Radiotherapy combined with hormonal therapy (RT-HT) in prostate cancer patients with low, intermediate, and high risk of biochemical recurrence: perspective and therapeutic gain analysis.

Treatment of prostate cancer (PC) is a challenge for both urologists and radiation oncologists. Currently, two radical methods of treatment are recommended in localized prostate cancer (PC)--i.e. radical prostatectomy (RP) and radiotherapy (RT) with excellent long-term results. However, the outcome of RT, which is the treatment of choice in locally advanced stages of the disease, is unsatisfactory due to the high risk of regional or distant metastases and local failure. Lately, hormonal therapy (HT), which had mainly been indicated for treatment of patients with distant metastases, has been added to radiotherapy to improve the efficacy of treatment. The general rationales for combining RT and HT are four-fold: decreasing prostate gland volume, diminishing the number of cancer cells, improving tumor oxygenation, and eliminating distant and regional micrometastases. Over the last 20 years several randomized clinical trials evaluating the results of combined HT and RT treatment have been carried out. The RTOG 85-31, RTOG 86-10, EORTC 22863 and RTOG 92-02 trials were completed from the mid 80s to the mid 90s and long-term follow-up data on all important end-points are now available. These data have been evaluated by panels of experts and served as the basis for the latest American (NCCN 2005) and European (EAU 2005) recommendations on prostate cancer. However, despite the long-term results of these trials, there are still no clear-cut answers to the following crucial questions: What is the optimal timing of hormonal therapy? What types of patients can benefit most from combined strategies? What is the spectrum and potential reversibility of side effects of long-term combined treatment? How does it influence the patients quality of life and care costs? Other questions concern the possible role of androgen deprivation therapy combined with brachytherapy. The only randomized trial to evaluate this issue to date was stopped due to incomplete accrual. Therefore, answers must be sought in the large body of nonrandomized studies. There is a constant need for properly designed randomized clinical trials to precisely identify the subgroup of patients who will benefit most from combined RT and HT treatment. Results of ongoing clinical trials (RTOG 9901, RTOG 9408) are expected to yield some answers to the questions mentioned above. Currently, we can conclude that in the group of patients with high risk of relapse (T3 or GS > 7 or PSA >20 ng/ml), combined hormonal and radiation therapy improves prostate cancer treatment results and should be highly recommended.

A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.

BACKGROUND: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. PARTICIPANTS AND METHODS: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. RESULTS: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G-->A, 1100delC). CONCLUSION: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.

Flow cytometric analysis of tumour-infiltrating lymphocytes in patients with renal cell carcinoma.

OBJECTIVE: To determine the immunophenotype of tumour-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) isolated from patients with renal cell carcinoma (RCC) and to analyse the correlations between the quantity of analysed cell subsets and the progression of the disease. PATIENTS AND METHODS: PBL and TIL samples were obtained from 23 patients with RCC at different stages of disease. The immunophenotype of PBL and TIL was measured, and the TNM stage, tumour size, cellular type, histological grade, lymphocytic infiltration and performance status assessed. RESULTS: The predominant mononuclear cells infiltrating the tumour, in all patients, were T lymphocytes (CD3+ median 66.9%, CD8+ median 34.6%, CD4+ median 26.7%). The cells possessing gamma/delta type T cell receptor accounted for a small fraction of the T cells in PBL and TIL (median 5.6% and 3.7%). Tumour-infiltrating T lymphocytes had a significantly higher percentage of cells expressing human leucocyte antigen (HLA) DR (median 30.9%) and CD25 (median 6.2%) antigens than the equivalent populations in peripheral blood from the same patient group (P < 0.001). The degree of T cell activation appeared to negatively correlate with the tumour stage (K = -0.3, P = 0.04). The percentage of natural killer (NK) cells among TIL (median 15.4%) did not reflect the value in PBL. The percentage of B cells in TIL was slightly lower than in PBL and accounted for 5.0% of cells. There was no relationship between the degree of lymphocytic infiltration and either tumour stage or grade but there appeared to be a positive correlation between the intensity of lymphocytic infiltration and the percentage of CD4+ cells in TIL (K = 0.5, P = 0.001). Moreover, the composition of TIL depended on tumour grade, which positively correlated with the percentage of CD8+ cells (K = 0.4, P = 0.005) and negatively with the percentage of NK cells (K = -0.5, P = 0.005). There was an inverse correlation with the percentage of gamma/delta T cells in PBL and the TIL concentration (K = -0.3, P < 0.05). CONCLUSIONS: The TIL immunophenotype is different from PBL and is influenced by the histological grade of the tumour. The activation of TIL and its relationship with tumour progression suggests that they might be sensitized and activated by tumour cells.

Activated gamma/delta T lymphocytes infiltrating renal cell carcinoma.

Gamma/delta (gamma delta) T lymphocytes have been postulated to play a role in a surveillance mechanism that eliminates transformed or otherwise damaged cells. In this study, we examined by flow cytometry the frequency and phenotype of gamma delta T cells in the tumour infiltrating lymphocytes (TIL) and peripheral blood (PBL) from renal cell carcinoma patients. The TCR gamma delta + cells comprised an average of 3.8% of the CD3+ TIL and 5.2% of circulating T cells. Analysis of surface immunophenotype revealed that activation markers of T lymphocytes: CD25 and HLA DR were highly expressed on the tumour infiltrating gamma delta + T lymphocytes (median 27.6% for CD25 and 52.0% for HLA DR). More importantly, percentage of activated gamma delta T cells was found to be much higher than compared to all activated CD3+ cells. Furthermore, an unusually high proportion of gamma delta positive TILs express CD4 or CD8 molecules (17.2 and 36.8%, respectively), indicating that they might recognise antigen presented within MHC II or I context. These results suggest that gamma delta T lymphocytes may play a certain role in immune response against tumour cells.

[Chondrosarcoma of the small pelvis imitating an ovarian tumor]. / Chrzestniakomiesak miednicy mniejszej imitujacy guz jajnika.

The authors present diagnostic-therapeutic record concerning chondrosarcoma-tumor in 41-year-old women operated on ovary-tumor. They point out the rareness of chondrosarcoma within pelvis, the diagnostic and therapeutic difficulties and relapses into illness after radical remove of tumour without pelvis bones resection.

[Cardiac arrhythmias during extracorporeal shock wave lithotripsy]. / Zaburzenia rytmu serca w czasie kruszenia kamieni nerkowych za pomoca fali uderzeniowej.

Holter monitoring was performed in 55 patients (24 women, 31 men), mean age 50.7 +/- 11.3 who underwent ECG-triggered extracorporeal shock wave lithotripsy (ESWL). Patients were divided into two groups A--30 with history of cardiac disease and B--25 control. The heart rate was significantly higher before and after ESWL in the first group. The number of premature ventricular contractions was higher during ESWL in the same group. No other cardiac complication was observed.

[Treatment of ureter injuries after obstetric-gynecologic surgery]. / Leczenie uszkodzen moczowodu po operacjach ginekologiczno-polozniczych.

The article presents an analysis of 21 patients with ureter injuries originated during obstetric-gynaecological operations treated in Urology Clinic in Medical Academy Poznan. Attention was particularly focused on prevention and fast diagnosis of injuries based on intra-operation examination usg, urography, and ascending pyelography. This fast diagnosis is of crucial importance for the cure.

[Giant cyst of the spermatic vesicle imitating abdominal tumor]. / Olbrzymia torbiel pecherzyków nasiennych imitujaca guz brzucha.

A paper presents the case of big cystic degeneration of spermatic vesicle found accidentally. Diagnosis was established on the basis of the objective examination and the following additional examination: urography, computer tomography, cystoscopic examination and rectal examination. The radical excision was performed and as a result full cure was achieved.

[Involuntary ureteral micturition]. / Mimowolne moczenie moczowodowe.

The paper focuses on the problem of ureteric incontinence of urine caused by dislocation of bladder ureteral orifice. A case of a 15-year old patient suffering from incontinence of urine, admitted to the Urological Clinic has been described. In order to avoid vaginoscopy, the following examinations were performed: urography, chromocystoscopy, arteriography and computer tomography. The reason for such a large number of various examinations was an unclear picture of the left kidney and the shape of the ureter, suggesting a tumour in the retroperitoneal space. The treatment ended with a removal of the kidney. The disclosed retroperitoneal space turned out to be affected by hydronephrosis.

Seasonal variations in urinary excretion of calcium and magnesium in healthy subjects and patients with renal calculus and chronic renal failure.

Renal excretion of calcium in healthy subjects and in patients with renal stones increases in the summer, as compared to the winter values. In patients with chronic renal failure calciuria shows no seasonal variations. No essential difference in the monthly excretion of magnesium in 24-hour urine has been found between healthy persons and patients with renal stones.