Prognostic and predictive molecular biological markers in prostate cancer - significance of expression of genes PCA3 and TMPRSS2.

UNLABELLED: Prostate specific antigen and digital rectal examination have low specificity for detecting prostate cancer and they poorly predict the presence of aggressive disease. We present recent findings on PCA3 and TMPRSS:ERG fusion and assessed the relationship between PSA, urine PCA3 and TMPRSS2:ERG and corelation with pathological findings. We tested the PCA3 score in two groups. The first comprised 96 men treated in urology out-patient units with suspicion of prostate cancer, who had elevated PSA and/or positive DRE. The second group comprised 28 patients, who were treated by radiation for localised prostate cancer, and whose PCA3 was regularly monitored. A further cohort comprised patients with already-diagnosed tumors, who had undergone radical prostatectomy. With these, using histopathological samples, we examined samples of the TMPRSS2:ERG fusion gene and compared the results with Gleason score values and level of PSA. We also examined the TMPRSS2:ERG gene in patients who had positive biopsy. Part of the genetical analysis was also an examination of the MSMB gene.The sensitivity of PCA3 testing was 66.7% and the specificity 78.5%. TMPRSS2:ERG gene was correllated with the Gleason score. Neither the TMPRSS2:ERG (p=0.13) nor the MSMB (p=0.556) genotype had an influence on the value of the Gleason score. However a difference was found between the homozygote and wild type (WT) in the TMPRSS2 gene.FISH analysis of TMPRSS/ERG gene fusion was evaluated as positive in 8 (36.8%) of the biopsically verified tumors and in 20 (37.3%) of the evaluated patients after RAPE of parafin slicing.We did not confirm a corellation between fusion and Gleason score (p=0.29).PCA3, with its higher sensitivity in comparison with PSA, is more useful for eventual screening examination. Identification of further molecular markers such as TMPRSS2, may be very promising ways to determine further prognosis of patients with prostate cancer. KEYWORDS: prostate cancer, PSA, PCA3.

Acute toxicity of conformal high dose interstitial brachytherapy boost in prostate cancer.

Over the past few years, brachytherapy has become more and more common in the treatment of prostate cancer, largely thanks to the reduced amount of acute and chronic side effects. At the same time, brachytherapy also allows dose escalation, resulting in significant improvements in the treatment results. From August 2004 to June 2005, we irradiated 40 patients suffering from T1c-T3a prostate cancer. All of the patients underwent external beam radiotherapy with a median dose of 45-50.4 Gy and a conformal high dose interstitial brachytherapy boost (two fractions, 8 Gy per fraction). The patients were divided into three groups: low risk of recurrence (11 patients - 27.5%), intermediate risk (14 patients - 35%) and high risk (15 patients - 37.5%). The medium age of the patients was 68.7 years (between 55 and 77). Hormonal treatment was carried out 17 patients (42.5%). We evaluated the quality of each implantation, including the maximum urethral and rectal dose. The calculated doses were compared with measurements by in vivo dosimetry. Acute toxicity was evaluated in all of the patients according to the Radiation Therapy Oncology Group (RTOG) scale. Each of the patients completed an International Prostatic Symptom Score (IPSS) questionnaire. Acute genitourinary morbidity grade 1 was recorded in 37.5% of patients; grade 2 in 15% of patients. Urine retention in one of the patients resulted in the need to perform an epicystostomy. According to the IPSS score, the majority of patients (90%) experienced an improvement in symptoms related to quality of life. Grade 1 acute gastrointestinal toxicity was recorded in 40% of the patients. Grades 2-4 were not recorded. Here, we show that the combination of external beam radiotherapy and high dose rate (HDR) brachytherapy in the treatment of early prostate cancer to be feasible and well tolerated. Acute toxicity was low and scarcely influenced the quality of life. Among the risk factors of genitourinary toxicity was the volume of the prostate. For gastrointestinal toxicity, risk factors included the combination of HDR brachytherapy and external beam radiotherapy to the pelvis, as well as hormonal treatment.

[Laparoscopy-assisted exenteration of the pelvis in a locally advanced rectal carcinoma]. / Laparoskopicky asistovaná totálna exenterácia panvy u lokálne pokrocilého karcinómu rekta.

INTRODUCTION: In this pilot study, based on three case-reviews, the authors report on their initial experience with the laparoscopy-assisted total exenteration of the pelvis, conducted in patients with locally advanced rectal carcinomas. METHODS: In two patients with histologically confirmed rectal carcinomas, the neoadjuvant radiochemotherapy was initiated, due to the locally advanced tumor finding, aiming to downstage and locally control the disorder. The pelvic exenteration was indicated, based on the control findings of the imagining methods. In one patient, due to repetitive enterorrhagies, the primary surgical management was indicated. RESULTS: The surgical procedures were multidisciplinary, assisted by urologists. In all three cases, the laparoscopic resections, followed by planned conversions and constructions of the ileouretheral conduit and the terminal sigmoidostomies (resp. with their maintenance), were completed. Prior to the procedures, in all the three patients, the presence of distant metastases was excluded. No peroperative complications were recorded in the case-reviews. In one case, postoperative re-suturing of the wound was inevitable, due to its dehiscence. In this patient, the enzymatic acute MI, without the ECG correlate, was diagnosed. CONCLUSION: The laparoscopy-assisted pelvic exenteration may be a suitable modification of the classical surgical procedure in selected patient groups with locally advanced colorectal carcinomas. Good visualisation and exact orientation in the region of the small pelvis, as well as other generally accepted advantages of miniinvasive procedures, are the pros of the method.

[Prevention of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology]. / Prevence zilní tromboembolické nemoci v chirurgii, v laparoskopické chirurgii, v cévní chirurgii a v urologii.

The article summarizes published data regarding the prophylaxis of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology. In surgical patients with low risk, no specific thromboprophylaxis is needed. Patients with moderate risk levels are the candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3 400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression (IPC). At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration (LDUH) over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people with a history of heparin induced thrombocytopenia over the past three months. The sole use of acetylsalycilic acid is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis. Thromboprophylaxis with LMWH, LDUH, elastic panty-hose or IPC is indicated only in those patients who undergo laparoscopic surgeries and who moreover display the additional thrombosis factors. Patients with additional risk thrombosis factors undergoing major venous reconstructions require prophylaxis with LMWH (or LDUH). Uncomplicated patients undergoing transurethral or other low risk urologic surgery require no specific thromboprophylaxis. If they undergo a major intervention and/or they display additional risk thrombosis factors, they require the administration of LMWH or LDUH. Elastic panty-hose and/or intermittent pneumatic compression have the same indication as in abdominal surgeries.

[Acute adverse effects of high dose brachytherapy in combination with external radiotherapy in localized prostate cancer]. / Akutní nezádoucí ucinky brachyterapie s vysokým dávkovým príkonem v kombinaci se zevní radioterapií u lokalizovaného karcinomu prostaty.

BACKGROUND: Over the past few years, brachytherapy has become more and more common in the treatment of prostate cancer. Part of the reason behind this growth in the use of brachytherapy for the treatment of organ-confined prostate cancer is the reduced amount of acute and chronic side effects. On the other hand, brachytherapy allows for dose escalation, resulting in significant improvements in the treatment results. METHOD AND RESULTS: From August 2004 to June 2005, we irradiated 40 patients with T1c-T3a prostate cancer. All of the patients underwent transperineal transrectal guided high dose rate (HDR) brachytherapy (two fractions, 8 Gy per fraction) and course of external beam radiotherapy with a median dose of 45-50.4 Gy. The patients were classified into three groups: low risk of recurrence (11 patients - 27.5%), medium risk (14 patients - 35%) and high risk (15 patients - 37.5%). The medium age of the patients was 68.7 years (range of between 55 and 77). Hormonal treatment was carried out with 17 of the patients (42.5%). We evaluated the quality of each implantation, including the maximum urethral and rectal dose. The calculated doses were compared with measurements by in vivo dosimetry. Acute toxicity was evaluated in all of the patients according to the Radiation Therapy Oncology Group (RTOG) scale. Each of the patients completed an International Prostatic Symptom Score (IPSS) questionnaire. Acute genitourinary morbidity grade 1 was recorded in 37.5% of patients, and grade 2 in 15% of patients. Urine retention in one of the patients resulted in the need to perform an epicystostomy. According to the IPSS score, the majority of patients (90%) experienced an improvement in symptoms related to quality of life. Grade 1 acute gastrointestinal toxicity was recorded in 40% of the patients. Grades 2-4 were not recorded. CONCLUSIONS: We showed that the combination of external beam radiotherapy and HDR brachytherapy in the treatment of early prostate cancer to be feasible and well tolerated. Acute toxicity was low and scarcely influenced the quality of life. Among the risk factors of genitourinary toxicity was the volume of the prostate. For gastrointestinal toxicity, risk factors included a combination of HDR brachytherapy and external beam radiotherapy to the pelvis, as well as hormonal treatment.