S. Tschirdewahn

Validation of Circulating MMP-7 Level as an Independent Prognostic Marker of Poor Survival in Urinary Bladder Cancer

Molecular marker analyses aiming a more accurate disease characterization and risk stratification of cancer patients provided several promising marker candidates in the last few years. However, recent reviews underlined the paramount importance of validation, since many of the initially promising results could not be confirmed in independent patient cohorts. If serum or plasma is a more appropriate sample to test for prognostic markers is a matter of debate. We recently found serum MMP-7 levels to correlate with poor patients’ prognosis in urinary bladder cancer. In this study, we examined associations of the MMP-7 plasma levels with clinical follow-up data in an independent cohort of bladder cancer patients to validate our former results and to assess if plasma is also suitable for MMP-7 analysis. Plasma levels of 97 patients and 22 controls were analyzed, using enzyme-linked immunosorbent assay. Associations between MMP-7 plasma concentrations and clinical data were assessed applying both univariate and multivariate analysis. Plasma MMP-7 levels were significantly higher in patients than in controls. Similarly to our former findings in sera, high MMP-7 plasma levels proved to be significant and independent predictors of both overall and disease-specific survival. In addition, we observed a metastasis-specific difference in MMP-7 levels between serum and plasma. In summary, we confirmed the prognostic relevance of circulating MMP-7 levels in an independent cohort of patients and concluded that circulating MMP-7 levels may help to identify bladder cancer patients at high-risk of disease progression who could benefit from an adjuvant chemotherapy or from an extended lymph node dissection.

Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer

In this study, we assessed the changes and prognostic relevance of syndecan-1 (SDC1) tissue and serum levels in bladder cancer (BC). SDC1 levels were analyzed in 213 samples (119 paraffin-embedded and 79 serum samples of BC patients and 15 controls) using immunohistochemistry and enzyme-linked immunosorbent assay. Results were correlated with clinicopathological characteristics and follow-up data, as well as previously determined serum levels of angiogenic factors (basic fibroblast growth factor, endostatin, angiostatin, angiopoietin, vascular endothelial growth factor, Tie2 and MMP-7). SDC1 staining was present in the cell membrane of normal bladder epithelium and non-muscle-invasive BC cells but was absent in a significant proportion of muscle-invasive carcinomas (P < .001). In contrast, stromal SDC1 expression was enhanced in muscle-invasive compared to non-muscle-invasive BCs (P = .001). Serum concentrations of the SDC1 ectodomain were higher in muscle-invasive BCs compared to controls or non-muscle-invasive carcinomas (P < .001 each). Lymph node-positive cases had the highest SDC1 serum concentrations (P < .001). SDC1 expression in stromal cells was independently associated with survival (hazard ratio = 2.034, 95% confidence interval 1.176-3.519, P = .011). SDC1 serum concentrations correlated with those of endostatin and matrix metalloproteinase 7. Loss of SDC1 in tumor cells and the parallel increase of serum SDC1 ectodomain concentration in high-stage, high-grade BCs suggest the involvement of SDC1 shedding in BC progression. In addition, high preoperative SDC1 serum levels may help to identify patients with lymph node metastases, supporting therapeutic decision-making. Presence of SDC1 in tumor stroma is an independent risk factor for patient survival and may therefore be used to select patients for more aggressive therapy.

Prognostic effect of serum and tissue YKL-40 levels in bladder cancer

OBJECTIVESnYKL-40 is a novel inflammatory serum protein shown to be associated with the presence and prognosis of several malignancies. However, its prognostic relevance has not yet been analyzed in bladder cancer (BC). Therefore, the aim of this study was to assess the tissue, serum, and urinary levels of YKL-40 and their prognostic value in BC.nnnMETHODS AND MATERIALSnYKL-40 gene expression levels were analyzed in frozen tissue samples of 91 patients with BC; YKL-40 concentrations were measured in 120 serum (101 patients with BC and 19 controls) and 154 urine samples (125 patients with BC and 29 controls). In 16 cases, corresponding serum samples collected before and after radical cystectomy were analyzed for YKL-40. Results were correlated with clinicopathological parameters and follow-up data.nnnRESULTSnYKL-40 gene expressions and serum concentrations were higher in patients with BC compared with controls; however, urinary YKL-40 levels remained under the detection limit in both patients and controls. Higher tissue gene expressions and serum concentrations were associated with poor patients survival in the univariable analysis (P = 0.037 and 0.022, respectively), but only high YKL-40 serum levels proved to be independent prognostic factors in BC (hazard ratio = 1.755, 95% CI: 1.014-3.039, P = 0.045). We found no significant difference between preoperative and postoperative serum concentrations of YKL-40.nnnCONCLUSIONSnYKL-40 serum levels are associated with the presence of BC and poor patients survival. The independent prognostic relevance of YKL-40 is of particular interest in patients with muscle-invasive BC treated with radical surgery. Our data suggest that BC tissue is not the main source of serum YKL-40 levels.

[Urothelial carcinoma of the bladder: evaluation by combined endoscopy and urine cytology: is incontrovertible assessment possible?].

ZusammenfassungHintergrundDie transurethrale Resektion von Tumoren der Harnblase dient der vollständigen Entfernung des Tumors, sowie der Entnahme von Gewebe zur histologischen Untersuchung. Nichtinvasive Low-grade-Tumoren mit geringem Progressionsrisiko sind durch eine oberflächliche Resektion ausreichend therapiert; um dies rechtfertigen zu können, muss eine sichere Unterscheidung zwischen nichtinvasiven Low-grade-, High-grade- und invasiven Tumoren möglich sein.Material und MethodeEs wurden 160xa0Patienten mit zystoskopisch gesichertem Urothelkarzinom der Harnblase einer fraktionierten transurethralen Resektion unterzogen. Der Tumor wurde perioperativ makroskopisch und mittels bimanueller Palpation und Urinzytologie eingeschätzt und im Verlauf mit der definitiven Histologie verglichen.ErgebnisseIn unserer Studie konnte sicher zwischen Low-grade- und High-grade-Tumoren unterschieden werden. Ebenso konnten alle nichtmuskelinvasiven Befunde makroskopisch auch als solche erkannt werden.SchlussfolgerungDer in der Urinzytologie erfahrene Urologe kann durch die intraoperative makroskopische Tumoreinschätzung in Verbindung mit der perioperativen Bewertung der Urinzytologie gut differenzierte nichtmuskelinvasive Urothelkarzinome der Harnblase sicher einschätzen.AbstractBackgroundTransurethral resection of transitional cell carcinoma of the bladder provides a definitive surgical treatment and supplies tissue for histological evaluation. Superficial low-grade carcinomas with a small risk of progression are treated properly with fulguration alone. To justify fulguration as a definitive treatment of papillary bladder tumours, one must be able to safely distinguish low-grade, noninvasive tumours from those that are high grade and potentially invasive.Material and methodsA total of 160 patients with a transitional cell carcinoma at cystoscopy underwent transurethral resection of the tumour. The macroscopic appearance of the tumour, the aspect with bimanual palpation and the perioperative urine cytology were compared with the histological report.ResultsIn our study we were able to safely distinguish low-grade tumours from high-grade tumours. All noninvasive tumours could be identified visually as such.ConclusionUrologists skilled in the evaluation of urine cytology can distinguish low-grade noninvasive tumours of the bladder from high-grade and potentially invasive tumours by means of appearance at cystoscopy and perioperative urine cytology.

Soluble syndecan-1 (SDC1) serum level as an independent pre-operative predictor of cancer-specific survival in prostate cancer

PSA‐screening detects many cases of clinically non‐aggressive prostate cancer (PC) leading to significant overtreatment. Therefore, pre‐operatively available prognostic biomarkers are needed to help therapy decisions. Syndecan‐1 (SDC1) is a promising prognostic tissue marker in several cancers including PC but serum levels of shedded SDC1‐ectodomain (sSDC1) have not been assessed in PC.

Endoscopic management of urethral stricture

ZusammenfassungSeit der ersten endoskopischen Urethrotomie 1893 durch Felix Martin Oberländer in Dresden haben sich große Fortschritte in der Behandlung der Harnröhrenstriktur ergeben. Mit der Einführung der endoskopischen Lasertherapie und der Vielfalt rekonstruktiver Operationsverfahren der Harnröhre wurden verschiedene Möglichkeiten zur Behandlung dieser wichtigen urologischen Erkrankung verfügbar. Trotz dieses Fortschrittes stellt die Urethrotomie immer noch das bevorzugte Behandlungskonzept für primäre, kurzstreckige, bulbäre Harnröhrenstrikturen dar.Im Rahmen dieser Studie wurden 20xa0Patienten retrospektiv über einen Beobachtungszeitraum von 2xa0Jahren untersucht. Alle 20xa0Patienten wurden primär endoskopisch aufgrund einer singulären bulbären oder penilen Enge urethrotomiert. Die Häufigkeit von Rezidiven in diesem Patientenkollektiv lag bei 70%. Trotzdem erwies sich die Urethrotomie unter Sicht als sichere und effektive Methode zur Behandlung dieser Patienten. Selbst im Falle eines Rezidivs bevorzugten 80% der Patienten eine wiederholte Urethrotomie.Obwohl Langzeitergebnisse hohe Rezidivraten nach erster oder zweiter Schlitzung zeigen, gibt es bislang in der Literatur keine ausreichenden Daten, welche die Verwendung anderer Methoden unterstützen würden. Daher bleibt das primär endoskopische Management der Harnröhrenenge ein einfaches, sicheres und kosteneffektives Verfahren, welches vor einer operativen Rekonstruktion in Betracht gezogen werden sollte.AbstractGreat progress has been seen in the treatment of urethral strictures since the first endoscopic urethrotomy was performed in 1893 by Felix Martin Oberländer in Dresden, Germany. With the introduction of endoscopic laser therapy and the variety of urethral reconstruction methods other ways to treat this important urologic entity became available. Despite this progress, urethrotomy still represents the preferred treatment concept for primary, short and bulbar urethral strictures. In this study we performed a 2-year retrospective analysis of 20 patients undergoing primary endoscopic urethrotomy by single bulbar or penile narrowing. A high incidence of recurrence was seen in 70% of the patients. Nevertheless, direct vision urethrotomy represented a safe and effective transitory method to treat these patients. Moreover, 80% of the patients preferred, in cases of recurrence, a repeated urethrotomy as the treatment of choice.Although the long-term results evidence high relapse rates after the first and second procedures, there have been no sufficient data in the literature which support the use of other methods. Furthermore, primary endoscopic management of urethral strictures remains a simple, safe, and cost-effective procedure that should be indicated before more invasive approaches are taken to provide relief to these patients from this limiting problem.Great progress has been seen in the treatment of urethral strictures since the first endoscopic urethrotomy was performed in 1893 by Felix Martin Oberländer in Dresden, Germany. With the introduction of endoscopic laser therapy and the variety of urethral reconstruction methods other ways to treat this important urologic entity became available. Despite this progress, urethrotomy still represents the preferred treatment concept for primary, short and bulbar urethral strictures. In this study we performed a 2-year retrospective analysis of 20 patients undergoing primary endoscopic urethrotomy by single bulbar or penile narrowing. A high incidence of recurrence was seen in 70% of the patients. Nevertheless, direct vision urethrotomy represented a safe and effective transitory method to treat these patients. Moreover, 80% of the patients preferred, in cases of recurrence, a repeated urethrotomy as the treatment of choice. Although the long-term results evidence high relapse rates after the first and second procedures, there have been no sufficient data in the literature which support the use of other methods. Furthermore, primary endoscopic management of urethral strictures remains a simple, safe, and cost-effective procedure that should be indicated before more invasive approaches are taken to provide relief to these patients from this limiting problem.

Correlation of pathological and cytological-cytometric grading of transitional cell carcinoma of the urinary tract.

Introduction: Cystoscopy and cytology are standard procedures for diagnosis and follow-up of patients with bladder cancer. Urinary cytodiagnosis is a descriptive method for tumor characterization. We correlated histopathologic diagnosis of noninvasive urothelial carcinomas with cytological evaluation and, furthermore, we validated cytology by cytometric analysis. Patients and Methods: 94 patients with a history of bladder cancer were included in the study. 25 patients were negative for tumors, 22 showed pTa G1 carcinomas, 25 had pTaG2 and 22 patients had G3 carcinomas. All patients underwent cytological and cytometric evaluation. Nuclear diameter and circumference were measured for 15 representative nuclei per specimen. Statistical evaluation was performed using Graph Pad Software. Results: Cytology showed excellent tumor detection for G2 and G3 carcinomas, with a sensitivity of 100% combined with a specificity of 100%. Using cytometry, we can significantly distinguish between unsuspicious patients and G1 carcinomas on the one hand and high-grade carcinomas on the other. Furthermore, in 6 of 25 patients (24%) with noninvasive G2 carcinomas, but G3 cytological evaluation, tumor progression occurred. Conclusions: Urinary cytology is an excellent instrument for detection of clinically relevant high-grade bladder cancer. Descriptive alterations of the cytopathology can be validated by objective data using cytometric analysis.

Renal cell carcinoma and tumour thrombus in the inferior vena cava: clinical outcome of 98 consecutive patients and the prognostic value of preoperative parameters.

AbstractObjectivesnTo evaluate the outcome of patients after nephrectomy and removal of tumour thrombus and to assess the prognostic value of preoperative parameters.Patients and methodsNinety-eight patients who were surgically treated between 2002 and 2011 were included. Patients’ charts were reviewed, and patients with renal cell carcinoma (RCC) and concomitant tumour thrombus in the renal vein (RV) were compared with those with extended inferior vena cava (IVC) thrombus. Wilcoxon rank-sum test, Kaplan–Meier analysis and uni- and multivariate Cox regression analysis were used for statistical evaluation.ResultsFollow-up was 36xa0months (20–122xa0months), and 5-year disease-specific survival (DSS) and overall survival were 68.4 and 54.1xa0%, respectively. Patients with extended thrombus (levels 2–4) had higher intraoperative transfusion rates of concentrated red cells (CRC) and fresh-frozen plasma (FFP) compared with patients with thrombus confined to the RV (CRC: 5.8 vs. 1.5, pxa0<xa00.0001; FFP: 2.3 vs. 0.4, pxa0=xa00.0032). Surgery time (190 vs. 107xa0min, pxa0<xa00.0001), duration of hospitalisation (16 vs. 11xa0days, pxa0=xa00.0269), serum phosphate (3.64 vs. 3.29xa0mmol/l, pxa0=xa00.0369) and CRP levels (6.7 vs. 4.4xa0mg/dl, pxa0=xa00.0194) as well as aPTT were increased (33.7 vs. 29.6xa0s, pxa0=xa00.0059) in extended thrombus disease. In multivariate analysis, the presence of distant metastasis (pxa0=xa00.03) and lymphovascular invasion (pxa0=xa00.001), high platelet counts (pxa0=xa00.001) and high serum potassium levels (pxa0=xa00.032) proved to be independent prognostic factors.ConclusionThe surgical treatment of RCC with tumour thrombus in the RV or IVC has favourable results. Extended thrombus disease requires multidisciplinary approach. High serum potassium levels and platelet counts are associated with reduced DSS.n

[Urine-based cytological diagnosis against the background of the new histopathological classification].

ZusammenfassungDie Urinzytologie ist neben der Zystoskopie und der transurethralen Resektion integraler Bestandteil in der Diagnostik und Charakterisierung von Urothelkarzinomen der Harnblase. Nach der neuen WHO-Klassifikation wird beim nichtinvasiven Karzinom die ehemalige Einteilung in den Differenzierungsgrad G1–3 aufgehoben und Low-grade- von High-grade-Urothelkarzinomen unterschieden. Es stellt sich die Frage, wo sich die ehemaligen nichtinvasiven G2-Karzinome in dieser neuen Klassifikation positionieren. In einer Analyse von 44xa0Patienten mit pTaG2- und 17 Patienten mit pT1G2-Urothelkarzinomen konnten wir zeigen, dass diese Karzinome zytologisch heterogen sind und sehr gut in Low-grade- und High-grade-Karzinome unterteilt werden können. Eine zytometrische Analyse unterstreicht die Ergebnisse der zytologischen Diagnostik. High-grade-Karzinome weisen eine höhere Rezidiv- und Progressionsrate auf. Die zytologische Diagnostik hilft somit in der Unterscheidung von Low- und High-grade-Urothelkarzinomen.AbstractUrinary cytology is a basic adjunct to cystoscopy and transurethral resection in the diagnosis and characterization of high-grade urothelial carcinomas of the bladder. According to the new WHO classification the former tumor grading G1-3 for non-invasive carcinomas has been replaced by a separation into low-grade and high-grade urothelial carcinomas. An interesting question is where the former non-invasive G2 carcinomas will be positioned in this new classification. In a retrospective analysis we focused on 44 patients with pTaG2 and 17 patients with pT1G2 carcinomas and found that this group of tumors is cytologically heterogeneous but easily differentiated into low-grade and high-grade lesions. A cytometrical analysis significantly underlines the results of the cytological diagnostics. High-grade tumors show a higher recurrence and progression rate. Cytological diagnostics can therefore assist in differentiating low-grade from high-grade urothelial carcinomas.Urinary cytology is a basic adjunct to cystoscopy and transurethral resection in the diagnosis and characterization of high-grade urothelial carcinomas of the bladder. According to the new WHO classification the former tumor grading G1-3 for non-invasive carcinomas has been replaced by a separation into low-grade and high-grade urothelial carcinomas. An interesting question is where the former non-invasive G2 carcinomas will be positioned in this new classification. In a retrospective analysis we focused on 44 patients with pTaG2 and 17 patients with pT1G2 carcinomas and found that this group of tumors is cytologically heterogeneous but easily differentiated into low-grade and high-grade lesions. A cytometrical analysis significantly underlines the results of the cytological diagnostics. High-grade tumors show a higher recurrence and progression rate. Cytological diagnostics can therefore assist in differentiating low-grade from high-grade urothelial carcinomas.

Urinzytologische Diagnostik vor dem Hintergrund der neuen histopathologischen Klassifikation

ZusammenfassungDie Urinzytologie ist neben der Zystoskopie und der transurethralen Resektion integraler Bestandteil in der Diagnostik und Charakterisierung von Urothelkarzinomen der Harnblase. Nach der neuen WHO-Klassifikation wird beim nichtinvasiven Karzinom die ehemalige Einteilung in den Differenzierungsgrad G1–3 aufgehoben und Low-grade- von High-grade-Urothelkarzinomen unterschieden. Es stellt sich die Frage, wo sich die ehemaligen nichtinvasiven G2-Karzinome in dieser neuen Klassifikation positionieren. In einer Analyse von 44xa0Patienten mit pTaG2- und 17 Patienten mit pT1G2-Urothelkarzinomen konnten wir zeigen, dass diese Karzinome zytologisch heterogen sind und sehr gut in Low-grade- und High-grade-Karzinome unterteilt werden können. Eine zytometrische Analyse unterstreicht die Ergebnisse der zytologischen Diagnostik. High-grade-Karzinome weisen eine höhere Rezidiv- und Progressionsrate auf. Die zytologische Diagnostik hilft somit in der Unterscheidung von Low- und High-grade-Urothelkarzinomen.AbstractUrinary cytology is a basic adjunct to cystoscopy and transurethral resection in the diagnosis and characterization of high-grade urothelial carcinomas of the bladder. According to the new WHO classification the former tumor grading G1-3 for non-invasive carcinomas has been replaced by a separation into low-grade and high-grade urothelial carcinomas. An interesting question is where the former non-invasive G2 carcinomas will be positioned in this new classification. In a retrospective analysis we focused on 44 patients with pTaG2 and 17 patients with pT1G2 carcinomas and found that this group of tumors is cytologically heterogeneous but easily differentiated into low-grade and high-grade lesions. A cytometrical analysis significantly underlines the results of the cytological diagnostics. High-grade tumors show a higher recurrence and progression rate. Cytological diagnostics can therefore assist in differentiating low-grade from high-grade urothelial carcinomas.Urinary cytology is a basic adjunct to cystoscopy and transurethral resection in the diagnosis and characterization of high-grade urothelial carcinomas of the bladder. According to the new WHO classification the former tumor grading G1-3 for non-invasive carcinomas has been replaced by a separation into low-grade and high-grade urothelial carcinomas. An interesting question is where the former non-invasive G2 carcinomas will be positioned in this new classification. In a retrospective analysis we focused on 44 patients with pTaG2 and 17 patients with pT1G2 carcinomas and found that this group of tumors is cytologically heterogeneous but easily differentiated into low-grade and high-grade lesions. A cytometrical analysis significantly underlines the results of the cytological diagnostics. High-grade tumors show a higher recurrence and progression rate. Cytological diagnostics can therefore assist in differentiating low-grade from high-grade urothelial carcinomas.