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Ljungberg, Börje, ProfessorORCID iD iconorcid.org/0000-0002-4121-3753
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Publications (10 of 283) Show all publications
Tumkur Sitaram, R. & Ljungberg, B. (2024). Expression of HIF‑α and their association with clinicopathological parameters in clinical renal cell carcinoma. Upsala Journal of Medical Sciences, 129, Article ID e9407.
Open this publication in new window or tab >>Expression of HIF‑α and their association with clinicopathological parameters in clinical renal cell carcinoma
2024 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 129, article id e9407Article in journal (Refereed) Published
Abstract [en]

Objectives: This study aimed to assess the cellular localization and expression levels of hypoxia-inducible factor (HIF) -α proteins (specifically HIF-1α, HIF-2α, and HIF-3α) that play a role in the hypoxia pathway and to determine their correlation with clinicopathological parameters and patient survival in renal cell carcinoma (RCC).

Materials and methods: Tissue microarray (TMA) with cores from 150 clear cell RCCs and 31 non-ccRCC samples. HIF-1α, HIF-2α, and HIF-3α antibodies were used for immunohistochemistry (IHC) of TMA to evaluate the cellular localization and expression levels of HIF-α proteins, specifically in relation to the hypoxia pathway.

Results: The expression levels of the HIF-α proteins were higher in the nucleus than in the cytoplasm. Furthermore, the nuclear expression levels of all HIF-α proteins were significantly higher in clear cell RCC (ccRCC) than in non-ccRCC. Cytoplasmic HIF-3α expression was also higher in ccRCC than in non-ccRCC, whereas cytoplasmic HIF-1α and HIF-2α expression levels were similar between the different RCC types. In ccRCC, nuclear HIF-1α expression levels correlated with both nuclear HIF-2α and HIF-3α levels, whereas cytoplasmic HIF-3α expression levels were associated with HIF-1α only.In non-ccRCC, there was a positive correlation observed between nuclear HIF-1α and HIF-3α expression, but no correlation was found with HIF-2α. In patients with ccRCC, the nuclear expressions of HIF-1α and HIF-3α was significantly associated with cancer-specific survival (CSS) in univariate analysis. This association was no longer evident in multivariate analysis. Notably, there was no correlation observed between nuclear HIF-2α expression and CSS in these patients. In contrast, cytoplasmic expression levels showed no association with CSS.

Conclusion: The expression levels of the three primary HIF-α proteins were found to be higher in the nucleus than in the cytoplasm. Furthermore, the results indicated that HIF-3α and HIF-1α expression levels were significant univariate factors associated with CSS in patients with clear cell RCC. These results highlight the critical role that HIF-3α and HIF-1α play in the hypoxia pathway.

Place, publisher, year, edition, pages
Uppsala Medical Society, 2024
Keywords
renal cell carcinoma, ccRCC, non-ccRCC, HIF-1α, HIF-2α, HIF-3α, prognosis, tumor stage
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-223493 (URN)10.48101/ujms.v129.9407 (DOI)38571885 (PubMedID)2-s2.0-85190074794 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP19-976Lions Cancerforskningsfond i Norr, AMP20-1009
Available from: 2024-04-23 Created: 2024-04-23 Last updated: 2024-04-23Bibliographically approved
Iisager, L., Ahrenfeldt, J., Donskov, F., Ljungberg, B., Bex, A., Lund, L., . . . Fristrup, N. (2024). Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial. BMC Cancer, 24(1), Article ID 260.
Open this publication in new window or tab >>Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial
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2024 (English)In: BMC Cancer, E-ISSN 1471-2407, Vol. 24, no 1, article id 260Article in journal (Refereed) Published
Abstract [en]

Background: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment.

Methods/design: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis.

Discussion: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management.

Trial registration: ClinicalTrials.gov NCT03977571 June 6, 2019.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Biomarkers, Deferred cytoreductive nephrectomy, Immunotherapy, Synchronous metastatic renal cell carcinoma, Translational research
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-221845 (URN)10.1186/s12885-024-11987-3 (DOI)38402173 (PubMedID)2-s2.0-85186231542 (Scopus ID)
Available from: 2024-03-12 Created: 2024-03-12 Last updated: 2024-03-12Bibliographically approved
Capitanio, U., Bedke, J., Albiges, L., Volpe, A., Giles, R. H., Hora, M., . . . Bex, A. (2023). A renewal of the tnm staging system for patients with renal cancer to comply with current decision-making: Proposal from the European Association of Urology guidelines panel. European Urology, 83(1), 3-5
Open this publication in new window or tab >>A renewal of the tnm staging system for patients with renal cancer to comply with current decision-making: Proposal from the European Association of Urology guidelines panel
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2023 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 83, no 1, p. 3-5Article in journal (Refereed) Published
Abstract [en]

Risk classification for patients with renal cell carcinoma (RCC) is critical for clinical decision-making and ultimately for patient outcomes [1]. Staging is the single most informative piece of information for risk assessment in patients with cancer. Currently, the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM scheme is the most universally accepted staging system [2]. Since its first publication in 1977, the UICC/AJCC TNM staging system has changed while still retaining its characteristics of simplicity, reproducibility, and user-friendliness.

Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-202688 (URN)10.1016/j.eururo.2022.09.026 (DOI)36253306 (PubMedID)2-s2.0-85143732083 (Scopus ID)
Available from: 2023-01-12 Created: 2023-01-12 Last updated: 2024-02-01Bibliographically approved
Boot, I. W. .., Wesselius, A., Yu, E. Y. .., White, E., Brustad, M., Marques, C., . . . Zeegers, M. P. (2023). Dietary vitamin D intake and the bladder cancer risk: a pooled analysis of prospective cohort studies. Clinical Nutrition, 42(8), 1462-1474
Open this publication in new window or tab >>Dietary vitamin D intake and the bladder cancer risk: a pooled analysis of prospective cohort studies
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2023 (English)In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 42, no 8, p. 1462-1474Article in journal (Refereed) Published
Abstract [en]

Background & aims: Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk.

Methods: Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose–response relationships (Model 1) were examined using a nonparametric test for trend.

Results: In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HRhigh vitD, mod Ca, low P: 0.77, 95% CI: 0.59–1.00). No significant dose–response analyses were observed.

Conclusion: The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Bladder cancer, Calcium, Nutritional oncology, Phosphorus, Pooled cohort analysis, Vitamin D
National Category
Nutrition and Dietetics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-211136 (URN)10.1016/j.clnu.2023.05.010 (DOI)37321901 (PubMedID)2-s2.0-85162168198 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, FP7-PEOPLE-618308Swedish Cancer SocietyRegion Skåne
Available from: 2023-07-04 Created: 2023-07-04 Last updated: 2024-01-15Bibliographically approved
Hora, M., Albiges, L., Bedke, J., Campi, R., Capitanio, U., Giles, R. H., . . . Trpkov, K. (2023). European association of urology guidelines panel on renal cell carcinoma update on the new world health organization classification of kidney tumours 2022: the urologist's point of view. European Urology, 83(2), 97-100
Open this publication in new window or tab >>European association of urology guidelines panel on renal cell carcinoma update on the new world health organization classification of kidney tumours 2022: the urologist's point of view
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2023 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 83, no 2, p. 97-100Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-201470 (URN)10.1016/j.eururo.2022.11.001 (DOI)000982566400001 ()36435661 (PubMedID)2-s2.0-85142695711 (Scopus ID)
Available from: 2022-12-06 Created: 2022-12-06 Last updated: 2024-02-01Bibliographically approved
de Alwis, R., Schoch, S., Islam, M., Möller, C., Ljungberg, B. & Axelson, H. (2023). Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma. The journal of pathology. Clinical research, 9(4), 261-272
Open this publication in new window or tab >>Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma
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2023 (English)In: The journal of pathology. Clinical research, ISSN 2056-4538, Vol. 9, no 4, p. 261-272Article in journal (Refereed) Published
Abstract [en]

Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression and malignancy, as a blueprint. Through transcriptomic analyses, we show that the nuclear factor I A (NFIA)-driven transcription network is active in primary RCC and that higher levels of NFIA confer a survival benefit. We validate our findings using immunohistochemical staining and analysis of a 363-patient tissue microarray (TMA), showing for the first time that NFIA can independently predict poor cancer-specific survival in clear cell RCC (ccRCC) patients (hazard ratio = 0.46, 95% CI = 0.24–0.85, p value = 0.014). Furthermore, we confirm the association of HNF4A with higher grades and stages in ccRCC in our TMA cohort. We present novel data that show HNF4A protein expression does not confer favourable prognosis in papillary RCC, confirming our survival analysis with publicly available HNF4A RNA expression data. Further work is required to elucidate the functional role of NFIA in RCC as well as the testing of these markers on patient material from diverse multi-centre cohorts, to establish their value for the prognostication of RCC.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
biomarker, cancer-specific survival, immunohistochemistry, renal cell carcinoma
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-206374 (URN)10.1002/cjp2.316 (DOI)000951105100001 ()36947439 (PubMedID)2-s2.0-85150875044 (Scopus ID)
Funder
Swedish Cancer Society, CAN2018/1153
Available from: 2023-04-04 Created: 2023-04-04 Last updated: 2024-02-01Bibliographically approved
Marconi, L., Kuusk, T., Capitanio, U., Beisland, C., Lam, T., Pello, S. F., . . . Bex, A. (2023). Local treatment of recurrent renal cell carcinoma may have a significant survival effect across all risk-of-recurrence groups. European Urology Open Science, 47, 65-72
Open this publication in new window or tab >>Local treatment of recurrent renal cell carcinoma may have a significant survival effect across all risk-of-recurrence groups
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2023 (English)In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 47, p. 65-72Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias.

OBJECTIVE: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence.

DESIGN SETTING AND PARTICIPANTS: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively.

INTERVENTION: Local treatment of recurrence.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups.

RESULTS AND LIMITATIONS: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.8), respectively. Limitations include retrospective design.

CONCLUSIONS: This is the first study assessing the effectiveness of LTR in RCC in a comparable population with RD. This study supports the role of LTR across all RoR groups.

PATIENT SUMMARY: We assessed the effectiveness of local treatment of resectable recurrent renal cell carcinoma after surgical treatment of the primary kidney tumour. Local treatment of recurrence was associated with longer survival across groups with a risk of recurrence.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Metastasectomy, Metastatic, Radiotherapy, Renal cell cancer, Stereotactic body radiotherapy, Surgery, Systemic therapy
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-202681 (URN)10.1016/j.euros.2022.11.008 (DOI)000976143000001 ()36601038 (PubMedID)2-s2.0-85143648585 (Scopus ID)
Available from: 2023-01-12 Created: 2023-01-12 Last updated: 2024-02-01Bibliographically approved
Almdalal, T., Karlsson Rosenblad, A., Hellström, M., Kjellman, A., Lindblad, P., Lundstam, S., . . . Ljungberg, B. (2023). Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma: results from the National Swedish Kidney Cancer Register. Scandinavian journal of urology, 57(1-6), 67-74
Open this publication in new window or tab >>Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma: results from the National Swedish Kidney Cancer Register
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2023 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 57, no 1-6, p. 67-74Article in journal (Refereed) Published
Abstract [en]

Objective: Patients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort.

Materials and methods: A total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models.

Results: Age, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69–5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44–0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71–0.95, p < 0.001) than patients treated with radical nephrectomy.

Conclusions: Age, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2023
Keywords
cryoablation, overall survival, partial nephrectomy, Radical nephrectomy, radiofrequency ablation, RCC type, renal cell carcinoma, T-stage, TNM stage, tumor recurrence, tumor size
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-202009 (URN)10.1080/21681805.2022.2154383 (DOI)000897992900001 ()36520023 (PubMedID)2-s2.0-85144116341 (Scopus ID)
Available from: 2022-12-29 Created: 2022-12-29 Last updated: 2024-02-01Bibliographically approved
Åkerlund, J., Sundqvist, P., Ljungberg, B., Lundstam, S., Peeker, R., Månsson, M. & Grenabo Bergdahl, A. (2023). Predictors for complication in renal cancer surgery: a national register study. Scandinavian journal of urology, 58, 38-45
Open this publication in new window or tab >>Predictors for complication in renal cancer surgery: a national register study
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2023 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 58, p. 38-45Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Nationwide register data provide unique opportunities for real-world assessment of complications from different surgical methods. This study aimed to assess incidence of, and predictors for, post-operative complications and to evaluate 90-day mortality  following different surgical procedures and thermal ablation for renal cell carcinoma (RCC).

MATERIAL AND METHODS: All patients undergoing surgical treatment and thermal ablation for RCC in Sweden during 2015-2019 were identified from the National Swedish Kidney Cancer Register. Frequencies and types of post-operative complications were analysed. Logistic regression models were used to identify predictors for 90-day major (Clavien-Dindo grades III-V) complications, including death.

RESULTS: The overall complication rate was 24% (1295/5505), of which 495 (8.7%) were major complications. Most complications occurred following open surgery, of which bleeding and infection were the most common. Twice as many complications were observed in patients undergoing open surgery compared to minimally invasive surgery (20% vs. 10%, P < 0.001). Statistically significant predictors for major complications irrespective of surgical category and technique were American society of anesthiologists (ASA) score, tumour diameter and serum creatinine. Separating radical and partial nephrectomy, surgical technique remained a significant risk factor for major complications. Most complications occurred within the first 20 days. The overall 90-day readmission rate was 6.2%, and 30- and 90-day mortality rates were 0.47% and 1.5%, respectively.

CONCLUSIONS: In conclusion, bleeding and infection were the most common major complications after RCC surgery. Twice as many patients undergoing open surgery suffer a major post-operative complication as compared to patients subjected to minimally invasive surgery. General predictors for major complications were ASA score, tumour size, kidney function and surgical technique.

Place, publisher, year, edition, pages
Medical Journals Sweden, 2023
National Category
Urology and Nephrology Surgery
Identifiers
urn:nbn:se:umu:diva-214059 (URN)10.2340/sju.v58.12356 (DOI)37605443 (PubMedID)2-s2.0-85168450636 (Scopus ID)
Funder
Anna-Lisa and Bror Björnsson Foundation
Available from: 2023-09-06 Created: 2023-09-06 Last updated: 2024-02-01Bibliographically approved
Capitanio, U., Bedke, J., Albiges, L., Volpe, A., Giles, R. H., Hora, M., . . . Bex, A. (2023). Reply to Yaxiong Tang, Xu Hu, Kan Wu, Yanxiang Shao, and Xiang Li’s Letter to the Editor re: Umberto Capitanio, Jens Bedke, Laurence Albiges, et al. A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel. Eur Urol. 2022;83:3–5 [Letter to the editor]. European Urology, 83(3), e74-e75
Open this publication in new window or tab >>Reply to Yaxiong Tang, Xu Hu, Kan Wu, Yanxiang Shao, and Xiang Li’s Letter to the Editor re: Umberto Capitanio, Jens Bedke, Laurence Albiges, et al. A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel. Eur Urol. 2022;83:3–5
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2023 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 83, no 3, p. e74-e75Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-202684 (URN)10.1016/j.eururo.2022.12.001 (DOI)000948090500001 ()36526491 (PubMedID)2-s2.0-85147814507 (Scopus ID)
Available from: 2023-01-12 Created: 2023-01-12 Last updated: 2024-02-01Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-4121-3753

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