Treatment of high risk prostate cancer with combined radiotherapy and hormonal treatment- results and identification of factors influencing outcome.

PURPOSE: The aim of this work was to prospectively analyze the outcome of combined hormonal treatment and radical radiotherapy in high risk non metastatic prostate cancer patients (T1=4, N0-1, M0). METHODS: Between April 2003 and December 2007 196 patients with high risk prostate cancer were treated with curative intent. The treatment consisted of 2-month neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68-78 Gy, conformal technique) and an optional 2-year adjuvant hormonal treatment. RESULTS: The median follow up time was 59 months. Fiveyear overall survival was 86% and 5-year biochemical disease free survival (DFS) 70%. Factors found to be statistically significant relative to outcomes were Gleason score (p=0.017), initial PSA value (p=0.039) and adjuvant hormonal treatment (p=0.035). There was no significant association between radiotherapy dose or volume and biochemical DFS (bDFS). Late genitourinary and gastrointestinal toxicity was acceptable. CONCLUSION: Treatment combining hormonal therapy and radical radiotherapy can be recommended for this subgroup of prostate cancer patients. Adjuvant hormonal treatment should also be used.

Radiation induced lymphopenia - a possible critical factor in current oncological treatment.

BACKGROUND: The effect of ionizing radiation on the immune system during the treatment of malignant tumors has long remained a point of great interest. This issue is currently gaining importance, especially in connection with the advancing development and availability of immunotherapeutic treatment. During cancer treatment, radiotherapy has the ability to influence the immunogenicity of the tumor by increasing the expression of certain tumor-specific antigens. These antigens can be processed by the immune system, stimulating the transformation of naïve lymphocytes into tumor-specific lymphocytes. However, at the same time, the lymphocyte population is extremely sensitive to even low doses of ionizing radiation, and radiotherapy often induces severe lymphopenia. Severe lymphopenia is a negative prognostic factor for numerous cancer dia-gnoses and negatively impacts the effectiveness of immunotherapeutic treatment. AIM: In this article, we summarize the possible influence of radiotherapy on the immune system, with a particular emphasis on the impact of radiation on circulating immune cells and the subsequent consequences of this influence on the development of cancer. CONCLUSION: Lymphopenia is an important factor influencing the results of oncological treatment, with a com-mon occurrence during radiotherapy. Strategies to reduce the risk of lymphopenia consist of accelerating treatment regimens, reducing target volumes, shortening the beam-on time of irradiators, optimizing radiotherapy for new critical organs, using particle radiotherapy, and other procedures that reduce the integral dose of radiation.

[Treatment for volume upgrading of the low-grade supratentorial glioma after the subtotal neurosurgical resection]. / Lécba nízkostupnového gliomu supratentoriální oblasti mozku po neurochirurgické subtotální resekci s projevy objemového up-gradingu.

BACKGROUND: Low-grade gliomas WHO II (LGG) are mostly detected in patients with neurological symptomatology between 20 and 45 years of age very often as secondary epilepsy. We present two cases in which low-grade gliomas attacked neurological zones. Neurosurgical resection was subtotal because of the risk of the damage in neurocognitive functions in both these patients. After the operation, both patients were followed at neurosurgery department in regular intervals using different imaging methods (MRI, MRS and PET). After resections, the MRI detected the enlargement of the volumes of the tumor residua in both patients. PATIENTS AND METHODS: Owing to the risk of up-grading to high-grades glial tumors (overexpression of EGFR and VEGF), both patients were indicated for curative treatment by external beam radiotherapy combined with chemotherapy (Temodal®) and adjuvant chemotherapy. RESULTS: After the end of this treatment, the MRI proved considerable partial regressions in both patients. Moreover, three months later, the MRI did not prove any residual disease. CONCLUSION: Radiotherapy combined with the administration of Temodal should prolong the OS and TTP in patients with a high risk of up-grading of low-grade gliomas of the brain. Both the patients are in a follow-up program, also because of the risk of duplicite brain tumor.

Symptomatic severe tricuspid insufficiency as a late complication of pulmonary balloon valvuloplasty.

The authors describe an unusual case of a young adult patient with symptomatic tricuspid valve insufficiency as a late consequence of pulmonary valve balloon dilatation in childhood. Patient was successfully treated by tricuspid valve repair with neo-chordae implantation and a ring plasty. Two years after the operation the patient, an active sportsman, is asymptomatic with trace tricuspid regurgitation on the echo examination.

Spectra of photoneutrons produced by high-energy X-ray radiotherapy linacs.

Spectral fluence of photoneutrons generated in the head of the radiotherapeutic linac Varian 2100 C/D was measured by means of the Bonner spheres spectrometer whose active detector of thermal neutrons was replaced by a track detector, i.e. a sandwich of four CR-39s with the boron radiator inserted between them. Measurements with different collimator settings showed that the fluence of photoneutrons was higher for the more open collimator.

Perturbations of radiation field caused by titanium dental implants in pencil proton beam therapy.

The aim of this study was to investigate the absorbed dose and the linear energy transfer (LET) of a scanning proton pencil beam at the Proton Therapy Center Czech, applied to phantoms containing metal implants. We investigated two different phantoms composed of commonly used metals with a known chemical composition. Two rectangular phantoms consisted of water-equivalent environment material with a 65 mm thickness surrounding the 2, 5, 10 and 15 mm inserts of grade-2 and grade-5 Titanium. Track-etched detectors (TEDs) were placed behind the phantoms to gather the data. The measured LET spectra behind the implants were compared with Monte Carlo simulations using the Geant4 toolkit, version 10.03.p01. The simulations were used to provide additional information regarding the contribution of each type of particles to the LET spectra (protons, alpha particles, deuteron, neutrons, photons, and electrons) and to estimate the LET spectra above the TED's detection threshold. We used two different beam energies to study the most pertinent irradiation scenarios, one in the Bragg curve plateau and one at the maximum. The measurement of the LET spectra behind phantoms irradiated with a proton beam in the plateau region of the Bragg curve led to the detection of numerous particles with a very high LET. Lateral dose enhancement at the border between implants and the plastic material was detected when the phantoms were exposed to a proton beam and the data were recorded in the Bragg peak maximum. In this area, the dose increased 13 times for grade-2 Ti and 12 times for grade-5 Ti. The performed experimental study highlights the effect of dental implants on the LET spectra and absorbed dose when a proton pencil beam is crossing high-density titanium.

MEASUREMENT OF SECONDARY NEUTRONS GENERATED DURING PROTON THERAPY.

Measurements described in this article were carried out with the aim of evaluating risks of the patient exposure to secondary neutrons during treatment at the Proton Therapy Centre Prague. The neutron spectral fluence was measured by means of the extended Bonner sphere spectrometer (EBS). The article presents secondary neutron spectral fluences obtained by the EBS with passive thermoluminescent detectors, i.e. pairs of 6LiF and 7LiF chips. Measurements were performed in two positions: the first one behind the Nylon 6 phantom, and the second one close to the range shifter to evaluate their contribution to the generation of neutrons. Both the Nylon 6 phantom and the range shifter were irradiated with a pencil beam of protons 4 mm in diameter and the energy of 200 MeV. The results are supplemented with the values of effective dose derived from neutron spectral fluences.

Microdosimetry for a carbon ion beam using track-etched detectors.

Track-etched detectors (TED) have been used as linear energy transfer (LET) spectrometers in heavy ion beams for many years. LET spectra and depth-dose distribution of a carbon ion beam were measured behind polymethylmethacrylate degraders at Heavy Ion Medical Accelerator in Chiba, Japan. The measurements were performed along monoenergetic beam with energy 290 MeV u(-1) in different positions: (1) at beam extraction area, (2) at beginning, (3) maximum and (4) behind the Bragg peak region (0, 117, 147 and 151 mm of water-equivalent depth, respectively). The LET spectra inside and outside of the primary ion beam have been evaluated. TED record only heavy charged particles with LET above 8-10 keV µm(-1), while electrons and ions with lower LET are not detected. The Geant4 simulation toolkit version 4.9.6.P01 has been used to estimate the contribution of non-detected particles to absorbed dose. Presented results demonstrate the applicability of TED for microdosimetry measurements in therapeutic carbon ion beams.

Analysis of ventricular activation in patients with chronic non-Q wave myocardial infarction: comparison with left ventricular asynergy and myocardial perfusion defects.

In this report, we dealt with ventricular activation abnormalities in 30 patients with previous non-Q myocardial infarction (MI) by means of the CARDIAG 128.1 device, which enables analysis of ECGs, VCGs and body surface potential maps. The diagnosis was verified by left ventriculography, echocardiography and perfusion scintigraphy. Twenty-nine healthy subjects served as the control group. Morphological findings confirmed the presence of a significant subgroup with serious left ventricular asynergy. Seven electrocardiological variables, which significantly differed from control values, disclosed that non-Q MI is responsible for localized activation time prolongation, and that inferoposterior scars tend to delay the entire activation of ventricles, and to cause disturbances of the terminal depolarization phase together with a decrease in voltage production during QRS. Lesions of the anterior wall and the apicomesial part of the inferoposterior wall affect the distribution of the Q wave more often than the posterior basal ones. The probability of such abnormalities increases with the degree of asynergy. Some VCG criteria increase the sensitivity of electrocardiological analysis. These parameters will be used for evaluating the diagnostic value of electrocardiological analysis in the chronic non-Q MI. Non-Q myocardial infarctions represent a heterogeneous group of infarctions from both electrophysiological and morphological aspects.

[Main clinical and surgical determinants of in-hospital mortality after surgical revascularization of left main coronary artery stenosis: 2 year retrospective study (1998-1999)]. / Les facteurs cliniques et opératoires associés à la mortalité hospitalière après chirurgie d'une sténose du tronc commun de l'artère coronaire gauche. Analyse rétrospective de janvier 1998 à décembre 1999.

UNLABELLED: Stenosis of left main coronary artery (LMCA) is a common finding on coronary angiographies (7 to 10%). Mortality is very high for conservative therapy in comparison with surgery, which provides very good long-term outcome and is accepted as the standard therapy of this condition. Over the last few years, percutaneous coronary intervention (PCI) has become a new alternative in selected patients. AIM OF THE STUDY: To assess in hospital mortality in subjects referred to our surgical unit for coronary artery bypass grafting (CABG) and to identify the main clinical and surgical determinants of in-hospital mortality. METHODS: Two year retrospective analysis (1998-1999) of in-hospital mortality and morbidity of patients having left main stenosis referred for CABG. RESULTS: Among a group of 1443 patients operated for coronary heart disease, LMCA stenosis was found in 330 patients (22.9%). The mean age was 63 +/- 8.6 years. Elective surgery was done in 173 patients (52.4%), and acute operation (i.e. urgent, emergent or desperate) in 157 patients (47.6%). The total in-hospital mortality was 4.2% (14/330). Elective surgery in-hospital mortality was 1.7% (3/173) and urgent surgery in-hospital mortality was 7% (11/157). The main risk factors of in-hospital mortality were age > 68 years, low ejection fraction (LVEF<0.4), history of myocardial infarction, gender (female) and urgency of the operation. CONCLUSION: The proportion of patients undergoing CABG for left main stenosis is relatively high in our center and their mortality is quite low especially for elective operations. As the mortality of patients treated by PCI for LMCA stenosis is similar to surgery in high-risk patients, we postulate that this approach can be a real alternative treatment for such patients. Because of its potential benefit, combined revascularisation is also an alternative that should be considered in some cases. Furthermore, as a new generation of coated stents has emerged in the treatment of restenosis after PCI, we hypothesize that this method can in the near future be accepted as equivalent to surgery. However several randomized clinical trials must first be conduced prove this point.

[Follow-up of patients with valve prostheses using one- and two-dimensional echocardiography]. / Sledování nemocných s chlopenními náhradami jednorozmernou a dvourozmernou echokardiografií.

The authors examined by one- and two-dimensional echocardiography 28 patients with valvular prostheses, divided into groups, depending on the type and position of the prosthesis. They assessed the excursions of the disc or ball, the speed of opening and closure, time intervals A2-MVO and S1-AVO and the size of the left cardiac compartments. They investigated the occurrence of paradoxical movements of the interventricular septum, the diastolic wave in mitral prostheses and the flutter of the anterior cusp of the mitral valve in aortic prostheses. The results of these observations were confronted with data in the literature. In the investigated group of patients no pathological findings were detected. In mitral ball prostheses greater excursions were recorded than in eccentric disc-shaped prostheses. The closing speed was always greater than the opening speed. The A2-MVO interval was approximately double, as compared with S1-AVO. It was found that the paradoxical movement of the interventricular septum persists longer than reported in the literature. One-dimensional echophonocardiography and 2-D echocardiography retains its importance for the follow-up of patients with valvular prostheses.

[Diagnosis of conditions following myocardial infarct using complex analysis of electrical cardiac fields]. / Diagnostika stavu po srdecním infarktu komplexní analýzou elektrického srdecního pole.

In 22 patients with ischaemic heart disease and conditions after infarction and angina pectoris a coronarographic examination was made as well as other auxiliary examinations incl. a complex analysis of the electrical cardiac field (KAESP) (23), using a Cardiac apparatus (manufacturer ZPA Cakovice). Using the KAESP method fibroses in the heart muscle were found in all 22 patients, while a classical electrocardiogram revealed them only in 12 patients (54.5%). Post-infarction fibrous changes on the inferior cardiac wall were detected by ECG in 10 patients, KAESP revealed this localization of changes in 17 patients. The difference was particularly marked as regards localization on the anterior cardiac wall, according to ECG it was in 2 patients, according to KAESP in 17 patients. The authors investigated also on isopotential repolarization maps focal changes caused by cardiac ischaemia associated with organic affection of the appropriate coronary artery as revealed by coronarography. Identical sites were proved in 18 patients by the two methods, i. e. in 81.8%. In the discussion the authors analyse the causes which influence the accuracy of assessment of the coronary artery in KAESP. In KAESP in addition to isopotential maps also other maps were used such as isointegral, iso-areal, asynchronic potential maxima and minima, isochronic maps, maps of negative isodivergencies, profile sections etc. (20).

[Trends and results of mitral valve surgery]. / Trendy a výsledky operací mitrální chlopne.

BACKGROUND: Retrospective study of 303 patients with mitral valve surgery operated in the last 7 years is evaluated. A mitral valve replacement was done in 271 patients (89.4%), mitral valve reconstruction in 32 patients (10.6%). Only the replacement of mitral valve was done in 70 patients (23.1%), replacement in combination with some other intervention, most frequently the revascularization was done in 27 patients. METHODS AND RESULTS: The total mortality in mitral valve replacements was 7.7% with the prevalence of combined surgery, including the acute cases. Mortality for patients with prosthetics was 8.6% during 1996 to 98, and only 6.5% in the following years. From patients with the mitral reconstruction four has died (12.5%), all were acute or emergent cases with combined surgery. The average length of hospitalisation was 7.5 days. Postoperative Q-IM occurred in one patient (0.41%), revision for bleeding was necessary in 16 patients (5.3%), neurological complications developed in 14 patients (4.6%). CONCLUSIONS: Results of early mitral replacements are comparable or in some combined surgeries better to the results given in the literature or in the international register. In the aetiology of disease, a comparative decrease of rheumatic origin and an increase of ischaemic and degenerative disorders become apparent. The paper demonstrates improving results in this field of cardiosurgery, shows the new trends in the development of surgical treatment of the mitral valve and it also stresses the necessity of early indication to the surgery.

[Mycotic aneurysm of the coronary artery]. / Mykotické aneuryzma koronární arterie.

Mycotic aneurysm of the coronary artery occurs in less than 1% of patients with infective endocarditis and only few cases of successful treatment has been described in the literature. The paper presents a case of 64 years old man with infective endocarditis of the mitral valve, complicated with a development of mycotic aneurysm of the right coronary artery, who was successfully surgically treated.

[Humoral profile of patients with severe aortic stenosis]. / Humorální profil pacientu s tesnou aortální stenózou.

BACKGROUND: While the effect of neurohormones is often studied in congestive heart failure, their role in aortic stenosis needs to be elucidated. METHODS: 54 consecutive patients with symptomatic aortic stenosis without overt heart failure were studied at the age of 64.4 +/- 9.3 yrs with echocardiography, x-ray and catheterization. Levels of circulating atrial natriuretic factor endothelin-1, catecholamines, plasma renin activity, immunoreactive insulin and C-peptide were assessed, related to hemodynamic data and compared to those in 23 healthy controls, aged 59.2 +/- 12.8 yrs. RESULTS: Patients had significantly higher plasma levels of endothelin-1 (z-value 0.64 +/- 1.19, p = 0.019), atrial natriuretic factor (z-value 2.46 +/- 2.46, p < 0.001) and dopamine (z-value 0.91 +/- 2.33, p = 0.02). Levels of endothelin-1 and ANF positively correlated with mean (r = 0.631, p < 0.001) and wedged pulmonary artery pressures and with left atrial diameter index (r = 0.602, p < 0.001). Endothelin-1 levels correlated negatively with aortic valve area (r = -0.306, p = 0.041). No correlation was found between neurohumoral plasma concentrations and left ventricular mass index. CONCLUSIONS: In patients with symptomatic aortic stenosis without overt heart failure, elevated plasmatic levels of endothelin-1, atrial natriuretic factor and dopamine were documented. The increase of ET-1 levels is related to pulmonary hypertension and severity of the disease. Left ventricular hypertrophy is not related to neurohormonal levels. Neither circulating system renin-angiotensin nor noradrenaline are activated in these patients.

[A proposal for a standardized protocol for echocardiographic examinations of valvular defects, valve prostheses and atrial septal defects]. / Návrh standardních protokolu echokardiografického vysetrení chlopenních vad, chlopenních náhrad a defektu septa síní.

The authors summarize in standard protocols the spectrum of possible examinations made by means of a modern echocardiographic apparatus in valvular defects and prostheses and in septal atrial defects. They discuss some evaluations and their practical importance. Standardization contributes towards a comprehensive and more illustrative character and facilitates comparison of findings. A structured concept of the protocol is selected with the perspective of its deposition in a data base of an interactive external computer. The work should serve as a stimulus for discussion in other echocardiographic departments and elaboration of their own working procedure.

[Diagnosis of syndrome X using comprehensive analysis of the electrical field of the heart]. / Diagnostika syndromu X komplexní analýzou elektrického srdecního pole.

The authors describe the clinical picture and results of some auxiliary examinations in 18 patients with the X syndrome, i.e. with angina pectoris with a normal angiographic finding on the coronary arteries. For the diagnosis of ischemic cardiac changes, which are an integral part of this syndrome, the authors used a complex analysis of the electric cardiac field by means of a Cardiac 128.1 apparatus (manufactured by ZPA-Cakovice). In patients with the X syndrome they observed a significant reduction of some potential and integral values, as compared with an equally sized group of healthy subjects. On maps of the electric manifestation of cardiac activity on the chest surface ischemic changes were revealed on the antrior and lower cardiac wall but also in its lateral and posterior wall. These changes were older and were found in the subendocardial layer or concurrently in another area of the heart with affection of the subepicardial layer. Minor non-transmural fibroses, most frequently on the septum, in some instances spreading to the anterior and lower cardiac wall, were a surprising finding. At present it is not possible to differentiate merely by analysis of the electric cardiac field the X syndrome and ischemic heart disease. This should be made possible by further comparative studies. The present paper is the first description of ischemic and fibrous cardiac changes in X syndrome diagnosed by a complex analysis of the electric cardiac field in the professional literature published in Czechoslovakia and other countries.

[Modern cardiac pacing. I. Dual-chamber pacemakers: 10 years' experience]. / Moderní kardiostimulace. I. Dvoudutinové kardiostimulátory: desetileté zkusenosti.

Dual chamber cardiac pacemakers restoring an impaired atrioventricular synchrony meet a demand of contemporary so-called physiologic cardiac pacing. 39 dual chamber (DDD) pacers were implanted in 1982-1991 in our center. They improved both well-being and hemodynamic values (doppler echocardiography) more distinctly than common ventricular demand devices did. P-wave driven ventricular pacing in normal sinus node function (in 40 per cent of our DDD patients) made a frequency response in physical exercise possible. A short atrioventricular delay in DDD pacing proved to be helpful in the treatment for reentry tachycardias refractory to antiarrhythmic drug administration. Demanding implant, high price, lengthy programming as well as a higher incidence of complications (30.7 per cent) as compared to ventricular pacemakers (7.6 per cent) were the main problems of DDD ones.

[Effect of a revascularization procedure on functioning of the hibernating myocardium]. / Ovlivnení funkce hibernujícího myokardu revaskularizacním výkonem.

Persistent abnormalities of left ventricular wall motion in patients with chronic coronary artery disease can be reversed by successful coronary artery bypass surgery or coronary angioplasty. The identification of hibernating myocardium has therefore important therapeutic and prognostic implications. Echocardiography with low dose dobutamine infusion can detect viable myocardium in patients with chronic left ventricular dysfunction. We have studied 32 patients with angiographically confirmed coronary artery disease and left ventricular dysfunction. The effect of dobutamine infusion (5 micrograms/kg/min. followed by 10 micrograms/kg/min) on left ventricular function was evaluated before coronary revascularization (PTCA, n = 20); CABGm b = 12) and compared with early period after revascularization (1-7 days) and 6-7 months later. Before revascularization 226 segments were hypokinetic, akinetic or dyskinetic, improvement was observed in 122 segments during dobutamine echocardiography. Mean (+/- SD) segment score indexes were 2.50 +/- 0.17 at baseline, 2.04 +/- 0.19 (p < 0.001) after dobutamine infusion, 2.24 +/- 0.25 (p < 0.001) early after and 1.87 +/- 0.25 (p < 0.001) late after revascularization. Sensitivity of dobutamine infusion to predict improvement early and late after revascularization was 84% and 85% respectively, specificity was 85% and 90% respectively. Echocardiography during low dose dobutamine infusion is save and accurate method for identifying of hibernating myocardium and predicts early and late reversibility of wall motion in selected patients with coronary artery disease and chronic left ventricular dysfunction.

[Early results of mitral valve surgery]. / Casné výsledky operací mitrálních chlopní.

The authors submit a retrospective group of 245 patients operated in the course of 6 years at the Second Surgical Clinic of Cardiovascular Surgery of the General Faculty Hospital and First Medical Faculty Charles University on account of mitral valve disease. The early results of mitral valve prostheses are comparable or in some combined operations better than reported in world statistics. In the etiology the authors found a relative decrease of rheumatic defects and higher incidence of ischaemic affections. The general mortality in mitral valve prostheses was 7.1%, combined operations incl. acute ones being predominant. In mitral plastic operations the authors lost 4 patients, i.e. 19%. In all instances acute combined operations were involved and the result is consistent with the predicted mortality according to the Merged Cardiac Registry. The mean hospitalization period was 7.52 days. A postoperative QIM was recorded in one patient, i.e. in 0.46%, revision after mediastinitis also in one patient (0.41%) and revision after haemorrhage in 14 patients, i.e. in 5.7%. Neurological complications were recorded in 10 patients i.e. 4%. The work emphasizes the trend of improving results in this important area of cardiosurgery and indicates further possibilities and ways of development in the treatment of mitral valve diseases.