| 1. |
- Crnalic, Sead, 1960-
(författare)
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Metastatic spinal cord compression in prostate cancer : clinical and morphological studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Bone metastases occur in most patients with advanced hormone-refractory prostate cancer causing pain, pathologic fractures, and spinal cord compression. Few studies specifically address surgical treatment of metastatic spinal cord compression (MSCC) in prostate cancer. Criteria for identifying patients who may benefit from surgery are poorly defined. Most of the current knowledge regarding tumor biology in prostate cancer is based on studies of primary tumors or soft tissue metastases. The mechanisms regulating growth of bone metastases are not fully established. Aims: a) to evaluate outcome after surgery for MSCC in prostate cancer and to identify prognostic factors for survival and functional recovery; b) to evaluate current practice for referral of prostate cancer patients with MSCC; c) to analyze expression of androgen receptor (AR), cell proliferation, apoptosis, and prostate-specific antigen (PSA) in bone metastases with regard to survival after surgery for complications of bone metastases. Patients and Methods: We retrospectively evaluated the hospital records of 68 consecutive patients operated for metastatic spinal cord compression. Tumor tissue from bone metastases was obtained on spinal surgery (54 patients), fracture surgery (4 patients) and biopsy (2 patients), and analyzed by immunohistochemistry. Results: Study I: Mortality and complication rate after surgery was high. Patients with hormone-naïve disease and those with hormone-refractory disease with good performance status and without visceral metastases had more favorable survival. The ability to walk after surgery was related to better survival. Study II: A new score for prognosis of survival after surgery for spinal cord compression includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The score is simple, tumor specific, and easy to apply in clinical practice. Study III: Our results suggest that delays in diagnosis and treatment may have negative impact on functional outcome. Pretreatment ability to walk, hormone status of prostate cancer, and time from loss of ambulation influenced neurological recovery after surgery for spinal cord compression. Study IV: High nuclear AR immunostaining in bone metastases and high preoperative serum PSA were associated with a poor outcome after metastasis surgery in patients with hormone-refractory prostate cancer. Short-term effect of castration therapy disclosed that nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected. Conclusion: Prostate cancer patients with metastatic spinal cord compression represent a heterogeneous group. We identified prognostic factors for survival and functional outcome, which may help clinicians in making decisions about treatment. Our results also implicate the need for development of local and regional guidelines for treatment of patients with spinal cord compression, as well as the importance of information to patients at risk.
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| 2. |
- Hedström, Erik, 1977-
(författare)
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Fractures in children : a population-based study from northern Sweden
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fractures and other injuries are notoriously common in childhood and adolescence and a major cause of morbidity. They place a heavy burden on individuals, families, health systems and society. In a population-based study using data from the Injury Database at Umeå University Hospital we analysed injuries, and especially fractures, in Umeå and it´s five surrounding municipalities to increase knowledge on the epidemiology of injuries in children. We found an injury rate requiring visits to the hospital’s emergency department of 110/1000 person-years among those 0-19 years of age. For the same age group, the incidence of injuries resulting in admittance to hospital was 132/104 person-years. The incidence of fractures was 201/104 person-years. The accumulated risk of sustaining a fracture before 17 years of age was 34%, and the peak sex-specific incidence of fractures coincided with the pubertal growth spurt in both sexes. Fractures were more common from May-September when temperatures were warmer and days longer. The most common activity at injury in toddlers and preschool children was play, whereas teenagers were more often injured in sports and traffic-related activities. In an analysis of fracture incidence between municipalities we noted that children and adolescents growing up in rural communities appeared to sustain fewer fractures than their peers in an urban municipality, risk ratio 0.81 (95 % confidence interval 0.76-0.86). We speculated that this observation might be due to differences in behaviour and activities among teenagers in rural and urban communities. In a further analysis we combined data from the Injury Database with socioeconomic microdata. By linking data between individual children and their parents/families we could analyse the relevance of socioeconomic variables and the number of siblings on fracture rate. We observed that children in households with higher incomes sustained significantly more fractures. Comparing the highest and lowest quintiles for income, the rate ratio was 1.40 (1.28-1.54). We also found that having siblings correlated with an increased risk of fractures, rate ratio 1.28 (1.19-1.38). Parents’ education level and family type did not influence the prevalence of fractures significantly. It appeared that the association between variables at the individual level and fractures was stronger than the association between municipality and fractures. Conclusions: Our results show that the incidence of fractures varies with sex, age, developmental stages, skeletal growth, activities of daily life, and seasons. However, it is also influenced by place of residence, family’s socioeconomic status and having siblings. Refined methods and data allowing an analysis of subsets of fractures and other injuries on the individual/family- and area-level simultaneously should lead to further insights into the possible causal mechanisms underlying observed correlations.
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| 3. |
- Mahmood, Sarwar, 1975-
(författare)
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Leg length discrepancy and femoral offset after total hip arthroplasty : clinical and radiological studies
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year, about 1 million patients worldwide and 16000 patients in Sweden undergo total hip arthroplasty (THA). This surgical intervention is considered a successful, safe and cost-effective procedure to regain pain-free mobility and restore hip joint function in patients suffering from severe hip joint disease or trauma. Besides relieving the pain, restoration of biomechanical forces around the hip with appropriate femoral offset (FO), leg length and proper component position and orientation are important goals. The radiographic preoperative planning and postoperative evaluation of these parameters require good validity, interobserver reliability and intraobserver reproducibility. It remains controversial as to how much postoperative leg length discrepancy (LLD) and FO change are acceptable. Generally, lengthening of the operated leg ≥ 10mm and FO reduction of the operated hip > 5mm should be avoided by using preoperative radiological templating and intraoperative measurement methods. There is no consensus on the association between LLD and FO and outcome after THA.The aims of this thesis were to:1. To determine the influence of non-corrected LLD after THA on patients’ reported hip function and quality of life (QoL).2. To study the association of global FO changes after THA with patients’ reported hip function, QoL and abductor muscle strength.3. To evaluate the concurrent validity of the Sundsvall method of measuring postoperative global FO by comparing it to a standard method and to evaluate the interobserver reliability and intraobserver reproducibility of measurement of postoperative global FO, LLD and acetabular cup inclination and anteversion.4. To analyse the postoperative radiographs of THA patients with leg lengthening and FO reduction to determine whether the problem is located in the stem, cup or both.Study I: A prospective cohort study of 174 patients with unilateral osteoarthritis (OA), comparing patients with lengthening ≥ 10mm, restoration (between 9 mm lengthening and 5 mm shortening) or shortening > 5 mm of the operated leg after THA. Follow up was 12–15 months. We found that a LLD of up to 20 mm did not influence the functional outcome (WOMAC) or QoL (EQ-5D). However, the lengthening group showed less improvement in WOMAC and more use of a shoe lift.Study II: A prospective cohort study of 222 patients with unilateral hip OA, comparing patients with decreased global FO (> 5 mm reduction), restored FO (within 5 mm restoration), and increased FO (> 5 mm increment) after THA. Follow up was was 12–15 months. The unadjusted results showed that the decreased FO group had a worse WOMAC index, less abductor muscle strength, and more use of walking aids. When these results were adjusted for possible confounding factors, only global FO reduction was statistically significantly associated with reduced abductor muscle strength. The incidence of residual hip pain and analgesics use was similar in the 3 groups.Study III: A prospective cohort study of 90 patients with primary unilateral OA treated with THA. Global FO using the Sundsvall method, global FO (standard method), LLD, acetabular cup inclination and anteversion were measured on postoperative radiographs. The interobserver reliability and intraobserver reproducibility were tested using three independent observers. We found that the Sundsvall method is as reliable as the standard method and the evaluated radiographic measurement methods have the required validity and reliability to be used in clinical practice.Study IV: A prospective cohort study of 174 patients with unilateral primary OA treated with THA. LLD and global FO were measured on postoperative radiographs. Patients with lengthening of the operated leg ≥ 10mm (n=41) and patients with reduction of global FO > 5mm (n=58) were further studied to investigate the amount of lengthening and global FO reduction that took place in the stem and in the cup compared with the contralateral side. The interobserver reliability and intraobserver reproducibility were tested using two independent observers. We found that post-THA lengthening of the operated leg ≥ 10mm was mainly caused by improper placement of the femoral stem, whereas a decrease of global FO > 5 was caused by improper placement of both acetabular and femoral components. The radiological measurement methods used showed substantial to excellent interobserver reliability and intraobserver reproducibility and are therefore clinically useful.The main conclusions of this thesis are:LLD up to 20 mm and reduced global FO more than 5 mm did not influence the functional outcome or quality of life at 12–15 months postoperatively.Lengthening ≥ 10mm was associated with increased use of a shoe lift. A reduction of global FO more than 5 mm compared to the contralateral hip was associated with weaker hip abductor muscles and more use of walking aids. Therefore both should be avoided.The radiographic measurement methods of LLD, global FO, cup inclination and anteversion have the required validity and reliability to be used in clinical practice.Lengthening of the operated leg is mainly caused by improper femoral stem positioning while global FO reduction results from improper positioning of both acetabular and femoral components. Surgeons should be aware of these operative pitfalls in order to minimize component malpositioning.
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| 4. |
- Otten, Volker T C, 1973-
(författare)
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The Uncemented Cup in Total Hip Arthroplasty : stability, Wear and Osteolysis
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Artificial hip joint replacement has undergone tremendous development in the past 100 years. In the beginning, complications, such as infection and early loosening, were the rule rather than the exception. Today, complications of any sort are rare during the first decade after the operation. Artificial hip joint replacement has been chosen as the "Operation of the Century" and has dramatically improved the quality of life of millions of patients. Unfortunately, in the long-term, prosthesis loosening due to pathological bone resorption (osteolysis) around the prosthesis is still common. Traditionally, the prosthesis is anchored in the bone with bone cement (Plexiglas). However, since this cementation method was suspected to cause late loosening, alternative methods, such as the implantation of so-called uncemented prostheses, have been developed and are being increasingly applied. Because the early movement of a prosthesis (migration) increases the risk of loosening, uncemented cups are often augmented with additional screws. The mechanisms regulating the early and late loosening of uncemented cups are not fully established. Wear particles from the artificial joint and intermittent fluid pressure on the bone appear to accelerate or even cause bone loss and can eventually lead to loosening of the prosthesis. Therefore, screw holes in the uncemented cup have been suspected to be a risk factor.Aims: We have studied whether the additional augmentation of modern uncemented cups with screws, pegs or hydroxyapatite increases the long-term stability, affects the wear rate, influences the development of osteolysis, or has any impact on the risk of cup revision. Furthermore, we investigated whether computed tomography (CT), which is needed to detect osteolysis around the prosthesis, could also be used in the follow-up of migration studies without losing significant precision compared to radiostereometry (RSA), which is the gold standard for these measurements.Patients and Methods: In studies I-III, we evaluated 48 hips (45 patients) randomized to receive cups with or without augmentation. As part of the 14-year follow-up with conventional radiographs of the pelvis, two pairs of stereo radiographs and a CT scan were obtained. Migration and wear were measured by RSA. The volume and type of osteolysis were determined on CT. Furthermore, we calculated the precision and limit of agreement of RSA and CT to compare these two modalities as tools for migration measurements.In study IV, we compared the risk of cup revision between 10,371 uncemented cups with and 12,354 without screw holes, using data from the Swedish Hip Arthroplasty Register.Results: Study I: Cup stability was equally good regardless of cup augmentation. The mean wear rate of the cup liner was high, at 0.21 mm/year, with no significant difference between the groups.Study II: The limit of agreement between CT and RSA was 1.15°, 1.51°, and 0.70° for rotation and 0.46, 0.43, and 0.52 mm for translation. These results were within the described normal 99% confidence limits for precision in RSA: 0.3° to 2° for rotation and 0.15 to 0.6 mm for translation.Study III: Osteolysis of some degree was visible in all 48 hips on CT. We found three different types of osteolytic lesions: type 1A, absent trabecular bone and a sclerotic border around the lesion; type 1B, absent trabecular bone and no sclerotic border; and type 2, reduced radiodensity and reduced trabecular number. Cups with screw holes were surrounded with larger osteolytic lesions, and osteolysis around these cups was more likely to be a type 1A lesion.Study IV: Cups without screw holes showed a decreased risk of cup revision (implant exchange or removal) due to any reason at both 2 years (adjusted hazard ratio, HR: 0.6, confidence interval, CI: 0.5-0.8) and 10 years (HR: 0.7, CI: 0.5- 0.9). However, for aseptic loosening, there was no significant difference between cups with and without screw holes, with an implant survival rate of 99.9% (CI: 99.8-99.9) at 2 years and 99.1% (CI: 98.6-99.7) at 10 years.Conclusion: Uncemented cups augmented with screws, pegs, or hydroxyapatite do not have improved long-term stability compared with cups with press-fit only. Unsealed screw holes in uncemented cups appear to be a risk factor for the development of larger osteolytic lesions. CT showed three different types of osteolytic lesions. The risk of aseptic loosening for modern uncemented cup designs is very low, and cups without additional augmentation do not have an increased revision rate. In contrast, the risk of cup revision for any reason was higher for cups with screw holes. CT can be used for migration studies for the longitudinal evaluation of patients with tantalum markers with precision comparable to that of RSA.
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| 5. |
- Wänman, Johan, 1983-
(författare)
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Clinical and morphological aspects of metastatic spinal cord compression
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Metastatic spinal cord compression (MSCC) is a serious complication of cancer leading to demyelination and axonal damage of the spinal cord with a risk of para/tetraplegia. It is most common in patients with known cancer but may also be the initial manifestation of malignancy (IMM). Patients with MSCC as the IMM have rarely been studied as a separate group. The interaction between the tumour and bone in spinal bone metastasis interferes with regulatory mechanisms, causing the formation of less mechanically competent bone and increasing the risk of spinal instability and fracture. The Spinal Instability Neoplastic Score (SINS) has been proposed as a tool in order to help clinicians evaluate tumour-related spinal instability. The SINS has shown excellent inter- and intraobserver reliability, but its prognostic value is still controversial. Bone metastases from prostate cancer are generally classified as osteoblastic due to increased bone formation. However, this categorization is probably oversimplified since there are overlapping bone cell activities between osteoblastic and osteolytic metastases. Prostate cancer bone metastases can also have a myeloma-like radiological appearance, but little is known about this subgroup of lesions. Aims: The aims of this work were as follows: a) to evaluate outcomes after surgery in patients with MSCC as the IMM; b) to analyse the prognostic value of the SINS regarding survival and neurological function after surgery for MSCC in patients with prostate cancer and haematological malignancies; and c) to analyse the clinical and morphological features of prostate cancer spinal bone metastases with a myeloma-like radiological appearance. Patients and methods: In studies I-III, we retrospectively evaluated the outcomes after surgery for MSCC in patients with MSCC as the IMM (study I, n=69), prostate cancer (study II, n=110) and haematological malignancies (study III, n=48). In study IV, tumour tissue samples from bone metastases obtained during surgery for MSCC in 110 patients with prostate cancer were analysed by immunohistochemistry and molecular transcriptomic analyses, and the results were related to the radiological appearance and clinical outcomes. Results: Study I: The primary tumour was identified in 59 of 69 patients. The median postoperative survival after surgery for MSCC was 20 months. Patients with prostate cancer had the longest median survival (6 years), and patients who were defined as having cancer of unknown primary tumour had the shortest median survival (3.5 months). Surgery maintained and improved the ability to walk in these patients. Study II: A total of 106 of 110 patients met the SINS criteria for potential instability or instability. There was no statistically significant difference in the overall risk of death between the SINS potentially unstable and unstable SINS categories, or in the risk of loss of ambulation one month after surgery. Study III: The median postoperative survival was 71.5 months in patients with myeloma and 58.7 months in patients with lymphoma. The SINS was not related to postoperative survival or neurological outcomes. The ability to walk before surgery was strongly associated with the postoperative ambulatory status. On multivariate Cox regression analysis, the ability to walk and a higher blood haemoglobin level prior to surgery were associated with superior survival. Study IV: A myeloma-like radiological appearance of prostate cancer spinal bone metastases was associated with poor survival and neurological outcomes after surgery for MSCC. Conclusions: Patients with MSCC as the IMM resemble a heterogeneous group in which survival is highly dependent on the type of primary tumour. A diagnostic workup is essential before a prognosis can be estimated in order to select candidates for surgery. The SINS may be helpful in selecting patients for surgery for MSCC, but it cannot be used to predict postoperative survival or neurological outcomes in patients with prostate cancer or in patients with haematological malignancies. A myeloma-like radiological appearance of prostate cancer spinal bone metastases is a strong negative predictor for survival and neurological outcomes after surgery for MSCC.
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