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  • 1.
    Holmberg, Lars
    et al.
    Uppsala Univ, Sweden; Kings Coll London, England.
    Skogmar, Sten
    Lund Univ, Sweden.
    Garmo, Hans
    Uppsala Univ, Sweden; Kings Coll London, England.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Hosseini, Abolfazl
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Ullen, Anders
    Karolinska Inst, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Liedberg, Fredrik
    Lund Univ, Sweden; Skane Univ Hosp, Sweden; Lund Univ, Sweden; Lund Univ, Sweden.
    Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations2024Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectivesTo investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guerin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC).Patients and MethodsWe analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs.ResultsThe cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk.ConclusionsThese data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

  • 2.
    Saudi, A.
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Takhar, P.
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Ochoa-Figueroa, Miguel
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Fysiologiska kliniken US. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    99mTc-MIP-1404 CZT SPECT/CT versus 68Ga/PSMA-11 PET/CT: Imaging of prostate cancer metastasis2023Ingår i: Revista Española de Medicina Nuclear e Imagen Molecular (English Edition), ISSN 2253-8089, Vol. 42, nr 6, s. 413-415Artikel i tidskrift (Refereegranskat)
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  • 3.
    Jahnson, Staffan
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jancke, Georg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Olsson, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Bladder cancer grading using the four-tier combination of the World Health Organization (WHO) 1973 and WHO 2004 classifications2023Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 132, nr 6, s. 656-663Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectiveTo investigate the impact of grading in urothelial bladder cancer (UBC) stages Ta and T1, comparing the World Health Organization (WHO) grading classifications of 1973 (WHO73) and 2004 (WHO04) and a combination of these (WHO73/04).Patients and MethodsAll patients with primary Ta and T1 UBC in the ostergotland region, Sweden, between 1992 and 2007 were included. From 1992, we introduced a new programme for management and follow-up of UBC, including prospectively performed registration of all patients, a systematic description of the location and size of all tumours, primary resection and intravesical treatment in the case of recurrence. All tumour specimens were retrospectively reviewed in 2008 and graded according to the WHO73 and WHO04. A combination of WHO73/04, Grade 1 (G1), Grade 2 low grade (G2LG), Grade 2 high grade (G2HG) and Grade 3 (G3) was analysed in relation to clinical variables and outcomes.ResultsThere were 769 patients with a median age of 72 years and a median follow-up duration of 74 months. Recurrence was noted in 484 patients (63%) and progression in 80 patients (10%). Recurrence was more common in multiple tumours, larger tumours and in tumours of higher grade (G2LG, G2HG and G3). Progression was more common in tumours classified as larger, T1 and G2HG and G3. Notably, in tumours classified as G2HG, recurrence and progression were more common than in the G2LG group. Harrells concordance index for the WHO73/04 was higher for recurrence and progression than in the WHO73 or WHO04.ConclusionIn the four-tier combined WHO73/04 for urothelial cancer, we observed two G2 sub-groups, G2HG and G2LG. There was a better outcome in the latter group, and the importance of G1 and G3 tumours could be fully evaluated. The WHO73/04 had greater accuracy for recurrence and progression than either the WHO73 or WHO04.

  • 4.
    Lind, Anna Karin
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Bläckberg, Mats
    Department of Urology, Helsingborg County Hospital, Helsingborg, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Hosseini, Abofazl
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Stenzelius, Karin
    Malmö University, Department of Care Science, Faculty of Health and Society, Malmö, Sweden.
    Health-related quality of life prior to and 1 year after radical cystectomy evaluated with FACT-G and FACT-VCI questionnaires2023Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 58, s. 76-83Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate health-related quality of life (HRQoL) before and 1 year after radical cystectomy in relation to age and gender. METHODS: This prospective study involves 112 men and 40 women with bladder cancer treated with radical cystectomy between 2015 and 2018. HRQoL was assessed preoperatively and 1 year post-surgery through Functional Assessment of Cancer Therapy Scale - General (FACT-G) and Functional Assessment of Cancer Therapy Scale - Vanderbilt Cystectomy Index (FACT-VCI) questionnaires. The median age of the 152 patients was 71.5 years. RESULTS: Preoperatively, emotional and functional well-being were negatively affected. Physical, emotional and functional well-being presented higher values 1 year after surgery compared to before radical cystectomy, that is, better HRQoL. Social well-being showed a reduction, especially regarding closeness to partner and support from family. Men and women were equally satisfied with their sex life before radical cystectomy, but less so 1 year after, where men were less satisfied compared to women. Additionally, one out of five patients reported that they had to limit their physical activities, were afraid of being far from a toilet and were dissatisfied with their body appearance after surgery. CONCLUSIONS: Recovery regarding HRQoL was ongoing 1 year after radical cystectomy. Patients recovered in three out of four dimensions of HRQoL, but social well-being was still negatively affected 1 year after treatment. Sexual function after radical cystectomy was exceedingly limited for both men and women. An individual sexual rehabilitation plan involving the couple with special intention to encourage intimacy, might not only improve sexual life but also have a positive effect on social well-being as a consequence.

  • 5.
    Saudi, Aws
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Banday, Viqar
    Umea Univ, Sweden; Umea Univ, Sweden.
    Zirakzadeh, A. Ali
    Immuneed AB, Sweden.
    Selinger, Martin
    Lab Mol Infect Med Sweden MIMS, Sweden; Umea Univ, Sweden.
    Forsberg, Jon
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Holmbom, Martin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Henriksson, Johan
    Lab Mol Infect Med Sweden MIMS, Sweden; Umea Univ, Sweden.
    Walden, Mauritz
    Cent Hosp Karlstad, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Winqvist, Ola
    ABClabs, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Immune-Activated B Cells Are Dominant in Prostate Cancer2023Ingår i: Cancers, ISSN 2072-6694, Vol. 15, nr 3, artikel-id 920Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Simple Summary Contrary to the common belief that prostate cancer is an immune desert, our study shows tumor-associated B-cell responses in prostate cancer. We demonstrate mature and activated phenotypes of B cells with an increased frequency of effector plasmablasts in tumor-draining sentinel lymph nodes. These findings indicate a B-cell-specific antitumor immune response, emphasizing the importance of further trials targeting B cells in prostate cancer immunotherapy. B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19(+) B-cell compartment was significantly decreased in PCa patients and dominated by naive B cells. The nodal B-cell compartment had significantly increased fractions of CD19(+) B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.

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  • 6.
    Liedberg, Fredrik
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Hosseini, Abolfazl
    Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Ullen, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Bobjer, Johannes
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma: A population-based study2023Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 18, nr 2, artikel-id e0281304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundIntravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes. MethodsWe investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015-2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models. ResultsThe study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis. ConclusionsWorse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.

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  • 7.
    Bergengren, Oskar
    et al.
    Uppsala Univ, Sweden.
    Belozerov, Alexej
    Uppsala Univ, Sweden.
    Bill-Axelson, Anna
    Uppsala Univ, Sweden.
    Garmo, Hans
    Uppsala Univ Hosp, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Souroderkvist, Karin
    Umea Univ, Sweden.
    Ullen, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Liedberg, Fredrik
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study2023Ingår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 49, nr 4, s. 868-874Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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  • 8.
    Aljabery, Firas
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Shabo, Ivan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Saudi, Aus
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Holmbom, Martin
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Olson, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Jahnson, Staffan
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer2023Ingår i: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 41, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy. Methods: Tumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients and tumor characteristics and outcome. Results: Out of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors. Conclusions: In the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC. (c) 2022 Published by Elsevier Inc.

  • 9.
    Hagersten, Emma Schulz
    et al.
    Umea Univ, Sweden.
    Ottosson, Kristoffer
    Umea Univ, Sweden.
    Pelander, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Johansson, Markus
    Umea Univ, Sweden; Sundsvall Harnosand Hosp, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Svensson, Johan
    Umea Univ, Sweden.
    Styrke, Johan
    Umea Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    The Risk of Thromboembolism in Patients with Muscle Invasive Bladder Cancer before and after Cystectomy Depending on Blood Group and Neoadjuvant Chemotherapy-A Multicentre Retrospective Cohort Study2023Ingår i: Journal of Personalized Medicine, E-ISSN 2075-4426, Vol. 13, nr 9, artikel-id 1355Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Previous studies have indicated that patients with muscle-invasive bladder cancer with non-O blood types have an increased risk of experiencing thromboembolic events (TEEs). This is finding is in relation to neoadjuvant-chemotherapy (NAC)-naive patients. Aim: to establish the risk of TEEs and any association with blood types among NAC patients as well as NAC-naive patients. Methods: Cystectomized patients at four centres treated from 2009 to 2018 (n = 244) were analysed. The quantities of patients corresponding to each blood group were as follows: A-108 (44%); O-99 (41%); B-30 (12%); and AB-7 (3%). NAC patients (n = 167) and NAC-naive NAC-eligible patients (n = 77) were assessed. In total, 54 women (22%) and 190 men (78%), with a median age of 69 years, were included in the study. The occurrence of any type of TEE from six months pre-cystectomy to 12-24 months after was analysed using logistic regression adjusted for NAC and confounders. Results: Sixty-six TEEs were detected in 21% of the patients (n = 52). Pulmonary embolus (n = 33) and deep venous thrombosis (n = 11) were the most common forms. No significant differences between blood types were found in the analysis, although B blood type had a nearly significant increased crude risk compared with O blood type, for which there was an OR of 2.48 (95% CI 0.98-6.36). Adjustment for NAC and covariates weakened the OR, which plummeted to 1.98 (95% CI 0.71-5.51). Conclusions: No significant associations were found between blood types and TEE occurrences in this cohort including both NAC and NAC-naive NAC-eligible patients.

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  • 10.
    Asad, Danna
    et al.
    Umea Univ, Sweden.
    Styrke, Johan
    Umea Univ, Sweden.
    Hagsheno, Mohammad
    Uppsala Univ, Sweden.
    Johansson, Markus
    Umea Univ, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Svensson, Johan
    Umea Univ, Sweden.
    Pelander, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Lauer, Jan
    Nykoping Cty Hosp, Sweden.
    Netterling, Hans
    Umea Univ, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Sherif, Amir
    Umea Univ, Sweden.
    A prospective multicenter study of visual response-evaluation by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 1, s. 20-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose To evaluate a method of transurethral visual response-staging in patients with urothelial muscle-invasive urinary bladder cancer (MIBC), undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Methods A prospective study at four Swedish cystectomy centers, cystoscopy was performed after final NAC-cycle for MIBC. Fifty-six participants underwent cystoscopy for visual staging of the tumor immediately pre-RC. Visual assessments were correlated to pathoanatomical outcomes post-RC. Results Seventeen tumors were classified as complete response (CR), i.e. pT0. Twenty-five patients had residual MIBC and 14 had non-muscle invasive residual tumors (NMIBC). Of the 39 patients with residual tumor, 25 were correctly identified visually (64%). Eleven patients were pN+. The diagnostic accuracy of cystoscopy to correctly identify complete response or remaining tumor was 70% (CI = 56-81%) with a sensitivity of 64% (CI = 47-79%), specificity 82% (CI = 57-96%), PPV 89% (CI = 74-96%) and NPV 50% (CI =38-61%). Twenty-eight cystoscopy evaluations showed signs of residual tumors and 3/28 (11%) were false positive. In 4/14 patients assessed having residual NMIBC the estimates were correct, 8/14 had histopathological MIBC and 2/14 had CR. In 11/14 patients (79%), the suggested visual assessment of MIBC was correct, 2/14 had NMIBC and 1/14 had CR. Twenty-eight cystoscopies had negative findings, 14 were false negatives (50%), when cystoscopy falsely predicted pT0. Among them there were eight patients with pTa, pT1 or pTis and six MIBC-tumors. In 17 patients with histopathological pT0, 14 were correctly identified with cystoscopy (82%). Conclusion Cystoscopy after the final NAC-cycle cannot robustly differentiate between NAC-responders and non-responders. Visually, negative MIBC-status cannot be determined safely.

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  • 11.
    Eriksson, Victoria
    et al.
    Umea Univ, Sweden.
    Holmkvist, Oscar
    Umea Univ, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Johansson, Markus
    Sundsvall Harnosand Cty Hosp, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Svensson, Johan
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Sherif, Amir
    Umea Univ, Sweden.
    A Retrospective Analysis of the De Ritis Ratio in Muscle Invasive Bladder Cancer, with Focus on Tumor Response and Long-Term Survival in Patients Receiving Neoadjuvant Chemotherapy and in Chemo Naïve Cystectomy Patients - A Study of a Clinical Multicentre Database2022Ingår i: Journal of Personalized Medicine, E-ISSN 2075-4426, Vol. 12, nr 11, artikel-id 1769Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A high pre-treatment De Ritis ratio, the aspartate transaminase/alanine aminotransferase ratio, has been suggested to be of prognostic value for mortality in muscle-invasive bladder cancer (MIBC). Our purpose was to evaluate if a high ratio was associated with mortality and downstaging. Methods: A total of 347 Swedish patients with clinically staged T2-T4aNOMO, with administered neoadjuvant chemotherapy (NAC) or eligible for NAC and undergoing radical cystectomy (RC) 2009-2021, were retrospectively evaluated with a low ratio < 1.3 vs. high ratio > 1.3, by Log Rank test, Cox regression and Mann-Whitney U-test (MWU), SPSS 27. Results: Patients with a high ratio had a decrease of up to 3 years in disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) (p = 0.009, p = 0.004 and p = 0.009) and 5 years in CSS and OS (p = 0.019 and p = 0.046). A high ratio was associated with increased risk of mortality, highest in DFS (HR, 1.909; 95% CI, 1.265-2.880; p = 0.002). No significant relationship between downstaging and a high ratio existed (p = 0.564 MWU). Conclusion: A high pre-treatment De Ritis ratio is on a population level, associated with increased mortality post-RC in endpoints DFS, CSS and OS. Associations decrease over time and require further investigations to determine how strong the associations are as meaningful prognostic markers for long-term mortality in MIBC. The ratio is not suitable for downstaging-prediction.

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  • 12.
    Eriksson, Victoria
    et al.
    Umea Univ, Sweden.
    Holmlund, Jennie
    Umea Univ, Sweden.
    Wiberg, Erik
    Umea Univ, Sweden.
    Johansson, Markus
    Umea Univ, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Svensson, Johan
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Sherif, Amir
    Umea Univ, Sweden; Umea Univ, Sweden.
    Adverse events during neoadjuvant chemotherapy for muscle invasive bladder cancer - a Swedish retrospective multicentre study of a clinical database2022Ingår i: Translational Andrology and Urology, ISSN 2223-4683, Vol. 11, nr 8, s. 1105-1115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Adverse events (AEs) during neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC) are known but insufficiently reported. Clinical implications include affected cardiac, pulmonary, urinary, vascular and haematological organ systems. The main purpose was to evaluate the incidence and severity of AEs for ascertaining possible clinical significance. Further investigating possible effects of AEs on downstaging outcomes-downstaging is considered a surrogate marker for overall survival (OS).Methods: A retrospective evaluation of AEs during ongoing NAC for MIBC patients analysing individual patient data in a clinical database. We identified 687 cystectomies between 2009-2020 at four Swedish urological centres. Inclusion criteria were cT2-4aN0M0 in 261 NAC patients undergoing radical cystectomy (RC). Medical files were reviewed and AEs were assessed and graded, including detailed measurements by the Common Terminology Criteria for Adverse Events (CTCAE) v.5. Data were retrospectively analysed in SPSS statistics 27.0 with Spearman rank-order correlation coefficient and Mann-Whitney U-test (MWU).Results: A total of 251/261 patients [95% confidence interval (CI), 93-98%] experienced AEs during NAC pre-RC (mean two AEs/patient). In total, 208 (80%) patients received methotrexate, vinblastine, adriamycin (doxorubicin) and cisplatin (MVAC). In the total cohort, 200 (76.6%) received all pre-planned NAC-cycles. Most common AEs were anaemia (88.9%), thrombocytopenia (44.8%) and acute kidney injury (40.6%). Patients with prematurely terminated cycles had higher AE-grades (P=0.042 MWU). A correlation between higher AE-grades and decrease in downstaging existed, in the entire cohort (-0.133; P=0.033) and in patients undergoing all pre-planned NAC-cycles (-0.148; P=0.038). Anaemia and acute kidney injury were individually associated with decreased downstaging (-0.360, P=0.025 and -0.183, P=0.010, respectively).Conclusion: NAC in MIBC poses a significant risk for AEs before RC with clinical implications. For instance, patients terminating chemotherapy prematurely, have higher AE-grades and decreased downstaging. Further, acute kidney injury and anaemia are individually associated with decreased downstaging. We propose that early detection and prevention of AEs may increase downstaging of the primary tumour.

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  • 13.
    Bobjer, Johannes
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Simoulis, Athanasious
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 1, s. 14-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories. Patients and methods In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004-2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region). Results At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2-2.0) at 5-year follow-up, while progression events were too few to compare. Conclusions The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.

  • 14.
    Rydell, Harriet
    et al.
    Umea Univ, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Eriksson, Victoria
    Umea Univ, Sweden.
    Johansson, Markus
    Umea Univ, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Svensson, Johan
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Sherif, Amir
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Umea Univ, Sweden.
    Central Venous Access and the Risk for Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer2022Ingår i: Life, E-ISSN 2075-1729, Vol. 12, nr 8, artikel-id 1198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Thromboembolic events (TEE) are high-risk complications in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for urothelial muscle-invasive bladder cancer (MIBC). The purpose of the study was to investigate any differences in TEE-incidence, comparing peripherally inserted central catheter (PICC) versus a totally implanted port (PORT) as CVA (central venous access) during NAC. We identified 947 cystectomized MIBC-patients from four Swedish medical centers in 2009-2021. Inclusion criteria were cT2-T4aN0M0 and 375 patients were finally eligible and evaluated, divided into: NAC-administered (n = 283) resp. NAC-naive-NAC-eligible (n = 92), the latter as tentative control group. Data on TEEs and types of CVA were retrospectively collected and individually validated, from final transurethral resection of the bladder tumor (TUR-B) to 30 days post-RC. Adjusted logistic regression and log rank test were used for statistical analyses. Amongst NAC-administered, 83% (n = 235) received PICCs and 15% (n = 42) PORTs. Preoperative TEEs occurred in 38 PICC-patients (16.2%) and in one PORT-patient (2.4%), with 47 individual events registered. We found a significantly increased odds ratio of TEE in NAC-administered PICC-patients compared to in PORT-patients (OR: 8.140, p-value: 0.042, 95% CI 1.078-61.455). Our findings indicate a greater risk for pre-RC TEEs with PICCs than with PORTs, suggesting favoring the usage of PORTs for MIBC-NAC-patients.

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  • 15.
    Häggstrom, Christel
    et al.
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Ullen, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Liedberg, Fredrik
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Cohort profile: Bladder Cancer Data Base Sweden (BladderBaSe) 2.02022Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 12, nr 12, artikel-id e064898Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PurposeWe constructed Bladder Cancer Data Base Sweden (BladderBaSe) 2.0 to expand studies in BladderBaSe on incidence, treatment outcomes, side effects, survival and health economic aspects of men and women with cancer in the urinary bladder, upper tract urothelial carcinoma (UTUC) (renal pelvis and ureter) and urethral carcinoma.ParticipantsBladderBaSe 2.0 includes 53 298 patients with cancer in the urinary bladder, diagnosed from 1 January 1997 to 31 December 2019, and 961 patients with UTUC in the renal pelvis and 792 in the ureter, and 146 patients with urethral urothelial carcinoma, diagnosed from 1 January 2015 to 31 December 2019, and in total 275 816 participants in reference groups, free of cancer in the urinary tract, matched 1:5 on sex, age and county.Findings to dateTo date, 18 published studies based on data from the BladderBaSe have investigated calendar time trends in survival; impact of gender, socioeconomic factors, tumour aggressiveness and hospital volume for radical cystectomy on prognosis; survival after radical cystectomy compared with radical radiotherapy; risk factors for complications and side effects after radical cystectomy such as thromboembolism, strictures of ureteroenterostomies and incisional hernia.Future plansThe BladderBaSe initiators are currently investigating gender-dependent detection delays due to urinary tract infections; survival after non-muscle invasive bladder cancer with respect to the number of transurethral resections; short-term outcomes comparing open and robot-assisted radical cystectomy; studies on risk for intravesical recurrence after different diagnostic measures in UTUC, and suicide risk after bladder cancer diagnosis. The BladderBaSe project group is open for collaborations with national and international colleagues.

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  • 16.
    Holmbom, Martin
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Andersson, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Infektionskliniken i Östergötland.
    Grabe, Magnus
    Lund Univ, Sweden.
    Peeker, Ralph
    Univ Gothenburg, Sweden.
    Saudi, Aus
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Styrke, Johan
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Community-onset urosepsis: incidence and risk factors for 30-day mortality - a retrospective cohort study2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 5-6, s. 414-420Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Urosepsis is a life-threatening condition that needs to be addressed without delay. Two critical issues in its management are: (1) Appropriate empirical antibiotic therapy, considering the patients general condition, comorbidity, and the pathogen expected; and (2) Timing of imaging to identify obstruction requiring decompression. Objectives To identify risk factors associated with 30-day mortality in patients with urosepsis. Methods From a cohort of 1,605 community-onset bloodstream infections (CO-BSI), 282 patients with urosepsis were identified in a Swedish county 2019-2020. Risk factors for mortality with crude and adjusted odds ratios were analysed using logistic regression. Results Urosepsis was found in 18% (n = 282) of all CO-BSIs. The 30-day all-cause mortality was 14% (n = 38). After multivariable analysis, radiologically detected urinary tract disorder was the predominant risk factor for mortality (OR = 4.63, 95% CI = 1.47-14.56), followed by microbiologically inappropriate empirical antibiotic therapy (OR = 4.19, 95% CI = 1.41-12.48). Time to radiological diagnosis and decompression of obstruction for source control were also important prognostic factors for survival. Interestingly, 15% of blood cultures showed gram-positive species associated with a high 30-day mortality rate of 33%. Conclusion The 30-day all-cause mortality from urosepsis was 14%. The two main risk factors for mortality were hydronephrosis caused by obstructive stone in the ureter and inappropriate empirical antibiotic therapy. Therefore, early detection of any urinary tract disorder by imaging followed by source control as required, and antibiotic coverage of both gram-negative pathogens and gram-positive species such as E. faecalis to optimise management, is likely to improve survival in patients with urosepsis.

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  • 17.
    Abuhasanein, Suleiman
    et al.
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gårdmark, Truls
    Karolinska Inst, Sweden.
    Jerlström, Tomas
    Örebro Univ, Sweden.
    Liedberg, Fredrik
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Sherif, Amir
    Umeå Univ, Sweden.
    Ströck, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Do not throw out the baby with the bath water2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 3, s. 235-236Artikel i tidskrift (Övrigt vetenskapligt)
  • 18.
    Holmberg, Lars
    et al.
    Uppsala Univ, Sweden; Kings Coll London, England.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Enlund, Mats
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Liedberg, Fredrik
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer2022Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 17, nr 9, artikel-id e0274859Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer. Aim We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample. Methods We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years. Results Overall survival and survival from causes other than bladder cancer estimated with Kaplan-Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up. Conclusion The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding.

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  • 19.
    Russell, Beth
    et al.
    Kings Coll London, England.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Holmberg, Lars
    Kings Coll London, England; Uppsala Univ, Sweden.
    Bryan, Richard T.
    Univ Birmingham, England.
    Enting, Deborah
    Guys St Thomas NHS Fdn Trust, England.
    Van Hemelrijck, Mieke
    Kings Coll London, England.
    Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 1, s. 27-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction and objectives Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged Materials and methods The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study. Cox proportional hazard regression models were adjusted for appropriate variables. All analyses were stratified by disease stage (non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Furthermore, we compared the frequency of lower urinary tract infections within 24 months prior to bladder cancer diagnosis by sex and age groups. Results The study included 15,452 newly-diagnosed BC patients (1997-2014); 1,207 (8%) patients were <50 whilst 14,245 (92%) were aged 50-70. Patients aged <50 at diagnosis were at a decreased risk of bladder cancer death (HR = 0.82, 95%CI: 0.68-0.99) compared to those aged 50-70. When stratified by non-muscle-invasive and muscle-invasive bladder cancer, this association remained in non-muscle-invasive patients only (<50, HR = 0.43, 95% CI: 0.28-0.64). The frequency of lower urinary tract infection diagnoses did not differ between younger and older patients in either men or women. Conclusions Patients diagnosed with non-muscle-invasive bladder cancer when aged <50 are at decreased risk of bladder cancer-specific death when compared to their older (50-70) counterparts. These observations raise relevant research questions about age-related differences in diagnostic procedures, clinical decision-making and, not least, potential differences in tumour biology.

  • 20.
    Abuhasanein, Suleiman
    et al.
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gårdmark, Truls
    Karolinska Inst, Sweden.
    Jerlström, Tomas
    Orebro Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Ströck, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 3, s. 227-232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives To compare time intervals to diagnosis and treatment, tumor characteristics, and management in patients with primary urinary bladder cancer, diagnosed before and after the implementation of a standardized care pathway (SCP) in Sweden. Materials and methods Data from the Swedish National Register of Urinary Bladder Cancer was studied before (2011-2015) and after (2016-2019) SCP. Data about time from referral to transurethral resection of bladder tumor (TURBT), patients and tumor characteristics, and management were analyzed. Subgroup analyses were performed for cT1 and cT2-4 tumors. Results Out of 26,795 patients, median time to TURBT decreased from 37 to 27 days after the implementation of SCP. While the proportion of cT2-T4 tumors decreased slightly (22-21%, p < 0.001), this change was not stable over time and the proportions cN + and cM1 remained unchanged. In the subgroups with cT1 and cT2-4 tumors, the median time to TURBT decreased and the proportions of patients discussed at a multidisciplinary team conference (MDTC) increased after SCP. In neither of these subgroups was a change in the proportions of cN + and cM1 observed, while treatment according to guidelines increased after SCP in the cT1 group. Conclusion After the implementation of SCP, time from referral to TURBT decreased and the proportion of patients discussed at MDTC increased, although not at the levels recommended by guidelines. Thus, our findings point to the need for measures to increase adherence to SCP recommendations and to guidelines.

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  • 21.
    Liedberg, Fredrik
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Kjellstrom, Sofia
    Skane Univ Hosp, Sweden.
    Lind, Anna-Karin
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Falkman, Karin
    Soder Sjukhuset, Sweden.
    Thulin, Helena
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Papantonio, Dimitrious
    Ryhov Cty Hosp, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Ofverholm, Elisabeth
    Sahlgrens Univ Hosp, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sandzen, Johan
    Karlstad Cty Hosp, Sweden.
    Verbiene, Ingrida
    Uppsala Akad Hosp, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Swedish National Guidelines on Urothelial Carcinoma: 2021 update on non-muscle invasive bladder cancer and upper tract urothelial carcinoma2022Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, nr 2, s. 137-146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To overview the updated Swedish National Guidelines on Urothelial Carcinoma 2021, with emphasis on non-muscle-invasive bladder cancer (NMIBC) and upper tract urothelial carcinoma (UTUC). Methods: A narrative review of the updated version of the Swedish National Guidelines on Urothelial Carcinoma 2021 and highlighting new treatment recommendations, with comparison to the European Association of Urology (EAU) guidelines and current literature. Results: For NMIBC the new EAU 2021 risk group stratification has been introduced for non-muscle invasive bladder cancer to predict risk of progression and the web-based application has been translated to Swedish (https://nmibc.net.). For patients with non-BCG -responsive disease treatment recommendations have been pinpointed, to guide patient counselling in this clinical situation. A new recommendation in the current version of the guidelines is the introduction of four courses of adjuvant platinum-based chemotherapy to patients with advanced disease in the nephroureterectomy specimen (pT2 or higher and/or N+). Patients with papillary urothelial neoplasms with low malignant potential (PUNLMP) can be discharged from follow-up already after 3 years based on a very low subsequent risk of further recurrences. Conclusions: The current version of the Swedish national guidelines introduces a new risk-stratification model and follow-up recommendation for NMIBC and adjuvant chemotherapy after radical surgery for UTUC.

  • 22.
    Jahnson, Staffan
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Olsson, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Telomerase reverse transcriptase mutation and the p53 pathway in T1 urinary bladder cancer2022Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 129, nr 5, s. 601-609Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To study the telomerase reverse transcriptase (TERT) mutation and the p53 pathway in T1 urinary bladder cancer (UBC). Materials and Methods This prospectively performed population-based study included all patients in the Southeast Healthcare Region in Sweden with T1 UBC registered in the period 1992-2001, inclusive. Given that p53 and TERT are important factors for tumour proliferation, although their interrelationships are unknown, we assessed both the TERT and the p53 mutations. Furthermore, we conducted a p53 immunohistochemistry (IHC) analysis using two thresholds for p53 positivity: 10% of tumour cells and 50% of tumour cells (p53 IHC50%). Cox proportional hazards analysis and Kaplan-Meier curves were used to study time to tumour progression. Results Out of 158 patients, we observed the TERT mutation in 74 (47%), the p53 mutation in 48 (30%), and p53 IHC50% positivity in 72 patients (46%). The TERT mutation was more common in p53 mutation-positive patients (P = 0.009), and the latter group also had more patients with p53 IHC50%-positive tumour cells (P = 0.02). In the TERT mutation-negative tumours a p53-positive mutation was associated with a shorter time to progression (P = 0.03) compared to patients with p53-negative mutation. In contrast, in tumours with both TERT mutation positivity and p53 mutation positivity, a longer time to progression was observed in the group with p53 IHC50% positivity compared to the group with p53 IHC50%-negative tumours. Conclusions In stage T1 UBC, the combination of the TERT mutation and the p53 mutation was associated with tumour progression. A protective effect of the TERT promotor mutation against tumour progression induced by the p53 mutation and subsequent p53 accumulation in tumour cells might be possible, but further investigations are necessary.

  • 23.
    Bobjer, Johannes
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    A population-based study on the effect of a routine second-look resection on survival in primary stage T1 bladder cancer2021Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, nr 2, s. 108-115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To assess the value of second-look resection (SLR) in stage T1 bladder cancer (BCa) with respect to progression-free survival (PFS), and also the secondary outcomes recurrence-free survival (RFS), bladder-cancer-specific survival (CSS), and cystectomy-free survival (CFS). Patients and methods The study included 2456 patients diagnosed with stage T1 BCa 2004-2009 with 5-yr follow-up registration in the nationwide Bladder Cancer Data Base Sweden (BladderBaSe). PFS, RFS, CSS, and CFS were evaluated in stage T1 BCa patients with or without routine SLR, using univariate and multivariable Cox regression with adjustment for multiple confounders (age, gender, tumour grade, intravesical treatment, hospital volume, comorbidity, and educational level). Results SLR was performed in 642 (26%) individuals, and more frequently on patients who were aged < 75 yr, had grade 3 tumours, and had less comorbidity. There was no association between SLR and PFS (hazard ratio [HR] 1.1, confidence interval [CI] 0.85-1.3), RFS (HR 1.0, CI 0.90-1.2), CFS (HR 1.2, CI 0.95-1.5) or CSS (HR 1.1, CI 0.89-1.4). Conclusions We found similar survival outcomes in patients with and patients without SLR, but our study is likely affected by selection mechanisms. A randomised study defining the role of SLR in stage T1 BCa would be highly relevant to guide current praxis.

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  • 24.
    Tenninge, S.
    et al.
    Umea Univ, Sweden.
    Mogos, H.
    Umea Univ, Sweden.
    Eriksson, E.
    Umea Univ, Sweden.
    Netterling, H.
    Umea Univ, Sweden.
    Pelander, Sofia
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Johansson, M.
    Umea Univ, Sweden; Sundsvall Hosp, Sweden.
    Alamdari, F.
    Vastmanland Hosp, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Svensson, J.
    Umea Univ, Sweden.
    Styrke, J.
    Umea Univ, Sweden; Sundsvall Hosp, Sweden.
    Sherif, A.
    Umea Univ, Sweden.
    Control computerized tomography in neoadjuvant chemotherapy for muscle invasive urinary bladder cancer, has no value for treatment decisions and low correlation with nodal status2021Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, nr 6, s. 455-460Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Control computerized tomography (cCT) is routinely used in many cystectomy centres before the final treatment cycle in patients with muscle-invasive urinary bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC). This is for evaluating response or nonresponse to NAC treatment. In a real-world retrospective cohort, we intended to evaluate the frequency of changed individual treatment strategies following cCT and to investigate any discrepancies between cCT-results on nodal staging and final pN-stages. Methods We performed a retrospective data-based, multicenter study of 242 MIBC-patients, staged cT2N0M0-cT4aN0M0, having undergone NAC and radical cystectomy (RC) between 2008 and 2019 at four Swedish cystectomy centres. Statistical analysis was performed using IBM SPSS statistics 26. Results Overall, 139/242 patients were examined with cCT. Six patients were staged as progressive at cCT and 5/139 (3.6%) underwent a change of previously planned treatment strategy. 2/6 patients with suspected progression (33%) did not change strategy and underwent all preplanned NAC-cycles plus RC. Only 1/6 patients assigned as progressive at the cCT, showed progression in the postoperative pathology specimen. In total 133/139 patients were considered being without progress on cCT, yet 28/133 (21%) presented with nodal progression at postoperative pathology examinations. Only 1/29 patients with histopathologically verified nodal dissemination were detected with cCT, thus 28/29 (96.6%) with pN + were undetected. The sensitivity for cCT to predict pTNM was 17% CI [0%-64%] and the specificity was 78% CI [71%-86%]. Conclusions CCT prior to the final treatment cycle of NAC in MIBC, leads to a low percentage of treatment strategy changes and cCT cannot accurately predict pN-status.

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  • 25.
    Liedberg, Fredrik
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden; Reg Canc Ctr South, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Montgomery, Agneta
    Lund Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden.
    Haggstrom, Christel
    Umea Univ, Sweden; Uppsala Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Cumulative incidence of midline incisional hernia and its surgical treatment after radical cystectomy and urinary diversion for bladder cancer: A nation-wide population-based study2021Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 16, nr 2, artikel-id e0246703Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective To study the cumulative incidence and surgical treatment of midline incisional hernia (MIH) after cystectomy for bladder cancer. Methods In the nationwide Bladder Cancer Data Base Sweden (BladderBaSe), cystectomy was performed in 5646 individuals. Cumulative incidence MIH and surgery for MIH were investigated in relation to age, gender, comorbidity, previous laparotomy and/or inguinal hernia repair, operative technique, primary/secondary cystectomy, postoperative wound dehiscence, year of surgery, and period-specific mean annual hospital cystectomy volume (PSMAV). Results Three years after cystectomy the cumulative incidence of MIH and surgery for MIH was 8% and 4%, respectively. The cumulative incidence MIH was 12%, 9% and 7% in patients having urinary diversion with continent cutaneous pouch, orthotopic neobladder and ileal conduit. Patients with postoperative wound dehiscence had a higher three-year cumulative incidence MIH (20%) compared to 8% without. The corresponding cumulative incidence surgery for MIH three years after cystectomy was 9%, 6%, and 4% for continent cutaneous, neobladder, and conduit diversion, respectively, and 11% for individuals with postoperative wound dehiscence (vs 4% without). Using multivariable Cox regression, secondary cystectomy (HR 1.3 (1.0-1.7)), continent cutaneous diversion (HR 1.9 (1.1-2.4)), robot-assisted cystectomy (HR 1.8 (1-3.2)), wound dehiscence (HR 3.0 (2.0-4.7)), cystectomy in hospitals with PSMAV 10-25 (HR 1.4 (1.0-1.9)), as well as cystectomy during later years (HRs 2.5-3.1) were all independently associated with increased risk of MIH. Conclusions The cumulative incidence of MIH was 8% three years postoperatively, and increase over time. Avoiding postoperative wound dehiscence after midline closure is important to decrease the risk of MIH.

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  • 26.
    Magnusson, Jenny
    et al.
    Sahlgrens Univ Hosp, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Kjolhede, Henrik
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Cumulative incidence of ureteroenteric strictures after radical cystectomy in a population-based Swedish cohort2021Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, nr 5, s. 361-365Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The incidence of benign ureteroenteric strictures following radical cystectomy (RC) for urinary bladder cancer (UBC) is investigated mainly in single-centre studies from high-volume centres. The aim of this study was to evaluate the cumulative incidence of strictures and risk factors in a population-based cohort. Patients and methods Data was collected from Bladder Cancer Data Base Sweden (BladderBaSe). The primary endpoint was stricture with intervention. Secondary endpoint included hydronephrosis both with/without intervention. Results In total, 5,816 patients were registered as having had RC due to UBC between 1997 and 2014. After a median follow-up of 23.5 months (IQR = 9.0-63.1 months; range = 0.0-214.0 months), we found that 515 (8.9%) patients underwent intervention for stricture. Seven hundred and sixty-one (13.1%) patients were diagnosed with hydronephrosis without intervention. The cumulative incidence of strictures with intervention was 19.7% (95% CI = 16.7-23.1%) during the 17 years of follow-up. In the first year, the cumulative incidence of strictures was 5.6% (95% CI = 5.0-6.2%), and in the first 2 years 8.4% (95% CI = 7.6-9.3%). For the secondary endpoint, the cumulative incidence was 30.4% (95% CI = 26.7-33.1%) after 17 years. Only the year of RC was associated with stricture incidence in Cox regression analysis, whereas hospital cystectomy volume, patient age and patient sex were not. Conclusion Ureteroenteric strictures requiring intervention may be more common than previously reported, affecting nearly one fifth of patients who have undergone RC for UBC. The annual incidence was highest in the first 2 years after surgery but the cumulative incidence increased continuously during 17 years of follow-up.

  • 27.
    Abdul-Sattar Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jancke, Georg
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Skoglund, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Hallböök, Olof
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Stapled versus robot-sewn ileo-ileal anastomosis during robot-assisted radical cystectomy: a review of outcomes in urinary bladder cancer patients2021Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, nr 1, s. 41-45Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    BackgroundWhereas the literature has demonstrated an acceptable safety profile of stapled anastomoses when compared to the hand-sewn alternative in open surgery, the choice of intestinal anastomosis using sutures or staples remains inadequately investigated in robotic surgery. The purpose of this study was to compare the surgical outcomes of both anastomotic techniques in robotic-assisted radical cystectomy.MethodsA retrospective analysis of patients with urinary bladder cancer undergoing cystectomy with urinary diversion and with ileo-ileal intestinal anastomosis at a single tertiary centre (2012–2018) was undertaken. The robotic operating time, hospital stay and GI complications were compared between the robotic-sewn (RS) and stapled anastomosis (SA) groups. The only difference between the groups was the anastomosis technique; the other technical steps during the operation were the same. Primary outcomes were GI complications; the secondary outcome was robotic operation time.ResultsThere were 155 patients, of which 112 (73%) were male. The median age was 71 years old. A surgical stapling device was used to create 66 (43%) separate anastomoses, while a robot-sewn method was employed in 89 (57%) anastomoses. There were no statistically significant differences in primary and secondary outcomes between RS and SA.ConclusionsCompared to stapled anastomosis, a robot-sewn ileo-ileal anastomosis may serve as an alternative and cost-saving approach. 

  • 28.
    Liedberg, Fredrik
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden; Reg Skane, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Hosseini, Abolfazl
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Survival after radical cystectomy during holiday periods2021Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, nr 4, s. 276-280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective For patients undergoing radical cystectomy for bladder cancer, a procedure requiring complex urinary tract reconstruction prone to major postoperative complications, the timing and quality of the surgery have been associated with outcomes. Patients and methods This study investigated if radical cystectomy for bladder cancer performed during holiday periods had worse disease-specific (DSS) and overall survival (OS), higher 90-day mortality and risk of readmissions. All patients operated on with radical cystectomy for primary bladder cancer during 1997-2014 with holiday periods as exposure (with one narrow (7 weeks) and one wider (14 weeks) definition) in the Swedish population-based bladder cancer research-database (BladderBaSe) were studied. DSS and OS after radical cystectomy during holiday periods were analysed with Cox regression models adjusted for sex, age, comorbidity, marital status, T-stage and nodal metastases, neoadjuvant chemotherapy, hospital volume and year of cystectomy. Results Surgery during the holiday periods (narrow and wide definitions) were not associated with DSS (Hazard ratio [HR] = 1.05, 95% confidence interval [95% CI] = 0.90-1.21 and HR = 1.04, 95% CI = 0.91-1.17), respectively. HRs for OS were similar, and no associations between radical cystectomy during any of the holiday period definitions and 90-day mortality and readmission were found. Conclusion Survival after radical cystectomy in Sweden is similar during holiday and non-holiday periods.

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  • 29.
    Jahnson, Staffan
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Ullen, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Thromboembolism in Muscle-Invasive Bladder Cancer. A Population-based Nationwide Study2021Ingår i: BLADDER CANCER, ISSN 2352-3727, Vol. 7, nr 2, s. 161-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking. OBJECTIVE: To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy. MATERIALS AND METHODS: We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE. RESULTS: In 9720 patients (71% males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patients and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease. CONCLUSION: VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken.

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  • 30.
    Alvaeus, Julia
    et al.
    Umea Univ, Sweden.
    Rosenblatt, Robert
    Umea Univ, Sweden; Stockholm South Gen Hosp, Sweden.
    Johansson, Markus
    Umea Univ, Sweden; Sundsvall Hosp, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Jakubczyk, Tomasz
    Lanssjukhuset Ryhov, Sweden.
    Holmstrom, Benny
    Uppsala Univ, Sweden.
    Hemdan, Tammer
    Uppsala Univ, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gabrielsson, Susanne
    Karolinska Inst, Sweden.
    Riklund, Katrine
    Umea Univ, Sweden.
    Winqvist, Ola
    Karolinska Univ Hosp, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy2020Ingår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, s. 2207-2213Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naive. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only. Results In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004). Conclusions The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.

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  • 31.
    Jerlstrom, Tomas
    et al.
    Orebro Univ, Sweden.
    Chen, Ruoqing
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Andren, Ove
    Orebro Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Hosseini, Abolfazl
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Malmstrom, Per-Uno
    Inst Surg Sci, Sweden.
    Ullen, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Fall, Katja
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study2020Ingår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, nr 2, s. 381-388Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking. Methods We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not. Results Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81). Conclusion This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

  • 32.
    Ottosson, Kristoffer
    et al.
    Umea Univ, Sweden.
    Pelander, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Johansson, Markus
    Umea Univ, Sweden; Sundsvall Hosp, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Sherif, Amir
    Umea Univ, Sweden.
    The increased risk for thromboembolism pre-cystectomy in patients undergoing neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer is mainly due to central venous access: a multicenter evaluation2020Ingår i: International Urology and Nephrology, ISSN 0301-1623, E-ISSN 1573-2584, Vol. 52, s. 661-669Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose To investigate if patients receiving neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) had an increased risk of thromboembolic events (TEE) and to evaluate when these events occur on a timeline starting from 6 months pre-cystectomy, during NAC-administration and 60 months post-cystectomy. Methods Two hundred and fifty five patients undergoing radical cystectomy during 2009-2014 at three Swedish cystectomy centers (Umea, Linkoping and Sundsvall) were in-detail reviewed retrospectively, using individual medical records. One hundred and twenty nine patients were ineligible for analysis. NAC patients (n = 67) were compared to NAC-naive NAC-eligible patients (n = 59). The occurrence of TEE was divided into different periods pre-cystectomy and post-cystectomy. Statistical analyses included Chi-squared and logistical regression tests. Results Significant associations were found between receiving NAC and acquiring a TEE during NAC therapy pre-cystectomy. All but one pre-cystectomy event was venous and all but one of the patients received NAC. 31% (14/45) of TEEs occurred pre-cystectomy. The incidence of TEEs pre-cystectomy in NAC-naive NAC-eligible patients was only 10% (2/20), whereas the incidence of TEEs in NAC patients occurred pre-cystectomy in 48% (12/25) and 11/12 incidents were detected during NAC therapy-this including 7/11 (64%) incidents affecting veins in anatomical conjunction with the placement of central venous access for chemotherapy administration. Conclusions There is a significantly increased risk for TEE pre-cystectomy during chemotherapy administration in MIBC patients receiving NAC, compared to the risk in NAC-naive NAC-eligible MIBC patients. In 64% of the pre-RC TEEs in NAC patients, there was a clinical connection to placement of central venous access.

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  • 33.
    Abdul-Sattar Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe)2020Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, nr 5, s. 625-632Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis. Patients And Methods Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patients characteristics, UBC tumour stage at diagnosis, and site of OPC. Results There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis. Conclusions OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

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  • 34.
    Abdul-Sattar Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases. A nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)2019Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 5, s. 332-338Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the clinical management and outcome of patients with muscle-invasive bladder cancer with clinical lymph node involvement, using longitudinal nationwide population-based data. Methods: In the Bladder Cancer Data Base Sweden (BladderBaSe), treatment and survival in patients with urinary bladder cancer clinical stage T2-T4 N + M0 diagnosed between 1997 and 2014 was investigated. Patients characteristics were studied in relation to TNM classification, curative or palliative treatment, cancer-specific (CSS) and overall survival (OS). Age at diagnosis was categorised as amp;lt;= 60, 61-70, 71-80 and amp;gt;80 years, and time periods were stratified as follows: 1997-2001, 2002-2005, 2006-2010 and 2011-2014. Results: There were 786 patients (72% males) with a median age of 71 years (interquartile range = 64-79 years). The proportion of patients with high comorbidity increased over time. Despite similar low comorbidity, curative treatment was given to 44% and to 70% of those in older (amp;gt;70 years) and younger age groups, respectively. Curative treatment decreased over time, but chemotherapy and cystectomy increased to 25% during the last time period. Patients with curative treatment had better survival compared to those with palliative treatment, both regarding CSS and OS in the whole cohort and in all age groups. Conclusions: The low proportion of older patients undergoing treatment with curative intent, despite no or limited comorbidity, indicates missed chances of treatment with curative intent. The reasons for an overall decrease in curative treatment over time need to be analysed and the challenge of coping with an increasing proportion of node-positive patients with clinically significant comorbidity needs to be met.

  • 35.
    Jahnson, Staffan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Abdul-Sattar Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Modulation of the inflammatory response after sclerotherapy for hydrocoele/spermatocoele2019Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, nr 5A, s. E63-E68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To investigate the modulation of the inflammatory response after sclerotherapy for hydrocoele/spermatocoele.

    Patients and Methods

    All patients with hydrocoele or spermatocoele presenting at the Department of Urology, University Hospital, Linköping, Sweden, from 2006 to 2012, were included in this prospective observational study of sclerotherapy for hydrocoele/spermatocoele using polidocanol as a sclerosing agent and adjuvant antibiotic and anti‐inflammatory medication (AAAM) for modulation of the inflammatory response. Patients were clinically evaluated within 24–48 h after a complication or adverse event possibly related to sclerotherapy. Evaluation of cure was scheduled after 3 months and re‐treatment, if necessary was carried out in the same manner as the first treatment. Groups of patients were compared using the chi‐squared test and logistic regression analysis.

    Results

    From a total of 191 patients, AAAM was given to 126, of whom 5% had subclinical epididymitis/swelling (SES) compared to 26% of the patients without AAAM (P < 0.001). No other complication was observed. The rate of cure for the whole group of patients was 93% after one or two treatments and significantly higher in the group with AAAM than in the group without AAAM (96% vs 88%, P = 0.03).

    Conclusions

    Modulation of the inflammatory response after sclerotherapy resulted in a lower incidence of SES and an increased cure rate.

  • 36.
    Liedberg, Fredrik
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Reg Canc Ctr South, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Jancke, Georg
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study2019Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, nr 3, s. 449-456Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at amp;gt;= 25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually. Results PSMAV in the highest tertile (amp;gt;= 25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of amp;gt;3 months after diagnosis. Conclusions The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

  • 37.
    Jancke, Georg
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Reply to Francesco Montorsi and Giorgio Gandaglias Letter to the Editor re: Georg Jancke, Firas Aljabery, Sigurdur Gudjonsson, et al. Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, nr 2, s. E32-E33Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 38.
    Haggstrom, Christel
    et al.
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Garmo, Hans
    Kings Coll London, England; Reg Canc Ctr Uppsala Orebro, Sweden.
    de Luna, Xavier
    Umea Univ, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, England; Karolinska Inst, Sweden.
    Soderkvist, Karin
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study2019Ingår i: Cancer Medicine, E-ISSN 2045-7634, Vol. 8, nr 5, s. 2196-2204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC. Methods We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period. Results The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29. Conclusion(s) Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

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  • 39.
    Bergman, Emma Ahlen
    et al.
    Karolinska Univ Hosp, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Univ Hosp, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Sweden; Umea Univ, Sweden.
    Linton, Ludvig B.
    Karolinska Univ Hosp, Sweden.
    Berglund, Sofia
    Karolinska Univ Hosp, Sweden.
    Hyllienmark, Martin
    TLA Targeted Immunotherapies AB, Sweden.
    Lundgren, Christian
    Karolinska Univ Hosp, Sweden.
    Holmstrom, Benny
    Akad Univ Hosp, Sweden.
    Palmqvist, Karin
    Umea Univ, Sweden; Ostersund Cty Hosp, Sweden.
    Hansson, Johan
    Uppsala Univ, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Riklund, Katrine
    Umea Univ, Sweden.
    Winerdal, Malin E.
    Karolinska Univ Hosp, Sweden.
    Krantz, David
    Karolinska Univ Hosp, Sweden.
    Zirakzadeh, A. Ali
    Karolinska Univ Hosp, Sweden; Umea Univ, Sweden.
    Marits, Per
    Karolinska Univ Hosp, Sweden.
    Sjoholm, Louise K.
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden; Umea Univ, Sweden.
    Winqvist, Ola
    Karolinska Univ Hosp, Sweden.
    Increased CD4(+) T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients2018Ingår i: Clinical epigenetics, ISSN 1868-7075, Vol. 10, artikel-id 102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4(+) T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-gamma, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4(+ )T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy. Results: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4(+ )lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4(+) lymphocytes in lymph nodes and blood (lymph nodes vs rumour-infiltrating lymphocytes: IFNG -4229 bp p amp;lt; 0.0001, IL13 -11 bp p amp;lt; 0.05, IL17A -122 bp p amp;lt; 0.01 and FOXP3 -77 bp pamp;gt; 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4(+ )T cells for all four investigated loci, most prominently in IFNG p amp;lt; 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4(+) T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3. Conclusion: Increased lineage commitment in CD4(+) T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4(+) T cell lineages as a useful readout for clinical staging.

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  • 40.
    Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Shabo, Ivan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer2018Ingår i: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 36, nr 4, artikel-id 159.e19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Tumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer(UBC) is controversial.

    Methods

    We prospectively studied 103 patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.

    Results

    The mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).

    Conclusions

    M2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.

  • 41.
    Krantz, David
    et al.
    Karolinska Inst, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Inst, Sweden.
    Winerdal, Malin E.
    Karolinska Inst, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Sweden; Umea Univ, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Jakubczyk, Tomasz
    Ryhov Cty Hosp, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Palmqvist, Karin
    Umea Univ, Sweden; Ostersund Cty Hosp, Sweden.
    Zirakzadeh, A. Ali
    Karolinska Inst, Sweden; Umea Univ, Sweden.
    Holmstrom, Benny
    Akad Univ Hosp, Sweden.
    Riklund, Katrine
    Umea Univ, Sweden.
    Sherif, Amir
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Umea univ, Sweden.
    Winqvist, Ola
    Karolinska Inst, Sweden.
    Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 688-692Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8(+) effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4(+) Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs. Patient summary: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients. (C) 2018 Published by Elsevier B.V. on behalf of European Association of Urology.

  • 42.
    Jancke, Georg
    et al.
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Wiklund, Peter
    Karolinska Univ Hosp, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 4, s. 641-642Artikel i tidskrift (Övrigt vetenskapligt)
  • 43.
    Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Shabo, Ivan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    The expression profile of p14, p53 and p21 in tumour cells is associated with disease-specific survival and the outcome of postoperative chemotherapy treatment in muscle-invasive bladder cancer2018Ingår i: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 36, nr 12, s. 530.e7-530.e18, artikel-id 530.e7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy.

    Materials and methods: We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival.

    Results: The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P = 0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03).

    Conclusions: The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.

  • 44.
    Hartana, C. A.
    et al.
    Karolinska Inst, Sweden.
    Bergman, E. Ahlen
    Karolinska Inst, Sweden.
    Broome, A.
    Karolinska Inst, Sweden.
    Berglund, S.
    Karolinska Inst, Sweden.
    Johansson, M.
    Sundsvall Hosp, Sweden.
    Alamdari, F.
    Vastmanland Hosp, Sweden.
    Jakubczyk, T.
    Lanssjukhuset Ryhov, Sweden.
    Huge, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Palmqvist, K.
    Ostersund Cty Hosp, Sweden.
    Holmstroem, B.
    Akad Univ Hosp, Sweden.
    Glise, H.
    Karolinska Inst, Sweden.
    Riklund, K.
    Umea Univ, Sweden.
    Sherif, A.
    Umea Univ, Sweden.
    Winqvist, O.
    Karolinska Inst, Sweden.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, nr 1, s. 39-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tissue-resident memory T (T-RM) cells are CD8(+) T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T-RM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T-RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate T-RM cell phenotypes. We discovered that tumour T-RM cells have low DNA methylation in the PRF1 locus (32amp;lt;boldamp;gt;amp;lt;/boldamp;gt;9% methylation), which corresponds to increased numbers of perforin-expressing T-RM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour T-RM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that T-RM cells from tumours are not terminally exhausted. Moreover, a high number of T-RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T-RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T-RM cells as potential new targets for cancer immunotherapy.

  • 45.
    Sjostrom, Carin
    et al.
    Capio St Gorans Hosp, Sweden; Karolinska Inst, Sweden.
    Thorstenson, Andreas
    Capio St Gorans Hosp, Sweden; Karolinska Inst, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden.
    Hosseini-Aliabad, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Liedberg, Fredrik
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Malmstrom, Per-Uno
    Akad Univ Hosp, Sweden.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Gardmark, Truls
    Danderyd Hosp, Sweden; Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Treatment according to guidelines may bridge the gender gap in outcome for patients with stage T1 urinary bladder cancer2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 3, s. 186-193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this investigation was to study differences between male and female patients with stage T1 urinary bladder cancer (UBC) regarding intravesical instillation therapy, second resection and survival. Materials and methods: This study included all patients with non-metastatic primary T1 UBC reported to the Swedish National Register of Urinary Bladder Cancer (SNRUBC) from 1997 to 2014, excluding those treated with primary cystectomy. Differences between groups were evaluated using chi-squared tests and logistic regression, and survival was investigated using Kaplan-Meier and log-rank tests and Cox proportional hazards analysis. Results: In all, 7681 patients with T1 UBC (77% male, 23% female) were included. Females were older than males at the time of diagnosis (median age at presentation 76 and 74 years, respectively; p amp;lt; .001). A larger proportion of males than females underwent intravesical instillation therapy (39% vs 33%, pamp;lt;.001). Relative survival was lower in women aged amp;gt;= 75 years and women with G3 tumours compared to men. However, women aged amp;gt;= 75 years who had T1G3 tumours and underwent second resection followed by intravesical instillation therapy showed a relative survival equal to that observed in men. Conclusions: This population-based study demonstrates that women of all ages with T1 UBC undergo intravesical instillation therapy less frequently than men, and that relative survival is poorer in women aged amp;gt;= 75 years than in men of the same age when intravesical instillation therapy and second resection are not used. However, these disparities may disappear with treatment according to guidelines.

  • 46.
    Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Halili, Shefqet
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Hildebrand, Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Vesico-Uterine Fistula after TURB in pregnancy, a rare cause of genitourinary fistula2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 2, s. 162-163Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 47.
    Häggström, Christel
    et al.
    Uppsala University, Sweden; Umeå University, Sweden.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Hagberg, Oskar
    Regional Cancer Centre South, Sweden.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Strock, Viveka
    Sahlgrens University Hospital, Sweden.
    Hosseini, Abolfazl
    Karolinska University Hospital, Sweden.
    Gardmark, Truls
    Karolinska Institute, Sweden.
    Sherif, Amir
    Umeå University, Sweden.
    Malmstrom, Per-Uno
    Uppsala University, Sweden.
    Garmo, Hans
    Kings Coll London, England; Regional Cancer Centre Uppsala Örebro, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Holmberg, Lars
    Uppsala University, Sweden; Kings Coll London, England.
    Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)2017Ingår i: BMJ Open, E-ISSN 2044-6055, Vol. 7, nr 9, artikel-id e016606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). Participants The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Findings to date Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. Future plans The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

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  • 48.
    Aljabery, Firas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Shabo, Ivan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden .
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Jahnson, Staffan
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi.
    Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.2017Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, nr 3, s. 329-336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

  • 49. Beställ onlineKöp publikationen >>
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

    Delarbeten
    1. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Öppna denna publikation i ny flik eller fönster >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.