The most important prognostic factor in breast cancer is the presence or absence of metastases in axillary lymph nodes. Frozen section and touch imprint cytology are conventional intra-operative methods used in the detection of metastatic breast cancer with varying sensitivities and specificities. The limitation of these methods led to the development of alternative molecular diagnostic tests, such as GeneSearch, a commercial real-time quantitative Polymerase Chain Reaction (RT-qPCR) assay that allows for an intra-operative diagnosis of metastatic breast cancer. When the GeneSearch assay was discontinued, Metasin was developed as an in-house RT-qPCR replacement assay. Metasin targets the epithelial cell marker cytokeratin 19 (CK19) and the breast marker mammaglobin (MGB) mRNA to confirm the presence or absence of metastatic disease, whilst the reference gene porphobilinogen deaminase (PBGD) acts as a positive control for the performance of the assay. The optimised assay can produce a result within 32 minutes allowing it to be used in the intra-operative setting to detect metastatic breast cancer in sentinel lymph nodes. 154 archived lymph node homogenates that were previously analysed by both GeneSearch and histology in parallel were used to validate Metasin. Out of 154 cases, 148 showed concordance with both GeneSearch and Metasin with 111 cases being negative and 37 cases being positive. There were six discordant cases, four in which only Metasin detected metastases and two in which only GeneSearch picked up metastases. Out of the four Metasin-only positive cases, three were found to be positive on histology after deeper levels were cut in the slices sent for histological assessment. Therefore, one case could not be shown histologically to be positive for metastases. There were two cases that were missed by Metasin but picked up by GeneSearch. One case was positive on histology and the second case negative for histology. The error rate for Metasin was 3.89%. The sensitivity and specificity of the Metasin assay were found to be 95% and 98% respectively, and the positive and negative predictive values were 90% and 98% respectively. These results are comparable to those of GeneSearch. Metasin had an assay time of less than 45 minutes and was operated by biomedical scientists. The results of the validation process were deemed acceptable for the assay to be run live and used in the clinical setting. Metasin continues to provide breast cancer patients at Princess Alexandra Hospital with all the advantages that a molecular intra-operative diagnostic service provides.

Aim: The overall aim of this thesis was to study prognostic factors for prolonged disability in back pain in the general population and physiotherapists’ screening for prolonged disability, applying a social cognitive learning perspective. Methods and results: Studies I and II were based on a survey in the general population in Sweden. Study I included 1024 individuals aged 20-50 years, reporting non-specific back pain. Four groups (n = 100, 215, 172 and 537) based on duration and recurrence of back pain were formed and compared. After controlling for pain intensity, catastrophising and expectations of future pain were positively correlated to pain duration. Perceived social support was negatively correlated to pain duration. Study II was longitudinal over 12 months and analysed one group reporting first-episode back pain (n = 77), and one group reporting long-term back pain (n = 302). Future pain intensity and disability were predicted by initial levels of pain and disability and pain-related cognitions in both groups. Study III examined the inter-rater reliability of a research protocol for assessment of physiotherapists’ telephone screening for prolonged disability. The results demonstrated sufficient inter-rater reliability. Study IV evaluated the effect of a tailored skills training intervention on physiotherapists’ screening for prolonged disability in back pain. Four physiotherapists in primary care participated in four quasi-experimental single-subject studies. Effects were seen in all participants, with increased screening of prognostic factors and less time spent on detailed discussions about back pain. Conclusions: The identification of mainly cognitive explanatory variables indicates the relevance of a social cognitive perspective of back pain-related disability (studies I and II). Physiotherapists’ telephone screening for prolonged disability in back can be reliably assessed (study III). It is suggested that interventions based on social cognitive theory are effective in producing change in specified clinical behaviours in physiotherapists (study IV).

Dupuytren's contracture (DC) is a fibromatous disease of the palmar fascia of unknown etiology. The present study was undertaken in order to assess pathophysiological mechanisms and consequences. In a cohort study of 2,375 patients operated for DC at the Department of Hand Surgery, Uppsala there was a male: female ratio of 5.9:1. Women had a higher mean age at first operation than men. One-third of the men and one-quarter of the women required repeated surgery. Early age at first operation was associated with recurrent disease. The risk of cancer was determined in 15,212 patients operated on for DC in Sweden. The overall relative risk was increased by 24%. There was a significantly increased risk for buccal, oesophageal, gastric, lung and pancreatic cancers, which indicates that smoking and alcohol abuse are probable risk factors for DC. Furthermore, there was an increased frequency of fibrosarcoma and malignant fibrous histiocytoma, the cause of which is unexplained The causes of death were evaluated in a national cohort of 16,517 patients operated for DC. There was an overall increased mortality (SMR=1.06), inversely related to age and significant for both sexes, in patients under 70 years. The risk estimate was highest for endocrine-, gastrointestinal-, and respiratory diseases, and accidents. There was also an increased SMR for cardiovascular diseases in younger patients more than 10 years after surgery. The most probable mechanism is related to smoking and other lifestyle factors. Outcome after surgery was not related to the immunohistochemical expression of connective tissue activation markers, such as collagen type IV, integrin α5, laminin, smooth muscle α-actin, procollagen type I, and desmin, in surgical specimens in a prospectively investigated group of patients. Furthermore, there were no associations between gender, age at onset of DC, number of operations, heredity, diabetes mellitus, or medication for cardiovascular disease, and the expression of the different markers. The individual characteristics that place a person at high risk are, thus, not obviously related to ongoing connective tissue production at time of surgery or to connective tissue activity in its conventionally used sense.

Chronic Myeloid Leukemia is a kind of blood cancer with around 1 incidence per 100 000 persons/year. After the development of an effective treatment, imatinib, in the late 1990:s, the survival percentage has increased drastically. The high survival has turned the attention to different kinds of treatment responses, which in turn are good prognostic factors to future health status. In this thesis, the focus is on whether or not the patient has achieved a so called major molecular response after 12 month, or not. More precisely, the aim is to find prognostic factors to the 12 month response. In order to find prognostic factors for this binary response variable, a multivariate logistic regression analysis is conducted, with the goal of finding a parsimonious logistic model that describes the data. The analysis is done from a merged dataset from three earlier studies. The prognostic factors in the final model are treatment, 3 month response, and enlarged spleen. However, the residual analysis indicates that the model is incomplete, implying that further research needs to be done.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous peritoneal metastasis (PM). Different loco-regional treatment strategies, i.e. debulking surgery and cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), have changed the prognosis for these patients. CRS is an aggressive surgical procedure with a long learning curve. PMP exists in different types; how many depends on which classification is used. The aims of this thesis were to investigate the time-frame of PMP development from an isolated appendiceal neoplasm, examine the learning process for CRS, evaluate the differences in treatment outcome between debulking surgery and CRS in combination with HIPEC, to evaluate a more detailed PMP classification and to investigate particularly interesting new cysteine-histidine (PINCH) protein as a prognostic factor for PMP. Retrospectively 26 PMP patients were identified as having had an appendectomy with a neoplasm in the appendix but with no evidence of PM at the appendectomy. They were treated for PMP within a median of 13.1 months (3.8-95.3) after the appendectomy. No difference was seen between the types of PMP regarding the time to a clinically significant development of PMP and how much tumour was found at treatment. CRS is a highly invasive treatment and stabilization in the learning curve was seen after 220±10 procedures. Patients treated with CRS+HIPEC had a better 5-year overall survival (OS) than patients treated with debulking surgery, 74% vs. 40%. CRS increased the rate of complete cytoreduction from 25% in patients treated with debulking surgery to 72%. The new four-grade PMP classification showed very good inter-rater agreement between two independent pathologists and a difference in survival rates was observed between the different grades. A positive PINCH staining was recorded in 83% of the tumours and that was associated with poorer survival.

Es wurden 177 Patientinnen mit zwischen 1999 und 2005 an der Universitätsfrauenklinik Leipzig operativ therapiertem Mammakarzinom und vorangegangener Stanzbiopsie, für die vollständige Befunde vorlagen und bei denen keine neoadjuvante Chemotherapie stattfand, hinsichtlich der prognostischen und prädiktiven Faktoren und deren Vergleich zwischen Stanzbiopsie und dem endgültigen Tumorexzidat untersucht. Unsere Daten zeigten, dass die Stanzbiopsie in der Einschätzung des Differenzierungsgrades mit einer Konkordanz von 62,9% und der Lymphgefäßinvasion mit einer Konkordanz in 69,8% keine hohe Genauigkeit besitzt. Bezüglich des histologischen Typs mit einer Übereinstimmung von 77%, der Östrogen- und Progesteronrezeptorbestimmung mit Konkordanzen von 87% und 83% sowie hinsichtlich des Her-2/neu-Status mit einer Konkordanz von 79% fand sich eine moderate bis gute Übereinstimmung mit dem Exzidat, wobei zu diskutieren ist, ob bei initial an der Stanzbiopsie negativem Östrogen- und/oder Progesteronrezeptorstatus oder auch bei positivem Progesteronrezeptor- und negativem Östrogenrezeptornachweis eine erneute immunhistochemische Hormonrezeptoruntersuchung am Exzidat erfolgen sollte sowie ob bei einer Konkordanzrate des Her-2/neu von weniger 95% immer eine zweite Bestimmung am Operationspräparat als Basis einer definitiven Therapieplanung durchgeführt werden muß. In 8,5% wurde an der Biopsie keine Malignität festgestellt. Der Vergleich des Malignitätsgrades mit der Tumorkategorie als auch mit dem Lymphknotenstatus zeigte keine signifikante Korrelation. Eine fortgeschrittene Tumorkategorie war mit dem Vorhandensein von Lymphknotenmetastasen korreliert.

Prediction of outcome in colorectal cancer (CRC) is currently based on the TNM staging classification; however, histopathological classification alone is insufficient for accurately predicting survival in stage II and III patients. Studies indicate that microarray gene expression profiles can predict survival in CRC. We hypothesize that tumor gene expression in combination with clinical parameters, is a better predictor of outcome in stage II and III colorectal cancers than the TNM stage classification alone. Clinical records and follow-up data were retrospectively reviewed for 58 Stage II and Stage III patients with primary colorectal cancer, who did not receive any neoadjuvant therapy preoperatively and whose samples had been previously analyzed for gene expression profiles using the Affymetrix U 133a Gene chip. For molecular classification of patients as being at high or low risk for poor survival, samples were divided into two clusters by hierarchical cluster analysis of genes selected by SAM. Univariate and multivariate analyses using Cox proportional hazard models were done to identify significant prognostic factors. The 3-year and 5-year survival estimates were 72.41% (SE=5.8%) and 55.17% (SE=6.7%), respectively, for all 58 patients. Univariate analysis showed that advanced stage, older age, high-risk molecular classification, positive lymph nodes were the statistically significant prognostic factors of poor survival (p<0.05), while gender, preoperative CEA level, and family history of CRC in first degree relatives were not statistically significant. In multivariate analysis molecular classification, age and body mass index were independent significant prognostic factors. In Cox proportional hazard model, the estimated hazard ratios for Stage III vs II was 2.45 (95%CI: 0.85-7.04), for high vs low molecular risk was 3.83 (95%CI: 1.22-12.06) and old vs young age was 3.72 (95%CI: 1.2-11.49). Model containing clinical stage in conjunction with molecular risk, body mass index, and age was a stronger indicator of clinical outcome (p= 0.0056) than model with clinical stage alone. Gene expression profiles predict survival independent of clinical parameters, and the addition of gene expression profiles to stage is more predictive of survival than stage alone. Further analysis needs to be done to validate the molecular classification on an independent dataset.

Galvos smegenų insultas dėl aukštų mirtingumo ir ilgalaikio neįgalumo rodiklių išlieka viena didžiausių visuomenės sveikatos problemų daugelyje pasaulio šalių, tarp jų ir Lietuvoje. Didelei daliai sergančiųjų galvos smegenų insultu išlieka judėjimo, apsitarnavimo, pažinimo funkcijų sutrikimų, kurie blogina jų gyvenimo pilnatvę. Ligonių, ištiktų galvos smegenų insulto, funkcinės būklės atsigavimas yra skirtingas, todėl labai svarbu nustatyti veiksnius, kurie gali turėti įtakos reabilitacijos efektyvumui. Darbo tikslas: įvertinti veiksnius, turinčius įtakos ligonių, patyrusių galvos smegenų insultą, reabilitacijos efektyvumui antrajame reabilitacijos etape ir nustatyti jų prognozinę vertę. Darbo uždaviniai: 1. Įvertinti galvos smegenų insultą patyrusių asmenų klinikinę ir bendrą funkcinę būklę bei susijusių su motorika ir pažinimo funkcijomis gebėjimų sutrikimus ir jų kitimą antrajame reabilitacijos etape. 2. Įvertinti kompleksinės reabilitacijos efektyvumą antrajame reabilitacijos etape priklausomai nuo ligonių amžiaus, lyties, insulto pobūdžio, galvos smegenų pažeidimo lokalizacijos ir insulto sunkumo. 3. Nustatyti veiksnius, turinčius įtakos reabilitacijos efektyvumui ir jų prognozinę vertę. Mūsų atliktas tyrimas parodė, kad vyresnis amžius, kairiojo galvos smegenų pusrutulio pažeidimas ir sunkesnė neurologinė būklė antrojo reabilitacijos etapo pradžioje turi reikšmingos įtakos funkcinės būklės sunkumui antrojo reabilitacijos etapo pabaigoje. Įrodyta, kad sunkūs motorikos... [toliau žr. visą tekstą] / Stroke is one of the most relevant public health issues due to high mortality and long-lasting disability rates around the world and in Lithuania. As a consequence, stroke patients stay with such functional disorders as motoric, self-care, and cognitive dysfunctions, that impair their life satisfaction. Complex rehabilitation improves functional status in stroke patients. However, the recovery of functional status in stroke patients is different even if stroke diagnosis is the same. Aim of the study: to establish factors, influencing the effectiveness of second stage rehabilitation, and to evaluate their predictive value in stroke patients. Goals of the study: 1. to evaluate clinical and functional status, motoric and cognitive dysfunctions and its dynamics during second stage rehabilitation in stroke patients; 2. to establish the effectiveness of complex second stage rehabilitation depending on patients' age, gender, type of stroke, damage localization, and severity of stroke; 3. to establish the factors, influencing the effectiveness of rehabilitation and to evaluate their predictive value in stroke patients. Our study demonstrated, that older age, damage in left brain hemisphere, and severity of neurologic condition as measured at baseline all are related with subsequent functional status at the end of second stage rehabilitation. The study investigated, that low rehabilitation effectiveness during second stage rehabilitation on general functional status is predicted... [to full text]

1. INTRODUCTION Ovarian cancer is now the most common gynaecological cancer and the fourth the most common cancer among women in Lithuania. Referring to the epidemiological research ovarian cancer has the tendency to become more common: in 1990 there were 345 new cases of ovarian cancer and in 2004 - already 406 new cases. In 2004 ovarian cancer morbidity was 22.2/100 000 of inhabitants in Lithuania. Ovarian cancer is in the fifth position in the structure of death to cancer.Since there are no specific early symptoms and effective diagnostics of ovarian cancer so even 70 percent of diagnosed cases were stages III or IV. After the cytoreduction surgery and adjuvant chemotherapy with cysplatin / cyclophosphamide (CP) the survival among stage III cases was 10-20 percent and among stage IV cases not even 10 percent. In the structure of death to cancer ovarian cancer is in the sixth position - 16.1/100 000 of women. Since there is no effective prevention so the only way to prolong survival of patients is to optimise the treatment. It has been set that the optimal cytoreduction surgery could be performed only for about 50 percent of patients with stages III or IV ovarian cancer. As an alternative to conventional surgery for this group of patients the neoadjuvant chemotherapy - medical cytoreduction was applied. It could lead to the optimal conditions for cytoreduction surgery and further to prolongation of the survival. Referring to the literature the influence of neoadjuvant... [to full text]

In 1981, no representative study of the medical and social conditions among elderly persons in northern Scandinavia was performed. Nor was there such a study in a smaller Swedish town than Gothenburg. This study was initiated to fill that knowledge gap. The aim of the study was to evaluate gender and age differences in medical and social conditions among elderly people, including the reference intervals of clinical chemistry parameters and characteristic features of the 24-hour electrocardiogram (ECG) in healthy elderly. By way of longitudinal design with birth cohorts stratified by gender, it was assumed that the effects could be demonstrated. Also, the death risk of various social and medical variables was to be assessed. During the study period 1981 to 1990, the subjects were between 70 and 88 years of age. The proportion of persons living in private housing decreased from almost all at the age of 70 to slightly more than half at 88 years of age. The number of socially active persons decreased considerably during the period. The need of help increased from almost none to 60 % of the persons. The proportions of persons with normal sight and hearing decreased from two thirds to around one tenth The most frequent symptoms were general tiredness, pains, dyspnoea, constipation and dryness of the mouth. Cardiovascular diseases were the most frequent. Hypertensive disease became less, and congestive heart failure more frequent with age. The frequency of dementia increased steeply among the oldest persons; at 88 years of age, 40 % were demented. Drug consumption increased; the oldest persons in both age cohorts used 5 different drugs or more per person regularly. The consumption increase was mainly due to the increasing morbidity accompanying age. The most common drugs taken were cardiovascular preparations, psychoactive agents, drugs to alleviate gastrointestinal symptoms, and analgesics. Drug intake and symptom prevalence were generally higher in women, despite the fact that there was no gender difference in the number of diseases. The reference intervals of many blood components in healthy elderly were shown to be broader than those of younger persons. The intervals of P(lasma)-folate and P- potassium were on a lower and those of the erythrocyte sedimentation rate, P-creati- nine and, in women, S(erum)-cholesterol, were on a higher level than among younger persons. Several features of the 24-hour ECG, e.g. the number of episodes of supraventricular tachycardia as well as supraventricular and ventricular premature beats in healthy elderly were more frequent than among younger persons. Between 80 and 88 years of age, many functions crucial to the chances of living a rich and vital life were found deteriorating in the elderly persons. High age, male sex, dementia, congestive heart failure, and low values of S-creatinine were shown to be independent factors connected with an increased death risk. / <p>S. 1-112: sammanfattning, s. 115-177: 5 uppsatser</p> / digitalisering@umu.se