence thus far. Whole foods plant-based diets have shown to significantly protect against these cancers, as well as additional cancers and other chronic disease states. Nutritional interventions in the prevention of various cancers offer a significant benefit to currently used medical therapies, and should be employed more often as an adjunct to first-line medical therapy. Although the effects of diet are becoming more well-known and the role of diet and lifestyle factors in health and disease is gaining more attention and emphasis, the benefits or detriments are still underestimated and undervalued.

Aim: The hypothesis is that the production of leukocyte and platelet-rich fibrin (L-PRF) is easy in horses without modifying human protocol, thus allowing better standardization of human protocol. In this study, the aim is to standardize the production of L-PRF in horses to direct it to human production.

Methods: The authors took 9 mL of blood from the jugular vein of 6 horses to produce L-PRF membranes at a temperature > 21 °C by measuring the size of the membranes (height, length, thickness, weight, surface) and clot. Therefore we analyzed their microbiological characteristics.

Results: The production of leukocyte and platelet-rich fibrin (L-PRF) is easy in horses without modifying human protocol, thus allowing better standardization of human protocol. The parameters found in the horse are clearly similar to the parameters found in humans. In optical microscopy, most of the cellular bodies were found and concentrated in the proximal portion of each membrane, with the last 1/4 observed in the center; the distal part only had residual traces of cellular bodies. The L-PRF is composed constantly when the production process below described is strictly respected. The success of L-PRF depends entirely on blood collection, on the quick transfer to a centrifuge (within 1 min) and on centrifugation and squeezing temperatures (between 21 and 30 °C) of the clot.

Conclusion: The experiments on horses for the standardization of L-PRF production will improve our understanding about wound healing, particularly in the regenerative therapy of chronic skin lesions in humans. The data collected show that the best preparation method is the 2 min compression of the clot after 0 min of blood sampling, using the 9 mL vacutainer system and not a 9 mL syringe.

Aim: The low bioavailability of curcumin, a polyphenol, limits its use as an antitumor agent. Identifying mechanisms to improve the bioavailability and effectiveness of curcumin can modify utilization of other plant-derived phenolic compounds. This study was conducted with an aim to determine the influence of some flavonoids on the effects of curcumin in an HL-60 cell line.

Methods: Cells were incubated in the presence of different concentrations of curcumin and several flavonoids for 20 h. Cytotoxicity was evaluated using propidium iodide staining. The evaluation of γH2AX expression using a specific antibody, together with study of the cell cycle, was analyzed using flow cytometry.

Results: A synergistic effect was obtained only using a combination of curcumin and lower concentrations of epicatechin. The low concentration of quercetin exerted an additive effect only in combination with curcumin. Moreover, incubation with curcumin and epicatechin resulted in a significant increase in the γH2AX level.

Conclusion: Combination treatment with epicatechin and curcumin can potentially be considered for improving the effectiveness and bioavailability of curcumin in cell lines of myeloid leukemia.

Aim: Oral fluid represents a mirror of the body and saliva has the potential to be used in the detection and diagnosis of diseases. The present study aimed to investigate the potential of salivary carbonic anhydrase (CA), salivary pH and phosphate buffer concentration as biomarkers of dental caries in children saliva.

Methods: The study included 120 children of 3-5 years and 13-15 years of age group. Each age group was divided into two subgroups according to risk of dental caries: low and high caries risk groups. Two saliva samples, stimulated and non-stimulated, were collected from each child in all groups and were analyzed for CA, phosphate buffer concentration as well as pH values.

Results: The investigations found significantly higher CA level in saliva samples of low dental caries risk groups children compared to high caries risk groups. Saliva samples from children with low dental caries risk showed significantly higher phosphate buffer concentrations as well as higher pH levels compared to saliva samples from children in high dental caries risk groups.

Conclusion: The results suggest that salivary CA, phosphate buffer concentration and pH values represent potential biomarkers for the estimation of dental caries risk incidence in children, however, further studies with more patients’ samples are recommended to confirm the results.

Opioid consumption in the United States is the highest of all nations, with 42,000 people dying from opioid overdose in 2016. Patients with breast cancer undergoing curative-intent surgery are particularly vulnerable to developing persistent opioid use. It is anticipated that postoperatively nearly all of these women will receive prescription pain medication and that 20%-50% of patients will go on to develop acute and chronic pain after breast cancer surgery. In this review, we aim to better understand opioid use and ongoing efforts to reduce opioid abuse in breast cancer surgery patients.

This article aims to review the role of immunotherapy in tumors of the head and neck, focusing primarily on US Food and Drug Administration (FDA) approved checkpoint inhibitors in squamous cell histology. The data showing superiority of checkpoint inhibitors over cytotoxic chemotherapy that led to FDA approval of two agents (Keytruda^® Merck and Opdivo^® Bristol-Myers-Squibb) in the recurrent and metastatic setting will be reviewed in detail, as well as summaries of ongoing trials for checkpoint inhibitor and combination therapies in both the curative and metastatic settings. Upcoming positive data regarding immunotherapy use and other innovative immune based therapies in rare histologies such as nasopharyngeal carcinoma and salivary gland tumors will also be reviewed. Additionally, data regarding management of immunotherapy side effects will be discussed and a brief review of recently published guidelines will be provided. Lastly, we will address risks to special patient populations that need further study.

Colon cancer is still one of the most common neoplasias every year, although screening strategies have reduced its incidence. Unfortunately, the median survival in metastatic cases, not candidates to surgery, remains less than 3 years, far away from the expectations. A few years back, new agents were introduced in its armamentarium. Bevacizumab and cetuximab created hopes then. However, systemic options have not evolved as quickly as expected and fluorouracil-based chemotherapy is still the standard. Moreover patients stop responding at some point due to resistance to these agents and disease progression after two lines of treatment entails a short survival. However, some patients are still able to receive further treatment and thus, new agents are urgently needed. The appearance of immunotherapies has opened a hopeful new therapeutic approach. These treatments alter the immune system and although these have shown efficacy in multiple cancers, colon is not one of them. However, emerging data show that there are some patients who may benefit. This article will review published and ongoing clinical trials of immunotherapy in colon cancer.

Aim: To evaluate the association between local-regional treatment strategies on overall survival (OS), we compared elderly patients with ductal carcinoma in situ (DCIS) who underwent lumpectomy alone vs. lumpectomy + radiation or mastectomy.

Methods: Patients ≥ 70 years in the National Cancer Data Base (2004-2015) with DCIS who underwent lumpectomy or mastectomy were selected. Kaplan-Meier curves were used to visualize the unadjusted OS. A Cox proportional hazards model was used to estimate the effect of local-regional treatment on OS after adjustment. Separate subgroup analyses were conducted for grade 1, estrogen receptor positive (ER+), and low-volume (< 3 cm) disease.

Results: 18,451 patients met inclusion criteria (n = 13,284 lumpectomy + radiation or mastectomy; n = 5,167 lumpectomy alone). The unadjusted 10-year OS was 54% for the entire cohort. After adjustment, patients who underwent lumpectomy + radiation or mastectomy had a slightly improved OS (vs. lumpectomy alone; HR = 0.841, 95%CI: 0.774-0.914). For patients with grade 1 disease, lumpectomy + radiation or mastectomy was not associated with an improved OS (P = 0.12). For patients with ER+ disease, (lumpectomy + radiation or mastectomy) + endocrine therapy yielded the most significant improvement in OS (HR = 0.669, 95%CI: 0.598-0.748). Among patients with low-volume disease, lumpectomy + radiation or mastectomy was associated with an improved OS (HR = 0.812, 95%CI: 0.725-0.91).

Conclusion: Our data suggest that chronologic age alone should not preclude a patient from receiving standard therapy for DCIS, while patient fitness, competing comorbidities, and patient preferences are critical factors to consider in light of potentially limited benefits of treatment. In favorable cancer diagnoses such as DCIS, thoughtful omission of standard therapy may be considered.

Aim: To assess for factors contributing to the total delay in care, and specifically the behavioral delay-interval portion of that delay, experienced by a group of symptomatic breast cancer patients.

Methods: This retrospective cohort pilot study included 24 females greater than 40 years-old with symptomatic breast cancer at time of diagnosis (including palpable mass, breast pain, other pain, discharge, nipple inversion). Participants were asked demographic information, as well as to identify, from a predefined list of options, the three most relevant causes for their delayed breast cancer diagnosis. Data sources included electronic medical record query and phone surveys.

Results: Overall, 21/24 of our study’s participants identified at least one of our predetermined barriers to care as relevant to their cause for delay. The most commonly identified reasons for delay were health system utilization factors contributing to behavioral delay, including dependents/pressing matters, employment responsibilities, transportation costs and difficulty, fear of being judged by healthcare workers, and fear of not being able to afford treatment.

Conclusion: Women with breast cancer can experience delays to eventual diagnosis and treatment during various timeintervals between first noticing a symptom and finally presenting to medical attention. This study provides evidence that one such possible interval is the behavioral delay interval. Health system utilization factors, psychological factors, demographic factors and help-seeking habits can contribute to an increased behavioral delay interval. Further research is warranted to address these factors and minimize their impact on patient care delivery.

There is emerging evidence that endogenous microvesicles released by platelets may play a pivotal role in pathogenesis of numerous diseases including stable and unstable ischemic heart disease, atherosclerosis, hypertension, idiopathic pulmonary hypertension, atrial fibrillation/flutter, acute and chronic heart failure, as well as systemic vasculitis, systemic lupus erythematosus, antiphospholipid syndrome, transplant rejection, diabetes-induced angiopathy. Microvesicles that leased from the platelets exist as cargo for a large of number biological-active molecules including regulatory peptides, hormones, growth factors, active molecules coordinating cell-to-cell cooperation. Moreover, platelet-derived microvesicles are concerned about a conspicuous component in regulating angiogenesis, cardiac protection, and vascular repair. Recent animal and clinical studies have shown that the number of circulating platelet-derived microvesicles may sufficiently increase in accelerating atherosclerosis, acute atherothrombotic events, i.e., recurrent ischemia, myocardial infarction, thrombosis, hypertension, and stroke, microvascular inflammation. It is suggested that exaggerating levels of circulating platelet-derived microvesicles is strongly associated with endothelial dysfunction. The review is discussed the role of platelet-derived vesicles in the pathogenesis of the cardiovascular disease, as well as diagnostic and predictive capabilities of platelet-derived vesicles as biomarkers of a natural evolution of the diseases.

Lymphedema is a chronic and morbid complication that can result from breast cancer treatment involving surgery and/or radiation therapy. Breast cancer related lymphedema (BCRL) can result in functional and psychological problems that can affect a patient’s quality of life. Lymphedema is a pathologic condition of the lymphatic system in which protein-containing fluid accumulates in the interstitial tissue leading to tissue inflammation, fibrosis, and adipose hypertrophy. Clinical manifestations of lymphedema include swelling, induration, skin changes, and decreased functionality of the affected limb. A common risk factor associated with BCRL is the management of the axilla. Advances in research have shown sentinel lymph biopsy to be equally effective as axillary lymph node dissection in staging the axilla, in appropriate cases. In addition, with breast-conserving therapy it has been shown that radiation therapy also increases the risk of BCRL. Overall, approximately 1 in 6 women treated for breast cancer will develop lymphedema within months to years after diagnosis and treatment. Lymphedema is a progressive disease with a subclinical phase that can last for years before becoming clinically evident. While management of breast cancer has improved, it is important that we develop a coordinated and standardized approach to better diagnose, assess, and manage BCRL. This includes patient education, a thorough physical examination, access to confirmatory testing when necessary, a conservative multimodality treatment plan that includes compression and decongestive therapy, and being able to offer operative management when conservative management is ineffective.