| 1. |
- Gerdtsson, Axel, et al.
(author)
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Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients
- 2023
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In: Bju International. - 1464-4096 .- 1464-410X. ; 132:3, s. 329-336
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Journal article (peer-reviewed)abstract
- Objective To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. Materials and methods Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alphafetoprotein; b-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and postchemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out), was analysed using decision curve analysis. Results Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. Conclusions The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.
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| 2. |
- Ladfors, S. W., et al.
(author)
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Longitudinal Follow-Up on Cardiopulmonary Exercise Capacity Related to Cardio-Metabolic Risk Factors in Children With Renal Transplants
- 2021
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In: Frontiers in Sports and Active Living. - : Frontiers Media SA. - 2624-9367. ; 3
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Journal article (peer-reviewed)abstract
- Background: Children with chronic kidney disease, including those treated with kidney transplantation (KT), have an increased risk of cardiovascular disease. The aim of this study was to examine the cardiopulmonary exercise capacity after KT compared to matched controls, to relate the results to physical activity, blood pressure and biochemical findings and to follow exercise capacity over time. & nbsp; Methods: Patients with KT (n = 38, age 7.7-18 years), with a mean time from transplantation of 3.7 years (0.9-13.0) and mean time in dialysis 0.8 years, were examined at inclusion and annually for up to three years. Healthy controls (n = 17, age 7.3-18.6 years) were examined once. All subjects underwent a cardiopulmonary exercise test, resting blood pressure measurement, anthropometry and activity assessment. Patients also underwent echocardiography, dual-energy X-ray absorptiometry (DXA), 24-h ambulatory BP measurements (ABPM), assessment of glomerular filtration rate (GFR) and blood sampling annually. & nbsp; Results: As compared to healthy controls, KT patients showed decreased exercise capacity measured both as VO2peak (34.5 vs. 43.9 ml/kg/min, p < 0.001) and maximal load (2.6 vs. 3.5 W/kg, p < 0.0001), similarly as when results were converted to z-scores. No significant difference was found in weight, but the KT patients were shorter and had higher BMI z-score than controls, as well as increased resting SBP and DBP z-scores. The patient or parent reported physical activity was significantly lower in the KT group compared to controls (p < 0.001) In the combined group, the major determinants for exercise capacity z-scores were activity score and BMI z-score (beta = 0.79, p < 0.0001 and beta = -0.38, p = 0.007, respectively). Within the KT group, low exercise capacity was associated with high fat mass index (FMI), low activity score, low GFR and high blood lipids. In the multivariate analysis FMI and low GFR remained predictors of low exercise capacity. The longitudinal data for the KT patients showed no change in exercise capacity z-scores over time. & nbsp; Conclusion: Patients with KT showed decreased exercise capacity and increased BP as compared to healthy controls. Exercise capacity was associated to GFR, physical activity, FMI and blood lipids. It did not improve during follow-up.
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| 3. |
- Conway, Louis P., et al.
(author)
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Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine N-Acetyltransferase NAT2
- 2020
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In: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 59:34, s. 14342-14346
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Journal article (peer-reviewed)abstract
- N-Acetyltransferases play critical roles in the deactivation and clearance of xenobiotics, including clinical drugs. NAT2 has been classified as an arylamine N-acetyltransferase that mainly converts aromatic amines, hydroxylamines, and hydrazines. Herein, we demonstrate that the human arylamine N-acetyltransferase NAT2 also acetylates aliphatic endogenous amines. Metabolomic analysis and chemical synthesis revealed increased intracellular concentrations of mono- and diacetylated spermidine in human cell lines expressing the rapid compared to the slow acetylator NAT2 phenotype. The regioselective N8 -acetylation of monoacetylated spermidine by NAT2 answers the long-standing question of the source of diacetylspermidine. We also identified selective acetylation of structurally diverse alkylamine-containing drugs by NAT2, which may contribute to variations in patient responses. The results demonstrate a previously unknown functionality and potential regulatory role for NAT2, and we suggest that this enzyme should be considered for re-classification.
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| 4. |
- Gerdtsson, Axel, et al.
(author)
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Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours
- 2024
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In: BJU INTERNATIONAL. - : John Wiley & Sons. - 1464-4096 .- 1464-410X.
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Journal article (peer-reviewed)abstract
- Objectives To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. Patients and methods Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. Results Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. Conclusions Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.
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| 5. |
- Gerdtsson, Axel, et al.
(author)
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Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group
- 2022
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In: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:2, s. 235-243
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Journal article (peer-reviewed)abstract
- BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.
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| 6. |
- Thor, Anna, et al.
(author)
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Primary retroperitoneal lymph node dissection as treatment for low-volume metastatic seminoma in a population-based cohort : the Swedish Norwegian testicular cancer group experience
- 2024
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In: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 65, s. 13-19
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Journal article (peer-reviewed)abstract
- Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy.Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS).Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13–24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16–30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4–14). PFS was 90% (95% confidence interval: 0.86–1) and OS was 100% at 24 mo.Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity.Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
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