| 1. |
- Boström, Peter J., et al.
(författare)
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Clinical markers of morbidity, mortality and survival in bladder cancer patients treated with radical cystectomy : A systematic review
- 2020
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 54:4, s. 267-276
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Forskningsöversikt (refereegranskat)abstract
- Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.Objective:To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice.
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| 2. |
- Kalinen, Sofia, et al.
(författare)
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Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.
- 2024
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Ingår i: European urology open science. - 2666-1683. ; 62, s. 140-150
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Tidskriftsartikel (refereegranskat)abstract
- Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.Characterization of the gut microbiota and its functions associated with PCa.In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.
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| 3. |
- Oscarsson, Nicklas, 1974, et al.
(författare)
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Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial
- 2019
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 20:11, s. 1602-1614
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Elsevier Ltd Background: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. Methods: We did a randomised, controlled, phase 2–3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen—A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18–80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30–40 sessions, 100% oxygen, breathed at a pressure of 240–250 kPa, for 80–90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6–8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. Findings: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210–262) in the hyperbaric oxygen therapy group and 217 days (195–237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2–18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1–2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. Interpretation: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. Funding: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.
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| 4. |
- Wahlström, Gudrun, et al.
(författare)
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The variant rs77559646 associated with aggressive prostate cancer disrupts ANO7 mRNA splicing and protein expression.
- 2022
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Ingår i: Human molecular genetics. - 1460-2083. ; 31:12, s. 2063-2077
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is among the most common cancers in men, with a large fraction of the individual risk attributable to heritable factors. A majority of the diagnosed cases does not lead to a lethal disease, and hence biological markers that can distinguish between indolent and fatal forms of the disease are of great importance for guiding treatment decisions. Although over 300 genetic variants are known to be associated with prostate cancer risk, few have been associated with the risk of an aggressive disease. One such variant is rs77559646 located in ANO7. This variant has a dual function. It constitutes a missense mutation in the short isoform of ANO7 and a splice region mutation in full-length ANO7. In this study, we have analyzed the impact of the variant allele of rs77559646 on ANO7 mRNA splicing using a minigene splicing assay and by performing splicing analysis with the tools IRFinder (intron retention finder), rMATS (replicate multivariate analysis of transcript splicing) and LeafCutter on RNA sequencing data from prostate tissue of six rs77559646 variant allele carriers and 43 non-carriers. The results revealed a severe disruption of ANO7 mRNA splicing in rs77559646 variant allele carriers. Immunohistochemical analysis of prostate samples from patients homozygous for the rs77559646 variant allele demonstrated a loss of apically localized ANO7 protein. Our study is the first to provide a mechanistic explanation for the impact of a prostate cancer risk SNP on ANO7 protein production. Furthermore, the rs77559646 variant is the first known germline loss-of-function mutation described for ANO7. We suggest that loss of ANO7 contributes to prostate cancer progression.
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