| 11. |
- Nordgren, Ann, 1964, et al.
(författare)
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Precision medicine and rare diseases in pediatric urology
- 2023
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Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131 .- 1873-4898. ; 19:3, s. 335-338
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Tidskriftsartikel (refereegranskat)abstract
- Precision Medicine holds promise for helping us manage specific phenotypes of common diseases. For rare diseases such as hypospadias, DSD, and pediatric solid tumors, it can also reveal underlying risk factors and pathogenesis. Professors Ann Nordgren and Anna Lindstrand share their experi-ences in the development and ongoing initiatives of the Swedish national project on Precision Medicine and how it could change the care of pediatric urol-ogy patients.
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| 12. |
- Ying, T. M., et al.
(författare)
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Automated artificial intelligence-based analysis of skeletal muscle volume predicts overall survival after cystectomy for urinary bladder cancer
- 2021
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Ingår i: European Radiology Experimental. - : Springer Science and Business Media LLC. - 2509-9280. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Radical cystectomy for urinary bladder cancer is a procedure associated with a high risk of complications, and poor overall survival (OS) due to both patient and tumour factors. Sarcopenia is one such patient factor. We have developed a fully automated artificial intelligence (AI)-based image analysis tool for segmenting skeletal muscle of the torso and calculating the muscle volume. Methods All patients who have undergone radical cystectomy for urinary bladder cancer 2011-2019 at Sahlgrenska University Hospital, and who had a pre-operative computed tomography of the abdomen within 90 days of surgery were included in the study. All patients CT studies were analysed with the automated AI-based image analysis tool. Clinical data for the patients were retrieved from the Swedish National Register for Urinary Bladder Cancer. Muscle volumes dichotomised by the median for each sex were analysed with Cox regression for OS and logistic regression for 90-day high-grade complications. The study was approved by the Swedish Ethical Review Authority (2020-03985). Results Out of 445 patients who underwent surgery, 299 (67%) had CT studies available for analysis. The automated AI-based tool failed to segment the muscle volume in seven (2%) patients. Cox regression analysis showed an independent significant association with OS (HR 1.62; 95% CI 1.07-2.44; p = 0.022). Logistic regression did not show any association with high-grade complications. Conclusion The fully automated AI-based CT image analysis provides a low-cost and meaningful clinical measure that is an independent biomarker for OS following radical cystectomy.
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| 13. |
- Nordin, Elise, 1985, et al.
(författare)
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An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3–19.4 nmol/L in plasma) vs. refined wheat (0.05–2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma (p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.
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| 14. |
- Bratt, Ola, 1963, et al.
(författare)
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Prostate cancer in kidney transplant recipients - a nationwide register study
- 2020
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Ingår i: Bju International. - : Wiley. - 1464-4096 .- 1464-410X. ; 125:5, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether post-transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients. Patients and Methods We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998-2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case-control study was designed to compare time period and risk category-specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher's exact test were used and 95% confidence intervals (CIs) calculated. Results Almost half of the 133 kidney transplantation recipients were transplanted before the mid-1990s, when PSA testing became common. The transplant recipients were not more likely than age-matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70-0.99) or high-risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62-1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer-specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant. Conclusions This Swedish nationwide, register-based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low-grade prostate cancer can be accepted for transplantation.
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| 15. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Goteborg Randomized Population-based Prostate Cancer Screening Trial
- 2023
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 83:2, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of death from prostate cancer (PC) depends on age, but the age at which to start prostate-specific antigen (PSA) screening remains uncertain. Objective: To study the relationship between risk reduction for PC mortality and age at first PSA screening. Design, setting, and participants: The randomized Goteborg-1 trial invited men for bien-nial PSA screening between the ages of 50 and 70 yr (screening, n = 10 000) or no invi-tation but exposure to opportunistic PSA testing (control, n = 10 000). Intervention: Regular versus opportunistic PSA screening or no PSA. Outcome measurements and statistical analysis: We modeled the nonlinear association between starting age and the absolute risk reduction in PC mortality in three settings: (1) intention-to-screen (randomized arms); (2) historical control (screening group and 1990-1994 registry data); and (3) attendees only (screening attendees and matched controls). We tested whether the effect of screening on PC mortality depends on the age at starting screening by comparing survival models with and without an interaction between trial arm and age (intention-to-screen and attendees only). Results and limitations: Younger age on starting PSA testing was associated with a greater reduction in PC mortality. Starting screening at age 55 yr approximately halved the risk of PC death compared to first PSA at age 60 yr. The test of association between starting age and the effect of screening on PC mortality was slightly greater than the con-ventional level of statistical significance (p = 0.052) for the entire cohort, and statistically significant among attendees (p = 0.002). This study is limited by the low number of disease-specific deaths for men starting screening before age 55 yr and the difficulty in discriminating between the effect of starting age and screening duration. Conclusions: Given that prior screening trials included men aged up to 70 yr on starting screening, our results suggest that the effect size reported in prior trials underestimates that of currently recommended programs starting at age 50-55 yr. Patient summary: In this study from the Goteborg-1 trial, we looked at the effect of prostate-specific antigen (PSA) screening in reducing men's risk of dying from prostate cancer given the age at which they begin testing. Starting at a younger age reduced the risk of prostate cancer death by a greater amount. We recommend that PSA screen-ing should start no later than at age 55 yr. (c) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 16. |
- Gedeborg, Rolf, et al.
(författare)
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Susceptibility to SARS-Cov-2 infection and risk for severe COVID-19 in patients with prostate cancer on androgen deprivation therapy
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:11, s. 1925-1934
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Tidskriftsartikel (refereegranskat)abstract
- Androgen deprivation therapy (ADT) has been hypothesized to protect against COVID-19, but previous observational studies of men with prostate cancer on ADT have been inconsistent regarding mortality risk from coronavirus disease 2019 (COVID-19). Using data from the Prostate Cancer data Base Sweden (PCBaSe), we identified a cohort of 114 547 men with prevalent prostate cancer on the start of follow-up in February 2020, and followed them until 16 December 2020 to evaluate the association between ADT and time to test positive for COVID-19. Among men testing positive for COVID-19, we used regression analyses to estimate the association between ADT and risk of COVID-19-related hospital admission/death from any cause within 30 days of the positive test. In total, 1695 men with prostate cancer tested positive for COVID-19. In crude analyses, exposure to ADT was associated with a 3-fold increased risk of both testing positive for COVID-19 infection and subsequent hospital admission/death. Adjustment for age, comorbidity and prostate cancer risk category substantially attenuated the associations: HR 1.3 (95% CI: 1.1-1.5) for testing positive for COVID-19, and OR 1.4 (95% CI: 1.0-1.9) for risk of subsequent hospital admission/death. In conclusion, although these results suggest increased risks of a positive COVID-19 test, and COVID-19-related hospital admission/death in men on ADT, these findings are likely explained by confounding by old age, cancer-associated morbidity and other comorbidities being more prevalent in men on ADT, rather than a direct effect of the therapy.
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| 17. |
- Orrason, Andri Wilberg, 1988-
(författare)
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Trends in Prostate Cancer Mortality
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the early 20th century, cancer of the prostate was considered a rare and deadly disease with little to no possibility of cure. Since then, prostate cancer management has improved substantially with earlier detection, hormonal therapy, surgery and radiotherapy of the prostate. Nevertheless, prostate cancer remains the leading cause of cancer death in men in Western countries. The purpose of this thesis was to study trends in prostate cancer mortality including investigations of adjudication and measures of prostate cancer death. In paper I, we studied whether increased use of radical treatment in men with locally advanced prostate cancer diagnosed between 2000-2016 has affected prostate cancer mortality in the Swedish population. The use of radical treatment almost tripled and 5-year cumulative incidence of prostate cancer death declined from 17% to 10% for all men below age 80 with locally advanced prostate cancer. In paper II, we compared relative and cause-specific survival in all men with prostate cancer, according to age at death and risk category at diagnosis. Older men with low-risk prostate cancer at diagnosis had a substantially higher relative survival compared to cause-specific survival, 116% vs. 96% at five years after diagnosis. Despite efforts to increase comparability of expected survival, relative survival remained above 100% in these men due to healthy selection bias. In paper III, we assessed the amount of evidence in support of prostate cancer as the cause of death by review of health care records for 495 men who between 2011-2018 died of prostate cancer according to the Cause of Death Register. Older men and men with low-risk prostate cancer at diagnosis had considerably less evidence in support of prostate cancer death compared with younger men and men with high-risk disease. In paper IV, we applied a simulation model to estimate the lifetime risk of prostate cancer for different levels of diagnostic activity and life expectancy. Men exposed to high diagnostic activity had five-fold life-time risk of low or intermediate-risk prostate cancer and half the lifetime risk of high-risk or metastatic prostate cancer compared to men exposed to low diagnostic activity. Long life expectancy moderately increased the lifetime risk of prostate cancer in all risk categories, especially high-risk disease.
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| 18. |
- Polymeri, Erini, et al.
(författare)
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Artificial intelligence-based measurements of PET/CT imaging biomarkers are associated with disease-specific survival of high-risk prostate cancer patients
- 2021
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 55:6, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- Objective Artificial intelligence (AI) offers new opportunities for objective quantitative measurements of imaging biomarkers from positron-emission tomography/computed tomography (PET/CT). Clinical image reporting relies predominantly on observer-dependent visual assessment and easily accessible measures like SUVmax, representing lesion uptake in a relatively small amount of tissue. Our hypothesis is that measurements of total volume and lesion uptake of the entire tumour would better reflect the disease`s activity with prognostic significance, compared with conventional measurements. Methods An AI-based algorithm was trained to automatically measure the prostate and its tumour content in PET/CT of 145 patients. The algorithm was then tested retrospectively on 285 high-risk patients, who were examined using F-18-choline PET/CT for primary staging between April 2008 and July 2015. Prostate tumour volume, tumour fraction of the prostate gland, lesion uptake of the entire tumour, and SUVmax were obtained automatically. Associations between these measurements, age, PSA, Gleason score and prostate cancer-specific survival were studied, using a Cox proportional-hazards regression model. Results Twenty-three patients died of prostate cancer during follow-up (median survival 3.8 years). Total tumour volume of the prostate (p = 0.008), tumour fraction of the gland (p = 0.005), total lesion uptake of the prostate (p = 0.02), and age (p = 0.01) were significantly associated with disease-specific survival, whereas SUVmax (p = 0.2), PSA (p = 0.2), and Gleason score (p = 0.8) were not. Conclusion AI-based assessments of total tumour volume and lesion uptake were significantly associated with disease-specific survival in this patient cohort, whereas SUVmax and Gleason scores were not. The AI-based approach appears well-suited for clinically relevant patient stratification and monitoring of individual therapy.
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| 19. |
- Rosenblatt, Robert, 1982-
(författare)
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Neoadjuvant chemotherapy in muscle-invasive urinary bladder cancer : studies on treatment response, tumor draining lymph nodes and blood transfusion
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Muscle-invasive urinary bladder cancer is a deadly disease. Mortality rates remained unchanged for decades despite radical surgery.After several randomized trials, we today know that cisplatin based chemotherapy given prior to cystectomy, improves survival for every tenth patient. Markers that predict responsiveness to chemotherapy would spare unnecessary treatment to the majority of patients. In the search for signs of chemosensitivity, we performed a retrospective analysis of the Nordic cystectomy trials 1 & 2: Chemo treated patients had an almost doubled increase in tumor downstaging compared to the controls. More importantly, this group presented with a reduced absolute risk of death of more than 30% compared to the rest of the patients. These results were presented in paper I.Many cancers spread through the lymphatic system. Usually, there is at least one tumor draining lymph node, referred to as the sentinel node. If this node is free of metastases, there is no lymphatic spread of the disease, and consequently, no use of excavating all neighboring lymph nodes.Sentinel node detection, is an established method in breast cancer, penile cancer and malignant melanoma. Based on the same principles, members of our group developed a similar detection technique in bladder cancer. Unfortunately, sensitivity and specificity were too low to rely on this method as a diagnostic tool for lymphatic spread. Instead, it turned out in recent years that sentinel nodes in muscle invasive bladder cancer are valuable for translational research-lines - mainly in tumor immunology. As for example, sentinel nodes contain tumor specific T cells that are useful in adoptive immunotherapy.In paper II, we set out to test whether sentinel node detection was feasible after chemotherapy and/or tumor downstaging. In a prospective cohort of patients, we saw no difference in detection rates between the groups. Thus, we concluded, neither chemotherapy nor downstaging appeared to hamper the identification of sentinel nodes.The concept was expanded in paper III. After recruiting more patients to the cohort mentioned above, the average numbers of sentinel nodes in different categories of patients were compared. We saw a pattern of decreased number of sentinel nodes in those with locally advanced tumors. It seemed that the number of sentinel nodes had prognostic implications.In the last study, published in paper IV, we wanted to widen our knowledge on the clinical effects of blood transfusion. Mounting data suggests that perioperative blood products have a negative impact on long term survival after cancer surgery. How much allogenic blood was given during the chemotherapy prior to surgery ? It turned out that one third of the bladder cancer patients received blood, and these patients demonstrated a significantly worse overall survival.Neoadjuvant chemotherapy has added a new beneficial dimension to the treatment of muscle invasive bladder cancer. In these four studies, we addressed the effects of chemotherapy on pathoanatomical outcomes, on tumor lymphatics and further; we are suggesting consequences of neoadjuvant chemotherapy in conjunction with blood transfusion. It appears that the immune system is involved in all aspects investigated above. Most likely, an improved scientific understanding of the immune system will be crucial for future bladder cancer treatment options.
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| 20. |
- Welén, Karin, 1970, et al.
(författare)
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A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
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Tidskriftsartikel (refereegranskat)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
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