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- Davidsson, Sabina, 1972-
(författare)
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Infection induced chronic inflammation and it's association with prostate cancer initiation and progression
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An association between cancer development and inflammation has long been suggested. Approximately 20% of all human cancers in adults are assumed to result from chronic inflammation. The aim of this thesis was to investigate if infection-induced chronic inflammation plays a role in prostate carcinogenesis.Our results revealed a greater infiltration of the bacterium Propionibacterium acnes in the prostate tissue obtained from men with prostate cancer compared to men without any histological evidence of the disease. These findings indicate that prostate cancer could potentially be included in the list of cancers with an infectious etiology.Further, we investigated whether chronic inflammation has a role in disease progression. Our results demonstrated that men with lethal prostate cancer had pronounced infiltration of immune cells with suppressive function of the anti-tumor immune response compared to men with a more indolent prostate cancer.Confirmation of our results may open up avenues for targeted prostate cancer treatment by offering men with chronic inflammation alternative therapies such as anti-inflammatory drugs. If the involvement of P. acnes in prostate cancer development is replicated in other studies, vaccination therapies may be feasible. To further individualize prostate cancer therapy, bolstering the anti-tumor immune response in order to reduce tumor progression may be determined to be advantageous for some patients.
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| 2. |
- Jerlström, Tomas, 1969-
(författare)
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Clinical aspects of cystectomy and urinary diversion
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore different aspects of treatment of advanced urinary bladder cancer with radical cystectomy, pelvic lymph node dissection, and urinary diversion. Surgery that carry a high risk of complications as well as mortality. Aside from complications and risk of recurrance, patients have to cope with lifelong postoperative changes of body function, including sexual function, and body image, all affecting quality of life (QoL). The thesis comprises four papers. In the first paper, we compared functional outcome and QoL following two types of ileal orthotopic neobladder substitution. The results suggest that the S-shaped substitute entails better functional results than the U-shaped substitute, with better continence, especially at night. There was no difference in QoL. The second paper reports results from the first year of registration in the nation-wide Swedish Cystectomy Register. Analysis of risk factors for complications showed that high age and prolonged operation are associated with increased risk of short-term complications. The third paper investigated whether preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC) affects the risk of shortterm complications after radical cystectomy, using data from the Cystectomy Register covering 1340 patients of whom 39 percent received preoperativevchemotherapy. We found no such increase in risk. In the fourth paper, we analysed the results of a validation study of the Cystectomy Register. The validation showed 17 percent more low grade complications, three percent more high grade complications, and five percent more readmissions, within 90 days of surgery. Hence, a third-party validation may improve the validity of the register
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| 3. |
- Klaff, Rami, 1971-
(författare)
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Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionProstate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.AimsTo explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)Material and methodsThe study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.Result and conclusionsThe long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
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| 4. |
- Andrén, Ove, 1963-
(författare)
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Natural history and prognostic factors in localized prostate cancer
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects. The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden. Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer. The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment. Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.
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| 6. |
- Ugge, Henrik, 1987-
(författare)
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Inflammation and prostate carcinogenesis : influence of immune characteristics and early-adulthood exposure to inflammatory conditions on prostate cancer risk
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic inflammation has been implicated in the development of several types of cancer, and evidence from observational and animal studies suggests that it may play a role also in prostate carcinogenesis. Recent observations have brought Cutibacterium acnes (C. acnes) forward as a possible causative agent in pro-oncogenic prostatic inflammation. However, evidence also suggest that underlying immune characteristics contribute to prostate cancer risk. The overall aim of this thesis was to explore potential mechanisms underlying the proposed link between inflammation and prostate cancer, by evaluating associations between inflammatory conditions during early adulthood, circulating inflammation markers, and prostate cancer. Due to the suggested role of C. acnes in both diseases, we aimed to investigate whether acne vulgaris is a determinant of prostate cancer. Using prospectively collected data from Swedish national registers, we observed that presence of acne during early adulthood conferred an increased risk of prostate cancer later in life. Similarly, we found that appendicitis before late adolescence – a proposed marker of individual immune characteristics – to be positively associated with subsequent prostate cancer. We further evaluated whether prostatic C. acnes infection is linked with elevated systemic levels of IL6 and CXCL8, two inflammation markers previously associated with prostate cancer. No association was observed, however, potentially explained by the subclinical low-grade infection typically caused by C. acnes. Finally, we evaluated 52 circulating inflammation markers as determinants for prostate cancer in a population-based case-control study. In this hypothesis-generating study, we identified CX3CL1, CCL21, PDGF-BB, CCL11 and IL10 as candidate markers for evaluation in prospective studies. If confirmed, these markers may hint at targetable molecular pathways involved in prostate carcinogenesis.
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