The Scientific World Journal: Oncology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Screening of Trace Elements in Hair of the Female Population with Different Types of Cancers in Wielkopolska Region of Poland Mon, 15 Dec 2014 07:53:45 +0000 Background. Cancer constitutes a major health problem worldwide. Thus, search for reliable and practical markers of the disease process remains the key issue of the diagnostic process. Objectives. The study aims at linking the trace element status of an organism, assessed by hair analysis, with the occurrence of cancer diseases. Material and Methods. Hair samples were collected from 299 patients with cancer diseases confirmed by a histopathological test and from 100 controls. Cancer patients were divided into three groups, depending on cancer type: hormone-dependent cancer, cancer of the alimentary tract, and cancer with high glycolytic activity. Mineral element analysis of hair was performed using an atomic emission spectrophotometer with inductively coupled plasma (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). Results. Statistically significantly lower concentrations of selenium, zinc, copper, germanium and boron, iron, and magnesium were observed in the three groups of cancer patients. Disturbance in the axis glucose-insulin and changes in concentrations of heavy metals and toxic elements were also noted. Conclusions. It seems safe to conclude that our results confirmed usefulness of hair element analysis in screening tests for the assessment of the biomarker of various cancer diseases in a female population. Bogusław Czerny, Krzysztof Krupka, Marcin Ożarowski, and Agnieszka Seremak-Mrozikiewicz Copyright © 2014 Bogusław Czerny et al. All rights reserved. Correlations of Ezrin Expression with Pathological Characteristics and Prognosis of Osteosarcoma: A Meta-Analysis Thu, 27 Nov 2014 07:32:37 +0000 We conducted a meta-analysis to comprehensively evaluate the correlations of ezrin expression with pathological characteristics and the prognosis of osteosarcoma. The MEDLINE (1966–2013), the Cochrane Library Database, EMBASE, CINAHL, Web of Science (1945–2013), and the Chinese Biomedical Database were searched without language restrictions. Meta-analyses conducted using STATA software were calculated. Ten studies met the inclusion criteria, including 459 patients with osteosarcoma. Meta-analysis results illustrated that ezrin expression may be closely associated with the recurrence of osteosarcoma or metastasis in osteosarcoma. Our findings also demonstrated that patients with grade III-IV osteosarcoma showed a higher frequency of ezrin expression than those with histological grade I-II osteosarcoma. Furthermore, we found that patients with positive expression of ezrin exhibited a shorter overall survival than those with negative ezrin expression. The results also indicated that positive ezrin expression was strongly correlated with poorer metastasis-free survival. Nevertheless, no significant relationships were observed between ezrin expression and clinical variables (age and gender). In the current meta-analysis, our results illustrated significant relationships of ezrin expression with pathological characteristics and prognosis of osteosarcoma. Thus, ezrin expression could be a promising marker in predicting the clinical outcome of patients with osteosarcoma. Da-Hang Zhao, Jiang Zhu, Wen-Bo Wang, Feng Dong, Qiao Zhang, Hong-Wu Fan, Jing-Zhe Zhang, and Yong-Ming Wang Copyright © 2014 Da-Hang Zhao et al. All rights reserved. Evaluating Medicinal Plants for Anticancer Activity Thu, 13 Nov 2014 06:51:33 +0000 Plants have been used for medical purposes since the beginning of human history and are the basis of modern medicine. Most chemotherapeutic drugs for cancer treatment are molecules identified and isolated from plants or their synthetic derivatives. Our hypothesis was that whole plant extracts selected according to ethnobotanical sources of historical use might contain multiple molecules with antitumor activities that could be very effective in killing human cancer cells. This study examined the effects of three whole plant extracts (ethanol extraction) on human tumor cells. The extracts were from Urtica membranacea (Urticaceae), Artemesia monosperma (Asteraceae), and Origanum dayi post (Labiatae). All three plant extracts exhibited dose- and time-dependent killing capabilities in various human derived tumor cell lines and primary cultures established from patients’ biopsies. The killing activity was specific toward tumor cells, as the plant extracts had no effect on primary cultures of healthy human cells. Cell death caused by the whole plant extracts is via apoptosis. Plant extract 5 (Urtica membranacea) showed particularly strong anticancer capabilities since it inhibited actual tumor progression in a breast adenocarcinoma mouse model. Our results suggest that whole plant extracts are promising anticancer reagents. Elisha Solowey, Michal Lichtenstein, Sarah Sallon, Helena Paavilainen, Elaine Solowey, and Haya Lorberboum-Galski Copyright © 2014 Elisha Solowey et al. All rights reserved. Achyranthes aspera Root Extracts Induce Human Colon Cancer Cell (COLO-205) Death by Triggering the Mitochondrial Apoptosis Pathway and S Phase Cell Cycle Arrest Mon, 27 Oct 2014 06:43:08 +0000 Achyranthes aspera (AA) has been used traditionally for the cure of various disorders. However, the action of root extracts of AA as anticancer agent and its cellular mechanism remain unclear. The aim was to screen the antitumor effect of ethanolic (EAA) and aqueous (AAA) root extracts on the growth of colon cancer COLO-205 cells by testing their cytotoxicity, followed by their effect on clonogenicity, migration, and induction of apoptosis. Mechanisms leading to apoptosis and cell cycle arrest were also investigated by expression studies of caspase-9, caspase-3, Bax, Bcl-2, p16, p21, and p27 genes, followed by flow cytometric analysis for cell cycle distribution. Cytotoxicity screening of AA extracts indicated greater cytotoxic activity of AAA extract against COLO-205 cells. A series of events marked by apoptosis revealed loss of cell viability, chromatin condensation, and DNA fragmentation in AAA treated cells to a greater extent. The mRNA expression levels of caspase-9, caspase-3, Bax, p16, p21, and p27 were markedly increased in the AAA treated cells, along with decreased Bcl-2 expression. The cell cycle arrest at S phase was detected by flow cytometric analysis after treatment with AAA. Overall the study signifies the aqueous extracts as a promising therapeutic candidate against cancer. Shagun Arora and Simran Tandon Copyright © 2014 Shagun Arora and Simran Tandon. All rights reserved. Overexpression of MMP13 Is Associated with Clinical Outcomes and Poor Prognosis in Oral Squamous Cell Carcinoma Thu, 23 Oct 2014 11:48:06 +0000 Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis () and tumor staging (). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC. Vui King Vincent-Chong, Iman Salahshourifar, Lee Peng Karen-Ng, Ming Yhong Siow, Thomas George Kallarakkal, Anand Ramanathan, Yi-Hsin Yang, Goot Heah Khor, Zainal Ariff Abdul Rahman, Siti Mazlipah Ismail, Narayanan Prepageran, Wan Mahadzir Wan Mustafa, Mannil Thomas Abraham, Keng Kiong Tay, Sok Ching Cheong, and Rosnah Binti Zain Copyright © 2014 Vui King Vincent-Chong et al. All rights reserved. Intensity-Modulated and Image-Guided Radiotherapy in Patients with Locally Advanced Inoperable Pancreatic Cancer after Preradiation Chemotherapy Mon, 20 Oct 2014 12:04:01 +0000 Background. Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. Methods. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. Results. 15 (68%) women and 7 men (median age 64 years; range 40–77) were identified. Median duration of PRCT was 11.1 months (range 4.3–33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9–54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); . Median RT-specific PFS for patients with prolonged PRCT 9 months was 8.5 months compared to 5.6 months for PRCT 9 months (). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT 9 months group, with 19.0 months compared to 8.5 months in the PRCT    9 months group (). Conclusions. IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy. M. Sinn, R. Ganeshan, R. Graf, U. Pelzer, J. M. Stieler, J. K. Striefler, M. Bahra, P. Wust, and H. Riess Copyright © 2014 M. Sinn et al. All rights reserved. Expression of Angiogenesis Regulatory Proteins and Epithelial-Mesenchymal Transition Factors in Platelets of the Breast Cancer Patients Tue, 14 Oct 2014 07:16:04 +0000 Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were collected by routine protocols. Vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet factor 4 (PF4), and transforming growth factor-β1 (TGF-β1) were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/106 platelets versus 0.9 pg/106 platelets, ), PF4 (21.2 ng/106 platelets versus 10.2 ng/106 platelets, ), PDGF-BB (42.9 pg/106 platelets versus 19.1 pg/106 platelets, ), and TGF-β1 (15.3 ng/106 platelets versus 4.3 ng/106 platelets, ) differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics . Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-β1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-β1 concentrations in platelets may be associated with prognosis. Hui Han, Fang-Li Cao, Bao-Zhong Wang, Xue-Ru Mu, Guang-Yao Li, and Xiu-Wen Wang Copyright © 2014 Hui Han et al. All rights reserved. Radixin Enhances Colon Cancer Cell Invasion by Increasing MMP-7 Production via Rac1-ERK Pathway Mon, 21 Jul 2014 07:37:41 +0000 As a member of the ezrin-radixin-moesin (ERM) family, radixin is overexpressed in many tumor tissues. However, little is known about its role in the progression of colon cancer. So we here aimed to determine the function of radixin in colon cancer cell invasion. Interestingly, we found that the expression of radixin was significantly elevated in colon cancer cells. Knockdown of radixin suppressed the invasion and migration of colon cancer cells. Further, knockdown of radixin inhibited the activation of Rac1 and ERK1/2, and decreased the expression and secretion of MMP-7. In addition, Rac1-ERK signaling pathway was required for the radixin-promoted invasion and MMP-7 production. Together, our findings suggest that radixin enhances the invasion and migration of colon cancer cells. Activation of Rac1-ERK pathway and consequent upregulation of MMP-7 production may contribute to the function of radixin in the regulation of colon cancer cell invasion. Thus, radixin may act as a novel target for the diagnosis and treatment of colon cancer. Qi-Hong Jiang, Ai-Xiang Wang, and Yan Chen Copyright © 2014 Qi-Hong Jiang et al. All rights reserved. Heat Shock Protein 70 Gene Polymorphisms and Cancer Risk: A Meta-Analysis Sun, 20 Jul 2014 12:35:10 +0000 The polymorphisms in the three main heat shock protein 70 (HSP70-1, HSP70-2, and HSP70-hom) genes were identified to be associated with cancer risk. However, the results are inconsistent. We perform a meta-analysis to evaluate the association between the three HSP70 polymorphisms and cancer risk. Relevant studies were identified using PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases up to March 29, 2014. The cancer risk associated with the HSP70 polymorphisms was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively. Twenty case-control studies from eighteen publications were included; a significant association was observed for HSP70-2 polymorphism (dominant model: OR = 1.53, 95% CI: 1.11–2.09; recessive model: OR = 1.91, 95% CI: 1.06–3.45; AG versus AA: OR = 1.38, 95% CI: 1.03–1.84; GG versus AA: OR = 2.34, 95% CI: 1.21–4.54), while there was no significant association for HSP70-1 and HSP70-hom polymorphisms. Besides, in stratification analyses by ethnicity, cancer type, and source of control, significant association was detected for HSP70-2 polymorphism, while for HSP70-hom polymorphism, we found a significant association in hospital-based population under homozygote comparison model. This meta-analysis suggests that the HSP70-2 polymorphism rather than HSP70-hom and HSP70-1 polymorphisms was associated with the risk of cancer. Lei He, Tao Deng, and He-sheng Luo Copyright © 2014 Lei He et al. All rights reserved. Neoadjuvant Chemotherapy with FOLFOX4 Regimen to Treat Advanced Gastric Cancer Improves Survival without Increasing Adverse Events: A Retrospective Cohort Study from a Chinese Center Thu, 17 Jul 2014 13:48:59 +0000 Background/Aim. To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). Patients and Methods. Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. Results. The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0–49) versus 13 (3–40)) between the two groups . The number of lymph node metastases in the neoadjuvant group (3 (0–14)) was significantly fewer than that in the adjuvant group (6 (0–27)) . The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group . The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; ). Conclusion. The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC. Zhen Sun, Rui-Juan Zhu, Gui-Fang Yang, and Yan Li Copyright © 2014 Zhen Sun et al. All rights reserved. The MicroRNAs as Prognostic Biomarkers for Survival in Esophageal Cancer: A Meta-Analysis Sun, 06 Jul 2014 10:09:39 +0000 Objectives. We performed this meta-analysis to summarize all the results from available studies, aiming delineating the prognostic role of miRNA in esophageal cancer. Design and Methods. We searched the electronic databases PubMed, EMBASE, and ISI Web of Science without time restrictions for the correlative literature to aggregate the survival results. Relevant data were extracted from studies investigating the relationship between miRNAs expression and survival in esophageal cancer patients. Pooled hazard ratios of miR-21and miR-375 for OS in ESCC were calculated. Results. A total of 25 studies involving 2,258 subjects analyzed the relationship between miRNA and prognosis of EC. In all, thirty-nine miRNAs associated with prognosis were reported in these studies. The pooled HR of higher miR-21 expression compared with lower miR-21 expression in ESCC was 1.84 (95% CI: 1.41–2.40, ), which could significantly predict poorer OS in ESCC. Besides, higher miR-375 was also a significant predictor for OS in ESCC, with a pooled HR of 0.55 (95% CI: 0.42–0.72, ). Conclusions. Our results support that miR-21 and miR-375 have a prognostic role in ESCC and may be useful therapeutic targets for the treatment of ESCC and meticulous follow-up for early detection of recurrence. Wenbo Fu, Lijuan Pang, Yunzhao Chen, Lan Yang, Janbo Zhu, and Yutao Wei Copyright © 2014 Wenbo Fu et al. All rights reserved. Blocked Autophagy by miR-101 Enhances Osteosarcoma Cell Chemosensitivity In Vitro Mon, 09 Jun 2014 12:31:57 +0000 The adjuvant chemotherapy, such as cisplatin, doxorubicin, and methotrexate has significantly improved survival of osteosarcoma patients. However, the chemoresistance which arose with the chemotherapy blocks achieving favorable outcomes for some patients and finally led to relapse or metastatic disease. Studies have shown paradoxical functions of autophagy in tumor development, which has been demonstrated by microRNAs. In the present study, we determined the involvement of autophagy during the chemotherapy of osteosarcoma cell line, U-2 OS, and further determined the regulation of miR-101 on the autophagy in the U-2 OS cells. Results demonstrated that doxorubicin treatment of U-2 OS cells induced significantly high level of autophagy-characteristic acidic vesicular organelles (AVOs), and induced significant autophagy related protein expression in U-2 OS cells. While the miR-101 could significantly reduce the doxorubicin-induced AVOs and block the autophagy related protein expression in U-2 OS cells. Moreover, the autophagy blockage by miR-101 sensitized the U-2 OS cells to doxorubicin treatment. In summary, miR-101 blocks autophagy during the chemotherapy in osteosarcoma cells and enhances chemosensitivity in vitro. Zhiqiang Chang, Lifeng Huo, Kun Li, Yiming Wu, and Zhenming Hu Copyright © 2014 Zhiqiang Chang et al. All rights reserved. Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases Mon, 02 Jun 2014 11:15:30 +0000 Purpose. To study the clinical, radiological, and pathological characteristics of abdominal desmoplastic small round cell tumor (DSRCT) and investigate the optimal therapy modalities. Patients and Methods. A retrospective cohort study was performed on 12 abdominal DSRCT patients; all pathological, radiological, and prognostic data were analyzed. There were 3 patients (25%) with metastatic disease at presentation. In all 12 cases, 6 cases underwent operation and adjuvant chemotherapy (group 1, 6/12, 50%). The other 6 cases were diagnosed by fine needle aspiration or exploratory laparotomy biopsy (group 2, 6/12, 50%); all cases received four to six courses of multiple agents chemotherapy, respectively. Results. All cases were finally diagnosed as DSRCT pathologically. Among group 1, all cases underwent en bloc resection (2/6, 33%) or tumor debulking (4/6, 67%) and, following four courses of multiple agents chemotherapy, Kaplan-Meier analysis revealed that 3-year survival was 50% in group 1 versus 16.7% in group 2 (). Gross tumor resection was highly significant in prolonging overall survival; patients with localized solitary lesion have a better prognosis, most likely due to increased feasibility of resection. Conclusions. DSRCT is a rare malignant tumor with poor prognosis. Surgical excision with combination chemotherapy as an adjunct is mandatory for nonmetastatic cases because these modalities used in isolation may have less impact. Guangzhao Zhang, Guangjun Liu, Dahua Zhao, Xijun Cui, and Gang Li Copyright © 2014 Guangzhao Zhang et al. All rights reserved. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma Thu, 22 May 2014 12:29:58 +0000 Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2) and cisplatin (50 mg/m2) infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR) was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I) and those who received several cycles (group II). The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (). The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (). The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT. Ming-Chun Ma, Yen-Yang Chen, Shau-Hsuan Li, Yu-Fan Cheng, Chih-Chi Wang, Tai-Jan Chiu, Sung-Nan Pei, Chien-Ting Liu, Tai-Lin Huang, Chen-Hua Huang, Yu-Li Su, Yen-Hao Chen, Sheng-Nan Lu, and Kun-Ming Rau Copyright © 2014 Ming-Chun Ma et al. All rights reserved. Determination of Acquisition Frequency for Intrafractional Motion of Pancreas in CyberKnife Radiotherapy Tue, 13 May 2014 09:26:44 +0000 Purpose. To report the characteristics of pancreas motion as tracked using implanted fiducials during radiotherapy treatments with CyberKnife. Methods and Materials. Twenty-nine patients with pancreas cancer treated using CyberKnife system were retrospectively selected for this study. During the treatment, the deviation is examined every 3-4 nodes (~45 s interval) and compensated by the robot. The pancreas displacement calculated from X-ray images acquired within the time interval between two consecutive couch motions constitute a data set. Results. A total of 498 data sets and 4302 time stamps of X-ray images were analyzed in this study. The average duration for each data set is 634 s. The location of the pancreas becomes more dispersed as the time elapses. The acquisition frequency depends on the prespecified movement distance threshold of pancreas. If the threshold between two consecutive images is 1 mm, the acquisition frequency should be less than 30 s, while if the threshold is 2 mm, the acquisition frequency can be around 1 min. Conclusions. The pancreas target moves significantly and unpredictably during treatment. Effective means of compensating the intrafractional movement is critical to ensure adequate dose coverage of the tumor target. Huailing Zhang, Guoru Zhao, David Djajaputra, and Yaoqin Xie Copyright © 2014 Huailing Zhang et al. All rights reserved. Effect of Preventive Hormonal Therapy on Breast Density: A Systematic Qualitative Review Sun, 27 Apr 2014 08:23:08 +0000 Breast density (BD) is recognized as one of the strongest independent risk factors of breast cancer (BC). Unlike most other risk factors, BD can be modified, suggesting that it may be a biomarker for preventive interventions. We conducted a qualitative systematic review to address the effect of preventive hormonal therapy on BD. Among the 26 relevant studies, 10 assessed the effect of tamoxifen on BD (TAM: ), 9 that of raloxifene (RLX: ), and 7 that of aromatase inhibitors (AI: ). The studies were characterized by a large heterogeneity in designs and in methods of BD measurement. BD could be reduced by TAM (10 studies/10). However, the effect of RLX and AI on BD remains unclear due to conflicting results between studies. Consequently, it is crucial to develop practical, accurate, and reproducible methods of measurement in order to be able to compare the effect of preventive hormonal agents on BD and to determine whether change in BD can be used as a predictor of response to therapy. Virginie Lienart, Birgit Carly, Xin Kang, Laura Guzy, Anna-Maria Sajovitz, and Fabienne Liebens Copyright © 2014 Virginie Lienart et al. All rights reserved. MicroRNA-222 Expression and Its Prognostic Potential in Non-Small Cell Lung Cancer Sun, 13 Apr 2014 11:18:19 +0000 Overexpression of miR-222 has been found in several types of cancers; however, the expression of miR-222 in non-small cell lung cancer (NSCLC) and its prognostic values are unclear. This study aimed to investigate whether the miR-222 expression level is related to clinicopathological factors and prognosis of NSCLC. Through a prospective study, 100 pairs of NSCLC tissues and adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between miR-222 expression and clinicopathological features was analyzed, and the significance of miR-222 as a prognostic factor and its relationship with survival were determined. Results showed that the expression levels of miR-222 were significantly elevated in the NSCLC tissue compared with that in adjacent normal tissue. In addition, Cox’s proportional hazards model analysis confirmed that miR-222 high expression level was an independent predictor of poor prognosis. In conclusion, miR-222 overexpression is involved in the poor prognosis of NSCLC and can be used as a biomarker for selection of cases requiring especial attention. Kai-ping Mao, Wei-na Zhang, Xiao-min Liang, and Yu-rong Ma Copyright © 2014 Kai-ping Mao et al. All rights reserved. Extracorporeal Ultrasound-Guided High Intensity Focused Ultrasound: Implications from the Present Clinical Trials Thu, 03 Apr 2014 09:46:54 +0000 Extracorporeal ultrasound-guided high intensity focused ultrasound (HIFU) has been clinically used for 15 years, and over 36000 cases have been reported. However, there yet lacked a consensus in the clinical values, suggesting the necessity of checking clinical findings. Clinical trials were searched and data reevaluated. HIFU was hardly performed alone; almost all present anticancer means have been applied during an HIFU treatment, and a specific regimen varied between trials; there were heterogeneity and disagreement between trials. The complexity made it difficult to distinguish the effect of HIFU. Based upon evaluable data, the efficacy of HIFU was similar to that of radio frequency, chemoembolization, chemotherapy, radiotherapy, or hormone therapy; a combined therapy did not improve the efficacy. The survival rate of HIFU plus radiotherapy was lower than that of radical surgery in liver cancers. Adverse events had no downtrend in the past years. HIFU was not a standardized procedure where the intensity and insonation mode were modified constantly throughout a treatment, limiting an evaluation from the perspective of ultrasonics. These implied that HIFU should be applied as an alternative at most occasions. The present clinical trials had defects making against the understating of HIFU. Tinghe Yu and Xiao Fu Copyright © 2014 Tinghe Yu and Xiao Fu. All rights reserved. Fragile Histidine Triad (FHIT) Suppresses Proliferation and Promotes Apoptosis in Cholangiocarcinoma Cells by Blocking PI3K-Akt Pathway Sun, 16 Mar 2014 08:25:27 +0000 Fragile histidine triad (FHIT) is a tumor suppressor protein that regulates cancer cell proliferation and apoptosis. However, its exact mechanism of action is poorly understood. Phosphatidylinositol 3-OH kinase (PI3K)-Akt-survivin is an important signaling pathway that was regulated by FHIT in lung cancer cells. To determine whether FHIT can regulate this pathway in cholangiocarcinoma QBC939 cells, we constructed an FHIT expression plasmid and used it to transfect QBC939 cells. Protein and mRNA expression were measured by western blotting and qRT-PCR, respectively. The viability and apoptosis of QBC939 cells were then assessed using MTT assays and flow cytometry. Our results revealed that the expression of survivin and Bcl-2 was downregulated, and caspase 3 was upregulated, in cells overexpressing FHIT. In addition, FHIT suppressed the phosphorylation of Akt. The changes in cell proliferation and apoptosis were obvious in cells overexpressing FHIT which parallels that of treatment with LY294002, a potent inhibitor of phosphoinositide 3-kinases. Treatment with LY294002 further decreased the expression of survivin and Bcl-2 and increased caspase-3 levels. These results suggest that FHIT can block the PI3K-Akt-survivin pathway by suppressing the phosphorylation of Akt and the expression of survivin and Bcl-2 and upregulating caspase 3. Qiang Huang, Zhen Liu, Fang Xie, Chenhai Liu, Feng Shao, Cheng-lin Zhu, and Sanyuan Hu Copyright © 2014 Qiang Huang et al. All rights reserved. Expression of Interleukin-17A in Lung Tissues of Irradiated Mice and the Influence of Dexamethasone Wed, 12 Mar 2014 11:17:11 +0000 Purpose. To investigate the expressions of IL-17A in different phases of radiation-induced lung injury and the effect of dexamethasone. Methods. The thorax of C57BL/6 mice was irradiated with 15 Gy rays. Mice from dexamethasone-treated group were injected intraperitoneally with dexamethasone (0.42 mg/kg/day) every day for the first month after irradiation. IL-17A in lung tissues was detected by immunohistochemistry. IL-17A, TGF-1, and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. Lung inflammation and collagen deposition were observed by H&E and Masson methods. The degree of alveolitis and fibrosis was judged according to scoring. Results. IL-17A expression was appreciable at 1 week, peaked at 4 weeks, and subsequently declined at 8 weeks after irradiation. IL-17A was reduced after dexamethasone application at all the observation periods. Dexamethasone also inhibited expressions of TGF-, IL-6, and TNF- in bronchoalveolar lavage fluid. Moreover, dexamethasone attenuated the severity of lung injury by reducing the infiltration of inflammatory cells and collagen deposition. Terms of survival and the time of death in mice of treatment group were postponed and survival rate was improved. Conclusions. IL-17A plays an important role in the process of radiation-induced lung injury. And dexamethasone may provide a protective role in lung injury induced by radiation. Li-Ping Wang, Yan-Wen Wang, Bao-Zhong Wang, Gui-Ming Sun, Xiu-Yu Wang, and Jun-long Xu Copyright © 2014 Li-Ping Wang et al. All rights reserved. Immunomodulatory Effects of Hemagglutinin- (HA-) Modified A20 B-Cell Lymphoma Expanded as a Brain Tumor on Adoptively Transferred HA-Specific CD4+ T Cells Sun, 16 Feb 2014 07:03:36 +0000 Previously, the mouse A20 B-cell lymphoma engineered to express hemagglutinin (HA) antigen (A20HA) was used as a systemic tumor model. In this work, we used the A20HA cells as a brain tumor. HA-specific CD4+ T cells were transferred intravenously in a tail vein 5 days after A20HA intracranial inoculation and analyzed on days 2, 9, and 16 after the adoptive transfer by different methods. The transferred cells demonstrated state of activation as early as day 2 after the adoptive transfer and most the of viable HA-specific cells became anergic on day 16. Additionally, symptoms of systemic immunosuppression were observed in mice with massive brain tumors at a late stage of the brain tumor progression (days 20–24 after the A20HA inoculation). Despite that, a deal of HA-specific CD4+ T cells kept the functional activity even at the late stage of A20HA tumor growth. The activated HA-specific CD4+ T cells were found also in the brain of brain-tumor-bearing mice. These cells were still responding to reactivation with HA-peptide in vitro. Our data support an idea about sufficient role of both the tumor-specific and -nonspecific mechanisms inducing immunosuppression in cancer patients. Valentin P. Shichkin and Roman M. Moriev Copyright © 2014 Valentin P. Shichkin and Roman M. Moriev. All rights reserved. The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma Tue, 21 Jan 2014 00:00:00 +0000 There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)—the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. The present review is an attempt to conceptualize the role of CSCs in HNSCC—its implication in tumorigenesis and the possible additional approach in current treatment strategies. Amit Shah, Shilpa Patel, Jigna Pathak, Niharika Swain, and Shwetha Kumar Copyright © 2014 Amit Shah et al. All rights reserved. The Incidence and Predictors of Thromboembolic Events in Patients with Lung Cancer Mon, 20 Jan 2014 06:46:18 +0000 Patients with lung cancer experience elevated risk of venous thromboembolism. Cancer patients with thrombosis have a shorter life expectancy and the occurrence of VTE worsens the quality of life and may delay, interrupt, or completely halt the cancer therapy. In a large cohort of lung cancer patients we monitored the incidence of venous thromboembolism and we identified groups of patients with the highest risk of venous thromboembolism suitable for antithrombotic prophylaxis, which could favourably affect their morbidity and mortality. Bohdan Kadlec, Jana Skrickova, Zdenek Merta, Ladislav Dusek, and Jiri Jarkovsky Copyright © 2014 Bohdan Kadlec et al. All rights reserved. The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells Sun, 19 Jan 2014 11:59:52 +0000 Multidrug resistance (MDR) is a major obstacle to the successful chemotherapy of solid tumors. We compared the resistance of the most popular solid tumors, breast adenocarcinoma (MCF-7 cell line) and nonsmall cell lung (A549 cell line) hepatocellular liver carcinoma (HepG2 cells), to aclarubicin (ACL) and doxorubicin (DOX). This research aimed at determining the relation between the toxicity of ACL and DOX, their cell accumulation, and then effect on P-glycoprotein functionality. ACL is more cytotoxic for tumor cells compared to DOX. The intracellular concentration of drugs in cancer cells was dependent on the dose of the drugs and the time of incubation. The P-gp inhibitor Verapamil (V) increased DOX accumulation in all tested cell lines. By contrast, the intracellular level of ACL was not affected by this modifying agent. The assessment of the uptake of 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide (JC-1) or Rhodamine 123 (R123) allows the evaluation of the different influence of drugs on P-gp activity which is in agreement with the estimation of expression measured by MDR-1 shift assay. These data suggest that ACL is less P-gp dependent than DOX and consequently may be used in a clinical setting to increase treatment efficacy in resistant human tumors. Aneta Rogalska, Marzena Szwed, and Błażej Rychlik Copyright © 2014 Aneta Rogalska et al. All rights reserved. Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics Tue, 14 Jan 2014 10:16:02 +0000 Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. Petra Hudler, Nina Kocevar, and Radovan Komel Copyright © 2014 Petra Hudler et al. All rights reserved. HPV Infection in Esophageal Squamous Cell Carcinoma and Its Relationship to the Prognosis of Patients in Northern China Sun, 12 Jan 2014 13:56:13 +0000 Purpose. Human papillomavirus (HPV) as a risk factor for esophageal squamous cell carcinoma (ESCC) has previously been studied, but importance of HPV status in ESCC for prognosis is less clear. Methods. A total of 105 specimens with ESCC were tested by in situ hybridization for HPV 16/18 and immunohistochemistry for p16 expression. The 5-year overall survival (OS) and progression-free survival were calculated in relation to these markers and the Cox proportional hazards model was used to determine the hazard ratio (HR) of variables in univariate and multivariate analysis. Results. HPV was detected in 27.6% (29) of the 105 patients with ESCC, and all positive cases were HPV-16. Twenty-five (86.2%) of the 29 HPV-positive tumors were stained positive for p16. HPV infected patients had better 5-year rates of OS (65.9% versus 43.4% among patients with HPV-negative tumors; P = 0.002 by the log-rank test) and had a 63% reduction in the risk of death (adjusted HR = 0.37, 95% CI = 0.16 to 0.82, and P = 0.01). Conclusions. HPV infection may be one of many factors contributing to the development of ESCC and tumor HPV status is an independent prognostic factor for survival among patients with ESCC. Fangli Cao, Hui Han, Fang Zhang, Baozhong Wang, Wei Ma, Yanwen Wang, Guiming Sun, Miao Shi, Yubo Ren, and Yufeng Cheng Copyright © 2014 Fangli Cao et al. All rights reserved. Molecular Alterations of PI3K/Akt/mTOR Pathway: A Therapeutic Target in Endometrial Cancer Sun, 12 Jan 2014 13:29:27 +0000 It is well established that the PI3K/Akt/mTOR pathway plays a central role in cell growth and proliferation. It has also been suggested that its deregulation is associated with cancer. Genetic alterations, involving components of this pathway, are often encountered in endometrial cancers. Understanding and identifying the rate-limiting steps of this pathway would be crucial for the development of novel therapies against endometrial cancer. This paper reviews alterations in the PI3K/Akt pathway, which could possibly contribute to the development of endometrial cancer. In addition, potential therapeutic targets of this pathway with emphasis on the mTOR inhibitors are also presented. Athanasia Pavlidou and Nikos F. Vlahos Copyright © 2014 Athanasia Pavlidou and Nikos F. Vlahos. All rights reserved. Anticancer and Antitumor Potential of Fucoidan and Fucoxanthin, Two Main Metabolites Isolated from Brown Algae Thu, 02 Jan 2014 14:17:39 +0000 Seaweed is one of the largest producers of biomass in marine environment and is a rich arsenal of active metabolites and functional ingredients with valuable beneficial health effects. Being a staple part of Asian cuisine, investigations on the crude extracts of Phaeophyceae or brown algae revealed marked antitumor activity, eliciting a variety of research to determine the active ingredients involved in this potential. The sulfated polysaccharide of fucoidan and carotenoid of fucoxanthin were found to be the most important active metabolites of brown algae as potential chemotherapeutic or chemopreventive agents. This review strives to provide detailed account of all current knowledge on the anticancer and antitumor activity of fucoidan and fucoxanthin as the two major metabolites isolated from brown algae. Soheil Zorofchian Moghadamtousi, Hamed Karimian, Ramin Khanabdali, Mahboubeh Razavi, Mohammad Firoozinia, Keivan Zandi, and Habsah Abdul Kadir Copyright © 2014 Soheil Zorofchian Moghadamtousi et al. All rights reserved. Pancreaticobiliary Maljunction Is Associated with Common Bile Duct Carcinoma: A Meta-Analysis Mon, 30 Dec 2013 11:23:56 +0000 Objective. Pancreaticobiliary maljunction (PBM) has been reported to be associated with an increased risk of gallbladder carcinoma. However, the relationship between PBM and common bile duct carcinoma (CBDC) remains unclear. We aimed to conduct a meta-analysis to determine the available evidence on the association between PBM and CBDC. Methods. The pooled odds ratio (OR) and standard mean differences (SMD) with 95% confidence interval (95% CI) were used to estimate the effects. Results. A total of eight case-control studies and two cohort studies were identified. The incidence of PBM was higher in CBDC patients than in controls (; 95% CI, 1.19–1.76). Compared with patients without PBM, CBDC patients with PBM were younger at the diagnosis age (; 95% CI, −0.64 to −0.28). A difference in the incidence of associated CDC was found between CBDC patients with or without PBM (; 95% CI, 1.60–2.87). Conclusions. Compared with benign biliary tract diseases, the incidence of PBM was higher in CBDC patients, especially in relatively young patients. We also found that the incidence of CDC was higher in CBDC patients with PBM. These findings showed positive association between PBM and CBDC, which may help in identifying high-risk individuals. Yang Li, Jun Wei, Zhongxin Zhao, Tiangeng You, and Mingan Zhong Copyright © 2013 Yang Li et al. All rights reserved. Lack of Significant Association between Plasma/Serum miR-221 Expression and Poor Survival of Carcinoma: A Meta-Analysis Mon, 04 Nov 2013 13:31:59 +0000 Background. MicroRNAs (miRNAs) exhibit altered expression levels in cancers, and they may play a potential role as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis was to summarize recent advances in miR-221 involvement in a variety of carcinomas and derive a more precise estimation of the relationship between circulating miR-221 level and survival of cancer patients. Methods. We searched online PubMed, EMBASE, and Cochrane Library up to August 2013 to identify relevant studies. Data were collected from studies comparing survival in patients with various carcinomas with higher miR-221 expression to those with lower levels. Pooled hazard ratios (HRs) of miR-221 for survival were calculated. Results. There were 4 studies included in the meta-analysis. The results of meta-analysis suggested that no significant difference in poor overall survival between miR-221 high and low groups (OR = 0.94, 95%, CI = 0.47–1.87, , and ). Conclusions. The current meta-analysis showed the equivalence of high and low plasma/serum miR-221 expression for carcinomas in terms of survival. Min-hua Rong, Yi-wu Dang, and Gang Chen Copyright © 2013 Min-hua Rong et al. All rights reserved. Clinical Implications of Girdin Protein Expression in Glioma Sun, 27 Oct 2013 11:38:42 +0000 Objective. To investigate the expression status of Girdin in glioma and the relationship between Girdin expression and the biological behavior of glioma. Materials and methods. The expression status of Girdin in glioma from 560 cases was evaluated by RT-PCR, Western Blot and immunohistochemistry. The relationship between Girdin expression and clinic-pathological parameters as well as prognosis was also studied. Results. The expression of Girdin in high grade glioma was significantly higher than low grade glioma. After universal analysis, the expression of Girdin protein is closely related to KPS score, extent of resection, Ki67 and WHO grade, but it was not related to sex and age. Finally, extent of resection, Ki67 and WHO grade were indentified to be related to the Girdin protein expression in logistic regression. Interestingly, we found that the expression of Girdin is significantly related to the distant metastasis of glioma. After COX regression analysis, KPS score, Extent of resection, Ki67, WHO grade as well as Girdin were observed to be independent prognostic factors. Conclusions. Girdin is differential expressed in the glioma patients and closely related to the biological behavior of Glioma. Finally, Girdin was found to be a strong predictor for the post-operative prognosis. Liwei Zhao, Shuyin Ma, Qing Liu, and Peng Liang Copyright © 2013 Liwei Zhao et al. All rights reserved. Expression and Significance of MicroRNA-183 in Hepatocellular Carcinoma Thu, 10 Oct 2013 15:53:22 +0000 Objective. In our previous study, we found that some miRNAs were deregulated in hepatocellular carcinoma (HCC), including miR-183. However, the expression of miR-183 in the progression of benign liver diseases to HCC and its correlation with clinicopathologic factors remain undefined. Methods. MiR-183 expression was measured in normal controls (NC) (), chronic viral hepatitis B or C (CH) tissues (), liver cirrhosis (LC) tissues (), HCC tissues (), and adjacent nontumor tissues (NT) () by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). Results. The expression levels of miR-183 were significantly higher in HCC than in NT, LC, CH, and NL (, , , , resp.). The upregulated miR-183 in HCC was correlated with TNM stage () and cirrhosis (). The Kaplan-Meier survival analysis showed that miR-183 expression was not associated with the survival of HCC patients. However, miR-183 yielded an area under the curve (AUC) of 0.808 with 59.8% sensitivity and 91.8% specificity in discriminating HCC from benign liver diseases (CH and LC) or NC. Conclusions. The upregulated miR-183 may associate with onset and progression of HCC, but not with the patient survival. A further research is needed to determine the potential of miR-183 as biomarker for HCC. Zenghui Liang, Yingtang Gao, Wenxia Shi, Daokuan Zhai, Shilei Li, Li Jing, Hua Guo, Tong Liu, Yajie Wang, and Zhi Du Copyright © 2013 Zenghui Liang et al. All rights reserved. Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Meta-Analysis Thu, 03 Oct 2013 18:47:35 +0000 Recently, there have been a number of studies on the association between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between cyclin D1 G870A polymorphism and the risk of nasopharyngeal carcinoma. No significant association was found between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Caucasian subgroup, and no significant association in any genetic models among Asians was observed. In summary, positive results have been shown on the search for polymorphic variants influencing the risk of NPC. This meta-analysis provides evidence of the association between CCND1 G870A polymorphism and NPC risk, supporting the hypothesis that CCND1 870A allele probably acts as an important NPC protective factor in Caucasians but not in Asians. Since the results of our meta-analysis are preliminary and may be biased by the relatively small number of subjects, they still need to be validated by well-designed studies using larger samples in the future. Meng Li, Weijian Dai, and Huanqin Zhou Copyright © 2013 Meng Li et al. All rights reserved. A Mathematical Model of Tumor Volume Changes during Radiotherapy Thu, 03 Oct 2013 08:35:31 +0000 Purpose. To develop a clinically viable mathematical model that quantitatively predicts tumor volume change during radiotherapy in order to provide treatment response assessment for prognosis, treatment plan optimization, and adaptation. Method and Materials. The correction factors containing hypoxia, DNA single strand breaks, potentially lethal damage, and other factors were used to develop an improved cell survival model based on the popular linear-quadratic model of cell survival in radiotherapy. The four-level cell population model proposed by Chvetsov et al. was further simplified by removing the initial hypoxic fraction and reoxygenation parameter, which are hard to obtain in routine clinics, such that an easy-to-use model can be developed for clinical applications. The new model was validated with data of nine lung and cervical cancer patients. Results. Out of the nine cases, the new model can predict tumor volume change in six cases with a correlation index greater than 0.9 and the rest of three with greater than 0.85. Conclusion. Based on a four-level cell population model, a more practical and simplified cell survival curve was proposed to model the tumor volume changes during radiotherapy. Validation study with patient data demonstrated feasibility and clinical usefulness of the new model in predicting tumor volume change in radiotherapy. Ping Wang and Yuanming Feng Copyright © 2013 Ping Wang and Yuanming Feng. All rights reserved. Synthesis and Properties of Macrocyclic Butanoic Acid Conjugates as a Promising Delivery Formulation for the Nutrition of Colon Wed, 18 Sep 2013 14:02:46 +0000 Butanoic acid plays a significant role in the maintenance of mucosal health and is the preferred energy substrate for the cells in the colon. Here, butanoic acid was selectively conjugated to the secondary hydroxyl group of β-cyclodextrin through ester bond using sodium hydride as the deprotonation reagent. The preliminary release behaviors of butanoic acid in rat gastrointestinal tract contents were investigated at 37°C within 12 h. In the contents of stomach, the conjugates did seldom release butanoic acid, released butanoic acid only 5.8% in the contents of small intestine, and released butanoic acid significantly up to 38.4% in the contents of colon. These results indicate that the conjugate activation took place site specifically in the rat colonic contents, via the biodegradation by glycosidases and hydrolases in the colon. Therefore, the β-cyclodextrin conjugates of butanoic acid may be of value as an orally administered colon-specific formulation for the nutrition of colon. Jingui Cheng, Benpeng Li, Peipei Ma, Mengying Liu, and Zhizhong Wang Copyright © 2013 Jingui Cheng et al. All rights reserved. Clinical Significance of Preoperative Neutrophil Lymphocyte Ratio versus Platelet Lymphocyte Ratio in Patients with Small Cell Carcinoma of the Esophagus Thu, 05 Sep 2013 15:34:49 +0000 Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various of cancers. The aim of this study was to determine the prognostic values of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with small cell carcinoma of the esophagus (SCCE). Preoperative NLR and PLR were evaluated in 43 patients with SCCE from January 2001 to December 2010. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC) curves were also plotted to verify the accuracy of NLR and PLR for survival prediction. Patients with PLR ≥150 had significantly poorer (relapse-free survival) RFS and (overall survival) OS compared to patients with PLR <150. However, RFS or OS did not differ according to NLR categories (<3.5 and ≥3.5). The areas under the curve (AUC) indicated that PLR was superior to NLR as a predictive factor. The results of the present study conclude that PLR is superior to NLR as a predictive factor in patients with SCCE. Ji-Feng Feng, Ying Huang, Qiang Zhao, and Qi-Xun Chen Copyright © 2013 Ji-Feng Feng et al. All rights reserved. Elevated Preoperative Serum CA19-9 Levels in Patients with Hepatocellular Carcinoma Is Associated with Poor Prognosis after Resection Wed, 12 Jun 2013 17:29:10 +0000 Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status, α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC. Yu-Ling Chen, Chien-Hung Chen, Rey-Heng Hu, Ming-Chih Ho, and Yung-Ming Jeng Copyright © 2013 Yu-Ling Chen et al. All rights reserved. 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns Thu, 04 Apr 2013 16:27:52 +0000 Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity. 18F-Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of 18F-FLT-PET in a GBM mouse model, especially after radiation therapy (RT), and its correlation with useful biomarkers, including proliferation and DNA damage. Methods. Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with 18F-FDG and 18F-FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki-67), DNA damage and repair (H2AX), hypoxia (HIF-1), and angiogenesis (VEGF). Results. We confirmed that 18F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that 18F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. 18F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers. Sanjay Chandrasekaran, Andrew Hollander, Xiangsheng Xu, Joseph L. Benci, James J. Davis, Jay F. Dorsey, and Gary Kao Copyright © 2013 Sanjay Chandrasekaran et al. All rights reserved. Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells Sun, 03 Mar 2013 15:19:53 +0000 Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting. Lei-qing Li, Fang Shen, Xiao-yan Xu, Hong Zhang, Xiao-feng Yang, and Wei-guo Liu Copyright © 2013 Lei-qing Li et al. All rights reserved. VEGF Promotes Proliferation of Human Glioblastoma Multiforme Stem-Like Cells through VEGF Receptor 2 Thu, 28 Feb 2013 17:52:57 +0000 Cancer stem-like cells, which have been described as tumor-initiating cells or tumor-propagating cells, play a crucial role in our fundamental understanding of glioblastoma multiforme (GBM) and its recurrence. GBM is a lethal cancer, characterized by florid vascularization and aberrantly elevated vascular endothelial growth factor (VEGF). VEGF promotes tumorigenesis and angiogenesis of human GBM stem-like cells (GBSCs). However, whether and how VEGF contributes to GBSCs proliferation remain largely uncertain. In this study, human GBSCs were isolated from surgical specimens of glioblastoma and cultured in medium favored for stem cell growth. Neural Colony-Forming Cell Assay and ATP assay were performed to measure GBSC proliferation under normoxia (20% O2) and hypoxia (1% O2). Our observations demonstrate that exogenous VEGF stimulates GBSC proliferation in a dose-dependent manner via VEGF Receptor 2 (VEGFR2); while VEGF Receptor 1 (VEGFR1) has a negative feedback effect on VEGFR2 when cells were exposed to higher concentration of VEGF. These results suggest that suppressing VEGFR2-dependent GBSC proliferation is a potentially therapeutic strategy in GBM. Chengshi Xu, Xing Wu, and Jianhong Zhu Copyright © 2013 Chengshi Xu et al. All rights reserved. Delivery Parameter Variations and Early Clinical Outcomes of Volumetric Modulated Arc Therapy for 31 Prostate Cancer Patients: An Intercomparison of Three Treatment Planning Systems Tue, 15 Jan 2013 16:01:59 +0000 We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)—ERGO++, Monaco, or Pinnacle—and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3 ± 17.7, 149.7 ± 8.4, and 185.8 ± 15.6 MU/min and 132.7 ± 8.4, 217.6 ± 13.1, and 127.5 ± 27.1 sec. During a follow-up period of 486.2 ± 289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (). Each TPS was successfully used for prostate VMAT planning without significant differences in early clinical outcomes despite significant TPS-specific delivery parameter variations. Shinichi Tsutsumi, Masako N. Hosono, Daisaku Tatsumi, Yoshitaka Miki, Yutaka Masuoka, Ryo Ogino, Kentaro Ishii, Yasuhiko Shimatani, and Yukio Miki Copyright © 2013 Shinichi Tsutsumi et al. All rights reserved. Fluctuating Roles of Matrix Metalloproteinase-9 in Oral Squamous Cell Carcinoma Tue, 08 Jan 2013 13:19:49 +0000 One hallmark of cancer is the degradation of the extracellular matrix (ECM), which is caused by proteinases. In oral cancers, matrix metalloproteinases (MMPs), especially MMP-9, are associated with this degradation. MMPs break down the ECM allowing cancer to spread; they also release various factors from their cryptic sites, including cytokines. These factors modulate cell behavior and enhance cancer progression by regulating angiogenesis, migration, proliferation, and invasion. The development of early metastases is typical for oral cancer, and increased MMP-9 expression is associated with a poor disease prognosis. However, many studies fail to relate MMP-9 expression with metastasis formation. Contrary to earlier models, recent studies show that MMP-9 plays a protective role in oral cancers. Therefore, the role of MMP-9 is complicated and may fluctuate throughout the different types and stages of oral cancers. Suvi-Tuuli Vilen, Tuula Salo, Timo Sorsa, and Pia Nyberg Copyright © 2013 Suvi-Tuuli Vilen et al. All rights reserved. Outcome of R-CHOP or CHOP Regimen for Germinal Center and Nongerminal Center Subtypes of Diffuse Large B-Cell Lymphoma of Chinese Patients Sun, 04 Nov 2012 09:13:41 +0000 Diffuse large B-cell lymphoma (DLBCL) can be molecularly subtyped as either germinal center B-cell (GCB) or non-GCB. The role of rituximab(R) in these two groups remains unclear. We studied 204 patients with de novo DLBCL (107 treated with first-line CHOP; 97 treated with first-line R-CHOP), patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10, and MUM1 protein expression. The relationships between clinical characteristics, survival data, and immunophenotype (IHC) were studied. The 5-year overall survival (OS) in the CHOP and R-CHOP groups was 50.4% and 66.6% (), respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP or not (65.0% versus 40.9%; ). In contrast, there is no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% versus 61.3%; ). In non-GCB subtype, additional rituximab improved survival better than CHOP (61.3% versus 40.9%; ). These results indicated that addition of rituximab to standard chemotherapy eliminates the prognostic value of IHC-defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL. Ying Huang, Sheng Ye, Yabing Cao, Zhiming Li, Jiajia Huang, He Huang, Muyan Cai, Rongzhen Luo, and Tongyu Lin Copyright © 2012 Ying Huang et al. All rights reserved. Brain Metastases Research 1990–2010: Pattern of Citation and Systematic Review of Highly Cited Articles Mon, 17 Sep 2012 12:36:45 +0000 Background. High and continuously increasing research activity related to different aspects of prevention, prediction, diagnosis and treatment of brain metastases has been performed between 1990 and 2010. One of the major databases contains 2695 scientific articles that were published during this time period. Different measures of impact, visibility, and quality of published research are available, each with its own pros and cons. For this overview, article citation rate was chosen. Results. Among the 10 most cited articles, 7 reported on randomized clinical trials. Nine covered surgical or radiosurgical approaches and the remaining one a widely adopted prognostic score. Overall, 30 randomized clinical trials were published between 1990 and 2010, including those with phase II design and excluding duplicate publications, for example, after longer followup or with focus on secondary endpoints. Twenty of these randomized clinical trials were published before 2008. Their median number of citations was 110, range 13–1013, compared to 5-6 citations for all types of publications. Annual citation rate appeared to gradually increase during the first 2-3 years after publication before reaching high levels. Conclusions. A large variety of preclinical and clinical topics achieved high numbers of citations. However, areas such as quality of life, side effects, and end-of-life care were underrepresented. Efforts to increase their visibility might be warranted. Carsten Nieder, Anca L. Grosu, and Minesh P. Mehta Copyright © 2012 Carsten Nieder et al. All rights reserved. Temozolomide as Second or Third Line Treatment of Patients with Neuroendocrine Carcinomas Wed, 22 Aug 2012 10:29:21 +0000 Background. Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results. Patients and Methods. Analysis of consecutive patients with neuroendocrine carcinomas (Ki-67 proliferation index >20%) and performance status 0–2 treated with temozolomide 200 mg/sqm orally days 1–5 every 28 days after at least one previous platin-containing chemotherapy regimen. Results. Twenty-eight eligible patients received a median of 3 courses. Sixteen patients were evaluable for response: Six achieved stable disease and ten progressed. The median survival for the 28 patients was 3.5 months. Survival in patients with tumors of pancreatic origin (𝑛=7) was 7.0 months versus 2.9 months in non-pancreatic origin (𝑛=21). Patients in PS 0-1 (𝑛=22) had a median survival of 4.5 months versus 1.1 months in patients in PS 2 (𝑛=6). Ki-67 index ≥50% was associated with a significantly shorter median survival than Ki-67 index <50% (2.7 months versus 10.9 months). The treatment was well tolerated. Conclusion. Temozolomide monotherapy has limited effect in treatment of recurrent neuroendocrine carcinomas. Second line treatment with temozolomide in combination with other compounds should be further investigated in patients in good performance with Ki-67 index <50%. Ingrid H. Olsen, Jens B. Sørensen, Birgitte Federspiel, Andreas Kjaer, Carsten P. Hansen, Ulrich Knigge, and Seppo W. Langer Copyright © 2012 Ingrid H. Olsen et al. All rights reserved. Erratum to “The Role of Neurokinin-1 Receptor in the Microenvironment of Inflammation and Cancer” Thu, 02 Aug 2012 10:29:26 +0000 Marisa Rosso Copyright © 2012 Marisa Rosso. All rights reserved. Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas Thu, 02 Aug 2012 08:47:28 +0000 Aberrant wnt pathway activation through cytoplasmic stabilization of β-catenin is crucial for the development of various human malignancies. In gliomagenesis, the role of canonical (i.e., β-catenin-dependent) signalling is largely unknown. Here, we studied canonical wnt pathway activation in 15 short-term cultures from high-grade gliomas and potential pathomechanisms leading to cytoplasmic β-catenin accumulation. Furthermore, we assessed the prognostic relevance of β-catenin expression in a tissue microarray comprising 283 astrocytomas. Expression of β-catenin, its transcriptional cofactors TCF-1 and TCF-4 as well as GSK-3β and APC, constituents of the β-catenin degradation complex was confirmed by RT-PCR in all cultures. A cytoplasmic β-catenin pool was detectable in 13/15 cultures leading to some transcriptional activity assessed by luciferase reporter gene assay in 8/13. Unlike other malignancies, characteristic mutations of β-catenin and APC leading to cytoplasmic stabilization of β-catenin were excluded by direct sequencing or protein truncation test. In patient tissues, β-catenin expression was directly and its degradation product's (β-catenin-P654) expression was inversely correlated with WHO grade. Increased β-catenin expression and low β-catenin-P654 expression were associated with shorter survival. Altogether, we report on potential canonical wnt pathway activation in high-grade gliomas and demonstrate that β-catenin expression in astrocytomas is associated with increased malignancy and adverse outcome. Rebecca Schüle, Christine Dictus, Benito Campos, Feng Wan, Jörg Felsberg, Rezvan Ahmadi, Franz-Simon Centner, Niels Grabe, Guido Reifenberger, Justo L. Bermejo, Andreas Unterberg, and Christel Herold-Mende Copyright © 2012 Rebecca Schüle et al. All rights reserved. Local Treatment of Hand-Foot Syndrome with Uridine/Thymidine: In Vitro Appraisal on a Human Keratinocyte Cell Line HaCaT Tue, 31 Jul 2012 12:53:31 +0000 5-fluorouracil (5-FU) is one of the most commonly used antineoplastic drugs in the anticancer therapy. The hand-foot (HF) syndrome (palmar-plantar erythrodysesthesia) is an adverse effect frequently related to long-term i.v. administration of 5-FU or its orally applicable prodrug capecitabine. Its severity can even lead to interruption of the otherwise effective anticancer therapy. Tentative practice in some clinics has shown that topical application of 10% uridine ointment is beneficial for calming down the HF syndrome. This study is focused on verifying the alleged protective activity of uridine in the in vitro model of cultured human keratinocyte cell line HaCaT. We also tested the protective effects of thymidine alone or uridine-thymidine combination. The cellular viability time progression was measured in order to evaluate the effect of protective agents by three different types of cytopathogenicity tests—NTCA test (non-destructive test of cellular activity), modified MTT test and RTCA (real-time cell analyser, Roche). All three methods proved the ability of uridine and uridine-thymidine combination to protect keratinocytes against 5-FU damage in vitro. While thymidine alone did not show any remarkable effect, the thymidine-uridine combination demonstrated enhanced protective activity compared to uridine alone. Our findings provided the supporting rationale for using uridine or uridine-thymidine ointments in the HF syndrome local therapy. J. Hartinger, P. Veselý, E. Matoušková, S. Argalacsová, L. Petruželka, and I. Netíková Copyright © 2012 J. Hartinger et al. All rights reserved. 18FDG Uptake in Sinonasal Inverted Papilloma Detected by Positron Emission Tomography/Computed Tomography Tue, 31 Jul 2012 09:12:05 +0000 Inverted papilloma (IP) is a benign but locally aggressive sinonasal tumour. Aggressive surgical treatment has thus been traditionally recommended because of the risk of transformation in squamous carcinoma. CT and MRI are used to evaluate bone destruction and soft-tissue extension before surgery but may be ineffective to differentiate an inverted papilloma from squamous cell carcinoma. In recent years, F-18 Fluorodeoxyglucose positron emission tomography (18FDG-PET) is widely used as diffuse imaging procedure for diagnosis and followup of malignancy affecting the head and neck district. To evaluate the utility of 18FDG-PET/CT in the diagnosis of patients with suspicious lesions for IP, twelve patients with suspicious sinonasal inverted papilloma were selected for this study. 18FDG-PET/CT imaging was performed, and standard uptake value (SUV) was calculated for each patient. SUVmax was considered as the maximum value measured in the visualized lesions. Seven of the twelve cases exhibited uptake of 18FFDG with an SUVmax ranging from 1 to 8.1. Histopathologic diagnosis after surgery confirmed the diagnosis of IP in five cases; all these cases had an SUVmax>3. The five cases, which exhibited absence of 18FDG uptake, had a histological diagnosis of absence of IP. E. Allegra, M. G. Cristofaro, L. G. Cascini, N. Lombardo, O. Tamburrini, and A. Garozzo Copyright © 2012 E. Allegra et al. All rights reserved. The Association between Single-Nucleotide Polymorphisms of ORAI1 Gene and Breast Cancer in a Taiwanese Population Mon, 18 Jun 2012 10:29:34 +0000 Background. Breast cancer is the most common malignancy in women. There is increasing evidence suggesting that ORAI1, components of store-operated calcium channel, play a pivotal role in breast cancer progression and metastasis. Methods. A total of 384 female patients with breast cancer were included in this study. We selected five representative tagging ORAI1 SNPs from HapMap database with minimum allele frequency (MAF) >10%. Genotyping was performed using TaqMan allelic discrimination assay. Chi-square (χ2) test was used to analyze statistical differences among control and patient groups in genotype and allelic frequencies. Results. Two of the ORAI1 SNPs (rs12320939 and rs12313273) were associated with estrogen receptors positive in breast cancer patients under the recessive model. When the Bonferroni correction was performed, the significance still existed. In addition, rs12320939 also associated with the lymph nodal involvement. Conclusion. We showed that genetic polymorphisms of ORAI1 associated strongly with lymph nodal involvement and estrogen receptors (ERs) positive breast cancer patients in a Taiwanese population. Wei-Chiao Chang, Peng Yeong Woon, Yu-Wen Hsu, Shengyu Yang, Yi-Ching Chiu, and Ming Feng Hou Copyright © 2012 Wei-Chiao Chang et al. All rights reserved. Screening for Depression, Sleep-Related Disturbances, and Anxiety in Patients with Adenocarcinoma of the Pancreas: A Preliminary Study Tue, 22 May 2012 17:34:21 +0000 Purpose. Screening for depression, sleep-related disturbances, and anxiety in patients with diagnosed adenocarcinoma of the pancreas. Materials and Methods. Patients were evaluated at initial consultation and subsequent visits at the multidisciplinary pancreatic cancer clinic at our University Cancer Center. Cross-sectional and longitudinal psychosocial distress was assessed utilizing Personal Health Questionnaire 9 (PHQ9) to screen for depression and monitor symptoms, the Penn State Worry Questionnaire (PSWQ) for generalized anxiety, and the University of Michigan Sleep Questionnaire to monitor sleep symptoms. Results. Twenty-two patients diagnosed with pancreatic cancer participated during the 6-month pilot study with longitudinal followup for thirteen patients. In this study, mild-to-moderate depressive symptoms, anxiety, and potential sleep problems were common. The main finding of the study was 23% of the patients who were part of this pilot project screened positive for moderately severe major depressive symptoms, likely anxiety disorder or a potential sleep disorder during the study. One patient screened positive for moderately severe depressive symptoms in longitudinal followup. Conclusions. Depression, anxiety, and sleep problems are evident in patients with pancreatic cancer. Prospective, longitudinal studies, with larger groups of patients, are needed to determine if these comorbid symptoms impact outcome and clinical course. Andrew D. Boyd, Doris Brown, Chris Henrickson, Janet Hampton, Bin Zhu, Farideh Almani, Edgar Ben-Josef, Mark Zalupski, Diane M. Simeone, Jeremy M. G. Taylor, Roseanne Armitage, and Michelle Riba Copyright © 2012 Andrew D. Boyd et al. All rights reserved. Survival after Locoregional Treatments for Hepatocellular Carcinoma: A Cohort Study in Real-World Patients Thu, 03 May 2012 10:55:21 +0000 Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79–1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64–1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66–1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment. Simona Signoriello, Annalisa Annunziata, Nicola Lama, Giuseppe Signoriello, Paolo Chiodini, Ilario De Sio, Bruno Daniele, Giovanni G. Di Costanzo, Fulvio Calise, Graziano Olivieri, Vincenzo Castaldo, Rosario Lanzetta, Guido Piai, Giampiero Marone, Mario Visconti, Mario Fusco, Massimo Di Maio, Francesco Perrone, Ciro Gallo, and Giovanni B. Gaeta Copyright © 2012 Simona Signoriello et al. All rights reserved. Lymph Node Harvest in Dukes' A Cancer Pathologist May Need to Consider Fat Dissolving Technique: An Observational Study Thu, 03 May 2012 08:51:36 +0000 Background. National institute of clinical excellence (NICE) recommends that a median of 12 lymph nodes be examined in patients operated on with curative intent- to- treat colorectal cancer (CRC). Patients with lymph node harvest less than this may be considered under staged and may receive adjuvant chemotherapy. The aim of our study was to ascertain median number of lymph nodes examined in early colorectal cancers. Method. Patients undergoing colorectal resection between June 2007 and May 2008 were identified and pathological staging obtained using pathology database. Results. 146 patients underwent standardised laparoscopic or open resection of colorectal cancers during this period. Overall median number of lymph nodes harvested/patient was 14 (3–40). When analysed by stage, median number of lymph nodes harvested in Dukes' A, B, and C cancers was 10, 14, and 15, respectively. 11/18 (61%) patients with Dukes’ A carcinoma had lymph node harvest of less than 12 compared with 15/55 (27%) patients with Dukes’ B. Conclusion. Lymph node harvest in Dukes' A cancers using standard techniques tends to be low. Pathologists may have to consider special techniques in harvesting lymph nodes for early colorectal cancers. A. P. Saklani, T. Udy, T. V. Chandrasekaran, M. Davies, and J. Beynon Copyright © 2012 A. P. Saklani et al. All rights reserved. A Review for Solitary Plasmacytoma of Bone and Extramedullary Plasmacytoma Wed, 02 May 2012 13:57:05 +0000 Solitary plasmacytoma (SP) is characterized by a mass of neoplastic monoclonal plasma cells in either bone (SBP) or soft tissue without evidence of systemic disease attributing to myeloma. Biopsy confirmation of a monoclonal plasma cell infiltration from a single site is required for diagnosis. The common presentation of SBP is in the axial skeleton, whereas the extramedullary plasmacytoma (EMP) is usually seen in the head and neck. The ratio of SP seen at males to females is 2 : 1 and the median age of patients is 55 years. The incidence rate of SP in black race is approximately 30% higher than the white race. Incidence rate increases exponentially by advancing age. SBP has a significant higher risk for progression to myeloma, and the choice of treatment is radiotherapy (RT) that is applied with curative intent at min. 4000 cGy. By only RT application, long-term disease-free survival (DFS) is possible for approximately 30% of patients with SBP and 65% of patients with EMP. Sevil Kilciksiz, Omur Karakoyun-Celik, Fulya Yaman Agaoglu, and Ayfer Haydaroglu Copyright © 2012 Sevil Kilciksiz et al. All rights reserved. Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma Wed, 02 May 2012 11:53:56 +0000 Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC). Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation. Swati Saawarn, Madhusudan Astekar, Nisheeth Saawarn, Nidhi Dhakar, and Shitalkumar Gomateshwar Sagari Copyright © 2012 Swati Saawarn et al. All rights reserved. Diagnostic Value of Breast Proton Magnetic Resonance Spectroscopy at 1.5T in Different Histopathological Types Tue, 01 May 2012 15:52:52 +0000 The purpose of this study was to investigate the usefulness of quantitative proton magnetic resonance spectroscopy (1H-MRS) for characterizing breast lesions at 1.5T, and to evaluate the diagnostic performance of in vivo breast 1H-MRS using receiver operating characteristics (ROC) analysis. 112 patients (99 malignant and 13 benign tumors) who were scanned with the MRI/MRS protocol were included in this study. Choline-containing compounds (tCho) levels were measured and compared with histological findings. The measured tCho levels in this work had range of 0.08–9.99 mmol/kg from 65 (66%) of 99 patients with malignant tumors. Of the 13 benign lesions, 1H-MRS detected one as false positive, with tCho level of 0.66 mmol/kg. The optimal tCho level cutoff point that yielded the highest accuracy was found to be >0.0 mmol/kg. The resulting sensitivity was 66% and specificity 92% for distinguishing benign from malignant lesions. The tCho levels were found to be higher in invasive cancer compared to ductal carcinoma in situ or benign lesions, possibly associated with more aggressive behavior or faster cell replication in invasive cancer. Quantitative in vivo  1H-MRS may provide useful information for characterizing histopatholoigical types in breast cancer. Hyeon-Man Baek Copyright © 2012 Hyeon-Man Baek. All rights reserved. Growth Inhibition by Caffeic Acid, One of the Phenolic Constituents of Honey, in HCT 15 Colon Cancer Cells Sun, 29 Apr 2012 10:48:46 +0000 Previous work from our laboratory showed that the mechanism of crude-honey induced apoptosis in colon cancer cells. Since phenolic constituents of honey were attributed to its apoptosis-inducing ability, we studied caffeic acid, one of the phenolic constituents of honey, induced effect on colon cancer cells. Antiproliferative effect of caffeic acid was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. MTT assay signified the antiproliferative nature of caffeic acid against the HCT 15 colon cancer cells. A time-dependent inhibition of colony formation was evident with caffeic acid treatment. Cell-cycle analysis of caffeic acid- (CA-) treated cells indicated increasing accumulation of cells at sub-G1 phase. Photomicrograph images of treated cells showed membrane blebbing and cell shrinkage. Yo-pro-1 staining of caffeic-acid-treated cells confirmed apoptosis in dose- and time-dependent manner. Increasing ROS generation and reduction in the mitochondrial membrane potential were also accompanied in the caffeic acid-induced apoptosis. This work will promote caffeic acid as a likely candidate in the chemoprevention of colon cancer. Saravana Kumar Jaganathan Copyright © 2012 Saravana Kumar Jaganathan. All rights reserved. Colorectal Cancer Chemoprevention: Is This the Future of Colorectal Cancer Prevention? Sun, 29 Apr 2012 09:59:17 +0000 Colorectal cancer (CRC) is presently one of the most common causes of cancer-related death in our setting and affects a great number of people each year. Screening strategies are commonly used but they do not seem enough to avoid CRC development or prevent completely its mortality. Because of this fact other prevention strategies have gained interest in recent years. Chemoprevention seems to be an attractive option in this setting and several drugs have been studied in this field. This review is focused on salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs) and cycloxygenase-2 inhibitors (COXIBs), whose mechanism of action could be directly related to colon cancer chemoprevention. A. Manzano and P. Pérez-Segura Copyright © 2012 A. Manzano and P. Pérez-Segura. All rights reserved. Prognostic Significance of Serum Proangiogenic Molecules in Patients with De Novo Non-Hodgkin Lymphomas Thu, 26 Apr 2012 15:20:38 +0000 This study was aimed to assess the clinical significances of the serum VEGF and bFGF in Thai patients with de novo NHL. Serum VEGF and bFGF concentrations were measured from 79 adult patients with newly diagnosed stage 2–4 non-Hodgkin lymphomas by quantitative sandwich enzyme immunoassay. At the time of diagnosis, the serum VEGF concentrations from 79 patients ranged from 72.0 to 2919.4 pg/mL, with a mean of 668.0 pg/dL. The serum bFGF concentrations ranged from undetectable to 2919.4 pg/mL, with a mean of 12.15 pg/dL. Multivariate analysis identified higher than the mean of serum VEGF, B symptoms, bulky diseases, anemia, and treatment with CHOP or R-CHOP as independent variables influencing the complete remission rate. From a Cox proportional hazards model, variables independently associated with overall survival were bone marrow involvement, more extranodal involvement, poor performance status, anemia, and higher than the mean of serum bFGF. Pairaya Rujirojindakul and Arnuparp Lekhakula Copyright © 2012 Pairaya Rujirojindakul and Arnuparp Lekhakula. All rights reserved. Comparing Health-Related Quality of Life of Cancer Patients under Chemotherapy and of Their Caregivers Tue, 24 Apr 2012 11:44:49 +0000 Introduction. Cancer is a major disorder physically and psychologically affecting both patients and their caregivers. In this study, health-related quality of life (HRQoL) of patient-caregiver dyads during the period of chemotherapy was assessed. Material and Methods. Two hundred twenty-two cancer patient-caregiver dyads were enrolled in the study, which was conducted from October 2008 to March 2009. HRQoL was evaluated with EQ-5D. Results. The mean age of the sample was 57.4 and 48.9 for patients and caregivers, respectively. The EQ-5D descriptive system indicates that female patients more frequently experience anxiety and depression than male patients. Male and higher-education caregivers had higher VAS scores, while demographic factors did not seem to influence patients’ HRQoL. Anxiety and depression of caregivers were correlated with patients’ problems in self-care and usual activities. Conclusions. Quality of life is highly influenced during the period of chemotherapy for both patients and caregivers and is often under reported. Interventions that can improve HRQoL, especially in the domain of mental health for both cancer patients and their caregivers, need to be implemented. Ioannis Vrettos, Konstantinos Kamposioras, Nick Kontodimopoulos, Evelina Pappa, Elissavet Georgiadou, Dionysios Haritos, Angelos A. Papadopoulos, and Dimitris Niakas Copyright © 2012 Ioannis Vrettos et al. All rights reserved. Towards Improved Prognostic Scores Predicting Survival in Patients with Brain Metastases: A Pilot Study of Serum Lactate Dehydrogenase Levels Thu, 19 Apr 2012 16:15:51 +0000 Accurate prognostic information is desirable when counselling patients with brain metastases regarding their therapeutic options and life expectancy. Based on previous studies, we selected serum lactate dehydrogenase (LDH) as a promising factor on which we perform a pilot study investigating methodological aspects of biomarker studies in patients with brain metastases, before embarking on large-scale studies that will look at a larger number of candidate markers in an expanded patient cohort. For this retrospective analysis, 100 patients with available information on LDH treated with palliative whole-brain radiotherapy were selected. A comprehensive evaluation of different LDH-based variables was performed in uni- and multivariate tests. Probably, the most intriguing finding was that LDH kinetics might be more important, or at least complement, information obtained from a single measurement immediately before radiotherapy. LDH and performance status outperformed several other variables that are part of prognostic models such as recursive partitioning analyses classes and graded prognostic assessment score. LDH kinetics might reflect disease behaviour in extracranial metastatic and primary sites without need for comprehensive imaging studies and is a quite inexpensive diagnostic test. Based on these encouraging results, confirmatory studies in a larger cohort of patients are warranted. Carsten Nieder, Kirsten Marienhagen, Astrid Dalhaug, and Jan Norum Copyright © 2012 Carsten Nieder et al. All rights reserved. Genetic Aspects of Gastric Cancer Instability Thu, 19 Apr 2012 15:58:43 +0000 Unravelling the molecular mechanisms underlying gastric carcinogenesis is one of the major challenges in cancer genomics. Gastric cancer is a very complex and heterogeneous disease, and although much has been learned about the different genetic changes that eventually lead to its development, the detailed mechanisms still remain unclear. Malignant transformation of gastric cells is the consequence of a multistep process involving different genetic and epigenetic changes in numerous genes in combination with host genetic background and environmental factors. The majority of gastric adenocarcinomas are characterized by genetic instability, either microsatellite instability (MSI) or chromosomal instability (CIN). It is believed that chromosome destabilizations occur early in tumour progression. This paper summarizes the most common genetic alterations leading to instability in sporadic gastric cancers and its consequences. Petra Hudler Copyright © 2012 Petra Hudler. All rights reserved. The Role of Neurokinin-1 Receptor in the Microenvironment of Inflammation and Cancer Sun, 01 Apr 2012 08:50:19 +0000 The recent years have witnessed an exponential increase in cancer research, leading to a considerable investment in the field. However, with few exceptions, this effort has not yet translated into a better overall prognosis for patients with cancer, and the search for new drug targets continues. After binding to the specific neurokinin-1 (NK-1) receptor, the peptide substance P (SP), which is widely distributed in both the central and peripheral nervous systems, triggers a wide variety of functions. Antagonists against the NK-1 receptor are safe clinical drugs that are known to have anti-inflammatory, analgesic, anxiolytic, antidepressant, and antiemetic effects. Recently, it has become apparent that SP can induce tumor cell proliferation, angiogenesis, and migration via the NK-1 receptor, and that the SP/NK-1 receptor complex is an integral part of the microenvironment of inflammation and cancer. Therefore, the use of NK-1 receptor antagonists as a novel and promising approach for treating patients with cancer is currently under intense investigation. In this paper, we evaluate the recent scientific developments regarding this receptor system, its role in the microenvironment of inflammation and cancer, and its potentials and pitfalls for the usage as part of modern anticancer strategies. Marisa Rosso, Miguel Muñoz, and Michael Berger Copyright © 2012 Marisa Rosso et al. All rights reserved. Sociodemographic Determinants of Nonattendance in a Population-Based Mammography Screening Program in the City of Manisa, Turkey Mon, 12 Mar 2012 14:21:53 +0000 Objectives. Community based breast cancer screening has decreased breast cancer mortality in women. This study examined the predictors of nonattendence for invitational breast cancer screening in relation to socioeconomic status in the city of Manisa, in western Turkey. Study Design. For the evaluation of the reasons for refusing to participate in the study, two districts were selected. 446 women aged between 50 and 69 years were selected from the program database by systematic random sampling. Methods. The questionnaire consisted of sociodemographic variables and the adapted version of Champion's Health Belief Model Scale. Univariete and multivariete logistic regression analysis were performed throughout the data analysis. Results. Being from an urban district and being from the western region were the risk factors for not participating in the screening program (𝑃=0.014, 𝑃=0.023). A statistical significance was found between mammography-benefit, mammography-barrier and program participation (𝑃=0.044, 𝑃=0.006). Although there were many more barriers for not participating in the screening program for the women of the slum district, the attendence rate of the slum district was higher than that of the urban district. Conclusions. Increased attendance may be achieved through enhancement of breast cancer awareness and by reducing some of the modifiable barriers. Pınar Erbay Dundar, Beyhan Cengiz Ozyurt, and Koray Erdurak Copyright © 2012 Pınar Erbay Dundar et al. All rights reserved. Skin and Soft Tissue Infections in Patients with Solid Tumours Wed, 01 Feb 2012 14:28:32 +0000 Background. Skin and soft tissue infections (SSTIs) in cancer patients represent a diagnostic challenge, as etiologic diagnosis is often missing, and clinical assessment of severity is difficult. Few studies have described (SSTIs) in patients with solid tumours (STs). Patients and Methods. Records of patients with ST and SSTI, cared for at the University Hospital of Heraklion, from 2002 to 2006 were retrospectively studied. Results. A total of 81 episodes of SSTIs, occurring in 71 patients with ST, have been evaluated. Their median age was 65 years (34–82). The most common underlying malignancy was breast cancer in 17 patients (24%). Most episodes (89%) occurred in nonneutropenics. Cellulitis/erysipelas was the most common clinical presentation (56; 69%). Bacterial cultures were possible in 29 (36%) patients. All patients received antimicrobial therapy, while in 17 episodes (21%) an incision and drainage was required. Treatment failure occurred in 20 episodes (25%). Five patients (7%) died due to sepsis. None was neutropenic. Severe sepsis on admission (𝑃=0.002) and prior blood transfusion (𝑃=0.043) were independent predictors of treatment failure. Conclusion. SSTIs can be life threatening among patients with ST. Early diagnosis and appropriate treatment are of the utmost importance, since sepsis was proven a significant factor of unfavourable outcome. Diamantis P. Kofteridis, Antonios Valachis, Eirini Koutsounaki, Sofia Maraki, Eleni Mavrogeni, Foteini N. Economidou, Dimitra Dimopoulou, Kostas Kalbakis, Vassilis Georgoulias, and George Samonis Copyright © 2012 Diamantis P. Kofteridis et al. All rights reserved. Cancer Surgery in the Elderly Tue, 03 Jan 2012 16:04:27 +0000 The proportions both of elderly patients in the world and of elderly patients with cancer are both increasing. In the evaluation of these patients, physiologic age, and not chronologic age, should be carefully considered in the decision-making process prior to both cancer screening and cancer treatment in an effort to avoid ageism. Many tools exist to help the practitioner determine the physiologic age of the patient, which allows for more appropriate and more individualized risk stratification, both in the pre- and postoperative periods as patients are evaluated for surgical treatments and monitored for surgical complications, respectively. During and after operations in the oncogeriatric populations, physiologic changes occuring that accompany aging include impaired stress response, increased senescence, and decreased immunity, all three of which impact the risk/benefit ratio associated with cancer surgery in the elderly. Gopal C. Kowdley, Nishant Merchant, James P. Richardson, Justin Somerville, Myriam Gorospe, and Steven C. Cunningham Copyright © 2012 Gopal C. Kowdley et al. All rights reserved. Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications Thu, 27 Oct 2011 00:00:00 +0000 Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Although early diagnosis has contributed to therapeutic success, breast cancer remains a major health issue. In the last few year the hormone therapy for estrogen-dependent breast cancer has evolved achieving significant clinical results; at the same time, it has enabled us to better define the role of estrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. Specific obesity-associated factors, including leptin, insulin and inflammatory mediators, seem to influence breast cancer growth and prognosis independently of estrogens and at least in part by interacting with estrogen signalling at a cellular level. Therefore, a careful assessment of the nutritional status and body composition is paramount for a proper therapeutic approach for postmenopausal breast carcinoma. The use of antidiabetic and anti-inflammatory drugs associated with conventional hormone therapies and dietary/physical interventions could offer a new therapeutic approach for breast carcinoma that develops in the context of adiposity. Antonio Macciò and Clelia Madeddu Copyright © 2011 Antonio Macciò and Clelia Madeddu. All rights reserved. Update on Chemotherapy in the Treatment of Urothelial Carcinoma Wed, 26 Oct 2011 00:00:00 +0000 Urothelial carcinoma is the fifth most common malignancy diagnosed each year in the United States. Neoadjuvant and adjuvant chemotherapy are given to decrease the risk of recurrent or metastatic disease with the more robust clinical data supporting the former. Bladder preservation utilizes a trimodality approach with maximal transurethral resection followed by concurrent chemotherapy and radiation and is appropriate for select patients. Gemcitabine and cisplatin is the current standard of care for first-line treatment in fit patients with metastatic disease. Optimal second-line therapy remains undefined, and targeted agents are under investigation. Clinical trial participation should be encouraged in patients with urothelial carcinoma of the bladder to help improve treatment regimens and outcomes. Synopsis. Chemotherapy is commonly used in the treatment of urothelial carcinoma of the bladder. This paper will review the role of chemotherapy in the neoadjuvant, adjuvant, bladder sparing, and metastatic settings. Carrie Costantini and Frederick Millard Copyright © 2011 Carrie Costantini and Frederick Millard. All rights reserved. Rubin H. Flocks and Colloidal Gold Treatments for Prostate Cancer Tue, 16 Aug 2011 00:00:00 +0000 In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au198) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks' time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments. Henry M. Rosevear, Andrew J. Lightfoot, Michael A. O'Donnell, Charles E. Platz, Stefan A. Loening, and Charles E. Hawtrey Copyright © 2011 Henry M. Rosevear et al. All rights reserved. Rapid Treatment of Leukostasis in Leukemic Mantle Cell Lymphoma Using Therapeutic Leukapheresis: A Case Report Tue, 16 Aug 2011 00:00:00 +0000 We describe a case of severe leukocytosis caused by leukemic mantle cell lymphoma (MCL), complicated by leukostasis with myocardial infarction in which leukapheresis was used in the initial management. A 73-year-old male presented to the emergency department because of fatigue and thoracic pain. Blood count revealed 630 × 109/L WBC (white blood cells). The electrocardiogram showed ST-elevation with an increase of troponin and creatinine kinase. The diagnosis was ST-elevation myocardial infarction (STEMI) induced and complicated by leukostasis. Immunophenotyping, morphology, cytogenetic and fluorescence-in-situ-hybridization analysis revealed the diagnosis of a blastoid variant of MCL. To remove leukocytes rapidly, leukapheresis was performed in the intensive care unit. Based on the differential blood count with 95% blasts, which were assigned to the lymphocyte population by the automatic hematology analyzer, leukapheresis procedures were then performed with the mononuclear cell standard program on the Spectra cell separator. The patient was treated with daily leukapheresis for 3 days. The WBC count decreased to 174 × 109/L after the third leukapheresis, with a 72% reduction. After the second apheresis, treatment with vincristine, cyclophosphamide, and prednisolone was started. The patient fully recovered in the further course of the treatment. To the best of our knowledge, this is the first report on blastoid MCL with leukostasis associated with a STEMI that was successfully treated by leukapheresis. Effective harvest of circulating lymphoma cells by leukapheresis requires adaptation of instrument settings based on the results of the differential blood count prior to apheresis. Xuan Duc Nguyen, Paul La Rosée, Thomas Nebe, Harald Klüter, and Dieter Buchheidt Copyright © 2011 Xuan Duc Nguyen et al. All rights reserved. Xanthogranulomatous Cystitis: A Challenging Imitator of Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature. Sinan Ekici, Isin Dogan Ekici, Sevket Ruacan, and Ahmet Midi Copyright © 2010 Sinan Ekici et al. All rights reserved. Best Approach for Low-Risk Superficial Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 In order to create better criteria for different grades of superficial bladder tumor, the WHO and ISUOP develop a new classification in 1998, which was modified in 2004. Although the new classification might be more reproducible, it has not yet been widely accepted. The low risk groups include patients with single Ta, G1, ≤3cm diameter tumors. This group has high recurrence and low progression rates. The standard treatment is the complete resection and postoperative single immediate instillation of whatever chemotherapy agent should be considered. Eduardo Solsona Copyright © 2006 Eduardo Solsona. All rights reserved. Comorbidity, Use of Common Medications, and Risk of Early Death in Patients with Localized or Locally Advanced Prostate Cancer Mon, 01 Jan 1900 00:00:00 +0000 In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer) in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years). Actuarial survival analyses were performed. During the first 3 years, two patients (1.1%) died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4%) was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI) scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition). The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis). However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis. Carsten Nieder, Astrid Dalhaug, Adam Pawinski, Gro Aandahl, and Jan Norum Copyright © 2011 Carsten Nieder et al. All rights reserved. Changing Management of Clinical Low-Stage Testicular Cancer Mon, 01 Jan 1900 00:00:00 +0000 Stage I and II testicular germ cell tumors (GCTs) are almost always cured with appropriate treatment and most ongoing research regarding these tumors focuses on minimizing treatment toxicity. The management of clinical stage I testicular GCTs has grown more complicated due to the emergence of a brief course of chemotherapy as an additional treatment option for stage I seminomas and stage I nonseminomas. In addition, growing concern about radiation-induced cancers and other late toxicity has dulled enthusiasm for radiotherapy as a treatment for stage I seminomas. However, recent randomized trials have shown that radiotherapy doses and field sizes can be lowered without compromising cure rates and it is possible that this reduction in radiation exposure will reduce the rate of secondary cancers. At this point in history, stage I patients have three treatment options following radical orchiectomy: adjuvant (sometimes called “primary”) chemotherapy (carboplatin for seminomas and the combined regimen of bleomycin, etoposide, and cisplatin for nonseminomas), surveillance, and either retroperitoneal lymph node dissection (for nonseminomas) or radiotherapy (for pure seminomas). Clinical studies have made it possible to identify subgroups of patients at high and low risk for relapse and this has made it possible to tailor treatment decisions to the individual patient's postorchiectomy relapse risk. Timothy Gilligan Copyright © 2005 Timothy Gilligan. All rights reserved. Practical Aspects of Allogeneic Hematopoietic Cell Transplantation for Patients with Poor-Risk Chronic Lymphocytic Leukemia Mon, 01 Jan 1900 00:00:00 +0000 Allogeneic hematopoietic cell transplantation has become a viable option for younger patients with poor-risk chronic lymphocytic leukemia. The results obtained with either conventional or reduced-intensity conditioning regimens have been recently evaluated and compared with alternative nontransplant strategies. This manuscript deals with practical aspects of the procedure, including patient and donor selection, conditioning regimen, GVHD prophylaxis, disease monitoring, infectious and noninfectious complications, and timing of the procedure. Finally, we speculate on how we could improve the results obtained with the procedure and new advances currently in clinical trials. Julio Delgado and Rafael F. Duarte Copyright © 2011 Julio Delgado and Rafael F. Duarte. All rights reserved. Five-Year, Disease-Free Survival after Repeat Palliative Multimodality Therapy in a Patient with Recurrent Metastastic Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 In appropriately selected cases, palliative therapeutic strategies can be adapted to those special features of cancer biographies that indicate an atypical course of disease. Elucidating these features, and adapting multimodal treatment strategies to them, can lead to significantly superior effects when compared to the routine application of conventional treatment algorhythms. A case of regionally metastactic bladder cancer is presented that documents the value of repeat debulking-surgery and repeat radiotherapy leading to unexpected short-term and long-term treatment results. Sebastian Fetscher, Jan Schmielau, and Wolfgang Schulze-Seemann Copyright © 2007 Sebastian Fetscher et al. All rights reserved. Predictors of Outcome of Non–Muscle-Invasive and Muscle-Invasive Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non–muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10–30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non–muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinoma in situ are the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies. Ramy F. Youssef and Yair Lotan Copyright © 2011 Ramy F. Youssef and Yair Lotan. All rights reserved. Laparoscopic Radical Nephrectomy: The New Gold Standard Surgical Treatment for Localized Renal Cell Carcinoma Mon, 01 Jan 1900 00:00:00 +0000 We will try to demonstrate that laparoscopic radical nephrectomy could be the new gold standard treatment for renal cell carcinoma with the aid of the current reports exploring the advantages and disadvantages of laparoscopic radical nephrectom overopen surgery. Saadettin Yilmaz Eskicorapci, Dogu Teber, Michael Schulze, Mutlu Ates, Christian Stock, and Jens J. Rassweiler Copyright © 2007 Saadettin Yilmaz Eskicorapci et al. All rights reserved. Radiotherapeutic Strategies in the Management of Low-Risk Prostate Cancer Mon, 01 Jan 1900 00:00:00 +0000 Prostate cancer is the most common nonskin malignancy among men in the United States. Since the introduction of screening with prostate-specific antigen (PSA), most patients are being diagnosed at an early stage with low-risk disease. For men with low-risk prostate cancer, there exists an array of radiotherapeutic strategies that are effective and well tolerated, such as external-beam radiotherapy and brachytherapy. In recent years, there have been tremendous advances in the field of radiation oncology that have transformed the way radiation is used to treat prostate cancer, such as intensity-modulated radiotherapy, image-guided radiotherapy, and stereotactic radiotherapy. It is now feasible to deliver high doses of radiation to the target volume with improved precision and spare more of the neighboring tissues from potentially damaging radiation. Disease outcomes are generally excellent in low-risk prostate cancer. Improvements are expected with further integration of innovative technologies in radiation delivery, tumor imaging, and target localization. Kevin S. Choe and Stanley L. Liauw Copyright © 2010 Kevin S. Choe and Stanley L. Liauw. All rights reserved. Physician Satisfaction in a Cancer Prevention Program for Low-Income Women in Nevada Mon, 01 Jan 1900 00:00:00 +0000 Physicians and health care organizations that provide services to low-income patients are valuable partners in improving health care access for the uninsured and medically underserved. In this pilot study, we explored physicians' needs and factors for satisfaction in the Women's Health Connection (WHC), a breast and cervical cancer-screening program for low-income women in Nevada. Of the 126 physicians in the WHC program, 50 physicians completed a needs-and-satisfaction questionnaire. Survey data were subjected to factor analysis using Varimax rotation. The results yielded three components, which accounted for 65% of the variance. The three components or dimensions for physician satisfaction were: (1) appropriate administrative support and documentation, (2) availability of support for medical management, and (3) timeliness of diagnostic reports. Amount of reimbursement was not a significant factor. The respondents serving in this cancer prevention program for low-income women were satisfied in their involvement in the program. Further attention should be given on the identified issues for satisfaction among physicians, which could lead to quality improvement and serve as a model for other programs that serve low-income patients in cancer prevention. Christopher R. Cochran and Emmanuel C. Gorospe Copyright © 2007 Christopher R. Cochran and Emmanuel C. Gorospe. All rights reserved. Internal Iliac Artery Embolization for the Control of Severe Bladder Hemorrhage Secondary to Carcinoma: Long-Term Follow-Up Mon, 01 Jan 1900 00:00:00 +0000 The purpose of this study was to evaluate the efficacy and long-term complications of internal iliac artery embolization as a palliative measure in the control of intractable hemorrhage from advanced bladder malignancy. From January 1998 through December 2005, seven patients underwent transcatheter arterial embolization (TAE) of anterior division of internal iliac artery bilaterally for intractable bladder hemorrhage. After embolization, patients were followed for the efficacy of the procedure in controlling hematuria and complications. TAE was successful in immediate control of severe hemorrhage in all seven patients after a mean period of 4 days. At a mean (range) follow-up of 10 (6–12) months, the hemorrhage was permanently controlled in four (57%) patients. Three patients developed hematuria and required emergency admissions; two had mild hematuria and were managed conservatively, and the remaining one required a second attempt of embolization after 2 months from the first one. During the whole period of follow-up, there were no significant complications related to embolization. Internal iliac artery embolization is an effective and minimally invasive option when managing advanced bladder malignancies presenting with intractable bleeding. The long-term follow-up showed control of bleeding in the majority of such patients with no serious complications. Ahmed El-Assmy and Tarek Mohsen Copyright © 2007 Ahmed El-Assmy and Tarek Mohsen. All rights reserved. The Utilization of Gleason Grade as the Primary Criterion for Ordering Nuclear Bone Scan in Newly Diagnosed Prostate Cancer Patients Mon, 01 Jan 1900 00:00:00 +0000 Utilization of nuclear bone scans for staging newly diagnosed prostate cancer has decreased dramatically due to PSA-driven stage migration. The current criteria for performing bone scans are based on limited historical data. This study evaluates serum PSA and Gleason grade in predicting positive scans in a contemporary large series of newly diagnosed prostate cancer patients. Eight hundred consecutive cases of newly diagnosed prostate cancer over a 64-month period underwent a staging nuclear scan. All subjects had histologically confirmed cancer. The relationship between PSA, Gleason grade, and bone scan was examined by calculating series of crude, stratified, and adjusted odds ratios with corresponding 95% confidence intervals. Four percent (32/800) of all bone scans were positive. This proportion was significantly lower in patients with Gleason score ≤7 (1.9%) vs. Gleason score ≥8 (18.8%, p < 0.001). Among patients with Gleason score ≤7, the rate of positive bones scans was 70-fold higher when the PSA was >30 ng/ml compared to ≤30 ng/ml (p < 0.001). For Gleason score ≥8, the rate was significantly higher (27.9 vs. 0%) when PSA was >10 ng/ml compared to ≤10 ng/ml (p = 0.002). The combination of Gleason score and PSA enhances predictability of bone scans in newly diagnosed prostate cancer patients. The PSA threshold for ordering bone scans should be adjusted according to Gleason score. For patients with Gleason scores ≤7, we recommend a bone scan if the PSA is >30 ng/ml. However, for patients with a high Gleason score (8–10), we recommend a bone scan if the PSA is >10 ng/ml. Chad W. M. Ritenour, John T. Abbott, Michael Goodman, Naomi Alazraki, Fray F. Marshall, and Muta M. Issa Copyright © 2009 Chad Ritenour et al. All rights reserved. Giant Spermatic Cord Lipoma Mon, 01 Jan 1900 00:00:00 +0000 Robert A. Edelstein Copyright © 2009 Robert Edelstein. All rights reserved. Epididymal Metastasis from Carcinoma of the Prostate Mon, 01 Jan 1900 00:00:00 +0000 Epididymal Metastasis from a primary carcinoma of the prostate gland is a rare but recognised phenomena. We describe a case of such metastasis which, unlike previous reports, presents as a painful epididymal mass. Therefore it is important for urologists to consider epididymal metastasis as part of the differential diagnosis in a patient with known carcinoma of the prostate and a tender epididymal mass. C. Heman-Ackah, Dip Urol, A. T. Fox, and J. El-Jabbour Copyright © 2004 C. Heman-Ackah et al. All rights reserved. Intraprostatic Injection of Alcohol Gel for the Treatment of Benign Prostatic Hyperplasia: Preliminary Clinical Results Mon, 01 Jan 1900 00:00:00 +0000 Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-based procedures offer the advantage of being more effective than medications, while limiting the adverse effects, cost, and recovery of surgery. This study presents preliminary data on a new procedure that utilizes intraprostatic alcohol gel injection to ablate prostatic tissue. The purpose of this study is to evaluate the feasibility of using this gel as a treatment for BPH. Benjamin T. Larson, Nelson Netto, Christian Huidobro, Marcelo Lopez de Lima, Wagner Matheus, Cristian Acevedo, and Thayne R. Larson Copyright © 2006 Benjamin T. Larson et al. All rights reserved. Osteosclerotic Prostatic Metastasis Mon, 01 Jan 1900 00:00:00 +0000 Edmund C.P. Chedgy, Ibrahim Niematallah, and Amr Hawary Copyright © 2010 Edmund C.P. Chedgy et al. All rights reserved. A Unique Case of a Malignant Sertoli Cell Tumour with Cutaneous Metastasis Mon, 01 Jan 1900 00:00:00 +0000 Pure Sertoli cell tumours (SCTs) represent less than 1% of testicular neoplasms and malignant forms are rare. We present a unique case of a 69-year-old man who initially underwent inguinal orchidectomy for a malignant SCT. He then subsequently developed a paraumbilical cutaneous lesion which was histologically identical to the primary tumour. SCTs rarely metastasise. This is the first case of SCT with cutaneous metastasis described in the literature. C. Blick, S. Abdelhadi, D. Bailey, J. Kelleher, and A. Muneer Copyright © 2008 C. Blick et al. All rights reserved. Reversible Renal Insufficiency Secondary to Extrinsic Splenic Compression of the Kidney in a Patient with Chronic Lymphocytic Leukemia Mon, 01 Jan 1900 00:00:00 +0000 While increased renal venous and direct renal parenchymal pressure may cause renal insufficiency, there are no prior reports of hypersplenism secondary to chronic lymphocytic leukemia (CLL) doing so. This first report of massive splenomegaly leading to marked compression of the left kidney associated with renal insufficiency that resolved after splenectomy illustrates that profound extrinsic renal compression from splenomegaly may significantly compromise left renal function and splenectomy should be considered in this situation. Miriam Hadj-Moussa and James A. Brown Copyright © 2010 Miriam Hadj-Moussa and James A. Brown. All rights reserved. Primary Paratesticular Osteosarcoma: Case Report and A Review of the Literature Mon, 01 Jan 1900 00:00:00 +0000 Primary paratesticular osteosarcoma is an extremely rare malignancy and, to date, only a few cases have been reported. To our knowledge, no such case arising directly from paratesticular soft tissue has been described. We describe a 52-year-old man who presented with left scrotal swelling and an excisional biopsy that revealed a sarcomatous lesion. Left inguinal orchiectomy was performed and histologic examination of the extensively sampled lesion revealed a pure paratesticular osteosarcoma. The patient died 6 months after the diagnosis with disseminated disease. Anwar Al-Masri, Mubarak Al-Shraim, Ahmad Abu Al-Samen, Runjan Chetty, and Andrew Evans Copyright © 2007 Anwar Al-Masri et al. All rights reserved. Role of Re-Resection in Non–Muscle-Invasive Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Restaging, or second transurethral resection (TUR), is essential to successful management of high-risk, non–muscle-invasive bladder cancer. Here we review the relevant literature documenting the role of restaging TUR. Cohort and randomized studies show that restaging TUR detects more tumors than initial TUR, improves clinical staging, and reduces the frequency of early tumor recurrences. Our conclusions show thatrestaging TUR improves the outcomes of high-risk, non–muscle-invasive bladder neoplasms. Harry W. Herr Copyright © 2011 Harry W. Herr. All rights reserved. New Strategies in the Treatment of Ta-T1 Transitional Cell Carcinoma (TCC) of the Bladder Mon, 01 Jan 1900 00:00:00 +0000 In recent years, there have been many advances in the treatment of superficial bladder cancer. Standard intravesical chemotherapeutic agents can now be delivered more effectively thanks to new technological advances in drug delivery. Local microwave hyperthermia and electromotive drug administration are of particular interest. Research has also shown that different combinations of drugs and sequential drug delivery of two or more different drugs for differing periods of time also increase the effectiveness of possible treatments of superficial bladder cancer. Furthermore, new chemotherapeutic drugs for intravesical use are being investigated in various clinical trials, with gemcitabine showing particularly promising results. Also in the pipeline are new approaches to treatment such as gene therapy, but these will need to be developed much more before they become part of routine practice. Maurizio A. Brausi Copyright © 2006 Maurizio A. Brausi. All rights reserved. A Special Key for Unlocking the Door to Targeted Therapies of Breast Cancer Mon, 01 Jan 1900 00:00:00 +0000 Kristina Lindemann, Nadia Harbeck, Ernst Lengyel, and James H. Resau Copyright © 2008 Kristina Lindemann et al. All rights reserved. Robot-Assisted Radical Cystectomy in the Management of Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 The application of robotic technology to laparoscopic surgery has the potential to revolutionize the entire field of urology. The use of robotic-assisted radical cystectomy has been demonstrated in the literature only within the past 3 years, as much of the reconstruction and urinary diversion techniques associated with radical cystectomy are considered more technically challenging than other procedures. Here we review the available literature pertaining to this procedure, which consists of a limited number of case reports, case series, and pilot or feasibility studies. While theses results seem to point towards less blood loss, lower transfusion rates, and shorter hospital stays compared to open radical cystectomy, definitive conclusions and recommendations cannot yet be made because of a lack of larger and/or prospective studies or randomized trials. Jessica L. Keim and Dan Theodorescu Copyright © 2006 Jessica L. Keim and Dan Theodorescu. All rights reserved. Testicular Polyarteritis Nodosa Mimicking Testicular Neoplasm Mon, 01 Jan 1900 00:00:00 +0000 Polyarteritis nodosa (PAN) presents mostly as a systemic disease characterized by necrotizing vasculitis affecting small- and medium-sized arteries. Rarely, the inflammatory process is isolated and involves a single organ without systemic manifestations. We described the case of a 57-year-old patient with isolated testicular PAN who presented with a testicular mass mimicking a primary testicular tumor. Gokhan Atis, Omer Faruk Memis, Hasan Samet Güngör, Ozgur Arikan, Yesim Saglican, and Turhan Caskurlu Copyright © 2010 Gokhan Atis et al. All rights reserved. Diffusion-Weighted MR Imaging in Diagnosis of Superficial and Invasive Urinary Bladder Carcinoma: A Preliminary Prospective Study Mon, 01 Jan 1900 00:00:00 +0000 We conducted a prospective study to demonstrate the feasibility of using diffusionweighted (DW) magnetic resonance imaging (MRI) for the detection of urinary bladder carcinomas. Between January to June 2007, 43 patients with single bladder tumor were included in our study. Before taking a biopsy, DW MRI was obtained in the axial plane under free breathing scanning with a multisection, spin-echo type, single-shot echo planar sequence with a body coil. Moreover, the apparent diffusion coefficient (ADC) value was measured in a circular region of interest within the carcinoma, urine, normal bladder wall, prostate, and seminal vesicle. All carcinomas in the 43 patients were clearly shown as high signal intensity relative to the surrounding structure. The sensitivity and positive predictive values of DW MRI were 100% in terms of correctly detecting the carcinomas. The ADC value in the carcinoma (1.40 ± 0.51) was significantly lower compared with that of urine (3.50 ± 0.43) (p < 0.001), normal bladder wall (2.29 ± 0.78) (p < 0.001), peripheral zone of prostate (1.77 ± 0.44) (p < 0.05), transition zone of prostate (1.88 ± 0.54) (p < 0.05), and the seminal vesicle (2.12 ± 0.43) (p < 0.001). There was no statistical difference in ADC values between different histological subtypes. There was no overlap between the ADC values of the tumors and the urine, but there was no clear cutoff between the tumor and bladder wall, prostate, or seminal vesicles. Bladder carcinomas have significantly lower ADC when compared to surroundings. Clinical experience with this method is still preliminary and further studies are required. Ahmed El-Assmy, Mohamed E. Abou-El-Ghar, Huda F. Refaie, and Tarek El-Diasty Copyright © 2008 Ahmed El-Assmy et al. All rights reserved. Rationality and Irrationality in Ryke Geerd Hamer's System for Holistic Treatment of Metastatic Cancer Mon, 01 Jan 1900 00:00:00 +0000 The aim of this paper is to examine if the “medical laws” found by the German physician Ryke Geerd Hamer are substantiated by contemporary holistic medical theory. He developed a psychosomatic theory after a personal emotional trauma that he believed resulted in his subsequent development of a testicular cancer. From our analysis, it is clear that the two most fundamental principles of Hamer's work, the psychosomatic “iron law of cancer” (Hamer's first “law”) and the principle of pathogenesis being reversed into salutogenesis (Hamer's second “law”), are well-established principles of holistic medicine today. Hamer's understanding of symbols in medicine, virus and bacteria, and the evolutionary process itself (Hamer's third, fourth, and fifth “law”) differs a great deal from both traditional and contemporary holistic medical theory and we did not find them substantiated. Hamer's understanding of cancer metastasis was built on these failing principles and therefore not substantiated either. Altogether, it seems that Hamer's thinking was basically sound as the most fundamental principles of his work were built on an understanding very similar to holistic medical thinkers of today. We found his postulate that metastatic cancer patients can be healed or their health improved by using his system of holistic medicine likely to be true, at least for some motivated patients. This must be tested scientifically, however, before being accepted. His presentation of his system and work has been idiosyncratic and highly provocative, which has alienated him from the whole medical community. Søren Ventegodt, Niels Jørgen Andersen, and Joav Merrick Copyright © 2005 Soren Ventegodt et al. All rights reserved. The Role of Pelvic Lymphadenectomy in the Management of Prostate and Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 A pelvic lymph node dissection is commonly performed by urologists in the surgical management of prostate and bladder cancer. Identification of lymph node metastases provides important prognostic information for both diseases. Despite advances in radiographic imaging, a pelvic lymphadenectomy remains the most accurate method to stage lymph node involvement. In the past two decades, there has been an increase in the diagnosis of early stage prostate cancer, which has led some to omit a pelvic lymphadenectomy in patients thought to have low probability of positive lymph nodes. There is little debate, however, over the inclusion of a lymph node dissection in bladder cancer given the approximately 25% incidence of unsuspected nodal disease at the time of surgery. Controversy exists over the extent of an appropriate lymphadenectomy and its therapeutic efficacy. This review will examine the need, extent, and the potential prognostic and therapeutic benefits of a pelvic lymphadenectomy in prostate and bladder cancer. Michael E. Woods, Michael Ouwenga, and Marcus L. Quek Copyright © 2007 Michael E. Woods et al. All rights reserved. Minimal Residual Disease Diagnostics and Chimerism in the Post-Transplant Period in Acute Myeloid Leukemia Mon, 01 Jan 1900 00:00:00 +0000 In acute myeloid leukemia (AML), the selection of poor-risk patients for allogeneic hematopoietic stem cell transplantation (HSCT) is associated with rather high post-transplant relapse rates. As immunotherapeutic intervention is considered to be more effective before the cytomorphologic manifestation of relapse, post-transplant monitoring gains increasing attention in stem cell recipients with a previous diagnosis of AML. Different methods for detection of chimerism (e.g., microsatellite analysis or quantitative real-time PCR) are available to quantify the ratio of donor and recipient cells in the post-transplant period. Various studies demonstrated the potential use of mixed chimerism kinetics to predict relapse of the AML. CD34+-specific chimerism is associated with a higher specificity of chimerism analysis. Nevertheless, a decrease of donor cells can have other causes as well. Therefore, efforts continue to introduce minimal residual disease (MRD) monitoring based on molecular mutations in the post-transplant period. The NPM1 (nucleophosmin) mutations can be monitored by sensitive quantitative real-time PCR in subsets of stem cell recipients with AML, but for approximately 20% of patients, suitable molecular mutations for post-transplant MRD monitoring are not available so far. This emphasizes the need for an expansion of the panel of MRD markers in the transplant setting. Ulrike Bacher, Torsten Haferlach, Boris Fehse, Susanne Schnittger, and Nicolaus Kröger Copyright © 2011 Ulrike Bacher et al. All rights reserved. Perils and Pitfalls Regarding Differential Diagnosis and Treatment of Primary Cutaneous Anaplastic Large-Cell Lymphoma Mon, 01 Jan 1900 00:00:00 +0000 Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL), belonging to the CD30+ T-cell lymphoproliferative disorders (PCLPDs), is a rare T-cell lymphoma, presenting on the skin and characterized by very good prognosis and response to treatment in the majority of cases. Nevertheless, PC-ALCL must be distinguished from secondary skin lesions in systemic ALCL, which confer a poor prognosis, and other CD30+ PCLPDs, reactive conditions, or borderline cases. Given their rarity and heterogeneity, these entities represent diagnostic and therapeutic challenges, thus requiring a multidisciplinary approach and expertise to ensure appropriate diagnosis and management. There are several perils and pitfalls that exist regarding the differential diagnosis, the possible progression, and the treatment of PC-ALCL. Careful staging, correlation of clinical findings with histopathology and immunopathology, and thorough follow-up are essential in order to achieve a correct diagnosis and proper treatment of the disease. Michael D. Diamantidis and Athena D. Myrou Copyright © 2011 Michael D. Diamantidis and Athena D. Myrou. All rights reserved. Routine PSA Testing: An Analysis of the Controversy Concerning Its Use Mon, 01 Jan 1900 00:00:00 +0000 Prostate cancer is the leading cause of cancer in American males today. PSA screening has been used for over 10 years as an important diagnostic tool for the disease. Because of its lack of sensitivity and specificity, however, PSA testing should be used with caution. Namath S. Hussain Copyright © 2005 Namath S. Hussain. All rights reserved. Tubulocystic Carcinoma of the Kidney: A Case Report of Natural History and Long-Term Follow-Up Mon, 01 Jan 1900 00:00:00 +0000 Tubulocystic carcinoma (TC) is a rare primary renal tumor that has been recently described in the pathology literature. Formerly termed low-grade collecting duct carcinoma, further molecular analysis has shown TC to be a distinct entity that is separate from the more aggressive collecting duct carcinoma. Previous series have described the microscopic and immunohistochemical features of this tumor. We describe the natural history of this tumor in a patient who was followed with active surveillance for several years and then underwent partial nephrectomy. Long-term follow-up has shown no evidence of disease. A review of the pertinent literature is performed. Kelvin A. Moses, John J. DeCaro, Adeboye O. Osunkoya, and Muta M. Issa Copyright © 2010 Kelvin A. Moses et al. All rights reserved. Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties Mon, 01 Jan 1900 00:00:00 +0000 Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM) targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg®), have been approved by the FDA for cutaneous T-cell lymphoma (CTCL) and relapsed acute myeloid leukemia (AML), respectively. Such targetable agents, including RFB4(dsFv)-PE38 (BL22), IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed. Koji Kawakami, Oumi Nakajima, Ryuichi Morishita, and Ryozo Nagai Copyright © 2006 Koji Kawakami et al. All rights reserved. Epidemiology and Pathogenesis of Nasal NK/T-Cell Lymphoma: A Mini-Review Mon, 01 Jan 1900 00:00:00 +0000 Nasal NK/T-cell lymphoma (NKTCL) frequently presents with necrotic, granulomatous lesions in the upper respiratory tract, and usually shows a highly aggressive clinical course. Thus, it was initially included in the clinical condition of lethal midline granuloma. Recently, the disease has been recognized as a neoplastic proliferation of NK/T cells. The disease is much more frequent in Asian and Latin American countries than in Western countries, and is universally associated with Epstein-Barr virus (EBV) infection. Analyses of gene mutations, especially p53 and c-kit, revealed the different frequencies by district. Abnormalities of other genes have also been reported. Case-control studies showed that the exposure to pesticides and chemical solvents could be causative of NKTCL. Further studies including HLA antigen typing of patients is necessary to further clarify the disease mechanism. Katsuyuki Aozasa and Mona A. A. Zaki Copyright © 2011 Katsuyuki Aozasa and Mona Zaki. All rights reserved. Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni2+, Cd2+) and to an Understanding of Chemotherapy? Mon, 01 Jan 1900 00:00:00 +0000 The biological application of stoichiometric network analysis (SNA) permits an understanding of tumour induction, carcinogenesis, and chemotherapy. Starting from the Biological System of the Elements, which provides a comprehensive treatment of the functions and distributions of chemical (trace) elements in biology, an attempt is made to interrelate the essential feature of biology and — regrettably — of tumour genesis by superimposing SNA reasoning on common features of all crucial biological processes. For this purpose, aspects, effects and drawbacks of autocatalysis (identical reproduction which can occur either under control or without control [in tumours]) are linked with the known facts about element distributions in living beings and about interference of metals with tumours (in terms of both chemotherapy and carcinogenesis). The essential role of autocatalysis in biology and the drawbacks of either controlled or spontaneous cell division can be used to understand crucial aspects of carcinogenesis and chemotherapy because SNA describes and predicts effects of autocatalysis, including phase effects that may be due to some kind of intervention. The SNA-based classifications of autocatalytic networks in cell biology are outlined here to identify new approaches to chemotherapy. Stefan Franzle and Bernd Markert Copyright © 2003 Stefan Franzle and Bernd Markert. All rights reserved. Use of the Appendix as Ureteral Substitute in a Patient with a Single Kidney Affected by Relapsing Upper Urinary Tract Carcinoma Mon, 01 Jan 1900 00:00:00 +0000 The treatment of upper urinary tract transitional cell carcinoma (UT-TCC) in single-kidney patients requires the radical removal of cancer, but also, when feasible, the preservation of the continuity of the urinary tract by various surgical techniques. In case of wide resections during ureteral surgery, a ureteral replacement could be advocated. In the literature, the cecal appendix has rarely been used as a ureteral substitute, moreover in benign pathological conditions, showing encouraging early results. The positive functional and oncological outcomes obtained after a lengthy follow-up in a single-kidney patient with UT-TCC treated by ureteral resection and appendix interposition confirm the viability of this surgical option. Alessandro Antonelli, Danilo Zani, Paolo Dotti, Luigi Tralce, Claudio Simeone, and Sergio C. Cunico Copyright © 2005 Alessandro Antonelli et al. All rights reserved. Comparison of Three Different Chemotherapy Regimens Containing Epirubicin in Hormone-Refractory Prostate Cancer Patients Mon, 01 Jan 1900 00:00:00 +0000 We compared three different chemotherapy regimens containing epirubicin in hormonerefractory prostate cancer (HRPC) patients. Sixty-nine patients with HRPC were randomized into three groups. The first group (22 patients) received 30 mg/m2/week i.v. epirubicin for 8 weeks. The second group (24 patients) received 30 mg/m2/week i.v. epirubicin for 8 weeks followed by monthly maintenance therapy for 4–6 months. The third group (23 patients) received oral estramustine phosphate (EMP) at a dose of 840 mg/day together with weekly and monthly maintenance epirubicin. The response rates, mean survival times, and toxicity were determined. Within the first 3 months, pain and performance scores were improved by at least one degree in all the groups. One patient in group two and three patients in group three had complete response. Partial response rates were 23% in group 1, 25% in group 2, and 17% in group 3. Stable disease rates were 41% in group 1, 33% in group 2, and 26% in group 3. The progression rates within the first 3 months were 36% in group 1, 38% in group 2, and 44% in group 3. None of the patients developed complications that were significant enough to terminate the treatment. Two patients in group 3 died of cardiotoxicity. The mean survival times were 10.1, 15.8, and 16.1 months in groups 1, 2, and 3, respectively. It was determined that weekly and maintenance epirubicin treatment protocol, and estramustine treatment protocol in addition to this treatment, was only meaningfully more effective against weekly epirubicin treatment in the statistical sense (0.01 < p < 0.05). However, due to the complications of EMP, which influence the quality of life, we believe that this was usable only when measures were adopted against these effects. Hamit Ersoy, Orhan Yigitbası, Levent Sagnak, Hikmet Topaloglu, and Ahmet Kiper Copyright © 2008 Hamit Ersoy et al. All rights reserved. Role of CT in Assessment of Unresectable Wilms' Tumor Response after Preoperative Chemotherapy in Pediatrics Mon, 01 Jan 1900 00:00:00 +0000 The purpose of this study was to define the structural response of unresectable Wilms' tumor following preoperative chemotherapy by computed tomography (CT). We also compared CT changes in relation to histopathological nature. The study included 36 patients with 41 nephroblastomas. All were examined by CT before preoperative chemotherapy using multiphasic CT protocol study. The unresectability was diagnosed by CT imaging. All patients were subjected to fine-needle biopsy (FNB) to confirm the diagnosis and to define the histopathological type before preoperative chemotherapy. Five patients had unfavorable pathology and 31 patients with 36 nephroblastomas had favorable pathology. All patients received first line of treatment. Follow-up of these patients by CT at the 6th week was reviewed. All of our patients were diagnosed as unresectable Wilms' tumor by CT. Preoperative chemotherapy was started. Among our patients, 28 (77.8%) gave good response in the form of significant reduction in tumor size, disappearance of one tumor in two cases with bilateral WT and inferior vena cava (IVC) thrombus, and increased nonenhancing necrotizing content. Two patients with unfavorable pathology did not show any response. The remaining six patients gave partial response. CT can be used to evaluate tumor response and resectability after preoperative chemotherapy with high accuracy. The response to preoperative chemotherapy is not related to the histopathological classifications. Huda Refaie, Mohamed Sarhan, and Ashraf Hafez Copyright © 2008 Huda Refaie et al. All rights reserved. The Role of the Surgeon and Transurethral Resection in the Treatment of Superficial Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Non-muscle invasive bladder cancers are a heterogeneous group of cancers whose spectrum includes low grade Ta lesions and high-grade T1 lesions. Accurate staging and grading during initial evaluation and TUR ensures appropriate treatment and prevents the risk of understaging. TUR should be ideally performed under spinal anesthesia, with a continuous flow video resectoscope to maintain a stable bladder capacity, and a video monitor. The entire bladder must be visualized, with both 30- and 70-degree lenses, and all abnormal areas must be resected, with separate biopsies from each tumor's base. Repeat TUR is recommended for all high grade tumors and T1 tumors, especially if muscle was not present in the initial specimen. Immediate instillation of single dose chemotherapy agents following TUR is highly recommended to reduce the risk of tumor recurrences. Alan M. Nieder and Murugesan Manoharan Copyright © 2006 Alan M. Nieder and Murugesan Manoharan. All rights reserved. Editorial: Superficial Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Ziya Kirkali Copyright © 2006 Ziya Kirkali. All rights reserved. Carcinosarcoma of the Urinary Bladder: A Case Report Mon, 01 Jan 1900 00:00:00 +0000 Carcinosarcomas are rare tumours containing both malignant mesenchymal and epithelial elements. This reports presents a 70-year-old man with carcinosarcoma of the urinary bladder, which is proven histologically. Limci Gupta and Jacqueline Elder Copyright © 2005 Limci Gupta and Jacqueline Elder. All rights reserved. Open Surgery for Localized RCC Mon, 01 Jan 1900 00:00:00 +0000 The only possibility for cure in localized renal cell carcinoma (RCC) is surgery. Open radical nephrectomy (RN), as described by Robson, has long been the gold standard. Nevertheless, as a consequence of the increased use of abdominal imaging modalities, a continuing stage migration towards small, low-grade RCC lesions has become evident during the last decades. Together with this stage migration, nephron-sparing surgery (NSS), less-invasive therapies (laparoscopic RN and NSS), and minimally invasive therapies (radiofrequency ablation [RFA], cryoablation) have been developed and are gaining popularity. The value of laparoscopic RN and open NSS are acknowledged worldwide, but the value of laparoscopic NSS, RFA, and cryoablation remains to be established. Despite this evolution, there is still a place for open surgery for localized RCC. Open NSS is, at present, considered the standard of care for localized RCC less than 4 cm, while open RN still has a place for larger lesions, certainly when an extended lymph node dissection or adrenalectomy is warranted, or when a tumor thrombus is extending into the inferior vena cava. This review provides the data that support open surgery in clear, selected cases of RCC. Kathy Vander Eeckt, Steven Joniau, and Hein Van Poppel Copyright © 2007 Kathy Vander Eeckt et al. All rights reserved. The Role of Targeted Therapy in Metastatic Renal Cell Carcinoma Mon, 01 Jan 1900 00:00:00 +0000 Renal cell carcinoma (RCC) is a highly vascular tumor in which a growing understanding of disease biology has been translated into clinically active systemic therapies. The most clinically developed targeted therapies in advanced RCC are those that target the vascular endothelial growth factor (VEGF) ligand or receptor (VEGFR) and therapy directed against the mammalian target of rapamycin (mTOR). Sutent and sorafenib are orally available inhibitors of the VEGFR and platelet derived growth factor receptor (PDGFR). Temsirolimus is an mTOR inhibitor that leads to G1 cell cycle arrest and may affect VEGF production. This article briefly describes the biological pathways involved in the development of RCC and the results of clinical trials using targeted therapy in metastatic RCC. Jaya Unnithan and Brian I. Rini Copyright © 2007 Jaya Unnithan and Brian I. Rini. All rights reserved. Clinical Holistic Medicine: Metastatic Cancer Mon, 01 Jan 1900 00:00:00 +0000 We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients and, as a consequence, designed a treatment for the patient with metastasized cancer. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called “a blockage”, where the function of the cells is allocated from their original function in the tissue to a function of holding emotions. We hope to be able not only to improve the quality of life, but also to improve survival and in some cases even induce spontaneous remission of the metastasized cancer. This paper describes how work with a patient with metastasized cancer can be done in the holistic clinical practice in 14 days on an individual basis, helping the patient to recover her human character, purpose of life, coherence, and will to live, thus improving quality of life and possibly also survival time. The holistic therapeutic work includes (1) teaching existential theory, (2) working with life perspective and philosophy of life, (3) helping the patient to acknowledge the state of the disease and the feelings connected to it, and finally (4) getting the patient into the holistic state of healing: (a) feeling old repressed emotions, (b) understanding why she got sick from a holistic point of view, and finally (c) letting go of the negative beliefs and decisions that made her sick according to the holistic theory of nongenetic diseases. The theory of the human character, the quality of life theories, the holistic theory of cancer, the holistic process theory of healing, the theory of (Antonovsky) coherence, and the life mission theory are the most important theories for the patient to find hope and mobilize the will to fight the cancer and survive. The patient went through the following phases: (1) finding the purpose of life and hidden resources; (2) confronting denial; (3) taking responsibility for being very ill; (4) severe existential crises with no wish to live while still fighting; (5) integration of many repressed feelings and negative decisions thus rehabilitating character; (6) confronting lack of intimacy and trust in others and this way rehabilitating the ability to love; (7) rehabilitating the will to live, breaking through and falling in love with life; (8) assuming responsibility for the social relations; and sometimes (9) quality of life is improved radically with indications of spontaneous remission of the liver tumors. Søren Ventegodt, Elin Solheim, Mads E. Saunte, Mohammed Morad, Isack Kandel, and Joav Merrick Copyright © 2004 Søren Ventegodt et al. All rights reserved. Central Pain and Complex Motoric Symptoms after Gosarelin Therapy of Prostate Cancer Mon, 01 Jan 1900 00:00:00 +0000 A 76-year-old man with prostate cancer T3N0M0 and increasing PSA was treated with goserelin three times in a half year. As soon as the first treatment, he described subjective muscle weakness. After the third treatment, he developed complex motoric symptoms and atypical central pain with a likely association to goserelin. His left arm had signs of spastic movement; pain deteriorated after relaxation. The right hand showed muscle cramps under passive movements of the left arm that were not typical for rigor. He felt aching and partial burning pain in his whole body. There were few allodynic areas, mainly in the left arm. Several treatment approaches failed and the patient died some weeks after the first contact with our pain clinic due to pneumonia. G. Ernst, A. Gericke, and P. Berg Copyright © 2004 G. Ernst et al. All rights reserved. Focal Treatment of Prostate Cancer with Vascular-Targeted Photodynamic Therapy Mon, 01 Jan 1900 00:00:00 +0000 Epidemiologic and pathologic features of prostate cancer have given rise to an interest in focal treatment for carefully selected patients. Prostate cancer remains highly prevalent, particularly in the U.S. and Europe. As screening programs have become more aggressive and widespread, a substantial proportion of men diagnosed with localized prostate cancer have disease characteristics associated with a low risk of progression. Treatments such as radical prostatectomy and radiation therapy can lead to durable recurrence-free survival in most patients, but carry variable risks of bowel, urinary, and sexual side effects. Few men and few urologists are comfortable leaving a potentially curable prostate cancer untreated. Focal therapy offers an attractive alternative for the patient faced with a choice between aggressive local intervention (radiation or surgery) and watchful waiting. Contemporary diagnostic biopsy strategies and imaging tools, and the development of predictive statistical models (nomograms), have led to improvements in tumor characterization and risk stratification, making focal therapy a viable treatment option for specific men. This article reviews the rationale and indications for focal therapy and highlights vascular-targeted photodynamic therapy (PDT) as one of many promising focal therapy techniques. Scott E. Eggener and Jonathan A. Coleman Copyright © 2008 Scott E. Eggener and Jonathan A. Coleman. All rights reserved. Case Study: The Surgical Management of Angiokeratoma Resulting from Radiotherapy for Penile Cancer Mon, 01 Jan 1900 00:00:00 +0000 Angiokeratoma is a rare, benign skin lesion and a recognised complication of radiation therapy. Here we describe a case of extensive angiokeratoma of the groin and external genitalia resulting from external beam radiation to that area in a patient with penile carcinoma. Furthermore, we outline the management of this problem by surgical reconstruction. Rowland Rees, Alex Freeman, Peter Malone, Giulio Garaffa, Asif Muneer, and Suks Minhas Copyright © 2009 Rowland Rees et al. All rights reserved. The Management of Nonseminomatous Testicular Cancer Mon, 01 Jan 1900 00:00:00 +0000 Graeme S. Steele and Jerome P. Richie Copyright © 2004 Graeme S. Steele and Jerome P. Richie. All rights reserved. Intratesticular Adenomatoid Tumor Radiographically Mimicking A Primary Testicular Malignancy Mon, 01 Jan 1900 00:00:00 +0000 Howard L. Adler, John L. Haddad, Thomas M. Wheeler, and Edward D. Kim Copyright © 2004 Howard L. Adler et al. All rights reserved. Thermal Ablation of Small Renal Tumors – Present Status Mon, 01 Jan 1900 00:00:00 +0000 Thermal ablation of renal tumors is achieved by the delivery of extreme heat or extreme cold directly to the lesion in order to obtain in situ destruction of the malignant cells without having to remove the entire organ. Cryotherapy and radiofrequency ablation are becoming more and more attractive for the treatment of small lesions in select cases. Other types of energy such as microwave, laser and high intensity ultrasound have also been used to destroy kidney lesions but must still be considered in the experimental stage. Cryotherapy and radiofrequency ablation are minimally invasive and have been shown to be safe and effective in treating tumors up to 3–4 cm in diameter. However, the number of case series is rather limited and follow-up, especially for radiofrequency ablation, is short. Only now are workers beginning to present outcomes after 5 years for cryoablation. Therefore, the long-term oncological efficacy of these ablation techniques remains to be seen. As longer follow-up and greater patient numbers are reported we will get a clearer picture of the true potential of these modalities. Randomized prospective trials would be auspicable. For now, CA and RFA should be limited to few select patients i.e. patients with comorbidities which render them at high risk for a surgical procedure and possibly patients with genetic conditions such as Von Hippel Lindau disease who will probably develop multiple tumors. Jon A. J. Lovisolo, Claudio P. Legramandi, and Aldo Fonte Copyright © 2007 Jon A.J. Lovisolo et al. All rights reserved. RBM5/LUCA-15 — Tumour Suppression by Control of Apoptosis and the Cell Cycle? Mon, 01 Jan 1900 00:00:00 +0000 The candidate tumour suppressor gene, LUCA-15, maps to the lung cancer tumour suppressor locus 3p21.3. The LUCA-15 gene locus encodes at least four alternatively spliced transcripts, which have been shown to function as regulators of apoptosis, a fact that may have a major significance in tumour regulation. This review highlights evidence that implicates the LUCA-15 locus in the control of apoptosis and cell proliferation, and reports observations that significantly strengthen the case for tumour suppressor activity by this gene. Mirna Mourtada-Maarabouni and Gwyn T. Williams Copyright © 2002 Mirna Mourtada-Maarabouni and Gwyn T. Williams. All rights reserved. Superficial Urothelial Cancer in the Prostatic Urethra Mon, 01 Jan 1900 00:00:00 +0000 Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12—40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS) in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG) seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression. Ziya Kirkali and A. Erdem Canda Copyright © 2006 Ziya Kirkali and A. Erdem Canda. All rights reserved. Premalignant Lesions in the Kidney Mon, 01 Jan 1900 00:00:00 +0000 Renal cell carcinoma (RCC) is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1) morphological similarity; (2) spatial association; (3) development of microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive carcinoma; (5) progression to invasive cancer; and (6) similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered. Ziva Kirkali and Kutsal Yorukoglu Copyright © 2001 Ziva Kirkali and Kutsal Yorukoglu. All rights reserved. Natural History, Recurrence, and Progression in Superficial Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Superficial bladder cancer encompasses patients with stage Ta T1 tumors and patients with carcinoma in situ (CIS). The natural history or treatment-related prognosis of these patients varies considerably from one patient to the next based on the patient’s clinical and the tumor's pathological characteristics. Based on a review of the literature, the most important prognostic factors for recurrence are the prior recurrence rate, number of tumors, and tumor size; whereas for progression, the most important prognostic factors are the T category, grade, and presence of CIS. Treatment with intravesical bacillus Calmette-Guerin reduces both the risk of recurrence and the risk of progression, and is the treatment of choice in high-risk papillary tumors and in patients with CIS. Assessment of a patient's prognostic factors and his or her risk of recurrence and progression is a prerequisite for determining the most appropriate treatment and frequency of follow-up for a given patient. Richard J. Sylvester Copyright © 2006 Richard J. Sylvester. All rights reserved. Rapidly Shifting Concepts Regarding Androgens and Prostate Cancer Mon, 01 Jan 1900 00:00:00 +0000 There has been a recent dramatic shift in our understanding of the relationship between androgens and prostate cancer (PCa). Whereas for several decades it had been assumed that higher serum testosterone (T) concentrations would lead to ever-greater PCa growth, current literature indicates that PCa growth is unaffected by changes in serum T throughout most of the naturally occurring range. A Saturation Model has been proposed to explain how prostate tissue can be exquisitely sensitive to changes in serum T at the very low end of the concentration range, but appears indifferent to such changes above the near-castrate range. This has special applicability to T-deficient men, since this means that T therapy may not be nearly as risky as once assumed. Indeed, one of the more interesting changes over the last several years has been the growing acceptance of the use of T therapy in men with a prior history of PCa, with early data indicating minimal risk of cancer recurrence or progression. Provocative new evidence suggests that it is not high serum T that is problematic for PCa, but low serum T that is associated with worrisome cancer features and outcomes, such as high Gleason score, advanced stage of presentation, and increased risk of biochemical recurrence after surgery. It will be interesting to see what changes will occur in this rapidly changing field over the next several years. Abraham Morgentaler Copyright © 2009 Abraham Morgentaler. All rights reserved. Adenomatous Polyp of the Verumontanum Causing Bladder Outlet Obstruction Mon, 01 Jan 1900 00:00:00 +0000 Siamak Daneshmand Copyright © 2004 Siamak Daneshmand. All rights reserved. Transitional Cell Carcinoma of the Upper Ureter Metastatic to the Thoracic Spine Presenting as a Spinal Cord Compression Mon, 01 Jan 1900 00:00:00 +0000 We performed a left nephroureterectomy for a gentleman with transitional cell carcinoma of the upper ureter. Histological analysis revealed it to be a T1 lesion, but to be highly mitotically active. The gentleman defaulted on adjuvant therapy and defaulted on follow-up. He represented with symptoms of acute spinal cord compression and magnetic resonance imaging demonstrated a lesion at T6/7. Neurosurgical resection of the lesion showed it to be a metastatic deposit from the ureteric primary. Despite surgical debulking and subsequent radiotherapy to the lesion, the patient died secondary to metastatic complications. This case report is of interest to the surgeon as it demonstrates both the high metastatic potential of upper tract carcinomas and educates the surgeon on the presentation of acute spinal cord compression. J. O. Larkin, I. M. Cullen, M. O. Kelleher, J. Fitzgibbon, K. Keohane, M. G. J. O'Sullivan, and E. Rogers Copyright © 2008 J. O. Larkin et al. All rights reserved. Complete Atelectasis of the Left Lung from Anaplastic Large-Cell Lymphoma Mon, 01 Jan 1900 00:00:00 +0000 Liling Zhang and Gang Wu Copyright © 2010 Liling Zhang and Gang Wu. All rights reserved. Significant Delay of Lethal Outcome in Cancer Patients Due to Peroral Administration of Bacillus oligonitrophilus KU-1 Mon, 01 Jan 1900 00:00:00 +0000 Treatment of cancer patients remains a serious medical problem and the development of alternative treatment strategies is therefore of great importance. In this connection, we developed a new bacterial-based, anticancer method. Ten cancer patients (three males, seven females) were involved in this study. Bacterial suspension of stationary phase Bacillus oligonitrophilus KU-1 was used as a remedy for peroral administration. In five patients, side effects (sicchasia, slight blood, and intracranial pressure gain) were detected, but all patients showed significant delay of lethal outcome without serious side effects. In conclusion, the suggested method was, in our opinion, a good alternative to conventional chemo- and radiotherapy techniques. In order to evaluate its efficiency for various tumors, a double-blind, placebo-controlled, multicenter study is needed. Sergey V. Malkov, Vladimir V. Markelov, Gleb Y. Polozov, Boris I. Barabanschikov, Alexander Y. Kozhevnikov, and Maxim V. Trushin Copyright © 2006 Sergey V. Malkov et al. All rights reserved. Editorial: Special Issue. Current Treatment of Localized Renal Cancer Mon, 01 Jan 1900 00:00:00 +0000 Ziya Kirkali Copyright © 2007 Ziya Kirkali. All rights reserved. Comorbidities and the Risk of Late-Stage Prostate Cancer Mon, 01 Jan 1900 00:00:00 +0000 The degree to which comorbidities affect the diagnosis of prostate cancer is not clear. The purpose of this study was to determine how comorbidities affect the stage at which prostate cancer is diagnosed in elderly white and black men. We obtained data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute merged with Medicare claims data. For each patient, we estimated associations between stage of disease at diagnosis and each of the 27 comorbidities. The sample included 2,489 black and 2,587 white men with staged prostate cancer. Coronary artery disease, benign hypertension, and dyslipidemia reduced the odds of late-stage prostate cancer. A prior diagnosis of peripheral vascular disease, severe renal disease, or substance abuse increased the odds of being diagnosed with late-stage disease. The study shows some effect modification by race, particularly among white men with substance abuse, cardiac conduction disorders, and other neurologic conditions. The strongest predictors of late-stage prostate cancer diagnosis for both white and black men were age at diagnosis of at least 80 years and lack of PSA screening. Comorbidities do affect stage at diagnosis, although in different ways. Four hypotheses are discussed to explain these findings. Steven T. Fleming, Kathleen McDavid, Kevin Pearce, and Dmitri Pavlov Copyright © 2006 Steven T. Fleming et al. All rights reserved. Active Surveillance for Localized Prostate Cancer – Current Practices and Recommendations Mon, 01 Jan 1900 00:00:00 +0000 Prostate cancer is now the most commonly diagnosed solid tumor in American men, due in part to widespread screening and aggressive diagnostic practices. Prostate cancer autopsy studies show the uniquely high prevalence rates of small, indolent tumors in men dying of other causes. These findings have led to increased concern for the overdetection and overtreatment of prostate cancer. Active surveillance for prostate cancer allows one to limit prostate cancer treatment with concomitant risks of treatment-related morbidity to the men who will benefit the most from aggressive therapies. Several tools have been developed in treated and surveyed men to assist physicians in selecting men with potentially indolent tumors amenable to active surveillance. Recent published results describe institutional experiences with active surveillance and delayed selective therapy for men with low-grade, early prostate cancer. Although median follow-up from these studies is relatively short, the outcomes appear favorable. Data from these reports provide information for selecting men for this approach, as well as for following them over time and determining triggers for further intervention. Ongoing clinical trials with watchful waiting and active surveillance for prostate cancer will ultimately provide improved evidence for managing early, localized disease. Jennifer N. Wu and Marc A. Dall'Era Copyright © 2010 Jennifer N. Wu and Marc A. Dall'Era. All rights reserved. Publication of a Special Issue: Superficial Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 Claire Redhead Copyright © 2006 Claire Redhead. All rights reserved. Hope and Challenges in the Management of Advanced Renal Cell Carcinoma Mon, 01 Jan 1900 00:00:00 +0000 Peter E. Clark Copyright © 2007 Peter Clark. All rights reserved. Procollagen-Like Protein as a Molecular Target in the Treatment of Primary Brain Tumor Mon, 01 Jan 1900 00:00:00 +0000 Medhi Wangpaichitr, Howard Landy, Chun Jing Wu, Lynn G. Feun, Rong Xu, Jenny Xu, and Niramol Savaraj Copyright © 2002 Medhi Wangpaichitr et al. All rights reserved. Bilateral Renal Angiomyolipomas with Invasion of the Renal Vein: A Case Report Mon, 01 Jan 1900 00:00:00 +0000 An angiomyolipoma (AML) is usually a benign, rare, and, more commonly, a unilateral renal tumour. Bilateral tumours are very rare, particularly in the absence of tuberous sclerosis complex. Only in a few isolated cases have features of malignancy been associated with an AML. We present a unique case of bilateral AMLs mimicking invasive tumours in the absence of any other features of tuberous sclerosis complex. C. Blick, N. Ravindranath, A. Muneer, and A. Jones Copyright © 2008 C. Blick et al. All rights reserved. Angiosarcoma of the Bladder: Case Report and Review of the Literature Mon, 01 Jan 1900 00:00:00 +0000 Our objective was to present a new case of angiosarcoma of the bladder after therapeutic radiation of the prostate, and discuss the treatment and clinical course of this rare tumor; the role of multimodality treatment is also discussed. We report a case of angiosarcoma of the bladder. Presentation, clinical course, and treatment were outlined and discussed. A MEDLINE search of all reported cases of angiosarcoma in the English language literature was performed. Thirteen previous cases of bladder angiosarcoma have been reported and three previous cases have been reported after therapeutic radiation. Hematuria was the most common presentation. Overall survival is poor, with 5-year survival rates at 35%. Longer-term survival has been demonstrated in patients who have had a multimodal approach to treatment, which combines radical surgery with chemotherapy and radiotherapy. Angiosarcoma of the bladder is a rare disease with overall poor prognosis. Optimal treatment has not been defined, but multimodality approaches appear to have a survival benefit. Steve K. Williams, Rita L. Romaguera, and Bruce Kava Copyright © 2008 Steve Williams et al. All rights reserved. The Role of Surveillance in the Management of Small Renal Masses Mon, 01 Jan 1900 00:00:00 +0000 Incidentally detected, small renal masses (SRMs) have been increasing significantly in recent years due to the widespread use of improved cross-sectional imaging. A significant number of incidental SRMs are diagnosed in elderly patients who are more likely to undergo imaging for other medical issues. The natural history of SRMs has not been historically well understood because most masses are surgically removed soon after diagnosis. Alessandro Volpe Copyright © 2007 Alessandro Volpe. All rights reserved. Suppression of Tumor Angiogenesis by Nonsteroidal Anti-Inflammatory Drugs: A New Function for Old Drugs Mon, 01 Jan 1900 00:00:00 +0000 There is solid epidemiological evidence demonstrating that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing colorectal cancer, and to a lesser extent gastric and esophageal cancers[1]. Importantly, NSAIDs suppress colon polyp formation and progression in patients diagnosed with familial adenomatous polyposis coli (APC)[2]. In many animal studies, NSAIDs have been shown to prevent tumor formation and slow tumor progression, thus confirming and extending the clinical observations[3,4,5]. Recent findings have demonstrated that NSAIDs inhibit angiogenesis, suggesting that the tumor suppressive activity of these drugs may be due, at least in part, to their ability to inhibit tumor angiogenesis[6]. The study of the mechanism by which NSAIDs suppress tumor angiogenesis, is matter of intense research. Curzio Raegg and Olivier Dormond Copyright © 2001 Curzio Raegg and Olivier Dormond. All rights reserved. Glioblastoma Multiforme Stem Cells Mon, 01 Jan 1900 00:00:00 +0000 Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies. Irena Dimov, Deasanka Tasic-Dimov, Irena Conic, and Vladisav Stefanovic Copyright © 2011 Irena Dimov et al. All rights reserved. Solitary Endobronchial Lymphangioma: A Case Report and Review of Literature Mon, 01 Jan 1900 00:00:00 +0000 Shylashree Chikkamuniyappa, Josefine Heim-Hall, and Jaishree Jagirdar Copyright © 2005 Shylashree Chikkamuniyappa et al. All rights reserved. Rapid onset of nucleolar segregation followed by DNA fragmentation in roscovitine-treated MCF-7 cells supports its pro-apoptotic potential Mon, 01 Jan 1900 00:00:00 +0000 V. Kotala, M. Horky, S. Uldrijan, M. Strnad, and B. Vojtesek Copyright © 2001 V. Kotala et al. All rights reserved. Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis Mon, 01 Jan 1900 00:00:00 +0000 The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cells in vivo and markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell–derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer. Chery A. Whipple, Arthur D. Lander, and Murray Korc Copyright © 2008 Chery A. Whipple et al. All rights reserved. Testicular Abscess an Unusual Cause for Febrile Neutropenia Mon, 01 Jan 1900 00:00:00 +0000 Patients with good-risk disseminated testicular cancer are effectively managed with platinum-based chemotherapy. Febrile neutropenia is a dose-limiting event for many chemotherapy regimens. The risk of developing febrile neutropenia is related both to the chemotherapy dose and schedule, and to patient-related factors. Among patients who require ongoing chemotherapy for metastatic disease, it is very unusual for surgical complications to delay the initiation of chemotherapy. We describe a patient who developed febrile neutropenia with testicular abscess when treated with BEP 2 weeks following inguinal orchiectomy. Tal Grenader Copyright © 2008 Tal Grenader. All rights reserved. Evidence-Based Comparison of Robotic and Open Radical Prostatectomy Mon, 01 Jan 1900 00:00:00 +0000 The rapid adoption of robotic-assisted laparoscopic radical prostatectomy (RALP) has occurred despite a lack of high-quality evidence demonstrating its oncologic advantages, safety, or cost effectiveness compared with open radical retropubic prostatectomy (ORP). This review examines the current literature comparing ORP and RALP, focusing on perioperative, oncologic, functional, and economic outcomes. William T. Lowrance, Tatum V. Tarin, and Shahrokh F. Shariat Copyright © 2010 William T. Lowrance et al. All rights reserved. TRP Channels in Human Prostate Mon, 01 Jan 1900 00:00:00 +0000 This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP) channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed. Carl Van Haute, Dirk De Ridder, and Bernd Nilius Copyright © 2010 Carl Van Haute et al. All rights reserved. Superficial Bladder Cancer Therapy Mon, 01 Jan 1900 00:00:00 +0000 Bladder cancer treatment remains a challenge despite significant improvements in preventing disease progression and improving survival. Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (i.e. Ta, T1, and carcinoma in situ) with specific objectives which include treating existing or residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival regardless of the treatment. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Intravesical chemotherapy reduces short-term tumor recurrence by about 20%, and long-term recurrence by about 7%, but has not reduced progression or mortality. Presently, BCG immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, T1, CIS) and reduces tumor recurrence, disease progression, and mortality. Interferons, Keyhole-limpet hemocyanin (KLH), bropirimine and Photofrin-Photodynamic Therapy (PDT) are under investigation in the management of TCC and early results are encouraging. This review highlights and summarizes the recent advances in therapy for superficial TCC. Emmanuel Schenkman and Donald L. Lamm Copyright © 2004 Emmanuel Schenkman and Donald L. Lamm. All rights reserved. An Unusual Presentation of a Mixed Epithelial and Stromal Tumor in an Elderly Male Mon, 01 Jan 1900 00:00:00 +0000 Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms characterized by mixed cystic and solid components. These tumors are typically present in middle-aged women as a flank mass, or as a cause of flank pain or hematuria. We outline the case of an older male who presented with an enlarging abdominal mass causing symptoms that suggested a partial small bowel obstruction. Management of the patient and a brief review are discussed. Kelvin A. Moses, Irma V. Oliva, Adeboye O. Osunkoya, and K. Jeff Carney Copyright © 2010 Kelvin A. Moses et al. All rights reserved. Robotic-Assisted Surgery for Benign Urological Conditions Mon, 01 Jan 1900 00:00:00 +0000 Robotic technology for use in surgery has advanced considerably in the past 10 years. This has become particularly apparent in urology where robotic-assisted radical prostatectomy using the da VinciTM surgical system (Intuitive Surgical, CA) has become very popular. The use of robotic assistance for benign urological procedures is less well documented. This article considers the current robotic technology and reviews the situation with regard to robotic surgery for benign urological conditions. Declan G. Murphy, Ben J. Challacombe, Lail-U-Mah Zaheer, M. Shamim Khan, and Prokar Dasgupta Copyright © 2006 Declan G. Murphy et al. All rights reserved. Ovarian Epithelial Cancer Stem Cells Mon, 01 Jan 1900 00:00:00 +0000 The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance. Irena Conic, Irena Dimov, Desanka Tasic-Dimov, Biljana Djordjevic, and Vladisav Stefanovic Copyright © 2011 Irena Conic et al. All rights reserved. Epithelial Tight Junctional Changes in Colorectal Cancer Tissues Mon, 01 Jan 1900 00:00:00 +0000 Colorectal cancer (CRC) is one of the most common cancers in the western world. Early screening and detection could be highly preventative and therefore reduce mortality. Tight junctions (TJ) are well known for their function in controlling paracellular traffic of ions and molecules. It has become increasingly evident that TJs play a crucial role in maintaining cell-cell integrity, and the loss of cell junctional sealing could involve itself in the processes of carcinoma and cancer metastasis. If correlations between altered TJ proteins and CRC presence or invasiveness could be established, they may serve as important markers and guidelines for prophylactic and prognostic purposes, along with other screening methods. This review will present recent data from clinical and animal studies showing how altered TJ protein expression is a feature of certain CRCs. The up-regulation of claudin-1 in many CRCs is especially noteworthy. The focus of this article is simply on the association – however imperfect – between CRC and the major TJ transmembrane barrier proteins, namely claudins and occludin. Any causal relationship between TJ protein change and neoplasia remains conclusively unproven at present. Xuexuan Wang, Owen Tully, Benjamin Ngo, Marc Zitin, and James M. Mullin Copyright © 2011 Xuexuan Wang et al. All rights reserved. Transferrin Ensures Survival of Ovarian Carcinoma Cells Subjected to Deferoxamine, TNFA, FASL, Trail or MYC -Activation Mon, 01 Jan 1900 00:00:00 +0000 Georg Rosenberger, Michael Grusch, Gerhard Fuhrmann, Katharina Leuhuber, Doris Polgar, and Georg Krupitza Copyright © 2001 Georg Rosenberger et al. All rights reserved. Performance Evaluation of Calypso® 4D Localization and Kilovoltage Image Guidance Systems for Interfraction Motion Management of Prostate Patients Mon, 01 Jan 1900 00:00:00 +0000 Prostate cancer represents a model site for advances in understanding inter- and intrafraction motion for radiotherapy. In this study, we examined the correlation of the electromagnetic transponder system/Calypso® 4D Localization System with conventional on-board imaging (OBI) using kilovoltage imaging. Initially using a quality assurance (QA) phantom and subsequently using data of seven patients, the vector distances between Calypso- and OBI-recorded shifts were compared using the t-test. For the 30 phantom measurements, the average differences between the measured Calypso offset and the calculated OBI shift were 0.4 ± 0.4, 0.2 ± 0.3, and 0.4 ± 0.3 mm in the lateral, longitudinal, and vertical directions, respectively (p = 0.73, p = 0.91, and p = 0.99, respectively), and the average difference vector for all sessions was 0.8 ± 0.4 mm. For the 259 patient measurements, the average differences between the measured Calypso offset and the calculated OBI shift were 0.7 ± 0.5, 1.1 ± 0.9, and 1.2 ± 0.9 mm in the lateral, longitudinal, and vertical directions, respectively (p = 0.45, p = 0.28, and p = 0.56, respectively), and the average difference vector for all sessions was 2.1 ± 1.0 mm. Our results demonstrated good correlation between Calypso and OBI. While other studies have explored the issue of Calypso/OBI correlation, our analysis is unique in our use of phantom validation and in our performing the patient analysis on an initial population prior to routine setup using Calypso without OBI. Implications for Calypso's role as a QA tool are discussed. Tomi Ogunleye, Peter J. Rossi, Ashesh B. Jani, Tim Fox, and Eric Elder Copyright © 2009 Tomi Ogunleye et al. All rights reserved. EGFR-Targeted Therapeutics: Focus on SCCHN and NSCLC Mon, 01 Jan 1900 00:00:00 +0000 Cancers of the head and neck and of the lung are associated with high morbidity and mortality rates that have remained relatively unchanged for more than 3 decades, despite advances in radiation therapies and chemotherapies over the same time. It is generally believed that the efficacy of standard therapy regimens has reached a plateau for these cancers. The discovery of specific aberrant molecular signaling pathways in solid tumors has afforded promising new directions for newer “targeted” cancer therapeutics. Among these, the epidermal growth factor receptor (EGFR) shows promise as a therapeutic target. Clinical studies have demonstrated that this targeted approach provides clinically meaningful benefit. This article reviews EGFR-targeted therapies in use and in development, with a focus on the role of EGFR in the pathophysiology of head and neck and lung cancer, and new concepts being investigated to improve outcomes with these agents. Martin Sattler, Oyewale Abidoye, and Ravi Salgia Copyright © 2008 Martin Sattler et al. All rights reserved. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer Mon, 01 Jan 1900 00:00:00 +0000 According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70%) and/or progression to muscle invasive bladder cancer(1-15%).Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG) prevents or delays progression. Patients at high risk for progression may need upfront cystectomy. A.P.M. van der Meijden Copyright © 2006 A.P.M. van der Meijden. All rights reserved. Delayed Local Recurrence Following Radiation Therapy for Muscle-Invasive Bladder Cancer Emphasizing the Need for Lifelong Surveillance: a Case Report Mon, 01 Jan 1900 00:00:00 +0000 We report a case of 68-years-old gentleman who developed a delayed local recurrence, 30 years following curative radiation treatment for muscle-invasive bladder cancer. This case emphasizes the importance of lifelong post-treatment surveillance for bladder cancer. Rajitha Sunkara, Rajinikanth Ayyathurai, Alan Nieder, and Murugesan Manoharan Copyright © 2008 Rajitha Sunkara et al. All rights reserved. Prostatic Adenosquamous Carcinoma Metastasizing to Testis Mon, 01 Jan 1900 00:00:00 +0000 Adenosquamous carcinoma of the prostate is an unusual tumor with poor prognosis. Most arise after hormonal or radiotherapy of conventional prostatic adenocarcinoma. Sarcomatous transformation in them has been reported in only a few cases. Here, we present a unique case of “de novo prostatic adenosquamous carcinoma with focal sarcomatoid areas” that showed testicular metastasis, detected after scrotal orchiectomy. Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Bulent Akdogan, and Haluk Ozen Copyright © 2006 Dilek Ertoy Baydar et al. All rights reserved. The Chances of Subsequent Cancer Detection in Patients with a PSA > 20 ng/ml and an Initial Negative Biopsy Mon, 01 Jan 1900 00:00:00 +0000 Transrectal ultrasound (TRUS)–guided prostate biopsy is known to carry a significant false-negative rate, leading some patients to have multiple biopsies. We investigated cancer detection rates in patients with a PSA >20 ng/ml and a negative initial biopsy. We reviewed our database of 2396 TRUS-guided biopsies done between 1997 and 2002 in order to give a follow-up of at least 6 years. PSA, PSA density (PSAD), PSA velocity (PSAV), prostate volume, and DRE findings were analysed in relation to cancer status. Of the patients, 388 (16%) had a PSA >20 ng/ml, including 99 (26%) with benign biopsies. Of those, 67 were rebiopsied, including 19 (28%) with cancer on the first rebiopsy and four (6%) on further biopsies. PSAD, DRE, and volume significantly differed between rebiopsied patients with and without cancer (p <0.05). Patients who present with a PSA >20 ng/ml and have an initial negative biopsy have a high chance of malignancy being detected on a second biopsy. However, if a second biopsy is also negative, then the chances of subsequent biopsies showing signs of cancer are very low if the DRE is normal and particularly if the PSAD is >0.35 ng/ml/cm3. Nadeem Shaida, Catherine M. Jones, Navin Ravindranath, and Peter R. Malone Copyright © 2009 Nadeem Shaida et al. All rights reserved. Urothelial Cancer Stem Cells Mon, 01 Jan 1900 00:00:00 +0000 There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs), which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs) raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies. Irena Dimov, Milan Visnjic, and Vladisav Stefanovic Copyright © 2010 Irena Dimov et al. All rights reserved. Cytoreductive Nephrectomy and Nephrectomy/Complete Metastasectomy for Metastatic Renal Cancer Mon, 01 Jan 1900 00:00:00 +0000 The objective of this study was to determine our institutional experience with cytoreductive nephrectomy alone or in conjunction with nephrectomy complete metastasectomy. Between July 1989 and September 2003, we queried our department's renal tumor database for patients undergoing cytoreductive nephrectomy alone or in conjunction with complete metastasectomy. Clinical and pathological factors analyzed included primary tumor size, stage and histological subtype, age, gender, Karnofsky Performance Status (KPS) prior to nephrectomy, number and location of metastatic sites, and the presence or absence of any systemic therapy. Preoperative laboratory values analyzed included hemoglobin (HGB), calcium (CA), albumin (ALB), lactose dehydrogenase (LDH), alkaline phosphatase (ALP), and corrected calcium. Corrected calcium was defined as follows: corrected calcium = total calcium - 0.707*(albumin - 3.4). During this time frame, 1628 patients underwent nephrectomy (partial or radical) for renal masses, 91 (5.6%) of whom had metastatic disease. In this group, 71% of patients were male, 88% of patients had a KPS of 80% or greater, and 92% had conventional clear cell histology. Sixty-four percent of patients had a single site of metastatic disease, with lung the most common, followed by bone, adrenal, brain, and liver. Sixty-one patients (67%) had nephrectomy with removal of all metastatic sites (nephrectomy/complete metastasectomy) and 30 (33%) had cytoreductive nephrectomy alone. Median survival for patients undergoing nephrectomy/complete metastasectomy was 30 months. Median survival for patients undergoing cytoreductive nephrectomy alone was 12 months. Perioperative complications occurred in 13% of patients and four patients died within 30 days of their operation. For patients with metastatic renal cell carcinoma, surgical resection of the primary tumor alone (cytoreductive nephrectomy) or in conjunction with metastasectomy can be accomplished with acceptable perioperative morbidity and mortality. This surgical experience provides a contemporary foundation as new targeted therapeutic agents are integrated into the neoadjuvant or adjuvant treatment of locally advanced and metastatic renal cancer. Paul Russo, Mark Synder, Andrew Vickers, Varuni Kondagunta, and Robert Motzer Copyright © 2007 Paul Russo et al. All rights reserved. Type B Lactic Acidosis Secondary to Malignancy: Case Report, Review of Published Cases, Insights into Pathogenesis, and Prospects for Therapy Mon, 01 Jan 1900 00:00:00 +0000 Most of the information about type B lactic acidosis associated with cancer is derived from case reports and there are no randomized controlled trials to compare different therapeutic modalities. Previous reviews of cases only refer to hematologic malignancies. We present a patient with non-Hodgkin's lymphoma who developed type B lactic acidosis. We performed a search of the PUBMED database using the MESH terms “neoplasms” AND “acidosis, lactic”, limited to the English language, and written between the years 2000 and 2010. A total of 31 cases were retrieved. These cases were identified and reviewed. The possible pathophysiologic mechanisms and treatment options are discussed. Type B lactic acidosis is most commonly seen in patients with lymphoma or leukemia. Although formal prospective trials are lacking, type B lactic acidosis in patients with cancer seems to be a marker of poor prognosis regardless of the treatment offered and may be invariably fatal. Future research should focus on potential therapy based on the pathogenic mechanisms that lead to type B lactic acidosis in cancer patients. Juan P. Ruiz, Ashok Singh, and Peter Hart Copyright © 2011 Juan P. Ruiz et al. All rights reserved.