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- Jonsson, Pär, et al.
(författare)
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Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples
- 2015
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 11:6, s. 1667-1678
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Tidskriftsartikel (refereegranskat)abstract
- Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.
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- Lundström, Karl-Johan, et al.
(författare)
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Epidemiology of hydrocele and spermatocele; incidence, treatment and complications
- 2019
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 53:2-3, s. 134-138
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate the incidence of men seeking specialized care and receiving treatment for hydro or spermatocele complaints. Also, to determine the risk of complications of treatment.Materials and methods: The total number of men living in Sweden each year from 2005 to 2014 was used to calculate incidence and age distribution of adult (≥18 years) men seeking specialized healthcare with either hydro or spermatocele. This was done by using nationwide registries, mandatory by law. They contain information on primary or discharge diagnosis, procedure codes and antibiotic prescriptions. Also, complication rates comparing aspiration (with or without sclerotherapy) and conventional surgery were analysed.Results: The incidence of men with either hydro or spermatocele diagnosis in specialized healthcare was ∼100/100,000 men. The treatment incidence was 17/100,000 men. Orchiectomy was used as primary treatment in 2.4% of cases. The risk of experiencing a complication was clinically and statistically significantly increased with conventional surgery as compared with aspiration, 17.5% (1607/9174) vs 4.6% (181/3920), corresponding to relative risk of 3.79 (95% CI = 3.27–4.40). Hematoma and infections were the most common complications.Conclusion: Hydro and spermatoceles are common, affecting elderly men. Aspiration seems advantageous with respect to complications and can be recommended due to the benign course of the disease. The indication for conventional surgery might be questioned such as the use of orchiectomy as primary treatment.
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4. |
- Lundström, Karl-Johan, 1977-
(författare)
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Outcomes and complications in surgical and urological procedures
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background:Minor procedures in surgery and urology such as groin hernia and hydrocele repair, as well as prostate biopsies are very frequently done in routine practice. Complications and insufficient outcomes thus affecting many patients and the cumulative effect of this are of major importance in a population perspective.Aim:To explore complications and outcomes of surgical or diagnostic procedures and possible risk factors or predictors for adverse effects. Methods: By using both national quality and administrative registers, and by complementing registers with patient reported outcome measures, examine outcomes such as complications, persistent pain and recurrences. Also, in the case of hydro and spermatoceles, report incidence numbers. Further, by using a randomized trial, explore minimally invasive procedure such as sclerotheraphy compared to conventional surgery in respect to cure and adverse events.Results:When comparing with the open anterior mesh repair, endoscopic technique is advantageous in respect to the patient reported outcome of persistent pain. The drawback was an increased risk of postoperative complications and reoperation for recurrence. Incidence numbers for hydro and spematocele were 100/100000 men. Aspiration (± sclerotherapy) had a significantly lower rate of complications as compared to conventional surgery. In the interim analysis of the randomized trial, comparing sclerotherapy to Lord´s procedure for hydroceles, the cure rate was similar between treatments. Definite conclusions cannot be made due to the risk of type 2 errors, and the study will thus continue. In the case of trans-rectal prostate biopsy, the rates increased every year during the study time frame, up to an approximate risk of two per cent in 2012 for hospital readmission within 30 days, without an increased mortality within 30 days.Conclusions:The open anterior mesh procedure is still the preferred method for groin hernia repair in routine surgical practice. Hydro and spermatocele surgery is associated with high rates of complications, and the indication for repair should be scrutinized. The rates of infection after prostate biopsy is increasing and methods to reduce unnecessary biopsies as well as improved prophylaxis should be investigated.
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5. |
- Lundström, Karl-Johan, et al.
(författare)
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Small bowel obstruction and abdominal pain after robotic versus open radical prostatectomy
- 2016
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Ingår i: Scandinavian journal of urology. - : Informa UK Limited. - 2168-1805 .- 2168-1813. ; 50:3, s. 155-159
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to examine whether intraperitoneal robot-assisted surgery leads to small bowel obstruction (SBO), possibly caused by the formation of intra-abdominal adhesions.Materials and methods: In total, 7256 men treated by intraperitoneal robot-assisted radical prostatectomy (RARP) and 9787 men treated by retropubic radical prostatectomy (RRP) in 2005-2012 were identified in the Prostate Cancer data Base Sweden (PCBaSe). Multivariable Cox proportional hazards models were used to calculate the risk of readmission for SBO, SBO-related surgery and admissions due to abdominal pain up to 5 years postoperatively.Results: During the first postoperative year, the risk of readmission for SBO was higher after RARP than after RRP [hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.14-3.25] but after 5 years there was no significant difference (HR 1.28, 95% CI 0.86-1.91), and there was no difference in the risk of SBO surgery during any period. The risk of admission for abdominal pain was significantly increased after RARP during the first year (HR 2.24, 95% CI 1.50-3.33) but not after 5 years (HR 1.23, 95% CI 0.92-1.63).Conclusion: Intraperitoneal RARP had an increased risk of SBO and abdominal pain in the short term during the first year, but not in the long term, compared to RRP.
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6. |
- Nilsson, Hanna, et al.
(författare)
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Incidence of groin hernia repair after radical prostatectomy : a population-based nationwide study
- 2014
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 259:6, s. 1223-1227
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the incidence of groin hernia repair after radical prostatectomy for prostate cancer compared with the incidence in a control population without prostate cancer in a nationwide, population-based study.Background: Recent reports indicate an increase in the incidence of groin hernia repair after radical prostatectomy. Inadequate knowledge of the incidence of groin hernia in the general population makes this information hard to interpret.Methods: Information was retrieved from the Prostate Cancer Database (PCBaSe) and Swedish Hernia Register for events between 1998 and 2010. The incidence of groin hernia surgery was calculated for a group of men treated with radical prostatectomy (open and minimally invasive) and for a group treated with radiation therapy, and these were compared with the incidence in a control cohort of men matched for age and county of residence. Multivariate analysis was used to assess the hazard ratio (HR) of groin hernia repair according to age, tumor risk category, and Charlson Comorbidity Index.Results: A total of 28,608 cases and 105,422 controls were included in the study. Men treated with radical prostatectomy and radiation therapy had a significantly higher incidence of groin hernia repair than the control cohort: HR: 3.95 (95% confidence interval: 3.70-4.21) for retropubic prostatectomy, HR: 3.37 (95% confidence interval: 2.95-3.87) for minimally invasive prostatectomy, and HR: 1.84 (95% confidence interval: 1.66-2.04) for radiation therapy.Conclusions: An almost 4-fold increase in groin hernia repair was observed after radical prostatectomy compared with controls, and men who received radiation therapy had an almost 2-fold increase in incidence. As well as postoperative changes in the abdominal wall, increased vigilance for groin hernia seems to be important for the increased incidence of groin hernia repair seen after radical prostatectomy or radiation therapy for prostate cancer.
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- Stranne, Johan, 1970, et al.
(författare)
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Single institution followed by national implementation of systematic surgical quality control and feedback for radical prostatectomy: a 20-year journey
- 2020
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 38, s. 1397-1411
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The demand for objective and outcome-based facts about surgical results after radical prostatectomy (RP) is increasing. Systematic feedback is also essential for each surgeon to improve his/her performance. Methods: RP outcome data (e.g., pT-stage and margin status) have been registered at Sahlgrenska University Hospital (SUH) since 1988 and patient-related outcome measures (PROM) have been registered since 2001. The National Prostate Cancer Registry (NPCR) has covered all Regions in Sweden since 1998 and includes PROM-data from 2008. Initially PROM was on-paper questionnaires but due since 2018 all PROMs are collected electronically. In 2014 an on-line “dashboard” panel was introduced, showing the results for ten quality-control variables in real-time. Since 2017 all RP data on hospital, regional, and national levels are publicly accessible on-line on “www.npcr.se/RATTEN”. Results: The early PROM-data from SUH have been used for internal quality control. As national clinical and PROM-data from the NPCR have been made accessible on-line and in real-time we have incorporated this into our pre-existing protocol. Our data are now internally available as real-time NPCR reports on the individual surgeons’ results, as well as ePROM data. We can compare the results of each surgeon internally and to other departments’ aggregated data. The public can access data and compare hospital level data on “RATTEN”. Conclusions: The process of quality control of RP locally at SUH, and nationally through the NPCR, has been long but fruitful. The online design, with direct real-time feedback to the institutions that report the data, is essential.
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8. |
- Adam, Meike, et al.
(författare)
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Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a Combination of Prostatectomy with Radiation and Hormonal Therapy
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:3, s. 330-336
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Tidskriftsartikel (refereegranskat)abstract
- Background: While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy.Objective: To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP.Design, setting, and participants: Among 13 150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT.Outcome measurements and statistical analyses: Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP.Results and limitations: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (> 3 pads/24 h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received.Conclusions: Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment.Patient summary: Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.
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9. |
- Adamo, Hanibal Hani, 1984-, et al.
(författare)
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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
- 2019
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Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 79:5, s. 435-445
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Tidskriftsartikel (refereegranskat)abstract
- Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.
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10. |
- Adamo, Hanibal, et al.
(författare)
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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome.
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