| 1. |
- Liedberg, Fredrik, et al.
(författare)
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Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective : results from a prospective intervention study
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115, s. 770-775
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Tidskriftsartikel (refereegranskat)abstract
- Background:The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long.Methods:We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with macroscopic haematuria. The control group comprised 101 patients diagnosed with bladder cancer in the same catchment area with macroscopic haematuria who underwent regular diagnostic process.Results:In all 275 patients who called ‘the Red Phone’ hotline were investigated, and 47 of them (17%) were diagnosed with cancer and 36 of those had bladder cancer. Median time from patient-reported haematuria to diagnosis was 29 (interquartile range (IQR) 14−104) days and 50 (IQR 27−165) days in the intervention and the control group, respectively (P=0.03). The median health-care costs were lower in the intervention group (655 (IQR 655−655) EUR) than in the control group (767 (IQR 490−1096) EUR) (P=0.002).Conclusions:Direct access to urologic expertise and fast-track diagnostics is motivated for patients with macroscopic haematuria to reduce diagnostic intervals and lower health-care expenditures.British Journal of Cancer advance online publication, 25 August 2016; doi:10.1038/bjc.2016.265 www.bjcancer.com.
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| 2. |
- Abdul-Sattar Aljabery, Firas, et al.
(författare)
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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)
- 2019
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 332-338
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Tidskriftsartikel (refereegranskat)abstract
- 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 ≤60, 61-70, 71-80 and >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 (>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.
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| 3. |
- Abuhasanein, Suleiman, et al.
(författare)
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A novel model of artificial intelligence based automated image analysis of CT urography to identify bladder cancer in patients investigated for macroscopic hematuria
- 2024
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Ingår i: Scandinavian journal of urology. - : Medical Journal Sweden AB. - 2168-1805 .- 2168-1813. ; 59, s. 90-97
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate whether artificial intelligence (AI) based automatic image analysis utilising convolutional neural networks (CNNs) can be used to evaluate computed tomography urography (CTU) for the presence of urinary bladder cancer (UBC) in patients with macroscopic hematuria. Methods: Our study included patients who had undergone evaluation for macroscopic hematuria. A CNN-based AI model was trained and validated on the CTUs included in the study on a dedicated research platform (Recomia.org). Sensitivity and specificity were calculated to assess the performance of the AI model. Cystoscopy findings were used as the reference method. Results: The training cohort comprised a total of 530 patients. Following the optimisation process, we developed the last version of our AI model. Subsequently, we utilised the model in the validation cohort which included an additional 400 patients (including 239 patients with UBC). The AI model had a sensitivity of 0.83 (95% confidence intervals [CI], 0.76-0.89), specificity of 0.76 (95% CI 0.67-0.84), and a negative predictive value (NPV) of 0.97 (95% CI 0.95-0.98). The majority of tumours in the false negative group (n = 24) were solitary (67%) and smaller than 1 cm (50%), with the majority of patients having cTaG1-2 (71%). Conclusions: We developed and tested an AI model for automatic image analysis of CTUs to detect UBC in patients with macroscopic hematuria. This model showed promising results with a high detection rate and excessive NPV. Further developments could lead to a decreased need for invasive investigations and prioritising patients with serious tumours.
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| 4. |
- Abuhasanein, Suleiman, et al.
(författare)
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A novel model of artificial intelligence based automated image analysis of CT urography to identify bladder cancer in patients investigated for macroscopic hematuria
- 2024
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Ingår i: Scandinavian Journal of Urology. - : Medical Journal Sweden AB. - 2168-1805 .- 2168-1813. ; 59, s. 90-97
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate whether artificial intelligence (AI) based automatic image analysis utilising convolutional neural networks (CNNs) can be used to evaluate computed tomography urography (CTU) for the presence of urinary bladder cancer (UBC) in patients with macroscopic hematuria. METHODS: Our study included patients who had undergone evaluation for macroscopic hematuria. A CNN-based AI model was trained and validated on the CTUs included in the study on a dedicated research platform (Recomia.org). Sensitivity and specificity were calculated to assess the performance of the AI model. Cystoscopy findings were used as the reference method. RESULTS: The training cohort comprised a total of 530 patients. Following the optimisation process, we developed the last version of our AI model. Subsequently, we utilised the model in the validation cohort which included an additional 400 patients (including 239 patients with UBC). The AI model had a sensitivity of 0.83 (95% confidence intervals [CI], 0.76-0.89), specificity of 0.76 (95% CI 0.67-0.84), and a negative predictive value (NPV) of 0.97 (95% CI 0.95-0.98). The majority of tumours in the false negative group (n = 24) were solitary (67%) and smaller than 1 cm (50%), with the majority of patients having cTaG1-2 (71%). CONCLUSIONS: We developed and tested an AI model for automatic image analysis of CTUs to detect UBC in patients with macroscopic hematuria. This model showed promising results with a high detection rate and excessive NPV. Further developments could lead to a decreased need for invasive investigations and prioritising patients with serious tumours.
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| 5. |
- Abuhasanein, Suleiman, et al.
(författare)
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Computed tomography urography with corticomedullary phase can exclude urinary bladder cancer with high accuracy
- 2022
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Ingår i: BMC Urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To evaluate the diagnostic accuracy of computed tomography-urography (CTU) to rule out urinary bladder cancer (UBC) and whether patients thereby could omit cystoscopy. Methods All patients evaluated for macroscopic hematuria with CTU with cortico-medullary phase (CMP) and cystoscopy at our institute between 1(st) November 2016 and 31(st) December 2019 were included. From this study cohort a study group consisting of all UBC patients and a control group of 113 patients randomly selected from all patients in the study cohort without UBC. Two radiologists blinded to all clinical data reviewed the CTUs independently. CTUs were categorized as positive, negative or indeterminate. Diagnostic accuracy and proportion of potential omittable cystoscopies were calculated for the study cohort by generalizing the results from the study group. Results The study cohort consisted of 2195 patients, 297 of which were in the study group (UBC group, n = 207 and control group, n = 90). Inter-rater reliability was high (kappa 0.84). Evaluation of CTUs showed that 174 patients were assesessed as positive (showing UBC), 46 patients as indeterminate (not showing UBC but with limited quality of CTU), and 77 patients as negative (not showing UBC with good quality of CTU). False negative rate was 0.07 (95%, CI 0.04-0.12), false positive rate was 0.01 (95% CI 0.0-0.07) and negative predictive value was 0.99 (95% CI 0.92-1.0). The area under the curve was 0.93 (95% CI 0.90-0.96). Only 2.9% (3/102) with high-risk tumors and 11% (12/105) with low- or intermediate-risk tumors had a false negative CTU. Cystoscopy could potentially have been omitted in 57% (1260/2195) of all evaluations. Conclusions CTU with CMP can exclude UBC with high accuracy. In case of negative CTU, it might be reasonable to omit cystoscopy, but future confirmative studies with possibly refined technique are needed.
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| 6. |
- Abuhasanein, Suleiman, et al.
(författare)
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Diagnostic value of repeated comprehensive investigation with CT urography and cystoscopy for recurrent macroscopic haematuria
- 2024
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Ingår i: BJUI Compass. - : John Wiley & Sons. - 2688-4526. ; 5:2, s. 253-260
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To perform a descriptive analysis of a series of patients with recurrent macroscopic haematuria after a primary standard evaluation including computed tomography urography (CTU) and cystoscopy negative for urinary bladder cancer (UBC) and upper tract urothelial cancer (UTUC) and to identify potential factors associated with occurrence of recurrent macroscopic haematuria.Methods: All patients older than 50 years who underwent urological investigation for macroscopic haematuria with both cystoscopy and CTU 2015-2017 were retrospectively reviewed. A descriptive analysis of the primary and later investigations for recurrent macroscopic haematuria was performed. To investigate the association between explanatory variables and the occurrence of recurrent macroscopic haematuria, a Poisson regression analysis was performed.Results: A total of 1395 eligible individuals with primary standard investigation negative for UBC and UTUC were included. During a median follow-up of 6.2 (IQR 5.3-7) years, 248 (18%) patients had recurrent macroscopic haematuria, of whom six patients were diagnosed with UBC, two with prostate cancer, one with renal cell carcinoma and one had a suspected UTUC at the repeated investigation. Within 3 years, 148 patients (11%) experienced recurrent macroscopic haematuria, of whom two patients were diagnosed with low-grade UBC (TaG1-2), one with T2G3 UBC and one with low-risk prostate cancer. The presence of an indwelling catheter, use of antithrombotic medication, pathological findings at CTU or cystoscopy or history of pelvic radiotherapy were all statistically significant independent predictors for increased risk for recurrent macroscopic haematuria.Conclusion: In the case of recurrent macroscopic haematuria within 3 years of primary standard evaluation for urinary tract cancer, there was a low risk of later urological malignancies in patients initially negative for UBC and UTUC. Therefore, waiting 3 years before conducting another complete investigation in cases of recurrent macroscopic haematuria might be appropriate.
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| 7. |
- Abuhasanein, Suleiman, et al.
(författare)
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Do not throw out the baby with the bath water
- 2022
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Ingår i: Scandinavian Journal of Urology. - Abingdon, Oxfordshire, United Kingdom : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:3, s. 235-236
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Abuhasanein, Suleiman, et al.
(författare)
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Shortened time to diagnosis for patients suspected of urinary bladder cancer managed in a standardized care pathway was associated with an improvement in tumour characteristics
- 2024
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Ingår i: BJUI COMPASS. - : WILEY. - 2688-4526. ; 5:2, s. 261-268
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To evaluate whether the implementation of standardized care pathway (SCP) for patients with suspected urinary bladder cancer (UBC) was associated with changes in tumour characteristics. Additionally, the study aims to explore whether there was a shift in the selection of patients prioritized for immediate evaluation regarding suspicion of UBC.Materials and Methods The study included all patients diagnosed with UBC in the NU Hospital Group between 2010 and 2019. To evaluate changes associated with SCP, patients were divided into two diagnostic time periods, either before (2010-2015) or during (2016-2019) the implementation of the SCP. To evaluate which patients were prioritized for prompt evaluation within 13 days, logistic regression analysis was performed on all patients before and during SCP.Results Median time to transurethral resection of the tumour in urinary bladder (TURBT) decreased from 29 days (interquartile range [IQR] 16-48) before SCP to 12 days (IQR 8-19) during SCP (p < 0.001) with a clear break from 2016. The proportion of cT2 + tumours decreased during SCP from 26% to 20% (p = 0.035). In addition, tumours detected during SCP were smaller (p = 0.023), but with more multiple lesions (p = 0.055) and G3 tumours (p = 0.007). During SCP, there was no statistically significant difference between the groups of patients with TURBT within or after 13 days. In contrast, before SCP, a majority of the patients treated within 13 days had advanced tumours and were admitted from the emergency ward.Conclusions The implementation of an SCP for suspected UBC was associated with improved tumour characteristics. Interestingly, during SCP, there were no substantial differences in patients' or tumours' characteristics among those who underwent TURBT within or after 13 days. This indicates that the 13-day timeframe for TURBT might be prolonged, especially in less urgent cases in order to facilitate a prioritization of more severe cases with treatable disease.
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| 9. |
- Abuhasanein, Suleiman, et al.
(författare)
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Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:3, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 10. |
- Aljabery, Firas, et al.
(författare)
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M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer
- 2018
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 36:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTumor-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.MethodsWe 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.ResultsThe 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).ConclusionsM2-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.
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| 11. |
- Aljabery, Firas, et al.
(författare)
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PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
- 2015
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Ingår i: BMC Urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 15:1, s. 87-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. 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 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.
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| 12. |
- Aljabery, Firas, et al.
(författare)
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Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer : a prospective clinical study.
- 2017
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Ingår i: BJU International. - : Wiley-Blackwell Publishing Inc.. - 1464-4096 .- 1464-410X. ; 120:3, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
- Aljabery, Firas
(författare)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 14. |
- Aljabery, Firas, et al.
(författare)
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The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer
- 2023
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Ingår i: Urologic Oncology. - : ELSEVIER SCIENCE INC. - 1078-1439 .- 1873-2496. ; 41:3
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 15. |
- Aljabery, Firas, et al.
(författare)
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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 cancer
- 2018
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 36:12, s. 530.e7-530.e18
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 16. |
- Bergengren, Oskar, et al.
(författare)
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Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
- 2023
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Ingår i: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 17. |
- Berrum-Svennung, Ingela, et al.
(författare)
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A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences
- 2008
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 179:1, s. 101-105
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. Materials and Methods: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. Results: Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. Conclusions: We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent I recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.
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| 18. |
- Bobjer, Johannes, et al.
(författare)
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A population-based study on the effect of a routine second-look resection on survival in primary stage T1 bladder cancer
- 2021
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 55:2, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 19. |
- Bobjer, Johannes, et al.
(författare)
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Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 20. |
- Danielsson, Gun, et al.
(författare)
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Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment
- 2018
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:5-6, s. 377-384
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) instillations.Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients’ life.Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being.Conclusion: Patients with bladder cancer T1G2–G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patient’s well-being. It is important to record the patients’ baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.
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| 21. |
- Duchek, Milos, et al.
(författare)
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Bacillus Calmette-Guerin Is Superior to a Combination of Epirubicin and Interferon-alpha 2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bacillus Calmette-Guerin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. Objective: To compare BCG to the combination of epirubicin and interferon-alpha 2b as adjuvant therapy of T1 tumours. Design, setting, and participants: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. Measurements: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. Results and limitations: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p = 0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p = 0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. Conclusions: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.
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| 22. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
- 2012
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 110:2B, s. E41-E45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
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| 23. |
- Gårdmark, Truls, et al.
(författare)
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Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer
- 2007
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:4, s. 817-820
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up. Patients and methods: Between 1987 and 1992, 261 patients were included; they had frequently recurring Ta/T1G1–G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death. Results: The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98); most (95, 68%) died from other causes. Conclusion: Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival.
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| 24. |
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| 25. |
- Hemdan, Tammer, et al.
(författare)
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5-Year Outcome of a Randomized Prospective Study Comparing bacillus Calmette-Guerin with Epirubicin and Interferon-alpha 2b in Patients with T1 Bladder Cancer
- 2014
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Ingår i: Journal of Urology. - : Elsevier. - 0022-5347 .- 1527-3792. ; 191:5, s. 1244-1249
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guerin alone compared to a combination of epirubicin and interferon-alpha 2b in the treatment of patients with T1 bladder cancer. Materials and Methods: Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. Results: The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guerin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guerin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. Conclusions: Bacillus Calmette-Guerin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guerin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guerin therapy.
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