ADIOLOGY - 11111 NCOLOGY December 2000 Vol. 34 No. 4 Ljubljana ISSN 1318-2099 Ni pomembno zgolj preživetje Lilly Onkologija Eli Lilly (Suisse) S. A.. Pod•.. .. i.o v Ljubljani WTC. Dunajska 156. 1113 Ljubljana Telefon, (01) 5688 280. faks, (01) 5691 705 www.lilly.com Dodatne informacije o zdravilu so na voljo v strokovnih publikacijah. ki jih dobite na našem naslovu. ADIOLOGY AND NCOLOGY .TI. Editorial office Radiologij and OncologiJ December 2000 Institute oj Oncology Vol. 34 No. 4 Vrazov trg 4 Pages 319-402 SI-1000 Ljublja11a ISSN 1318-2099 Slovenia UDC 616-006 Plwne: +386 1 4320 068 CODEN: RONCEM P/1011e/Fax: +386 1 4337 410 E-mail: gsersa@onko-i.si Aims and scope Radiology and Oncology is a journal devoted to publication oj original co11tributio11s in diagnostic a11d i11terve11tio11al rndiology, computerized to111ogrnplzy, ultrasound, 11,agnetic resona11ce, nuc/ear 111edici11e, radiotherapy, clinical a11d experimental oncology, radiobiology, radioplzysics and radia/hm protection. Editor-in-Chief Editor-in-Chief Emeritus Gregor Serša Tomaž Benulic Ljubljana, Slovenia Ljubljana, Slovenia Executive Editor Editor Viljem Kovac Uroš Smrdel Ljubljana, Slovenia Ljublja11a, Slove11ia Editorial board Marija Auersperg Bila Fomet Maja Osmak Ljubljana, Slovenia Budapest, Hungary Zagreb, Croatia Nada Bešenski Tullio Giraldi Branico Palcic Zagreb, Croatia Trieste, ltaly Va11couve1; Cmrnda Karl H. Bolmslavizki Andrija Hebrang ]urica Papa Hamburg, Germany Zagreb, Croatia Zagreb, Croatia Haris Boka Lasz/6 Horvath Dušan Pavcnik Zagreb, Croatia Pecs, Hungary Portla11d, USA Nataša V. Budihna Berta Jereb Stojan Plesnicar Ljubljana, Slovenia Ljubljana, Slovenia Ljubljmrn, S/ovenia Marjan Budihna Vladimir Jevtic Ervin B. Podgoršak Ljubljana, Slovenia Ljubljana, Slovenia Mo11/real, Ca11ada Malte Clausen H. Dieter Kogelnik Jan C. Roos Hamburg, Germany Salzburg, Austria A111sterda111, Netherlands Christoph Clemm Jurij Lindtner Slavko Šimunic Miinchen, Gennany Ljubljana, Slovenia Zagreb. Croatia Mario Corsi Ivan Lovasic Lojze Smid Udine, Italy Rijeka, Croatia Ljubljm.a,Slovenia Christian Dittrich Marijan Lovrencic Borut Stabuc Vienna, Austria Zagreb, Croatia Ljubljana, Slove11ia Ivan Drinkovic Luka Milas Andrea Veronesi Zagreb, Croatia Housto11, USA 1viano, Italy Gillian Duchesne Metka Milcinski Ziva Zupancic Melbourne, Australia Ljubljana, Slovenia Ljublja11a, Slove11ia Publishers S/ove11im1 Medica/ Associatio11 -S/ove11ia11 Associatio11 of Radiology, Nuclear Medicine Society, S/ovenimz Society far Radiotlzerapy muf 011€0/ogy, and Slovenian Ca11cer Society Croatian Medica! Association -Croatimz Society of Radiology Affiliated with Societas Radiologorzmz Hungarorum Friuli-Venezia Giulia regional groups of S.I.R.M. (Italimz Society of Medica/ Radiology) Copyright © Radiology and Oncology. Ali riglzts reserved. Reader for English Mojca Cakš Key words Eva Klemencic Secretaries Milica Harisch Mira Klemencic Design Monika Fink-Serša Printed by I111pri11t d.o.o., Lj11blja11a, Slove11ia Published quarterly hz 700 copies Bank nccozznt number 50101 679 901608 Foreig11 currency nccount number 50100-620-133-900-27620-978-515266/6 NLB -Ljublja11ska lm11kn d.d. -Ljubljana Subscription fee far institutions $ 100 (16000 SIT), i11divid11als $ 50 (5000 SIT) The pub/ication of this jounzal is subsidized by the Ministry of Science and Technology of the Republic of Slovenia. lndexed and abstracted by: BIOMEDICINA SLOVENICA CHEMICAL ABSTRACTS EMBASE / Excerpta Medica This jounzal is printed on acid-free paper Radiology a11d Oncology is available on the internet at: http://www.onko-i.sijradiolog/rno.htm Ljubljana, Slovenia December 2000 Vol. 34 No. 4 CONTENTS MAGNETIC RESONANCE .TI. ISSN 1318-2099 UDC 616-006 CODEN: RONCEM Magnetic resonance cholangiography in patients with bile duet obstruction Lineender L, Sadagie E, Vreže D, Vegar S, Stevie N 319 SONOGRAPHY Duplex-Doppler ultrasound evaluation of intrapancreatic blood flow in patients with insulin-dependent diabetes mellitus Drinkovic I, Brnic Z, Hebrang A 325 Renal vascular resistance in patients with chronic renal failure Prkacin I, Dabo N, Palcic I, Brkljacic B, Sabljar-Matovinovic M, Babic Z 331 NUCLEAR MEDICINE Bone marrow protection by amifostine in Re-186-HEDP treatment: first results obtained in a rabbit animal model Klutmann S, Bohuslavizki KH, Kroger S, Jenieke L, Buchert R, Mester ], Clausen M ONCOLOGY Algorithm for percutaneous stenting in patients suffering from superior vena cava syndrome Vodvrirka P, Štverrik P Electrochemotherapy with cisplatin of breast cancer tumor nodules in male patient Reberšek M, Cufer T, Rudolf Z, Serša G Synchronous and metachronous bilateral germ cell tumours of the testis Berkmen F, Peker AF, Basay S, Ayy1ld1z A, Arik j The relationship between DNA methylation and expression of the different DNA methyltrans­ferases in ovarian cancer Cor A RADIOPHYSICS Logit modeling of the Modulation Transfer Function (MTF) of metal/film portal detectors Falco T, Fallone BG 375 Current trends in diagnostic nuclear medicine instrumentation Fidler V 381 SLOVENIAN ABSTRACTS 387 NOTICES 395 REVIEWERS IN 2000 398 AUTHOR INDEX 2000 398 SUBJECT INDEX 2000 401 Rndiol Oncol 2000; 34(4): 319-24. Magnetic resonance cholangiography in patients with bile duet obstruction Lidija Lincender, Ermina Sadagic, Dunja Vrcic, Sandra Vegar, Nataša Stevic Institute oj Radiology, Clinical Center oj Sarajevo University, Sarajevo, Bosnia and Herzegovina Background. The aim of this study was to assess the diagnostic value of magnetic resonance cholangiogra­phy (MRC). This is a new non-invasive imaging technique far the evaluation of bile duet obstruction. Patients and method. MRC was pe1jorrned on patients with bile duet obsh-uction at 1.0 TU. Over a peri­od of 26 months, 44 patients, 23 rnales and 21 fernales, rnean age 51years, were examined. The basis were T2-weighted sequences through the /iver to accentuate the fluid fill bile duet, and fast spin echo sequences. Usually, the thickness of the slices was 4 mm. Two spatial planes were pe1jonned, coronal and axial, with the breath held and released, and with maximum intensity projection (MIP) reconstruction. In our case, with Machine 1.0T, we compared the results of ultrasound and CT with MRC in the patients with bile duet obstruction before surgical intervention ar drainage procedure. Results. We examined 44 patients with jaundice by MRC and with the 100% accuracy identified the leve/ of the obstruction. Clinical applications of MRC were evaluated on the basis of personal experience, and data literature. The main indication far MRC study was the evaluation of common bile duet obstruction without using conh-ast medium and biliary intervention. Conclusions. MR technique has been dictated by image pe1jormance and sequence availability. Our expe­ rience and results confirmed that MRI is more accurate than US and CT in patients with bile duet obstruc­ tion. Key words: c/wlestasis-diagnosis; magnetic resonance imaging; bile ducts neoplasms; cholelithiasis, Received 19 June 2000 Accepted 6 July 2000 Correspondence to: Prof. Lidija Lincender, MD, PhD, Institute of Radiology, Clinical Center of Sarajevo University, Bolnicka 52, BH-71000Sarajevo, Bosnia and Herzegovina. E-mail: lidijal@yahoo.com Introduction Current non-invasive imaging teehniques, sueh as ultrasound (US) and eomputerized tomography (CT), have a limited potential in diagnosing biliary duet disorders. As a result, many patients with suspeeted biliary duet disorders undergo more invasive diagnostie proeedures, sueh as endoseopie retrograde eholangiopanereatography (ERCP) and percu­taneous transhepatie eholangiography (PIC). Lincender Le/ ni./ Magnelic resonance cholnngiogrnphy Those procedures have low, yet significant morbidity and mortality.1 Magnetic reso­nance cholangiography (MRC) techniques can be an alternative to non-invasive meth­ods of imaging of the biliary duct.2 The tech­niques developed over the past 5 years have a diagnostic performance comparable to diag­nostic ERCP and are being utilized clinically in the management of the biliary and pancre­atic disease.3, 4 The interpretation involves the review of typically maximum intensity pro­jection (MIP} after the processing of the vol­ume 3 months, (GFR-glomerular filtration rate is about 20 to 35 percent of nor­mal); (2) Prolonged symptoms or signs of ure­mia; (3) Symptoms or signs of renal osteodys­trophy; (4) Kidneys reduced in size bilaterally. The patients with chronic renal failure have glomerular disease (N=9) (primary glomerular disease (N=7), such as focal seg­menta! glomerulosclerosis, membranous glomerulo nephropathy, membranoprolifera­tive glomerulonephritis and multisystem dis­eases (N=2), such as systemic lupus erythe­matosus), tubulointerstitial disease (N= ll) and nephroangiosclerosis (N=lO). The patients with a history of heart disease or diabetes mellitus, as well as all patients with conventional US findings of renal calculi, col­lecting system dilatation, or suspected expan­sive processes were excluded from the study. The control subjects were 20 healthy vol­unteers, mean age 49.3 years. Ris and Pis of control subjects were compared with those of the patients with chronic renal failure. Methods Real-tirne and color duplex US examinations were performed using a color Doppler scan­ner (Radius CF, general Electric Medica! Systems), with a 3.75 MHz curved-array transducer. Pulsed Doppler US studies of the segmenta!, interlobar and arcuate arteries were performed in both kidneys in each patient. The segmenta!, interlobar and arcu­ate arteries were distinguished with respect the position of the Doppler sample volume for the inner kidney zone (renal sinus), mid­dle zone (corticocentral boundary) and outer zone (corticomedullary border). RI was mea­sured according to the following formula (peak systolic frequency shift-minimum dias­tolic frequency shift)/ peak systolic frequency shift. The PI was measured with the formula: (peak systolic frequency shift-minimum dias­tolic frequency shift)/mean frequency shift during the whole cardiac cycle. All control subjects and patients were examined in the supine and semioblique positions; they had to suspend respiration for 10 seconds so that a representative spectra could be obtained. For all patients, laboratory findings for the presence of proteinuria and serum creatinine levels and creatinine clearance rates were available. Normal values for serum creatinine and creatinine clearance are 62-124 mikro- Prkncin l et ni. / Rena/ vnsculnr resistn11ce in chronic re11nl /ni/ure mol/L (Jaffe method) and 1.2-2.4 ml/sec, respectively.14 In healthy adults, urinary pro­tein excretion, as measured in the 24-hour urine specimen, is up to 150 mg. Mild protein excretion is referred to as low-grade protein­uria when urinary protein excretion is less than 1 to 2g/24 h, whereas the excretion of 3.5g/24 h or more is defined as nephrotic range proteinuria.1s Doppler sonographic indices were corre­lated with systolic and diastolic blood pres­sure values, which had been measured prior to US examination. The interval between US examination and blood or urine sampling for laboratory examination was less than 5 days in all cases. All laboratory examinations were performed in the same laboratory. Results Mean RI in the control subjects and in the patients with chronic renal failure was 0.59±0.03 (±SD) and 0.71±0.11, (p<0.01), respectively. Mean PI in the controls and in the patients with chronic renal failure was 1.00±0.11 and 1.69±0.21, (p<0.01), respective­ly. The patients with chronic renal failure were classified by RI values into two groups. Group I included 15 patients with normal RI, mean age 43.7 years. Group II was composed of 15 patients with elevated RI (more than 0.70), mean age 63.4 years. Of the 30 patients with chronic renal failure (50%), 12 of whom were found to be hypertensive (blood pres­sure> 140/90mmHg), an elevated RI was noted in 15 patients. Mean values of systolic and diastolic blood pressure were 160±15mmHg and 105±13mmHg, respectively. An RI <0.70 was observed in the remaining 15 patients of the 30 (50%), of whom 12 were normotensive. In hypertensive patients, mean RI and mean PI were 0.74±0.12 and 1.90±0.20, respectively. In the normotensive patients, mean RI and mean PI were 0.64±0.09 and 1.19±0.32, respectively. The statistical significance of RI and PI differences in normotensive and hypertensive patients with chronic renal fail­ure was calculated to be p<0.02 and p<0.04, respectively. In the patients of group I, who were younger (mean 43.7 years), glomerular dis­ease was present in 60% (N=9) of patients, and tubulointerstitial diseases in 40% (N=6). In 86% of these patients, the creatinine clear­ance rate was higher than 0.25ml/sec, and in 10 patients, proteinuria was lower than 3g/l. In the patients of group II, who were older (mean 63.4 years), nephroangiosclerosis was present in 66.6% (N=10) of patients, and tubu­lointerstitial diseases in 33.3% (N=5) of patients. In 80% of the patients of group II, the creatinine clearance rate was lower than 0.25 ml/sec, and proteinuria was higher than 3g/l in 8 patients. Discussion Normal RI values have been established in native kidneys, and the cut off value of 0.70 or greater is generally considered to represent an abnormal RI.16 The age was shown to be_ an important variable that affected RI values as well as arterial hypertension.5 A highly signif­icant correlation was found between the RI, the serum creatinine levels and creatinine clearance rates in patients with diabetic nephropathy and several other parenchymal diseases, particulary those affecting the tubu- ' lointerstitial and vascular compartments o( the kidney.5, 16 Our results show that Doppler indices do accurately reflect an elevated RI, especially in the patients with the creatinine clearance rate of less than 0.25ml/s (p<0.001). RI has been found to correlate with renal function much better than PI. Based on the results of our study, an ele­vated RI appears to reflect progression of renal failure, while hypertension without TOD (target organ damage) does not seem to affect RI. Prkacin I et al. / Rena/ vascular resistance in chronic renal failure Studies suggest that RI elevation is more likely to occur with a vascular or tubulointer­stitial renal process, and is much less likely with the disease limited to the glomeruli.3 Furthermore, RI is not a measure of renal function per se, but rather reflects renal vas­cular resistance. When an elevated renal arte­rial resistance accompanies abnormal renal function, RI is more closely related to renal function, especially in diabetes mellitus.3,5,6,17 Conversely, some renal pathology causes a sig­nificant loss of renal function with little or no change in renal vascular resistance. In these instances, RI does not reflect the loss of renal function.14 In patients with chronic renal dis­ease, RI is closely related to certain haemody­namic and functional parameters.10,17 The drawback of the present study is a rel­atively small number of patients studied. Moreover, it was not designed in a longitudi­nal fashion as each patient was examined only once by duplex Doppler US. Further­more, it is not surprising that the disease with a destructive and deformative effect on the renal parenchyma increases RI. Therefore, measuring RI and PI alone cannot alter the patient's outcome. However, a good correla­tion between RI and renal functional parame­ters on the one hand and the development of arterial hypertension in the patients with chronic renal failure, on the other, that was observed in our study, may eventually prove that duplex Doppler US could be used as an additional parameter in the assessment of severity of chronic renal failure. In conclusion, color duplex Doppler US in intrarenal arteries proved to be useful in the assessment of increased RI in chronic renal failure patients. Elevated RI and PI heralded the progression of renal failure. Doppler indices correlated significantly with renal function tests. However, additional longitudi­nally designed studies on a larger patient group will be necessary to evaluate in full the clinical usefulness of duplex Doppler US in patients with chronic renal failure. Radio/ Oncol 2000; 34(4): 331-5. References 1. Burns PN. The physical principles of Doppler and spectral analysis. J Ciin Ultrasound 1987; 15: 567­90. 2. Plat JF. Duplex Doppler evaluation of native kid­ney dysfunction. Obstructive and nonobstructive disease. AJR 1992; 158: 1035-9. 3. Platt JF. Doppler ultrasound of the kidney. Semin Utrasound CT 1997; 18: 22-32. 4. Knapp R, Plotzenedes A, Frausher F. Variability of Doppler pararneters in the healty kidney: An anatornic-physiologic correlation. J Ultrasound Med 1995; 14: 427-9. 5. Brkljacic' B, Drinkovic' N, Sabljar-Matovinovic' M, Soldo D, Morovic' Vergles J, Vidjak V, et al. Intrarenal duplex doppler sonographic evaluation of unilateral native kidney obstruction. J Ultra­sound Med 1994; 13: 197-204. 6. Kirn SH, Kirn SM, Lee HK, Kirn S, Lee JS, Han MC. Diabetic nephropathy:dupplex Doppler ultra­sound findings. Diabetes Res Ciin Pract 1992; 18: 75-81. 7. Platt JF, Rubin JM, Ellis JH. Acute renal failure. Possible role of duplex Doppler ultrasound in dis­tinction between acute prerenal failure and acute tubular necrosis. Radiology 1991; 179: 419-21. 8. Platt JF, Rubin JM, Ellis JH. Diabetic nephropathy. Evaluation with renal duplex Doppler US. Radiology 1994; 190: 343-7. 9. Brkljacic' B, Mrzljak V, Drinkovic' I, Soldo D, Sabljar-Matovinovic' M, Hebrang A. Rena! vascular resistance in diabetic nephropathy: duplex Doppler US evaluation. Radiology 1994; 192: 549­54. 10. Terry JD, Rysavy JA, Frick MP. Intrarenal Doppler characteristics of aging kidneys. J Ultrasound Med 1992; 11: 647-51. 11. Greene ER, Avasthi PS, Hodges J. Noninvasive doppler assessrnent in renal artery stenosis and haernodynarnics. J Ciin Ultrasound 1987; 15: 653-9. 12. Halpern EJ, Needlernan L, Nack TL, East SE. Rena! artery stenosis -should we study the rnain renal artery or segmenta! vessels. Radiology 1995; 195: 799-804. 13. Pozniak MA, Kelez F, Stratta RJ. Extraneous fac­tors affecting resisitve index. Invest Radio/ 1988; 23: 899-904. Prkacin I et a/. / Rena/ vascular resistance in chronic renal failure 14. Becker JA. Evaluation of renal function. Radiology 1991; 179: 337-8. 15. Larson TS. Evaluation of proteinuria. Mayo Ciin Proc 1994; 69: 1155-8. 16. Brkljacic B, Sabljar-Matovinovic' M, Putarek K, Soldo D, Morovic'-Vergles J, Hauser M. Rena! vas­cular resistance in autosomal dominant polycistic kidney disease: Evaluation with color Doppler ultrasound. Acta Radiol 1997; 38: 840-6. 17. Petersen LJ, Petersen JR, Ladefoged SD. The pul­satility index and the resistive index in renal arter­ies in patients with hypertensio and chronic renal failure. Nephrol Dial Transplant 1995; 10: 2060-4. Radio/ 011co/ 2000; 34(4): 337-47. Bone marrow protection by amifostine in Re-186-HEDP treatment: first results obtained in a rabbit animal model Susanne Klutmann, Karl H. Bohuslavizki, Sabine Kroger, Lars Jenicke, Ralph Buchert, Janos Mester, Malte Clausen Department oj Nuclear Medicine, University Hospital Eppendorf, Hamburg, Germany Baclcground. In the last few years various reports dealt with radioprotective effects oj amifostine (Ethyol®, USB, Philadelphia, PA). Since anzifostine is markedly accumulated in bone marrow it looks worthwhile to study the radioprotective effects oj amifostine on bone marrow in patients treated with Re-186-HEDP. As a first step animal studies were performed using New Zealand White rabbits. Materials and methods. A tata/ oj 18 rabbits received 300 MBq Tc-99m-HDP far whole-body scintigraphy. Thereafte1; 9 animals were h·eated with 200 mg/kg body weight mnifostine, and 9 rabbits served as controls receiv­ing physiological saline solution. Then, these 18 rabbits received 400 MBq Re-186-HEDP i.v. Two rabbits served as untreated conh·ols and received neither Tc-99m-HDP nor Re-186-HEDP. Blood samples were taken at the begin­ ning and in huo-week-intervals far the duration oj huo months in ali 20 animals. Laboratory findings were deter­mined far white and red blood cel/s, far platelet count and far hemoglobin. Two months after therapy ali animals were sacrificed, and both femora were removed surgically far histopathological examination oj bone marrow. Results. In controls as well as in amifostine-treated anirnals, the red blood celi count and the hemoglobin were almost constant at ali times oj observation. In 9 control rabbits the mean platelet count was 265.22±127.41 Mrd/l prior to Re-186-HEDP-therapy. Two weeks after therapy the mean platelet count was reduced to 211.22±52.8 Mrd/l. Prior to Re-186-HEDP-therapy the mean platelet count oj amifostine-treated rabbits was not significantly different (p>0.05) from control rabbits. Two weeks after injection oj the radionuclide the mean platelet count decreased to 180.67±37.43 Mrd/l in the amifostine group. There was no significant difference behueen rabbits oj the control group and amifostine-h-eated animals (p>0.05). Thus, amifostine was not able to prevent a transient thrombocytopenia. Two weeks after therapy only a slight decrease oj the white blood celi count was recognized in controls. In contrast, amifostine-treated rabbits showed a considerable decrease oj the white blood celi count huo weeks after therapy with a mean value oj 3.39±0.91 Mrd/l. This difference was statistically significant (p<0.0002). Discussion. The insufficient radioprotection oj amifostine concerning the platelet count was probably due to phar­macocinetics oj amifostine. Since the generation oj Jree radicals in the bone marrow caused by Re-186-HEDP lasts severa/ times longer than the radioprotective effect oj amifostine given as one single dose prior to the application oj Re-186-HEDP. However, the observed decline oj white blood cel/s due to amifostine application is yet unknown. Conclusion. In order to use mnifostine as a suitable agent far radioprotection multiple doses oj amifostine might be applied, i.e. huo shots per day far the duration oj 3 to 4 days after the application of Re-186-HEDP. The observed leucopenia should be studied in further animal studies. Key words: Radiation-protection agents; bone marrow; amifostine; erythrocyte count; platelet count, hemoglobin; Re-186-HEDP; bone metastases Klutmann Set al. / Ethyol in Re-186-HEDP treatment Introduction Patients with prostate cancer will develop bone metastases in nearly 70 %,1 which may result in pathological fractures as well as in severe bone pain.2 ,3 The application of .-­emitting osteotropic radionuclides, i.e. Sr-89­chloride, Sm-153-EDTMP, and Re-186-HEDP is one therapeutic approach in palliative treat­ment of painful, multilocular bone metas­tases.4-10 Since bone metastases show a pref­erential uptake of bone-seeking radionu­clides, i.e. Re-186-HEDP, this therapy is rather specific, while non-affected tissue is spared from the effects of the .--irradiation.11 In 75% of the patients pain relief occurs within one to two weeks after the application of Re-186­HEDP and lasts for about 1-6 months.3,10,12 However, Re-186-HEDP delivers a substantial 0.05) from control rabbits amounting to 286.22±73.2 Mrd/1. Two weeks after injection of the radionuclide the mean platelet count of the amifostine group decreased to 180.67±37.43 Mrd/1. There was no significant difference between rabbits of the control group and ami­fostine-treated animals (p>0.05). Four, six and eight weeks after Re-186-HEDP-therapy the platelet count increased to 214.78±121.97, 267.67±89.6 and 251.44±102.89 Mrd/1, respec­tively. Moreover, there was no significant dif­ference between animals treated with either physiological saline solution or amifostine. Laboratory findings of two untreated ani­mals revealed platelet count of 378±161.22 Mrd/1 at the beginning and 315.5±129.4, 379.5±112.43, 275.5±105.36 and 237±70.71 Mrd/1 at two-week-intervals follow-up. White b/ood cel/s Values of the white blood cell count are given in detail in Table l. Prior to Re-186-HEDP­therapy mean white blood cell count of Figure l. Whole body scintigraphy after injection of 300 MBq Tc-99m-HDP prior to (left column) and 2 months after Re-186-HEDP-therapy (right column) in a rabbit of the control group (lower row) and in an amifostine-treat­ed animal (upper row). Distribution of Re-186-HEDP 48 hrs after i.v. application is displayed in the middle column. Klutmann Se/ al. / Ethyol in Re-186-HEDP trea/111enl 6.64±1.27 Mrd/1 was measured for rabbits of the control group. Two weeks after therapy a slight decrease of white blood celi count was recognized in this animal group with a mean value of 5.43±0.88 Mrd/1. Four, six, and eight weeks after therapy white blood celi count increased to mean values of 6.96±1.41, 8.1±1.46 and 7.97±0.84 Mrd/1, respectively. Amifostine-treated animals revealed mean white blood celi count of 5.73±2.1 Mrd/1 prior to the injection of the radionuclide. In con­trast to the control group, amifostine-treated rabbits showed a considerable decrease of white blood celi count two weeks after thera­py with a mean value of 3.39±0.91 Mrd/1. This difference was statistically significant (p<0.0002). In follow-up studies the white blood celi count removed to 4.61±1.48, 5.29±1.24 and 5.76±1.34 Mrd/1 at four, six and eight weeks after therapy, respectively. In two completely untreated animals white blood celi count remained almost unchanged with values of 6.6±1.41, 6.15±0.21, 6.75±1.63, 9.2±4.53 and 9±2.55 Mrd/1 at the beginning and in two-week intervals, respectively. Scintigraphic findings Left column of Figure 1 shows examples of whole-body scintigraphy 2 hrs after injection of Tc-99m-HDP of one animal of the control group (lower row) and one animal of the ami­fostine-treated group (upper row). Prior to Re-186-HEDP-therapy there was no difference between the control animals and the amifos­tine-treated animals concerning the distribu­tion of Tc-99m-HDP. Examples of whole-body scintigraphy 48 hrs after injection of Re-186­HEDP are displayed in the middle column of Figure 1. The visual evaluation of the scinti­gramms showed a distribution of Re-186­HEDP comparable to bone seans in both groups of rabbits. Examples of bone scintig­raphy at 8 weeks after Re-186-HEDP-therapy are shown in the right column of Figure 1. There was no visual difference of the distrib­ution of Tc-99m-HDP in either control ani­mals or amifostine-treated animals. Moreo­ver, there was no visual difference between the distribution of the Tc-99m-HDP prior to and eight weeks after therapy with Re-186­HEDP. Histopathologica/ findings Eight weeks after Re-186-HEDP-therapy ali 18 rabbits showed hyperemic bone marrow vessels as compared to untreated animals (Figure 2). A B C Figure 2. Histological exarnination of bone rnarrow in conventional Giernsa stammg, rnagnification: 200fold. A: animal which received neither Tc-99111­HEDP nor Re-186-HEDP. B: animal of the control group. C: animal of the amifostine group. Note the comparable cellularity and differentiation of the dif­ferent cell lines of B and C as compared to the bone marrow of the completely untreated animal (A). However, in contrast to the untreated animal the blood vessels of B and C are filled with red blood cells, and thus, appear hyperernic. Klutmmrn Seta/./ Ethyol in Re-186-I-IEDP treat111e11t There was no difference between animals treated with or without amifastine concern­ing the cellularity of bone marrow, the num­ber and differentiation of erythropoesis, gran­ulopoesis and thrombocytopoesis, and the quantity of iron. Moreover, histopathological examination revealed no difference between animals treated with amifastine and those rabbits, which received physiological saline solution only. Discussion Prostate cancer is the second most common malignancy in men in Western Europe.1 The incidence is 15-16 per 100.000 habitants per year with increasing tendency. As much as 80% of patients with prostate cancer will develop bone metastases.1 In about one third of all patients osseous metastases are detect­ed at primary staging. Moreover, the skeleton is the only single site of metastases in a rea­sonable amount of patients.3 In case of multi­locular, osseous metastases a complete remis­sion of prostate cancer is nearly impossible. Since osseous metastases are often associ­a ted with bone pain, effective pain relief is the primary goal when caring far patients with prostate cancer and multiple osseous metastases. Traditional therapeutic approach is the application of central or peripheral analgesics in combination with neuroleptics.6 Moreover, a steroid medication, diphospho­nates and hormona! drugs may complete analgesic effects. However, the therapy with opioids is limited in many patients due to side-effects, i.e. nausea, vomits and gastroin­testinal symptoms and thus, often associated with a loss of patient's quality of life.7 Skeleta! pain confined to a single site metastasis usually responds to external beam radiotherapy in 70-80 %.6A0,4l In case of mul­tilocular, osseous metastases external beam radiation is helpful to avoid pathologic frac­tures or compression of the spina! cord.42 However, hemibody or whole-body irradia­tion far pain relief is often limited by bone marrow suppression, gastrointestinal symp­toms and a radiation pneumonitis.14 , 43 The­refare, an effective relief of pain with low side-effects and an improvement in patient's quality of life is warranted in these patients. The application of .--emitting osteotropic radionuclides is a promising method to selec­tively irradiate osseous metastases by sparing normal tissues from short-range irradia­tion.11,13 Due to the osteoblastic character of osseous metastases the radiopharmaceutical is predominantly accumulated in malignant transfarmed cells, which leads to a rather selective irradiation of bone metastases. Re-186-hydroxyethylidendiphosphonate (Re-186­HEDP) has recently been developed far pal­liative treatment of painful osseous metas­tases.5 Re-186 has a therapeutic .--emission of 1,07 Me V associated with a y--emission of 137 keV. Moreover, Re-186-HEDP and Tc-99m-HDP, which is commonly used far diag­nostic bone scintigraphy, have an almost exactly similar bone distribution since both sorts of diphosphonates bridge to the hydrox­yapatite of bone substance. Therefare, pretherapeutic and posttherapeutic scinti­graphic imaging is possible which allows a control of Re-186-HEDP distribution as shown in Figure 1 (middle column). Re-186 has a short physical half-life of 3,8 days that allows a single application of activities of 1110 to 1850 MBq with high tumor doses as well as an easy handling of radioactive waste, i.e. urine. About 50 % and 70 % of the activity injected are excreted via the kidneys into the urine within the first 6 hours and 24 hours after application, respectively. Apart from the distribution in osseous structures Re-186­HEDP is not accumulated in any other struc­tures of the body. Pain relief is attained within two weeks after application of Re-186-HEDP and lasts far about 1-6 months. Response rates of Re-186-HEDP-therapy of 70-80 % have been K/11t111a1111 Set a/./ Ethyol in Re-186-HEDP treat111e11t reported.3,10,12 Especially in patients with oral medication of non-opioid analgesics, Re-186­HEDP-therapy led either to a reduction or to a stop of oral drug medication. Due to the short physical half-life, Re-186-HEDP treatment can be repeated after 4-6 months. The main radiobiological side-effect of bone seeking radiotherapeuticals is their potential bone marrow toxicity.11,13-15 Throm­bocytopenia plays the major role in this bone marrow suppression. The decline of platelets presents with a nadir about two to three weeks after its application. Since patients with prostate cancer often show a bleeding tendency caused by the additional use of non­steroid anti-inflammatory drugs and by a tumor infiltration of the bladder frequent controls of platelet count are necessary in posttherapeutic follow-up. In clinical practice platelet counts are regularly defined in two­week intervals for the duration of two months after Re-186-HEDP-therapy. Since thrombocy­topenia was proven to be the main side-effect a reduction of the platelet counts' decline would improve tolerability of Re-186-therapy. On the other hand, thrombocytopenia is the dose-limiting factor. Thus, by reducing the bone marrow toxicity of Re-186-HEDP higher activities of more than 1200 MBq might be injected as one single dose in the future. Thus, Re-186-HEDP might be applied not only as a palliative but also as curative means in patients with prostate cancer. The pro-drug amifostine emerged as the most promising radioprotector synthesized and tested in a large study funded by the US army. In clinical trials amifostine was shown to protect salivary glands from irradiation damage in patients with thyroid cancer under high-dose radioiodine therapy. 26-29,31,32,44.45 Moreover, amifostine was proven helpful in patients with cancer of the head and neck 45 treated with chemo-irradiation.30.,46 In these patients amifostine was able to significantly reduce side-effects, i.e. mucositis, xerostomia and thrombocytopenia as compared to a non- Radiol Oncol 2000; 34(4): 337-47. amifostine treated patient group. Moreover, either in patients with thyroid cancer nor in patients with head and neck cancer amifos­tine was shown not to protect tumor tissue, which is a prerequisite for its potential use in tumor therapy. 25,33.47 When administered intravenously, amifos­tine is rapidly cleared from the plasma with an alpha half-life of as less than one minute and a beta half-life of less than 10 minutes.48 In con­trast to its brief systemic half-life, there is a prolonged retention of the drug and its metabolites in normal tissues.36 In the first 30 minutes after amifostine administration, the drug uptake into normal tissues such as sali­vary glands, !iver, kidney, heart and bone-mar­row demonstrated an up to 100-fold greater difference as compared to tumor tissue.36 In this preclinical study the radioprotective effect of amifostine on bone marrow suppres­sion under Re-186-HEDP-therapy was studied using a rabbit bone marrow model. Therefore, in a total of 18 rabbits, 400 MBq Re-186-HEDP were applied intravenously in order to evalu­ate the bone marrow suppression in rabbits pretreated either with amifostine or with physiological saline solution only. Neither red blood cell count nor hemoglobin was changed by Re-186-HEDP in controls and in rabbits pretreated with amifostine. Moreover, by histopathological examination there was no difference concerning the red blood cell line in all three groups of animals. This is in accor­dance with the observations of other investi­gators who reported no influence of Re-186­HEDP on hemoglobin and red blood cells.16 In contrast, a marked decline of the platelet count of about 20% was observed two weeks after application of Re-186-HEDP in controls. This is again in accordance with the 11 13-16 observation of other investigators.7, ,Following whole-body exposure by external radiation, thrombocytopenia develops slowly over a period of approximately 30 days after doses of 200-400 cGy. After the application of a dose of 600-1000 cGy the production of K/u/111am1 S et a/. / Ethyol in Re-186-HEDP treatmenl platelets is completely stopped, which leads to a decrease of the platelet count reflecting the life range of the platelets of approximate­ly 9 days.15 It was estimated that standard activities of 1200 MBq Re-186-HEDP deliver a radiation /= 3 Triage Pulse >/= 110/min Respiration >/= 28/min If the response is "GOOD", go to the Question No. 3. Treatment No. 2 Palliative treatment at the hospice or at the palliative care unit for the symptomatic treat­ment (corticosteroids, diuretics, positioning, oxygen, antibiotics, etc.) Question No. 3: 1s the stenting of SVC contraindicated? (What is the origin of SVCS, what is the severity of SVCS?) Reason for the question No. 3 Stenting is contraindicated in patients with excessive obliteration of the large veins or their extensive invasion by of cancer (SVC and both brachiocephalic veins). Table 2. Kishi's scoring system far signs and symptoms of SVCS obstruction Signs and symptoms grade Neurological symptoms Stupar, coma, or blackout 4 Blurry vision, headache, dizziness, or amnesia 3 Changes in mentation 2 Uneasiness 1 Laryngopharyngeal or thoracic symptoms Orthopnea or laryngeal edema 3 Stridor, hoarseness, dysphagia, glossal edema, or shortness of breath 2 Cough or pleural effusions or rhinorhea Facial swelling Venous dilatation Neck vein or arm vein distension, upper extremity swelling, or upper body plethora Vodvtii'ka P and Štvertik P / Superior vena cava syndrome Response Response can be given by phlebography with digital subtraction (DSA) and spiral compu­terized tomography with contrast medium. Clinically, a severity of SVCS can be evalua­ted by Kishi's48 or Nicholson's49 classifica­tions (Table 2). If the response is "YES", go to the Treatment No. 3. If the response is "NO", go to the Questions No. 4. Treatment No. 3 Supportive care with corticosteroids, diure­tics, oxygen, positioning, anticoagulants, anti­biotics; relevant histopathology (endoscopy and/or biopsy); anticancer palliative therapy may be applied (chemotherapy or radiothera­py, or consider bypass). Question No. 4a: 1s the histopathology of the process causing SCVS known? Reason far the questions No. 4 73 -97% of SVCSs are caused by cancer. (Table 3) The question is raised by different treat­ments of different cancers. Table 3. The rate of benign and malignant causes of SVCS during the tirne since its first observation If the response is "NO", go to Treatment No. 4A. If the response is "YES", go to Question No. 4B. Treatment No 4A Supportive care: Percutaneous stenting and endoscopy and/or bioptic methods to obtain tissue sample. Question No. 4B: What is the histopatholo­gy of the process causing SVCS? SVCS can appear in patients suffering from malignant tumors in three situations:10, 44 Group A: SVCS is the first sign of cancer (its histopathology is not known). Group B: SVCS appears during a diagnostic process due to suspect for cancer (its histopathology can or cannot be known). Group C: SVCS appears during the follow-up period (histopathology is usually known if cancer progression is revealed), in some cases, an onco­logical treatment is exhausted and cannot be repeated (group Cl), in other cases, progressive disease is not praven -a cause of SVCS may be late sequels of the previous treat­ ment (group C2). According to our assessment of 151 1757 Hunter3 3 patients with SVCS, the rates of patients in 1934 Ehrlich12 54 46 the groups are as follows: A -25%, B -65%, C -10%.10,50 1949 Mcintire13 67 1954 Schechter14 40 60 1975 Lokich8 3 Chemosensitive cancers (groups A, B, C) 1987 Fincher15 13 1992 1993 1994 Baker1 Escalante2 Tayade16 10 3 13 90 97 87 -Lymphomas -Small cell lung cancer -Germ celi tumors 1998 Kee17 27 73 -Ete Radio/ Oncol 2000; 34(4): 349-55. Vodvlirka P and Štverlik P / Superior vena cava syndrome Rather chemoresistant cancers (groups A, B, C) -Non small celi lung cancer -Malignant melanoma Progressive cancer -all oncological treatment is already exhausted (group CI) -Further oncological treatment is not possible any more The cause of SVCS is late sequel of previous oncologica/ treatment (group C2) -Radiation fibrosis of mediastinum Treatment No. 4B -Differentiated chemotherapy according to the diagnosis (as curative or palliative treat­ment of patients of groups A, B, and the rest of group C -see the group definitions) -Percutaneous stenting or surgical methods (bypass) (both as a palliative treatment in patients of the groups Cl and C2 and as supportive care in patients of groups A and B and rest of group C), and -Chemotherapy and/or radiotherapy (as cura­tive or palliative treatment in patients of groups A, B, and the rest of group C) In summary, endovascular treatment is a simple and safe procedure to restore the patency of SVC in patients with malignan­cies. In most cases, it should be indicated as the first-line treatment and performed as early as possible. With proper knowledge of the SVCS cases, the best results could be obtained, if stenting follows the correct treat­ment schedule. References l. Baker GL, Barnes HJ. Superior vena cava syn­drome: etiology, diagnosis, and treatment. Am J Critic Care 1992; 1: 54-64. 2. Escalante CP.Causes and management of superior vena cava syndrome. Oncology 1993; 7: 61-68. 3. Hunter W. History of aneurysm of the aorta with some remarks on aneurysm in general. Med Observ Inquir (London) 1757; 1: 323-8. 4. Ahmann FR. A reassessment of the clinical impli­cations of the superior vena cava syndrome. J Ciin Oncol 1984; 2: 961 -969 5. Bell DR, Woods RL, Levi JA. Superior vena caval obstruction: 10-year experience. Med J Aust 1986; 145: 566-8. 6. Chen YM, Yang S, Perng RP, Tsai CM. Superior vena cava syndrome revisited. ]pn ] Ciin 011col 1995; 25: 32-6. 7. Gauden SJ. Superior vena cava syndrome induced by bronchogenic carcinoma: is this an oncological emergency? Australian Radiol 1993; 37: 363-6. 8. Lokich JJ, Goodman R. Superior vena cava syn­drome. JAMA 1975; 231: 58 -61. 9. Schraufragel DE, Hill R, Leech JA, Pare JAP. Superior vena caval obstruction -is it a medica! emergency? Am J Med 1980; 70: 1169-74. 10. Vodvai'ka P. Therapy of the supe[ior vena cava syn­drome [Summary in English]. Cs Radiol 1989; 43: 185-193. 11. Vodvai'ka P.Superior vena cava syndrome. Stud P11eu111ol Phtiseol 1999; 59: 151-5. 12. Ehrlich W, Ballon HC, Graham EA (1934) Superior vena caval obstruction with a consideration of the possible relief of symptoms by mediastinal decom­pression. J Thorac Surg 1934; 3: 352-64. 13. Mclntire FT, Sykes EM. Obstruction of the superi­or vena cava: A review of the literature and report of two personal cases. A1m Intern Med 1949; 30: 925-60. 14. Schechter MM. The superior vena cava syndrome. A111] Med Sci 1954; 227: 46-56. 15. Fincher RE. Superior vena cava syndrome: Experience in a teaching hospital. South Med J 1987; 80: 1243-5. 16. Tayade BO, Salvi SS, Agarwal IR. Study of superi­or vena cava syndrome -aetiopathology, diagnosis and management. J Assoc Plzysicians India 1994; 42: 609-11. 17. Kee SI, Kinoshita L, Razavi MK, Nyman UR, Semba CP, Dake MD. Superior vena cava syn­drome: treatment with catheter-directed thrombo- Radio/ 011col 2000; 34( 4): 349-55. Vodvdfka P a11d Štverdk P / Superi01· vena cava syndrome lysis and endovascular stent placement. Radiology 1998; 206: 187-93. 18. Davenport D, Ferree C, Blake D, Raben M. Radiation therapy in the treatment of superior vena caval obstruction. Cancer 1978; 42: 2600-3. 19. Fletcher GH. Textbook oj radiotherapy. 3th ed. Philadelphia: Lea and Febiger; 1980. 20. Levitt SH, Jones KT, Kilpatrick SJ, Bogardus CR. Treatment of malignant superior vena caval obstruction. Cancer 1969; 24: 447-51. 21. Perez CA, Brady LW. Principles and practices oj radi­a/ion oncology. 3th ed. Philadelphia: L.B.Lippincott Company; 1992. 22. Perez CA, Presant CA, VanAmburg III AL. Management of superior vena cava syndrome. Semi11 Oncol 1978; 5: 123-34. 23. Roswitt B, Kaplan G, Jacobson HG. The superior obstruction vena cava syndrome in bronchogenic carcinoma. Radiology 1953; 61: 722-37. 24. Rubin P, Green J, Holtzwasser G, Gerle R. Superior vena caval syndrome. Slow-dose vs. rapid high-dose schedules. Radiology 1963; 81: 388-401. 25. Armstrong BA, Perez CA, Simpson JR, Hederman MA.Role of irradiation in the management of superior vena cava syndrome. In/ ] Radia/ Oncol Biol Phys 1987; 13: 531-9. 26. Egelmeers A, Goor C, Meerbeeck van J, Weyngaert van den D, Scalliet P. Palliative effectiveness of radi­ation therapy in the treatment of superior vena cava syndrome. Buli Cancer Radiot/zer 1996; 83: 153-7. 27. Carlson HA. Obstruction of the superior vena cava. An experimental study. Arch Surg 1934; 29: 669-77. 28. Vodvarka P, Štverak P. Algorithm for percutaneous stenting in patients suffering from superior vena cava syndrome. Support Care Cancer 2000; 8: 251. 29. Štverak P, Skotnicova S, Vodvarka P, Martfnek A, Haringova M, Matoška P, et al. Malignant stenosis of the upper caval vein -casuistuics. Cas Lek Ces 1999; in press. 30. Ampil FL, Burton GV, Mills GM, Hollenberg HG. Long-term survival in small celi Jung cancer with superior vena caval obstruction. J Louisiana Stale Med Soc 1994; 146: 384-8. 31. Wiirschmidt F, Bunermann H, Heilmann HP. Small celi Jung cancer with and without superior vena cava syndrome; a multivariate analysis of prognostic factors in 408 cases. Int J Radini Oncol Biol Plzys 1995; 33: 77-82. Radio! Oncol 2000; 34(4): 349-55. 32. Charnsangavej C, Carrasco C, Wallace S, Wright KC, Ogawa K, Richli W. Stenosis of the vena cava: preliminary assessment of metallic stent. Radiology 1986; 161: 295-8. 33. Ali MK, Ewer MS, Balakrishnan PV, Ochoa DA, Morice RC, Raizner AE, et al. Balloon angioplasty for superior vena cava obstruction. Ann In tem Med 1987; 107: 856-7. 34. Crowe MT, Davies CH, Gaines PA. Percutaneous management of the superior vena cava oclusions. Cardiovasc Intervent Radiol 1995; 18: 367-72. 35. Dyet JF, Nicholson AA, Cook AM. The use of Wallstent endovascular prostesis in the treatment of malignant obstruction of the superior vena cava. Ciin Radiol 1993; 48: 381-5 36. Eng J, Sabanathan S. Management of superior vena cava obstruction.with self-expanding intralu­minal stents. Two cases report. Scand J Thorac Cardiovasc Surg 1993; 27: 53-5. 37. Elson JD, Becker GJ, Wholey MH, Ehrman KO. Vena caval and central venous stenoses: manage­ment with Palmaz balloon-expandable intralumi­nal stents. J Vase Intervent Radiol 1991; 2: 215-23. 38. Furui S, Sawada S, Kuramoto K, Inoue Y, Irie T, Makita K, et al. Gianturco stent placement in malig­nant caval obstruction: analysis of factors for pre­dicting the outcome. Radiology 1995; 195: 147-52. 39. Gaines PA, Belli AM, Anderson PB, McBride K, Hemingway AP. Superior vena caval obstruction managed by Gianturco Z Stent. Cli11 Radio/ 1994; 49: 202-6. 40. Hochrein J, Bashore TM, O'Laughlin MP, Harrison JK. Percutaneous stenting of superior vena cava syndrome: a case report and review of the litera­ture. Am J Med 1998; 104: 78-84. 41. Irving JD, Dondelinger RF, Reidy JF, Schild H, Dick R, Adam A, et al. Gianturco self-expanding stents: clinical experience in the vena cava and large veins. Cardiovasc Intervent Radio/ 1992; 15: 328-33. 42. Ostler PJ, Clarke DP, Watkinson AF, Gaze MN. Superior vena cava obstruction: a modern man­agement strategy. Ciin Oncol (Royal College of Radiologists) 1997; 9: 83-9. 43. Oudkert M, Heystraten FM, Stoter G. Stenting in malignant vena caval obstruction. Cancer 1993; 71: 142-6. 44. Oudkerk M, Kuijpers TJ, Schmitz PI, Loosveld O, deWit R. Self-expanding metal stents for palliative treatment of superior vena caval syndrome. Cardiovasc Intervent Radiol 1996; 19: 146-51. Vodvdfka P and Štverdk P / Superior vena cava syndrome 45. Peregrin JH, Krajcfkova D, Peš! L, Pfadna J, Kasalova D. Recanaculazation of the vena cava superior by a Gianturco stent [Summary in English]. Cs Radiol 1992; 46: 283-8. 46. Rocchini AP, Meliones JN, Beekman RH, Moorehead C, London M. Use of ballon expand­able stents to treat experimental peripheral artery and superior vena cava stenoses. Pedialr Cardiol 1992; 13: 92-6. 47. Salajka F, Boudny J, Valek V. Endovascular stents in palliation of malignant superior vena cava obstruction syndrome -the first experience [Summary in English]. Shtd Pneumol Plztiseol 1997; 57: 187-8. 48. Kishi K, Sonomura T, Mitsuzane K, Nishida N, Yang R, Sato Z, et al. Self expandable metallic stent therapy for superior vena cava syndrome: clinical observations. Radiology 1993; 189: 531-5. 49. Nicholson AA, Ettles DF, Arnold A, Greenstone M, Dyet JF. Treatment of malignant superior vena cava obstruction: metal stents or radiation therapy. J Vase fotervent Rndiol 1997; 8: 781-8. 50. Vodvai'ka P, Foukalova J, Cerny J. Syndrome of superior vena cava [Summary in English]. Vnitf Lek 1984; 30: 337-43. 51. Escalante C, Martin C, Rivera E, Pisters K, Truong M, Manzullo E, et al. Validation of a model for pre­dicting imminent death in acutelly ill cancer patients with dyspnea. Proc ASCO 1999; 18: 57 7a. Radio/ Oncol 2000; 34(4): 357-61.. case report Electrochemotherapy with cisplatin of breast cancer tumor nodules in a male patient Martina Reberšek, Tanja Cufer, Zvonimir Rudolf, Gregor Serša Institute of Oncology, Ljubljana, Slovenia Background. The metastases of breast cancer in a male patient were treated with electrochemotherapy by intratumoral injection of cisplatin. Electrochemotherapy is chemotherapy with the subsequent local appli­cation of e/ectric pulses to the tumor nodules in order to increase drug delivery into the cel/s. Case report. Cutaneous metastases of breast cancer were treated with the intratumora/ administration of cisplatin and by 8 electric pulses (1300 V/cm) applied a minute later to each cutaneous metastasis. The treatment resulted in complete response of two electrochemotherapy treated cutaneous metastases and par­tial response of the third metastasis. In cutaneous metastases treated with intratwnoral administration of cisplatin without electric pulses, only partial response was obtained. Conclusion. This study confirms that electrochemotherapy with cisplatin is effective in the treatment of breast cancer metastases, too, as it was a/ready proved far e/ectrochemotherapy with bleomycin. Key words: breast neoplasms, male -therapy -drug therapy; cisplatin; electroporation; drug de/ivery sys­tem, electrochemotherapy Introduction Electrochemotherapy is a treatment approach that utilizes the application of electric pulses to tumors in order to facilitate the accumula­tion of chemotherapeutic drugs in the cells.1 In preclinical studies, it was demonstrated in Received 22 June 2000 Accepted 8 August 2000 Correspondence to: Gregor Serša, Ph.D., Institute of Oncology, Zaloška 2, SI-1000 Ljubljana, Slovenia. Phone: +386 (0)1 433 74 10; Fax: +386 (0)1 433 74 10; E-mail: gsersa@onko-i.si vitro and in vivo that cytotoxicity and antitu­mor effectiveness of bleomycin and cisplatin is potentiated severa! fold by electrochemo­therapy. 2 These favorable preclinical data have been confirmed in the clinical studies on cancer patients with cutaneous and subcutaneous tumors treated by electrochemotherapy with bleomycin and with cisplatin.3 Objective responses were obtained for the majority of the electrochemotherapy -treated lesions, whereas the lesions that were only exposed to electric pulses or only treated with bleomycin or cisplatin did not respond. Electrochemotherapy with cisplatin, given Reberšek Met ni./ Electroc/zemotlzerapy oj breast cancer intratumorally, was demonstrated to be effec­tive on many different tumor types, but not on breast cancer metastases.4, 5 Therefore, the aim of this study was to determine whether electrochemotherapy with cisplatin would also be effective in the treatment of cutaneous metastases of breast cancer. Case report Patients' history A male patient, born in 1932 (H.F. No.: 6804/90) has been treated for locally advanced right breast cancer since 1990. He received 4 cycles of chemotherapy, consisting of epidox­orubicin, cyclophosphamide and 5-FU and was also irradiated to the right mammary region. Clinically, complete remission was achieved, but it was never histologically proved. He was then treated with hormona! therapy with tamoxifen until the first progres­sion of disease in July 1997 with lung metas­tases and locoregional progress in the right mammary region. After the progress, the patient was treated with the second and third line hormona! therapy with aminog­lutethimide and anastrozole. Both treatments resulted in stagnation of lung and cutaneous metastases and lasted approximately 1 year. In July 1999, the second line chemotherapy with etoposide was started due to the progression of lung metastases. With chemotherapy, the stagnation of lung metastases was achieved only until November 1999 when the lung and cutaneous metastases in the right mammary region progressed again. We started to apply electrochemotherapy to the cutaneous metas­tases in right mammary region; the possibili­ties of standard treatment were tired out. Electrochemotherapy protocol Electrochemotherapy consisted of intratu­moral administration of cisplatin and subse­quent exposure of cutaneous breast cancer Radio/ Oncol 2000; 34(4): 357-61. nodules to electric pulses. Cisplatin was administrated intratumorally, at a dose of 1 mg per 100 mm3 of nodule. The tirne interval between the cisplatin administration and of electric pulses application was 1 minute. The nodules to be treated were sprayed with Xylocaine in order to avoid pain. Square wave electric pulses of 100 µs, 910 V amplitude (1300 V /cm), frequency 1 Hz were delivered through two parallel stainless steel electrodes (distance 7 mm, width 7 mm, length 14 mm, with rounded tips) with an electropulsator Jouan GHT 1287 Oouan, France). Electric parameters were controlled by oscilloscope HM 205-3 (Hameg Instruments, Germany). Electric pulses were delivered in two trains of 4 pulses with one-second interval, in two per­pendicular directions (4+4 configuration). A good contact between electrodes and the skin was assured by means of conductive gel. When severa! nodules were treated at the same tirne (in the same session), electric puls­es were delivered one after the other at the intervals of at least 1 minute. Fol/ow up During electrochemotherapy, the patient was monitored for the evaluation of acute treat­ment side effects. Immediately after the ther­apy, the patient remained in the outpatient clinic for two hours before he was released home. The patient was examined in two-week intervals for the evaluation of response to electrochemotherapy. Tumor nodules were measured with calliper and photographed before and after treatment. According to WHO guidelines, the res­ponse to electrochemotherapy was assessed as complete response (CR), if nodules became impalpable, partial response (PR), if nodules decreased in size by more than 50%, no change (NC), if they decreased in size by less than 50 % or increased in size by less than 25 %, and progressive disease (PD), if they increased in size by more than 25%. Reberšek Met al./ Electrochemotherapy of breast cancer Results oj the treatment In November 1999, the patient agreed to enter the electrochemotherapy protocol. Three of 10 cutaneous metastases, one on the right shoulder and two in the right mammary region, were treated with electrochemothera­py. Two cutaneous metastases in right mam­mary region were treated with intratumoral administration of cisplatin without electric pulses. Five cutaneous metastases served as controls (Table 1). Eight weeks later, CR was obtained in two metastases treated with electrochemotherapy, and PR was obtained in the third metastasis (Figure 1). In both metastases treated with intratumoral administration of cisplatin with­out electric pulses, partial response was obtained 8 weeks later (Figure 2). Three of control metastases progressed, and two of them were the same size. Six months after the beginning of treat­ment, in May 2000, another progress of dis­ease in the lung was found and the patient died due to lung metastases at the end of the same month. The two metastases in which CR was achieved with electrochemotherapy, remained in CR until the patient's death, whereas the third metastasis in which only PR was achieved has already progressed by that tirne. Electrochemotherapy was well tolerated by the patient. There were no major local or gen­eral side effects. The intratumoral route of cis- Table 1. Summary of tumor response platin was tolerable, the patient did not com­plain of the pain. The application of electric pulses induced muscle contractions beneath the site of treatment after each pulse, but they were released immediately after the pulse was discontinued. After the treatment, only erythema and slight oedema occurred at the treated area, but both disappeared in one day. There were no exulcerations of cutaneous nodules. After electrochemotherapy, the patient did not complain of fatigue or other kind of discomfort. The treatment with intra­tumoral cisplatin did not cause any local or systemic toxicity. Discussion This case report shows that electrochemo­therapy is effective also in the treatment of cutaneous breast cancer nodules, because in two electrochemotherapy treated cutaneous nodules CR was obtained and, in the third nodule, PR was obtained. Electrochemotherapy was already proved to be effective in the treatment of cutaneous and subcutaneous nodules of different histo­logical types of tumors. Mostly used chemotherapeutic drugs were bleomycin and cisplatin. The results of numerous trials per­formed at five cancer centers demonstrated that electrochemotherapy with bleomycin is very effective in the treatment of cutaneous Size of the treated nodules (mm3) Treatment Before treatment After 8 weeks Response Control nodules 417.8 2436.3 PD-· 9.4 10.6 NC 10.5 13.0 NC 34.5 57.6 PD 22.0 41.9 PD Electrochemotherapy 37.7 o CR 30.2 o CR 13.9 3.1 PR Reberšek Met al./ Electrochemotherapy oj breast cancer A B Figure l. Photomicrograph of tumor nodule before electrochemotherapy (A) and 8 weeks after it (B). The nodule (V= 37.7 mm3) was injected with 0.377 mg of cisplatin and, after 1-minute, 8 electric pulses (1300 V/cm, 1 Hz, 100 (s) were applied to the nodule. Eight weeks after the treatment, the tumor nodule was in CR. A B Figure 2. Photomicrograph of tumor nodule before treatment with cisplatin (A) and 8 weeks after it (B). The nodule (V= 37.7 mm3) was injected with 0.377 mg of cisplatin intratumorally. Eight weeks after the treat­ment, the tumor nodule was in PR. and subcutaneous nodules of different tumors, including breast adenocarcinoma no­dules. 6 In ali of the nodules CR was obtained. Eight additional metastatic breast cancer nod­ules were treated with electrochemotherapy; but they couldn't be evaluated because the follow-up was too short. The first clinical study of electrochemo­therapy was performed at the Institute of Oncology, Ljubljana, by evaluating antitumor effectiveness of electrochemotherapy with intratumorally administered cisplatin. In ali electrochemotherapy treated nodules of his­tological different tumors, CR was obtained.4 Another clinical study on malignant mela- Radiol Oncol 2000; 34(4): 357-61. noma patients showed that electrochemother­apy with intratumoral administration of cis­platin is effective, resulting in 68% of CR in the treated cutaneous tumor nodules.5 No clinical study on electrochemotherapy of cutaneous breast cancer nodules with cis­platin administered intratumorally has been done so far. Some preclinical studies were made on electrochemotherapy and intramus­cular administration of bleomycin to breast cancer nodules in experimental animals.7 Thirty-three of 38 electrochemotherapy treat­ed nodules regressed at least partially within 2-3 weeks, three of them were cured. In none of the control nodules treated only with bleomycin given intramuscularly neither par­tial response nor growth arrest were attained. In conclusion, clinical studies of elec­trochemotherapy with cisplatin administrat­ed intratumourally have demonstrated to be effective and safe in the treatment of differ­ent histological types of tumors. Our case report demonstrates it is effective in the treatment of breast cancer nodules, too. The clinical study on more breast cancer patients is going on. Acknowledgement This work was funded by research grant from the Ministry of Science and Technology of the Republic of Slovenia and in part by IGEA s.r.l. Carpi (Modena) Italy. References 1. MirLM, Orlowski S. The basis of electrochemo­therapy. In: Jaroszeski MJ, Heller R, Gilbert R, and editors. Electrochemotherapy, electrogenetherapy and transdermal drug delivery. New Jersey: Humana Press; 2000. p. 99-117. 2. Serša G. Electrochemotherapy: animal model work review. In: Jaroszeski MJ, Heller R, Gilbert R, editors. Elech·oche111otherapy, electrogenetherapy mzd transdermal drug delivery. New Jersey: Humana Press; 2000. p. 119-36. Reberšek Met al. / Electroche111otherapy of breast ca11cer 3. Heller R, Gilbert R, Jaroszeski MJ. Clinical trials for solid tumours nsing electrochemotherapy. In: Jaroszeski MJ, Heller R, Gilbert R, editors. Electroc/1emotherapy, e/eclroge11etherapy and transder­mal drug delivery. New Jersey: Humana Press; 2000. p. 137-56. 4. Serša G, Štabne B, Cemažar M, Jancar B, Miklavcic D, Rudolf Z. Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effec­tiveness by application of electric pnlses in cancer patients. Eur J Cancer 1998; 34: 1213-8. 5. Serša G, Štabne B, Cemažar M, Miklavcic D, Rudolf Z. Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients. Ciin Cancer Res, 2000; 6: 863-7. 6. Mir LM, Glass LF, Serša G, Teissie J, Domenge C, Miklavcic D, et al. Effective treatment of cuta­neous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer 1998; 77: 2336­42. 7. Belehradek JrJ, Orlowski S, Poddevin B, Paoletti C, Mir LM. Electrochemotherapy of spontaneons mammary tumours in mice. Eur J Ca11cer 1991; 27: 73-6. Radio/ Onco/ 2000; 34( 4): 363-8. Synchronous and metachronous bilateral germ cell tumours of the testis Ferhat Berkmen, Ahmet Fuat Peker, Sinan Ba§ay, Ali Ayyild1z, Ali ihsan Ank Department oj Urologic Oncology, Ankara Oncology Education and Research Hospital, Turkey Background. We reported fourteen patients with bilateral testicular tumours, and discussed the need far contralateral testicular biopsy during orchiectomy to detect carcinoma in situ (CIS). Patients and methods. Fourteen patients with bilateral testicular tumours were reviewed in order to estab­lish the incidence, histologic findings, predisposing jactors, interval between the development of two pri­maries, type of treatment administered and the overall outcome. Results. Bilateral tumours were identified fourteen times between 1984 and 1996. The tumours occurred simultaneously in five patients, and a contralateral malignancy developed in the others after a time ranging between 6 and 107 months. The most frequent histologic diagnosis was seminoma and was confirmed in 10 cases. Four patients had a history of undescended testis. One patient a/so had persistent miillerian duet syn­drome. Ali patients were initially treated with radical orchiectomy. According to their stage, ali patients were treated with radiotherapy and/or clzemotherapy. Four patients died in the period between 6 and 33 months after the diagnosis. The remaining 10 are stili alive with, no evidence oj disease. Conclusions. The second tumour is diagnosed more often due to prolonged jollow-up examinations; peri­odic self-examination by patients; ultrasonography of the testis; tumour markers AFP and beta-HCG and a contralateral testicular biopsy during orchiectomy. CIS of the contralateral testis evolves into invasive can­cer in probably most oj the patient germ celi tumours and usually cured by radiotherapy. Despite that, we do not advocate a routine biopsy of the contralateral testis in the patients with unilatera/ testicular tumour due to the jollowing reasons: 1. CIS oj the testis is the precursor of most malignant testicular gemz celi tumours except for spennatocytic seminoma, Teratoma and Paediatric yolk sac tumours. 2. CIS is not diag­nosed in about 95 % oj ali cases with testicular tumours. 3. CIS may be randomly distributed and a single biopsy may not detect it. 4. Testicular biopsy does not only devoid nzinor complications but also affects sper­matogenesis. 5. Development oj a germ celi twnour in general takes 3 and 5 years, a non-palpable testicu­lar tumour can be loca/ised by ultrasonography and ultrasound scanning occasionally identifies CIS based 011 irregular pattenz secondary to the normal tubules. 6. Scar lesions in tlze testis after biopsy may render sonographic interpretation more difficult. 7. The natura/ history of CIS is unknown and the precise method of treatment is controversial. 8. There is no data that CIS has an impact on survival. 9. A careful fol!ow-up is warranted to ali germ celi tumour patients, including those with negative biopsies. So, a watchful waiting policy to the problem of the CIS should be the choice. Key words: testicular neoplasms-pathology; orchiectomy; carcinoma in situ -diagnosis; ger111ino111a Berkmen F et a/. / Bila/era/ genu celi tumors of the testis Introduction Results Testicular carcinomas are relatively rare tumours; however, they are the most common solid tumours occurring in males between the ages of 20 and 34 years. The incidence of tes­ticular tumours is 2.1 to 2.3 per 100 000 males.1 The metachronous appearance of second tumours deserves a particular attention be­cause it has been reported that once a patient has a malignant tumour of one testis, the risk of developing a tumour on the opposite side is much higher than that of the general popu­lation.1 The increase of the bilateral testicular cancer may be due not only to higher survival rates obtained with cisplatin based chemo­therapy but also to its early detection by the ultrasound of the testes. The aim of the present paper was to analyse a group of patients with bilateral germ cell tumours of the testis and to discuss the need for a biopsy of the contralateral testis during orchiectomy for the first primary. Patients and methods From 1984 to 1996, 876 patients, 17 to 68 years of age, were treated for a testicular germ cell tumour in Ankara Oncology Education and Research Hospital. We reviewed the medica! records of these patients to identify and study bilateral testis tumours (BTT) with respect to their incidence, histopathologic findings, predisposing factors, interval between the development of two primaries, type of treatment administered, and the over­all outcome. Received 3 May 2000 Accepted 19 May 2000 Correspondence to: Associate. Prof. Ferhat Berkmen, MD, Necatibey Cad., Sezenler Sok. 2/12, Sihhiye, Ankara, 06430 Turkey; Phone: +312 336 09 09 / 333; Fax: +312 345 49 79; E-mail: defne@mail.koc.net Radio/ Oncol 2000; 34(4): 363-8. Bilateral invasion was identified in fourteen patients (1.6%). The tumours occurred simul­taneously in five patients (0.57%). In nine cases, a contralateral malignancy developed after a tirne interval ranging between 6 and 107 months. The age of patients ranged from 21-58 years (median 34.5 years). Seminoma was the most frequent pathologic diagnosis (10/14 cases), followed by mixt tumours (2/14 cases: seminoma + embryonal carcinoma, se­minoma + teratocarcinoma), and each one had embryonal carcinoma and teratocarcino­ma (Figure 1). Four of fourteen patients (28.5%) had a history of undescended testis. One of these patients also had persistent Miillerian duet syndrome with bilateral abdominal testicular seminoma.2 . nonseminoma m seminoma and nonseminoma .seminoma Figure 1. Histologic findings in consecutive bilateral testicular tumors. Initially, all patients were treated with rad­ical orchiectomy. In accordance with the stag­ing system used in our hospital3 the patients were classified as follows: -stage I: four patients -stage Ilb: one patient -stage Ilc: five patients -stage III: one patient -stage IV: three patients Four of ten seminoma patients in stages I and Ilb, and seminoma + teratocarcinoma case in stage I, received radiotherapy. Of the remaining eight patients in stages between Ilc and IV were treated with the reduced dose PVB chemotherapy protocol (cisplatin, vin­blastine, bleomycin).3 Three months after radiotherapy, the seminoma + teratocarcino­ma case in stage I was also treated with Berkmen F et al. / Bila/era/ genn celi lumors of tile testis chemotherapy because the leve! of tumour marker AFP was noted to be high. Four patients died 6, 9, 20 and 33 months, respec­tively after the diagnosis of the second tumour. Three of four patients died due to central nervous system metastases, and the fourth died because of myocardial infarction. All other patients are stil! alive and the longest survival tirne is 8 years and 11 months. Discussion Although the average incidence of testicular tumours is in the range of 2.1 to 2.3 per 100.000 males, it seems to have increased in the last three decades. It remains the most common solid tumour in men between the 45 ages of 20 and 34 years.1,, In patients who survive one testicular malignancy, the risk of developing a con­tralateral testicular malignancy is 500 to 1000 times greater than in healthy male subjects. The risk is again increased by the factor 2 to 4 in cases of previous cryptorchidism. 6-8 The risk factors like cryptorchidism in unilateral malignancy were reported to range between 7 and 35% of the total number of patients with 10 testicular cancer. 9, In our series, the incidence of cryp­torchidism is 2.7% (24 patients) and 28.5% of these (4 patients) had BTT. More recent stud­ies document an increased incidence of BTT. The relative incidence of BTT reported in the literature from 1981 to 1995, can be calculat­ 11 ed as 2.36%.8, -15 In the current study, BTT is 1.7% of the total incidence of testicular carci­nomas. In principle, bilateral tumours can occur synchronously or metachronously, i.e. at dif­ferent times. Recent literature suggests that approximately two thirds of the metachro­nous testicular tumours occur within 5 years of the first diagnosis.16 Our study disagrees with this maintaining that 33.3% of all metachronous tumours occurred within 5 year of the first diagnosis and that 66.6% were diagnosed after a period of more than 5 years (Figure 2). The incidence of synchronous BTT have been reported in the range of 16.6% to 31.5%.16-18 Our incidence is 35.75%. lO 9 8 7 6 5 4 3 2 0-1 Figure 2. Time-interval until the diagnosis of the con­tralateral testicular tumour. In Denmark, the incidence of carcinoma in situ (CIS) in the contralateral testis in patients with testicular malignancy has been reported to be 5% to 6%; however, 50% of these men had a history of cryptorchidism. Though the reports of sequentially diagnosed BTT are increasing in number, routine biopsy of the opposite testis remains controversial. CIS is a characteristic pattern within the seminiferous tubules. In typical cases, such tubules contain two types of cells: CIS germ cells and Sertoli cells, and CIS is the precursor of most types of malignant testicular tumours, except of ter­atoma, spermatocytic seminoma, paediatric yolk sac tumours and epidermoid cyst (mono­dermal teratoma).19 Thus, CIS is found in only 5% of patients with the primary tumour of the testicle. Biopsy carries the risk of a transscrotal procedure in consecutive tumour and scar lesions in the testis may render sono­graphic interpretation more difficult. A technique that seems to have a bright future is non-invasive CIS detection employ­ing ejaculate examination for the presence of aneuploid cells in flow cytometry or detection of tumour cells in the ejaculate using a spe­cific monoclonal antibody.20 There is no doubt that an impalpable testicular tumour Radio/ Oncol 2000; 34(4): 363-8. Berkmen F et 11/. / Bila/era/ germ celi tumors of the testis can be localised by ultrasound, and ultra­ crease of adrenergic activity from which hot sound scanning occasionally identifies CIS flushes result. Although these flushes ar.e not based on irregular pattern secondary to the dangerous, they can sometimes be extremely abnormal tubules.5 Thus, no risk of implanti­ bothersome and, as a result, can potentially ng the carcinoma in the scrotal wall or alter­ reduce the quality of life of patients.24 Only ing the lymphatic drainage has been involved. one of our cases experienced hot flushes. Realistically, we do not recommend a routine Since in the case of post-menopausal hot flu­ biopsy of the contralateral testicle to detect shes in women, sufficiently high-doses of CIS during radical orchiectomy, except in oestrogen lead to complete disappearance of cryptorchidic patients, as cryptorchidism is their complaint, a replacement of testos­ an important indication for biopsy of the terone for bilaterally orchiectomised patient other testicle and as a tumour in the con­ with BTT is however indicated. tralateral testicle occurs in around 50% of all these cases. Table 1. Sexual dysfunction in patients treated for The management plan of the tumour in the bilateral testicular cancer contralateral testis depends upon the tirne Number of patients Tota!(%) interval between the development of the two No current sexual activity 1 10 tumours, extent of the therapy of the original Erectile dysfunction 4 40 tumour and the histologic type and stage of Low sexual desire 8 80 the second tumour. There is no standard ther­ Reduced ejaculate 10 100 apy for patients with consecutive tumour, and Reduced orgasmic intensity 2 20 each patient requires an individual therapeu­ tic approach. The prognosis of patients de­ pends on the same factors that affect the Conclusions prognosis of unilateral testis tumours. In the absence of an identifiable disease, a policy of Second tumors are being increasingly diag­ watchful waiting and for identifiable metas­ nosed due to the following reasons: (1) tases cisplatin based chemotherapy should be Prolonged follow-up examinations; (2) 21 treatment of choice.20, Periodic self-examination by patients; (3) Treatment at each major site of urologic Ultrasonography of the testis; (4) Tumour malignancy has characteristic side effects on markers AFP and beta-HCG; (5) A contralat­ sexuality and fertility. Bilateral orchiectomy eral testicular biopsy at the tirne of orchiecto­ have a negative effect not only on potency but my. also on sexual life because serum testosterone CIS of the contralateral testis evolves into reaches castrate levels in mean of 3 hours.22 invasive cancer in probably most of the An abnormally low level of testosterone may patients with germ cell tumours and cured by cause difficulty in achieving full erection, a radiotherapy. Although CIS of the testis is the loss of sexual desire, reduced ejaculate, a precursor of most malignant germ cell need for prolonged stimulation to reach tumours we do not advocate routine biopsy of orgasm and often a decrease in the intensity the contralateral testis with unilateral testicu­ of pleasure produced during penile caressing lar tumour. It is estimated that only the typi­ and orgasm.23 , 24 The rates of sexual dysfunc­ cal form of seminoma could be diagnosed and tion in our cases are shown in Table 1. The CIS occurs in the testicle containing semino­ reduction of the testosterone levels secondary ma in more than 85% of the cases.25,26 to an orchiectomy provokes a counter-regula­ The natural history of CIS is unknown and tory effect with an intra-hypothalamic in- the precise method of treatment is controver- Radiol 011co/ 2000; 34(4): 363-8. Berk111en F et ni./ Bilntera/ gen11 celi tu111ors oj the testis sial. In a large study involving 87 institutions in Europe, the prevalence of TIN in the con­tralateral testis was found to be 4.9%. Testi­cular atrophy was reported to be an indepen­dent factor for prevalence in a multivariate analysis.27 Since CIS is not randomly dis­persed throughout the testis a single biopsy may not detect it.28 There is a small but defi­nite false-negative detection rate, and there are reported cases of the development of neo­plasia despite the earlier negative biopsy for testicular intraepithelial neoplasia. 28 A 3 mm surgical testicular biopsy has a diagnostic sensitivity close to 100%, it is not devoid of minor complications such as infec­tion, superficial serous exudates, localised induration and pain. It has been suggested that biopsy of the contralateral testis affects spermatogenesis.29 Thus, ultrasound scan­ning occasionally identifies CIS based on irre­gular pattern secondary to the normal tubules and scar lesions in the testis after biopsy may render sonographic interpretation more diffi­cult. On the other hand, searching for more disease in the contralateral testis and facing treatment of CIS, since 95% of patients does not have CIS in the other testis, may impose unnecessary emotional stress in some patients.27,30 Radiotherapy can eradicate CIS and, there­by, prevent cancer development; but, to date, there is no data whether Leydig cell function is affected or not at even low doses (14 Gy).31 Furthermore, close follow-up is warranted to all germ cell tumour patients, including those with negative biopsies. So, to our opinion, a watchful waiting policy to the problem of CIS in the contralateral testis should be the choice. The treatment principles of secondary tumours should be similar to that for primary tumours. In order to prevent sexual dysfunc­tion and hot flushes, administration of andro­gens may be mandatory in some cases. Thus, an artificial testicular implant can be per­formed if psychological resistance occurs. References 1. Morse MJ, Whitmore WF Jr. Neoplasms of the testis. In: Walsh PC, Gittes RF, Perlmutter AD, Stamey TA, editors. Cnmpbel/'s Urology. 5th ed. Philadelphia: WB Saunders; 1986. p. 1539-44. 2. Berkmen F, Alagiil H. Germinal celi tumors of the testis in cryptorchids. J Exp Ciin Cnncer Res 1998; 17: 409-12. 3. Berkmen F. Reduced :vi -zXx; -x) id film combinations.9 We also analyze the MTF data reported by other investigators7 to authenticate this type of modeling. 2 f '( _)2 sx=.L.iwixi-x (6) Logit analysis and The logit analysis transforms sigmoidally ( = In{MTF(.f)/[1-MTF(.t;)]} (7) shaped functions into straight-line func­tions10 that can then be analyzed in terms of the "slope" and "intercept" regression para­meters. Following the approach described by Bencomo and Fallone6 for diagnostic screen/­film systems, we can fit the MTF of metal/film detectors by a function MTFi(f) given by: n w( = wi / L, wi , i=l 1 MTF/f) = l -(a+bln(f/ J')) (1) +e where f is spatial frequency and f' is a con­stant (typically 1, with units of /) to ensure correct dimensionality. The straight-line logit transform of Eq. 1 is:10 f logit(MTFU)) = In [ MTF1, () j . (2) L 1-MTFL (f) Radio/ Oncol 2000; 34(4): 375-80. (10) w; = MTF(.t; ){1-MTF(.t;)} where Ž and x are mean values of l and x respectively, and MTF(f;) is the value of the MTF, at the spatial frequency f; averaged over the three or four measurements. The summa­tion is over the n frequency components of the MTF. Logit analysis has been most widely used for accurate modeling of bio-assay dose sur­vival curves. Berkson assumed that when a system is exposed to a dose y the fractional response P which measures the observed por­ Falco T, Fnl/011e BG / Logi! 111odeli11g oj the Modulation Trm1sfer Fu11clio11 (MTF) tion p affected out of m exposed, is a random variable that is binomially distributed.11-13 Fram binomial statistical theory, the variance of the distribution p is sfi = P[l -P]/m. We can view the MTF as the fractional intensity response of the front-metal/film system to an input composed of sinusoidals of equal inten­sity for all spatial frequencies f In our case, P = MTF(f) , and the regression parameters a and b can be obtained from a simple least squares calculation which minimizes the weighted-square difference between the observed MTF(f) and the estimated MTFL(f)· The weighting w;, of Eq. 10, equals msp. The goodness-of-fit of the logit function to the MTF(f) data can be specified with the regression correlation coefficient r, and the uncertainties in a and b can be specified by s a and s /J, respectively. The best fit regression correlation coefficient is given by: r= ,J .J=. (11) SS I xI °l S where Sx and s 1 are the standard deviations on x and /, respectively.14 The standard devia­tions of a and b are (12) (13) with s = (14) n-2 and the data consists of Iz spatial frequency observations.15 The experimental uncertainty in the individual MTF(f;) is not taken into account in the logit model. Results and discussion The detectors from Falco and Fallone9 having front-plates only, are listed in Table 1 with their best fit a and b regression parameters. Plots of the logit fits to the measured MTF(f) are shown in Figures 1 and 2 for detectors irradiated by the 10 MV and Co-60 spectrum, respectively. The correlation coefficients r (Table 1) range from -0.995 to -0.999, and for a particular metal, the parameter a decreases with front plate thickness (or mass thick­ness). The decrease of a with front plate thickness corresponds to the decrease of the MTF with front plate thickness for a given metal. To further demonstrate the fitting capabili­ties of the logit technique, the technique was also applied to the MTF's of front-metal/film detectors measured by other investigators. Table 2 shows the logit best-fit parameters for the MTF's reported by Munro et a/. 7 for the 18 MV and Co-60 spectra. The correlation coeffi­cients range between -0.994 and -0.999 except for one value at -0.991. Plots of the logit regTession fits to these data are shown in Figure 3. To avoid clutter, some of the curves in these figures have been offset vertically. The decrease in parameter a with beam ener­gy cannot be verified with the Munro et al. data because they only used one thickness for each of the front-metal plates. The data of Droege and Bjarngard8 were not fitted because of a flaw in their technique as was discussed by Munro et al.7 In Figure 4, our measured MTF(f)' s are com­pared to the fitted MTFL(f) for the (a) typical and the (b) worst case. For the worst case, the MTFL (f) is within the uncertainty of the mea­sured MTF(f) for the whole spatial frequency range. The regression parameters a and b for the detectors in Table 1, are plotted in Figure 5 as a function of front-plate mass thickness. The plots exhibit a linear relationship between the regression parameters and the mass thick- Fa/co T, Fallone BG / Logi/ nwdeling of tlze Modula/ion Transfer Fzmction (MTF) Table l. Regression coefficients a and b for the metal-plate/film detectors studied. The correlation coefficient r, is also shown Front-"Intercept" "Slope" Correlation Plate a b Coefficient r Thickness Co-60 (mm) 0.95 Cu -0.150 ± 0.0101.75 Cu -0.369 ± 0.0102.40 Cu -0.617 ± 0.0080.39 Pb 0.108 ± 0.005 1.lOPb 0.033 ± 0.0081.31 Pb -0.046 ± 0.0072.05 Pb -0.174 ± 0.007 05. o . • ° lOMV Co-60 lOMV Co-60 10 MV -0.480 ± 0.014-0.834 ± 0.009 -0.982 ± 0.012 -0.995 -0.996-0.782 ± 0.015-0.750 ± 0.009 -0.927 ± 0.013 -0.996 -0.995-0.969 ± 0.007-0.700 ± 0.009 -0.809 ± 0.007 -0.997 -0.998 -0.142 ± 0.005-1.047 ± 0.004 -0.991 ± 0.005 -0.999 -0.999 -0.331 ± 0.007-0.932 ± 0.007 -0.968 ± 0.006 -0.998 -0.999 -0.415 ± 0.010-0.895 ± 0.006 -0.949 ± 0.008 -0.998 -0.998-0.586 ± 0.011 -0.810 ± 0.008 -0.917 ± 0.010 -0.997 -0.997 V.7J 111111 \..,U . 1.75 mm Cu 0 2.40 mm Cu ) • 0.95 mmCu 0.5. 1 . 1.75 mmCu 0 2.40mm Cu o Co-60 -..'-­ -0.5E 1 - ........, - . -1.5 1 '--' s ­ . -2 1 (a) -2.5 2 s 1.5 s :§_ 1 :§_ 0.5 o o -0.5 -0.5 -1 -1 -1.5 -1.5 -2 2() -2 t ,.111 •I,,,, 1,,,, 1,,,,1. -1.5 -1 -0.5 O 0.5 1.5 2 (b) -.. t ., , -2.5 -1.5 -1 -0.5 O 0.5 1.5 2 ln(f/f') Figure l. Logit fits to the MTF(f) 2mm = d<=0.056 mm, BGO 2R>=1.1mm Figure 2. An estimate of the limit for the crystal cross sectional size. The shadow region represents the vol­ume of induced ionization and the place from which the scintillation light contributes to the energy signal. The data for stopping power of electrons were taken from.1 If gamma ray hits the crystal too close to the reflector cover or to the optical fiber (crys­tal is inside optical fiber) then some of the ionization does not contribute to the scintilla­tion light; therefore, the energy signal is weaker. Consequently, a definite volume close to the edge is not useful and is treated as scattered. An estimate is given for the cir­cular shape of the crystal and for two popular scintillation materials (Nal and BGO). The scintillation light will be reduced in approxi­mately 20 % of absorbed gamma rays. Some of the signals coming from these 20 % will still be included in the lower part of the pho­topeak but some will be !ost. Therefore, there is no meaning of using thinner sized crystals than 1-2 mm depending on the material (for Nal crystal this size is limited to 2 mm and for BGO crystal 1 mm). The sensitivity increases with the crystal length, density and cross sec­tional size. The energy resolution is improved by more efficient PSPMT and more effective collecting of scintillation light in crystal. In the third method (Figure le) the incident gamma ray is absorbed in the region of "p-n junction" region of the semiconductor crystal and a large number of electron-hole pairs is created. Their number (approximately 3 -5 eV/electron-hole pair is spent on average) is proportional to the energy of the gamma ray and is nearly ten times greater than the quan­tity of the scintillation light (approximately 30 eV per ionization). For the same reason, the energy resolution is better. Because of the improved energy resolution the quantity of the Compton scattered gamma rays in the energy peak window is considerably reduced, whereas the contrast of the structures in the scan is much better (Figure 3). Figure 3. Comparison of breast seans from CZT and NaI Anger gamma camera. The efficiency of the lately developed CZT crystal is even better than for Nal. The intrin­sic spatial resolution of the CZT gamma cam­era is considerably better and is about 2 -3 mm for 140 keV compared to 3 -4 mm for Nal gamma camera. On the other hand, the col­lection tirne for electron-hole pairs is at least 100 times shorter than is the decay tirne for scintillation light in Nal crystal; therefore, the increased count rate can be achieved (250.000 counts/s). The weight of such imaging system is 100 times lower and the CZT gamma cam­era is easily portable to emergency depart­ments or elsewhere. It is expected that the price for such gamma camera will also be much lower because of the less complicated production. Fidler V/ Diag11ostic 1111c/ear medicine instrumenta/ion Table l. Physical properties far some interesting scintillation materials. NaI-Thalium-doped sodium iodide, BGO­Bismuth germanate (Bi4Ge3O12), LSO-Lutetium oxyorthosilicate, YSO-Yttrium oxyorthosilicate NaI BGO LSO YSO Density (glcm3) 3.67 7.13 7.40 4.54 Effective Z 51 74 66 Decay tirne (ns) 230 300 40 Relative light output 100 15 Energy resolution 7.8 % 10 % <10% <7.5 % 1/µ for 140 keV 4.2 mm 0.82 1.0 7.7 1/µ for 511 keV 30 mm 11 12 26 New materials far detection crystals Some new detector materials were developed recently which promise a considerable improvement of nuclear medicine imaging devices. These materials are presented in Table 1-2 The LSO is intrinsically radioactive and is not useful for SPET but can be used for PET (coincidence measurement excludes the sin­gle decay and absorption of gamma ray inside LSO crystal). The use of LSO and YSO is very promising in the so-called phoswhich detec­tor where the YSO crystal {l -2 cm) is in front and the LSO crystal {l -2 cm) is optically coupled to the YSO. The YSO is used for attenuation of low energy {in the range of 100 keV) and LSO serves as the light pipe and for attenuation of high energy gamma rays. The induced scintillation signals from both crys­tals can be separated because of their differ­ent decay times. The BGO is nearly exclusively used for PET, but will probably be replaced by this phoswhich detector. One of the most interesting detectors is semiconductor CZT (cadmium zine telluride) which has even better stopping power for 140 keV gamma rays than NaI {TI) and much bet­ter energy resolution (for factor of 10). An array with a large number of very small sen­sitive areas can be formed so that each of these areas is a separate pixel in the digital image. SPET The biggest improvement in the SPET was the development of severa! detector heads which drastically improved the system sensitivity. In cardiac SPET, the use of two heads at 90 ° and the whole-body bone SPET or scanning at 180 ° shortens the acquisition tirne or doubles the acquisition counts. The improvement of the gamma camera features was mainly due to the development of the so-called digital head electronics which replaced the old ana­log position circuit by the digital one. The out­put from each PMT is digitized and the spatial coordinates are then computed. Ali correc­tions for non-linearity, spatial and energy non-uniformity can be performed on-line by the use of special fast processors. In the future, the probable development of SPET will involve the building the tomo­graphic system of severa! modular multi-crys­tal detectors which will introduce even greater flexibility than that with two or three big planar gamma cameras at different angu­lar setup. Each module will probably be an array of very tiny crystals from YSO and LSO or semiconductor CZT detector. Another possible approach in modular design of SPET will be the development of special models for each organ (i.e. thyroid and cardiac tomograph needs relatively small sized detector's modules) and, possibly, much lower prices for small SPET systems. Fidler V/ Diagnoslic 1111clear medicine i11stru111e11tatio11 PET The latest improvements are mainly due to the development of the so-called 3-D tomo­graphs which do not use septa between planes with rings of crystals.3 By omitting the septa the sensitivity is increased by ten times and the amount of scattered photons for approximately 30 %. In such configuration of severa! thousands tiny crystals all possible coincidence events between any two crystals are used in the reconstruction algorithm. The system works in a trne 3-D mode. Another possibility of PET is the use of double-head SPET system with or without collimator (high-speed electronics is essential) in a coin­cidence mode. This type of PET is consider­ably less sensitive but is interesting to per­form both PET and SPET studies. A much better sensitivity of the system is expected in future from the new generation of the PET. It will be of extreme importance in the imaging of specific biochemical bindings, such as receptor binding. In this applications a small amount of the injected radioactivity is collected by a target organ (usually less than 1 %). Surgical gamma probe This application of radioactivity tracing becomes very important in surgery for identi­fying the regional metastases. Currently interesting clinical field where the small detector probe is of great importance is lymph node dissection of the axilla or region­al nodes in the breast cancer patients and in some melanoma patients. The role of the sur­gical gamma probe is to localize the sentinel node transcutaneously and intra-operatively. To meet a high sensitivity, good spatial and spectral resolution and appropriate ergonom­ic characteristics severa! of different commer­cially available probes were evaluated.4 It was found that CZT probe was the most appropri­ate for low energies (140 keV from 99111Tc) and the NaI probe for high energy (364 keV 131 I). Conclusions Nuclear Medicine instrumentation has been passing through vigorous development in the last years and will be most likely also in the near future. New detection materials with much better physical characteristics than the standard NaI as regards the stopping power, energy resolution, fragility, decay time, light output, and density will most likely replace the Nal. It is expected that new imaging devices with severa! thousands of tiny crys­tals or semiconductor array of small position sensitive areas will improve the sensitivity and specificity of clinical studies. At the same tirne, the small surgical probes made of these materials are also becoming very popular in surgery tracing the regional metastases. References 1. Mladjenovic M. Radioisotope and radia/ion plzysics. New York: Acadernic Press; 1973. p. 148-9. 2. Links JM. Advances in nuclear medicine instru­rnentation: consideration in the design and selec­tion of an irnaging systern. Eur J Nucl Med 1998; 25: 1453-66. 3. Meikle SR , Dahlborn M. Positron ernission tornog­raphy. In: Murray IPC, Ell P, editors. Nuclear medi­cine in clinical diagnosis and treat111e11t. New York: Churchill Livingstone Press; 1994. p. 1327 -37. 4. Tiourina T, Arends B, Huvsrnans D, Rutten H, Lernaire B, Muller S. Evaluation of surgical gamrna probes for radiological sentinel node localization. Eur J Nucl Med 1998; 25: 1224-31. Slovenian abstracl Radio/ On col 2000; 34( 4): 319-24. Magnetnoresonancna holangiografija (MRH) pri bolnikih z zaporo žolcnih vodov Lincender L, Sgadic E, Vrcic D, Vegar S, Stevic N Izhodišca. Z raziskavo smo nameravali oceniti diagnosticno vrednost holangiografije z magnet­no resonanco. To je nova neinvazivna slikovna preiskava za ugotavljanje vzroka zapore žolcnih vodov. Bolniki in metode. Pri bolnikih z zaporo žolcnih vodov smo naredili MRH z magnetnoreso­nancnim tomografom 1,0 T jakosti magnetnega polja. V 26 mesecih smo pregledali 44 bolnikov in sicer 23 moških in 21 žensk, povprecne starosti 51 let. Osnovo preiskave so predstavljala T2 poudarjena zaporedja za prikaz s tekocino izpolnjenih žolcnih vodov v jetrih in zaporedja hitre­ga spinskega odmeva. Obicajna debelina rezov je znašala 4 mm. Slikali smo v dveh ravninah, koronarni in transverzalni pri zadržanem in sprošcenem dihanju. Rekonstrukcije so bile nare­jene s tehniko "maximum intensitiy projection (MIP)". Rezultate MRH smo primerjali z rezultati ultrazvocne ali CT preiskave pred operacijo ali pred drenažo. Rezultati. Z magnetnorezonancno holangiografijo smo pregledali 44 bolnikov z zlatenico in 100­odstotno zanesljivo ugotovili nivo zapore voda. Klinicno uporabnost magnetnoresonancne holangiografije smo ovrednotili na osnovi osebnih izkušenj ter podatkov iz literature. Glavna indikacija za MRH je bila opredelitev mesta zapore žolcnih vodov, ki je na ta nacin mogoca brez uporabe kontrastnega sredstva ali kakršnegakoli posega v žolcnik. Zakljucki. Na osnovi izkušenj in rezultatov lahko potrdimo, da je slikanje z magnetno rezonan­co zanesljivejše pri odkrivanju zapore žolcnih vodov kot sta ultrazvok ali CT preiskava. Slove11im1 abstract Radio/ 011col 2000; 34(4): 325-9. Ultrazvocna preiskava krvnega obtoka z dvojnim Dopplerjem v trebušni slinavki pri sladkornih bolnikih, odvisnih od inzulina Drinkovic I, Brnic Z, Hebrang A Izhodišca. Z našo študijo smo želeleli oceniti pomen pulznega vala in ultrazvocne preiskave krvnega obtoka v trebušni slinavki z barvnim Dopplerjem ter preveriti hipotezo, da pospešeno napredovanje ateroskleroze pri sladkornih bolnikih, odvisnih od inzulina, stopnjuje vaskularno rezistenco. Bolniki in metode. Z ultrazvokom smo pregledali gastroduodenalne arterije 40 sladkornih bol­nikov, odvisnih od inzulina in 30 zdravih prostovoljcev ter pri obeh skupinah dolocili rezistencni (RI) in pulzni indeks (PI). Ugotavljali smo statisticno pomembne razlike Dopplerjevih indeksov med obema pregledanima skupinama ter korelacijo s starostjo in spolom bolnikov kot tudi s tra­janjem sladkorne bolezni. Rezultati. V kontrolni skupini je znašal povprešni RI 0,71, povprecni PI pa 1,46. Pri sladkornih bolnikih, odvisnih od inzulina je bil povprecni RI 0,74, povprecni PI pa 1,54. Razlike med Dopplerjevimi indeksi niso bile statisticno pomembne; za RI je ta razlika bila p=0,82, za PI p=0,74. Prav tako nismo ugotovili statisticno pomembne korelacije med RI in PI ter trajanjem bolezni. Zakljucki. Ultrazvocna preiskava z barvnim Dopplerjem je preprosta in neinvazijska slikovna metoda za preiskavo krvnega obtoka v gastroduodenalni arteriji. V tej študiji smo dokazali, da ta metoda nima tehtne vrednosti pri preiskavi krvnega obtoka v trebušni slinavki sladkornih bol­nikov, odvisnih od inzulina. Slovenian abstract Radio/ Oncol 2000; 34( 4): 331-5. Renalna vaskularna rezistenca pri bolnikih s kronicno ledvicno odpovedjo Prkacin I, Dabo N, Palcic I, Brkljacic B, Sabljar-Matovinovic M, Babic Z Izhodišca. Z ultrazvocno preiskavo z dvojnim Dopplerjem ugotavljamo fiziološko stanje led­vicnega arterijskega krvnega obtoka in njegovo rezistenco. S študijo smo nameravali oceniti vlogo in pomen ultrazvocne preiskave z dvojnim Dopplerjem za ugotavljanje renalno vaskularne rezistence pri bolnikih s kronicno ledvicno odpovedjo. Bolniki in metode. Pri 30 bolnikih z ledvicno odpovedjo in 20 kontrolnih osebah smo izmerili rezistencne indekse (RI) in pulzijske indekse (PI). Vrednosti RI in PI kontrolnih oseb smo primer­jali z vrednostmi RI in PI bolnikov s kronicno ledvicno odpovedjo ter ugotavljali korelacijo teh vrednosti z laboratorijskimi in klinicnimi rezultati. Rezultati. Povprecna vrednost RI kontrolnih oseb je bila 0,59±0,03 (±SD), povprecna vrednost PI pa 1,00±0,11. Pri bolniki s kronicno ledvicno odpovedjo je bil povprecni RI 0,71±0.11, povprecni PI pa 1,69±0,21. Višje vrednosti RI in PI so bile povezane s stopnjevanjem ledvicne odpovedi. Med vrednostmi RI in PI ter vrednostmi serumskega kreatinina, kreatininskega klirensa ter sis­tolicnega in diastolicnega krvnega tlaka je bila ugotovljena statisticno pomembna korelacija (p<0.001). Zakljucki. Iz Dopplerjevih indeksov je pri bolnikih s kronicno ledvicno odpovedjo mogoce ugo­toviti višjo renalno vaskularno rezistenco in njeno korelacijo z laboratorijskimi in klinicnimi parametri, medtem ko izmerjene vrednosti RI in PI kot napovedni dejavniki napredovanja bolezni niso ugodnejši od klasicnih parametrov. S/ovenin11 abstrnct Radio/ Oncol 2000; 34(4): 337-47. Zašcita kostnega mozga z amifostinom pri zdravljenju z Re-186-HEDP: prvi rezultati na živalskem modelu Klutmann S, Bohuslavizki lili, Kriiger S, Jenicke L, Buchert R, Mester J, Clausen M Izhodišca. V zadnjih nekaj letih porocajo o radioprotektivnem delovanju amifostina (Etyhol®, USB, Philadelphia, PA). Ker se amifostin znatno kopici v kostnem mozgu, se zdi zelo primeren za proucevanje radioprotektivnega ucinka na kostni mozeg pri bolnikih, ki so zdravljeni z Re-186-HEDP. Narejene so že zacetne raziskave na živalih, uporabili so novozelandske bele zajce. Material in metode. 18 zajcem smo naredili scintigrafijo celotnega telesa s Tc-99m-HDP, ki so ob tej preiskavi prejeli 300 MBq. 9 živali smo nato zdravili z amifostinom v odmerku 200 mg/kg telesne teže, 9 zajcev pa je služilo za kontrolnio skupino in smo jim dajali le fiziološko raztopino. Vsem 18 zajcem smo nato aplicirali 400 MBq Re-186-HEDP i.v. Dva zajca pa nista prejela ne Tc-99m-HDP ne Re-186-HEDP, ker smo ju že na zacetku raziskave dolocili -ob omenjeni kontrolni skupini -za netretirana kontrolna primera. Krvne preiskave smo naredili na zacetku raziskave in jih ponavljali dva meseca v dvotedenskih intervalih pri vseh 20 živali. Dolocali smo levkocite, eritrocite, trombocite in hemoglobin. Dva meseca po zdravljenju smo vse živali žrtvovali in jim kirurško odstranili femurje zaradi histopatološke preiskave kostnega mozga. Resultati. V obeh netretiranih kontrolnih živalih in v živalih, ki so prejele amifostin so bili eritrociti in hemoglobin skoraj nespremenjeni ves cas opazovanja. Pri 9 kontrolnih živalih, ki niso prejele amifostina, je bila srednja vrednost trombocitov pred apikacijo Re-186-HEDP 265.22±127.41 x 109/1. Dva tedna po aplikaciji omenjenega radiofarmaka je bila srednja vrednost trombocitov znižana na 211.22±52.8 x 109/1. Pri živalih, ki so prejele amifostin in pri tistih, ki ga niso, se pred zdravljenjem z Re-186-HEDP srednje vrednosti trombocitov niso bistveno razliko­vale (p>0.05). Dva tedna kasneje pa se je tudi v skupini živali, ki so prejele amifostin, znižala vrednost trombocitov na 180.67±37.43 x 109/1 in razlika vrednosti s kontrolno skupino ni bila sta­tisticno znacilna (p>0.05). Dva tedna po aplikaciji radiofarmaka smo ugotovili le rahlo znižanje vrednosti levkocitov v kontrolni skupini živali, nasprotno pa je skupina živali zdravljenih z ami­fostinom imela znacilno znižano vrednost levkocitov 3.39±0.91 x 109/1 (p<0.0002). Diskusija. Amifostin ne omogoca zašcite pred prehodno trombocitopenijo. Nezadostno radio­protektivno delovanje amifostina na trombocite si razlagamo z njegovo farmakokinetiko. Po aplikaciji Re-186-HEDP prihaja namrec do tvorbe prostih radikalov in njihovo nastajanje in delo­vanje je nekajkrat daljše kot pa radioprotektivni ucinek amifostina, ki ga predhodno apliciramo v enkratnem odmerku. Znižanje vrednosti levkocitov po amifostinu pa do sedaj ni bilo poznano. Zakljucki. Ce želimo uporabljati amifostin kot radioprotektivno sredstvo, je potrebno ugotoviti primernejšo aplikacijo. Predlagamo dvakratdnevno apliciranje, ki naj traja 3 do 4 dni od zacetka zdravljenja z Re-186-HEDP. Prav tako je potrebno v naslednjih raziskavah na živalih prouciti zgo­raj omenjeni leukopenicni ucinek amifostina. Slove11ia11 abstract Radio/ On col 2000; 34( 4): 349-55. Algoritem zdravljenja sindroma zgornje vene cave s perkutanim stentom Vodvarka P, Štverak P Izhodišca. Sindrom zgornje vene cave je dolgo veljal za življenjsko nevaren bolezenski pojav. Od leta 1757, ko je W. Hunter prvic opisal ta pojav pri bolniku s sakularno anevrizmo sifiliticne aorte, je bilo odkritih veliko zelo razlicnih vzrokov tega sindroma. Uporaba perkutanega stenta je z razvojem radioterapije postala osnovni in glavni nacin zdravl­jenja bolnikov s sindromom zgornje vene cave. Nenaden pojav tega sindroma je zahteval takojšnje zdravljenje z radioterapijo, cetudi histopatološka preiskava še ni potrdila vzroka sin­droma. Z razvojem radioterapije, kemoterapije in pomožnega zdravljenja raznih vrst raka ter hkrati s spoznanjem, da sindrom zgornje vene cave ni vedno življenjsko nevaren, je zaradi razlicnega nacina zdravljenja bolnikov s sindromom zgornje vene cave postalo nujno locevati bolnike med seboj. Zakljucki. S perkutanim stentom že od leta 1986 ucinkovito zdravimo bolnike s sindromom zgornje vene cave. Zdravljenje s perkutanim stentom uvajamo kot pomožno ali kot paliativno zdravljenje. Razvili smo tudi algoritem tega zdravljenja, ki temelji na štirih vprašanjih, osnovanih na klinicnih izkušnjah. Ce hocemo, da bi bili odgovori veljavni, moramo uporabiti dolocene diag­nosticne postopke in orodja, ki ustrezajo priporocilom in zahtevam. 1. Ali se je pri bolniku zares razvil sindrom zgornje vene cave? 2. Kakšno je splošno fizicno stanje bolnika? 3. Ali so bile ugotvljene kontraindikacije, ki pri zdravljenju sindroma zgornje vene cave ne dovoljujejo uporabe stenta? 4. Ali so znani rezultati histološke preiskave procesa, ki je povzrocil sindrom? Kakšni so rezul­ tati histološke preiskave procesa, ki je povzrocil sindrom? Odgovori na zgornja vprašanja odlocajo o izbiri nacina zdravljenja. Tako dosežemo racionalno uporabo perkutanih vstavljivih stentov pri bolnikih s sindromom zgornje vene cave z maligno eti­ologijo, ki potrebujejo pomožno zdravljenje in/ali paliativno zdravljenje. Radio/ Onco/ 2000; 34(4): 357-61. Elektrokemoterapija s cisplatinom pri bolniku z rakom dojke Reberšek M, Cufer T, Rudolf Z, Serša G Izvlecek. Avtorji so zdravili kožne metastaze pri bolniku z rakom dojke z elektrokemoterapijo s cisplatinom. Elektrokemoterapija je zdravljenje s kemoterapijo, ki ji sledi lokalna aplikacija elek­tricnih pulzov na tumorske lezije; elektricni pulzi povecajo vnos kemoterapevtika v celice. Prikaz primera. Avtorji so zdravili kožne metastaze raka dojke z intratumorsko aplikacijo cis­platina in 8 elektricnimi pulzi, ki so jih na vsako kožno metastazo aplicirali 1 minuto po vnosu cisplatina. Pri zdravljenju z elektrokemoterapijo so pri dveh kožnih metastazah dosegli popolni odgovor, pri 1 kožni metastazi pa delni odgovor. Pri kožnih metastazah, ki so jih zdravili samo z intratumorsko aplikacijo cisplatina, pa so dosegli le delni odgovor. Zakljucek. Elektrokemoterapija s cisplatinom je tako kot elektrokemoterapija z bleomicinom ucinkovita pri zdravljenju kožnih metastaz raka dojk. S/ove11ia11 abstract Radio/ 011col 2000; 34(4): 363-8. Sinhroni in metahroni bilateralni germinalni tumorji testisov Berkmen F, Peker AF, Ba§ay S, Ali Ayydd1z, Arik AI Izhodišce. Pregledali smo 14 bolnikov z bilateralnim tumorjem testisov in proucevali, ali je potrebno med orkidektomijo opraviti tudi kontralateralno biopsijo testisov za odkrivanje karci­noma in situ. Bolniki in metode. Z raziskovanjem teh 14 bolnikov z bilateralnim tumorjem testisov smo želeli ugotoviti incidenco, histološke podatke, napovedne dejavnike, casovno razliko med nastankom enega in drugega primarnega karcinoma, nacin zdravljenja in koncni uspeh. Rezultati. V letih med 1984 in 1996 smo odkrili 14 primerov bilateralnih tumorjev. Pri 5 bolnikih so se tumorji pojavili hkrati, pri ostalih pa se je kontralateralni tumor pojavil s casovnim zamikom od 6 do 107 mesecev. Najpogostejša histološka diagnoza je bila seminom, ki je bil ugo­tovljen v 10 primerih. Pri 4 bolnikih je bil ugotovljen retiniran testis, pri enem pa sindrom perzis­tentnega Miillerjevega voda. Pri vseh bolnikih je bila opravljena radikalna orkidektomija. Z oziram na stadij bolezni so bili vsi bolniki zdravljeni z obsevanjem in/ali kemoterapijo. Štirje bol­niki so umrli v casu od 6 do 33 mesecev po diagnozi. Preostalih 10 bolnikov je še vedno živih in brez znakov bolezni. Zakljucki. Diagnoza sekundarnega tumorja je danes pogostejša zaradi daljšega obdobja, dolocenega za nadzor bolezni, rednih samopregledovanj bolnikov, ultrazvocnega pregleda testi­sov, uporabe tumorski markerjev AFP in HCG ter biopsije kontralateralnega testisa med orkidek­tomijo. Karcinom in situ na kontralateralnem testisu skoraj pri vseh obsevanih bolnikih z germi­nalnim rakom napreduje v invazivni tumor. Kljub vsemu pa ne zagovarjamo rutinskega izvajan­ja biopsije na kontralaateralnem testisu pri bolnikih z unilateralnim testikularnim tumorjem iz naslednjih razlogov: (1) Testikularni karcinom in situ je obicajno prekurzor vecine malignih ger­minalnih tumorjev, razen spermatocitnih seminomov, teratomov in tumorjev rumenjakovega mehurcka. (2) Vendar karcinom in situ ni diagnosticiran v 95% vseh testikularnih tumorjev. (3) Karcinom in situ je poljubno porazdeljen, zato ga je težko odkriti z enim vzorcem biopsije. (4) Testikularna biopsija povzroca manjše zaplete in obenem tudi vpliva na spermatogenezo. (5) Germinalni tumor raste od 3 do 5 let. Netipljiv testikularni tumor lahko lokaliziramo z ultraz­vokom. Vcasih z ultrazvocno preiskavo odkrijemo tudi karcinom in situ, ce smo pozorni na spre­membe na normalnih tubulih. (6) Ultrazvocna preiskava pa je bolj zapletena po biopsiji zaradi nastalih brazgotin. (7) Naravni potek bolezni karcinoma in situ ni znan, zato so tudi mnenja o natancnem postopku zdravljenja mocno deljena. (8) Doslej še nimamo dokazov, da karcinom in situ vpliva na preživetje. (9) Izvajamo skrben zdravstveni nadzor vsem bolnikom z germinalnim tumorjem, cetudi je bila biopsija negativna. Najprimernejši pristop je torej pozorno spremljanje bolnika. S/ovelliall a/Jstract Radio/ 011co/ 2000; 34(4): 369-74. Odnos med stopnjo metilacije DNA in izražanjem treh razlicnih DNA metiltransferaz pri ovarijskem karcinomu CorA Izhodišca. Metilacija DNA igra pomembno vlogo v razvoju zarodka, pri inaktivaciji kromosoma X ter pri izražanju "imprinting" genov. Raziskave so pokazale, da imajo maligne celice spremen­jen vzorec metilacije DNA, spremembe DNA metilacije pa sodelujejo v procesu kancerogeneze. Namen dela je bil ugotoviti ali obstaja povezava med stopnjo metilacije DNA ter izražanjem treh DNA metil-transferaz (DNMT) in sicer DNMTl, DNMT3A in DNMT3B v vzorcih ovarijskih kar­ cinomov. Materiali in metode. Za dolocitev stopnje metilacije DNA v petih vzorcih ovarijskega karcinoma in treh vzorcih morfološko normalnih jajcnikov je bila DNA izpostavljena delovanju bodisi za metilacijo obcutljive HpaII, ali za metilacijo neobcutljive MspI restrikcijske endonukleaze. Za dolocitev stopnje izražanja treh DNMT v vzorcih smo uporabili metodo kvantitativnega PCR. Rezultati. DNA vseh petih ovarijskih karcinomov je bila globalno hipometilirana. Razlike med stopnjo metilacije DNA med ovarijskimi karcinomi in normalnim tkivom jajcnika so bile statis­ ticno znacilne (P<0.05). Vseh pet ovarijskih karcinomov je kazalo prekomerno izražanje DNMT3A in DNMT3B, medtem ko smo našli prekomerno izražanje DNMTl samo v dveh vzor­ cih. Med stopnjo globalne demetilacije in izražanjem treh razlicnih DNMT ni bilo statisticno znacilnih korelacij. Zakljucki. Hipometilacija genoma igra pomembno vlogo pri nastanku tumorjev saj vodi v struk­ turne in numericne kromosomske nepravilnosti v tumorskih celicah, vendar pa ostaja paradoks med stopnjo globalne hipometilacije na eni strani in povecanim izražanjem DNMT na drugi še vedno nerazjasnjen S/ove11ia11 abstrnct Radio/ On col 2000; 34( 4): 375-80. Analiza modulacijske prenosne funkcije za kovinske filmske slikovne detektorje s pomocjo logit modeliranja Falco T in Fallone BG Izhodišca. Logit analizo uporabljamo za prilagajanje izmerjenih podatkov modulacijske prenosne funkcije (MTF) za kovinske filmske detektorje v obmocju megavoltnih energij. Detektorji so sestavljeni iz rtg filma z dvojno emulzijo in frontalnih bakrenih ali svincenih kovin­skih plošc z debelinami od 0,39 mm do 2,40 mm. Analizirani so bili tudi MTF podatki drugih raziskovalcev. Logit funkcija napoveduje MTF znotraj eksperimentalne nenatancnosti, utežena linearna regresija pa pokaže, da je prilagajanje uspešno z visokim korelacijskim koeficientom: ­ 0.999 :s; r :s; -0.995. Logit funkcija parametrizira MTF z dvema regresijskima faktorjema, a in b. Parametra kažeta linearno odvisnost, ce je masna debelina frontalne kovinske plošce vecja od maksimalnega dosega elektronov. Zakljucki. Analiza logit prilagajanja nam dovoljuje izracun MTF za kovinske plošce, kar lahko uporabimo pri izdelavi prednjega dela elektronskih slikovnih naprav. Radio/ Oncol 2000; 34(4): 381-5. Razvojni trendi v nuklearnomedicinski instrumentaciji Fidler V Izhodišca. Prikazane so fizikalne osnove nuklearnomedicinskih slikovnih tehnik s poudarkom na razvoju novih tankih mnogokristalnih scintilacijskih in polprevodniških gama kamer, PET skenerjev brez vmesnih sten med obroci detektorskih kristalov, novih detektorskih materialov ter nove polprevodniške CZT kirurške detektorske sonde za ugotavljanje lokalnih metastaz. Za oceno minimalnega premera scintilacijskih kristalov je narejen izracun, ki upošteva 20% izgubo absorbiranih gama žarkov ob robu kristala. Zakljucki. V zadnjih letih se instrumentacija v nuklearni medicini hitro razvija predvsem, po zaslugi novih detekcijskih snovi, ki imajo v primerjavi z Nal kristalom boljšo atenuacijo, energi­jsko locljivost, manjšo krhljivost, krajši razpadni cas za scintilacijsko svetlobo, vecji svetlobni izkoristek in gostoto. Zelo verjetno bodo gama kamere z mnogokristalnimi detektorji ter pozici­jsko obcutljivimi polprevodniškimi detektorji znatno izboljšale obcutljivost detekcije kot tudi energijsko in prostorsko locljivost, s cimer se bo povecala tudi specificnost pri klinicnih scinti­grafskih preiskavah. Pomemben je tudi razvoj kirurških detekcijskih sond, ki so izboljšale zaz­navnost majhnih lokaliziranih metastaz. Radio/ 011col 2000; 34(4): 387-94. Notices Notices submitted far publication should contain a mailing address, phone and/ or Jax number and/or e-mail of a Contact person or department. Radiation therapy January 30 -February 2, 2001 The International Meeting ICRO 2001 will take place in Melbourne, Australia. Contact Frederique Arts, Av. E. Mounier, 83/4, B­1200 Brussels, Belgium, or call +32 2 775 9342; or fax +32 2 779 5494; or e-mail info@isro.be Radiation therapy January 31 -February 2, 2001 The International Meeting ICRO 2001 will take place in Melbourne, Australia. Contact Frederique Arts, Av. E. Mounier, 83/4, B­1200 Brussels, Belgium, or call +32 2 775 9342; or fax +32 2 779 5494; or e-mail info@isro.be Cardiovascular radiation therapy February 5-7, 2001 The conference on cardiovascular radiation therapy will take place in Washington DC, USA. Contact Cardiovascular Research Institute, 110 Irving st. NW, STE 6D, Washington DC 20010-2976; or call +1 202 877 7942; or fax +1 202 877 8141; or see Internet http:/ /www.radiationonline.com Brachyradiotherapy February 25-27, 2001 The ESTRO teaching course "Endovascular Brachytherapy" will take place in Wien, Austria. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Colorectal cancer Spri11g, 2001 The ESO conference will take place in Milan, ltaly. Contact ESO Office, Viale Beatrice d'Este 37, 20122 Milan, ltaly; or call +39 0258317850; or fax +39 0258321266: or e-mail esomi@tin.it Radiotherapy Marc/1 11-14, 2001 The "European Conference on Cancer Strategy and Outcomes" will take place in Edinburg, U.K. Contact ECSO 2001, !CM Conference Associates, 4 Cavendish Square, London WiM OBX, U.K.; or call +44 207 499 0900; or fax +44 207 629 3233; or e-mail boa@icmgb.com Radiotherapy Marc/z 25-29, 2001 The ESTRO teaching course "Radiotherapy Treatment Planning: Principles & Practice" will take place in Dublin, Ireland. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Brachyradiotherapy Marc/z 25-29, 2001 The ESTRO teaching course "Modem Brachytherapy Techniques" will take place in Paris, France. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be 396 Notices Oncology Radiophysics April 1-5, 2001 The ESTRO teaching course "Molecular Oncology for Radiotherapy" will take place in Venezia, Italy. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Rectal Cancer April 6-7, 2001 "2nd The International Symposium on Sphincter Saving Treatment in Rectal Cancer" will take place in Lyon, France. Contact FCSANTE@rockefeller.univ-lyonl.fr Clinical research April 22-26, 2001 The ESTRO teaching course "Clinical Research in Radiation Oncology" will take place in Izmir, Turkey. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Lung Cancer April 26-30, 2001 The "4th International Congress on Lung Cancer" will take place in Halkidiki, Greece. Contact FORUM International Congress Orga­nisers, 18 Mitropoleos str., GR-54624 Thessaloniki, Greece; or call +30 31 257 128; or fax +30 31 231 849; or e-mail forup@otenet.gr; or see Internet http://www.forumcongress.gr Prostate cancer May 13-14, 2001 The ESTRO teaching course "Brachytherapy for Prostate Cancer" will take place in Leeds, United Kingdom. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be May 20-24, 2001 The ESTRO teaching course "Dose and Monitor Unit Calculations for High Energy Photon Beams: Basic Principles & Application to Modem Techniques" will take place in Coimbra, Portugal. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Hyperthermic Oncology May 31 -June 2, 2001 The "19th Annual Meeting of the European Society of Hyperthermic Oncology" Ooint with the "12th European BSD Users Conference") will take place in Verona, Italy. Contact elmaluta@tin.it; or see Internet http:// www.esho2001.com Lung Cancer ]une 3-6, 2001 The Central European Lung Cancer Confe­ "7th rence" will take place in Prague, Czech Republic. Contact 7th CELCC, Conference Partners, Sokolska 10, 120 00 Prague 2, Czech Republic; or call/fax +420 2 2426 1371; or e-mail info@conference.cz Radiosurgery June 4-7, 2001. The International Stereotactic Radiosurgery "5th Society Congress" will be offered in Jerusalem, lsrael Republic. Contact 7ISRS Secretariat, c/o International Trave! & Congresses Ltd., 20 Rothschild Boulevard, POB 29313, Tei Aviv 61292, Israel; or phone +972 3 795 1444; or fax +972 3 510 7716; or email congs@interna­tionaltc.co.il; or see http://www.isrs-jerusalem.com. Radiotherapy June 7-9, 2001 The Annual Brachytherapy Meeting GEC/ESTRO will take place in Stresa, Italy. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Notices 397 Radiobiology June 10-12, 2001 The "1 st ESTRO Workshop on Biology in Radiation Oncology" will take place in Fuglso (Aarhus), Denmark. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiotherapy June 24-28, 2001 The ESTRO teaching course "IMRT and Other Conformal Techniques in Practice" will take place in Amsterdam, The Netherlands. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiotherapy June 24-28, 2001 The ESTRO teaching course "Imaging for Target Volume Determination in Radiotherapy" will take place in Krakow, Poland. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Obstetrics and gynaecology ]uly 10-13, 2001 The "29th British Congress of Obstetrics and Gynae­cology (BCOG)" will take place in Birmingham, U.K. Contact info@conforg.com Radiophysics August 26-30, 2001 The ESTRO teaching course "Physics for Clinical Radiotherapy" will take place in Leuven, Belgiurn. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgiurn; or call +32 7759340; or fax + 32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Brachytherapy August 29 -September 2, 2001 The ESTRO teaching course "Modem Brachytherapy" will take place in Bratislava, Slovakia. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiophysics September 17-22, 2001 The "6th Biennial ESTRO Meeting on Physics for Clinical Radiotherapy" and the "6th ESTRO Meeting on Radiation Technology for Clinical Radiotherapy" will be held in Sevila, Spain. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgiurn; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiotherapy October 7-11, 2001 The ESTRO teaching course "Evidence-Based Radiation Oncology: Principles & Methods" will take place in Cairo, Egypt. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiotherapy October 7-11, 2001 The ESTRO teaching course "Basic Clinical Radiobiology" will take place in Tenerife, Spain. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-rnail info@estro.be; or see Internet http://www.estro.be Radiation therapy October 21-25, 2001 The "20th Annual ESTRO Meeting / ECCO 11 Meeting" will take place in Lisbon, Portugal. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; web: http:// www.estro.be Radžo/ Onco/ 2000; 34(4): 395-7. Radio/ 011co/ 2000; 34(4): 398-402. Reviewers in 2000 Bilban-Jakopin C, Ljubljana, Slovenia -Bracko M, Ljubljana, Slovenia -Budihna M, Ljubljana, Slovenia -Budihna N, Ljubljana, Slovenia -Burger J, Ljubljana, Slovenia -Casar B, Ljubljana, Slovenia -Cervek J, Ljubljana, Slovenia -Cufer T, Ljubljana, Slovenia -Dominis M, Zagreb, Croatia -Fidler V, Ljubljana, Slovenia -Grošelj C, Ljubljana, Slovenia -Hertl K, Ljubljana, Slovenia -Jevtic V, Ljubljana, Slovenia -Kadivec M, Ljubljana, Slovenia -Kocijancic I, Ljubljana, Slovenia -Kotnik V, Ljubljana, Slovenia -Kovac V, Ljubljana, Slovenia -Kragelj B, Ljubljana, Slovenia -Kunst T, Ljubljana, Slovenia -Majdic E, Ljubljana, Slovenia -Milcinski M, Ljubljana, Slovenia -Miloševic Z, Ljubljana, Slovenia -Novakovic S, Ljubljana, Slovenia -Plaper-Vernik M, Ljubljana, Slovenia -Reiner S, Slovenj Gradec, Slovenia -Robar V, Ljubljana, Slovenia -Rozman B, Ljubljana, Slovenia -Serša G, Ljubljana, Slovenia -Snoj M, Ljubljana, Slovenia -Stanovnik M, Ljubljana, Slovenia -Šuštaršic J, Ljubljana, Slovenia -Tomšic-Demšar R, Ljubljana, Slovenia -Velenik V, Ljubljana, Slovenia -Vidmar-Kocjancic K, Ljubljana, Slovenia -Vodnik-Cerar A, Ljubljana, Slovenia Editors greatly appreciate the work of the reviewers who significantly contributed to the improved quality of our journal. Radio/ Onco/ 2000; 34(4): 398-402. Abramic M: 1/41-7 El-Agamawi AY: 1/27-33 Al tenhoff J: 1/1-9 Amichetti M: 3/226 Anicin A: 2/115-22 Antonello M: 3/226 Api P: 3/226 Arik Ai: 4/363-8 Aristei C: 3/226 Auersperg M: 1/49-57 1ld1z A: 4/363-8 Ayy Babic D: 1/47-7 Babic Z: 4/331-5 Babnik Peskar D: 2/175-84 Balanescu I: 3/234 Ba§ay S: 4/363-8 Berden P: 2/137-43, 2/151-8, 2/159-64 Berkmen F: 4/363-8 Bernstein S: 1/27-33 Bernstein Z: 1/27-33 Author Index 2000 Bešic N: 3/228, 3/244 Bleckmann Ch: 1/1-9 Blichert-Toft M: 3/223, 3/251-9 Blidaru A: 3/234 Bohuslavizki KH: 1/1-9, 1/11-9; 4/337-47 Bonetta A: 3/226 Bordea CI: 3/234 Brencic E: 2/191-8 Brkljkacic B: 4/331-5 Brnic Z: 4/325-9 Bruns J: 1/11-9 Buchert R: 1/1-9, 1/11-9; 4/337-47 McCarthy Ph: 1/27-33 Clausen M: 1/1-9, 1/11-9; 4/337-47 Ci.ir A: 4/369-74 Czuczman M: 1/27-33 Cemažar M: 1/49-57 Cernelc B: 2/115-22 Cervek J: 3/248 Index 2000 399 Cufer T: 1/21-5; 3/219, 3/248, 3/285-8; 4/357-61 Lee RJ: 1/27-33 Lincender L: 4/319-24 Dabo N: 4/331-5 Lindtner J: 3/228, 3/232 Dobrowolskij D: 1/11-9 Lora O: 3/226 Drinkovic !: 4/325-9 Majdic E: 3/225 Ecimovic P: 3/307-8 Mattson H: 3/237 El-Agamawi A: 1/27-33 Mayer A: 3/240 Eržen D: 3/232 Mayer R: 3/295-300 Evangeliou A: 3/281-4 McCarthy P: 1/27-34 Mester J: 1/11-9; 4/337-47 Fahey TJ, Jr: 3/229 Miklavcic D: 1/59-65 Fajdiga 1: 3/249, 3/289-94 Milici<' D: 1/41-7 Falco T: 4/375-80 Miller RC: 3/237 Fallone BG: 4/375-80 Miloševi<' Z: 2/123-36 Fidler V: 4/381-5 Mavrin-Stanovnik T: 3/227, 3/244 Fischinger J: 3/249, 3/289-94 Forsthuber E: 3/230 Neri S: 3/226 Frkovic-Grazio Snežana: 3/228 Neuber K: 1/1-9 Novak Janez: 3/246 Gazic Barbara: 3/228 Novak Janko: 3/239 Giannakopoulou Ch: 3/281-4 Novakovi<' S: 3/301-6 Glušic M: 2/191-8 Golouh R: 1/35-9; 3/227 Oblak C: 3/245 Gorenc M: 2/115-22 Orner JB: 1/27-33 Guss H: 3/295-300 Osmak M: 1/41-7 Hackl A: 3/295-300 Palcic !: 4/331-5 Hager E: 3/230 Peker AF: 4/363-8 Hamrner J: 3/231, 3/236, 3/243 Podobnik B: 1/59-65 Hatzidaki E: 3/281-4 Praprotnik A: 2/145-50 Hebrang A: 4/325-9 Prassopoulos P: 3/281-4 Hidvegi M: 3/240 Prettenhofer U: 3/295-300 Hocevar-Boltežar I: 3/249, 3/289-94 Primik F: 3/230 Hocevar M: 3/228, 3/244 Prkacin !: 4/331-5 Hoffmanu A: 3/240 Proulx MG: 1/27-33 Putz E: 3/236 lannone T: 3/226 Quehenberger F: 3/295-300 Jakab F: 3/240 Jamar B: 2/85-91 Raunik W: 3/242 Jarc A: 3/249, 3/289-94 Reberšek M: 4/357-61 Jenicke L: 4/337-47 Rener M: 3/228 Jereb J: 2/93-9 Repše S: 3/238 Jevtic V: 2/79, 2/81-3, 2/145-50, 2/199-200 Rudolf Z: 4/357-61 Jezeršek B: 3/301-6 Juvan R: 3/238 Sabitzer H: 3/230, 3/242 Sabljar-Matovinovic M: 4/331-5 Klocker J: 3/242 Sadagic E: 4/319-24 Klutmann S: 1/1-9, 1/11-9; 4/337-47 Salapura V: 2/101-6, 2/107-13 Korakaki E: 3/281-4 Sedmak B: 3/248 Kragelj B: 3/248 Seewald D: 3/231, 3/236, 3/243 Kriiger S: 1/1-9, 1/11-9; 4/337-47 Sencar M: 3/246 Kubista E: 3/233 Serša G: 1/49-57; 4/357-61 Kunst T: 2/101-6, 2/137-43 Snoj M: 3/227, 3/244 Stanovnik M: 2/191-8 Labeck W: 3/236 Stevic N: 4/319-24 Szalay S: 3/230 Škrk J: 1/41-7 Šmid L: 2/115-22; 3/249, 3/289-94 Špiler M: 1/35-9; 3/246 Šprem M: 1/41-7 Štor Z: 3/238 Štrus B: 3/245 Štverak P: 4/349-55 Šurlan K: 2/85-91 Šurlan M: 2/93-9, 2/101-6, 2/107-13 Tannock IF: 3/247, 3/275-9 Temple WJ: 3/235, 3/241, 3/265-8, 3/269-73 Track Ch: 3/231, 3/236, 3/243 Valli MC: 3/226 Vegar S: 4/319-24 Viale G: 3/224, 3/261-4 Vidali Cr: 3/226 Index 2000 Vidmar D: 2/115-22, 2/165-73 Viisoreanu Cr: 3/234 Višnar-Perovic A: 2/115-22, 2/175-84 Vodvarka P: 4/349-55 Voloudaki A: 3/281-4 Vrcic D: 4/319-24 Vrhovec I: 1/41-7 Wedler J: 1/1-9 Weis E: 3/243 Wieser S: 3/242 Zini G: 3/226 Zoidl J: 3/231, 3/236, 3/243 Zupancic Ž: 2/115-22, 2/185-90 Žargi M: 3/249, 3/289-94 Žgajnar J: 3/227, 3/228 Župevc A: 3/249, 3/289-94 lndex 2000 401 Subject Index 2000 adult: 3/295-300 amifostine: 4/337-47 angiography: 2/123-36 -angiography, digital subtraction: 2/101-6 aorta thoracic: 2/159-64 aortic aneurysm: 2/107-13 -aortic aneurysm -diagnosis -therapy: 2/101-6 aortic disease: 2/159-64 -aortic disease -ultrasonography -radiography: 2/137-43 axilla: 3/251-9, 3/261-4, 3/285-8 bile ducts neoplasms: 4/319-24 biopsy needle: 2/115-22 bladder neoplasms -therapy, combined modality therapy: 1/21-5 bleomycin: 1/49-57 blood vessel prosthesis: 2/101-6, 2/107-13 bone marrow: 4/337-47 bone metastases: 4/337-47 breast conserving: 3/251-8 breast neoplasms -male-therapy -drug therapy: 4/357-61 breast neoplasms -surgery: 3/251-9, 3/261-4 breast neoplasms -therapy: 3/285-8 carcinorna in sity -diagnosis: 4/263-8 carcinoma -renal celi: 2/191-8 cathepsin D, plasminogen activator inhibitor type 1: 1/41-7 cerebral aneurysm -diagnosis: 2/123-36 cerebral artery diseases -diagnosis: 2/123-36 cerebral infarction: 3/281-4 child: 2/185-90 cholelethiasis: 4/319-24 cholestasis -diagnosis: 4/319-24 cisplatin: 4/357-61 colonic diseases -ultrasonography: 2/165-73 colonic neoplasms -ultrasonography: 2/165-73 cystectomy, bladder preservation: 1/21-5 defecation: 2/85-91 dental status: 3/289-94 diabetes mellitus, insulin -dependent: 4/325-9 drug delivery system, electrochemotherapy: 4/357-61 18F-FDG-PET: 1/1-9 electroporation: 4/357-61 ependymoma -surgery -radiotherapy: 3/295-300 erythrocyte count: 4/337-47 experimental -drug therapy: 1/59-65 extracellular space: 1/59-65 extremities: 3/269-73 fibrosarcoma: 1/ 49-57 gamma cameras: 4/381-5 germinoma: 4/363-8 head and neck neoplasms -pathology -ultrasonogra­ phy: 2/115-22 head and neck neoplasms -rehabilitation: 3/289-94 hearing disorders: 3/289-94 heart neoplasms: 2/151-8 histology: 1/1-9 hydralazine: 1/59-65 hydrocolonic ultrasonography: 2/165-73 immunohistochemistry: 3/261-4 infant, newborn: 3/281-4 interstitial fluid pressure: 1/59-65 intraoperative period: 3/261-4 intussusception: 2/85-91 kidney failure, chronic: 4/331-5 kidney neoplasms -diagnosis -ultrasonography ­surgery: 2/191-8 linear models: 4/375-80 local prevention and control: 3/265-8 logit, MTF, megavoltage, portal detectors: 4/375-80 Jung volume measurements: 3/289-94 lymphatic metastasis: 2/115-22 lymph node excision: 3/251-9, 3/261-4, 3/285-8 lymph nodes -pathology: 3/261-4 lymphoma, non-Hodgkin: 3/301-6 -lymphoma, non-Hodgkin -drug therapy -radiother­ apy, bone neoplasms, anthracyclins: 1/27-33 magnetic resonance angiography: 2/101-6, 2/159-64 magnetic resonance imaging: 2/145-50, 2/151-8; 4/319-24 manometry: 1/59-65 melanoma -diagnosis -pathology: 1/1-9 methyltransferases: 4/369-74 middle cerebral artery: 3/281-4 multi -crystal scintillation gamma camera, semicon­ ductor gamma camera, 2-D and 3-D PET scanner: 4/381-5 neoplasms recurrence, local prevention and control: 3/265-8 402 Index 2000 neoplasms -staging: 1/1-9 neoplasms -surgery: 3/275-9 orchiectomy: 4/363-8 organ sparing: 3/275-9 osteosarcoma, diagnosis, pathology, tomography, emission -computed, treatment outcome: 1/11-9 ovarian neoplasms: 1/41-7 -ovarian neoplasms, DNA methylation: 4/369-74 palliative care, algorithm for stenting: 4/349-55 pancreas -blood supply -ultrasonography: 4/325-9 platelet count, hemoglobin: 4/337-47 polyps: 2/165-73 protein p53: 3/301-6 protosystemic shunt, transjugular intrahepatic: 2/93-9 quality of life: 3/275-9 radiation -protection agents: 4/337-47 radiotherapy, adjuvant: 3/295-300 radiotherapy, high -energy: 4/375-80 rectal diseases -radiogra phy: 2/85-91 rectal neoplasms -surgery: 3/265-8 Re -186 -HEDP: 4/337-47 renal artery -ultrasonography: 4/331-5 rotator cuff: 2/145-50 sarcoma: 1/59-65 -sarcoma experimental: 1/49-57 -sarcoma surgery: 3/269-73 self concept: 3/251-9 sentinel node mapping: 3/285-8 shoulder joint -injuries: 2/145-50 soft tissue neoplasms: 3/269-73 South America: 1/35-9 speech disorders: 3/289-94 spina! canal -ultrasonography: 2/185-90 spina! dysraphism -ultrasonography: 2/185-90 stents: 4/349-55 superior vena cava syndrome -therapy: 4/349-55 surgical pathology: 1/35-9 survival analysis: 3/275-9 survival rate: 3/269-73 testicular neoplasms -pathology: 4/363-8 tomography, computed, magnetic resonance imaging: 2/191-8 tomography, emission -computed: 1/1-9 -tomography, emission -computed -instrumenta­ tion: 4/381-5 tomography scanners, X-ray computed: 2/137-43 tomography , X-ray computed: 2/101-6, 2/123-36 trave!: 1/35-9 treatment outcome: 1/27-33 trea tmen t stra tegy: 1/1-9 tumor markers, biological: 3/301-6 tunga penetrans: 1/35-9 tungiasis: 1/35-9 ulcer: 2/85-91 ultrasonography, Doppler, duplex: 4/325-9 urethral stricture -radiography -ultrasonography: 2/175-84 vascular resistance: 4/331-5 vinblastine: 1/49-57 ZVEZA SLOVENSKIH DRUŠTEV ZA BOJ PROTI RAKU LJUBLJANA BASIC ACTIVITY OF ASSOCIATIONS FIGHTING AGAINST CANCER Due to considerably high incidence and longer survival, there is more and more cancer patients ali over the world as well as in Slovenia. In 1997, the cancer incidence in Slovenia was as high as 8,178; of these 4,142 were males and 4,036 women. According to the information by Cancer Registry of Slovenia (1997), it is possible to pre­dict that, until the age of 75, one of three males and one of four females will fall ill. Cancer is the direct or indi­rect cause of death in 60% of cancer patients, meaning that only 40% patients recover. Today, it is well known that about 70% of cancer-related deaths have their root cause in personal lifestyle and environmental conditions. Consequently, a significant reduction in cancer and cancer-related mortality can be achieved only if the popula­tion could be persuaded to change certain habits and attitudes. A Eurobarometer survey recently conducted in the European Union show that one European in three did not believe that cancer could be prevented and that it is possible to avoid cancer by giving up noxious habits and also by healthier way of living. That is why the primary task of the associations fighting against cancer within the ten year program "Slovenia 2000 and Cancer" shall be to inform the Slovenian population that cancer can be avoid­ed and successfully treated provided that the recommendations of Slovenian and European codex against cancer are taken into consideration. In order to get the population better informed, the recommendations in the form of folders, leaflets, posters and brochures were issued containing also the description of the most frequent cancers and of their early symptoms. Special conferences how to prevent or avoid and treat different cancers are being organized on local and national radio and TV stations. Special attention should be paid to young people warning them to give up smoking. Our !atest campaign called "Don't light the first cigarette and the solemn promise" among 90.000 school children was favorably accepted and had a resounding success. We are convinced that a lot of school children will avoid smoking after having heard about the activity of our association. It is generally known that a balanced diet, including a sufficient amount of fruit and vegetables, offers significant protection against some of the most common cancers. Specific mention of the projects on proper nutrition should be made to target groups, such as young people, teachers and children. To obtain better alimentary habits of school children we started with campaigns, such as: "A new day should begin with an apple and carrot!" In addition to the campaigns for general population, information campaigns are also organized for health pro­fessionals in order to be able to relay the cancer prevention messages to their patients. Family doctors and other health service staff should educate the population. We are organizing yearly meetings of specialists led by experts from severa! spheres of activities. We would like to convey the necessary knowledge which could be helpful to health service staff in such education, specially on prophylaxis or early detection of cancer. When planning our work we can count on the assistance and knowledge of foreign and domestic specialists and on cooperation with severa! organizations. We have now been for a long tirne one of the members of International Union against Cancer -UICC. We are very proud to become a fully authorized member of European Cancer League -ECL this year. Having joined the European program in fighting against cancer we shall extend our program to include, in the future, also the areas, such as rehabilitation and screening. Severa! associations, together with health service staff, are taking care of rehabilitation of patients with cancer. We should stimulate the cooperation between them and also between regional associations. Last year, we observed that, despite the rapid increase of cancer, the mortality was increasing slower owing to early detection and successful treatment of cancer. Early detection of cancer, specially in risk groups of popula­tion, is possible only with screening programs. The Association of Slovenian Cancer Societies is very active at the early detection of uterocervical cancer (ZORA program) and, together with regional associations, in the education of breast examinations. We would really wish to organize and to cooperate in early detection of breast and intes­tine cancers according to the recommendations valid in European Union. Assist. Prof. Borut Štabuc, M.D., Ph.D. PRESIDENT OF SLOVENIAN ASSOCIATIONS FOR FIGHTING AGAINST CANCER FONDACIJA "DOCENT DR. J. CHOLEWA" JE NEPROFITNO, NEINSTITUCIONALNO IN NESTRANKARSKO ZDRUŽENJE POSAMEZNIKOV, USTANOV IN ORGANIZACIJ, KI ŽELIJO MATERIALNO SPODBUJATI IN POGLABLJATI RAZISKOVALNO DEJAVNOST V ONKOLOGIJI. MESESNELOVA 9 1000 LJUBLJANA TEL 061 1 5 91 277 FAKS 061 21 81 13 :ŽR: 50100-620-133-05-1 0331 15-214779 Activity of "Dr. J. Cholewa" Foundation for Cancer Research and Education -A Report for the Third Quarter of 2000 As through the whole year 1999, it has been generally agreed that it has become increas­ ingly difficult to entice individuals and business subjects to contribute to the special type of charities, as is the activity of the "Dr. J. Cholewa" Foundation. Fortunately, there are some of the donors from Slovenia and abroad who tirelessly continue to try to support it, and the members of the Foundation and its Executive and Supervisory Committees feel obliged to express their gratitude to ali who understand the importance of its goals and activities to reach them. The Foundation helped to finance the Annual Conference of the International Breast Cancer Study Group in Bled, Slovenia; the International Conference on Cancer in Opatija, Croatia; and the Plecnik Memorial Meeting in Ljubljana, Slovenia, in the course of 1999. A "14th Oncological Weekend" meeting with the themes concerning lung and thyroid cancers was also organised later with the help of the Foundation, and the Proceedings of this meet­ ing were published in a special publication. Severa! grants for participation on various inter­ national congresses and symposia were provided for the applicants from different regions of Slovenia. The Foundation continued to support the regular publication of "Radiology and Oncology" international scientific journal, and the regular publication of the "Challenge ESO Newsletter" in 1999. Both medica! journals are edited, published and printed in Ljubljana, Slovenia. In the past year the Foundation also contributed support for the publication of the Slovenian Dictionary of Medica! Terminology, while it will continue to further facilitate the access to oncology research and education to as many interested individuals and institutions in Slovenia as possible. In addition, special attention will be given to the requests for grants coming from the regions of Slovenia outside Ljubljana, it's capital city. The Foundation continued with its activity at an increasing pace throughout the autumn of 2000. To improve and upgrade its activity stili further, the meetings of its Executive Board and Advisory Board are to take place in the near future in order to take some necessary deci­ sions, including those concerning some of the personnel changes to be undertaken in the near future. Andrej Plesnicar, MD Borut Štabne, MD, PhD Tomaž Benulic, MD The Croatian Radiation Protection Association (CRPA) has the honour to organise the next IRPA REGIONAL CONGRESS ON RADIATION PROTECTION IN CENTRAL EVROPE Dubrovnik, Croatia, May 20-25, 2001 in co-operation with The Austrian Association for Radiation Protection The Czech Society for Radiation Protection The German-Swiss Radiation Protection Association The Health Physics Section of the Roland E{Jtv{Js Physical Society, Hungary The Italian Radiation Protection Association The Polish Radiation Protection Association The Romanian Society for Radiological Protection The Slovak Society for Nuclear Medicine and Radiation Hygiene The Radiation Protection Association of Slovenia The topic of the Congress is Radiation Protection and Health This topic enables an increased participation of health physicists and encourages the sub­mission of papers on medical aspects of radiation protection in addition to all other sub­jects. Correspondence IRPA Regional Congress Congress Secretariat c/o Croatian Radiation Protection Institute Trg Ivana Meštrovica 16 HR-10000 Zagreb, CROATIA Phone/Fax: +385 1 6601 031 E-mail: crpa.dubrovnik@hzzz.hr Information and Preliminary Registration Form available at: http://mimi.imi.hr/ crpa/ - - - 111111 kapsule v svetu najvec predpisovani sistemski1 antimikotik edini peroralni sistemski antimikotik za zdravljenje vaginalne kandidoze, ki ga je odobril FDA Skrajšano navodilo Flukonazol je sistemski antimikotik iz skupine triazolov. Odmerjanje pri razlicnih indikacijah: vaginalna kandidoza 150 mg v enkratnem odmerku mukozna kandidoza 50 do 100 mg na dan dermatomikoze 50 mg na dan ali 150 mg na teden sistemsl