The purpose of this study is to investigate whether a prolonged delay in diagnosis of bladder cancer will result in worse outcomes for those patients, compared to those patients with a shorter diagnostic time interval. Data was collected on 247 patients newly diagnosed with transitional cell carcinoma of the bladder from January 1996 to December 2006 (10 years). The medical records of these patients were reviewed for demographics, pathological stage, date of consultation to the genitourinary (GU) service, and date of diagnosis by transurethral resection of bladder tumor (TURBT). The specialty delay was calculated as the time between the date of consultation to the GU service to the establishment of a diagnosis by TURBT. Univariate analyses were performed to test the association of specialty delay with clinical features and all-cause mortality. The median specialty delay in this study was 100 days. There was a trend towards a longer specialty delay for muscle-invasive disease (T2-T4) in comparison to superficial disease (Ta and T1). There was a significant correlation between all-cause mortality and increasing clinical stage (p=0.01). There was a paradoxical finding that patients with a specialty delay greater than 100 days had a significant reduction in all-cause death in comparison to patients with a specialty delay of 100 days or less (relative risk=0.59; 95% CI 0.36-0.90; p=0.01). In conclusion, this study did not confirm the hypothesis that a prolonged specialty delay in patients diagnosed with bladder cancer would result in a worse prognosis. In fact, there was a paradoxical finding that patients with a specialty delay greater than the median delay of 100 days had a better prognosis.

Ziel der Studie war die morphologisch-funktionelle Charakterisierung der Endometrose mittels konventioneller histopathologischer und neuer immunhistologischer Methoden. Die Ergebnisse wurden mit den Abfohlraten der untersuchten Stuten verglichen, um eine genauere Prognose hinsichtlich der Fertilität zu erhalten. Innerhalb der physiologischen Decksaison wurden von 159 klinisch gesunden, östrischen Stuten (3 bis 21 Jahre alt) Endometriumbioptate entnommen. Die Stuten wurden danach im selben Jahr besamt und nach Erfassen der Abfohlraten im folgenden Jahr in zwei Gruppen eingeteilt: güste Stuten und nicht güste Stuten. Im Rahmen einer Doppelblind-Studie wurden endometriale Alterationen lichtmikroskopisch erfasst sowie Grad und Qualität der Endometrose histomorphologisch definiert. Repräsentativ ausgewählte Bioptate (n=82) wurden immunhistologisch auf die Expression der Steroidhormonrezeptoren (Östrogenrezeptor, ER; Progesteronrezeptor, PR) und ausgewählter endometrialer Proteine (Uteroglobin, UG; Uterokalin, UK; CalbindinD9k, CAL; Uteroferrin, UF) untersucht. 101/159 Stuten zeigen eine, qualitativ und quantitativ variierende, Endometrose. Die fibrotischen Uterindrüsen weisen, im Vergleich zu unveränderten Drüsen, ein zyklusasynchrones, teilweise innerhalb eines Drüsenquerschnittes ungleichmäßiges endometriales Proteinmuster auf. Das ungleichmäßige Expressionsmuster kann als Zeichen einer endometrialen Fehldifferenzierung innerhalb fibrotischer Areale interpretiert werden. Die Aktivität der Endometrose hat keinen Einfluss auf das endometriale Proteinmuster. Güste Stuten besitzen häufiger einemittelgradige, vorwiegend destruierende, inaktive oder gemischte Endometrose. Insbesondere in Arealen mittelgradiger destruierender Endometrosen ist eine deutlich verminderte Expression von UG und UK nachweisbar. Auch in der geringgradigen Endometrose werden häufiger beide Proteine gleichzeitig zyklusasynchron exprimiert. UF wird innerhalb höhergradiger destruierender fibrotischer Herde überweigend intensiver exprimiert als in den unveränderten Epithelien, während CAL vielfach ein variables Proteinmuster besitzt. Nicht güste Stuten hingegen zeigen häufig eine geringgradige aktive oder inaktive Endometrose. Bei diesen Stuten weist ein hoher Anteil betroffener glandulärer Epithelien in der mittelgradigen Endometrose entweder eine zyklussynchrone oder geringgradig zyklusasynchrone Expression von UG, UK und CAL auf. UF wird auch in dieser Gruppe häufig intensiver in fibrotischen Drüsen exprimiert. Zwischen güsten und nicht güsten Stuten bestehen charakteristische Unterschiede im Expressionsmuster von UG und UK: nicht güste Stuten besitzen in gering- und mittelgradig fibrotisch veränderten Uterindrüsen häufiger eine zyklussynchrone Proteinexpression als güste Stuten und seltener deutliche Abweichungen in der Expression von entweder UG oder UK. Stuten beider Gruppen besitzen eine zyklusasynchrone Expression der ER und PR sowohl in den periglandulären fibrotischen Stromazellen als auch im Drüsenepithel. Die glanduläre Hormonrezeptorexpression ist tendenziell abhängig von der Aktivität der Endometrose. Diese Resultate sprechen für eine Abkopplung fibrotischer Areale von den uterinen Kontrollmechanismen. Im Rahmen dieser Studie konnte überwiegend bei güsten Stuten in der Endometrose, im Vergleich zu unveränderten Drüsen, ein deutlich abweichendes endometriales Proteinmuster von UG und UK dargestellt werden. Insbesondere bei Tieren, die an einer mittelgradigen destruierenden Endometrose leiden, könnte diese Tatsache als Hinweis auf eine fertilitätsmindernde Beeinflussung des uterinen Mikromilieus im Rahmen der Endometrose interpretiert werden. Die vorliegende Untersuchung unterstreicht die Notwendigkeit einer genaueren Klassifizierung der Endometrose und empfiehlt, zusätzlich zum Grad auch die Qualität der Endometrose sowie das endometriale Expressionsmuster von UG und UK in der Epikrise für eine präzisere Fertilitätsprognose zu berücksichtigen.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010. / Härtill 5 uppsatser.

Information in the transition to the late palliative phase is not a well-studied area, especially not from the perspective of patients and family members. The aim of this thesis was to describe how cancer patients, family members and physicians experience information during the transition from a curative or early palliative phase to a late palliative phase, i.e. when tumour-specific treatment could not be offered. Cancer patients (n=30) admitted to palliative hospital based home care, family members (n=20) of cancer patients, and physicians (n=30) working with cancer patients in different settings were included in order to create a maximum variation sampling. Tape-recorded, semi-structured interviews and qualitative, phenomenographic analyses were done in all the studies. Patients described the physician as an expert (study I), an important person during this event, despite characterising him/her in different ways ranging from the empathetic professional to the rough and ready expert. Their relationship with the physician was also stressed. Their own resources, i.e. a sense of well being, a sense of security and individual strength, and their previous knowledge, were important components regarding their ability to take part in the communication (study II). Patients interpret words and phrases carefully and can perceive them as forewarnings, as being emotionally trying, and as fortifying and strengthening (study III). The overall message could be interpreted as either focused on quality if life, on treatment or on death and threat. Family members wanted to protect the patient during this period and could be very active and prominent in their protective role (study IV). However, other family members described themselves as being in the background more or less involuntarily. Family members also felt that there were expectations regarding their behaviour, either that they should take over in terms of communication, or that they should restrict their participation. When giving information, the physicians had a clear goal - to make the patient understand while being as considerate toward the patient as possible. However, the strategies for reaching this goal differed and included: explaining and convincing, softening the impact and vaguely suggesting, preparing and adapting. Some physicians had a main strategy while others mixed different strategies depending on the context. The experience of receiving and providing information about discontinuing tumour specific treatment is like crossing a border, where patients experience the behaviour of the physician and the words they express of great significance. Family members assume the role of protectors. Physicians use different strategies in order to help patients cross the border. / On the day of the public defence the status of the article II was: In press and the title was: Patient interpretation of verbal expressions when given information about ending cancer treatment.; the status of article V was: Submitted.

Autoimmune hepatitis (AIH) was identified as an entity by the Swedish professor Jan Waldenström in the 1950s. It was then denoted lupoid hepatitis, characterized by liver inflammation and most often affecting young women. During the years the diagnosis has become more defined (as the non A non B hepatitis has been identified as Hepatitis C) and now can be safely separated from other diseases with liver inflammation. Studies of epidemiological data and long term prognosis have been scarce in the literature. Within a collaboration between the university hospitals in Sweden, we collected what we believe is the largest cohort in the world of patients with AIH. Data from the medical records of 473 individuals was, after AIH-score calculations where the diagnosis was confirmed, collected in a data base, in which most of the analysis was done. Data from the Swedish national registers of cancer, death cause, and birth register was searched for these patients as well as controls. The aim of the thesis was to explore epidemiological and clinical outcome of AIH.The onset of AIH may be at any age, but the incidence seems to increase after 50 years of age; 75% are females, the overall incidence (0.85/ 100,000 inhabitants and year) and prevalence (11/100,000 inhabitants) are figures that are within the range of another but smaller Scandinavian study. Approximately 30 % had cirrhosis already at diagnosis and 87% displayed at some time positive auto-antibodies indicating AIH (Smooth muscle ab and or antinuclear ab).  Indications of future risk for liver transplantation or death is an advanced AIH at diagnosis with liver cirrhosis, decompensated liver disease, elevated PK INR as well as age. Acute hepatitis-like onset seems to carry a lower risk for later liver transplantation or death. Current Swedish national therapy traditions with immune suppression seem to be well tolerated. Five and ten years overall life expectancy does not differ from controls. Thirty-five women gave birth to 63 children, for 3 after liver transplantation of the mother. Thirteen of the women had liver cirrhosis. Current pharmacological treatment seems to be safe both for the patient and the foetus. Thirty percent of the patients experienced flair after delivery. It has been supposed that there is an overrisk for hepatocellular cancer (HCC) associated with AIH. Our figures are the first in the world to be presented that confirms a twenty-three fold overrisk (95% Confidence Interval 7.5-54.3) for hepatobiliar cancer. We found as well an overrisk of non-Hodgkin lymphomas of 13.09 (95% CI 4.2-30.6).Conclusion:  Our epidemiological results confirm that AIH is a fairly uncommon disease, and that many already at time of diagnosis have an advanced disease with liver cirrhosis. There is a clear overrisk for HCC and lymphoma. For those women with AIH who become pregnant the prognosis for the child as well as for the mother is good, even for those women who already have compensated cirrhosis. There is a risk for relapse after delivery. The overall survival for AIH patients with current therapy is good.

No description available.

Breast cancer is a very heterogeneous disease. This heterogeneity can be observed at many levels, including gene expression, chromosomal aberrations, and disease pathology. A clear understanding of these differences is important since they impact upon treatment efficacy and clinical outcome. Recent studies have demonstrated that the tumour microenvironment also plays a critical role in cancer initiation and progression. Genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer, and have identified gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer-related pathways and processes. However, little work has been done in this context to examine the role of the tumour microenvironment in determining breast cancer outcome, or in defining breast cancer heterogeneity. Additionally, little is known about gene expression in histologically normal tissue adjacent to breast tumour, if this is influenced by the tumour, and how this compares with non-tumour-bearing breast tissue. By applying laser--capture microdissection and gene expression profiling to clinical breast cancer specimens the research presented in this thesis addresses these questions. / We have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty. We determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumour-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumour tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favourable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression data set for comparative studies of tumour expression profiles. / We compared gene expression profiles of tumour stroma from primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumour--derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node--negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumour progression. / We show that gene expression in the breast tumour microenvironment is highly heterogeneous, identifying at least six different classes of tumour stroma with distinct expression patterns and distinct biological processes. Two of these classes recapitulate the processes identified in the stroma-derived prognostic predictor, while the others are new classes of stroma associated with distinct clinical outcomes. One of these is associated with matrix remodelling and is strongly associated with the basal molecular subtype of breast cancer. The remainder are independent of the previously published molecular subtypes of breast cancer. Additionally, based on independent data from over 800 tumors, the combinations of stroma classes and breast cancer subtypes identify new subgroups of breast tumors that show better discrimination between good and poor outcome individuals than the molecular breast cancer subtypes or the stroma classes alone, suggesting a novel classification scheme for breast cancer. This research demonstrates an important role for the tumour microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes suggesting new avenues for individualized treatment.

Indrulėnaitė R. Bendrojo lavinimo mokyklų finansavimas Panevėžio apskrityje: situacijos analizė ir prognostika Magistro darbas. Vadovas Prof. Dr. Vincentas Lamanauskas. Šiaulių Universitetas, Edukologijos fakultetas, Edukologijos katedra. Šiauliai, 2007 m. Temos aktualumas. Nors Lietuvos švietimo įstatyme teigiama, jog valstybinis finansavimas užtikrina normalias bendrojo lavinimo mokyklų veiklos sąlygas, tačiau dažnai kyla nepasitenkinimas, kai kalbama apie šių veiklų finansavimą: vieni tvirtina, kad lėšos naudojamo neskaidriai, švaistomos, o kiti skundžiasi nepakankamu finansavimu. Ši pasirinkta tema aktuali, nes nuo finansavimo priklauso ir ugdymo kokybė. Todėl šiame darbe analizuojama finansavimo situacija bendrojo lavinimo mokyklose Panevėžio apskrityje, apžvelgti švietimo finansavimo teoriniai ir praktiniai aspektai, atskleista finansavimo būklė išryškinant jos tendencijas, atlikta lyginamoji analizė tarp atskirų apskrities savivaldybių, suformuluota prognostika. Problema – nepakankamas bendrojo lavinimo mokyklų finansavimas Panevėžio apskrityje. Tyrimo objektas: bendrojo lavinimo mokyklų finansavimo situacija ir tikėtina kaita Panevėžio apskrityje. Hipotezė – galima manyti, kad bendrojo lavinimo mokyklų finansavimas Panevėžio apskrityje yra nepakankamas. Tyrimo tikslas – išanalizuoti bendrojo lavinimo mokyklų finansavimo būklę Panevėžio apskrityje, atlikti lyginamąją analizę tarp atskirų apskrities savivaldybių ir atskleisti finansavimo būklę išryškinant jos... [toliau žr. visą tekstą] / Reda Indrulėnaitė. Financing of General Secondary school in Panevėžys Region: analyses of the situation and prognosis. The work for the Master’s degree. Supervisor professor Dr. Vincentas Lamanauskas. Department of Educology Faculty of Educology of Šiauliai University, Šiauliai, 2007 The importance of the subject. In the Law of Education of Lithuania it is stated that the state financing creates normal conditions for the activity of general secondary schools, but when the questions of financing are discussed dissatisfaction is expressed: some say that the money is not always used transparently or not for the due purposes and others claim that the state financing is not enough. The chosen topic is very important as the quality of education depends on its financing. The financial situation in the general schools of Panevėžys region is analyzed in this paper, theoretical and practical aspects of financing are discussed, the status of financing and its tendencies are revealed, comparative analyses of different parts of the region is made and prognoses formulated. Problem: insufficient financing of general secondary schools in Panevėžys region. The object of the investigation: financial situation of general secondary schools and expected changes in Panevėžys region. Hipothesis. It can be thought that financing of general schools in Panevėžys district is insufficient. The aim of the investigation. To analyze the status of financing of general secondary schools in Panevėžys... [to full text]

Se estudiaron 136 carcinomas mamarios de perras y sus linfonódulos satélites. Se evaluaron la proliferación celular (mediante la marcación inmunohistoquímica del antígeno nuclear de proliferación celular) y la actividad angiogénica (mediante la inmunomarcación del receptor para el factor de crecimiento de endotelios vasculares 2 -VEGFR-2- y el recuento de microvasos). Se relacionaron ambos procesos y su repercusión en el estado del linfonódulo. Se estableció la asociación entre estas características y el tipo y grado histológicos, y la presencia de émbolos neoplásicos en los vasos tumorales. Para determinar su significación en el pronóstico, estos parámetros se relacionaron con el estado del linfonódulo (merced a la observación de cortes procesados mediante la técnica histopatológica de rutina y a la marcación inmunohistoquìmica de citoqueratinas) y con la supervivencia de un grupo de pacientes. Los tipos histológicos pudieron clasificarse en dos grupos teniendo en cuenta su comportamiento proliferativo, angiogénico e invasivo: uno constituido por carcinomas complejos, simples tubulares y de células escamosas, y el otro por carcinomas simples papilares, sólidos y anaplásicos y carcinosarcomas. A menor diferenciación histológica correspondieron mayores actividades proliferativa, invasiva y angiogénica. Con respecto a esta última, en neoplasias con mayor expresión del VEGFR-2, la densidad de microvasos y la proliferación fueron mayores. La mayor densidad de vasos favorece la invasión vascular. La presencia de émbolos, el grado histológico, el índice de proliferación, la expresión del VEGFR- 2 y la densidad de microvasos permitieron predecir la capacidad metastásica. El tipo histológico no se relacionó con la supervivencia de manera independiente. Los carcinosarcomas y los carcinomas simples anaplásicos presentaron mayor riesgo de metástasis que los carcinomas simples tubulares, complejos y de células escamosas. La probabilidad de supervivencia a 18 meses fue alta y estuvo influenciada por el estado del linfonódulo y la presencia de émbolos neoplásicos. / One hundred and thirty six canine mammary carcinomas and their satellite lymph nodes were studied. Proliferation and angiogenic activities were evaluated by means of immunohistochemical procedures. For the former, proliferating cell nuclear antigen was labelled. Vascular endothelial growth factor receptor-2 (VEGFR-2) expression and microvessel density were measured to estimate angiogenesis. Both processes were related and their influence on the status of the lymph nodes was investigated. An association was established between these characteristics and the histological type and grade, and the presence of neoplastic cells within tumor vessels. In order to determine their prognostic significance, these parameters were related to the lymph node status (defined after histopathological and immunohistochemical studies with anticytokeratin antibodies) and survival of a group of patients. According to their proliferative, angiogenic, and invasive behavior, histological types could be classified into two groups: one comprising complex, simple tubular, and squamous cell carcinomas, and the other comprising simple papillary, solid, and anaplastic carcinomas, and carcinosarcomas. A lower histological differentiation corresponded to higher proliferative, invasive, and angiogenic activities. Tumors with higher expression of VEGFR-2 exhibited more density of microvessels and higher proliferation rates. Vascular density favored vascular invasion. Metastatic potential could be predicted according to the presence of emboli, histological grade, proliferation index, expression of VEGFR-2, and density of microvessels. Independent correlation between histological type and survival was not found. Carcinosarcomas and simple anaplastic carcinomas presented a higher risk of metastasis than simple tubular, complex, or squamous cell carcinomas.Probability of survival at 18 months was high and was influenced by the status of the lymph node and the presence of neoplastic emboli.

Artificial neural networks (ANN) can detect complex non-linear relationships between independent and dependent variables. Properly trained ANNs have repeatedly demonstrated superior predictive accuracy to other predictive technologies when applied to non-linear systems. Currently there are no studies that have been carried out on predicting survival of leukaemia patients at all. The neural network prediction method adopted in this study aims to provide a robust and accurate method for predicting survival of leukaemia patients for both censored and uncensored patient data. The aim of this research was also to find out the effectiveness of neural networks in modelling leukaemia prognosis and to determine the factors that have the most influence. There is ongoing research into finding ways and means of extending the life span of diseased patients. There is great interest in identifying factors that will yield better predictions of survival for terminally ill leukaemia patients. Prognostic factors generally differ with the treatment of leukaemia. Clinicians face the problem of how to choose the appropriate treatment regime, therefore an analysis of prognostic factors that predict success or failure may identify patients who require an alternative approach of specialist or targeted treatment. Being able to predict an individual patient’s prognosis will enable clinicians to categorise them into the relevant high and low risk treatment groups for conventional treatment or allow for the patients to be incorporated into specialised treatment schedules and clinical trials if available. In this study there is believed to be relationship that exists between the results gained on diagnosis and the period of survival. A patient’s health status is dependent on various symptoms and the complexity of the medical condition is dependent on an individual’s biological system. This complexity allows for the application of artificial neural networks (ANN) in predicting outcomes in medical application, especially in prognosis prediction and survival rate. This thesis contains contributions to the development of neural network models for survival analysis of leukaemia patients. The feed forward back propagation algorithm (BPA) modified to the gradient descent BPA was identified for the training and building of the neural network for predicting survival of leukaemia patients. The prognostic factors that affect survival have also been determined by the neural networks. The comparisons of models were based on using combined groups of leukaemia patients and comparing them with individual groups of the sub-types of leukaemia, i.e. acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CLL) and chronic myeloid leukaemia (CML). A combination of 38 variables was used in the development of the neural networks. The variables were age, race, sex, gender, and results of full blood counts, differential tests and flow cytometry. The survival period of patients was based on the diagnosis date and the date of treatment. Those patients who status of mortality was known as of October 2008 were considered to be uncensored and were used for the 2-year and 3-year case studies. The patients with unknown mortality were considered as censored patients and used for the censored case study. The patient data was processed into a coded system and used to build the neural networks for each data set. The choice of patient groups used for the model building was prompted by the availability of uncensored data for analysis. For the group of combined leukaemia patients and the sub-group CML-CLL, it is recommended that the 2-year neural network model be used. The main prognostic factors affecting leukaemia survival were found to be the patient’s age, the mean haemoglobin concentration, % neutrophils and the markers CD13, CD20 and CD56. The race group, platelet count, % monocytes and the markers CD3, CD4, CD34 and LC lambda were found to significantly affect the CML-CLL group of patients. For the ALL and AML groups the 3-year neural network models were favoured. Prognostic factors for the survival of ALL patients were their age, the mean corpuscular haemoglobin concentration, % blasts and the markers CD8 and CD22. For the AML group the important prognostic factors were the patient’s age, the mean corpuscular haemoglobin concentration, the % neutrophils, % lymphocytes, and the markers CD7 and CD34. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.