| 1. |
|
|
| 2. |
- Drott, Jenny, 1976-
(författare)
-
Neurotoxic side effects and impact on daily life in patients with colorectal cancer with adjuvant oxaliplatin-based chemotherapy
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Colorectal cancer (CRC) is one of the most common cancers globally. Chemotherapeutic drugs are frequently used in postoperative treatment. The platinum compound oxaliplatin (OXA) is an option for adjuvant treatment of patients with resected CRC, and has been shown to improve survival. OXA-induced neurotoxic side effects are common (e.g. sensitivity to cold, numbness). Neurotoxicity can interfere with the patient’s daily living and affect ability to carry out activities. Because there is no evidence for effective treatment in terms of eliminating neurotoxic side effects, the most successful approaches include early identification, reduction of dose and interruption of treatment. Current research has identified a need for patient-oriented evidence in terms of long-term follow-up of neurotoxicity.Aim: The overall aim of this thesis was to explore OXA-induced neurotoxic side effects in patients with colorectal cancer, and the influence on patients’ daily lives during and post OXA treatment.Methods: The thesis is based on four studies, and includes an analysis of medical records, as well as prospective quantitative and qualitative approaches with longitudinal data collection through a mobile phone-based system. The studies were performed at oncology departments in four hospitals in Sweden. Inclusion criteria were that patients should be at least 18 years of age, and should have been treated with chemotherapy, including OXA (FOLFOX, XELOX), in an adjuvant setting for CRC stages II-III. Study I had a retrospective design, and data involved (n=61) medical records. A structured protocol was used to evaluate the documentation of patients’ neurotoxic side effects. In studies II and III, ten patients were recruited using a strategy of purposeful and consecutive selection according to the inclusion criteria, where OXA-related neurotoxic side effects were assessed. A total of 10 interviews were carried out when neurotoxic side effects appeared (II), and after completed OXA treatment (3, 6 and 12 month’s follow-up) 25 repeated interviews were conducted (III). The prospective longitudinal study IV aimed to identify and assess patient-reported outcomes in terms of neurotoxic side effects, and their impact on patients’ daily activities (n=46). An Oxaliplatin-associated Neurotoxicity Questionnaire (OANQ) was administered in real time to indicate patientreported outcomes. In total, 370 questionnaire responses were available for analysis.Results: The results from the retrospective study (I) showed that a free description of the degree of neurotoxic side effects was given in the patients’ medical records. No formal assessment had been used in the documentation. The findings of the two qualitative studies contribute knowledge about how patients endure neurotoxic side effects early in the treatment phase, and how they learn to live with neurotoxicity in the long-term perspective. Patients coped with their side effects by developing different self-care strategies to restore normality in their daily lives (II-III). Neurotoxic side effects interferes with the patient’s daily activities in a variety of ways. These side effects change in terms of their character and their location in the body over time. The most frequent side effects during treatment were cold-precipitated tingling in the upper extremities and in the mouth/throat. At the end of treatment, neurotoxicity in the lower extremities was considered high and interfered with the patients’ daily activities. The results show significant differences between baseline data, and nine of the patients had not returned to baseline after one year (IV).Conclusion: Neurotoxic side effects affect patients’ daily activities in different ways, with an impact on their physical, psychological, emotional and social life. Patients endured and coped with their side effects in different ways involving self-care strategies to restore normality. The patients’ daily lives were affected by numbness and tingling in the legs and tingling in upper extremity, and they had learned to live with these side effects. The neurotoxic side effects changed character and localisation over time. These results should be taken into account when patients are informed about treatment, and in the dialogue about the benefits and risks.
|
|
| 3. |
|
|
| 4. |
- Gnosa, Sebastian, 1984-
(författare)
-
Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The incidence and death rate for colorectal cancer (CRC) decreased during the last decades as a result of improved diagnosis and treatment. However, CRC is still the third most common cancer in the world, and is responsible for about 700 000 deaths per year worldwide. Therefore, it is important to understand the mechanisms of the disease, and to find molecular markers in order to further improve prognosis, and to develop new treatment strategies. Astrocyte elevated gene-1 (AEG-1), encoded by the MTDH gene, is upregulated in a variety of cancers. AEG-1 is involved in cell survival, proliferation, migration, invasion, metastasis, angiogenesis, and apoptosis.The aim of this thesis was to investigate the role of AEG-1 in CRC development and the impact of AEG-1 on the response of radiation treatment. The AEG-1 expression, analysed in different CRC patient cohorts in paper I and III, was increased in the tumour tissue compared with the normal mucosa, and higher in the lymph node and liver metastases. Expression analyses in normal and cancer cell lines confirmed these results. In paper II, sequencing of the complete coding sequence of the MTDH gene in 356 patients revealed 50 single nucleotide variants of which 29 were novel. Eight exonic variants were detected, including three frameshift variants which were probably pathogenic, and two missense variants located in functional protein regions. There was no correlation of the MTDH variants or AEG-1 expression with the patient survival. In paper III, we also investigated the impact of AEG-1 on the response to radiation treatment. AEG-1 knockdown decreased the cellular survival upon radiation in several colon cancer cell lines. The AEG-1 expression was furthermore analysed in patients, which were randomised to either surgery alone or preoperative radiotherapy (RT), followed by surgery. The rectal cancer patients with high AEG-1 expression treated with RT had a significantly higher risk of developing distant recurrence and had a worse disease free survival, likely due to the metastasis promoting properties of AEG-1. In paper IV, the impact of AEG-1 knockdown and radiation on migration and invasion was analysed in colon cancer cell lines in vitro and in a novel zebrafish model in vivo. AEG-1 knockdown decreased migration and invasion, and radiation-enhanced migration and invasion in the cell lines tested.In conclusion, our data suggest that AEG-1 is involved in CRC development, while MTDH gene variants probably not have a high clinical importance in CRC. Furthermore, AEG-1 is a promising radiosensitising target and a valuable prognostic marker in CRC. We further showed that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced cell migration and invasion.
|
|
| 5. |
- Lyth, Johan, 1980-
(författare)
-
Clinical-epidemiological studies on cutaneous malignant melanoma : A register approach
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The incidence of cutaneous malignant melanoma (CMM) is steadily increasing. Most of the patients have thin CMM with a good prognosis and a 5-year survival of about 90%. The prognosis is highly related to tumour thickness and clinical stage at diagnosis. Effective systemic treatment for patients with metastatic disease has only recently been available. This thesis aims to increase knowledge of trends in tumour thickness, prognostic factors, socioeconomic differences and medical costs in patients with CMM.The population-based Swedish melanoma register is the main source of data in all papers in the thesis. Papers I-III include patients from all of Sweden while paper IV is delimited to the County of Östergötland. Cox regression and logistic regression are the main multivariable methods used. Paper IV is focused on stage-specific costs of CMM by comparing direct healthcare costs to a general population.For men, there has been a shift over time towards thinner tumours at diagnosis accompanied by an improved survival. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men. Tumour ulceration, tumour thickness and Clark’s level of invasion all showed significant independent long-term prognostic information in T1 CMMs. By combining these factors, three distinct prognostic subgroups were identified. Lower level of education was associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. The direct healthcare costs for CMM patients were significantly higher than for the general population, independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs.Even though the survival among Swedish patients with CMM is among the highest in the world and still seems to improve, the results of this thesis emphasise the need of improved early detection strategies. This may be of particular concern in men, older women, and groups with a low level of education. The results also imply that the costs for the management of CMM patients may be reduced if early detection efforts are successful and lead to a more favourable stage distribution. The finding of a better risk stratification of thin CMMs may help to improve the management of this large patient group.
|
|
| 6. |
- Sandén, Inger, et al.
(författare)
-
Routinization and sensitivity : Interaction in oncological follow-up consultations
- 2001
-
Ingår i: Health. - : SAGE Publications. - 1363-4593 .- 1461-7196. ; 5:2, s. 139-163
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The empirical data of this study were gathered in the form of audio-taped recordings of dialogues between 21 patients, who had had operations for testicular cancer and three physicians during follow-up consultations. The aim is to inquire into how routine practices affect the goals of checking up the medical conditions and providing patients with reassurance, and how practices affect the treatment of sensitive topics and the patients’ possibilities of bringing up their own problems are affected. The results show that the routines built up by the medical care programme are used as recurrent opportunities for the parties to confirm that the situation is under control and as resources when they talk about the sensitive topics of sexuality and fertility. How the routinization affected the patients’ possibilities of bringing up their own problems cannot be fully determined. Of the 50 initiatives by patients to present their problems, only nine did so solely on their own initiative.
|
|
| 7. |
- Starkhammar, Josefin, et al.
(författare)
-
Editorial: 47-channel burst-mode recording hydrophone system enabling measurements of the dynamic echolocation behavior of free-swimming dolphins
- 2009
-
Ingår i: Journal of the Acoustical Society of America. - : A I P Publishing LLC. - 0001-4966 .- 1520-8524. ; 126:3, s. 959-962
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Detailed echolocation behavior studies on free-swimming dolphins require a measurement system that incorporates multiple hydrophones (often andgt; 16). However, the high data flow rate of previous systems has limited their usefulness since only minute long recordings have been manageable. To address this problem, this report describes a 47-channel burst-mode recording hydrophone system that enables highly resolved full beamwidth measurements on multiple free-swimming dolphins during prolonged recording periods. The system facilitates a wide range of biosonar studies since it eliminates the need to restrict the movement of animals in order to study the fine details of their sonar beams.
|
|
