| 1. |
- Rydell, Harriet, et al.
(författare)
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Thromboembolic events in patients undergoing neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer : a study of renal impairment in relation to potential thromboprophylaxis
- 2022
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies on patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) have shown an association between NAC and thromboembolic events (TEE) prior to radical cystectomy (RC). Recent studies suggest that central venous access catheters (CVAs) may induce TEEs, and low-molecular-weight heparin (LMWH) has been mentioned as possible prophylaxis. However, other studies have shown a high incidence of decreased renal function in these patients. The purpose of this study was to determine the portion of MIBC patients with NAC-induced TEEs who had decreased preoperative renal function for whom LMWH potentially would not be beneficial as prophylaxis. We identified 459 cystectomized MIBC patients from two Swedish medical centers from 2009 to 2021. The inclusion criterion of cT2-T4aN0M0 resulted in 220 eligible patients, who were further divided into NAC-administered (n = 187) and NAC-eligible (n = 33), the tentative control group. Values of renal function before, during, and after each NAC cycle were retrospectively collected from individual medical records. Amongst the NAC-administered patients with TEE (n = 29), 41% (95% CI 23.5-61.1%) of patients had decreased renal function. Thus, a substantial portion of NAC-administered patients who developed TEEs had reduced renal function and would have been less likely to have benefited from renal clearance-dependent LMWH prophylaxis.
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| 2. |
- Saudi, Aws, et al.
(författare)
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Immune-activated B cells are dominant in prostate cancer
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- 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 naïve 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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| 3. |
- Vollmer, Tino, et al.
(författare)
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The intratumoral CXCR3 chemokine system is predictive of chemotherapy response in human bladder cancer
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:576
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy has direct toxic effects on cancer cells; however, long-term cancer control and complete remission are likely to involve CD8+ T cell immune responses. To study the role of CD8+ T cell infiltration in the success of chemotherapy, we examined patients with muscle invasive bladder cancer (MIBC) who were categorized on the basis of the response to neoadjuvant chemotherapy (NAC). We identified the intratumoral CXCR3 chemokine system (ligands and receptor splice variants) as a critical component for tumor eradication upon NAC in MIBC. Through characterization of CD8+ T cells, we found that stem-like T cell subpopulations with abundant CXCR3alt, a variant form of the CXCL11 receptor, responded to CXCL11 in culture as demonstrated by migration and enhanced effector function. In tumor biopsies of patients with MIBC accessed before treatment, CXCL11 abundance correlated with high numbers of tumor-infiltrating T cells and response to NAC. The presence of CXCR3alt and CXCL11 was associated with improved overall survival in MIBC. Evaluation of both CXCR3alt and CXCL11 enabled discrimination between responder and nonresponder patients with MIBC before treatment. We validated the prognostic role of the CXCR3-CXCL11 chemokine system in an independent cohort of chemotherapy-treated and chemotherapy-naïve patients with MIBC from data in TCGA. In summary, our data revealed stimulatory activity of the CXCR3alt-CXCL11 chemokine system on CD8+ T cells that is predictive of chemotherapy responsiveness in MIBC. This may offer immunotherapeutic options for targeted activation of intratumoral stem-like T cells in solid tumors.
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| 4. |
- Wiberg, Erik, et al.
(författare)
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A validation study of cT-categories in the Swedish national urinary bladder cancer register - Norrland University Hospital
- 2023
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, Sweden, from 2009 to 2020, inclusive.METHODS: The medical records of all 295 patients who underwent radical cystectomy for the treatment of UBC were reviewed retrospectively. Possible factors impacting the cT-categories were identified. To optimise cT-classification, computed tomography urography of all patients with suspected tumour-associated hydronephrosis (TAH) or suspected tumour in bladder diverticulum (TIBD) were retrospectively reviewed by a radiologist. Discrepancy was tested with a logistic regression model.RESULTS: cT-categories differed in 87 cases (29.5%). Adjusted logistic regression analysis found TIBD and TAH as significant predictors for incorrect registration; OR = 7.71 (p < 0.001), and OR = 17.7, (p < 0.001), respectively. In total, 48 patients (68.6%) with TAH and 12 patients (52.2%) with TIBD showed discrepancy regarding the cT-category. Incorrect registration was mostly observed during the years 2009-2012.CONCLUSION: The study revealed substantial incorrect registration of cT-categories in SNRUBC. A major part of the misclassifications was related to TAH and TIBD. Registration of these variables in the SNRUBC might be considered to improve correct cT-classification.
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