Publications (15)26.3 Total impact
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Article: Role of Marker Lesion when Applying Intravesical Instillations of IL-2 for Non-muscle-invasive Bladder Cancer Comparison of the Therapeutic Effects in Two Pilot Studies.
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ABSTRACT: Aim: Comparison of the therapeutic effect of treatment of non-muscle invasive bladder carcinoma (NMIBC) after intravesical Interleukin-2 (IL-2) instillations in the presence and absence of a marker tumour. Two pilot studies were performed in patients with NMIBC. The first study (10 patients) was performed in Krakow (Poland), the second (26 patients) in Vilnius (Lithuania). In Krakow the tumours were treated with incomplete transurethral resection (TUR) leaving a marker tumour of 0.5-1.0-cm followed by IL-2 instillations (3×10(6) IU IL-2) on five consecutive days. In Vilnius the tumours were treated with complete TUR, followed by IL-2 instillations (9×10(6) IU IL-2) on five consecutive days. During 30 months follow-up, the recurrence-free survival was 5/10 (50%) and 6/26 (23%) after incomplete and complete TUR, respectively. So, the ratio of the recurrence-free survival after incomplete/complete TUR of 50/23=2.2. The median of the recurrence-free survival is >20.5 months and 7 months after incomplete and complete TUR, respectively. So, this ratio was >20.5/7= >2.9. The hazard ratio which combines both the chance of the disease recurrence and its timing for both censored and uncensored cases was 0.53, again confirming the better outcome after incomplete TUR. A possible explanation for the better therapeutic effects after incomplete TUR compared with complete TUR is that the marker tumour has tumour-associated antigens (TAA) that could lead to an immune reaction that is stimulated by local application of IL-2. After complete TUR, no TAA are available to initiate and to stimulate an immune reaction; consequently, local IL-2 therapy is less effective after complete TUR. The results of these two pilot studies have led to the recent start of a randomised prospective clinical trial in which therapeutic effects of local IL-2 therapy after complete and incomplete TUR are compared.Anticancer research 05/2013; 33(5):2099-105. · 1.73 Impact Factor -
Article: Non-linear optical microscopy of kidney tumours.
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ABSTRACT: The unregulated cancer cell growth leads to strong alterations in morphology and composition of the tissue. The combination of coherent anti-Stokes Raman scattering, two-photon excited fluorescence and second harmonic generation enables a high resolution imaging with strong information on tissue composition and can then provide useful information for tumour diagnosis. Here we present the potential of multimodal non-linear microscopy for imaging of renal tumours. Using cryosections of human oncocytoma and carcinoma, the method gave a detailed insight in cancer morphology and composition, enabling to discern between normal kidney tissue, tumour and necrosis. Several features significant for the diagnosis were clearly visualised without use of any staining. Translation of this method in clinical pathology will greatly improve speed and quality of the analyses. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).Journal of Biophotonics 01/2013; · 4.34 Impact Factor -
Article: Combined analysis of TMPRSS2-ERG and TERT for improved prognosis of biochemical recurrence in prostate cancer.
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ABSTRACT: Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2-ERG is the most common gene fusion in PCa, whereas activation of telomerase is a common feature of various malignancies. The aim of our study was to explore the combined utility of these and some other biomarkers in predicting biochemical recurrence after radical prostatectomy. Prostate specimens and urine sediments from 179 previously untreated patients with pT2-pT3 stage PCa were analyzed for expression of telomerase (TERT and TR) and the TMPRSS2-ERG fusion gene by means of reverse transcription PCR. Real-time PCR was used for quantification of ERG and SPINK1 expression. In total, 74% (117/158) of the prostate adenocarcinomas were positive for the TMPRSS2-ERG and/or TERT expression. Noninvasively, these transcripts were identified in 31% (19/61) of catheterized urine specimens. Significantly higher expression of ERG was detected in TMPRSS2-ERG-positive tumors (P<0.0001), whereas more intense expression of SPINK1 was characteristic for the TMPRSS2-ERG-negative tumors (P=0.003). TERT-positive cases also had elevated levels of ERG (P=0.016), suggesting a possible link between aberrant expression of ERG and reactivation of TERT in prostate tumors. The cases negative for both transcripts, TMPRSS2-ERG and TERT, rarely recurred (P=0.014) and showed significantly longer biochemical recurrence-free period (P=0.022) as compared to the TMPRSS2-ERG and/or TERT-positive cases. The results of our study suggest that combined analysis of TMPRSS2-ERG and TERT expression can be a valuable tool for early prediction of biochemical recurrence of PCa after radical prostatectomy.Genes Chromosomes and Cancer 04/2012; 51(8):781-91. · 3.31 Impact Factor -
Article: Infrared spectroscopic imaging of renal tumor tissue.
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ABSTRACT: Fourier transform infrared (FTIR) spectroscopic imaging has been used to probe the biochemical composition of human renal tumor tissue and adjacent normal tissue. Freshly resected renal tumor tissue from surgery was prepared as a thin cryosection and examined by FTIR spectroscopic imaging. Tissue types could be discriminated by utilizing a combination of fuzzy k-means cluster analysis and a supervised classification algorithm based on a linear discriminant analysis. The spectral classification is compared and contrasted with the histological stained image. It is further shown that renal tumor cells have spread in adjacent normal tissue. This study demonstrates that FTIR spectroscopic imaging can potentially serve as a fast and objective approach for discrimination of renal tumor tissue from normal tissue and even in the detection of tumor infiltration in adjacent tissue.Journal of Biomedical Optics 09/2011; 16(9):096006. · 3.16 Impact Factor -
Article: Prognostic significance of peripheral blood CD8highCD57+ lymphocytes in bladder carcinoma patients after intravesical IL-2.
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ABSTRACT: The objective of this study was to evaluate the recurrence-preventing effect of intravesical instillations of interleukin-2 (IL-2) in patients with non-muscle-invasive bladder carcinoma. In addition, this study aimed to determine the significance of immune parameters for recurrence-free interval. Twenty-six patients with non-muscle-invasive bladder carcinoma were treated with intravesical instillations of IL-2 (Proleukin®, Novartis, formerly Chiron) in doses of 9 × 10(6) IU on 5 consecutive days, beginning on the second day after transurethral resection (TUR) of tumours. CD8(high)CD57(+) lymphocytes in peripheral blood were determined before TUR and compared with the recurrence-free interval after treatment. The multivariate analysis showed that CD8(high)CD57(+) lymphocytes had a prognostic significance in combination with number of bladder tumours, prior recurrence rate and age of patients. Peripheral blood CD8(high)CD57(+) lymphocytes have prognostic significance for recurrence-free survival in patients with non-muscle-invasive bladder carcinoma after TUR and intravesical IL-2.Anticancer research 02/2011; 31(2):699-703. · 1.73 Impact Factor -
Article: The value of clinical prognostic factors for survival in patients with invasive urinary bladder cancer.
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ABSTRACT: The aim of the study was to evaluate the value of clinical prognostic factors for survival of patients with invasive urinary bladder cancer treated with radical cystectomy, chemotherapy, and radiotherapy. A total of 115 patients with invasive urinary bladder cancer were analyzed. Twenty-three patients with invasive urinary bladder cancer (pT2-T4) were treated according to the protocol of a prospective clinical study. In all the cases, transurethral resection was followed by radiation and chemotherapy. A total dose of 54-60 Gy of radiotherapy was delivered by daily fractions of 1.8-2.0 Gy each. Simultaneous chemotherapy was started on the same day as radiotherapy; gemcitabine at a dose of 175-300 mg/m(2) was delivered once a week intravenously for 6 weeks. Individual patient data was analyzed in a retrospective part of the study. Radical cystectomy was performed to 46 patients with invasive urinary bladder cancer, and radiotherapy was delivered to 46 patients. Inclusion criteria for patients into a prospective or retrospective trial were equal. We evaluated a prognostic value of various clinical factors for patients treated with radical cystectomy, chemoradiation with gemcitabine, and radiation alone. The 3-year overall survival in the cystectomy group was 51.1%, in the chemoradiation group 38.0%, and in the radiotherapy group 26.9% (P=0.001). In univariate analysis in the chemoradiation group, completion of treatment according to the protocol showed a significant influence on overall survival (P=0.03). In the radiation group, completion of treatment according to the protocol showed a significant influence on overall survival too (P=0.01). In the radical cystectomy group, an important factor was a complete or incomplete TUR (P=0.02). Multivariate analysis showed a significance of hydronephrosis (P=0.03) and T stage (P=0.04) in the radiation therapy group. Comorbidity was found to be an independent prognostic factors in the chemoradiation group (P=0.02). The best 3-year overall survival was in the radical cystectomy group. Chemoradiation with gemcitabine could be offered as an alternative to patients refusing cystectomy. Better overall survival in the chemoradiation group was for patients without comorbidities and when treatment protocol was completed.Medicina (Kaunas, Lithuania) 01/2010; 46(5):305-14. · 0.42 Impact Factor -
Article: Promoter hypermethylation in tumour suppressor genes and response to interleukin-2 treatment in bladder cancer: a pilot study.
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ABSTRACT: Non-muscle invasive bladder cancer (BC) is a highly recurrent disease, with the first recurrences arising shortly after transurethral resection of the bladder (TURB). Topical administration of interleukin-2 (IL-2) has been shown as an effective adjuvant therapy for BC; however, predictive biomarkers that may identify suitable subgroups of patients are lacking. In this pilot study we sought to determine the prognostic value of epigenetic and genetic inactivation of tumour suppressor genes (TSGs) among BC patients treated with IL-2. After complete TURB, patients with multifocal superficial BC were treated with five daily intravesical instillations of IL-2. Promoter hypermethylation in six TSGs and the TP53 gene mutations were prospectively assessed by methylation-specific PCR and automated capillary single-strand conformation polymorphism in 21 primary bladder cancer specimens and ten bladder wall biopsies collected during follow-up. After IL-2 treatment, 9 out of 21 (43%) patients did not develop recurrent tumour within the 1 year of follow-up period. The mean duration of recurrence-free survival in the rest of the study group was 112 days. In the current pilot study, BC with p16 gene hypermethylation had a lower risk of recurrence after treatment with IL-2, as compared to IL-2 treated BC without p16 hypermethylation (p = 0.02). Significant associations were observed between tumour grade and the mean methylation index (p = 0.003), as well as the hypermethylation of the RARbeta gene (p = 0.048). Our preliminary data suggest that DNA methylation biomarkers may assist in selection of BC patients for efficient IL-2 therapy.Journal of Cancer Research and Clinical Oncology 11/2009; 136(6):847-54. · 2.56 Impact Factor -
Article: Promoter hypermethylation in tumour suppressor genes shows association with stage, grade and invasiveness of bladder cancer.
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ABSTRACT: Superficial bladder cancer is a highly recurrent disease, with progression to muscle invasiveness occurring in 15-30% of cases. Promoter hypermethylation in a panel of tumour suppressor genes involved in cell cycle control, apoptosis and DNA repair was analyzed in superficial bladder tumours in order to evaluate the suitability of epigenetic biomarkers for an earlier prediction of the aggressive course of the disease. Promoter hypermethylation in p16, RARbeta, RASSF1A, DAPK, and MGMT genes was analyzed in 58 cases with superficial bladder cancer and 2 cases with benign urological disease using methylation-specific PCR. Promoter hypermethylation was frequently detected in RARbeta, RASSF1A and DAPK genes, and 62% of bladder tumours exhibited hypermethylation in at least one gene. The overall frequency of hypermethylation and the number of genes involved increased with tumour stage, grade and muscle invasiveness. Aberrant methylation of RASSF1A and RARbetawas predominant (p < 0.05) in muscle-invasive tumours and high-grade tumours, respectively. Cases with concurrent hypermethylation in DAPK, p16 and RARbeta genes were moresusceptible to relapse. The results suggest analysis of promoter hypermethylation as a valuable biomarker for prognosis of the aggressive course of disease in bladder cancer.Oncology 10/2008; 75(3-4):145-51. · 2.27 Impact Factor -
Article: [Bladder preservation possibilities in the treatment of muscle-invasive bladder cancer].
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ABSTRACT: Radical cystectomy is the standard of treatment for muscle-invasive transitional cell carcinoma of the bladder in European Union and in United States. During the last few decades, several clinical trials were performed with the aim to evaluate new treatment methods as an alternative to radical cystectomy for selected patient groups. According to some clinical trials, it is clear that bladder preservation is possible without compromising overall survival of these patients. Organ preservation requires a combined-modality treatment including transurethral resection of bladder tumor, radiation therapy, and systemic chemotherapy. Incorporation of chemotherapeutic agents such as gemcitabine or taxanes in bladder-sparing protocols improves the results of conservative treatment of locally advanced bladder cancer. Pretreatment selection criteria and the most important prognostic factors are macroscopically complete transurethral resection of bladder tumor, absence of hydronephrosis, and lower T stage.Medicina (Kaunas, Lithuania) 02/2006; 42(10):781-7. · 0.42 Impact Factor -
Article: [Use of strontium-89 in the analgesic treatment of cancer patients with bone metastases].
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ABSTRACT: The aim of this article was to review the available literature regarding to the use of strontium-89 in the palliation of osteoblastic bone pain. The data of many researchers showed that approximately 80% of patients with pain from osteoblastic lesions resulting from prostate or breast cancer experience significant pain relief by administration of strontium-89, with only mild levels of hematotoxicity. The duration of pain relief in some cases exceeded 3-6 months. Indications for administration of strontium-89, effectiveness and duration of the treatment, side effects are reviewed in this article.Medicina (Kaunas, Lithuania) 02/2006; 42(1):11-4. · 0.42 Impact Factor -
Article: [Prostatic biopsy technique. Historical review].
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ABSTRACT: This article contains histological review of prostate biopsies techniques from the digitally guided prostate biopsies to modern extended-core prostate biopsy protocols. The technique of transrectal ultrasonography (TRUS) guided biopsy of the prostate has evolved considerably since the original description by K. K. Hodge and colleagues. A better understanding of the zonal anatomy of the prostate coupled with 3-D mapping of tumors in early stage prostate cancer has led to more laterally-directed biopsies and an increase in the number of cores obtained in a single setting. Most investigators recommend sampling between 10 and 12 areas, with particular focus on the lateral segments of the gland. Data gained from systematic extended-core biopsy protocols offer the hope of providing both diagnostic and prognostic information and may help urologists and patients make better informed decisions when facing with the diagnosis of prostate cancer. The first TRUS-guided sextant biopsy in Lithuania was performed at the Department of Urology, Institute Oncology of Vilnius University in 2000. Today the techniques used for TRUS-guided biopsies have evolved and now a protocol as a standard for an initial biopsy recommends obtaining 10 to 12 cores extended to lateral pattern.Medicina (Kaunas, Lithuania) 02/2005; 41(11):957-67. · 0.42 Impact Factor -
Article: Nephron sparing surgery in renal cancer--individual decision or standard procedure?
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ABSTRACT: Organ-preserving surgery has gained widespread acceptance within the international urological community through the last decade. In consequence, the question of radical vs. nephron sparing surgery for the treatment of renal cancer is increasingly discussed in a controversial way. Today, even advocates of a radical nephrectomy must admit that long-term results obtained through nephron sparing surgery are excellent. In consequence, heminephrectomy has become a standard treatment in patients with impaired renal function. However, in patients with a normal contralateral kidney, national and international guidelines still favor radical nephrectomy. An increased morbidity and doubts on the efficacy of heminephrectomy concerning tumor control are the key reasons behind this strategy. Within this analysis the authors stress the hypothesis that the actual differences between organ-preserving surgery and radical nephrectomy concerning survival are marginal if the requirements for heminephrectomy are met. Therefore, the actual controversy appears to be rather based upon assumptions and convictions than on actual facts. To definitively answer this question a prospective randomized trial is suggested, however, the problems of this study may not be underestimated.Actas urologicas españolas 02/2003; 27(1):10-7. · 0.46 Impact Factor -
Article: p21 and p53 Immunostaining and survival following systemic chemotherapy for urothelial cancer.
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ABSTRACT: Induction of apoptosis and regulation of cell cycle checkpoints are important mechanisms of chemotherapy-induced cell death. The intact p53 tumor suppressor gene is required for efficient activation of apoptosis. The WAF1/p21 gene is transcriptionally activated by p53 and mediates p53-dependent G1 arrest following DNA damage. Therefore, p53 and p21 expression might be related to urothelial tumor response to cytotoxic therapy. In a retrospective study, archival tumor specimens from 60 patients treated with cisplatinum-based systemic chemotherapy for locally advanced and/or metastatic urothelial cancer were immunohistochemically stained for p53 and p21. Response to chemotherapy and overall survival were correlated with the results of immunohistochemistry. Thirty-five tumors (58%) of the 60 specimens showed p53 accumulation, and 25 (42%) expressed detectable p21. No association between p53 accumulation and expression of p21 was observed. Correlation with complete and partial remissions following inductive chemotherapy (n = 39) demonstrated that patients with intact p53 responded significantly better (70 vs. 31%, p < 0.05). However, no difference in overall survival was observed with regard to p53 immunostaining (median 12 and 17 months for p53-positive and p53-negative tumors, respectively). The p21 expression was related neither to response nor to overall survival following inductive chemotherapy. In patients receiving adjuvant chemotherapy after cystectomy (n = 21), the outcome was correlated with the immunohistochemistry results. While the survival times for p53-negative patients (60 months) and p53-positive patients (23 months) did not translate into a significant difference, the median overall survival for patients with p21-positive or p21-negative tumors (60 vs. 21 months) was significantly different (p < 0.005). The short survival of patients with metastatic bladder cancer may conceal putative differences between different prognostic groups in smaller trials. In contrast, p21 immunohistochemistry appears to be of prognostic value in patients receiving systemic adjuvant chemotherapy for locally advanced bladder cancer. The observations made in this retrospective study in a limited number of patients warrant further investigation on the correlation between G1/S checkpoint regulatory genes and adjuvant chemotherapy in larger prospective studies.Urologia Internationalis 01/2002; 69(3):174-80. · 0.99 Impact Factor -
Article: Prolonged remission in a patient with transitional cell carcinoma of the bladder developing brain metastases after systemic chemotherapy: a case report.
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ABSTRACT: We report a case of an excellent response to M-VAC chemotherapy in a patient with pulmonary metastases from transitional cell carcinoma of the bladder. He subsequently presented with acute neurological symptoms seven weeks after the completion of chemotherapy. Computed tomography of the brain revealed a solitary 24 mm x 26 mm lesion in the frontal lobe. The brain metastasis was resected. The patient was closely followed for disease progression and showed no evidence of disease up to 42 months after surgery. The presentation and treatment policy are discussed. This case suggests that long-term remission may be obtained after surgical resection of a single brain metastasis in patients with disseminated urothelial cancer who completely responded to systemic chemotherapy.Tumori 90(4):420-1. · 0.86 Impact Factor -
Article: Considerations on implementing diagnostic markers into clinical decision making in bladder cancer.
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ABSTRACT: Bladder cancer is a common disease that is often detected late and has a high rate of recurrence and progression. Cystoscopy is the main tool in detection and surveillance of bladder cancer but is invasive and can miss some cancers. Cytology is frequently utilized but suffers from a poor sensitivity. There are several commercially available urine-based tumor markers currently available but their use is not recommended by guideline panels. Markers such as the Urovysion FISH assay and the NMP22 BladderChek test are approved for surveillance and detection in patients with hematuria. The added benefit of these markers and other commercially available markers (e.g. Ucyt+, BTA stat) has not been well investigated though it appears these markers are insufficiently sensitive to replace cystoscopy. Additional studies are needed to determine the clinical scenarios where bladder markers are best utilized (screening, surveillance, early detection, evaluating cytologic atypia) and what impact they should have on clinical decision making. Furthermore, a variety of issues and barriers can affect the movement of clinical tests from research to clinical practice. This article addresses some of the challenges facing research and medical communities in the delivery and integration of markers for bladder cancer diagnosis. Moreover, we attempt to outline criteria for the clinical utility of new bladder cancer diagnostic markers.Urologic Oncology 28(4):441-8. · 3.22 Impact Factor
Top co-authors
Top Journals
Institutions
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2006–2010
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Vilnius University
- • Onkologijos institutas
- • Gamtos mokslų fakultetas
Vilnius, Vilniaus Apskritis, Lithuania
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2002
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Universitätsklinikum Düsseldorf
Düsseldorf, North Rhine-Westphalia, Germany
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