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Fredrik Liedberg

Publications and source records attributed to Fredrik Liedberg.

12 recordsLinked to original sources
PubMed2026

Stage-Independent Real-Time Subtype Classification and Comprehensive Biopsy Profiling of Urothelial Carcinomas by the Lund Taxonomy System.

Bladder cancer is a heterogeneous malignancy with diverse clinical outcomes, and conventional pathological assessment alone is insufficient to capture its underlying biology. Gene expression profiling can stratify tumors into molecular subtypes with prognostic and predictive potential, but the reliability of transcriptomic classification and its clinical utility remains to be established. The translational/observational UROSCANSEQ study (ISRCTN15459149) prospectively evaluates RNA-based Lund Taxonomy (LundTax) molecular subtype classification in a clinical setting. Among 784 consecutive biopsies collected between 2018 and 2022, RNA sequencing was successful for 90% of all biopsies, encompassing 662 bladder cancer patients with a stage distribution of 48% Ta, 27% T1, 24% ≥T2, and 1% CIS. We demonstrate that the LundTax subtype classification algorithm, applied to individual samples, accurately identifies cancer cell phenotypes with characteristic gene and protein expression patterns in a manner robust to RNA quality, data preprocessing strategies, and batch effects, supporting its clinical feasibility across both non-muscle-invasive and muscle-invasive disease. We further extend the LundTax framework by incorporating single-sample molecular risk scores reflecting tumor grade, proliferation, and progression risk, as well as tumor microenvironment signatures. Both risk scores and overall immune and stromal content in biopsies were significantly associated with an increased risk of clinical progression in noninvasive disease. In a separate analysis of the relative cellular composition of the tumor microenvironment, however, only the fraction of natural killer cells remained significant. Together, the expanded LundTax system provides a comprehensive molecular portrait of individual tumor biopsies. By explicitly separating cancer cell-intrinsic phenotypes, prognostic indexes, and microenvironmental signals, the framework minimizes biological confounding and establishes a strong foundation for future studies evaluating clinical outcomes and treatment responses.

Humans↗
PubMed2006

Intraoperative sentinel node detection improves nodal staging in invasive bladder cancer.

PURPOSE: We evaluated intraoperative SN detection in patients with invasive bladder cancer during radical cystectomy in conjunction with extended lymphadenectomy. MATERIALS AND METHODS: A total of 75 patients with invasive bladder cancer underwent radical cystectomy with extended lymphadenectomy. SNs were identified by preoperative lymphoscintigraphy, intraoperative dynamic lymphoscintigraphy and blue dye detection. An isotope (70 MBq (99m)Tc-nanocolloid) and Patent Blue(R) blue dye were injected peritumorally via a cystoscope. Excised lymph nodes were examined ex vivo using a handheld gamma probe. Identified SNs were evaluated by extended serial sectioning, hematoxylin and eosin staining, and immunohistochemistry. RESULTS: At lymphadenectomy an average of 40 nodes (range 8 to 67) were removed. Of 75 patients 32 (43%) were lymph node positive, of whom 13 (41%) had all lymph node metastases located only outside of the obturator spaces. An SN was identified in 65 of 75 patients (87%). In 7 patients an SN was recognized when the nodal basins were assessed with the gamma probe after lymphadenectomy and cystectomy. Of the 32 lymph node positive cases 26 (81%) had a positive (metastatic) SN. Thus, the false-negative rate was 6 of 32 cases (19%). Five false-negative cases had macrometastases and/or perivesical metastases. In 9 patients (14%) the SN contained micrometastases (less than 2 mm), in 5 of whom the micrometastasis was the only metastatic deposit. CONCLUSIONS: SN detection is feasible in invasive bladder cancer, although the false- negative rate was 19% in this study. Extended serial sectioning and immunohistochemistry revealed micrometastases in SNs in 9 patients and radio guided surgery after the completion of lymphadenectomy identified SNs in an additional 7. We believe that the technique that we used in this study improved nodal staging in these 16 of 65 patients (25%).

Aged↗
PubMed2005

Lymph node metastasis in bladder cancer.

OBJECTIVE: We reviewed the literature on nodal staging in patients with bladder cancer treated with radical cystectomy and lymphadenectomy. RESULTS: Fractionating the lymph node specimen significantly increases the node count, whereas results are contradictory as to whether that increase improves detection of positive nodes. Pathoanatomic data indicate that extending lymph node dissection to the aortic bifurcation improves nodal staging. That approach might be beneficial, especially in cases of T3/T4a tumours, which more often have lymph node metastases above the iliac bifurcation as compared to less advanced tumours. In node-negative patients, extended lymph node dissection probably removes undetected micrometastases and thereby increases disease-free survival. Four studies suggested that a minimum of 8, 10, 10-14, and 16 nodes must be removed, to improve survival, and in another investigation aortic bifurcation was proposed as the upper limit for dissection. Some patients with positive nodes can be cured by surgery alone, even those with gross adenopathy. There is no evidence that extended lymphadenectomy increases surgery-related morbidity. The TNM classification is apparently insufficient for stratifying node-positive patients because several larger cystectomy series could not verify differences in survival between N groups. CONCLUSIONS: Fractionating the lymphadenectomy specimen increases the lymph node count. In node-negative patients, more meticulous and extended lymph node dissection (8-16 nodes or to the aortic bifurcation) probably improves disease-free survival by removing undetected micrometastases. Patients with positive lymph nodes should also be offered radical cystectomy.

Humans↗
PubMed2005

Treatment delay and prognosis in invasive bladder cancer.

PURPOSE: We studied treatment delay, and the impact on disease specific survival and stage progression in a series of patients who had undergone cystectomy. MATERIALS AND METHODS: All 141 patients underwent radical cystectomy between 1990 and 1997 due to locally advanced bladder cancer. Treatment delay was defined as time from pathological confirmation of invasive disease to performance of cystectomy, and was registered retrospectively from the patient charts. Two patients received neoadjuvant chemotherapy and were excluded from further analyses. Followup continued until April 2003 with death due to bladder cancer as the end point. Causes of death were retrieved from the Swedish Cause of Death Registry. RESULTS: The median treatment delay was 49 days, but was significantly longer for the 71 cases who were referred from other hospitals (63 vs 41 days, p < 0.001). Treatment delay did not influence cumulative incidence of death from bladder cancer. Considering all cases, there was no significant correlation between treatment delay and stage progression. For clinical stage T2 tumors, median treatment delay was 76 days among patients with stage progression compared to 41 and 48 days for those with stage regression and stage equivalence, respectively (p = 0.20). CONCLUSIONS: Treatment delay was not found to influence disease specific survival in the present study. Furthermore, treatment delay was not significantly longer in cases that progressed compared to those with equal or lower pathological stage in the cystectomy specimen.

Adult↗
PubMed2003

Interstitial laser coagulation versus transurethral resection of the prostate for benign prostatic enlargement--a prospective randomized study.

OBJECTIVE: Interstitial laser coagulation (ILC) of the prostate is a minimally invasive method for treating symptomatic benign prostatic enlargement (BPE). We performed a prospective randomized study to compare the clinical outcomes of ILC and transurethral resection of the prostate (TURP). MATERIAL AND METHODS: Between December 1997 and February 2000, 38 patients with moderate-to-severe symptomatic BPE were included in the study. Seven were subsequently excluded due to intercurrent disease or protocol violation and the remaining 31 were randomized to either TURP (n=11) or ILC (n=20). A suprapubic tube was inserted in all ILC-treated patients, and ILC was performed as an outpatient procedure when feasible. Data were recorded preoperatively and at 3-month and 1-year follow-up. The assessment parameters were International Prostate Symptom Score (IPSS), uroflow, prostate volume determined by means of transrectal ultrasound and postvoid residue. RESULTS: At 1-year follow-up, uroflowmetry indicated a more pronounced increase in peak urinary flow rate (Qmax) in the TURP patients than in the ILC subjects (p<0.02). Differences in postvoid residue, IPSS and prostate volume between the two treatments could not be evaluated due to the small number of patients in each group. Postoperative urinary tract infections occurred in 13 ILC patients but in only one TURP subject, and catheterization was done for 24 days after ILC and for 2 days after TURP. The study was ended prematurely due to the prolonged postoperative catheterization and the high rate of urinary tract infections in the ILC patients. CONCLUSIONS: At 1-year follow-up, the increase in Qmax was smaller in the ILC subjects than in the TURP patients. The ILC subjects had comparatively more postoperative urinary tract infections and more prolonged postoperative catheterization than the TURP patients.

Aged↗
PubMed2003

Diagnostic delay and prognosis in invasive bladder cancer.

OBJECTIVES: To study diagnostic delay in invasive bladder cancer in a population-based material with long-term follow-up, and to evaluate whether delay in diagnosis affects the risk of bladder cancer death. MATERIAL AND METHODS: In a previous study, 177 patients with invasive bladder cancer (T1-T4) diagnosed in 1988 were investigated with regard to diagnostic delay. A review of all available clinical records was performed. In the present study, causes of death for these patients were registered over a 12-year follow-up period, and the impact of diagnostic delay on bladder cancer death was studied by means of survival analysis. RESULTS: The median diagnostic delay in the material was 144 days. When the patients were stratified into groups with diagnostic delays of 0-3, 3-6, 6-12 and >12 months, those with T1 tumours in the two groups with a diagnostic delay of <6 months showed a trend towards a decreased risk of bladder cancer death. In contrast, in patients with muscle-invasive disease, a significantly increased risk of bladder cancer death was noted for those with a diagnostic delay of <6 months. CONCLUSION: A trend towards better prognosis was found for patients with T1 tumours with a shorter diagnostic delay. The poor prognosis of patients with muscle-invasive disease and a short diagnostic delay suggests aggressive behaviour of the tumour and may explain the worse prognosis in these patients.

Age Distribution↗
PubMedDate not supplied

The nested variant of urothelial carcinoma: a rare but important bladder neoplasm with aggressive behavior. Three case reports and a review of the literature.

OBJECTIVE: To describe our experience with the nested variant of urothelial carcinoma (UC-NV) of the bladder, by characterization of the clinical picture and the prognostic implications of this rare form of bladder neoplasm. MATERIALS AND METHODS: Three cases of UC-NV of the bladder treated in our institutions were revised and data compared with previously published case-reports. RESULTS: Three patients presented with advanced muscle-invasive UC-NV, of which two had lymph node metastasis at cystoprostatectomy. The histopathology in the latter two cases showed the same picture in the lymph node metastasis as in the primary tumor with nests of tumor cells with mild-moderate atypia. In all three cases the tumor involved a ureteric orifice or the bladder neck. CONCLUSION: UC-NV is a rare but important histopathologic entity. It has a poor prognosis. At early stage, tumors might be difficult to differentiate from benign conditions and awareness of the condition is of outermost importance.

Aged↗