The collection of large volumes of medical data has offered an opportunity to develop prediction models for survival by the medical research community. Medical researchers who seek to discover and extract hidden patterns and relationships among large number of variables use knowledge discovery in databases (KDD) to predict the outcome of a disease. The study was conducted to develop predictive models and discover relationships between certain predictor variables and survival in the context of breast cancer. This study is Cross sectional. After data preparation, data of 22,763 female patients, mean age 59.4 years, stored in the Surveillance Epidemiology and End Results (SEER) breast cancer dataset were analyzed anonymously. IBM SPSS Statistics 16, Access 2003 and Excel 2003 were used in the data preparation and IBM SPSS Modeler 14.2 was used in the model design. Support Vector Machine (SVM) model outperformed other models in the prediction of breast cancer survival. Analysis showed SVM model detected ten important predictor variables contributing mostly to prediction of breast cancer survival. Among important variables, behavior of tumor as the most important variable and stage of malignancy as the least important variable were identified. In current study, applying of the knowledge discovery method in the breast cancer dataset predicted the survival condition of breast cancer patients with high confidence and identified the most important variables participating in breast cancer survival. Breast cancer is the most common malignancy among women that causes large number of neoplastic deaths across worldwide. It is the fifth cause of death due to malignancies among Iranian women with approximately 8500 incident cases per year . Once a The extraction of pattern representing survival status of patients with breast cancer from demographic and clinical data is the main object of KDD in the health domain . Data miPredicting survival condition of breast cancer patients by considering their risk factors is difficult. The abnormal values of some morphological and pathological tumor specifications and biological tumor markers are known as risk factors. Choosing the most appropriate treatment for the patients and assign those to high-risk groups are related to identification of risk factors that increase the mortality of cancer. The role of domain experts in predicting breast cancer survival with respect to important risk factors is undeniable. However, the availability of these experienced oncologists is limited. The support of less experienced oncologists with expert knowledge in order to care for their patients is a considerable challenge . In thesDelen and et al used a large breast cancer dataset and applied KDD to develop DSS for breast cancer survival. Their study showed the high potential of KDD process in accurate prediction of breast cancer survival . Jerez aThe purpose of this study is to develop predictive models and discover relationships between certain predictor variables and survival in the context of breast cancer.This study is Cross sectional. In this research, the Surveillance Epidemiology and End Results (SEER) breast cancer dataset was used. This study is a Cross sectional and the required data were obtained from the Surveillance Epidemiology and End Results (SEER) breast cancer dataset. This dataset contains 657,712 records and 72 variables. These variables provide socio-demographic and cancer specific information. Each record represents a particular patient within the database. In this study follow-up patients by 2009 that were diagnosed as breast cancer from 1999 to 2004 were selected. The records of patients diagnosed with breast cancer between 1999 and 2004 were selected. They had been followed for 5-years.In order to build the best possible predictive model, the following steps were performed as data preparation:After studying the data dictionary of dataset, the variables of unrelated to breast cancer were removed.Histology, Behavior and Grade code that are important variables to predict breast cancer survival were a part of Morphology variable. Also, aggregated Extent of Disease variable was separated into the six different tumor attributes. The variables integrated into a general variable were disintegrated because they contained distinct information about cancer. For example, variables: Histology, Behavior and Grade code that are important variables to predict breast cancer survival were a part of Morphology variable. Also, aggregated Extent of Disease variable was separated into the six different tumor attributes.The integrated variables were separated into the different variables. For example, variables: For extracting records between1999 and 2004, the dataset was exported from IBM SPSS Statistics 16 to Access 2003 and 22,763 records were obtained.Tumor Size, Extension and Lymph node involvement had missing values, but reviewing of data dictionary showed that they only had been registered for years between 1998 and 2003. For records related after 2003, variables: Collaborative Stage (CS) Tumor Size, Collaborative Stage (CS) Extension and Collaborative Stage (CS) Lymph node involvement were available and had 45, 0 and 45 percent missing values respectively. Some missing values of six old variables were in new variables and vice versa. To solve this problem, a simple mapping was done in Excel 2003 and these variables were converted to three ones. They were evaluated to determine inaccuracy, inconsistency and missingness in data. For instance, early evaluation demonstrated that 55 percent of variables: The review of published papers and counseling consulting with oncologists were performed to determine of predictor variables for survival modeling  Amna, U.death and aliveness respectively. The percentages of death and aliveness values are were 10.3 and 89.7 respectively.Dependent variable was created by the method introduced in by Bellaachia paper . This vaFor handling missing values, multiple imputation (MI) method was used in the IBM SPSS Statistics 16. This method analyzes the patterns of missing values and then produces the multiple versions of the dataset that each contains its own set of imputed values. When running the analysis on each complete dataset, results of all datasets are averaged and a single one is produced. For MI, the pattern of data must be missing at random .aliveness values were approximately nine times greater than death values). In these situations, the results of data mining are biased towards the majority value. For solving this problem, under-sampling or over-sampling is used. Under-sampling is used to decrease the size of the majority value to the same size of the minority value, whereas over-sampling is used to increase the size of the minority value to the same size of the majority value. The over-sampling method was used to increase dead values to the same numbers of aliveness values.The values of dependent variable were not balanced  and 30 (6829) percent of database records were selected as training and testing data respectively. Training data are used to construct or discover a predictive model and testing data are used to evaluate performance of model .Three different types of methods: Support Vector Machine (SVM), Bayes Net, and CHi-squared Automatic Interaction Detection (CHAID) were used as prediction models. SVM is one of the supervised learning algorithms with well-built regularization properties. The optimization procedure of SVM maximizes predictive accuracy and also reduces the overfitting (more accurate in fitting known data but less accurate in predicting new data) of the training data. Basically SVM spins around the idea of finding optimal decision boundary i.e. maximizing the margin by finding the largest achievable distance among the separating hyperplane and the instances on either side of it . The BayAccuracy, sensitivity, specificity and adjusted propensity were used for measuring the prediction models performances. Accuracy is the percentage of testing data that are correctly predicted by the model. Sensitivity and specificity are also calculated from the accuracy . In breaSVM outperformed other models in the prediction of breast cancer survival. This superiority was in all of the measurement criteria. The predictor variables: Behavior, Lymph node involvement, Extension of tumor, Grade, Number of positive nodes, Age, Site specific surgery code, PRStatus, Radiation and Stage contribute mostly to prediction of breast cancer survival in the SVM model. The relative importance of these variables has been showed in Based on above figure, 25 percent of model predictive power relates to Behavior variable and 6 percent to other variables (least important variables). The relative importance of some predictor variables  identified by the Bayes Net model were almost the same. The CHAID model for predicting breast cancer survival determined the following predictor variables (they are in descending order based on their relative importance): Extension of tumor, Number of positive nodes, Number of nodes, Tumor size, Behavior, ERStatus, PRStatus, Marital status, Age and Grade.The highest performance of accuracy in our study is 96.7% that belongs to the SVM model. The SVM revealed the highest performance (96.7%) of the accuracy among other models. In the previous studies  reportedSpecificity of SVM (95.6%) also is higher than other models. In the medical domain, predicting negative cases (i.e. not survived breast cancer patients) with high accuracy is more important than positive cases (i.e. survived breast cancer patients) . In otheThe key difference advantage between current study and other studies is reporting adjusted propensity scores. The adjusted propensity score of SVM was better than other models. It predicted breast cancer survival with higher confidence than Bayes Net and CHAID. Balancing of dependent variable in the current study has differentiated it with the previous researches and has necessitated the report of adjusted propensity as the most important criterion in the comparison of models performance. Another advantage of current study is in the way of missing values management. In contrast to this research, the missing values have been deleted in the related studies . The delth (3%) and 10th (9%) rank among other variables. Likely the used model and balancing outcome variable have caused this inconsistency with those studies. Behavior variable determines the general condition of breast cancer   identified by the best model of this work. This variable in the Bellaachia  and Delelignant) . Among tlignant)  and Delelignant)  studies.However in this study the models as artificial neural network, logistic regression and C5 were not used. The other missing values handling methods were not used in this study and a part of the SEER dataset was used other than complete dataset. The mentioned limitations can restrict the findings of this work for generalizing beyond the study conditions.In current study, applying of the knowledge discovery method in the breast cancer dataset predicted the survival condition of breast cancer patients with high confidence and identified the most important variables participating in breast cancer survival.


Ossification of the tentorium cerebelli over the trigeminal notch is rare, but it may cause compression of the trigeminal nerve, leading to trigeminal neuralgia (TN). We were unable to find any previously reported cases with radiological evaluation, although we did find one case with surgically proven ossification of the tentorium cerebelli. Here, we present a case of TN caused by tentorial ossification over the trigeminal notch depicted on magnetic resonance imaging (MRI) and computed tomography (CT). Calcifications or ossifications in the free edges of the tentorium cerebelli, in the so- called tentorial notch, are frequent and age-related physiologic and neurodegenerative changes . HoweverA 35-year-old woman visited the hospital with a chief complaint of left facial pain that had lasted one week. She had experienced three episodes of the pain over the past four years. Each pain attack lasted three or four months, with a pain-free period. The pain affected the left maxillary and temporal regions and the inside of the ear. The nature of the pain was electric-shock-like, paroxysmal, and lancinating. The intensity of the pain was 10 on the visual analogue scale . The pain was aggravated or precipitated by talking, swallowing, opening the mouth, and eating. Neurologic examination was negative including sensory deficits. The clinical diagnosis was TN in the left maxillary and mandibular distribution. A brain MRI was performed to rule out other causes of the patient's facial pain. The MRI scan was obtained using a 1.5 Tesla MRI scanner . Axial MR images with 3D fast imaging with steady-state acquisition (3D FIESTA) sequence  showed nodular lesions with dark signal intensity adjacent to the porus trigeminus. The lesions were impinging upon the cisternal segment of the left trigeminal nerve . There wThe tentorium cerebelli is one of the most common sites of intracranial physiologic calcification . In factOn initial examination, the patient in this case presented with paroxysmal pain in the temporal area and inner ear triggered by swallowing and the authors considered that the most likely diagnosis would be trigeminal neuralgia combined with glossopharyngeal neuralgia. However, diagnostic mandibular nerve block produced complete pain relief for the duration of action of the local anesthetic, and a subsequently performed neurolytic mandibular nerve block led the patient to be pain-free.We have described a case of TN caused by unusually prominent ossification of the tentorium cerebelli over the trigeminal notch that was depicted on MRI and CT.


It is unclear how medical journals address authors’ financial and non-financial conflict of interest (COI).To assess the policies of clinical journals for disclosure of financial and non-financial COI.Cross sectional study that included both review of public documents as well as a simulation of a manuscript submission for the National Library of Medicine’s “core clinical journals”. The study did not involve human subjects. Investigators who abstracted the data, reviewed “instructions for authors” on the journal website and, in order to reflect the actual implementation of the COI disclosure policy, simulated the submission of a manuscript. Two individuals working in duplicate and independently to abstract information using a standardized data abstraction form, resolved disagreements by discussion or with the help of a third person.All but one of 117 core clinical journals had a COI policy. All journals required disclosure of financial COI pertaining to the authors and a minority (35%) asked for financial COI disclosure pertaining to the family members or authors' institution (29%). Over half required the disclosure of at least one form of non-financial COI (57%), out of which only two (3%) specifically referred to intellectual COI. Small minorities of journals (17% and 24% respectively) described a potential impact of disclosed COI and of non-disclosure of COI on the editorial process.While financial COI disclosure was well defined by the majority of the journals, many did not have clear policies on disclosure of non-financial COI, disclosure of financial COI of family members and institutions of the authors, and effect of disclosed COI or non-disclosure of COI on editorial policies. An Institute of Medicine Report defined conflict of interest (COI) as “a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest” . That reA recent study surveyed 100 trial reported in medical journals, with at least one Danish author not employed by the pharmaceutical industry.  The inveet al found that the researcher's commitment to a particular school of thought biased the study design and outcome of psychotherapy research [While the focus has been on "financial" COI, about half of the conflicts of interest cases brought to Committee on Publication Ethics (COPE) forum for advice involved non-financial COIs . As an eresearch .One type of non-financial COI that has received increased attention is intellectual COI –9. We deThe International Committee for Medical Journals Editors (ICMJE) started to address conflicts of interest of authors in the mid-1980's . AlthougOne of the reasons for deficiencies in COI disclosures has been the absence of standardized COI forms . A satiset al and Cooper et al found that 89% of peer-reviewed biomedical journals and 93% of peer-reviewed medical journals had author COI policies [et al and Bosch et al found that the definition and the requirements for COI disclosure referred to financial rather than non-financial COI [Three recent cross sectional studies assessed the characteristics of the COI policies in high-impact biomedical journals. Blum policies , 15. Botcial COI , 16. NonThe primary objective of the study was to assess the policies of clinical journals for authors to disclose their financial and non-financial conflicts of interest as implemented during the submission process. This study was conducted in the context of a wider research project to better understand the reporting and handling of financial and non-financial COIs in health research.The Institutional Review Board of the American University of Beirut deemed the study as not human subject research. As detailed below, the research addressed the administrative process through review of public documents and a simulation of a manuscript submission, to assess the actual implementation of the COI disclosure policy.We used the Institute Of Medicine definition of COI for this study . We defihttp://www.nlm.nih.gov/bsd/aim.html). The Abridged Index Medicus was initiated in 1970 to enable direct access to selected biomedical journals of interest to practicing physicians. In February 2014, the list included 119 English language clinical journals.We wanted to cover a sample that is representative of clinical journals. For that reason, the study population consisted of the all peer-reviewed core clinical journals indexed under Abridged Index Medicus by the National Medical Library  article with a cover letter explaining the objective and methods of the current study. They reviewed all provided instructions, and assessed information and forms required by the submission system. They also included in the submission two email addresses, one for the ‘submitting author’ and another for a ‘co-author’. They then submitted the manuscript, checked for an email response from the journal to the submitting author and co-author email addresses. They abstracted from those emails any data that related to the COI disclosure .We did not contact the journal to request additional information. In order to minimize any potential burden on the journal editors, we submitted the empty manuscript to the journal only once and shared any resulting emails with the two data abstractors. We then deleted the submission within 24 hours, whenever the online system allowed deletion.Thus, we abstracted data from four sources:Instructions for authors on the journal website;Instructions and forms in the journal online submission system;Email from the journal to the submitting author and co-author email addresses;Publisher website when redirected from the online submission system.We conducted data collection of online material and any received emails in duplicate and independent manner with agreement checking for all the steps of data abstraction. The teams of data abstractors resolved discrepancies through discussion or through the help of a third reviewer. We used a standardized and pilot tested data abstraction form. We conducted calibration exercises prior to initiating data collection.We collected data regarding the characteristics of the journal, the COI disclosure policy.Impact factor according to the Journal Citation Report (JCR) Science Edition 2012;Journal category, according to the JCR Science Edition 2012. We reclassified these categories into: medical, surgical, other;Publisher;Membership of the ICMJE committee, according to ICMJE website;Abridged Index Medicus webpage or the journal website;Affiliation , according to the Asks authors to comply with reporting statements Existence of a COI policy;Basis of the COI policy The use of a standardized form;Disclosure requirements  covering both financial and non-financial COIs;Journal’s handling of disclosures .Disclosure of the financial relationships of authors, family members, etc…Financial relationships with regards to grant, personal fees, indirect financial support, stock ownership, direct employment, etc…Specification of the source and/or amount of payment/servicePersonal relationshipAcademic associationsProfessionalNon-Financial COIPolitical affiliationsNon-financial affiliationsReligious viewsIntellectualPersonal opinionAnything that affect objectivityAuthorship of original studies on the same subjectMembership of a guideline panelMembership of a particular school of thoughtAuthorship of an editorial on the same subjectAvailability of the disclosure within the body of the manuscript or separate from the manuscriptPotential impact of disclosed COI on editorial processPotential impact of non-disclosure on editorial processProcedures to verify authors' COI disclosuresWe conducted descriptive analyses of the characteristics of the journal, the COI disclosure policy. We used mean and standard deviation (or median and interquartile range (IQR)) for continuous variables and frequencies and percentages for categorical variables.Of the 119 journals indexed under Abridged Index Medicus, we included 117 as two journals proved to be non-peer reviewed . A total of eight journals published papers only by invitation; therefore, we were not able to simulate a submission of a manuscript to check for email replies. For eight journals, we limited our investigation to the review of public documents but did not simulate a manuscript submission due to associated submission fees .Out of the 117 included journals, 116 had a COI policy. Sixty-six journals (57%) required disclosure of non-financial COI. Journals stated that they made the COI disclosures available to the readers either within the body of the manuscript , or separately from the main manuscript . Twenty-six journals (22%) stated that they would make the COI disclosures available, but did not provide further details on how they would do that. Three journals stated they do not make the disclosures available .Some journals described a potential impact of disclosed COI on editorial process . About a quarter of journals described a potential impact of non-disclosure on the editorial process  . The impSeveral journals reported having procedures to verify authors' COI disclosures , with half (n = 10) not providing details about their procedures . AmongstAll but one of 117 core clinical journals has a COI policy, and all these journals require disclosure of financial COI pertaining to the authors; a minority asks for financial COI disclosure pertaining to the family members or institutions of the authors . About hThe results of this study are to a certain extent consistent with those of existing research, and may point to some positive trends. Our finding that all but one of 117 core clinical journal had a COI policy represents a proportion slightly higher than those found by previous similar studies. Blum et al found that, in 2008, 89% of “high-impact medical journals across 35 subject categories” had author COI policies . Bosch eIn our study 57% of journals required disclosure of at least one form of non-financial COI . Blum etA small minority of journals (17%) described a potential impact of disclosed COI on the editorial process . Even amThere is evidence that experts may fail to disclose all of their COI. One study found that 8% of experts failed to disclose their financial COI in clinical practice guidelines for hyperlipidemia or diabetes . A minorOne study investigated perceptions of COIs of reviewers of and applicants to French academic grants.  This quaThis study has a number of strengths. This is the first study to specifically address disclosure of intellectual COI, whether the journal makes the disclosure available, and the effect of disclosures on the editorial process. We have used systematic methods for data abstraction (duplicate process). This is the first study to evaluate the actual implementation of the COI disclosure policy during the submission process itself.The study also has limitations. Our design would not have captured journal requests for COI disclosure that might occur at later steps of the editorial process . We were not able to simulate a manuscript submission for seven journals that did not have a submission site and for eight journals that imposed submission fees.Our findings have a number of implications for editorial policies. Those policies should provide clear and explicit guidance to authors on disclosing non-financial COI. Based on the findings reported in The findings have a number of implications for future research. It would be valuable to explore how the standardized COI form  impacts the completeness and veracity of COI disclosures. It would also be helpful to address how frequently COI disclosures affect editorial decisions , and how frequently COI disclosures affect the perceptions of the readers regarding the trustworthiness of study findings. On a more general level, future research should assess whether all non-financial relationships discussed above should be deemed COI, whether they could be avoided, and whether they have as much influence as financial COI.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


Such synergistic action usually inhibits the efflux pump. The enhanced activity of plant-derived antimicrobials is being researched and is considered as the future treatment strategy to cure the incurable infections. The present paper reviews the advancement made in the researches on antimicrobial resistance along with the discovery and the development of more active PDAms. Infectious diseases caused by antimicrobial-resistant microbes (ARMs) and the treatment are the serious problems in the field of medical science today world over. The development of alternative drug line to treat such infectious diseases is urgently required. Researches on ARMs revealed the presence of membrane proteins responsible for effusing the antibiotics from the bacterial cells. Such proteins have successfully been treated by plant-derived antimicrobials (PDA Increasing antimicrobial resistance (AMR) among microbes caused the emergence of new resistant phenotypes and further caused the development of new antimicrobial compounds Goossens . InfectiMycobacteriumtuberculosis, resistant to virtually all classes of antimicrobials have also been identified in the Kwa Zulu Natal Province of South Africa  and vancomycin-resistant Enterococci spp.  and synergistic compounds as an alternative drug line.Multidrug-resistant (MDR) microbes are resistant to three or more antibiotics  was reported to contribute promising role, imparting resistance in S. aureus  imparting resistance in Gram-negative bacteria against natural products. AMR is a genetically-modified manifestation, linked to the point mutation in bacterial non-chromosomal DNA. As in case of MRSA, the resistance to methicillin is associated with acquisition of a mobile genetic element, SCCmec, which contains mecA-resistant gene  is a worldwide health problem, especially in UK,  susceptibility test performed on bacteria  are phenol derivatives, sufficiently able to control microbes by reducing pH, increasing membrane permeability, altering efflux pumping. Examples mentioned in Table ms largely depends upon the extraction methods  a real inhibitor of the pump enhancing the activity of berberine  and amphipathic antibiotic compounds (Lewis and Ausubel in Lewis . Plant ain Lewis . Studiesin Lewis  reported Gibbons . Wang et Gibbons  defined ms. A lot of research potential is also there to answer the questions for e.g. mechanism of resistance in different bacterial species, development of XDRs and their control.Researches on the AMR and alternating drug system are endless and a lot of scope is there in the field of ethno-pharmacology. Scientists are working on the development of safe and effective antimicrobials all over the world. Future studies may involve the development of new plant-derived synergistic compounds capable of enhancing the activity of PDAms and the synergistic compounds work efficiently on resistant strains ensuring no further resistance development. Moreover; concerted efforts have been solicited by the world community because poor countries are worst affected by the antimicrobial resistance and the developed countries are no longer safe (Diáz-Granados et al. ms in combination with plant-derived synergistic compounds may be the cost-effective approach to deal with global antimicrobial resistance.AMR is a worldwide problem. Research literatures suggest that the substandard living in major parts of developing world is one of the major causes of the development of resistance among bacteria. The developed world is also vulnerable of getting widespread infections for e.g. USA is surrounded by the developing countries having high rates of resistance development. Nosocomial, water borne, health care systems and food products especially meats are some of the most common means of widespread of resistant gene globally. Thanks to the modern molecular approaches for making better understanding of the pathways of resistance development and its remedy. Pharmacologists are developing new antibiotic drugs to treat and control various infections, however; the chances of the development of resistance are equal to the emergence of new drugs. In addition, research suggest that the combinations of PDA


The second Annual Meeting of the International Ovarian Cancer Consortium (IOCC) was held in conjunction with the Symposium on Tumor Microenvironment and Therapeutic Resistance at the Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, and USA. A brief welcoming event along with the banquet on Aug 16th was followed by the eight thematic scientific sessions from August 16 to 18, 2015. Forty-three lectures, organized in eight sessions, were discussed in front of an audience of more than hundred attendees. Emphasis was put on oncogene signaling in cancer genesis and progression, new approaches in Precision Medicine and therapy of ovarian cancer, the role of tumor microenvironment in carcinogenesis, and preventive/curative potential of natural products. In this meeting-report, we highlight the findings and the perspectives in cancer biology and therapeutic strategies that emerged during the conference. Ovarian cancer remains the leading cause of death from gynaecological malignancies in women, in spite of the progress in drug discovery and improvement in the clinical management of the disease that were made in the last fifty years. Due to non-specific symptoms in the early phases of the disease and the lack of reliable biomarkers, diagnosis of the disease in the early phase has proven to be a formidable challenge. More often than not, the tumor is diagnosed when it is already spread in the peritoneum. Genetic and epigenetic alterations accumulate during progression, that confer heterogeneity to the tumor, giving rise to metastatic and chemoresistant clones. Moreover, the presence of dormant cancer stem cells that show resistance to chemotherapy treatments contributes to the relapse soon after the chemotherapy is terminated. Clearly, to win the battle against ovarian cancer it is mandatory to pool all the expertise available, from cell and molecular biology to bioinformatics, genomics-epigenomics, and clinics.The International Ovarian Cancer Consortium (IOCC) was founded in 2014 in occasion of its first annual meeting that was held in February 9-11 at the Stephenson Cancer Center (SCC) at the University of Oklahoma Health Sciences Center, Oklahoma City. The Consortium aims to provide a platform for exchanging ideas and facilitating collaborations across the world for a better understanding of the biology and management of ovarian cancer. The scientific program listing the invited speakers and the titles of their lectures delivered at the 1st IOCC meeting is provided at the SCC website. The second meeting of IOCC was held on August 16-18, 2015 in conjunction with the third Symposium on Tumor Microenvironment and Therapeutic Resistance. This choice was quite appropriate, given that the cancer aggressiveness also reflects changes in the composition of the tumor microenvironment, with stromal cells secreting factors that facilitate cancer progression. The Stephenson Cancer Center hosted the event with the grant support from Presbyterian Health Foundation (Oklahoma), and the funding from the NIH COBRE Grant on “Mentoring Translational Cancer Research in Oklahoma (P20 GM103639)”. Other sponsors of the conference are Cancer Research Institute of Seoul National University , Tumor Microenvironment Research Center of Seoul National University , Oklahoma Tobacco Settlement Trust, and Oklahoma Medical Research Foundation. Forty-nine invited speakers from nine Countries presented their work in front of more than one hundred delegates. Additional Researchers presented their studies in the Poster session.http://stephensoncancercenter.org/Research/Research EventsandOther/OklahomaOvarianCancerConference. aspx). Below we summarize the novelties presented in the lectures and the perspectives emerged from the discussion.More information can be found on the website  presented the highlights on his early studies that led to the discovery of the oncogenic mutation in Dr. Jinsong Liu  recalled the attention on the polyploid giant cancer cells that can be seen in the context of ovarian cancer. These cells express the typical stem cells markers, such as CD44 and CD133, and may well represent a reservoir of cancer stem cells with a pivotal role in tumorigenesis and in chemoresistance . The ovaNewer insights into oncogenes and tumor suppressors were also presented. Using elegantly developed genetically engineered animal models, Dr. Gloria Su  presented her findings that establish premalignant pancreatic intraepithelial neoplasia (PanINS), pancreatic intraductal papillary mucinous neoplasm (IPMN), mucin-producing precursor neoplasm or mucinous cystic neoplasm are precursors of pancreatic cancer. By comparing the PanIN and IPMN mouse models, her studies provide clues to the intrinsic and extrinsic molecular differences involving p16, p19, p53, TGFβR2, Acvr1b, or Smad4 in addition to mutated K-Ras in pancreatic cancer genesis and progression [2This topic has been addressed in two specific sessions (II and III) and in two special lectures delivered, respectively, by Dr. Premkumar Reddy (see above) and by Dr. Channing Der . Dr. Christhardt Koeler  and Yong Beom Kim  introduced the theme of clinical management and the strategies to overcome the resistance to paclitaxel and cisplatin in ovarian cancer patients. Dr. Yong Sang Song  examined the role of the ascitic fluid in the progression of ovarian cancer and the onset of chemoresistance. It was found that the acellular fraction of ascitic fluid promoted the expression of genes associated with epithelial-to-mesenchymal transition and favored the invasive behavior of ovarian cancer cells through an IL-6-STAT3 signaling pathway . Other t3vice versa. Thus, the cells of the two compartments are subjected to a dynamic reciprocal reprogramming of their metabolism. Understanding the mechanisms that govern such cross-talk may pave the way to new therapeutic approaches. Dr. Maria Diaz-Meco  found that the loss of p62, a protein involved in the regulation of the autophagy-lysosomal degradation pathway, in cancer associated fibroblasts favors tumorigenesis because of the altered aminoacid metabolism in the stromal compartment that eventually results in increased production of IL-6 [Cancer cells are embedded in a stroma made up of a glyco-protein matrix containing a variety of host cells that include fibroblasts and immune cells. The secretions of these cells along with the blood-derived molecules constitute a microenvironment that influences the metabolism and the behavior of the cancer cells. The epithelial-stroma communication is bi-directional, as epithelial cancer cells release soluble factors  that modify the stroma composition and  of IL-6 . Interes of IL-6 . Consist of IL-6 .in vitro in 3-D cultures by Bonnie Sloane , who showed imaging of proteolysis that occurs in tumor microenvironment during cancer cell invasion [The dynamic (over-time) interactions between all the stromal components  and epithelial breast cancer cells have been modeled invasion . Clearlyinvasion .The inflammatory response and the generation of reactive oxygen species (ROS) in the microenvironment are important players in the development and progression of cancer. Role of redox signaling involving both cytosolic NAD(P)H oxidase and mitochondrial ROS-generating systems in conferring an aggressive invasive phenotype to prostate cancer was discussed by Hari Koul . David Wink  found that the nitric oxide produced in the stroma activates pro-oncogenic signaling pathway in (ER negative breast) cancer cells, while inducing the synthesis of immunosuppressive TGFβ and IL-10 in leukocytes. Consistently, the expression of iNOS (inducible NO synthase) is a strong predictor of poor outcome in patients bearing ER-negative breast cancers .4Cancer develops as a mixture of clones that have accumulated multiple genetic and epigenetic changes in individuals who present different genetic background and different history of carcinogen exposure. A big challenge in cancer therapy is to understand the differences and the similarities among cancer cells developing in the same organ of different individuals. Genomic analyses of the transcripts and microRNAs may serve to better delineate the altered pathways that characterize the cancer phenotype. Dr. Pradeep Chaluvally-Raghavan  identified two microRNAs, namely miR569 and miR551b, located in the 3q26 amplicon are highly amplified in high- grade serous ovarian cancers and they target proteins controlling apoptosis such as TP53INP1, STAT3, and KIT. Of note, it was found that the overexpression of these miRNAs correlates with poor prognosis in ovarian cancer patients . However5Excessive and sustained inflammation causes genomic instability, epigenetic dysregulation and alteration of intracellular signaling pathways. Fighting the generation of ROS in the tumor microenvironment may reduce the burden of genetic and epigenetic changes, thus limiting the progression and expansion of malignant clones. Dr. Duxin Sun  stressed the need for developing new strategies encompassing nanomedicine and natural products to target cancer stem cells. Dr. Shrikant Anant  reported the ability of gedunin, a heat shock protein (HSP)-90 inhibitor isolated from Indian Neem tree, to inhibit the growth of chemoresistant ovarian cancer cell lines. Dr. Chinthalapalli Rao  discussed the anticancer and protective effects of novel and safer nonsteroidal anti-inflammatory drugs. Dr. Doris Benbrook  outlined the chemoprevention strategy for ovarian cancer using a newly developed drug, ShetA2, which targets mortalin, a member of HSP-70 family . Dr. YouThe conference promoted the gathering of cancer researchers from more than thirty different institutions from nine different countries, thereby offering the participants with a cooperative network environment for future collaboration. The latest advances in the understanding of the biology of cancer and the possible translational impact on the clinical practice of this knowledge for a better management of cancer patients were successfully discussed among the participants. The conference was adjourned with the resolution that the next annual consortium meeting will be held in Oklahoma City while a satellite meeting will be held in South Korea.


The incidence of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) is increasing worldwide . These dWhile nutritional therapy has been shown to be efficacious in the treatment of CD, the mechanism of action has not been well characterized. Some hypotheses involve reduction in luminal antigens and food exclusion, a direct anti-inflammatory effect of the formula, improved nutrition, and changes in the gut microbiota -5. The dModulation of the gut microbiota composition is a proposed mechanism of action of enteral nutritional therapy, although the current data are sparse . The avaIn summary, it is clear that enteral nutritional therapy is a safe and effective approach to the treatment of Crohn's disease. Induction of remission and healing of the intestinal mucosa can be accomplished with enteral nutritional therapy. Enteral nutritional therapy may also be effective in maintaining remission and preventing post-operative recurrence of disease following resection. An enhanced understanding of the mechanism of action may allow for the development of less restrictive protocols which achieve the same effect. Additionally, mechanistic studies may help to identify patient populations who may be more likely to respond.


The clinical utility of tender point (TP) examination in patients reporting chronic widespread pain (CWP) is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity. 271 women with CWP were recruited from a clinical setting. Data collection included patient-reported symptoms, health-related quality of life variables, and observation-based measures of functional ability, muscle strength, 6-minute walk, and pressure pain thresholds measured by cuff algometry. TP examination was conducted according to ACR-guidelines. Relationships between disease variables and TP count (TPC) were analyzed with logistic regression in a continuum model, allowing the TPC to depend on the included disease variables and two regression models carried out for a TPC threshold level, varying between 1 and 17. The threshold analyses indicated a TPC threshold at 8, above which a large number of disease variables became consistently significant explanatory factors, whereas none of the disease variables reached a significance level in the continuum model. These results support the premise that the presence of mechanical hyperalgesia influences symptomatology in CWP and that the severity of clinical expression is related to a threshold of TPs, rather than being part of a continuum. Fibromyalgia is a characterized subgroup of patients presenting with chronic widespread pain (CWP) and widespread mechanical hyperalgesia. These characteristics are enshrined in the 1990-ACR criteria . The undA positive relationship between TP count (TPC) and psychological distress seems well established, although a quite variable association between the TPC and clinical disease severity has been reported –15. In tThe WHO international classification of functioning, disability, and health (ICF) can serve as a framework when defining clinical disease severity . The ICFThe objective of this study was to evaluate the relationship between TPC threshold and clinical disease severity in patients with CWP using the multidimensional ICF measurement framework. It was hypothesized that the clinical disease burden in patients with CWP would be influenced by the presence and spread of mechanical hyperalgesia, as evaluated by the manual TP examination.The study was cross-sectional with systematic data collection on consecutive female patients diagnosed with CWP at rheumatologic examination and accepted for enrolment in an interdisciplinary rehabilitation program tailored for this patient population at the department of rheumatology, Frederiksberg Hospital. A comprehensive baseline assessment based on the brief ICF core set for CWP  was implThe referral diagnosis of CWP was based on the 1990-ACR definition of wide spread pain  . Measures of psychological distress  were low to moderate in the overall study population and no significant group differences were present.Within the body domain, patients with a TPC above 8 reported significantly higher levels of pain intensity, tiredness, fatigability, and muscle stiffness and had lower levels of knee muscle strength and walking ability (6-MW) and lower pressure pain thresholds as measured with CPA. However, CPA pain thresholds overall showed only a weak correlation with the number of TPs [pain threshold: P = 0.004], indicating a higher degree of observable effort and/or fatigability during ADL-task performance. No significant differences between groups were noted for measures relating to the level of participation  or personal factors  at this TPC level.Within the domain of activity and participation, the TPC threshold of 8 or more was associated with significantly higher self-reported ratings of functional disability and also ADL motor ability measures of the AMPS were significantly lower in patients with a TPC above 8 [1.04 versus 1.29 logits,  threshold on the number of TPs rather than being part of a continuum. Logistic regression analyses indicated that a TPC of 8 defined a threshold above which a large number of variables linked to pain and pain-related interference with everyday life became consistently significant explanatory factors  and self-reported well-being measured with the SF-36. None of these variables appeared as significant explanatory factors at lower TPC thresholds and pain catastrophizing and pain self-efficacy variables never entered the model. This finding was in accordance with the results of the multivariate/full model and supports the notion that the relationship between psychological distress and CWP is not solely due to TPs, but most likely pertains to the affective component of pain.It is noteworthy that in the univariate/marginal model onlythe ADL motor ability measure of the AMPS was consistently significant throughout the entire range of TPC thresholds. Functional ability is considered a core outcome in clinical pain research , 29–31. TPC threshold analyses in the multivariate/full model with the TPC pain response cutoff set at 2 indicated a shift in explanatory variables similar to the shifts in the univariate/marginal model and at the same thresholds. However, whereas the results in the marginal model were more consistently significant, the behavior of the full model suggested a change in explanatory variables. The results of the multivariate/full model indicated that at lower TPC thresholds covariates related to function  seemed to show the strongest and most consistent relationship with number of TPs. Contrary to the findings in the univariate/marginal model, self-reported level of pain and fatigue never entered the full model as significant explanatory factors. Pain reduction following treatment has been shown to parallel improvements in other outcomes in patients with CWP, including self-reported physical and social functioning, sleep, and interference with work . The intSeveral studies have reported a positive relationship between number of TPs and self-reported somatosensory symptoms of neuropathic pain in patients with CWP and fibromyalgia –39, as wEvaluated in an ICF-measurement framework covering core set categories identified for the multidimensional assessment of CWP, the negative impact on measures obtained at the body level and level of activity and participation was substantial. In accordance with the existing literature , 42 the Limitations and Generalizability. The study was conducted in a specialized tertiary-care setting and patients encountered are not necessarily representative of patients from the overall referral population. It has been reported that patients with CWP in referral clinics demonstrate higher pain severity and negative consequences related to pain than similar patient groups found in the community [ommunity . Howeverommunity  the stud threshold rather than a TPC continuum. Provided the requirement of a moderate or greater pain response at palpation, the major shift of disease severity occurred at a TPC of ≥8. This relationship was not observed if the TPC in individual patients was based on a TP cutoff set at mild tenderness, suggesting that a hyperalgesic pain response at palpation should be required in order for TPs to be considered a primary identifier of pain hypersensitivity. These findings are at odds with the affective spectrum disorder hypothesis [Patients with CWP encountered in the clinical setting exhibit a positive relationship between the number of TPs and severity of the clinical pain condition through a TPCpothesis  and suppAnnex A contains a detailed description of the applied questionnaires and observation-based assessment methods, and two figures showing the distribution of patients according number of tender points with the cutoff for the pain response at tender point examination set at 1 and 2, respectively.Click here for additional data file.


Streptomyces.The exploration of habitats with unusual environment and poorly explored areas such as Antarctica is one of the strategies for discovery of new biologically active substances and/or new producers. The aim of this study was to identify the actinomycetes isolated from the soils of the island Livingston – Antarctica and to investigate their potential to synthesize antibacterial agents against phytopathogens. Twenty-three actinomycete strains were the object of this study. Using PCR (polymerase chain reaction) amplification all strains were affiliated to genus Streptomyces tendae for one of them, and revealed that the other strains had closest relations to streptomycetes isolated from anthropogenically unaltered regions including Antarctica.The sequencing of the 16S rRNA for three of the strains showed greatest similarity to The isolates were studied for production of antibacterial substances both by molecular and culture methods. PCR targeting specific biosynthetic genes involved in the production of some groups of antibiotics was performed. The screening showed that all strains possessed the gene for Type-II polyketide synthase, 11 strains – for non-ribosomal peptide synthetase; 6 strains – for polyene antibiotics; and 4 strains – for glycopeptide antibiotics. The production of antibacterial substances by the strains was tested in vitro against phytopathogenic bacteria. The strains differed in the number of inhibited test – bacteria and in their spectrum of action. Four strains showed a wide range of activity against Gram-positive and Gram-negative phytopathogens.The results obtained revealed that the Antarctic soils are potential source for isolation of streptomycetes producing antibiotics from different groups. Antarctica is the southernmost continent and is surrounded by the southern waters of the World Ocean. It is the coldest, driest and windiest continent; approximately 98% of it is covered by ice. Despite the harsh and unique environmental conditions, a greater than expected organism diversity was found – including a number of endemic and yet unknown species.Streptomyces is composed of a large number of species many of which synthesize a broad spectrum of secondary metabolites. Several studies have been focused on identifying biocontrol agents which could be used as an alternative to agrochemicals in plant protection.FigStreptomyces and Nocardiaceae strains , but their occurrence varied very much in the other taxa. In our study it was determined that 56% of the tested Antarctic Streptomyces strains possessed the NRPS sequences.The NRPS is a biosynthetic system involved in the synthesis of many important biologically active peptides produced by a range of microorganisms including the actinomycetes used in medicine, agriculture and biochemical studies. Using primers A3 and A7R, Ayuso-Sacido and Genilloud tested a large collection of 210 reference strains from all major families and genera of actinomycetes for NRPS. The resuS. avermitilis ATCC 31267T, and [The screening for PKS-II genes showed that all of the 23 analysed strains gave a positive result forming a product of about 500 bp . Type-IIStreptomyces. Analysing streptomycetes from Antarctica Mavengere did not detect the genes for glycopeptides.[The PCR screening for glycopeptides showed that four of the analysed strains showed a detectable amplification product with a length of 696 bp which is specific for the used primer pair FOXY/ROXY .12] Gly Gly12] Gpeptides. This couOf all streptomycete strains screened by PCR-amplification with degenerative primers, I and II, for six isolated products of about 350 bp were amplified, which correspond to the gene encoding polyene-specific enzyme CYP (cytochrome P450 hydroxylase) .Figure Streptomyces. The prevalence of fungal infections in recent decades, the low efficiency of the treatment of certain fungal infections, makes the search for new and more effective antifungal agents necessary. In the literature there is no information available on the potential of Antarctic streptomycetes to produce polyene antibiotics. Our study provides useful information for future research on this issue.Polyene antibiotics are a class of antimicrobial compounds with fungicidal activity which are usually produced by actinomycetes of genus Based on the PCR screening performed, the strains can be separated into four groups according to their genetic potential to synthesize various bioactive substances. The widest biosynthetic potential had six of the strains possessing the genes for PKS-II, NRPS and CYP; five strains had the genes for PKS-II and NRPS; four strains possessed the genes involved in the synthesis of glycopeptide antibiotics and PKS-II; and eight strains seemed to possess only the genes for PKS-II. Most common among the studied Antarctic streptomycetes are the genes for PKS-II.The streptomycete strains were screened for antibacterial activity against several Gram-positive and Gram-negative bacteria, most of which were phytopathogens .Burkholderia cepacia, B. gladioli, B. pyrrocinia, Erwinia amylowora and against E. coli. The strains possessed different spectrum of action. Four of the strains  demonstrated a broad spectrum of antibacterial activity and affected both Gram-positive and Gram-negative bacteria. Strain 13M showed the highest activity and inhibited the largest number of test-bacteria  and strain 1M has the broadest genetic potential for antibiotic synthesis (PKS-II/NRPS/polyenes). The reasons for this discrepancy might be different – inhibition of the expression of these genes, unfavourable for antibiotic synthesis cultivation conditions , and were not a subject of the present work. At the same time strain 13M which had the broadest spectrum of antimicrobial activity in vitro and strain 6M also with good activity possessed only the genes for PKS-II.The comparison of the data from the PCR screening for the biosynthetic genes involved in the production of antibiotics to the data from the Since the strains with greatest antimicrobial activity possess either PKS-II/NRPS/polyene, PKS-II/NRPS or only PKS-II genes, no clear statement of the nature of the particular substances responsible for this activity can be made. This study presents an initial screening for the biocontrol potential of the Antarctic streptomycetes and further research is needed to clarify the specific molecules involved in this process.Streptomyces. The Antarctic streptomycetes show a good potential to produce different biologically active substances active against phytopathogenic bacteria.Streptomycetes are an abundant group of soil microorganisms in Antarctica which was proved by cultural and molecular methods. All of our bioactive strains were proved to belong to the genus


Objectives. This study was conducted to verify the necessity of corresponding prescription to the diagnosed pattern in acute cerebral infarction patients. Methods. We studied cerebral infarction patients hospitalized within 30 days after the ictus. Forty-four clinical indicators, Motricity Index (MI) score, Scandinavian Stroke Scale (SSS) score, and herbal prescriptions were checked twice, two weeks apart. The probability of each pattern was calculated based on the clinical indicators. Changes in MI score, SSS score, and the probability of fire-heat pattern were compared between the pattern-prescription correspondence group and the noncorrespondence group. Results. Increments of MI score and SSS score in the correspondence group were significantly greater than those of the noncorrespondence group  while the baseline score of the two groups showed no significant difference. Probability of fire-heat pattern decreased significantly in the correspondence group (p = 0.013) while the noncorrespondence group showed no significant difference after the treatment. Conclusion. Acute cerebral infarction patients who are diagnosed as fire-heat pattern showed better improvement in dysfunctions caused by the disease when they took the pattern corresponding prescriptions. This study provides evidence for the necessity and usefulness of pattern identification in Traditional Korean Medicine. In South Korea, the political and social status of Traditional Korean Medicine (TKM) almost equals that of Western medicine. This is due to a strong preference for TKM in Korean people. When 1,000 people living in Seoul were asked to choose between Western medicine doctors and TKM doctors if they had developed a stroke, 25% of the subjects chose TKM doctors, and 45% of the subjects responded that they were willing to receive TKM treatments [Considering the large role in the treatment of stroke, significant amount of effort was put into accumulating scientific evidence of the efficacy and safety of TKM. As a result, questionnaire for the pattern identification and guidelines for assessing the clinical indicators were developed over the years , 4. ThesIn this study, to verify the necessity and usefulness of pattern identification, we compared the two groups of the patients diagnosed as fire-heat pattern. The group who took the herbal prescriptions in accordance with the pattern identification and the group of people who did not take the herbal prescriptions accordingly were compared to demonstrate if the corresponding prescription taking group shows better outcome. Also, we performed a correlation study between the changes in clinical indicators and the improvement in dysfunctions to identify if the changes in symptoms are relevant to recovery of poststroke dysfunctions.We enrolled ischemic stroke patients within 30 days after their ictus from Kyung Hee Korean Medical Center and Kyung Hee East-West Neo Medical Center. Imaging diagnosis such as computerized tomography (CT) or magnetic resonance imaging (MRI) was checked to confirm the ischemic stroke. We excluded traumatic strokes such as subarachnoid, subdural, and epidural hemorrhage. Also, we excluded patients with brain tumor, Alzheimer's disease, multiple sclerosis, or any other neurodegenerative diseases. Informed consent of all the participants was obtained after a thorough explanation of the details. Over a 3-year period from May 2011 to January 2014, 300 patients were included in the study. The Institutional Review Board of the Kyung Hee Korean Medical Center and Kyung Hee East-West Neo Medical Center approved the present study .After the admission, two different TKM doctors identified the pattern of each patient based on the clinical indicators they show, and we confirmed the pattern only if the two TKM doctors had the same opinion. We used the Case Report Form (CRF) and the Standard Operation Procedures (SOP) developed by the Korean Institute of Oriental Medicine , 10 to rAll subjects were studied twice, 2 weeks apart. During the 2-week period, all participants received conventional Western medicine treatment such as antiplatelet agent, risk factor control , and rehabilitation exercise. TKM treatment was also administered to all of the patients, which includes herbal prescription, acupuncture, and electroacupuncture. The contents of acupuncture and electroacupuncture treatment are shown in Baseline characteristics such as age, sex, Body Mass Index (BMI), period from onset to admission, medical history, alcohol and smoking habits, and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification , 12 of tTo assess the changes in the clinical indicators, we used the logistic equations for calculating the probability of each pattern suggested by Kim et al. . The samProbability of Fire-Heat Pattern. ConsiderProbability of Yin Deficiency Pattern. ConsiderProbability of Phlegm Dampness Pattern. ConsiderProbability of Qi Deficiency Pattern. Considerp < 0.05 was considered significant.Statistical analysis was performed by using the Statistical Package for the Social Sciences version 12.0 for Windows . Chi-square test was used for the categorical variables, and Mann-Whitney test was used for the continuous variables when comparing the two groups. Wilcoxon signed rank test was used for statistical comparisons between the values before and after the treatment. We correlated the changes in the probability of fire-heat pattern with the changes of SSS score and MI score, respectively, using Spearman's rank correlation. A Of the 300 patients enrolled in the study, 68 patients were discharged before the second checkup, and 44 patients with perfect MI and SSS score were excluded as they could not expect further improvement. 40 patients were unable to determine the pattern because the diagnosis of the two TKM doctors differed. 11 patients were dropped out due to missing data. Also, many patients diagnosed as Yin Deficiency Pattern, Phlegm Dampness Pattern, and Qi Deficiency Pattern received different types of herbal prescriptions during the treatment period. Only two patients in the Yin Deficiency Pattern, three patients in the Phlegm Dampness Pattern, and two patients in the Qi Deficiency Pattern received pattern corresponding herbal prescription for the whole 2-week period, so we were unable to secure a sufficient sample size for statistical analysis for those three patterns. Among the remaining 57 patients who were diagnosed as fire-heat pattern, we considered 40 patients who received herbal prescriptions targeting fire-heat pattern related symptoms into correspondence group and the other 17 patients who received herbal prescriptions focusing on clinical indicators of other patterns into noncorrespondence group . After 2General characteristics, period from onset to admission, medical history, alcohol and smoking experience, and proportion of ischemic stroke type according to TOAST classification showed no significant difference between the two groups .p = 0.003, p = 0.001) while the baseline scores of the two groups showed no significant difference . The baseline probability of fire-heat pattern between the two groups showed no significant difference. The probability of fire-heat pattern decreased significantly after the treatment in the correspondence group (p = 0.013) while the probability of fire-heat pattern in noncorrespondence group showed no significant change. Probability of other patterns showed no significant change after the treatment in both groups (The probability of fire-heat pattern was significantly higher than the probability of other patterns in both groups (h groups .p = 0.027) and missed statistical significance with the increase in the MI score (p = 0.058) . This suggests that taking herbal prescriptions in accordance with the diagnosed pattern is more effective in improving functional impairments of acute ischemic stroke patients diagnosed as fire-heat pattern.The aim of this study was to verify the usefulness of the pattern identification. To achieve this goal, we compared the outcome of the treatments in pattern-prescription correspondence group and the noncorrespondence group. While the baseline scores did not differ significantly between the two groups, increments of MI score and SSS score after the treatment were significantly higher in the correspondence group than the noncorrespondence group (p = 0.013) while there were no significant changes in the noncorrespondence group. Also, correlation study indicates that the patients with larger increment in the SSS score showed larger decrement in the probability of fire-heat pattern (p = 0.027). In our previous study concerning the treatment of acute ischemic stroke patients, motor function recovery in the patients correlated significantly with the improvement in the symptoms related to fire-heat pattern [A type of herbal prescription is selected based on the clinical indicators a patient is showing, and when used, the herbal prescriptions are expected to alleviate the clinical symptoms. We used the probability of fire-heat pattern as a scale to evaluate the changes in the clinical symptoms of patients diagnosed as fire-heat pattern. As expected, the probability of fire-heat pattern decreased significantly in the correspondence group ( pattern , which iUsage of herbal prescriptions on acute ischemic stroke patients has been studied over the years –9, but nWe could not verify the effectiveness of pattern identification in patients diagnosed as Yin Deficiency Pattern, Phlegm Dampness Pattern, and Qi Deficiency Pattern, because they were not consistent in consuming the herbal prescriptions corresponding with their pattern and therefore were not suitable for the subjects of this study. This was not expected when we designed the study, but due to this outcome, the application of the results in the present study should be limited only in the patients diagnosed as fire-heat pattern. Another limitation is that the probability of pattern does not properly evaluate the severity of the clinical symptoms related to each pattern since the scale was made to determine the pattern not to assess the clinical indicators. We used the probability of patterns in this study because this scale was created based on the data collected using the same CRF and SOP used in the present study. There is no widely accepted scale assessing the severity of the symptoms related to pattern identification, and it should be developed in the future for more researches concerning pattern identification.In the present study, correspondence group displayed better outcome than the noncorrespondence group, and in the correspondence group, patients with lesser clinical indicators related to fire-heat pattern after the treatment showed better improvement in the recovery of functional impairment. These results imply that herbal prescriptions in accordance with the diagnosed pattern alleviate the clinical symptoms in relation with the diagnosed pattern and are more effective in restoring the dysfunctions caused by the disease than the noncorresponding prescriptions. The results provide evidence for the necessity and usefulness of pattern identification in TKM, but further research is needed to confirm the effectiveness of pattern identification for the other pattern groups.


Ossifying metaplasia is an unusual feature of urothelial carcinoma, with only a few cases reported. The largest series included 17 cases and was published in 1991. The mechanism of ossification is unknown and hypotheses of osteogenic precursor cells, inducing bone formation, are proposed.A 75 year-old patient was treated for a high grade transitional cell carcinoma of the bladder by surgery, chemotherapy and radiotherapy. Histology showed foci of bone metaplasia, both at the periphery of the tumor, and in a lymph node metastasis. 1 year later, a heterotopic bone formation was discovered in the right retroperitoneal space, near the lumbar spine, increasing rapidly in size during follow-up. Several imaging exams were performed , but in the absence of typical features of sarcoma, diagnosis remained unclear.Histology of a CT-guided percutaneous biopsy showed urothelial carcinoma and mature lamellar bone. Integration of these findings with the radiological description of extraosseous localization was consistent with a diagnosis of osseous metaplasia of an urothelial carcinoma metastasis. The absence of bone atypia in both the primary and metastases argues against sarcomatoid urothelial carcinoma with osteosarcomatous differentiation.Osseous metaplasia of an urothelial carcinoma metastasis is unusual, and difficult to distinguish from radiotherapy induced sarcoma, or from sarcomatoid carcinoma. Rapid progression, sheathing of adjacent structures such as vessels (like inferior vena cava in our case) and nerves and bony feature of lymph node metastases necessitate histological confirmation and rapid treatment. Our case illustrates this disease and evaluates the imaging features. In addition we discuss the differential diagnosis of osseous retroperitoneal masses. Osseous metaplasia is rarely observed in the stroma of bladder carcinoma, either in the primary tumor  or in a Although the mechanisms are still hypothetical, osteogenic precursor cells, a favorable microenvironment, and ossification-inducing stimuli are prerequisites to the heterotopic formation of bone. The hypothesis is that a clone of tumor cells produces bone foci by inducing osteogenesis.Imaging revealed an osseous mass in the retroperitoneal space, infiltrating posterior structures including vessels and nerves and generating compression of adjacent tissues with bone invasion. We report the case of an osseous metaplasia in urothelial carcinoma, both in the primary and in metastases. This case is illustrative of the course of the disease with its imaging features (which are not specific), and allows discussion of the main differential diagnoses, particularly sarcoma and other rare ossifying pathologies.A 75-year-old man was treated for a high-grade bladder urothelial carcinoma (pT3b N1) by endoscopic resection of the bladder with neo-adjuvant chemotherapy, followed by a right nephro-uretrectomy, a radical cysto-prostatectomy and bilateral ilio-obturator lymph node dissection. Macroscopic invasion of perivesical soft tissue was observed, and histology showed poorly differentiated carcinoma Fig. , with peTreatment was completed by adjuvant chemotherapy and radiotherapy for positive lymph nodes. Two years later, during normally scheduled imaging follow up, the apparition of several osseous formations localized in the right retroperitoneal space within the psoas muscle at the level of the bodies of 4th and 5th lumbar vertebra was noted Fig. . The forA complementary MRI Fig.  was perfHistological study of the biopsy showed mainly crush artifacts, but also minute foci of lamellar bone trabeculae associated with broad spectrum keratin  and p63 positive epithelial cells consistent with metastatic urothelial carcinoma Fig. . Again, At the time of this report, the patient is still alive and only the mentioned lesions are progressing, without response to additional radiotherapy.Bone formation in the stroma of bladder carcinoma or in heterotopic sites has been noted in a few reports –8. 17 caTo our knowledge, this is the first reported case focusing on the aggressiveness of these metastases illustrated by a multimodality imaging approach. CT represents the best imaging procedure, and shows multiple osseous formations, located in the retroperitoneal space following lymph nodes sites, sheathing adjacent vessels, that may encase nerves and spinal ganglia, as in our case. Another finding was the invasion of adjacent bones with the same matrix. Furthermore, CT allows follow up of the lesions and detection of new lesions. The metabolic activity recorded on the PET-CT was moderate and the imaging pattern on MRI was non-specific, the osseous lesions appearing hypointense in all the sequences. The diffusion sequence does not contribute to the characterization of the lesion matrix due to the pronounced hypointensity on T2 sequences.The case presented here showed rapid progression of the disease with risk of local compression; no vascular erosion or fracture was noted during the follow up period of 2 years and a half. This osseous metaplasia leads to the differential diagnosis of bone formation. In the context of carcinoma treated with radiotherapy and if the disease appears in the irradiation field, a radiation induced sarcoma should be the first suspected diagnosis. It is a well-known entity and the major criteria for the definition, controversial in the literature, is the length between radiation exposure and tumor formation: it seems that a latency of 6 months is sufficient to affirm the diagnosis in some cases . ExtraskThese areas are heterogeneous with focal hypoattenuation on CT and intermediate signal on T1 with enhancement  or low sMalignant bone formation can be a feature of the sarcomatoid variant of infiltrating urothelial carcinoma, a well recognised entity , consideMyositis ossificans is a benign solitary soft tissue ossifying mass in skeletal muscle, with a history of traumatism. The pattern of peripheral ossification is important to establish the diagnosis; mature forms may present a complete ossification . The lesMelorheostosis is defined as a rare sclerosing bone dysplasia with a characteristic linear sclerosis of cortical bone; calcification and ossification of soft tissues are typically found near the large joints. It appears as low signal intensity in all MR sequences but intermediate signal is described with enhancement in soft tissue masses , 23. ComTumoral calcinosis can also be discussed in the presence of a massively calcified mass . It is aAmyloidosis was also considered in the differential diagnosis. It is a heterogeneous group of disorders and in systemic form, amyloid may infiltrate the retroperitoneal and pelvic soft tissues and undergo gradually progressive calcification over time with formation of soft tissue thickening, encasing the urinary tract and involving renal sinus. CT shows amorphous calcification associated with tissue thickening, MRI demonstrates intermediate signal intensity on T1 and decreased signal intensity on T2 .Other rare, benign neoplastic causes of calcified masses in the pelvic retroperitoneum include ganglioneuroma, schwannoma, paraganglioma, hemangioma, and presacral teratoma .To the best of our knowledge, this is the first reported case of retroperitoneal osseous metaplasia in a urothelial carcinoma metastasis studied with different imaging modalities and confirmed with percutaneous, CT guided biopsy. In this case we also demonstrated the aggressiveness of the disease, the rapid progression and the sheathing characteristic of adjacent organs including vessels and nerves. Sarcomatous carcinoma and radiation induced osteosarcoma are the most challenging differential diagnoses even though delay was short.Prognosis is likely determined by the extent of the high grade urothelial carcinoma, but independent of the benign metaplastic bone component.Written informed consent was obtained from the patient for publication of this case report and any accompanying images.