| 1. |
- Larsson, Gunnel, et al.
(författare)
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Importance-satisfaction discrepancies are associated with health-related quality of life in five-year survivors of endocrine gastrointestinal tumours
- 1999
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Ingår i: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 10:11, s. 1321-1327
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about the health-related-quality of life (HRQoL) of patients with endocrine gastrointestinal tumours. In this study, HRQoL was investigated in long-term survivors of endocrine GI tumours. Patients and methods: A questionnaire including the EORTC QLQ-C30 and ratings of importance of and satisfaction with a variety of HRQoL aspects was mailed to patients with carci-noid tumours (n = 64), or endocrine pancreatic tumours (EPT, n = 55). Median time since diagnosis was 120 months (range 60–360). The majority of patients (77 of 119) had ongoing treatment. Results: The EORTC QLQ-C30 ratings suggest that in spite of a long disease duration and treatment, patients perceived their HRQoL as relatively good. There were no major differences in HRQoL ratings between patients with carcinoid tumours and those with EPT. Patients whose ratings of importance was higher than their ratings of satisfaction with a specific HRQoL aspect also evidenced a low HRQoL for that aspect. Conclusions: The results indicate that survivors of endocrine GI tumours enjoy a relatively good HRQoL and suggest that importance < satisfaction discrepancies identify patients with a low quality of life.
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| 2. |
- Carlsson, Maria, 1958-
(författare)
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Informational support for patients with gynaecological cancer and their families
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of the present thesis was to gain a deeper knowledge and understanding of the informational need by women with gynaecological cancer and their families. The studies evaluate the experience of different kind of information giving; a telephone-help line; a 3 years educational group support programme; and information givings in ordinary care.There was a significant correlation to interest in an educational supportive group in the prestudy depending on age, legal status, educational level. Younger individuals, couples and people with a higher formal education were generally more interesting in participating (p<0.05). Patients who actively chose to participate m a an educational support group differed from the unselected control group even prior the intervention, they with a higher formal education were generally more interesting in participating, they felt more confused and angry than the control group. After intervention, the patients in the interventional group reported a significant improved level of knowledge about cancer.Both patients and next-of-kin request information about medical- and psychological aspects of the disease and its treatment. The evaluation of the questions in the educational supportive group show that patients and their relatives asked questions of a general nature, related to basic knowledge of cancer and treatment principles, and not directly related to their own illness. There was no general difference in knowledge level between cancer patients and the controls of healthy women. The length of formal education was the most important determinator of correct answers (p<0.01).Two main themes were revealed at the interviews about the patients informations preferences. These were to actively address questions and the right to receive honest information;It is concluded that differential information giving techniques are required to satisfy the patients' different preferences. The patients express an active role in the information giving process. They preferred information with numerous opportunities to address questions, that the staff have time for questions and that the questions are honestly answered.
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| 3. |
- Larsson, Gunnel, et al.
(författare)
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Health-related quality of life in patients with endocrine tumours of the gastrointestinal tract
- 1999
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 38:4, s. 481-490
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Tidskriftsartikel (refereegranskat)abstract
- Health-related quality of life (HRQOL) (EORTC QLQ-C30) and levels of anxiety and depression (HADS) were investigated in patients with endocrine tumours of the gastrointestinal tract treated with interferon and/or a somatostatin analogue. In addition, patient perceptions of the importance of and satisfaction with some HRQOL aspects were studied. QOL was perceived as quite good, but more than half of the patients reported diarrhoea. The levels of anxiety and depression were low. Patients perceived physical HRQOL aspects as most important for a good QOL and stated the highest satisfaction with some social aspects. Patients who reported high levels of anxiety or depression were less satisfied with several HRQOL aspects, had more health problems, and a lower level of functioning on several of the EORTC QLQ-C30 scales and single items. Neither demographic nor medical background variables seemed to have an influence on the results. The relatively high QOL could be explained by the fact that most patients had had their treatment for a long period and thus had time to adjust to the situation.
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| 4. |
- Isacsson, Ulf
(författare)
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Comparative treatment planning in external radiotherapy of malignant tumours : Potential gains using protons
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is well known that protons have physical characteristics superior to conventional radiation qualities in external beam radiotherapy. The primary aim of this work is to determine if the physical advantages also may lead to clinical advantages. A second aim is to evaluate the treatment planning algorithms incorporated into a 3D treatment planning system, used in the prediction, Helax-TMSTM. The potential benefits of using protons instead of conventional radiation qualities is evaluated by comparing treatment plans. Dose-response models of tumour control probability (TCP) and normal tissue complication probability (NTCP) were used to predict the treatment outcome for the different plans. Uncertainties in the results were studied in sensitivity analyses.Comparative studies were performed in four different tumour types, locally advanced rectal cancer, a paraspinal tumour, oesophageal cancer and left-sided node-positive breast cancer. Advantages with protons were seen in all cases, but the advantages were of different size.Proton therapy in patients with oesophageal carcinoma increases the TCP from 6 to 49% if a risk of 1% in the spinal cord and a total NTCP for the two lungs equivalent to a one-sided pulmectomy is allowed. This gain is relatively insensitive to variations, within reasonable limits, in the dose-response parameters.Proton therapy reduces the risk for cardiac mortality and radiation pneumonitis to almost zero when treating node-positive left-sided breast cancer after breast-conserving surgery.The evaluation of the treatment planning algorithms shows that pencil kernel algorithms are required in order to accurately calculate dose distributions in heterogeneous patient volumes. The scattering phenomenon in the vicinity of interfaces between different materials is modelled. The magnitude of the effect is underestimated (less than 1%) due to the inherent approximations.
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| 5. |
- Benda, Birgitta
(författare)
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Islet xenotransplantation : An immunological study in the pig-to-mouse model
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Successful clinical xenotransplantation, i.e., transplantation between species, would eliminate the shortage of donor organs. In order to study the acute cellular rejection reaction following discordant xenogeneic transplantation, an experimental pig-to- mouse islet xenotransplantation model was established. Further, immunological processes were evaluated using genetically deficient (knock-out) recipient mice and pharmacological agents exerting cytokine-modulatory actions.Xenogeneic islet transplantation persists in mice deficient in antibodies, interleukin-6, perforin or granzyme B, suggesting that neither xenoreactive antibodies or interleukin-6 nor granule-mediated lysis are of critical importance to the rejection process. Instead, the immune response following pig-to-mouse islet xenotransplantation bears a close morphological resemblance to a T helper (Th) 1-dependent delayed-type hypersensitivity-reaction with a massive infiltration of macrophages and comparatively small amounts of peripherally accumulated T cells. It may be speculated that islet xenograft destruction is a macrophage-mediated process regulated by T cells. Indeed, Th1-associated cytokines with macrophage-activating properties (interferon-γ and tumor necrosis factor-α) and interleukin-2 seem to be important to islet xenograft rejection, even though other cytokines eventually substitute for the lack of those in a majority of animals.Key words: xenotransplantation, porcine, islet, in vivo, knock-out mouse,immunohistochemistry, CsA, MDL 201,449A, Ig, FcR, IL-6, perforin, granzyme B,macrophage, eosinophilic granulocyte, T cell, TCR, IFN- g, TNF- a, IL-2.
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| 6. |
- Christiansen, Ilse
(författare)
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Soluble intercellular and vascular cell adhesion molecules-1 in lymphoid neoplasms : A clinical and prognostic study of Hodgkin's disease, non-Hodgkin's lymphomas and chronic B-lymphocytic leukaemia
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interaction of soluble adhesion molecules with adhesion ligands expressed by immunological cells interfere with the cell-cell adhesion essential for the signal transductions that initiate immunological responses. Preliminary data suggest that soluble adhesion molecules also promote angiogenesis. Thus dysregulated production of soluble adhesion molecules may emerge as participants of disturbed immuno- surveillance, lymphocyte trafficking and dissemination of cancer cells. Vascular cell adhesion molecule-l (VCAM-1) and intercellular adhesion molecule-l (ICAM-1) are inducible and/or upregulated by cytokines in different cells types such as endothelial cells, follicular dendritic cells, and stromal cells. Lymphoid neoplasms, representing malignant counterparts of immunological cells, are characterised by heterogeneous histopathologies and clinical manifestations.Serum levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were elevated in Hodgkin's disease (HD) and chronic B-lymphocytic leukaemia (B-CLL), while only sICAM-1 was elevated in non-Hodgkin's lymphomas (NHL). Serum levels of sICAM-1 and sVCAM-1 correlated with tumour burden and other known prognostic markers. sICAM-1 was an independent prognostic variable in HD and B-CLL. sVCAM-1 was an independent prognostic variable in HD. The discriminative power of serum levels of sVCAM-1 in smouldering and non-smouldering B-CLL could prove clinically valuable.Both ICAM-1 and VCAM-1 were overexpressed by vascular endothelium and stroma in biopsies of HD, B-CLL and NHL. No correlation between tissue expression of the adhesion molecules and the serum levels of sICAM-1 and sVCAM-1 appeared. VCAM-1 was expressed by two of seven HD cell lines, and sVCAM-1 was detectable in supernatants from these two cell lines. ICAM-1 was expressed by all I-ID cell lines and detectable in supernatants. In the majority of B-CLL and NHL cultures, ICAM-1 expression was upregulated by tumour cells, resulting in detectable sICAM-1 in supernatants.In conclusion, serum levels of both sICAM-1 and sVCAM-1 had prognostic powers equalling or surpassing known prognostic markers in lymphoid neoplasms. The functional consequences of dysregulated serum levels of sICAM-1 and sVCAM-1 in lymphoid neoplasms is at present largely unknown.
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| 7. |
- Hansson, Tony
(författare)
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Coeliac disease : Clinical and immunological aspects
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A better immunological definition of coeliac disease and highly discriminatory serum markers are needed to identify children with early mucosal lesions and for rapid follow-up and a better knowledge of antigen reactivity and cytokine production will be needed to clarify the pathogenic mechanisms.The numbers of circulating IgAanti-gliadin antibody-producing (IgAAGA SFC) cells were increased in patients with untreated coeliac disease compared to controls and treated coeliac disease patients. In children with coeliac disease the numbers of IgAAGA SFC increased rapidly after gluten challenge. The levels of IgA specific for human as well as guinea-pig tissue transglutaminase (tTG) were increased in the untreated coeliac diseasechildren compared to the control groups. A human erythrocyte tTG ELISAassay had the highest sensitivity (100%) and a specificity of 98%.The numbers of IFN-γ producing cells in the peripheral blood was increased in children with untreated celiac disease as compared to healthy controls. The IL-4 production correlated with the serum levels of total IgE. The numbers of IFN-γ producing cells increased after gluten challenge, whereas no such change was evident for IL-4 or IL-10 producing cells. Children with coeliac disease had more mononuclear cells expressing TGF-β1, TNF-αand IFN-γ in the lamina propria as compared to disease controls. TGFβ3 and IL-4 expressing cells were present in the lamina propria as well as in the epithelial layer in children with coeliac disease.In conclusion, our results indicate that: (1) the ELISPOT assay or other methods for detection of antibody production may be helpful in assessing the optimal timing of the biopsy to shorten the duration of gluten challenge, (2) anti-tTG IgA antibodies can be used as a sensitive and specific complement to existing serological tests for coeliac disease, (3) circulating mononuclear cells in children with active coeliac disease secrete cytokines compatible with a type 1 response, (4) mononuclear cells in the gut of children with activecoeliac disease produce type 1 cytokines as well asTGF-β and IL-4.
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| 8. |
- Jansson, Tomas
(författare)
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Methods for selection and optimisation of radiotherapy and early therapy evaluation in breast cancer
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adjuvant systemic therapy for breast cancer, the most common malignancy in females, increases survival and this has recently also been demonstrated for postoperative radiotherapy. The aims of this study were to develop an optimised radiotherapeutic technique for postoperative treatment, to analyse the association between p53 status in node-negative patients and radiotherapy, to investigate the incidence of in-breast relapses after conservative surgery and radiotherapy and to determine if positron emissiontomography could be useful for early evaluation of polychemotherapy.A technique with mixed photon and electron beams from an accelerator equipped with a multileaf collimator was developed for irradiation of the breast parenchyma and regional lymph nodes after breast-conserving surgery.Lymph node negative patients with p53 mutated cancers treated with radiotherapy to either the ipsilateral breast parenchyma after sector resection, or the parasternal and supraclavicular fossa after modified radical mastectomy due to medial or central tumours had a statistically significant longer relapse-free, breast cancer-corrected, and overall survival (p=0.0007, p=0.001, p=0.02, respectively) compared with non-irradiated patients.In 672 patients with pT1N0M0 cancers treated with radiotherapy (54 Gy) after breast-conserving surgery 2.5% in-breast relapses appeared after a mean follow-up of 6.8 years.Positron emission tomography with 18FDG and 11C-methionine revealed a decrease in tumour metabolism one to two weeks after the first course of polychemotherapy in 11 of 12 clinically responding patients.
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| 9. |
- Nordin, Karin
(författare)
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Psychological responses to gastrointestinal cancer
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of the present thesis is to gain knowledge about psychological distress and adjustment in gastrointestinal cancer patients (colon, rectum, gastric, pancreatic or biliary) at various phases of their disease.Reactions to the diagnosis, anxiety, depression and coping were investigated in newly diagnosed patients (n=139). Repeated assessments were performed throughout the fast year after the diagnosis. Only a limited group reported high levels of anxiety (17%) and depression (21%) close to the diagnosis. Patients with colon or rectal cancer, most of whom were potentially cured, had a more confronting attitude to their diagnosis and reported more 'Fighting Spirit' than patients with gastric and pancreatic/biliary cancer. These responses were associated with better emotional well-being. The former group also reported less `Hopeless/helplessness' and 'Anxious preoccupation', which were related to higher levels of psychological distress. There were no changes over time in mean levels of anxiety and depression and virtually no changes in mean values of the coping subscales. In a separate group (n=141), overall levels of anxiety, depression and worry were low in conjunction to a medical follow-up control visit approximately two years after diagnosis.Levels of anxiety and depression at diagnosis predicted a similar status six months later. A model based on standardised cut-off scores of moderate or high levels of anxiety or depression and intrusive thoughts close to the diagnosis was used to identity patients with prolonged psychological distress.A psychometric analysis was performed of the Mental Adjustment to Cancer (MAC) scale (n=868 patients with various cancers). The reliability of the original subscales was satisfying. A confirmatory factor analysis revealed a factor structure including 28 of the original 40 items in four factors. Both versions of the MAC confound coping efforts and emotional outcomes, preventing analyses of coping-outcome relations.The main conclusion is that a majority of gastrointestinal cancer patients cope well with their disease in the short as well as in the long run.
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| 10. |
- Weigelt, Cecilia
(författare)
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Tumor-targeted superantigens for experimental immunotherapy of human leukemia/lymphoma
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial superantigens (SAgs) have the property of stimulating high proportions of T cells expressing certain TCR Vβ sequences. The SAg first binds with high affinity to HLA class II molecules on the target cell and then stimulates the T cell to produce cytokines and to become cytotoxic. HLA class II+ target cells may be lysed by cytotoxic T cell cytokines such as TNFα and IFNγ but also by direct cell contact. Staphylococcus enterotoxin A (SEA) is a bacterial SAg produced by certain Staphylococcus areus strains. The HLA class II binding affinity of SEA was reduced by a point mutation (D227A, generating SEAm) not affecting T cell activating properties. This SEAm was first fused to protein A (PA) and later to the Fab-part of an anti-CD19 mAb. Using either fusion protein, cytotoxic T cells (CTLs) were successfully redirected from HLA class II molecules to a defined target structure.Cells from patients with chronic B-lymphocytic leukemia (B-CLL) were highly sensitive for SAg-dependent cell-mediated cytotoxicity (SDCC) using allogeneic SEA-reactive T cells in vitro. T cells targeted by the PA-SEAm fusion protein (FP) and B-cell reactive mAbs also killed the malignant cells. Activation of target cells with a phorbol ester, increased surface ICAM-1, LFA-1, LFA-3 and HLA-DR expression and enhanced their sensitivity for SDCC. The PA-SEAm FP was also used together with myeloid cell reactive mAbs and CTLs to kill 10 different acute or chronic myeloid leukemic (AML or CML) cell line cells in vitro.High concentrations of TNFα and IFNγ in vitro were not directly toxic to target cells exposed for 4h, arguing for other killing mechanisms. One likely mechanism was lytic killing by perforin and granzymes, since inhibition of granulae abolished the cytotoxic effect. MAbs against the Fas antigen did not interfere with killing.The anti-CD19-Fab-SEAm FP used together with CTLs efficiently killed CD19+ normal and malignant B cells. Malignant cells included both tumor B cell lines and tumor cells from patients with B non-Hodgkin's lymphoma (B-NHL). The sensitivity of target cells varied and was correlated to surface ICAM-1 expression. In vivo therapeutic effects were monitored in a humanized severe combined immunodeficiency disease (SCID) model. A significant reduction of tumor weight was registered in treated animals.In conclusion, antibody-superantigen FPs are attractive agents for treating human hematopoietic tumors resistant to conventional therapy. There are abundant numbers of potential effector T cells in lymphoma tissue and the bioaccessibility is good. The SAg activates about 1/5 of all T cells, leaving the majority unaffected. In this thesis, different immunotherapeutic concepts are discussed and compared with targeted SAg-therapy.
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