Journal of Oncology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. ErbB Proteins as Molecular Target of Dietary Phytochemicals in Malignant Diseases Mon, 13 Feb 2017 00:00:00 +0000 ErbB proteins overexpression, in both normal and mutated forms, is associated with invasive forms of cancer prone to metastasis and with stronger antiapoptotic mechanisms and therefore more challenging to treat. Downstream effectors of ErbB receptors mediating these phenotypic traits include MAPK, STAT, and PI3K/AKT/mTOR pathways. Various phytochemical compounds were studied for their large number of biological effects including anticancer activity. Among these compounds, epigallocatechin-3-gallate (EGCG), the main catechin from green tea leaves, and curcumin, component of the curry powder, constituted the object of numerous studies. Both compounds were shown to act directly either on ErbB expression, or on their downstream signaling molecules. In this paper we aim to review the involvement of ErbB proteins in cancer as well as the biologic activity of EGCG and curcumin in ErbB expressing and overexpressing malignancies. The problems arising in the administration of the two compounds due to their reduced bioavailability when orally administered, as well as the progress made in this field, from using novel formulations to improved dosing regimens or improved synthetic analogs, are also discussed. Alexandru Filippi, Oana-Alina Ciolac, Constanța Ganea, and Maria-Magdalena Mocanu Copyright © 2017 Alexandru Filippi et al. All rights reserved. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma Tue, 17 Jan 2017 00:00:00 +0000 Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (), number of tumors, lymph node metastasis, and tumor size (, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively). High NEDD9 and p38 detection had a worse 3-year OS ( and <0.001, respectively). By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients’ outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC. Ola A. Harb, Rasha Haggag, Maged M. Ali, Shereen El Shorbagy, Abeer M. Abdelbary, Lobna A. Abdelaziz, Reham A. Salim, and Khaled M. Abdel Wahab Copyright © 2017 Ola A. Harb et al. All rights reserved. Hyaluromycin, a Novel Hyaluronidase Inhibitor, Attenuates Pancreatic Cancer Cell Migration and Proliferation Tue, 20 Dec 2016 14:19:56 +0000 Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated production and degradation of hyaluronan (HA), a major component of extracellular matrix involved in the malignant phenotype of cancer. In particular, increased hyaluronidase (HYAL) activity plays a critical role in cancer progression, at least in part, by producing low-molecular-weight- (LMW-) HA or small fragments of HA, suggesting HYAL as a target for cancer treatment. Hyaluromycin, a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces hyaluromycini as a HYAL inhibitor. We investigated the antitumor effects of hyaluromycin in PDAC cells. We examined the effects of hyaluromycin on the proliferation and migration of PDAC cells. To elucidate the mechanisms underlying the effect of hyaluromycin on PDAC cells, we examined the concentration of LMW-HA in the conditioned media after treating PDAC cells with hyaluromycin. We demonstrate that hyaluromycin inhibits proliferation and migration of PDAC cells. We also found that these antitumor effects of hyaluromycin were associated with a decreased concentration of LMW-HA and a decreased phosphorylation of ribosomal protein S6. Our results suggest that hyaluromycin is a promising new drug against this highly aggressive neoplasm. Shiro Kohi, Norihiro Sato, Atsuhiro Koga, Keiji Hirata, Enjuro Harunari, and Yasuhiro Igarashi Copyright © 2016 Shiro Kohi et al. All rights reserved. Hypoxia-Inducible Factor-1α Expression in Indonesian Laryngeal Squamous Cell Carcinoma Patients Tue, 01 Nov 2016 09:06:36 +0000 Objectives. This research aimed to determine the association between hypoxia-inducible factor-1α (HIF-1α) expression and laryngeal squamous cell carcinoma clinical stage. Methods. We retrospectively analyzed paraffin-embedded tissue from 47 laryngeal squamous cell carcinoma (LSCC) patients from 2011 to 2014. HIF-1α expression was analyzed by immunohistochemistry using an anti-HIF-1α mouse monoclonal antibody. The association between HIF-1α expression and clinical stage was analyzed using the chi square test. Results. The glottis was the predominant site of laryngeal squamous cell carcinoma occurrence, and 43/47 (91.5%) patients presented at an advanced stage. Of the advanced stage patients, 27/43 stained positive for HIF-1α expression and 16/43 stained negative. Of the early stage patients, 2/4 stained positive for HIF-1α expression and 2/4 stained negative. Statistical analysis did not demonstrate significant association of HIF-1α expression. Conclusion. There was no statistically significant association between HIF-1α expression and the clinical stage or histological differentiation of LSCC. Agus Surono, Priyanto Priyanto, and Sagung Rai Indrasari Copyright © 2016 Agus Surono et al. All rights reserved. The Role of Pulmonary Veins in Cancer Progression from a Computed Tomography Viewpoint Thu, 22 Sep 2016 11:22:05 +0000 Background. We studied the role of pulmonary veins in cancer progression using computed tomography (CT) scans. Methods. We obtained data from 260 patients with pulmonary vein obstruction syndrome (PVOS). We used CT scans to investigate pulmonary lesions in relation to pulmonary veins. We divided the lesions into central and peripheral lesions by their anatomical location: in the lung parenchymal tissue or pulmonary vein; in the superior or inferior pulmonary vein; and by unilateral or bilateral presence in the lungs. Results. Of the 260 PVOS patients, 226 (87%) had central lesions, 231 (89%) had peripheral lesions, and 190 (75%) had mixed central and peripheral lesions. Among the 226 central lesions, 93% had lesions within the superior pulmonary vein, either bilaterally or unilaterally. Among the 231 peripheral lesions, 65% involved bilateral lungs, 70% involved lesions within the inferior pulmonary veins, and 23% had obvious metastatic extensions into the left atrium. All patients exhibited nodules within their pulmonary veins. The predeath status included respiratory failure (40%) and loss of consciousness (60%). Conclusion. CT scans play an important role in following tumor progression within pulmonary veins. Besides respiratory distress, PVOS cancer cells entering centrally can result in cardiac and cerebral events and loss of consciousness or can metastasize peripherally from the pulmonary veins to the lungs. Chuang-Chi Liaw, Hung Chang, Tzu-Yao Liao, Ming-Sheng Wen, Chih-Teng Yu, and Yu-Hsiang Juan Copyright © 2016 Chuang-Chi Liaw et al. All rights reserved. Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 Cells In Vitro and In Vivo Mon, 22 Aug 2016 14:21:24 +0000 We investigated the effects of betaine, C-phycocyanin (C-PC), and their combined use on the growth of A549 lung cancer both in vitro and in vivo. When cells were coincubated with betaine and C-PC, an up to 60% decrease in viability was observed which is significant compared to betaine (50%) or C-PC treatment alone (no decrease). Combined treatment reduced the stimulation of NF-κB expression by TNF-α and increased the amount of the proapoptotic p38 MAPK. Interestingly, combined treatment induced a cell cycle arrest in G2/M phase for ~60% of cells. In vivo studies were performed in pathogen-free male nude rats injected with A549 cells in their right flank. Their daily food was supplemented with either betaine, C-PC, both, or neither. Compared to the control group, tumour weights and volumes were significantly reduced in either betaine- or C-PC-treated groups and no additional decrease was obtained with the combined treatment. This data indicates that C-PC and betaine alone may efficiently inhibit tumour growth in rats. The synergistic activity of betaine and C-PC on A549 cells growth observed in vitro remains to be further confirmed in vivo. The reason behind the nature of their interaction is yet to be sought. Rea Bingula, Carmen Dupuis, Chantal Pichon, Jean-Yves Berthon, Marc Filaire, Lucie Pigeon, and Edith Filaire Copyright © 2016 Rea Bingula et al. All rights reserved. Precancerous Cervix in Human Immunodeficiency Virus Infected Women Thirty Years Old and above in Northern Uganda Sun, 10 Jul 2016 11:51:28 +0000 Background. Little is known about precancerous cervical lesion (PCCL), the precursor of cervical cancer among Human Immunodeficiency (HIV) infected women in a postconflict setting of Northern Uganda. Objective. To establish factors associated with PCCL among HIV infected women above thirty years of age in a postconflict setting of Northern Uganda. Method. This retrospective cohort study used electronic data from 995 HIV-positive women that attended cervical cancer screening during June 2014 and December 2015. Data on social, sexual, obstetric, and gynecological factors was analyzed at 95% confidence level. Multivariate analysis determined factors independently associated with positive PCCL. Probability value less than 5% was considered significant. Results. Prevalence of PCCL was 3.0% (95% confidence interval (CI): 2.0–4.3). A positive PCCL was significantly associated with absence of sexually transmitted diseases (STDs) during clinic visits (adjusted odds ratio, aOR = 0.24; 95% confidence interval (CI): 0.09–0.64; ) and first pregnancy before the age of 20 years (aOR = 3.09; 95% CI: 1.21–7.89; ). Conclusion. The prevalence of PCCL was low in the postconflict setting of Northern Uganda. HIV-positive women presenting with STDs and those with first pregnancy before the age of 20 years were at increased risk of PCCL. Jonathan Izudi, Norbert Adrawa, and Dinah Amongin Copyright © 2016 Jonathan Izudi et al. All rights reserved. Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study Thu, 30 Jun 2016 12:30:29 +0000 Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing. Thirty-seven patients in the prospective study were Class 1 and 33 were Class 2. Class 1 patients had 100% 3-year metastasis-free survival compared to 63% for Class 2 (log rank test ) with 27.3 median follow-up months in this interim analysis. Class 2 patients received significantly higher-intensity monitoring and more oncology/clinical trial referrals compared to Class 1 patients (Fisher’s exact test and , resp.). The results of this study provide additional, prospective evidence in an independent cohort of patients that Class 1 and Class 2 patients are managed according to the differential metastatic risk indicated by DecisionDx-UM. The trial is registered with Clinical Application of DecisionDx-UM Gene Expression Assay Results (NCT02376920). Kristen Meldi Plasseraud, Robert W. Cook, Tony Tsai, Yevgeniy Shildkrot, Brooke Middlebrook, Derek Maetzold, Jeff Wilkinson, John Stone, Clare Johnson, Kristen Oelschlager, and Thomas M. Aaberg Copyright © 2016 Kristen Meldi Plasseraud et al. All rights reserved. Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients Mon, 27 Jun 2016 06:22:17 +0000 The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (), associated with poorer differentiation () and TNM stage II/III of tumors (). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors () or in tumors located in the colon (). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location. Ehsan Nazemalhosseini Mojarad, Seyed Mohammad Hossein Kashfi, Hanieh Mirtalebi, Mohammad Yaghoob Taleghani, Pedram Azimzadeh, Sanaz Savabkar, Mohammad Amin Pourhoseingholi, Hasan Jalaeikhoo, Hamid Asadzadeh Aghdaei, Peter J. K. Kuppen, and Mohammad Reza Zali Copyright © 2016 Ehsan Nazemalhosseini Mojarad et al. All rights reserved. Changes in Pathological Complete Response Rates after Neoadjuvant Chemotherapy for Breast Carcinoma over Five Years Mon, 13 Jun 2016 08:50:15 +0000 Historically, neoadjuvant chemotherapy (NACT) was extrapolated from adjuvant regimens. Dual HER2 blockade and the introduction of carboplatin for triple negative breast cancers (TNBC) emerged by December 2013 and have improved pathological complete response (pCR) rates. The objective of this study was to assess the pCR rates before and after the introduction of these new neoadjuvant regimens. Materials and Methods. Stage I–III breast cancer patients who received NACT were analyzed for rates of pCR by clinical characteristics (i.e., age, BMI, axillary lymphadenopathy, and histologic subtype), by time period (1 = 3/2010–11/2013, 2 = 12/2013–3/2015), and by type of chemotherapy (e.g., anthracycline/taxane only, carboplatin-containing, and HER2 blockade). Results. 113 patients received NACT. Overall pCR rate was 26.5 percent (). The pCR rate increased from 14% to 43.1% () from time period 1 to time period 2 and were associated with HER2 positivity (), receiving treatment during time period 2 () and using an anthracycline/taxane plus additional agent type of regimen (). Conclusions. Our study revealed a significant difference in rates of pCR over five years. Window of opportunity trials and other trials that utilize pCR analysis should be encouraged. Daniel C. McFarland, Jessica Naikan, Mariya Rozenblit, John Mandeli, Ira Bleiweiss, and Amy Tiersten Copyright © 2016 Daniel C. McFarland et al. All rights reserved. Clinicopathological Profile of Pure Neuroendocrine Neoplasms of the Esophagus: A South Indian Center Experience Tue, 31 May 2016 08:20:55 +0000 Purpose. Neuroendocrine neoplasms (NENs) of the esophagus are very uncommon with only a few studies published worldwide. Studies on clinical profile, management, and outcomes are very uncommon. Methods. We report the largest single institution retrospective review of 43 patients of pure esophageal NENs out of our registry of gastrointestinal neuroendocrine tumors treated between 2005 and 2014. Data on the incidence, tumor location, clinical symptoms, stage at presentation, grading, treatment protocol, and treatment outcomes was collected and analyzed. Results. Among 1293 cases of esophageal cancers, pure esophageal NENs were diagnosed in 43 cases. The mean patient age was 55.8 years. The male : female ratio was 1.5 : 1. 81.4% of the tumors were located in the lower third of the esophagus and gastroesophageal junction. Neuroendocrine carcinomas (NEC; G3) accounted for the vast majority of NENs (83.7%). 53.5% patients were Stage IV and 32.5% were Stage III at presentation. The combined median survival of stages II and III patients was 18.25 months, with treatment. The median survival of treated patients with metastatic disease was 6.5 months. Conclusion. Esophageal NENs most commonly were neuroendocrine carcinomas, presented in metastatic stage and were associated with poor prognosis. Grade 2 (G2) tumors had better outcomes than NEC (G3). In nonmetastatic disease, presence of lymph node metastasis and unresectable disease had poorer outcomes. Govind Babu Kanakasetty, Loknatha Dasappa, Kuntegowdanahalli Chinnagiriyappa Lakshmaiah, Mangesh Kamath, Linu Abraham Jacob, Suresh Babu Mallekavu, Lakkavalli Krishnappa Rajeev, Rudresha Antapura Haleshappa, Lokesh Kadabur Nagendrappa, Smitha Carol Saldanha, and Rekha V. Kumar Copyright © 2016 Govind Babu Kanakasetty et al. All rights reserved. Frequency of BCR-ABL Transcript Types in Syrian CML Patients Mon, 30 May 2016 09:44:46 +0000 Background. In Syria, CML patients are started on tyrosine kinase inhibitors (TKIs) and monitored until complete molecular response is achieved. BCR-ABL mRNA transcript type is not routinely identified, contrary to the recommendations. In this study we aimed to identify the frequency of different BCR-ABL transcripts in Syrian CML patients and highlight their significance on monitoring and treatment protocols. Methods. CML patients positive for BCR-ABL transcripts by quantitative RT-PCR were enrolled. BCR-ABL transcript types were investigated using a home-made PCR method that was adapted from published protocols and optimized. The transcript types were then confirmed using a commercially available research kit. Results. Twenty-four transcripts were found in 21 patients. The most common was b2a2, followed by b3a2, b3a3, and e1a3 present solely in 12 (57.1%), 3 (14.3%), 2 (9.5%), and 1 (4.8%), respectively. Three samples (14.3%) contained dual transcripts. While b3a2 transcript was apparently associated with warning molecular response to imatinib treatment, b2a2, b3a3, and e1a3 transcripts collectively proved otherwise (). Conclusion. It might be advisable to identify the BCR-ABL transcript type in CML patients at diagnosis, using an empirically verified method, in order to link the detected transcript with the clinical findings, possible resistance to treatment, and appropriate monitoring methods. Sulaf Farhat-Maghribi, Wafa Habbal, and Fawza Monem Copyright © 2016 Sulaf Farhat-Maghribi et al. 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.