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J Roigas

Publications and source records attributed to J Roigas.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Laparoscopic radical nephrectomy: indications, techniques, and oncological outcome].

Renal cell carcinoma is likely to become one of the most important indications for laparoscopic surgery worldwide. The laparoscopic technique combines the benefits of the minimally invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen extraction has become the standard technique for radical nephrectomies. We report the indications, techniques, and oncological outcome in a single center experience in 100 cases. The mean tumor size was 5.9 cm (range: 2-11 cm), the blood loss was 220 ml, and the mean surgical time was 211 min, including the learning curves of five surgeons. Histological findings were pT1 in 66 (66%), pT2 in 11 (11%), and pT3 in 19 (19%) patients with an increasing tumor size according to the experience of the surgeons. In four cases (4%) histology did not prove malignant disease. Positive lymph nodes were detected in three cases (3%) and surgical margins were negative for tumor in all patients. To date 61 patients were available for follow-up; patients with primary metastatic disease were excluded from this analysis. Follow-up was between 1 and 30 months with an average of 12.9 months. Progressive disease occurred in two cases in patients with pT3G3 tumors. No cases of local recurrence or port metastasis occurred during observation. Laparoscopic radical nephrectomy is a routine, effective treatment for patients with renal cell carcinoma. Our follow-up data up to 30 months confirm the effectiveness of laparoscopic radical nephrectomy in terms of surgical principles and oncological outcome.

Adult↗
PubMed2003

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗
PubMed2002

[Systemic immunotherapy of metastatic renal cell carcinoma and long-term outcome].

Within the last 10 years, immunotherapy has progressively become an established treatment for patients with metastatic renal cell carcinoma. The cytokines interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are the substances that have shown the greatest effects. Both have been approved for the treatment of patients with metastatic renal cell carcinoma in Germany. Subcutaneous application of these frequently combined cytokines is the schedule of immunotherapy used most often in Germany. Combined cytokine therapy (IL-2 and IFN-alpha) achieves response rates comparable to more aggressive immunotherapies. The retrospective analysis of treatment results from 66 patients with a follow-up of at least 5 years after the start of combined s.c. IL-2 and s.c. IFN-alpha +/- 5-fluorouracil (response classification: CR: 7, PR: 11, SD: 20, PD: 28) shows that the classification of the treatment results according to WHO criteria is the strongest predictor for survival compared with basic factors such as TNM status, grading, or number of metastatic sites. The combination of cytokine treatment with other treatment modalities (for example, surgical intervention) leads to a differentiated treatment according to the tumor status of the patient with metastatic renal cell carcinoma. Specific immunotherapies are still experimental. No approval has been granted for any of these treatments. Only standardization of these protocols can lead to a supplemental form of immunotherapy. Although several aspects of cytokine-based immunotherapy need further scientific evaluation, it is the treatment of choice for patients with metastatic renal cell carcinoma. However, for further progress in this field, prospective evaluation of immunotherapy for metastatic renal cell carcinoma is still needed. The German society for immunotherapy serves as a platform for this research.

Adult↗
PubMed2002

Estramustine phosphate enhances the effects of hyperthermia and induces the small heat shock protein HSP27 in the human prostate carcinoma cell line PC-3.

The antimicrotubule drug estramustine phosphate (EMP) has been shown to sensitize prostate carcinoma cells to radiation via synchronization at the G2/M phase of the cell cycle. This synchronization may also render cells more sensitive to hyperthermia, providing a rationale for multimodal treatment approaches. We have investigated the effects of EMP and hyperthermia, as well as the regulation of heat shock proteins (HSP) in the PC-3 prostatic carcinoma cell line. Cells were incubated with four doses of EMP for 48 h followed by a 1-h hyperthermia treatment ranging from 41 degrees C to 44 degrees C. Cell cycle distribution at the end of the EMP incubation was investigated by flow cytometry. Cytotoxicity was assessed by colony formation assays. HSP accumulation was investigated by Western immunoblotting. Doses of 1, 5, 10 and 15 microM EMP synchronized 27, 28, 46, and 68% of PC-3 cells at G2/M. With 5, 10 and 15 microM, a sensitizing effect of EMP was assessed at hyperthermic temperatures of 42, 43 and 44 degrees C. EMP did not alter the expression of HSP72, but substantially induced the synthesis of HSP27 in PC-3 cells. Our data show that EMP sensitizes PC-3 cells to hyperthermia induced cytotoxicity. This observation supports the rationale for multimodal treatment approaches in locally advanced prostate cancer.

Antineoplastic Agents↗
PubMed2002

[Radical prostatectomy in clinically localized prostate carcinoma. Pro laparoscopic approach].

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.

Adult↗
PubMed2001

Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1alpha in clear cell renal carcinomas.

The transcription factor hypoxia-inducible factor (HIF)-1 is an important mediator of hypoxic adaptation of tumor cells and controls several genes that have been implicated in tumor growth. Oxygen-dependent degradation of HIF-1alpha, the regulatory subunit, requires binding to the von Hippel Lindau (VHL) protein. Because functional inactivation of the VHL tumor suppressor gene occurs in up to 70% of clear cell renal carcinomas, we investigated whether this results in overexpression of HIF-1alpha and its target genes. Immunoblotting revealed increased expression of HIF-1alpha in 24 of 32 (75%) clear cell renal carcinomas but only 3 of 8 non-clear cell renal tumors. Somatic mutations of the VHL gene were detected only in clear cell renal carcinomas that overexpressed HIF-1alpha. None of the HIF-1alpha-negative tumors displayed a VHL mutation. The level of HIF-1alpha mRNA was not different between tumors and adjacent kidney tissue. Immunohistochemistry revealed distinct patterns of nuclear staining for HIF-1alpha, depending on histological type and overall abundance of HIF-1alpha. In those clear cell renal carcinomas that showed increased expression on immunoblots, HIF-1alpha was expressed in almost all cells. In the remaining clear cell and in non-clear cell tumors, staining was focal; these different patterns thus were compatible with genetic stabilization in contrast to microenvironmental stimulation of HIF-1alpha as the primary mechanism. The mRNA expression of two known target genes of HIF-1alpha, vascular endothelial growth factor and glucose transporter 1, increased progressively with increasing amounts of HIF-1alpha in tumor extracts. In addition, glucose transporter 1 protein levels correlated with HIF-1alpha abundance. In conclusion, the data provide in vivo evidence for a constitutive up-regulation of HIF-1alpha in the majority of clear cell renal carcinomas, which leads to more widespread accumulation of this transcription factor than hypoxic stimulation. These observations are most likely linked to functional inactivation of the VHL gene product. Increased expression of HIF-1alpha is associated with alterations in gene expression patterns that are likely to contribute to tumor phenotype and progression.

Adenocarcinoma, Clear Cell↗
PubMed2001

[Brachytherapy of local prostatic carcinoma].

Brachytherapy of prostate cancer has become attractive in recent years in Germany. There are several radioactive sources available, which are physically different. Some of them are used as permanent or temporary implants. The permanent sources most frequently used are iodine 125, palladium 103, and gold 198. Iridium is a temporary implant. The techniques used in Germany are low-dose rate (LDR) and high-dose rate brachytherapy, which differ in dose distribution and patient population. The success of prostate cancer brachytherapy depends on patient selection and choosing the right source for the technique used. Best suited for LDR monotherapy is the low-risk patient with a prostate-specific antigen (PSA) level below 10 ng/ml, maximal tumor stage T2b, and a Gleason score of less than 7.

Brachytherapy↗
PubMed2001

[Thermoradiotherapy with interstitial thermoseeds in treatment of local prostatic carcinoma. Initial results of a phase II study].

Several experimental data are available regarding the efficacy of the combination of interstitial hyperthermia and conformal radiation therapy. We planned a phase II trial as a member of the special hyperthermia research group of the Deutsche Forschungsgemeinschaft (German Research Society) to determine the efficacy of thermoradiotherapy using interstitial cobalt-palladium thermoseeds in the treatment of patients with localized prostate cancer. Forty-one patients with localized prostate cancer were enrolled in the study between July 1997 and April 2000. The interstitial hyperthermia induced in a magnetic field was applied in six sessions once a week. Conformal three-dimensional radiation therapy was given simultaneously in daily fractions of 1.8 Gy with a total dose of 68.4 Gy. We measured intraprostatic temperatures between 42 degrees and 46 degrees C. No major side effects were observed during the hyperthermia session. The median level of prostate-specific antigen (PSA) decreased from 11.25 ng/ml to 0.88 ng/ml 3 months after treatment and to 0.38 ng/ml 12 months after treatment with a median follow-up of 10 months. The mean prostate volume decreased from 32.6 ml to 26 ml after 3 months of treatment and to 18.5 ml after 12 months. Interstitial hyperthermia is a feasible, well-tolerated procedure in prostate cancer therapy. A significant PSA decrease was observed. Longer follow-up is necessary to determine the efficacy.

Aged↗
PubMed2001

[Laparoscopic radical prostatectomy. Experiences with 145 interventions].

Encouraged by the groups in Paris, we performed 145 laparoscopic radical prostatectomies between June 1999 and the end of November 2000. The indication for laparoscopic prostatectomy is the same as for open surgery: an organ-confined cancer. Previous abdominal surgery, transurethral resection, and/or relative adiposity are not considered to be contraindications for this laparoscopic procedure. The mean operating time was 255 min; the last 60 procedures took an average of 200 min. In no case was it necessary to convert to open surgery. Worthy of note was the low blood loss of 185 ml on average so that in 98% of the patients no blood transfusion was required. After completing the learning curve, the average indwelling catheter time was only 5.5 days. The postoperative complication rate was 11.7%, consisting mainly of minor complications. Also with regard to continence and potency, the results were representative. Postoperatively, 75%, 86%, 92%, and 93% of the patients were continent after 3, 6, 9, and 12 months, respectively. In our opinion, laparoscopic radical prostatectomy is an alternative to open prostatectomy, offering a number of advantages for the patient and surgeon as well.

Aged↗
PubMed2000

[Tumor M2 pyruvate kinase in renal cell carcinoma. Studies of plasma in patients].

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.

Biomarkers, Tumor↗
PubMed1998

Effects of combined treatment of chemotherapeutics and hyperthermia on survival and the regulation of heat shock proteins in Dunning R3327 prostate carcinoma cells.

BACKGROUND: Hyperthermia can enhance the clinical response of chemotherapeutic agents in prostate cancer, but optimal sequencing of this combination therapy needs to be developed. Given the role of heat shock proteins (HSPs) in the development of resistance (thermotolerance) to subsequent hyperthermic stresses as well as to certain chemotherapeutics, the study of HSP regulation is important in the establishment of effective schedules in multimodal treatment strategies. METHODS: In this study we evaluated the effects of the chemotherapeutic agents cisplatin, 5-fluorouracil, and adriamycin in combination with hyperthermia. (43 degrees C, 1 h) on clonogenic survival and inducible HSP70 regulation in Dunning rat adenocarcinoma of the prostate. HSP70 was analyzed by Western blot and by measuring beta-galactosidase produced by cells stably transfected with a gene construct containing the E. coli beta-galactosidase gene driven by the Drosophila HSP70 promoter. RESULTS: Colony formation assays revealed a sensitizing effect of hyperthermia when simultaneously combined with each chemotherapeutic agent, resulting in a potentiated cytotoxicity compared to subsequenced treatments. Thermotolerant cells showed a significantly better survival when treated with adriamycin alone, but also when each chemotherapeutic agent was combined with hyperthermia. This enhanced survival was correlated with inducible HSP70 accumulation. The chemotherapeutics modified the HSP70 promoter activation induced by hyperthermia, suggesting changes in the development of cellular thermotolerance. CONCLUSIONS: Our data reveal synergistic cytotoxic effects of the synchronous application of chemotherapeutic agents and hyperthermia on this model of prostate cancer. Furthermore, they demonstrate that the induction of HSPs in thermotolerant cells, as measured by HSP70 induction, results in a modulation the chemotherapeutic-mediated cytotoxicity. Therefore, HSP70 is a useful marker of cellular resistance in multimodal approaches combining hyperthermia and chemotherapeutic agents in the treatment of locally advanced prostate carcinoma.

Animals↗
PubMed1998

Laparoscopic ureterolithotomy.

We report about the successful laparoscopic removal of ureteral stones. Since July 1993, 21 patients with large ureteral calculi have undergone laparoscopic ureterolithotomy. In 19 of 21 patients, laparoscopic ureterolithotomy was successful. The mean operating time was 90 minutes. The postoperative inhospital stay was 1 to 4 days. Laparoscopic ureterolithotomy offers an alternative to open surgery in patients with large ureteral stones or when less invasive measures fail.

Adult↗
PubMed1997

Beta-galactosidase as a marker of HSP70 promoter induction in Dunning R3327 prostate carcinoma cells.

Hyperthermia is known to improve the response of tumors to radiation or chemotherapeutic treatment when combined in multimodal strategies. The cellular response to hyperthermia is associated with the synthesis of heat shock proteins (HSP). To study the stress response in prostate cancer we have developed a clone of Dunning R3327 rat prostate carcinoma cells stably transfected with a gene construct containing the E. coli beta-galactosidase gene driven by the Drosophila HSP70 promoter. The measurement of beta-galactosidase serves as a rapid and semiquantitative assay of HSP70 gene activation. The Dunning cell clone showed evidence of incorporation of the HSP70/beta-galactosidase construct within the genomic DNA by Southern blot analysis. When compared to mock-transfected control cells, the clone showed minimal baseline beta-galactosidase activity, which significantly increased following a hyperthermic stress. The time course of beta-galactosidase elevation following heat stress paralleled the time course of cellular HSP70 elevation by Western blot analysis. These stably transfected Dunning R3327 cells may provide a useful tool to study the effects of hyperthermia, radiation, and chemotherapeutic agents on the cellular stress response and in the establishment of HSP70 as a marker of cellular resistance in the multimodal treatment of prostate cancer.

Adenocarcinoma↗
PubMed1997

High-dose rate iridium192 afterloading therapy in combination with external beam irradiation for localized prostate cancer.

Development of afterloading techniques in combination with external radiotherapy allows for curative therapy modality for stage C prostate cancer. Between 10/92 and 12/95 128 patients were treated. Stage B and C tumors were found in 36 and 89 cases, respectively. All patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. 9 Gy a week was applied during the first and second weeks of treatment (10/92-12/93: 10 Gy each week) interstitially with high-dose rate iridium192 brachytherapy to the prostate. After this, a four-field box of external beam radiation therapy was given to the prostate to a dose of 45 Gy/25 fractions (10/92-12/93: 40 Gy/20 fractions). Before starting treatment median PSA was 13.8 ng/ml. The median PSA 3, 12, and 24 months after completion of therapy was 1.2, 0.78, and 0.75 ng/ml, respectively. Negative biopsies 12 and 24 months after therapy were observed in 56% (49/87) and 72% (31/43), respectively.

Adenocarcinoma↗
PubMed1996

Prenatal hypoxia alters the postnatal development of beta-adrenoceptors in the rat myocardium.

The effect of prenatal hypoxia on the development of the beta-adrenoceptor during the ontogenesis of rats was investigated. It was shown that the offspring from hypoxic dams, in comparison with normoxic control animals, exhibited alterations of the density (Bmax) of the myocardial beta-receptors and of the catecholamine levels in heart tissue during development. The results suggest that the beta-adrenoceptor changes might be involved in the phenomenon of enhanced sensitivity of prenatal hypoxic animals to catecholamines in adult age.

Animals↗