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- Abrahamsson, Johan, et al.
(författare)
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Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder : Association with tumor stage, lymph node metastases, FDG-PET findings, and survival
- 2017
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Ingår i: Urologic Oncology. - : Elsevier BV. - 1078-1439. ; 35:10, s. 9-606
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells. Objective: To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer. Design, setting, and participants: Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients. Outcome measurements and statistical analysis: Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival. Results: CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6-21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005-7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM. Conclusions: CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen-based CTC detection methods.
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| 5. |
- Hultman Patschan, Oliver, et al.
(författare)
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Use of bacillus Calmette-Guerin in stage T1 bladder cancer : long-term observation of a population-based cohort
- 2015
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 49:2, s. 127-132
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to analyse the rate of use of bacillus Calmette-Guerin (BCG) at a population-based level, and the overall mortality and bladder cancer mortality due to stage T1 bladder cancer in a national, population-based register. Materials and methods. In total, 3758 patients with primary stage T1 bladder cancer, registered in the Swedish Bladder Cancer Register between 1997 and 2006, were included. Age, gender, tumour grade and primary treatment in the first 3-6 months were registered. High-volume hospitals registered 10 or more T1 tumours per year. Date and cause of death were obtained from the National Board of Health and Welfare Cause of Death Register. Results. BCG was given to 896 patients (24%). The use of BCG increased from 18% between 1997 and 2000, to 24% between 2001 and 2003, and to 31% between 2004 and 2006. BCG was given more often to patients with G3 tumours, patients younger than 75 years and patients attending high-volume hospitals. BCG treatment, grade 2 tumours and patient age younger than 75 years were associated with lower mortality due to bladder cancer. Hospital volume, gender and year of diagnosis were not related to bladder cancer mortality. However, selection factors might have affected the results since comorbidity, number of tumours and tumour size were unknown. Conclusions. Intravesical BCG is underused at a population-based level in stage T1 bladder cancer in Sweden, particularly in patients 75 years or older, and in those treated at low-volume hospitals. BCG should be offered more frequently to patients with stage T1 bladder cancer in Sweden.
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| 6. |
- Johansson Kollberg, Petter, et al.
(författare)
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[18F]Fluorodeoxyglucose-positron emission tomography/computed tomography response evaluation can predict histological response at surgery after induction chemotherapy for oligometastatic bladder cancer
- 2017
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:4, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with limited metastatic and locally advanced bladder cancer have a poor prognosis, and no definite treatment recommendations exist. However, long-term survival is possible for selected patients if surgery is combined with multiple courses of chemotherapy (i.e. induction chemotherapy). Patients with tumours that are insensitive to chemotherapy probably have little to gain from subsequent extensive surgery. The aim of this study was to evaluate sequential FDG-PET/CT examinations as an indicator of chemotherapy response. Materials and methods: Between 2007 and 2015, 50 patients with oligometastatic invasive bladder cancer selected for induction chemotherapy underwent two FDG-PET/CT examinations: the first before the start of chemotherapy and the second after three courses of cisplatinum-based combination chemotherapy. Responders were given up to six courses of chemotherapy. FDG-PET/CT response was correlated with histological response in excised lymph-node metastases. Results: Three patients showed progression to incurable disease during chemotherapy and another two patients did not undergo surgery, for medical reasons. Lymphadenectomy was performed in the remaining 45 patients, of whom 43 had lymph-node metastasis. FDG-PET/CT prediction of the histological nodal chemotherapy response was correct in 37 (86%) of those 43. The second FDG-PET/CT examination identified four out of nine non-responders. For response, the sensitivity, specificity, and positive and negative predictive values for FDG-PET/CT accuracy were 37 out of 37 (100%), one out of six (17%), 37 out of 42 (88%) and one out of one (100%), respectively. Conclusions: Repeated FDG-PET/CT seems to predict histological response. However, with the histological response criteria used in this study, five non-responders were not identified by the second FDG-PET/CT investigation.
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- Kollberg, Petter, et al.
(författare)
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[F-18]Fluorodeoxyglucose - positron emission tomography/computed tomography improves staging in patients with high-risk muscle-invasive bladder cancer scheduled for radical cystectomy
- 2015
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 49:4, s. 296-301
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to evaluate the clinical use of [F-18]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in addition to conventional preoperative radiological investigations in a defined group of patients with high-risk muscle-invasive bladder cancer. Materials and methods. In total, 103 patients with high-risk muscle-invasive bladder cancer defined as stage T3/T4 disease or as stage T2 with hydronephrosis or high-risk histological features, who were provisionally scheduled to undergo cystectomy, were prospectively recruited to the study. The patients were referred to FDG-PET/CT in addition to standard preoperative investigation with computed tomography (CT). The final treatment decision was reached at a multidisciplinary conference based on all available information including the FDG-PET/Cf findings. Results. Compared to CT alone, FDG-PET/CT provided more supplemental findings suggesting malignant manifestations in 48 (47%) of the 103 patients. The additional FDG-PET/CT findings led to an altered provisional treatment plan in 28 out of 103 patients (27%), detection of disseminated bladder cancer and subsequent cancellation of the initially intended cystectomy in 16 patients, and identification of disseminated disease and treatment with induction chemotherapy before radical cystectomy in 12 patients. Conclusions. Preoperative FDG-PET/CT changed the treatment plan for a considerable proportion (27%) of the present patients. Accordingly, such examination can potentially improve the preoperative staging of cystectomy patients with high-risk features, and may also reduce the number of futile operations in patients with advanced disease who are beyond cure.
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- Lauss, Martin, et al.
(författare)
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DNA methylation analyses of urothelial carcinoma reveal distinct epigenetic subtypes and an association between gene copy number and methylation status.
- 2012
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 7:8, s. 858-867
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Tidskriftsartikel (refereegranskat)abstract
- We assessed DNA methylation and copy number status of 27,000 CpGs in 149 urothelial carcinomas and integrated the findings with gene expression and mutation data. Methylation was associated with gene expression for 1,332 CpGs, of which 26% showed positive correlation with expression, i.e., high methylation and high gene expression levels. These positively correlated CpGs were part of specific transcription factor binding sites, such as sites for MYC and CREBP1, or located in gene bodies. Furthermore, we found genes with copy number gains, low expression and high methylation levels, revealing an association between methylation and copy number levels. This phenomenon was typically observed for developmental genes, such as HOX genes, and tumor suppressor genes. In contrast, we also identified genes with copy number gains, high expression and low methylation levels. This was for instance observed for some keratin genes. Tumor cases could be grouped into four subgroups, termed epitypes, by their DNA methylation profiles. One epitype was influenced by the presence of infiltrating immune cells, two epitypes were mainly composed of non-muscle invasive tumors, and the remaining epitype of muscle invasive tumors. The polycomb complex protein EZH2 that blocks differentiation in embryonic stem cells showed increased expression both at the mRNA and protein levels in the muscle invasive epitype, together with methylation of polycomb target genes and HOX genes. Our data highlights HOX gene silencing and EZH2 expression as mechanisms to promote a more undifferentiated and aggressive state in UC.
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| 9. |
- Liedberg, Fredrik, et al.
(författare)
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Long-term functional outcomes after radical cystectomy with ileal bladder substitute : does the definition of continence matter?
- 2017
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:1, s. 44-49
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Functional outcomes after ileal bladder substitution reflect the expectations of future patients at a particular centre. The aim of this study was to use validated questionnaires and a pad-weighing test to investigate functional outcomes after neobladder reconstruction at long-term follow-up in patients at a single centre. Materials and methods: During 2005 − 2015, 75 patients received a Studer ileal bladder substitute at the Department of Urology, Malmö. Forty-six of these patients were alive for follow-up and were evaluated using the pad-weighing test and the International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form (ICIQ-UI-SF), the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Results: Five of 37 evaluable patients (14%) were considered fully continent, reporting a pad-weighing test result of 0 g and an ICIQ-UI-SF score of 0. The median ICIQ-UI-SF score was 8 [interquartile range (IQR) 3–11], and seven patients (17%) were continent according to the ICIQ-UI-SF score only. In the pad-weighing test, 28 out of 37 patients (76%) reported 0 g day-time leakage whereas only 12 out of 37 patients (32%) reported 0 g night-time leakage. At follow-up, nine out of 39 (23%) of evaluable male patients were potent. The median ICIQ-UI-SF score was significantly lower during the second half of the study period [4 (IQR 0–8) vs 10 (IQR 6–14); p = .003]. The inverse applied to the median IIEF score [5 (IQR 3–12) vs 2 (IQR 1–4); p = .02]. Conclusions: Functional outcomes at long-term follow-up after radical cystectomy and Studer ileal bladder substitute were at best modest in this series. Better outcomes during the second half of the study period might be explained by improved patient selection and a refined surgical technique, but possibly also by longer follow-up of patients during the first half of the period resulting in a more pronounced time-dependent decline in functional outcomes.
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| 10. |
- Liedberg, Fredrik, et al.
(författare)
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Preventing Parastomal Hernia After Ileal Conduit by the Use of a Prophylactic Mesh : A Randomised Study
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 78:5, s. 757-763
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parastomal hernia (PSH) after urinary diversion with ileal conduit is frequently a clinical problem.OBJECTIVE: To investigate whether a prophylactic lightweight mesh in the sublay position can reduce the cumulative incidence of PSH after open cystectomy with ileal conduit.DESIGN, SETTING, AND PARTICIPANTS: From 2012 to 2017, we randomised 242 patients 1:1 to conventional stoma construction (n = 124) or prophylactic mesh (n = 118) at three Swedish hospitals (ISRCTN 95093825).OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was clinical PSH, and secondary endpoints were radiological PSH assessed in prone position with the stoma in the centre of a ring, parastomal bulging, and complications from the mesh.RESULTS AND LIMITATIONS: Within 24 mo, 20/89 (23%) patients in the control arm and 10/92 (11%) in the intervention arm had developed a clinical PSH (p = 0.06) after a median follow-up of 3 yr, corresponding to a hazard ratio of 0.45 (confidence interval 0.24-0.86, p = 0.02) in the intervention arm. The proportions of radiological PSHs within 24 mo were 22/89 (25%) and 17/92 (19%) in the two study arms. During follow-up, five patients in the control arm and two in the intervention arm were operated for PSH. The median operating time was 50 min longer in patients receiving a mesh. No differences were noted in proportions of Clavien-Dindo complications at 90 d postoperatively or in complications related to the mesh during follow-up.CONCLUSIONS: Prophylactic implantation of a lightweight mesh in the sublay position decreases the risk of PSH when constructing an ileal conduit without increasing the risk of complications related to the mesh. The median surgical time is prolonged by mesh implantation.PATIENT SUMMARY: In this randomised report, we looked at the risk of parastomal hernia after cystectomy and urinary diversion with ileal conduit with or without the use of a prophylactic mesh. We conclude that such a prophylactic measure decreased the occurrence of parastomal hernias, with only a slight increase in operating time and no added risk of complications related to the mesh.
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