Journal of Oncology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer Sun, 08 May 2016 07:03:30 +0000 Researchers have made considerable progress in last few decades in understanding mechanisms underlying pathogenesis of breast cancer, its phenotypes, its molecular and genetic changes, its physiology, and its prognosis. This has allowed us to identify specific targets and design appropriate chemical entities for effective treatment of most breast cancer phenotypes, resulting in increased patient survivability. Unfortunately, these strategies have been largely ineffective in the treatment of triple negative breast cancer (TNBC). Hormonal receptors lacking render the conventional breast cancer drugs redundant, forcing scientists to identify novel targets for treatment of TNBC. Two natural compounds, curcumin and resveratrol, have been widely reported to have anticancer properties. In vitro and in vivo studies show promising results, though their effectiveness in clinical settings has been less than satisfactory, owing to their feeble pharmacokinetics. Here we discuss these naturally occurring compounds, their mechanism as anticancer agents, their shortcomings in translational research, and possible methodology to improve their pharmacokinetics/pharmacodynamics with advanced drug delivery systems. Amol Shindikar, Akshita Singh, Malcolm Nobre, and Saurabh Kirolikar Copyright © 2016 Amol Shindikar et al. All rights reserved. Excisional Treatment of Cervical Dysplasia in Australia 2004–2013: A Population-Based Study Sat, 30 Apr 2016 13:35:41 +0000 Background. Excisional treatment of preinvasive cervical dysplasia has been associated with adverse pregnancy outcomes. We aimed to examine trends in the rate of excisional treatment in reproductive age women in the era of HPV vaccination. Methods. National data for Australia regarding histological diagnoses of cervical dysplasia and excisional treatment for the period from 2004 to 2013 inclusive were obtained from two datasets and used to calculate age-stratified incidence rates of excisional treatment and of excisional treatments per diagnosis of dysplasia. Results. The incidence of low-grade squamous dysplasia fell in all age groups, while the incidence of high-grade dysplasia fell in the 20-to-24-year group but rose slightly for older age groups. The rate of excisional treatment fell in women aged under 35 but there was no significant change for women 35 years or older. The rate of all excisional treatments (loop excision + cone biopsy) per high-grade diagnosis (CIN2 + CIN3 + adenocarcinoma in situ) fell across all three age-bands in both datasets. Conclusion. To ensure that the use of excisional treatment is appropriate, with lower rates for younger HPV-vaccinated women, close surveillance, audit, and ongoing education will be required. Gregory Robertson and Stephen J. Robson Copyright © 2016 Gregory Robertson and Stephen J. Robson. All rights reserved. Moving beyond Karnofsky and ECOG Performance Status Assessments with New Technologies Tue, 15 Mar 2016 16:47:34 +0000 Progress in cancer research is coupled with increased treatment complexity reliant upon accurate patient selection. Oncologists rely upon measurement instruments of functional performance such as the Karnofsky or Eastern Cooperative Oncology Group Performance Status scales that were developed over fifty years ago to determine a patient’s suitability for systemic treatment. These standard assessment tools have been shown to correlate with response to chemotherapy, chemotherapy tolerability, survival, and quality of life of cancer patients. However, these scales are subjective, subject to bias and high interobserver variability. Despite these limitations important clinical decisions are based on PS including eligibility for clinical trials, the “optimal” therapeutic approach in routine practice, and the allocation of healthcare resources. This paper reviews the past, present, and potential future of functional performance status assessment in an oncology setting. The potential ability of electronic activity monitoring systems to provide an objective, accurate measurement of patient functional performance is explored. Electronic activity monitoring devices have the potential to offer positive health-related opportunities to patients; however their introduction to the healthcare setting is not without difficulty. The potential role of this technology in healthcare and the challenges that these new innovations pose to the healthcare industry are also examined. Ciara M. Kelly and Armin Shahrokni Copyright © 2016 Ciara M. Kelly and Armin Shahrokni. All rights reserved. Correlation of Beta-2 Adrenergic Receptor Expression in Tumor-Free Surgical Margin and at the Invasive Front of Oral Squamous Cell Carcinoma Wed, 02 Mar 2016 06:34:26 +0000 Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and is correlated with a wide spectrum of tumor cell mechanisms including proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives. The present study aimed to analyze the expression of the beta-2 adrenergic receptor (β2-AR) in tumor-free surgical margins of oral squamous cell carcinomas (OSCC) and at the invasive front. Sixty-two patients diagnosed with OSCC, confirmed by biopsy, were selected for the study. The clinicopathological data and clinical follow-up were obtained from medical records and their association with β2-AR expression was verified by the chi-square test or Fischer’s exact test. To verify the correlation of β2-AR expression in tumor-free surgical margins and at the invasive front of OSCCs, Pearson’s correlation coefficient test was applied. Results. The expression of β2-AR presented a statistically significant correlation between the tumor-free surgical margins and the invasive front of OSCC (; ). The immunohistochemical distribution of β2-AR at the invasive front of OSCC was also statistically significant associated with alcohol (), simultaneous alcohol and tobacco consumption (), and T stage (). Conclusions. The correlation of β2-AR expression in OSCC and tumor-free surgical margins suggests a role of this receptor in tumor progression and its expression in normal oral epithelium seems to be constitutive. Denise Tostes Oliveira, Diego Mauricio Bravo-Calderón, Gustavo Amaral Lauand, Agnes Assao, José-Manuel Suárez-Peñaranda, Mario Pérez-Sayáns, Abel García-García, Aparecido Nilceu Marana, Suely Nonogaki, José Roberto Pereira Lauris, and Luiz Paulo Kowalski Copyright © 2016 Denise Tostes Oliveira et al. All rights reserved. TIMP-1 as well as Microvessel Invasion and High Nuclear Grade Is a Significant Determinant Factor for Extension of Tumor Diameter in Localized RCC Thu, 25 Feb 2016 12:44:46 +0000 Objectives. To clarify what kind of pathological factor is necessary for the extension of tumor diameter in localized RCC, we studied localized RCC patients. Methods. We retrospectively reviewed medical records of 237 RCC patients in our institute who underwent nephrectomy. We performed immune histological analysis of MMP-2, MMP-9, TIMP-1, TIMP-2, and MT-MMP-1 for all samples. Results. Among the clinicopathological factors, multivariate analysis revealed nuclear grade; TIMP-2 and MT-MMP-1 were independent prognostic factors of localized RCC (risk ratio 1.50, , risk ratio 1.12, , and risk ratio 1.84, , resp.). By the multiple logistic regression analysis among pT1a versus pT1b, TIMP-1 was an independent factor (risk ratio 3.30, ) whereas all pT1 versus pT2a and all pT1 + pT2a versus pT2b high nuclear grade (risk ratio 5.15, ) and Micro vessel invasion (MVI, risk ratio 3.08, ) were independent factors. For all pT1 + pT2a versus pT2b, nuclear grade (risk ratio 3.39, ) and MVI (risk ratio 2.91, ) were independent factors. Conclusion. Higher expression of TIMP-1 is necessary for advancement tumor diameter from pT1a to pT1b, and a process of tumor diameter extension beyond pT1 and pT2a category needs presence of MVI and high nuclear grade. Nozomu Kawata, Kenya Yamaguchi, Tomohiro Igarashi, and Satoru Takahashi Copyright © 2016 Nozomu Kawata et al. All rights reserved. Enchondroma versus Chondrosarcoma in Long Bones of Appendicular Skeleton: Clinical and Radiological Criteria—A Follow-Up Tue, 23 Feb 2016 12:27:45 +0000 As of today two types of cartilage tumors remain a challenge even for the orthopedic oncologist: enchondroma (E), a benign tumor, and chondrosarcoma (LGC), a malignant and low aggressiveness tumor. A prospective study of 133 patients with a cartilaginous tumor of low aggressiveness in the long bones of the appendicular skeleton was done to prove this difficult differential diagnosis. Parameters including medical history and radiological and nuclear imaging were collected and compared to the result of the biopsy. A scale of aggressiveness was applied to each patient according to the number of aggressiveness episodes present. A comparison of the results of the biopsy with the initial diagnosis made by the orthopedic oncologist based solely on clinical data and imaging tests was also made. Finally, a management algorithm for these cases was proposed. A statistical significance for LGC resulted from the parameter as follows: pain on palpation, involvement of cortical in either the CT or MRI, and Tc99 bone scan uptake equal or superior to anterosuperior iliac crest. In our series, a tumor scoring 5 points or higher in the scale of aggressiveness can have 50% more chance of being LGC. When compared with the gold standard (the biopsy), surgeon’s initial judgement showed a sensitivity of 73.5% and a specificity of 94.1%. Eugenio M. Ferrer-Santacreu, Eduardo J. Ortiz-Cruz, Mariana Díaz-Almirón, and Jose Juan Pozo Kreilinger Copyright © 2016 Eugenio M. Ferrer-Santacreu et al. All rights reserved. The Oncogenic Functions of Nicotinic Acetylcholine Receptors Sun, 14 Feb 2016 09:28:13 +0000 Nicotinic acetylcholine receptors (nAChRs) are ion channels that are expressed in the cell membrane of all mammalian cells, including cancer cells. Recent findings suggest that nAChRs not only mediate nicotine addiction in the brain but also contribute to the development and progression of cancers directly induced by nicotine and its derived carcinogenic nitrosamines whereas deregulation of the nAChRs is observed in many cancers, and genome-wide association studies (GWAS) indicate that SNPs nAChRs associate with risks of lung cancers and nicotine addiction. Emerging evidences suggest nAChRs are posited at the central regulatory loops of numerous cell growth and prosurvival signal pathways and also mediate the synthesis and release of stimulatory and inhibitory neurotransmitters induced by their agonists. Thus nAChRs mediated cell signaling plays an important role in stimulating the growth and angiogenic and neurogenic factors and mediating oncogenic signal transduction during cancer development in a cell type specific manner. In this review, we provide an integrated view of nAChRs signaling in cancer, heightening on the oncogenic properties of nAChRs that may be targeted for cancer treatment. Yue Zhao Copyright © 2016 Yue Zhao. All rights reserved. Recombinant Human Thyroid Stimulating Hormone versus Thyroid Hormone Withdrawal for Radioactive Iodine Treatment of Differentiated Thyroid Cancer with Nodal Metastatic Disease Tue, 09 Feb 2016 12:55:04 +0000 Introduction. Recombinant human thyroid stimulating hormone (rhTSH) is approved for preparation of thyroid remnant ablation with radioactive iodine (RAI) in low risk patients with well differentiated thyroid cancer (DTC). We studied the safety and efficacy of rhTSH preparation for RAI treatment of thyroid cancer patients with nodal metastatic disease. Methods. A retrospective analysis was performed on 108 patients with histopathologically confirmed nodal metastatic DTC, treated with initial RAI between January 1, 2000, and December 31, 2007. Within this selected group, 31 and 42 patients were prepared for initial and all subsequent RAI treatments by either thyroid hormone withdrawal (THW) or rhTSH protocols and were followed up for at least 3 years. Results. The response to initial treatment, classified as excellent, acceptable, or incomplete, was not different between the rhTSH group (57%, 21%, and 21%, resp.) and the THW group (39%, 13%, and 48%, resp.; ). There was no significant difference in the final clinical outcome between the groups. The rhTSH group received significantly fewer additional doses of RAI than the THW group (). Conclusion. In patients with nodal-positive DTC, preparation for RAI with rhTSH is a safe and efficacious alternative to THW protocol. Robert M. Wolfson, Irina Rachinsky, Deric Morrison, Al Driedger, Tamara Spaic, and Stan H. M. Van Uum Copyright © 2016 Robert M. Wolfson et al. All rights reserved. Does the Degree of Hepatocellular Carcinoma Tumor Necrosis following Transarterial Chemoembolization Impact Patient Survival? Tue, 02 Feb 2016 13:39:00 +0000 Purpose. The association between transarterial chemoembolization- (TACE-) induced HCC tumor necrosis measured by the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and patient survival is poorly defined. We hypothesize that survival will be superior in HCC patients with increased TACE-induced tumor necrosis. Materials and Methods. TACE interventions were retrospectively reviewed. Tumor response was quantified via dichotomized (responders and nonresponders) and the four defined mRECIST categories. Results. Median survival following TACE was significantly greater in responders compared to nonresponders (20.8 months versus 14.9 months, ). Survival outcomes also significantly varied among the four mRECIST categories (): complete, 21.4 months; partial, 20.8; stable, 16.8; and progressive, 7.73. Only progressive disease demonstrated significantly worse survival when compared to complete response. Multivariable analysis showed that progressive disease, increasing total tumor diameter, and non-Child-Pugh class A were independent predictors of post-TACE mortality. Conclusions. Both dichotomized (responders and nonresponders) and the four defined mRECIST responses to TACE in patients with HCC were predictive of survival. The main driver of the survival analysis was poor survival in the progressive disease group. Surprisingly, there was small nonsignificant survival benefit between complete, partial, and stable disease groups. These findings may inform HCC treatment decisions following first TACE. Nathan Haywood, Kyle Gennaro, John Obert, Paul F. Sauer Jr., David T. Redden, Jessica Zarzour, J. Kevin Smith, David Bolus, Souheil Saddekni, Ahmed Kamel Abdel Aal, Stephen Gray, Jared White, Devin E. Eckhoff, and Derek A. DuBay Copyright © 2016 Nathan Haywood et al. All rights reserved. Small Cell Carcinoma of the Gallbladder: Case Report and Comprehensive Analysis of Published Cases Mon, 28 Dec 2015 11:22:01 +0000 Background. Gallbladder small cell carcinoma is a rare and highly aggressive malignancy with no established standard of care treatment. We described here a case report of small cell gallbladder cancer and we then performed a comprehensive review of 72 case reports of this disease. Methods. Published case reports of small cell carcinoma of the gallbladder between 1983 and 2014 were reviewed. Treatment modalities and survival were analyzed for metastatic and localized disease. Results. Median overall survival for all patients was 13 months. Metastatic disease was identified in 72% of cases. Treatment of metastatic disease with chemotherapy showed a significant survival benefit () compared to no chemotherapy, and the use of platinum doublet with etoposide showed a nonsignificant 4-month improvement in survival compared to other chemotherapy regimens (). Adjuvant therapy did not demonstrate an improvement of median overall survival in local disease (). Conclusion. Given the limited available data, systemic therapy with platinum and etoposide should be considered for patients with metastatic small cell carcinoma of the gallbladder. Adjuvant chemoradiation or chemotherapy for treatment of local disease warrants further investigation. Carolyn Carrera, Paul Kunk, and Osama Rahma Copyright © 2015 Carolyn Carrera et al. All rights reserved. Adjuvant Iodine131 Lipiodol after Resection of Hepatocellular Carcinoma Wed, 02 Dec 2015 12:17:33 +0000 Background. Survival after liver resection for HCC is compromised by a high rate of intrahepatic recurrence. Adjuvant treatment with a single, postoperative dose of intra-arterial I131 lipiodol has shown promise, as a means of prolonging disease-free survival (DFS). Methodology. DFS and overall survival (OS) after a single dose of postoperative I131 lipiodol were compared to liver resection alone, for treatment of hepatocellular carcinoma (HCC). Data were collected retrospectively for patients who had a curative resection for HCC between December 1993 and September 2011. Seventy-two patients were given I131 lipiodol after surgery and 70 patients had surgery alone. Results. The DFS at 1, 3, and 5 years was 72%, 43%, and 26% in the surgery group and 70%, 39%, and 29% in the adjuvant I131 lipiodol group . The 1-, 3-, and 5-year OS was 83%, 64%, and 52% in the surgery group and 96%, 72%, and 61% in the adjuvant I131 lipiodol group . Conclusion. This retrospective study has found no significant benefit to survival, after adjuvant treatment with I131 lipiodol. Ruelan V. Furtado, Leo Ha, Stephen Clarke, and Charbel Sandroussi Copyright © 2015 Ruelan V. Furtado et al. All rights reserved. Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection Thu, 19 Nov 2015 13:03:30 +0000 Background. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection. Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed. Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31–85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60–100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively. Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate. Franziska M. Ippen, Anand Mahadevan, Eric T. Wong, Erik J. Uhlmann, Soma Sengupta, and Ekkehard M. Kasper Copyright © 2015 Franziska M. Ippen et al. All rights reserved. Stereotactic Ablative Radiotherapy for the Treatment of Clinically Localized Renal Cell Carcinoma Wed, 11 Nov 2015 08:57:26 +0000 Thermal ablation is currently the most studied treatment option for medically inoperable patients with clinically localized renal cell carcinoma (RCC). Recent evidence suggests that stereotactic ablative radiotherapy (SABR) may offer an effective noninvasive alternative for these patients. In this review, we explore the current literature on SABR for the primary treatment of RCC and make recommendations for future studies so that an accurate comparison between SABR and other ablative therapies may be conducted. Scott P. Campbell, Daniel Y. Song, Phillip M. Pierorazio, Mohamad E. Allaf, and Michael A. Gorin Copyright © 2015 Scott P. Campbell et al. All rights reserved. CT Findings of Patients Treated with Irreversible Electroporation for Locally Advanced Pancreatic Cancer Thu, 05 Nov 2015 06:53:57 +0000 Introduction. In patients with locally advanced pancreatic cancer (LAPC), IRE has been shown to be safe for local disease control and palliation. As IRE continues to gain acceptance it is important to characterize the expected imaging findings. Materials and Methods. A review of our prospective soft tissue ablation registry from July 2010 to June 2013 was performed on patients who had undergone IRE for LAPC. Five masses treated with intraoperative IRE ablation for pancreatic tumors that underwent CT imaging before and after ablation were reviewed. Results and Discussion. Following IRE, the postablation bed is larger than the original ablated tumor. This ablation zone may get smaller in size (due to decreased edema and hyperemia) in the following months and more importantly remains stable provided there is no recurrence. In cases of recurrent disease there is increased size of the ablation bed, mass effect, and new or worsening vascular encasement or occlusion. Conclusion. CT imaging remains the best current imaging modality to assess post-IRE ablation changes. Serial imaging over at least 2–6 months must be employed to detect recurrence by comparing with prior studies in conjunction with clinical and serum studies. Larger imaging studies are underway to evaluate a more ideal imaging modality for this unique patient population. Olaguoke Akinwande, Shakeeb S. Ahmad, Tracy Van Meter, Brittany Schulz, and Robert C. G. Martin Copyright © 2015 Olaguoke Akinwande et al. All rights reserved. The Past, Present, and Future in Management of Small Renal Masses Wed, 30 Sep 2015 13:52:09 +0000 Management of small renal masses (SRMs) is currently evolving due to the increased incidence given the ubiquity of cross-sectional imaging. Diagnosing a mass in the early stages theoretically allows for high rates of cure but simultaneously risks overtreatment. New consensus guidelines and treatment modalities are changing frequently. The multitude of information currently available shall be summarized in this review. This summary will detail the historic surgical treatment of renal cell carcinoma with current innovations, the feasibility and utility of biopsy, the efficacy of ablative techniques, active surveillance, and use of biomarkers. We evaluate how technology may be used in approaching the small renal mass in order to decrease morbidity, while keeping rates of overtreatment to a minimum. Sarah C. Ha, Haley A. Zlomke, Nicholas Cost, and Shandra Wilson Copyright © 2015 Sarah C. Ha et al. All rights reserved. Pulmonary Venous Obstruction in Cancer Patients Sun, 06 Sep 2015 14:08:08 +0000 Background. We study the clinical significance and management of pulmonary venous obstruction in cancer patients. Methods. We conducted a prospective cohort study to characterize the syndrome that we term “pulmonary vein obstruction syndrome” (PVOS) between January 2005 and March 2014. The criteria for inclusion were (1) episodes of shortness of breath; (2) chest X-ray showing abnormal pulmonary hilum shadow with or without presence of pulmonary edema and/or pleural effusion; (3) CT scan demonstrating pulmonary vein thrombosis/tumor with or without tumor around the vein. Results. Two hundred and twenty-two patients developed PVOS. Shortness of breath was the main symptom, which was aggravated by chemotherapy in 28 (13%), and medical/surgical procedures in 21 (9%) and showed diurnal change in intensity in 32 (14%). Chest X-rays all revealed abnormal pulmonary hilum shadows and presence of pulmonary edema in 194 (87%) and pleural effusion in 192 (86%). CT scans all showed pulmonary vein thrombosis/tumor (100%) and surrounding the pulmonary veins by tumor lesions in 140 patients (63%). PVOS was treated with low molecular weight heparin in combination with dexamethasone, and 66% of patients got clinical/image improvement. Conclusion. Physicians should be alert to PVOS when shortness of breath occurs and chest X-ray reveals abnormal pulmonary hilum shadows. Chuang-Chi Liaw, Hung Chang, Tsai-Sheng Yang, and Ming-Sheng Wen Copyright © 2015 Chuang-Chi Liaw et al. All rights reserved. Dissecting the Potential Interplay of DEK Functions in Inflammation and Cancer Sun, 06 Sep 2015 12:33:01 +0000 There is a long-standing correlation between inflammation, inflammatory cell signaling pathways, and tumor formation. Understanding the mechanisms behind inflammation-driven tumorigenesis is of great research and clinical importance. Although not entirely understood, these mechanisms include a complex interaction between the immune system and the damaged epithelium that is mediated by an array of molecular signals of inflammation—including reactive oxygen species (ROS), cytokines, and NFκB signaling—that are also oncogenic. Here, we discuss the association of the unique DEK protein with these processes. Specifically, we address the role of DEK in chronic inflammation via viral infections and autoimmune diseases, the overexpression and oncogenic activity of DEK in cancers, and DEK-mediated regulation of NFκB signaling. Combined, evidence suggests that DEK may play a complex, multidimensional role in chronic inflammation and subsequent tumorigenesis. Nicholas A. Pease, Trisha Wise-Draper, and Lisa Privette Vinnedge Copyright © 2015 Nicholas A. Pease et al. All rights reserved. Epithelial to Mesenchymal Transition in a Clinical Perspective Sun, 06 Sep 2015 11:58:59 +0000 Tumor growth and metastatic dissemination rely on cellular plasticity. Among the different phenotypes acquired by cancer cells, epithelial to mesenchymal transition (EMT) has been extensively illustrated. Indeed, this transition allows an epithelial polarized cell to acquire a more mesenchymal phenotype with increased mobility and invasiveness. The role of EMT is quite clear during developmental stage. In the neoplastic context in many tumors EMT has been associated with a more aggressive tumor phenotype including local invasion and distant metastasis. EMT allows the cell to invade surrounding tissues and survive in the general circulation and through a stem cell phenotype grown in the host organ. The molecular pathways underlying EMT have also been clearly defined and their description is beyond the scope of this review. Here we will summarize and analyze the attempts made to block EMT in the therapeutic context. Indeed, till today, most of the studies are made in animal models. Few clinical trials are ongoing with no obvious benefits of EMT inhibitors yet. We point out the limitations of EMT targeting such tumor heterogeneity or the dynamics of EMT during disease progression. Jennifer Pasquier, Nadine Abu-Kaoud, Haya Al Thani, and Arash Rafii Copyright © 2015 Jennifer Pasquier et al. All rights reserved. Gallbladder Cancer in the 21st Century Tue, 01 Sep 2015 11:38:11 +0000 Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC. Rani Kanthan, Jenna-Lynn Senger, Shahid Ahmed, and Selliah Chandra Kanthan Copyright © 2015 Rani Kanthan et al. All rights reserved. Evaluation of AgNORs in Oral Potentially Malignant Lesions Mon, 31 Aug 2015 14:11:21 +0000 Oral squamous cell carcinoma (OSCC) is usually preceded by detectable mucosal changes, as leukoplakias and erythroplakia. Histologically, these lesions can range from hyperkeratosis and acanthosis to epithelial dysplasia and even OSCC. The aim of this study was to investigate the proliferative activity, using AgNORs quantification proteins, in low- and high-risk oral epithelial dysplasia, OSCC, and nondysplastic epithelium (inflammatory fibrous hyperplasia). The sample was divided into 4 groups: G1: 10 cases of inflammatory fibrous hyperplasia (IFH), G2: 11 cases of low-risk epithelial dysplasia (LD), G3: 10 cases of high-risk epithelial dysplasia (HD), and G4: 11 cases of OSCC. The quantitative analysis was performed using an image processing software in photomicrographs at 1000x magnification. The one-way ANOVA was used for comparison of the mean AgNORs counts between the study groups. The mean AgNORs count was significantly higher in OSCC when compared to IFH and the LD; however, it was not statistically different from HD. The mean number of LD was significantly lower than the HD and OSCC, with no difference related to IFH. AgNORs quantification can be an important and cheap method to help in the determination of the degree of epithelial dysplasia and, consequently, in the analysis of their potential for malignant transformation. Karin Berria Tomazelli, Filipe Modolo, and Elena Riet Correa Rivero Copyright © 2015 Karin Berria Tomazelli et al. All rights reserved. Cancer and Cardiovascular Disease: The Complex Labyrinth Tue, 04 Aug 2015 11:17:31 +0000 Susan Dent, Peter Liu, Christine Brezden-Masley, and Daniel Lenihan Copyright © 2015 Susan Dent et al. All rights reserved. Right Ventricular Dysfunction in Patients Experiencing Cardiotoxicity during Breast Cancer Therapy Mon, 03 Aug 2015 12:14:26 +0000 Background. Right ventricular (RV) dysfunction during cancer therapy related cardiotoxicity and its prognostic implications have not been examined. Aim. We sought to determine the incidence and prognostic value of RV dysfunction at time of LV defined cardiotoxicity. Methods. We retrospectively identified 30 HER2+ female patients with breast cancer treated with trastuzumab (± anthracycline) who developed cardiotoxicity and had a diagnostic quality transthoracic echocardiography. LV ejection fraction (LVEF), RV fractional area change (RV FAC), and peak systolic longitudinal strain (for both LV and RV) were measured on echocardiograms at the time of cardiotoxicity and during follow-up. Thirty age balanced precancer therapy and HER2+ breast cancer patients were used as controls. Results. In the 30 patients with cardiotoxicity (mean ± SD age 54 ± 12 years) RV FAC was significantly lower (42 ± 7 versus 47 ± 6%, ) compared to controls. RV dysfunction defined by global longitudinal strain (GLS < −20.3%) was seen in 40% (). During follow-up in 16 out of 30 patients (23 ± 15 months), there was persistent LV dysfunction (EF < 55%) in 69% (). Concomitant RV dysfunction at the time of LV cardiotoxicity was associated with reduced recovery of LVEF during follow-up although this was not statistically significant. Conclusion. RV dysfunction at the time of LV cardiotoxicity is frequent in patients with breast cancer receiving trastuzumab therapy. Despite appropriate management, LV dysfunction persisted in the majority at follow-up. The prognostic value of RV dysfunction at the time of cardiotoxicity warrants further investigation. Anna Calleja, Frédéric Poulin, Ciril Khorolsky, Masoud Shariat, Philippe L. Bedard, Eitan Amir, Harry Rakowski, Michael McDonald, Diego Delgado, and Paaladinesh Thavendiranathan Copyright © 2015 Anna Calleja et al. All rights reserved. Orthotopic Heart Transplantation and Mechanical Circulatory Support in Cancer Survivors: Challenges and Outcomes Mon, 03 Aug 2015 12:12:26 +0000 Chemotherapy-induced cardiomyopathy (CCMP) is a significant cause of morbidity and mortality. Compared to cardiomyopathy due to other causes, anthracycline-induced cardiomyopathy is associated with a worse survival. As cancer survival improves, patients with CCMP can be expected to comprise a significant proportion of patients who may require advanced therapies such as inotropic support, cardiac transplantation, or left ventricular assist device (LVAD). Distinct outcomes related to advanced therapies for end-stage heart failure in this patient population may arise due to unique demographic characteristics and comorbidities. We review recent literature regarding the characteristics of patients who have survived cancer undergoing orthotopic heart transplantation and mechanical circulatory support for end-stage heart failure. The challenges and outcomes of advanced therapies for heart failure related specifically to anthracycline-induced cardiomyopathy are emphasized. Nina Ghosh and John Hilton Copyright © 2015 Nina Ghosh and John Hilton. All rights reserved. Exercise Prevention of Cardiovascular Disease in Breast Cancer Survivors Mon, 03 Aug 2015 09:08:52 +0000 Thanks to increasingly effective treatment, breast cancer mortality rates have significantly declined over the past few decades. Following the increase in life expectancy of women diagnosed with breast cancer, it has been recognized that these women are at an elevated risk for cardiovascular disease due in part to the cardiotoxic side effects of treatment. This paper reviews evidence for the role of exercise in prevention of cardiovascular toxicity associated with chemotherapy used in breast cancer, and in modifying cardiovascular risk factors in breast cancer survivors. There is growing evidence indicating that the primary mechanism for this protective effect appears to be improved antioxidant capacity in the heart and vasculature and subsequent reduction of treatment-related oxidative stress in these structures. Further clinical research is needed to determine whether exercise is a feasible and effective nonpharmacological treatment to reduce cardiovascular morbidity and mortality in breast cancer survivors, to identify the cancer therapies for which it is effective, and to determine the optimal exercise dose. Safe and noninvasive measures that are sensitive to changes in cardiovascular function are required to answer these questions in patient populations. Cardiac strain, endothelial function, and cardiac biomarkers are suggested outcome measures for clinical research in this field. Amy A. Kirkham and Margot K. Davis Copyright © 2015 Amy A. Kirkham and Margot K. Davis. All rights reserved. The Prevalence of Cardiac Risk Factors in Men with Localized Prostate Cancer Undergoing Androgen Deprivation Therapy in British Columbia, Canada Sun, 02 Aug 2015 13:37:29 +0000 Background. While androgen deprivation therapy (ADT) reduces the risk of prostate cancer-specific mortality in high-risk localized prostate cancer, it adversely affects cardiovascular (CV) risk factor profiles in treated men. Methods. We retrospectively reviewed the charts of 100 consecutive men with intermediate- or high-risk localized prostate cancer referred to the British Columbia Cancer Agency for ADT. Data on CV risk factors and disease were collected and Framingham risk scores were calculated. Results. The median age of the study cohort was 73 years. Established cardiovascular disease was present in 25% of patients. Among patients without established CV disease, calculated Framingham risk was high in 65%, intermediate in 33%, and low in 1%. Baseline hypertension was present in 58% of patients, dyslipidemia in 51%, and diabetes or impaired glucose tolerance in 24%. Hypertension was more prevalent in the study cohort than in an age- and sex-matched population sample (OR 1.74, ); diabetes had a similar prevalence (OR 0.93, ). Conclusions. Patients receiving ADT have a high prevalence of cardiovascular disease and risk factors and are more likely to be hypertensive than population controls. Low rates of CV risk screening suggest opportunities for improved primary and secondary prevention of CV disease in this population. Margot K. Davis, Jennifer L. Rajala, Scott Tyldesley, Tom Pickles, and Sean A. Virani Copyright © 2015 Margot K. Davis et al. All rights reserved. An International Survey of Health Care Providers Involved in the Management of Cancer Patients Exposed to Cardiotoxic Therapy Sun, 02 Aug 2015 13:14:52 +0000 Cardiotoxicity is the second leading cause of morbidity and mortality in cancer survivors. The objective of this international cardiac oncology survey was to gain a better understanding of current knowledge and practice patterns among HCPs involved in the management of cancer patients exposed to potentially cardiotoxic drugs. Between 2012 and 2013, we conducted an email-based survey of HCPs involved in the management of cardiac disease in cancer patients. 393 survey responses were received, of which 77 were from Canadian respondents. The majority of respondents were cardiologists (47%), followed closely by medical oncologists. The majority of respondents agreed that cardiac issues are important to cancer patients (97%). However, only 36% of total respondents agreed with an accepted definition of cardiotoxicity. While 78% of respondents felt that cardiac medications are protective during active cancer treatment, only 51% would consider prescribing these medications up-front in cancer patients. Although results confirm a high level of concern for cardiac safety, there continues to be a lack of consensus on the definition of cardiotoxicity and a discrepancy in clinical practice between cardiologists and oncologists. These differences in opinion require resolution through more effective research collaboration and formulation of evidence-based guidelines. Jeffrey Sulpher, Shrey Mathur, Daniel Lenihan, Christopher Johnson, Michele Turek, Angeline Law, Ellamae Stadnick, Franco Dattilo, Nadine Graham, and Susan F Dent Copyright © 2015 Jeffrey Sulpher et al. All rights reserved. Multimodality Imaging in Cardiooncology Sun, 02 Aug 2015 12:29:02 +0000 Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies. Fausto Pizzino, Giampiero Vizzari, Rubina Qamar, Charles Bomzer, Scipione Carerj, Concetta Zito, and Bijoy K. Khandheria Copyright © 2015 Fausto Pizzino et al. All rights reserved. Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology Clinic: An Observational Study Sun, 02 Aug 2015 11:08:58 +0000 Cardiotoxicity is the second leading cause of long-term morbidity and mortality among cancer survivors. The purpose of this retrospective observational study is to report on the clinical and cardiac outcomes in patients with early stage and advanced cancer who were referred to our multidisciplinary cardiac oncology clinic (COC). A total of 428 patients were referred to the COC between October 2008 and January 2013. The median age of patients at time of cancer diagnosis was 60. Almost half of patients who received cancer therapy received first-line chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to anthracyclines. The most common reasons for referral to the cardiac oncology clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were treated with cardiac medications. The majority (331, 77.3%) of patients were alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular review of cardiac oncology clinic referral patterns, management plans, and patient outcomes, we aim to continuously improve delivery of cardiac care to our patient population and optimize cardiac health. Jeffrey Sulpher, Shrey Mathur, Nadine Graham, Freya Crawley, Michele Turek, Christopher Johnson, Ellamae Stadnick, Angeline Law, Jason Wentzell, and Susan Dent Copyright © 2015 Jeffrey Sulpher et al. All rights reserved. Clinical and Microbiological Profile of Pathogens in Febrile Neutropenia in Hematological Malignancies: A Single Center Prospective Analysis Tue, 28 Jul 2015 07:33:44 +0000 Background. Febrile neutropenia is the consequence of treatment of hematological disorders. The first-line empirical treatment should cover the prevalent microorganism of the institute. The aim of study was to establish the effectiveness of current practices used at the institution and to review the culture sensitivity pattern of isolated microorganisms. Patients and Methods. Data was recorded and analyzed prospectively for 226 hospitalized patients of febrile neutropenia from January 2011 till December 2013. Results. Out of 226 cases, 173 were males and 53 were females. Clinically documented infections were 104 (46.01%) and microbiologically documented infections were 80 (35.39%), while 42 (18.58%) had pyrexia of undetermined origin. Gram negative infections accounted for 68 (85%) and Escherichia coli was the commonest isolate. Gram positive microorganisms were isolated in 12 (15%) cases and most common was Staphylococcus aureus. First-line empirical treatment with piperacillin/tazobactam and amikacin showed response in 184 patients (85.9%) till 72 hours. Conclusion. There is marked decline in infections due to Gram positive microorganisms; however, Gram negative infections are still of great concern and need further surveillance. In this study the antibiogram has shown its sensitivity for empirical antibiotic therapy used; hence, it supports continuation of the same practice. M. Taj, T. Farzana, T. Shah, S. Maqsood, S. S. Ahmed, and T. S. Shamsi Copyright © 2015 M. Taj et al. All rights reserved. Tumor Suppressor Inactivation in the Pathogenesis of Adult T-Cell Leukemia Wed, 10 Jun 2015 13:38:02 +0000 Tumor suppressor functions are essential to control cellular proliferation, to activate the apoptosis or senescence pathway to eliminate unwanted cells, to link DNA damage signals to cell cycle arrest checkpoints, to activate appropriate DNA repair pathways, and to prevent the loss of adhesion to inhibit initiation of metastases. Therefore, tumor suppressor genes are indispensable to maintaining genetic and genomic integrity. Consequently, inactivation of tumor suppressors by somatic mutations or epigenetic mechanisms is frequently associated with tumor initiation and development. In contrast, reactivation of tumor suppressor functions can effectively reverse the transformed phenotype and lead to cell cycle arrest or death of cancerous cells and be used as a therapeutic strategy. Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative disease associated with infection of CD4 T cells by the Human T-cell Leukemia Virus Type 1 (HTLV-I). HTLV-I-associated T-cell transformation is the result of a multistep oncogenic process in which the virus initially induces chronic T-cell proliferation and alters cellular pathways resulting in the accumulation of genetic defects and the deregulated growth of virally infected cells. This review will focus on the current knowledge of the genetic and epigenetic mechanisms regulating the inactivation of tumor suppressors in the pathogenesis of HTLV-I. Christophe Nicot Copyright © 2015 Christophe Nicot. All rights reserved.