UDC 616-006(05)(497.1) GODEN RDIUA 4 YU ISSN 0485-893X RADIOLOGIA IUGOSLAVICA ANNO 25 1991 FASC 3 PROPRIETARII IDEMQUE EDITORES: SOCIETAS RADIOLOGORUM IUGOSLAVIAE AC SOCIETAS MEDICINAE NUCLEARIS IN FOEDERATIONE SOCIALISTICA REI PUBLICAE IUGOSLAVIAE LJUBLJANA Radio! lugosl July -September 1991 ; 25 :179-284 Nova generacija cepiv HEPAGERIX B® injekcije cepivo proti hepatitisu B, izdelano z genetskim inženiringom • metoda genetskega inženiringa .izkljucuje prisotnost cloveške krvi • popolnoma varno in široko preizkušeno cepivo • visoko ucinkovito cepivo, ki varuje pred vsemi znanimi podvrstami hepatitisa B in pred hepatitisom D • dosega skoraj 100 % serokonverzijo • lahko ga dajemo v vseh starostnih obdobjih • vsi ga dobro prenašajo Bazicno cepljenje opravimo s 3 intramuskularnimi dozami po eni izmed shem (O, 1, 6) ali (O, 1, 2): a) osebe, ki so izpostavljene manjšemu ali zmernemu tveganju infekcije: prva doza: dan po izbiri (O) druga doza: mesec dni po prvi dozi (1) tretja doza: 6 mesecev po prvi dozi (6) b) osebe, ki potrebujejo hitro zašcito ali so pogosteje izpostavljene infekciji: prva doza: dan po izbiri (O) druga doza: mesec dni po prvi dozi (1) tretja doza: 2 meseca po prvi dozi (2) Odrasli in otroci starejši od 10 let: 20 µ.g proteina površinskega antigena v 1 ml suspenzije. Novorojencki in otroci do 1 O let: 1 O µ.g proteina površinskega antigena v 0,5 ml suspenzije. Podrobnejše informacije in literaturo dobite pri proizvajalcu. ... KRK. tovarna zdravil, p. o., Novo mesto UDC 616-006(05)( 497 .1) CODEN RDIUA 4 YU ISSN 0485-893X RADIOLOGIA IUGOSLA VICA PROPRIETARII IDEMQUE EDITORES: SOCIETAS RADIOLOGORUM IUGOSLAVIAE AC SOCIETAS MEDICINAE NUCLEARIS IN FOEDERATIONE SOCIALISTICA REI PUBLICAE IUGOSLAVIAE LJUBLJANA ANNO 25 1991 FASC 3 Editorial Board Avcin J, Ljubljana -Benulic T, Ljubljana -Bicaku E, Priština -Borata R, Novi Sad -Fettich J, Ljubljana -lvancevic D, Zagreb -Jamakoski B, Skopje -Jevtic V, Ljubljana -Karanfilski B, Skopje -Kostic K, Beograd -Lincender L, Sarajevo -Lovasic 1, Rijeka -Lovrencic M, Zagreb -Lucic Z, Novi Sad -Milatovic S, Niš -Mitrovic N, Beograd -Mušanovic M, Sarajevo -Nastic Z, Novi Sad -Odavic M, Beograd -Pavcnik D, Ljubljana -Plesnicar S, Ljubljana - Spaventi š, Zagreb -Tabor L, Ljubljana -Trbojevic P, Beograd -Velkov K, Skopje Editor-in-Chief: Benulic T, Ljubljana Technical Editor: Serša G, Ljubljana Editors: Bebar S, Ljubljana -Guna F, Ljubljana -Kovac V, Ljubljana -Rudolf Z, Ljubljana Radiol lugosl July-September 1991; 25:179-284 RADIOLOGIA IUGOSLAVICA The review for radiology, nuclear medicine, radiotherapy, oncology, radiophysics, radiobiology and radiation protection. Publishers: Udruženje za radiologiju Jugoslavije and Udruženje za nuklearnu medicinu Jugoslavije Advisory Board: Lovrincevic A, Sarajevo (president) -Boschi S, Split -Dakic D, Novi Sad -Dimitrova A, Skopje ­Dujmovic M, Rijeka -Goldner B, Beograd -Guna F, Ljubljana -Hebrang A, Zagreb -Ivkovic T, Niš -Jevtic V, Ljubljana -Kamenica S, Beograd -Lišanin Lj, Beograd -Lovasic 1, Rijeka -Miric S, Sarajevo -Milutinovic P, Beograd -Mitrovic N, Beograd -Plesnicar S, Ljubljana -Porenta M, Ljubljana -Radojevic M, Skopje -Rajicevic M, Titograd -Ristic S, Novi Sad -Ristov N, Skopje -Stankovic R, Priština -Šimonovic 1, Zagreb -Šimunic S, Zagreb -šurlan M, Ljubljana -Tadžer 1, Skopje Reader for English language: Shrestha Olga UDC and Key words: mag. dr. Klemencic Eva, Institute tor Biomedical lnformatics, Faculty of Medicine University of Ljubljana Secretary: Harisch Milica Address of Editorial Board: Radiologia lugoslavica The Institute of Oncology, Zaloška cesta 2, 61000 Ljubljana Phone: 061/110-165, Fax 38 61 329 177 ONK INST LJB YU Published quarterly: Subscription rate -tor institution 2300 SL T. individual 600 SL T. Subscription rate -tor institution 100 US $, individual 50 US $ Single issue -tor institution 700 SL T, individual 200 SL T. Single issue -tor institutions 30 US $, individual 20 US $. Bank account number: 50101-678-48454 Foreign currency account number: 50100-620-010-257300-5180/6 LB -Gospodarska banka -Ljubljana lndexed and/or abstracted by: BIOMEDICINA IUGOSLAVICA, BOWKER R.R. ULRICH'S INTERNAT. PERIOD. 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Equally important, they are made to work together to achieve remarkable performance and diagnostic quality. Contact your Kodak representative far more infarmation. - l 1 1 UDC 616-006 (05) (497.1) CODEN RDIUA 4 YU ISSN 0485-893X RADIOLOGIA IUGOSLAVICA ANNO 25 1991 FASC 3. EDITORIAL Benulic T Diagnostic radiology Percutaneous transluminal angioplasty: therapeutic treatment concerning arteriovenous fistula complications in hemodialysis (orig sci paper) Tkalec V, Fedel V, Jerin L, Pirot D, Fedel 1 183 Duplication ot the colon and ileum, hemivertebra, maltormation -rare combination ot anomalies (case report) Frkovic M, Mandic A, Bradic 1, Zupancic B 193 Ultrasound and computerized tomography Tracheobronchomegaly (Mounier-Kuhn syndrome) (case report) Dalagija F, Dizdarevic Z, Bešlic š, 0urkovic P 197 Ultrasonographically guided percutaneous therapy ot lobar nephronia (case report) Fuckar 2, Cohar F, Mozetic V, šustic A 201 A case ot sinchronous bilateral renal carcinoma: Ultrasound, CT and angiographic evaluation (case report) Kurbel S, Filakovic Z, Rubin O 205 From practice tor practice -Cardiovascular system (case 3) Klancar J 211 Nuclear medicine Model tor computer simulation ot multipinhole thallium-201 heart imaging (orig sci paper) Lokner V 213 Oncology Microvascular tree tlaps in reconstruction after ablative surgery ot head and neck tumors (orig sci paper) Šmid L, Žargi M, Župevc A, Arnež Z 219 Comparison ot tumor-associated trypsin inhibitor (TATI} and tissue polypeptide antigen (TPA) in serum and pleural effusion in patients with lung diseases (orig sci paper) Lazarev A, Plavec D, Odavic M, Dangubic V, Koljevic A 225 Radio! lugosl July -September 1991 : 25 :179-284 Therapy of bile duet tumors with a combination of resection and intraarterial intrahepatic•chemotherapy (otig sci paper) štabuc B, Markovic S, Gadžijev E, šurlan M, Brencic E, Perovic AV, Marolt-Ferlan V 229 Experimental oncology Monoclonal antibodies in the treatment of breast carcinoma (review paper) Beketic-Oreškovic L, Novak D 235 Radiophysics and protection Some applications of nondestructive radioactivation analysis in medicine (orig sci paper) Zovko E 241 Scintigraphic film sensitometry and image quality assurance in nuclear medicine using a microscope (orig sci paper) Kasal B 245 Effect of constant background on gamma camera uniformity at different count rates (orig sci paper) Kasal B, Popovic S 251 Letters to editor Lasersko zdravljenje stenozantnega raka požiralnika Laser treatment of stenotic esophageal cancer Pinter 2, Pocajt M, Benulic T, Jancar B 255 Epidemiološki pogled na problematiko raka v Sloveniji in Jugoslaviji Epidemiological aspect of cancer related problems in Slovenia and Yugoslavia Pompe-Kirn V 259 Report lnterrregional training course on nuclear medicine Kovac V 263 Radiol lugosl July-September 1991; 25:179-284 Dear Readers and Authors, We dare say that the present No. 3191 represents an important advance in our radio­logic and nuc/ear medica/ publishing. Ali until few years back, RADIOLOG/A IUGOSLA­VICA had been a mere reflection of the existing situation in our scientific and profes­sional work. Aimed to put a stop to such practice, this issue published exc/usively in English is in a way ahead of our reality, thus indicating the direction in further deve/opment of the specific branches of medicine covered by our journal. According to the policy of our Editorial Board, preference is given primarily to the pubblication of original scientific and review papers that cou/d prove valuab/e so in daily clinica/ practice as we/1 as in the education of professionals. We also continuously strive to expand the circle of our regu/ar coworkers, particularly foreign authors, with the intention to attract a larger number of readers and subscribers from abroad. The journal in the present form is therefore designed not to be ours a/one, but to be, hopeful/y, accepted by . broader European reading public. We be­lieve that such a concept is juštitied also by the present poiitical and economic situation in Yugoslavia; the near generalized war-like conditions threaten to severely affect the country's economy as we/1 as our health care and research activities. The first results of such negative tendencies have already be­come apparent: Thus, the number of papers submitted tor publication to our journal is daily decreasing, and so is also the number of our subscribers. Apart from that, it has become increasingly difficult to secure the financial means needed tor regular publica­tion. Now, it appears that it is up to us ­physicians and researchers, whose mission reaches beyond these present difficulties -to strive tor the international recognition and quality of our journal, and to ensure its regular publication. The editorial work on the jubilee issue dedicated to the 25th volume of Radio/ogia lugoslavica is proceeding as planned. The papers are being reviewed and proot-read. Essential corrections are done in collabora­tion with authors whenever necessary. Here it should be pointed out that we greatly appreciate such cooperation, and therefore ali the participating individuals and institutions are kindly asked to stay by our side til/ the publication is finally ready. I am convinced our mutual efforts wi/1 be rewarded by a fair share ot pride and satisfaction at a successful outcome. The coverage of articles reporting on the !atest advances and confronting ideas in the appointed fields of medicine shou/d be of interest to a wide circle of readers. On behalf of our journal Radiologia /ugo­ s/avica, I wish to our present and potential coworkers a lot of success in their work. Benulic T. Editor-in-Chief ® SOLVOLAN (ambroksol) tablete, sirup nov sinteticni mukolitik i.n bronhosekretolitik • uravnava intracelularno patološko spremenjeno sestavo izlocka v dihalih • stimulira nastajanje in izlocanje surfaktanta iz celic pljucne strukture • povecuje baktericidnost alveolarnih makrofagov • zmanjšuje adhezijo bakterij in levkocitov na sluznico dihalnih poti • sprošca zastojni in žilavi izlocek s stene bronhijev in olajšuje izkašljevanje • odstranjuje bronhialni izlocek s spodbujanjem mukociliarnega prenosnega sistema in neposrednim vplivom na delo cilij • zmanjšuje viskoznost bronhialne sluzi • ublažuje neproduktivni kašelj • olajšuje dihanje Oprema 20 tablet 100 ml sirupa Podrobnejše informacij_e in literaturo dobite pri proizvajalcu. f .i KRK. tovarna zdravil, p. o., Novo mesto MEDICAL CENTER PULA DEPARTMENT OF RADIOLOGY, DEPARTMENT OF UROLOGY, DIAL YSIS CENTER, DEPARTMENT OF SURGERY PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY: THERAPEUTIC TREATMENT CONCERNING ARTERIOVENOUS FISTULA COMPLICATIONS IN HEMODIAL YSIS Tkalec V, Fedel V, Jerin L, Pikat O, Fedel 1 Abstract -Ten patients on regular hemodialysis with arteriovenous fistula complications have been treated by percutaneous transluminal angioplasty (PTA) at Dialysis Center Pula, in the period from October 1986 to October 1990. From 1986 the color Doppler sonography has been combined with angiography in the diagnosis of AV fistula complications when PTA is planned. There were 31 combined examinations performed in 26 patients, the findings revealed 13 cases of arteriovenous fistula thrombosis, 8 venous stenoses exceeding 8 cm or multiple stenoses. Proximal radial artery stenoses were found in 3 cases, anastomotic venous stenosis in 2 and venous limb stenosis shorter than 4 cm iri 5 cases. A dilatation technique with PTA balloon catheter is described. Due to the high stenotic resistance (severe fibrosis), balloon inflation pressure of 8 to 12 atmospheres was used. Duration of inflation pressure was up to 2 minutes and was repeated 10 times. The criteria of successful PTA is dialysis duration of the same fistula after treatment, which should be at least 6 months at an adequate flow rate. Out of 1 o fistulas treated with PT A, only one artery and one venous stenosis ceased to function after 2 weeks and 1 month respectively from the treatment. The PT A treatment was successful in 4 venous stenoses, 2 artery stenoses and in an anastomotic stenosis. PTA is the treatment of choice in venous (limb) stenosis not exceeding 4 cm. Other complications should be treated surgically. UDC: 616.13-007.253-089.844 Key words: hemodialysis-adverse effects; arteriovenous fistula; angioplasty, transluminal; Orig sci paper Radiol lugosl 1991; 25:185-92. lntroduction -A chronic terminal renal insuf­ficiency can be treated by regular dialysis or kidney transplantation. For an adequate hemo­dialysis at least 300 ml/min blood flow is needed. An adequate vascular approach ensures such flow rate. Radiocephalic arteriovenous fistula on the distal forearm of the nondominant arm is the site of choice in a vascular access to the regular dialysis (1, 2). This type of fistula remains patent in 80 -90 % of patients, for a period of two years (3). The number of suitable sites for vascular access is limited, and therefore, it is important to maintain each fistula function for as long as possible. An AV fistula can undergo a lot of complications due to various reasons. The de­mand for a long-lasting fistula function and pre­vention of complications requires a perfect choice of the site, an evaluation of the vessel quality and a proper technique of fistula construction. The evaluation of the vascular tree is done by means of noninvasive mYthods: physical examination of the extremities and color Doppler sonography. Color Doppler sonography as a noninvasive and reliable, method has been preferred over all other examination techniques (2, 4). Color Dop­pler spectral blood flow analysis gives a very good and accurate image of the arterial and venous tree condition, and all pathological pro­cesses and complications of a,teries and veins can be found. Regarding its qualities, we use the Doppler technique in combination with angio­graphy to diagnose AV fistula complications (4, 5). Color Doppler sonography of the arterial and venous circulation, photoplethysmography and plethysmography give significant information on the blood vessefs and the methods should be used as a complementary method to angio­graphy (2, 4) to diagnose AV fistula complica­tions. In ti•~ case that we are sure about the fistu1 -type, if we know preoperative Doppler findi and dialysis treatment problems, we can determine the exact fistula site and type of complication by color Doppler sonography. The complication can be documented by spectral signal analysis; it can be shown in numerical frequency in KHz which directly points to the blood flow. Differences in flows in KHz of each fistula component, and a comparison of their interferences enable quite a precise diagnosis of stenosis and its localisation on fistula. These assumptions are based on the fact that an ideal fistula should have eG1ual blood flow in all three components (arterial limb-anastomosis-venous limb) which is shown in KHz frequency. The Received: March 11, 1991--Accepted: September 27, 1991 ,;,..:i MAXA KHz Tkalec V et al. Percutaneous transluminal angioplasty: therapeutic treatment concerning arteriovenous fistula complications in hemodialysis . . 11 F/2 .,. ..,_ , .., ,. •· . ·, . =-:},.,= . t. .. ·.-. •. ;l. .. - 1"22 . _r· :::·..--. ·: .... ·.·..f.rjri-l. . ,.._,._.., -.1 • ..,, .,..,.. "••Fv.,), . ;,.,.•J...H·. --•. -;., · :•· ::-.(_,, ,, ..•..1._..i.;-.. .---.·:•..;,...-... ___ ctF-·" -.. ·--··'.·--.·-·-.,;..,._ .. ,. . :. ... ,.---,l.-.... ·,, , .. , ... MAXO KHz Pl r RP H __ ,_.., ,H _H_.__l;]"Y'_ _H H RH . .:::;:. . TIME S 3.0 25/06/88 9:54 am BAZON NOEMI No FNOOOOO· 20 l12.51-_.,;\\., l ... .w ..,... •"?;Al}.'•' 1 ' 1 ' • }. ' •.. . '1t'-Y-Y• - .-:.:.·.i_.-­ - 2 MA><:A KHz MAXD KHz .,.;f.)?l:.{ii ,..iJ;p,,.­ ,, ->ll-,-,"".-'f ·'V·, .1ll ! „ i . ··"'l:• • ;;, '(!,..;.:_, . · It .-\}.1j'· tf " -:_: tY:.·.--:--f :'\.rr ,,·. s :-r i· .:. :!"+·.· ··-..;• .. .:'>:•,.;r . : /)},\'iJ.. d.·J?::· ". RP PI . . 88 % FI$TULA :· -· ;:,:,·'.:...'.: t. (FH.I At.ASTOMOZR) ..,,... TIME S ' 3.0 25/06/88 i0:25 am BRENKO f.LRI.WO Ho Fl'iOOOOO 20 -'• '-i.. KH l , ""'" GRitl 35 ,/ 8 MHz 1 2. 6 KHz- OOPl"LER HAP Lfff 'r'21 f­ MAXA MA:><:o O • 9 KHz RP O. 64 PI 1 S8 46 :-; H 6-._, .i....i..N.1 r?. :o.s RAK .,, ­ . TIME S 3.Cr L 25/06.-88 10:2;;' am H RIH BREMKO SLRl,tKO Ifo FNOOOOO Z(I 'I s. O\.'.HZ KH GAIH 35 v' 8 MHz 00t-'t'LER !'lHP LAT >::30 ' Mfr., KHz + 0,8 FISTULE A. RAD. TIME S .., H 3.0 RODIC KATICA 1947. No FNOOOOO S, 1.4t' t ·., . . ' cd ·"'".'°"'"t.' " "·\. J 1, Fig. 3 and 4 -Operative finding: a spherical duplication (c -colon, cd -colonic duplication) sb-'' Fig. 5 -Duplication of the ileum. Operative finding (i -ileum, di -duplication) with dense, pale and yellow liquid content. The distal end of the duplication was brought out as a cutaneous stoma in the left upper hemiabdo­men. The histologic examination (No. 3970/90) showed that the wall of the duplication had the same structure as the wall of the colon. Fig. 6 -A schematic presentation: spherical duplication Two months later, the baby had a second of the colon (cd) and ileum (di), malrotation, hemiverte­operation. A side to side anastomosis of the bra Th 12 (N -kidney, G -stomach, sb -small bowel, remaining colonic duplication segment with distal H -hernia inguinalis, c -colon). Radiol lugosl 1991 ; 25 :193·6. Frkovic M et al. Duplication of the colon and ileum, hemivertebra, malformation -a rare combination of anomalies. part of the colon was made and the cutaneous stoma closed. Both postoperative recoveries were without significant complications. Discussion -The case report presents a 4 month old infant with a voluminous spherical colonic and tubular ileal duplication, hemiverte­bra, and malrotation of the bowel. Until now, only a small number of cases of multiple colonic duplications combined with other anomalies have been reported (1 ). Three of these cases presen­ted colonic duplication associated with hemiver­tebra. AII three cases were also associated with genitourinary tract anomalies (1 ). There was no genitourinary anomaly in our case. Because of complications, as an obstruction. of the bowel, or an abdominal tumor as the most common, duplications are in most cases identi­fied in the first months of lite. This was also the case with our child. In 85%, the duplication is identified before the age of two (1, 2, 5, 6, 7). It rarely passes undetected until adulthood (8). Even with modem, highly diagnostic procedu­res, the exact preoperative diagnosis of this anomaly is rare (9). Because of malrotation the possibility of mesocolic chylous cyst was raised. In malrotation they usually appear due to distur­bance in the lymphatic drainage,. caused by chronic volvulus (1 O, 11, 12, 13). The presence of hemivertebra reminded us of simnar cases in literature, i. e. the combination of hemivertebra with colonic duplication (1 ). The therapy for duplication is surgical. The type and the extension of an operation depends on the location, volume, vascularity, and preope­rative complications, cau.ed by duplication. References 1. Bower RJ, Sieber WK, Kiesewetter WB. Ali­mentary tract duplications in children. Ann Surg 1978; 188(5) :669-7 4. 2. Gdaniets K, Wit J, Heller K et al. Die komplette DOnndarm-duplikatur im Kindesalter. Z l\inderchir 1983; 38:414-6. 3. Ravitch MM. Duplications of the gastrointesti­nal tract. In: Welch KJ, Randolph JG, Ravitch MM et al. Pediatric Surgery. 4th ed. vol 2. Chicago-London: Year Book Medical Publishers, inc. 1986; 915-20. 4. Grob M. Lehrbuch der Kinderchirurgie. Stutt­gart: Georg Thieme Verlag, 1957; 346-57. 5. Pasini M, Bradic l. Complete duplication of colon. Z Kinderchir 1969; 7:120-4. 6. Schwartz DL. Procaccino A, Becker M, et al. Segmenta! colonic duplication presenting as a sigmoid volvulus. Z Kinderchir 1983; 38 :338-40. 7. Schwartz DL, Becker JM, Schneider KM, et al. Tubular duplication with autonomous blood supply: resection with preservation of adjacent bowel. J Pediatr Surg 1980;15:341-2. 8. Kiesler J, Angelberger H, Dirschmid K, Duplica­tion of the large bowel with autonomous vasculariza­tion. Acta Chir Aust 1976:8:. 9. Janneck G, Schcich G, Hajek HW, Seltene Doppelbildungen des Digestionstraktes. Z Kinderchir 1980; 30:210-4. 10. Mori H, Havashi K, Futagawa S, et al. Vascular compromise in chronic volvulus with midgut malrota­tion. Pediatr Radio! 1987; 17 :279-81 . 11. Berdon WE, Baker DH, Buli S, Santulli TV. Midgut malrotation and volvulus: Which films are most helpful. Radiology 1970; 96 :375-83. 12. Colodny AH. Mesenteric and omental cysts in: Welch KJ, Randolph JG, Ravitch MM, et al. Pediatric Surgery. 4th ed, vol 2. Chicago-London: Year Book Medical Publishers, inc. 1986; 921-5. 13. Estourgie RJA, Van Beck MW. Mesenteric cysts. Z Kinderchir .1981 ; 32 :O. 135-8. Author's address: Dr. Marija Frkovic, Maksimirska 12/1 , 41000 Zagreb Radiol lugosl 1991; 25:193-6. 1111 Drr0(Q)[n] Corso ltalia 112 ff (0481) 32073 SIRION s.r.l. 34170 Gorizia -ITALY ft Fax (0481) 534753 P. Iva 00380480319 medlcal supplles Tx 461240 -SIRION -1 January 1989 BALT otfer far Transluminal Angioplasty the thinnest, most flexible and, at the same tirne, the most resistant device CRISTAL BALLOON January 1889 VAN GOGH painted "Man with a pipe" He. too, believed in the value of his work. (BALT) EXTRUSION 10, rue Croix-Vigneron -95160 Montmorency-France -Tel. (33/1) 39 89 46 41 -Telex 699 965 F -Fax (33/1) 3417 03 46 UNIVERSITY MEDICAL CENTER, INSTITUTE OF RADIOLOGY AND ONCOLOGY GLINIC FOR LUNG DISEASES »PODHRASTOVI«, SARAJEVO TRACHEOBRONCHOMEGAL Y (MOUNIER-KUHN SYNDROME) Dalagija F. Dizdarevic Z. Bešlic š. 0urkovi6 P Abstract -Tracheobronchomegaly (Mounier-Kuhn syndrome) is a very rare, probably congenital, disorder. lts clinical appearance, in the form of chronic inflammation symptoms of the respiratory tract, is non-specific. Radiological features are, however, unequivocal, thus leading to the correct diagnosis. But, such patients can remain undetected if they are asymptomatic or if only conventional radiography is used. Since the detection of this anomaly by CT is simple and accurate, it is suggested in all patients with recurrent infections of the respiratory tract. This report presents a 55-year-old patient with this rare condition. UDC: 616.23-007.61 Key words: tracheobronchomegaly Case report Radlol lugosl 1991; 25:197-200. lntroduction -Tracheobronchomegaly (TBM) is defined as a marked dilatation of the trachea and main bronchi. The first description of its pathologic changes is credited to Czylharz in 1897, but it was not until 1932 that the first clinical description was published by Mounier. Kuhn (1, 2, 3, 4, 5). The clinical presentation is non-specific. There are symptoms, frequently since the early childhood, of chronic respiratory tract disease, i. e., loud cough with or without sputum production, recurring pneumonia, hoarseness and even spontaneous pneumothoraces. Radiological fea­tures are, however, unequivocal, thus leading to the correct diagnosis. They are: marked dilata­tion of the trachea and main bronchi, tracheal diverticulosis, bronchiectasis and chronic inflam­matory changes of the lung parenchyma (1, 2, 5, 6). TBM is a very rare disorder and only 82 cases were reported in the literature since 1988. However, some patients with tracheobronchome­galy may be totally asymptomatic and are not detected, whereas those with symptoms frequen­tly are overlooked if chest radiography alone is used far diagnosis (4). The detection of TBM by CT is simple (and straightforward). It is believed that with wide applicat(on of CT in patients with recurrent pul­monary infections, more cases of tracheobron­chomegaly can be identified in the future (4, 7). Case report -A 55-year-old mailman, ciga­rette smoker of long duration with the recurrent pneumonia right, chronic rhinopharyngitls and maxillary sinusitis, was reffered to the Glinic of lung diseases far investigation and treatment. The pulmonary function tests revealed an increased resistance in respiratory tubes, cau­sing an moderately severe ventilatory insuffi­ciency of the obstructive type, followed by the averagely marked hyperinflation of lung paren­chyma. Chest radiograph showed the increased mar­kings in both peribronchovascular lobes, espe­cially on the right side basally, with stained-ho­neycomb shadows. Bronchograpy was perfor­med because of the suspected right bronchiecta­sis. The finding was impressive: a marked dilata­tion of the trachea and both main bronchi with ring-like enlargement, as the intestinal haustrum. Diascopy demonstrated a marked narrowing of the lumen during expiration, · and contrast me­dium did not pass ihto the far periphery. Received: May 6, 1991 -Accepted: May 14, 1991. Dalagija F et al. Tracheobronchomegaly (Mounier-Kuhn syndrome) Right bronchial tree had »scattered« bron­chiestases. The presence of TBM with diffus. bronchiestases on the right side was concluded (Fig. 1). During rehospitalisation, CT of the thoracic organs was performed. Transversal CT slices showed a greatly dilated trachea with a diameter of 4 cm, square in places, with ·sharp irregular Fig. 1 -PA bronchogram: marked dilatation of trachea and main bronchus with bronchiectasie right. Fig. 2. -CT slice: marked dilatation and deformity of trachea. contures (Fig 2). Both main bronchi were dilated with a diameter of 2,5 cm right and 2,4 cm left (Fig. 3). Para and retro-cardiobasally, lung mar­kings were expressive, rough, partially irregular, with post-inflammatory.and deformative changes (Fig 4). Discussion -Tracheobronchomegaly (TBM) has been described by a variaty of names, including tracheobronchiectasis, tracheal diverti­culosis, tracheocele, tracheomalacia, tracheo­bronchopathia malacia, and any diameter of the trachea that exceeds 3 cm (1 ), over 22 mm in men and 19 mm in women (8) is diagnostic for TBM, as well as the diameter of the right main bronchus over 2,4 cm (1 ), over 16 mm (8) and Fig. 3 -CT slice: marked dilatation of trachea and bolh main bronchi. ·· .. · .. -w . ;' . . . .· .. i•·..i /:t! ,;_, Fig. 4 -CT slice: postlnflammatory and deformative changes retrocardiobasally right. Radiol lugosl 1991; 25•197-200. Dalagija F et al. Tracheobronchomegaly (Mounier-Kuhn syndrome) left main bronchus over 2,3 cm (1) over 14 mm (8). The cause of TBM is unknown, although most authors believe in the congenital etiology. The first comprehensive description of the patho­logic changes in TBM is credited to Czyhlarz who in 1897 noted » marked atrophy of the longitudinal elastic fibers and thinning of the muscularis« in a postmortem specimen, suggesting a congenital weakness of the walls«. Although the association of this condition with Ehlers-Danlos syndrome reported in adults and with acquired cutis laxa in children (9) _may suggest a congenital defect in connective tissue as the basis for Ti3M, most cases, however, presented in the third or later decades of life and showed no evidence of other connective tissue disorders (4), as do other congenital lesions such as polycystic kidney (7). According to some authors, TBM is believed to be an acquired rather Ihan a developmental anomaly (2, 1 O, 11 ). It has been speculated that barotrauma is the primary pathopysiologic factor in neonates who have TBM after receiving inten­sive ventilatory and oxygen support, as well as the inhalation of chronic irritants found in ciga­rette smoke and air pollution, in adults (2, 12). But it seems likely that smoking and other irritants exacerbate the condition rather Ihan cause it (7). There is an almost invariable history of chro­nic infection, but this could just as easily be a result as the cause of the widened airways. A number of authors note the existence of TBM without clinical and pathologic evidence of inflam­mation and point out that while chronic inflamma­tory lung disease is common, TBM is rare. This further militates against TBM being an acquired disorder (1, 5, 7, 13). The consensus seems to be that there is a congenital anomaly, with or without overlying inflammatory changes (1, 5, 13, 14). Our patient is a cigarette smoker of long duration and besides the chronic rhinopharyngitis and maxillary sinusitis, this presents one of the causes of recurrent pneumonia. Radiographically, TBM is manifested by the marked dilatation of trachea and main bronchi with irregularly corrugated conture of the air columns, considered as a consequence of the protrusion of redundant musculomembronous tis­sue between the cartilaginous rings (4). The severe pass on the normal caliber of the termal airways has been presented as the bronchograp­hic characteristic of TBM (3.). Grossly enlarged but weakened airways and insufficient cough mechanism impede mucociliary clearance and lead to retention of mucus with resultant recurrent pneumonia, emphysema, bronchiectasis and pa­renchyma scarring (4, 5). CT, with the transversal slices, is superior over the standard radiography and conventional tomography because of the possibilities of accu­rate measurements of the tracheal and bronchial dilatation, and early and precise diagnosis of parenchymal changes and calcifit:ation. An expi­ratory collapse of the trachea and the main bronchi can also be identified by CT, but can normally be easily visualized by fluoroscopy. Discrete changes of the bronchial walls, like small diverticula, are best shown by broncho­graphy (6, 7, 15, 16, 17). Although only 82 cases of TBM have been reported, the actual number of cases could be much higher. Most cases of TBM probably are underdiagnosed if they are asymptomatic and if chest radiographs alone are used (the presen! case is such an example). Such patients are treated as the cases of chronic bronchitis or repeated pneumonia, not taking into account this anomaly (3, 4). Because TBM can be easily overlooked on plain chest film, and its detection by CT is simple and straight forward, CT should be done in patients with chronic recurrent pneu­monitis for the detection and evaluation of under­lying predisposing conditions, including TBM (4). Conclusion -Although the diagnosis of TBM in our patient was made by a previously perfor­med bronchography, this anomaly, -syndrome ­could be easily and accurately detected by CT. This is evident from the presented CT seans, and is in accordance with the reports in literature. Therefore, we support the suggestion that should be used patients with that CT should be used in reccurent pulmonary infections. Sažetak TRAHEOBRONHOMEGALIJA (Sindrom MOUNEIR-KUHN) Traheobronhomegalija (Sindrom Mounier-Kuhn) predstavlja izrazito rijetku, vjerovatno kongenitalnu, anomaliju. Njene klinicke manifestacije, u vidu simp­toma hronicnih upala respiratornog trakta, su nespeci­ficne. Radiološki znaci su karakteristicni i vode do lacne dijagnoze. Medutim, ovi pacijenti mogu ostati neotkriveni, ako su bez simptoma ili ako se koristi samo standardna radiografija. Pošto je detekcija ove anomalije, pomoc1,1 CT, jednostavna i pouzdana, to se on preporucuje kod svih pacijenata sa hronicnim recidi­virajucim upalama respiratornog trakta. Radiol lugosl 1991: 25:197-200. Dalagija F et al. Tracheobronchomegaly (Mounier-Kuhn syndrome) References 10. Griscom NT, Vawter GF, Stigol LC. Radiologic and pathologic abnormalities of the trachea in _older 1. Katz 1, LeVine M, Herman P. Tracheobroncho­patients with cystic fibrosis. AJR 1987; 148:691-3. • RO INSTITUT ZA NUKLEARNE NAUKE »BORIS KIDRIC«, VINCA OOUR INSTITUT ZA RADIOIZOTOPE »RI« 11001 Beograd, p.p. 522 • Telefon: (011) 438-134 • Telex: YU 11563 • Telegram: VINCA INSTITUT Uz našu redovnu proizvodnju i snabdevanje korisnika pribora za in vitro ispitivanja: T3-RIA T4-RIA lnsulin -RIA HR-RIA ACTH-RIA Služi za odredivanje hipofunkcije adrenalnih žljezda (primarna i sekundarna) i hiperfunkcije adrenalnog korteksa (Conn-ov, Cushing-ov i adrenogenitalni sindrom). U 1988. godini pustili smo u redovan promet za in vitro ispitivanje CEA-RIA Pribor za odredivanje karcinoembrionalnog antigena (CEA) u serumu metodom radioimunolo­ške analize. megaly: The Mounier-Kuhn Syndrome. P.JR 1962; 88:1084-94. 2. Bateson EM, Woo-ming M. Tracheo-broncho­megaly. Ciin Radiol 1973; 24:354-8. 3. Gay S, Dee P. Tracheobronchomegaly -the Mounier-Kuhn syndrome. Br J Radiol 1984; 640-4. 4. Shin MS, Jackson RM, Ho KJ. Tracheobron­chomegaly (Mounier-Kuhn syndrome): CT diagnosis. AJR 1988;150:777-9. 5. Meyer E, Dinkel E, Nilles A. Tracheobroncho­megaly: clinical aspects and radiological features. Eur J Radiol 1990; 10:126-9. 6. Dunne MG, Reine'r B. CT features of tracheo­bronchomegaly. J Comput Assist Tomogr 1988; 12(3) :388-91. 7. Doyle AJ. Demonstration on computed tomo­graphy of tracheomalacia in tracheobronchomegaly (Mounier-Kuhn syndrome). Br J Radiol 1989; 62:176-7. 7. 8. Vock P, Spiegel T, Fram EK, Effmann EL. CT assessment of the adult intrathoracic cross section of the trachea. J Comput Assist Tomogr 1984;8(6):1076­82. 9. Aaby GV, Blake HA. Tracheobronchomegaly. Ann Thorac Surg 1966; 2:64-70. 11. Woodring JH, Barrett PA, Rehm SR, Nurenberg P. Acquired tracheomegaly in adults as a complication of diffuse pulmonary fibrosis. AJR 1989; 152:743-7. 12. Engle WA, Cohen MD, McAlister WH, Griscom NT. Neonatal tracheobronchomegaly. Am J Perinatol 1987; 4:81-5. 13. Himalstein MA, Gallagher JC. • lcheobron­chomegaly. Ann Otol Rhinol Laryngol 19,J; 82:223-7. 14. Johnston RF, Green RA. Tracheobronchiome­galy: report of five causes and demonstration of familial occurrence. Am Rev Respir Dis 1965; 91 :35-50. 15. Naidich DP, McCauley DI, Khouri NF, Stitik FP, Siegelman SS. Computed tomography of bronchiecta­sis. J Comput Assist Tomogr 1982; 6:437-44. 16. Westcott JL, Cole SR. Traction bronchiectasis in endstage pulmonary fibrosis. Radiology 1986; 161 :665-9 . 17. Mildenberger P, Schild HH. Tracheobroncho­megalie. Radiologe 1988; 28:236-8. Author's address: Doc. dr sci. Faruk Dalagija, Insti­tut za radiologiju i onkologiju UMC-a Sarajevo, M. Pijade, 71000 Sarajevo Radiol lugosl 1991; 25:197-200. CLINICAL HOSPITAL RIJEKA FACUL TY OF MEDICINE RIJEKA GLINIC FOR SURGERY, UROLOGIC DEPARTMENT1 GLINIC FOR INTERNAL MEDICINE, NEPHROLOGICAL DEPARTMENT2 UL TRASOUND UNIT3, DEPARTMENT OF ANAESTHESIOLOGY4 ULTRASONOGRAPHICALLY GUIDED PERCUTANEOUS THERAPY OF LOBAR NEPHRONIA Fuckar ž1 , Cohar F2, Mozetic V3, šusti6 A4 Abstract -In our patient the diagnosis of lobar nephronia (acute focal bacterial nephritis) was suspected on the basis r' anamnesis, status, laboratory data and ulirasonography. A cytological examination of the specimen confirmed „1e diagnosis. Four times repeated instillation of Gentamycin (80 mg) »in loco« under ultrasound control resulted in the complete regression of local lesion. UDC: 616.61-002-073:534-8 Key words: nephritis-therapy; ultrasonic therapy Case report Radiol lugosl 1991 ; 25 :201-4. lntroduction -Lobar nephronia (acute focal bacterial nephritis) is a clinical entity which can be defined as an acute local infection of renal parenchyma without liquefaction (1, 2). In 90% of cases the infection was caused by e. coli and rarely by aerobacter aerogenes, pseudomonas aeruginosa, proteus and klebsiella (3, 4). Clinical symptoms correspond to acute pyelonephritis. Regarding ultrasonical examination the follo­wing possibilities should considered in the diffe­rential diagnosis: mixed tumor, column of Bertini, hematoma, lymphoma, urinoma and cyst (1, 5, 6). Some specific characteristics of focal lesions such as poorly limited solid mass usually with low-level echoes which disrupt continuity of the corticomedullary border (1, 2) and physician's experience improve the diagnosis. Ultrasonically guided punction and cytological examination of the specimen are the methods of choice tor final diagnosis (1, 4, 5, 7). Local topic antibiotic application (1, 5, 7) or ultrasonically controlled percutaneous drainage (1, 5, 7, 8) proved to be successful therapeutic procedures. Case Report -A 58-year old man was referred to the Department of Nephrology (152/ 90) as an emergency case after an episode of left flank pain, high temperature and dysuria during the last four days. He said that he had urinated blood several times. In the remaining history, he underwent malaria in childhood and a few attacks of erysipelas on the shin, joint inflam­mation and inflammation of the urinary system with symptoms which were similar with the pre­sen! ones and passed spontaneously. Physical examination revealed positive left lumbar succus­sion and palpation tenderness of the lower half of left kidney area. Laboratory data: urine lucid, yellow, sour, alb+ (4.3 g/1 ), sugar+ (1.6 mmol/1 ), acetone+. Microscopic specimen of urine: white blood cells, bacteria, 4-6 RBC. Urinoculture: e. coli ( > 100.000 per ml), Hemoculture: e. coli, SR 80/, WBC 9.8 BS 14.1, urea 10.1, creatinine 149. AII other biochemical investigations were normal. After anamnesis, status and laboratory data the working diagnosis was: urosepsis, acute left-side pyelonephritis and diabetes mellitus. An i. v. urography showed that the left kidney inefficiently concentrated contrast with pallid nephrographic effect and incapability of pyeloca­liceal system analysis. The left kidney was enlar­ged with irregular borders which corresponded to an expansive process and further treatment was recommended. Received: March 11, 1991 -Accepted: July 2, 1991. Fuckar 2 et al. Ultrasonographically guided percutaneous therapy of lobar nephronia Ultrasonography revealed gently hyperechoic area (2.6 x 2.3 cm) of the medial part of the left kidney which pressed echoes from the pyelocali­ceal system. According to the sonographic fin­dings, this focal lesion is probably column of Bertini. In the differential diagnosis lobar nephro­nia, which is often hypoechoic, has to be taken into consideration. The right kidney, !iver and Fig. 1 -Dorsal axial sector scan of the left kidney with presentation of mesonephric focal lesion (markers) gallbladder were sonographically normal. The prostate showed sonographic signs of chronic prostatitis with a few prostatoliths. Ultrasonically guided percutaneous puncture of the left kidney was recommended (Fig 1 ). Ultrasonically guided puncture was done in the following way: the patient lied on the right Fig. 2 -Semioblique linear feature of the left kidney during gentamycin application; hyperechogenic echoes of the pyelon (p), arrow shows the tip of the needle Fuckar 2: et al. Ultrasonographically guided percutaneous therapy of lobar nephronia Fig. 5 -The same scan as in Fig. 4; arrow shows a clear hyperechogenic reg ion; histogram was !aken from normal surrounding renal parenchyma (note the various curve·s and numbers) flank, upper pari of the abdomen was bolstered for better kidney fixation. Sterilisation and confi­ning of the operative field was done with standard solution and sterile compresses. With a sterilised ultrasound probe of 3.5 MHz the best position for puncture was fixed which meant that there was enough »protecting stratum« of healtny paren­chyma between the lesion and renal cap­sule to prevent the possibility of bacterial propa­gation into the perirenal compartment. Skin inci­sion (2-3 mm) was done under local anaesthesia. Pathological process as set in the position which corresponded to puncture-line of the probe. Fol­lowing puncture-line, a thick needle was stung through the lumbar muscles. It served as a canal for a thin aspiration needle with aspiration biopsy of focal kidney lesion was performed 4-5 times under the negative pressure. Cytologic specimen was prepared in standard way. The cytologic specimen showed dense mass of mature WBC and some macrophages. After sonographic and cytological confirma­tion, a therapy was started as follows: tour times, every 3-4 days, gentamycin (80 mg) was applied into the focal kidney lesion under ultra­sound guidance. Application procedure was the same as described previously. Antibiotic was injected directly »in loco« with a syringe through needle along the guideline (Fig 2 and 3). With the therapeutic procedure described, the regression of focal kidney lesion was com­plete and the patient was discharged with recom- -mendations for home care. Ultrasound follow-up examination after 3 weeks did not show presence of residual disease. Hyperechogenic area and its histogram analysis corresponded to fibrosis (Fig. 4 and 5). Discussion -It noninvasiveness, painles­ sness, the possibility of repetition without conse­ quences to the patients health and accuracy of diagnosis render ultrasonography the method of choice in the detection of kidney pathology. lnterventional ultrasonography, enabling visuali­ sation of diagnostic or therapeutic procedures (biopsy, nephrostomy, punction and cyst sclero­ sation, application of various drugs), represents an advantage which further promotes the appli­ cability of ultrasound. Histogram analysis of focal lesions, which is being investigated, facilitates the distinction between »pathological« and »nor­ mal«. Lobar nephronia is a localised form of pyelonephritis (2, 6, 9, 1 O) and is to be under­ stood as the midpoint in a spectrum of pyelo­ nephritis from acute pyelonephritis to abscess (6). Pathophysiologically a pronounced cortical vasoconstriction was localised in the areas of acute inflammation with clogging of the peritubu­ lar capillaries by inflammatory cells. After a few days this areas progressed to necrosis and/or abscess (10), This examination confirmed the thesis of lobar nephronia as a precursor of renal abscess. Ultrasonography, i.v. urography and compu­ terised tomography are the techniques used in the diagnosis of acute renal diseases. As the lobar nephronia comprises a spectrum of diffe­ rent pathological conditions with equal features the cytological puncture is necessary. The matu­ ration of inflammatory process changes the sono­ graphic image (enhancement of border echoes, separation from surrounding tissue). Liquefaction results in central hypo-or anechogeneity (1 ). lntravenous urography presents a solid expan­ sive process and CT shows a wedge shape area of decreased attenuation (2). Although hypoec­ hogenic area without increased posterior ultra­ sound beam enhancement is the most commonly described ultrasonographic findings in the recent literature (1, 2, 6, 9, 11 ), our patient had a slightly hyperechogenic solid mass, and therefore ultra­ sound diagnosis was implemented by sonograp­ hically guided puncture. In the recent literature, classic parenteral antibiotic therapy is _described as therapeutic procedure (2, 6, 11, 12). We decided for an intermittent topical antibiotic application with ul­ trasonical following of focal lesion regression. Radiol lugosl 1991 ; 25 :201-4. Fuckar 2 et .l. Ultrasonographically guided percutaneous therapy of lobar nephronia Considering the previously mentioned advanta­ges, complete r.gression was achieved after two weeks. Conclusion -We presented a case of lobar nephronia. The disease was verified after ultraso­nically guided puncture. We decided for a topical antibiotic application under ultrasonic control as a therapeutic procedure which proved to be successful. We believe that the described ultra­sonically guided diagnostic and therapeutic pro­cedures can be helpful in the treatment of some focal infections of the renal parenchyma. Howe­ver, when making selection between classic the­rapy and that !:Jescribed in our report, appropriate education and experience of the physician should be of decisive importance. Sažetak SONOGRAFSKI VODENA PERKUTANA TERAPIJA LOBARNE NEFRONIJE Prikazan je pacijent u kojeg je, na osnovu anamne­ze, statusa, laboratorijskih nalaza i ultrazvucnog pre­gleda postavljena sumnja na lobarnu nefroniju (akutni lokalni bakterijski nefritis). Izvršena je punkcija pod kontrolam ultrazvuka, te je citološki nalaz punktata potvrdio dijagnozu. U cilju terapije instiliran je u cetiri navrata pod vodstvom ultrazvuka, »in loco«, Gentami­cin (po 80 mg), šlo dovodi do potpune regresije lokalne lezije. References 1 . Fuckar L. Sonografija urogenitalnog sustava. Ljubljana-Rijeka: Partizanska knjiga, 1987. 2. Rosenfield AT, Glickman MG, Taylor KJW, Grade M, Hodson J. Acute focal bacterial nephritis (acute lobar nephronia). Radiol 1979; 132:553-61. 3. Hadžic N, Radonic M, Vrhovac B, Vucelic B. Prirucnik interne medicine (dijagnostika i terapija). 3.1 zd. Zagreb: Škalska knjiga, Ju mena, 1989 ;37 4. 4. Sharma SK, Kumar A, Sharma BK, Malik N, Fadnis P. lnternational gas abscess. J Ural 1986; 136:1059-60. 5. Fuckar L. Interventni ultrazvuk. In: Kurjak A et al eds. Ultrazvuk u klinickoj medicini. Zagreb: Medicinska naklada, 1989 :515-63. 6. Morehouse HT, Eeiner SN, Hoffman JC-lma­ging in lnflammatory Disease of the Kidney. AJR 1984;143:135-41. 7. šustic A. Prilog interventnoj sonografiji bubrega. Rijeka: Medicinski fakultet Rijeka, 1989. Diplomski rad. 8. Godeck CJ, Tsai SH, Smith SJ, Cass AS. Diag­nostic strategy in evaluation of renal abscess. Urology 1981 ;18 :535-41. 9. t.:.ee JKT, McClennan BL, Melson GL, Stanley RJ. Acute focal bacterial nephritis: emphasis on gray scale sonography and computed tomography. AJR 1980;135:87-92. 1 O. Hill GS, Clark RL. A comparative angiographic, micro-angiographic, and histologic study of experimen­tal pyelonephritis. lnvest Radiol 1972;7:33-47. 11. Funston MR, Fisher KR, Van Blerk JP, Bortz JH. Acute tacal bacterial nephritis or renal abscess: a sonographic diagnosis. Br J Radiol 1982;54:461-6. 12. Siegel MJ, Glasier CM. Acute bacterial nephri­tis in children: significance of ureteral reflux. ARK 1981 ;137:257-60. Author's address: L'.eljko Fuckar, MD, Ph D, Ass. Prof., Glinic tor Surgery, Urologic Depertment, Clinical Hospital Center Rijeka, 51 000 Rijeka Radiol lugosl 1991 ; 25 :201 -4. GENERAL HOSPITAL OSIJEK CENTER OF ONCOLOGY ANO RADIOTHERAPY, DEPARTMENT OF RADIOLOGY A CASE OF SINCHRONOUS BILATERAL RENAL CELL CARCINOMA: ULTRASOUND, CT AND ANGIOGRAPHIC EVALUATION Kurber S, Filakovic Z, Rubin O Abstract -A case history of a patient with sinchronous bilateral renal celi carcinoma is presented. Diagnostic procedures are discussed briefly utlrasound, CT, and angiography proved to be complementary diagnostic modalities with their own limitations. UDC: 616.61-006.6-073.75 Key words: kidney neoplasms-radiography; carcinoma, renal celi Case report Radiol lugosl 1991; 25:205-9. lntroduction -Recently, we had a case of a patient with sinchronous bilateral renal celi carci­noma as a diagnostic problem. The ultrasound finding of bilateral but not similar massive kidney lesions has forced us to be very cautious with temporary diagnosis. We belive that this rare case is worth presen­ ting. Case history -A 63 year old male patient T.J. was admitted to the Glinic of Interna! Medici­ne, Department of Hematology, General Hospital Osijek. He suffered myocardial infarction 5 years ago. Since then he had non serious hearth troubles except moderate hypertension. Two years ago he was hospitalised in another hospital because of anemia, accelerated sedimentation rate and unexplained fever, but no serious di­sease was revealed at that tirne. He had no documentation of previous abdominal radiologic or ultrasound examinations. The reason tor admittance to the hospital was blunt subcostal pain in the right side of the abdomen lasting for three weeks. Short periods of fever were present almost every afternoon reaching up to 38.5 ° C. He felt weak and had slight nausea with occasional vomiting. No car­diac, respiratory or urinary symptoms were no­ted. Stool was normal. Weight loss was 5 kg in 3 weeks. A short treatment with peroral antibiotics did not improve his condition. Some important laboratory values were alte­red: sedimentation rate (Westergreen) 80 mm/h, RBC 4.19x1012/L hemoglobin 97 g/L, Fe 3.7 µ,mol/L, WBC 34x109/L with 23% of band neu­trophils. Urine finding was normal without eryt­hrocytes in urine sediment. Abdominal ultrasound examination was per­formed using SONEL 3000, a mechanical sector ultrasound unit produced by CGR, France. Ultra­sound probes of 3 and 5 MHz were used. During the abdominal ultrasound examination no important changes were found in the liver, biliary ducts, gallbladder, pancreas and spleen. The upper lobe of the right kidney was occupied by an oval, well delineated zone measuring 7x5 cm (Fig. 1 and 2). The zone was slightly hyperec­hogenic when compared to the neighbouring renal tissue. Nume.rous small hypoechogenic spots rendered the image to appear «dirty». Accor­ding to the categorisation of the renal focal lesions proposed by Weill and colleagueas (1 ), the lesion was classified as type 111, lacking ultrasound signs of calcifications. Although the lesion was close to the liver, it clearly belonged Recived: September 18, 1990 -Accepted: May 16, 1991 Kurbel S et al. A case of sinchronous bilateral renal cell carcinoma: ultrasound, CT and angiographic evaluation to the right kidney. The rest of the right kidney seemed normal. The lower pole of the opposite and otherwise normal left kidney was covered with a dense hyperechogenic zone, forming a cap that contai­ned two smooth and fully sonolucent cysts (Fig. 3 and 4). The bigger echo-free area was 3 to 4 cm in diameter. The ultrasound image of the left kidney lesion was similar to type V according to Weill, although the cystic areas were smoothly delineated and did not seem to be necrotic. This was a fully different ultrasonic image. Far the difference from the lesion in the right kidney, this was a fully different ultrasonic image. The findings of the abdominal ultrasound examination were conclusive far the presence of a large expansive process in the right kidney. Cystic lesion in the left lower lobe of the kidney was considered as a probable another tumor. Abdominal CT examination was recommended. Computed tomography excrtnination was per­formed on SIEMENS DR-H scanner at our De­partment of Radiology, two days later. Tumor of the right kidney was found to originate from the ventral renal cortex at the level of the renal hilus with exophyfic spread in the ventral and cranial directions (Fig. 5 and .6). The liver appeared to be impressed by the tumor mass. Caudally, tumor spreaded to the level of the lower renal lobe leaving a narrow parenchymal bridge at the level of renal hilus as the only connection with the kidney. The rest of the tumor seemed well separated from the renal cortex. The tumor mass was of lesser density when compared to the normal renal tissue. Another smaller tumor of similar CT characte­ristics was found in the lower lobe of the left kidney. It contained a larger regular zone resem­bling a cyst. No signs of tumor calcifications were found. Renal veins seemed uninvolved. A small Fig. 1 and 2 -Right subcostal and coronar approach to the large hyperechoaenic lesion in the upper lobe of the right kidney. Notice the small dark areas suggesting the spots of necrosis. Fig. 3 and 4 -Coronar (Fig. 3) and dorsal (Fig. 4) approach to the smaller cystic tumor in the lower lobe of the left kidney. Radiol lugosl 1991 ; 25 :205-9. Kurbel S et al. A case of sinchronous bilateral renal cell carcinoma: ultrasound, CT and angiographic evaluation Fig. 5 and 6 -CT slices showing bilateral kidney tumors together with a metastatic lesion in the ventral part of the abdomen. Fig. 7 and 8 -CT slices after contrast application. Notice iregular tumor opacity. oval lesion of similar density was visible in the ventral part of the abdomen. Twenty seconds after the contrast applica­tion, necrotic tumor centers showed no signs ot opacification while the peripheral zone became highly opacified (Fig. 7 and 8). The border bet­ween two zones was fully irregular. The upper part of the tumor showed no clear distinction toward the liver. It was fully surrounded by liver tissue suggesting liver infiltration. Prescheduled static renal scintigraphy sho­wed diffuse cortical reduction of the right kidney with no signs of focal lesions. The left kidney was described as smaller because the lower lobe was not visualised. Previously planned uro­graphy was considered unnecessary and was therefore omitted. It was decided than angiograp­ hic procedures should be proceeded. Angiographic evaluation started with general abdominal aortography followed by the seleciive left and right renal angiographies and selective celiac axis angiography. Seldinger technique was used with Telebrix 380 and 300 as c_ontrast media. Selective right renal angiography showed a well delineated hypervascular tumor 14 x 1 O cm in the upper half of the right kidney. Numerous pathological blood vessels, irregular lakes of contrast and wide capsular arteries were noted. Left renal angiography showed scarce pathologi­cal vascularisation with few fine capsular arteries in the lower kidney pole. Late angiographic phase showed no tumor-like opacification. Both sides showed no signs of early venous drainage or pathological changes of the renal veins. Selective celiac axis angiography revealed no signs of pathological vascularisation of the right liver lobe. After all findings were put together, ultra­sound guided puncture of the larger and presu­mably malignant right kidney lesion was recom­mended on our radiological and oncological mee- Radiol lugosl 1991; 25 :205-9. Kurbel S et al. A case of sinchronous bilateral renal cell carcinoma: ultrasound, CT and angiographic evaluation tings. The patient preferred surgery and was transferred to the Department of Urology. Total right and partial left nephrectomies were performed in a single act. Hystopathologically, both kidney tumors and a small abdominal focal lesion were renal celi carcinomas. Discussion -Sinchronous renal celi carci­noma (SRCC) is usally regarded as extremely rare. SRCC and not-simultaneous or metachro­nous renal celi carcinoma (MRCC) are estimated to occur in 2 to 4 % of all renal celi carcinoma patients (2). One of the largest studies included 11 patients with bilateral renal neoplasms, six of them proven SRCC cases (2). Two patients out of 7 cases of bilateral renal tumors were renal carcinoma patients, both MRCC type (3). The post mortem studies revealed much higher per­centages (4, 5). When comparing diagnoshc tools used to evaluate 99 focal kidney lesions (37 cysts and 56 carcinomas) ultrasound proved to be exact in 88%, CT in 96 % and selective angiography in 84% (6). Diagnostic modalities can and should be used complementary to solve complicated cases. Fig. 9 and 1 O -Right and left kidney selective angio­graphies. In the presented case, the first approach to the patient with nonspecific symptoms was made by abdominal ultrasound. It revealed a puzzling finding of bilateral massive kidney lesions that appeared ultrasonically different. It was followed by CT and angiography. Conventional urography was not done in the first place, because the patient had no signs of urinary troubles. Differences between the tumors were obvious also on angiography. It verified the presence of a large hypervascular right kidney tumor, whe­reas the left kidney lesion finding was dubious because of extreme hypovascularity. On the contrary, both tumors showed very similar, if not identical CT characteristics (appearance, densi­ty, contrast opacity. An abdominal metastasis was found only by CT. Another valuable CT information was the irregular shape of te right kidney tumor necrotic zones. It was strongly consistent with tumor and not with an inflamma­tory process, although the clinical symptoms could be misleading. CT misguided us when it appeared that the right liver lobe was infiltrated by the tumor mass. Celiac axis angiography was normal and surgeons found that the intact liver capsule was only impressed by the kidney tumor. It can be concluded that although ultrasound screening in our patient pathed the way towards the final diagnosis, CT, within its limits, proved to be the most useful when comparing two lesions and estimating the extent of disease. Cases of SRCC and MRCC are usually un­derstood as an early or late metastasis in the opposite kidney (1,2,8). It is difficult or often impossible to distinguish bilateral primary tumors from a contralateral metastatic tumor. In the presented case, we were unable to solve this Radiol lugosl 1991; 25:205-9. Kurbel S et al. A case of sinchronous bilateral renal ceil carcinoma: ultrasound, CT and angiographic evaluation problem. Both lesions might have been the pri­mary tumors. The greater right kidney tumor with dominant necrotic areas did ·not contain cysts. In the smaller and cystic tumor of the left kidney necrotic areas were not so abundant. The first three criteria proposed by Hyman et al (9) to identify primary bilateral kidney tumor were fulfil­led. Both tumors seemed simulataneous and each kidney contained only one encapsulated tumor. But, histologically both tumors were simi­lar, thus suggesting to be of the same origin. Sažetak ISTOVREMENJ OBOSTRANI KARCINOM BUBREGA EVALUIRAN SA UZ, CT i ANGIOGRAFSKI Prikazan je bolesnik s istovremenim obostranim karcinomom bubrega. Kompjuterizirana tomografija, angiografija i ultrazvuk su se pokazale komplementar­nim dijagnostickim modalitetima sa sopstvenim ograni­cenjima. References 1. Weill FS, Bihr E, Rohmer P, Zeltner F. Renal Sonography. (2nd ed.) Berlin; Springer Verlag, 1986;83­102. 2. Stigsson L, Ekelund L, Karp W. Bilateral concur­rent renal neoplasms: Report of eleven cases. AJR 1979;132:37-42. 3. Radanovic B, Šimunic S, Agbaba M, cavka K, Stojanovic J, Mrazovac D. Bilateralni renalni tumori. Radiol lugosl 1987;21 :431-5. 4. Bastable JRG. Bilateral carcinoma of the kidney. Br J. Urol 1960;32:60-8. 5. Hajdu SI, Thomas AG. Renal celi carcinoma at autopsy. J Urol 1967;97:978-82. 6. Holmberg G, Hietala S, Hietala O, Ljunberg B. A comparison of radiologic methods in the diagnosis of renal mass lesions. Scand J Urol Nephrol 1988;22:187­93. 7. Golt H, Whaley MH. Bilateral renal celi carcino­ma. Am Farm Phys 1988;37:121-5. 8. Picciocchi A, D'Ugo D, Bruni V, Lemmo G. L'adenocarcinome nephrocellulaire bilateral synchrone traitement chirurgical en un seul temps. J Urol (Paris) 1987;93:517-21. 9. Hyman RA, Voges V, Finby N. Bilateral hyper­nephroma. AJR 1973;117:104-7. Author's adress: dr. Sven Kurbel, mr se., Opca bolnica Osijek, Centar za onkologiju i radioterapiju, Huttlerova 4, 54000 Osijek. TOSAMA Proizvaja in nudi kvalitetne izdelke: Komprese vseh vrst Gazo sterilno in nesterilno Elasticne ovoje Virfix mrežo Micropore obliže Obliže vseh vrst Gypsona in mavcene ovoje Sanitetno vato PhJ III Zdravniške maske in kape Sanitetne torbice in omarice Avtomobilske apoteke Radiol lugosl 1991; 25:205-9. == =l.le1vetius MEDICAL SUPPLIES DISTRIBUTOR OF THE 3M Trimax film/screen The highest quality radiographic imaging with reduced X-ray dose levels by as much as 90% compared to ordinary systems. The JC emulsion (J band and Gubic Grain) uses the newest 3M "anticrossover" technology guaranting high definition and high speed far an improved image quality. 1986 Film Trimax XD/A, XL/A "anticrossover" JC 34132 TRIESTE -ITAL Y -Piazza Liberta, 3 -Phone 040/65577 ·-Tlx 461109 HEL TS-1 From practice for practice FROM PRACTICE FOR PRACTICE CARDIOVASCULAR SYSTEM Case 3 What is this investigation? What abnormalities does it show? What further investigation(s) would you perform? What therapeutic options are available to deal with the main abr:iormality shown? Fig. 1a For answers see page 240 Radiol lugosl 1991; 25:211. !:SJ\NOLJ\BOR Izvozno uvozno podjetje za promet z medicinskimi instrumenti, aparati, opremo za bolnice, laboratorije in lekarne Predstavništvo: LJUBLJANA, Cigaletova 9 ZAGREB, Šulekova 12 Telefon: (061) 317-355 Telefon: (041) 233-369 Telex: 31-668 sanlab yu Telefax: (041) 228-298 Telefax: 325-395 Iz prodajnega programa trgovine na debelo nudimo široko izbiro domacega in uvoženega blaga po konkurencnih cenah in sicer: -rentgenske filme in kemikalije proizvajalcev »Fotokemika« , »KODAK«, »3. M -TRIMAX«, »AGFA GEVAERT« in drugih ter kontrastna sredstva firme »NICHOLAC« , -medicinske instrumente, specialno medicinsko in sanitetno blago, potrošno blago za enkratno uporabo, -medicinske aparate in rezervne dele zanje ter bolniško in drugo opremo, -tekstilne izdelke, konfekcijo in obutev za potrebe zdravstvenih, proizvodnih in varstvenih organizacij, -laboratorijske aparate, opremo, laboratorijsko steklovino, reagente, kemikalije in pribor, -aparate, instrumente in potrošno blago za zobozdravstvo. V prodajalni na Cigaletovi 9 v Ljubljani prodajamo izdelke iz asortimana trgovine na debelo, s posebnim poudarkom na blagu za zobozdravstvo, nego bolnikov, ortopedskih pripomockih in ostalemu blagu za široko potrošnjo. UNIVERSITY HOSPITAL »OR. MLADEN STOJANOVIC«, ZAGREB DEPARTMENT OF NUCLEAR MEDICINE ANO ONCOLOGY MODEL FOR COMPUTER SIMULATION OF MULTIPINHOLE THALLIUM-201 HEART IMAGING Lokner V Abstract -Seven pinhole collimator was modeled as a simple non-multiplexed form of multipinhole imaging system. The aim of modeling is computer simulation of imaging and generation of artificial images that can be used tor controlled testing of image processing algorithms as well as optimization of parameters. For thallium-201 heart imaging, physical model is described as well as corresponding mathematical model used as forma! framework tor computer implementation. The image generator works with the heart-phantom, simulating formation of no-noise image. Poisson noise is added to the image la ter on. The image normalized to 100 counts/pixel maximum and 620,000 total counts was gene"rated with the average signal to noise ratio of 6. lmage frequency properties are identical to those found on standard clinical nuclear medicine images. Further application of modeling on various types of apertures and/or objects is possible as well as addition of other image degrading mechanism. UDK: 616.12-073 :539.163(086.5) Key words: heart-radionuclide imaging; image processing, computer-assisted Orig sci paper Radlol lugosl 1991 ; 25 :213-8. lntroduction -Nuclear medicine (NM) ima­ges are of poor quality and therefore difficult for clinical interpretation due to deficient resolution and insufficient contrast discrimination. Main sources of image degradation are blur and Pois­son type of noise. Diagnostic assessment from clinically obtained NM images could be improved via image processing (1 ). There is no unique way for quality upgrade through image enhancement or restoration. Various design strategies for pro­cessing algorithms were tested and increase of detectability and contrast discrimination verified by receiver operated characteristics (ROG) was reported (2-5). However, proficiency testing of different numerical techniques for processing and their computer implementation is indicated and related to arbitrary definitions of optimality. Our study is focused on the model formulation for simple NM imaging system. The aim of modeling is computer simulation of imaging and generation of artificial images that can be used for controlled testing of processing algorithms as well as optimization of parameters. Such a model as well as corresponding simulated images are especially needed if noise suppression techni­ques are investigated. Seven pinhole (7P) collimator with standard large field of view (LFOV) gamma camera is chosen to be modeled as non-multiplexed form of multipinhole imaging system (6-8). Physical model of thallium-201 heart imaging is described as well as corresponding mathematical model used as formal framework for computer imple­mentation of image generator. Physical model of imaging (Theory) -In nuclear medicine the object (spatial distribution of radionuclide) and the image is complex and non-linear due to stohastic properties of decay process, absorption and scatter through the body and intrinsic non-linearity of detector. Linear mo­del of imaging could be constructed as useful approximation of such a system. Under certain imaging conditions (e.g. gamma camera count rate less then 50K counts/s (9) and with some supplementary assumptions, linearity supposi­tion is justified. We postulate that: • object is a source of isotropic and tirne stationary radiation with so small a wavelength that physical optics phenomena (e.g. diffraction) are disregarded; • noise is related to stohastic processes and of Poisson type; Received .April 15, 1991 -Accepted: May 9, 1991. Lokner V. .odel for computer simulation of multipinhole thallium-201 heart imaging • absorption is continuous and with known (PSF) for such systems is quite simple but absorption coefficient; there is no scattered ra­neveretheless, since pinhole systems are space diation; variant, full knowledge of TF is stili needed. lf the • aperture plate is ideally thin with zero object size is small compared to the aperture pla­ne/detector plane distance, and/or the pinhole si­ nings; ze is small, so that T(x,y; x',y',z') = T(x-x',y-y'; z'), • detector is ideally linear and uniform, with Since Poisson noise is additive and of con­stant mean value (1 O), modeling could be sepa­rated in two steps: in the first one, blurring model will be considered; in the second, model of direct noise addition to the image will be introduced. BI ur ring .mode 1 : Blur is limited to geo­metry distortion only so that linear deterministic model of imaging is: l{x,y) = f T(x,y,x' ,y' ,z') O(x' ,y' ,z') d(x' ,y' ,z') [1] 00 where (x,y) are the detector plane coordinates; (x' ,y' ,z') are the spatial coordinates above the aperture plane; 1( ... ) is the image; T( ... ) is the system transfer function (TF); O( ... ) is the object function. Eq (1] is stili far too complicated for practical purposes. In order to calculate image, full specification of TF is needed. Since this is not readily available, further approximations are ne­cessary. lmaging models could be solved only individually, using supplementary, problem speci­fic, simplifications. We will bound our interest to a special case of multipinhole apertures. Point spread function K MK f1Vk the system could be considered as isoplanatic or shift invariant for limited areas (1 ). For such isoplanatic patches, eq (1] could be transformed into convolution integral and the model of ima­ging simplified considerably. lf the object slice is !aken parallel with the aperture plane, and then projected through the center of a pinhole onto the detector plane, the sharpest possible image is formed to which we will give a special name -zerohole projection. The image of an object through aperture of finite (nonzero) dimension could be understood as being an integral over all slice images, which are zero-hole projections of particular slices convoluted with corresponding PSF. Computer implementation requires that conti­nuous form of model equations should be adop­ted. We will outline here only the ideas of discrete description of the imaging system. Half-space above the aperture, plane is divided into parallel slices which are subdivided into voxels. It is assumed that all the activity is concentrated in the center of the voxel. Since our interest is bounded to the limited pari of the space, there are K slices only, each of them with a total of MK voxels. The image is a square matrix divided into pixels. Eq.[1] in a discrete form reads (1 ). Z 2 k=1 m=1 k (x,y) are the coordinates in the center of a pixel; (xmk,Ymkl are the center of the m-th voxel, the k-th slice coordinates, zk from the surface of the detector; P is the pixel area; /1 V k is the voxel volume; O(xmk,Ymk) is the emission function; A(xmk,Ymk; x,y) is the aperture function; l(x,y)=P L L --O(Xmk, Ymk) A(Xmk, Ymk,x,y) cos3 O(xmk, Ymk; x,y). [2] described model, one of the image generation algorithms is: • for a given s lice, choose a voxel; find pixels where geometrically defined rays (center of the voxel/centers of the pinholes) intersect with the detector plane; add corresponding values of the O(xmk,Ymk;x,y) is the angle between voxel to pixel ray and system axis. lf imaging is non-multiple­xing and small enough to be considered as • next voxel; isoplanatic, we can recognize !hal all the rays contributing to one image pixel, pass through the same pinhole, so that to a good aproximation, O(xmk,Ymk; x,y) = O(x,y). Nearly shift invariant multipinhole imaging system could be transfor­med to exactly shift invariant system by scalar cos3 O( .. ) scaling of the image matrix. For the 214 • if all the voxels in a slice are projected, the zero-hole image of the s lice is generated; add this image to the zero-hole projection image matrix; calculate PSF for the slice; make fast Fourier transforms (FFT) of the zero-hole image of the slice and PSI"; multiply them to perform convolution and with inverse FFT return the Radiol lug osl 1991; 25:213-8. , result to the spatial domain; add the transform to the image matrix; • next sfice; • using cos3 O(x,y) scaling adjust tl:le image to shift-variant conditions. No ise ge nerator: Since noise is Pois­son c;listributed, additive, with a constant variance and uncorrelated to the object (1 O), noise addt­tion to the image could be done on a pixel by pixel basis. Poisson random number generator produces series of values having the initial pixel intensity taken to be the mean of distribution (12). Different image npise levels are regulated by predefined range around the mean, using variance as measure; for a given pixel, a se­quence of random numbers is repeated until one is found laying inside the given limits. Signal to noise ratio (SNR) is the local (pixel) property for all NM images. Describing the image as a whole, SNR could only be approximated as the mean noise level being equal to the sqaure root from the pixel mean value, in accordance with the definition. Mo del parameters and simulation -7P collimator was chosen to be modeled as a simple non-multiplexed form of a multipinhole imaging system. Syst em geom etry: The aperture plane is parallel with the detector surface wh'ich is circular having 380 mm effective diameter. The distance between the detector plane and the aperture plane is 127 mm. Seven circular pinho­les (7 mm diameter) are arranged in hexagonal pattern in such a way that system axes coincide with one pinhole, while 6 of them are circularly distributed on a 63.5 mm distance. The seven object projections are non-overlapping owing to the septa placed the between adjacent pinholes. Pixels and voxel : AII the images in this study are represented with a 128x128 matrix so that every pixel coers 3x3 mm2 .of the detector surface. AII voxels are having equal base 2x2 mm2 and increasing slice and voxel height from 4 to 16 mm, depending on Zk . Phantom object: Hollow half-ellipsoid represents a heart-like object (Fig. 1 ). The phan­tom object is placed above the central pinhole in such a way that object's long axes coincide with the system axes (Fig. 2). The body contour is simulated with the oblique plane that makes 15° and 30° angles with x and y axes, respectively. AII body voxels (voxels inside body contour) are emitting in accordance with heart tissue/surroun­ding tissue and heart tissue/blood ratios that are Radiol lugosl 1991; 25:213-8. Fig. 1 -Two half-ellipsoids, one inside another with the coinciding long axes, were used as outside and inside surfaces of numerical heart-phantom: long axes are 105 mm and 120 mm; both short axes are equal, and 25 mm and 45 mm, respectively. approximately 3:1 for thallium-201 in equilibrium few minutes after injection (13). Assuming homo­geneous tissue, for Ey -;; 167 keV, absorption coefficient for water µ = 0.02 cm-1 was used. For voxels more than 332 mm above the detector surface, absorption is so high that their effect on the image could be wholly disregarded. AII the rays originating in a particular voxel and passing through a given pinhole are equally absorbed. Data ge neration: Simulation was done using IMB-3083--JX1. Programmes were written on FORTRAN utilizing IMSL library for FFT routi­nes. For a single image 2.5 x 109 operations 128x128 matrix are needed. With 2 MIPS, the generation of a single image takes iO min of processor tirne. Resul ts -Simulated heart-phantom image was normalized to 100 counts/pixel maximum, resulting in -::c· 620,000 total counts that is the standard value for clinical images of the same type. The image contains 7 object projections (Fig. 3). Pixel values in the part of the image matrix outside 7 projections of pencil shaped simultaneous field of view (SFOV) were intentio­ nally set to zero. This part of the image contains incomplete information on object space voxels. Two variances widths was used as a bounding criterion of acceptable values for noise generator dissipation. Total number of counts on the image, after random noise generator, changed for less than 0.08%, proving that noise model is correct z :-;/ Fig. 2 -A cut through model: 7 pinhole collimator is indicated with positions of three visible pinholes; the heart phantom is placed along the system axes, inside SFOV, with it's top 332 mm above the detector plane; shaded area represents body tissue absorbing medium with lower thallium-201 concentration. -. . ··,_. •. ?\ . . J '\7 „ -;; Fig. 3 -The artificial heart phantom image without noise: 7 different heart projections are visible after background has been subtracted to stress the differen­ ces in absorption due to the oblique body contour. and that random noise generator was working appropriately. With approximately 60 counts per non-zero pixel, image average SNA is :::: 6 (Fig. 4). lmage spectral properties were analyzed in the frequency space. For that purpose the addi­tional im.age was calculated as a pixel by pixel difference of two matrices: one geometrically degraded without noise and a corresponding one with randomly added noise. After 2D Fourier transformation of all three images, their symme­trical power spectrum was calculated. In order to compensate for local fluctuations, 2D power spectra was compressed to 1 D by averaging in frequency domain over annuli (average of all the values with the same frequency vector). The results are plotted in Fig. 5. AII the power spec­trum properties are similar to those reported earlier for clinical images of different object and total number of counts (2,3). Discussion -A practical model of multipin­hole imaging could be constructed, computer implemented and used in simulation studies to Radiol lugosl 1991; 25:213-8. <::;., Fig. 4-(a) Pseudo the 3D display of the simulated image in Fig. 3. z-axes represents the number of counts in pixel. ·c The background is visible. (b) Same image after Poisson noise was added. , o.s frequency (cycles/pixel) Fig. 5 -Normalized power spectrums for three imaQes of the heart phantom: (a) the simulated image (image); (b) same image with added Poisson noise so that average SNR ""' 6 (image+noise); (c) image-formed as difference between the first two images (noise). The power spectrums are »compressed« to one d1mension by averaging over annuli in the frequency domain. The noise amplitude is having constant value over all frequef1cies. Radiol lugosl 1991 ; 25 :213-8. Lokner V. Model for computer simulation of multipinhole thallium-201 heart imaging generate sets of images. Artificial images meet frequency properties found on standard clinical images of the same type. The ease of imag.e generation control through parameter changes make such models convenient for image proces­sing studies because of possibility to tailor the structure of the image to a particular task, either through simulation of sharp (zero-hole projection) images, noise free images or ir'nages with con­trolled level of Poisson noise. By the same token, various numerical experiments could be perfor­med on the heart-phantom by simulating regional perfusion distrubances of different sizes. lmage analyses could be used for testing relation bet­ween location and size of low thallium-201 intake and corresponding changes (defect resolution) on simulated image. Also, some new types of phantom objects (e.g. thyroid) or degrading mec­hanisms (e.g. Compton scattering) could be in­corporated to basic model. Modeling and simula­tion approach 1:Jemonstrated in this work offers more posibilities than previously used low-pass filtering and scaling of measured high total count rate images of phantoms (3). Acknowledgement -Simulation studies were done at the Department for Mathematics and lnformatics, Technical University in Delft, The Netherlands. The stay was supported by IAEA. Sažetak MODEL ZA KOMPJUTERSKU SIMULACIJU MUL TI­PINHOL OSLIKAVANJA SRCANOG MIŠICA TALI­JEM-201 Sedam pinhole kolimator je modeliran kao jednosta­van oblik sustava za oslikavanje bez prekrivanja projek­cija. Cilj modeliranja je racunarska simulacija oslikava­nja generiranjem umjetnih slika koje se mogu koristiti za kontrolirano testiranje algoritama za obradu slike kao i optimizaciju parametara. Za oslikavanje srcanog mišica s talijem-201 opisan je fizikalni model kao i njemu odgovarajuci matematicki model koji se koristi kao formalni okvir implementacije na racunaru. Genera­tor slika radi sa fantom-objektom oblika srcanog mišica simuliraju.ci formiranje slike bez šuma. Poissonov šum je kasni je dodan slici. Slika je normalizirana maksimum od 100 impulsa/pikslu tako da ima 620,000 impulsa ukupno sa prosjecnim omjerom signala i šuma koji iznosi 6. Frekvencijska svojstva slike su identicna onima koja se nalaze na standardnim klinickim slikama u nuklearnoj medicini. Moguca je daljnja primjena modeliranja na razlicite tipove apertura i/ili objekata kao i ukljucivanje drugih mehanizama degradacije slike. References 1. Barret HH, Swindell W. Radiological lmaging: Theory of lmage Formation, Detection find Processing. New York: Academic Press, 1981. 2. King MA, Doherty PW, Schwinger RB, Jacobs DA, Kidder RE, Miller TR. Fast count-dependent digital filtering of nuclear medicine images: Concise communi­cation. J Nuc Med 1983; 24 :1039-45. 3. King MA, Doherty PW, Schwinger RB. A Wiener filter for nuclear medicine images. Med Phys 1983; 10:876-80. 4. Maeda J, Murata K. Digital restoration of scinti­graphic images by a two-step procedure. IEEE Trans Med lmaging 1987; Ml-6:320-4. 5. Fuderer M. Optimal non-linear filters for images with non-gaussian differential distributions. In: Vierge­ver MA and Todd-Pokropek A eds. Mathematics and Computer Science in Medica! lmaging. Berlin: Springer 1988; 517-25. 6. Vogel RA, Kirch DL, LeFree MT, Steel PP. A new method of multiplanar emission tomography using a seven pinhole collimator and an Anger scintillation camera, J Nucl Med 1978; 19 :648-54. 7. LeFree MT, Vogel RA, Kirch DL, Steele PP. Seven pinhole tomography -A technical description. J Nucl Med 1981; 22:48-54. 8. Viergever MA, Vreugdenhil E, Van Giessen JW. Mathematical description of seven pinhole tomography, Delft Progr Rep 1983; 8:311-21. 9. Todd-Pokropek A. lmage processing in nuclear medicine. IEEE Trans NS 1980; NS-27: 1080-94. 1 O. Goodman JW, Belsher JF. Fundamental limita­tions in linear invariant restoration of atmospherically degraded images. In: lmaging Through the Atmosphe­re. SPIE Vol 75. Society of Photo-Optical lnstrumenta­tion Engineers 1976; 141-54. 11. Van Giessen JW, Viergever MA, De Graaf CN. lmproved Tomographic Reconstruction in Seven-Pin­hole lmaging. IEEE Trans Ml 1985; Ml-4: 91-103. 12. Press WH, Flannery BP, Teukolsky SA, Vetter­ling WT. Numerical Recipes: The Art of Scientific Computing. Cambridge: Cambridge University Press, 1987. 13. Wackers FJ. Myocardial Perfusion lmaging. In: Gottschalk A, Hoffer PB, Potchen EJ eds. Diagnostic Nuclear Medicine. Vol 1. Baltimore: Williams&Wilkins, 1988; 291-354. Author's address: Dr. Vladimir Lokner, Department of Nuclear Medicine and Oncology, University Hospital »Dr. Mladen Stojanovic«, Vinogradska c 29, Zagreb Radio! lugosl 1991 ; 25 :213-8. UNIVERSITY DEPARTMENT OF OTORHINOLARYNGOLOGY ANO CERVICOFACIAL SURGERY 1 UNIVERSITY DEPARTMENT FOR PLASTIC SURGERY ANO BURNS2 UNIVERSITY CLINICAL CENTRE, LJUBLJANA MICROVASCULAR FREE FLAPS IN RECONSTRUCTION AFTER ABLATIVE SURGERY OF HEADANDNECKTUMORS Šmid L 1 , Žargi M 1 , Župevc A 1 , Arnež Z2 Abstract -In the reconstructions after extensive ablative surgery for head and neck carcinomas microvascular free flaps (MFF) have shown several advantages over pedicled flaps, particularly in preop.eratively irradiated patients, and therefore they represent the method of choice in this type of surgery. During the years 1985-1990, MFF were used in 28 patients treated at the University Department of Otorhinolaryngology and Cervicofacial Surgery in Ljubljana; of these, 10 had recurrent carcinoma of the facial skin, and 18 carcinoma of the oral cavity and oropharynx. Reconstruction of the mandible was performed in 5 patients with carcinoma of the floor of the mouth, in two cases by mec1,ns of an osteocutaneous flap of the iliac crest, whereas in another two a radial forearm flap and in one case a scapular flap were used. For reconstruction of the skin or mucosa radial forearm flaps were used most frequently, bul apart from these, upper forearm flap and latissirrius dorsi flap were used as well. As to the duration of surgery, hospitalization tirne and the rale of complications, our results are comparable with those reported in the literature. UDC: 616-006.6-089:617.51 :617.53 Key words: head and neck neoplasms-surgery;surgical flaps Orig sci paper Radiol lugosl 1991; 25:219-24. lntroduction -The treatment success in advanced head and neck tumors is greatly de­pendent on the extent of excision with convincing safety margins, which is primarily influenced by the possibility of related defect reconstruction. In comparison with other sites, extensive ablative surgical interventions in head and neck tumors result in more severe cosmetic and functional deformities. The ideal method of reconstruction of defect in this area should be a reliable and final one; with respect to the specificity of the treated site, it should offer a wide range of possibilities to achieve the optimum functional and cosmetic results. Of the numerous procedu­res available, the microvascular free tissue tran­sfer most closely complied with the above requi­rements. After the initial laboratory experiments perfor­med already in 1908 by Carrel (1 ), this surgical technique had been abandoned all until the 70's when it was again brought to attention. The first report on a successful microvascular skin tran­sfer was published in 1973 by Taylor and Daniel (2). The intraoral use of free skin flaps was introduced by Panje et al in 1976 (3) and Ackland and Flynn in 1978 (4), whereas the first mandibu­lar microvascular reconstruction was reported in 1977 by Serafin et al (5); in 1983 excellent results obtained by the use of radial forearm flap were reported by Soutar et al. (6). At the Univer­sity Clinical Center in Ljubljana the routine use of microvascular surgical technique was started in 1975 by Godina (7). In the last two decades, several different flaps have been introduced tor microvascular transfer. The selection of flap depends on the tissue to be substituted, e.g. the skin or mucosa alone, or deeper defects should be reconstructed including a missing bone. So, groin flap, dorsalis pedis flap, latissimus dorsi flap, scapular flap, radial forearm flap and lateral upper arm flap have been introduced tor skin and mucosa repla­cement, whereas rib, iliac, scapular, metatarsal, as well as radial and lateral upper arm flap are used in osteomyocutaneous reconstructions (.)­ Clinical data -In the years 1985-1990, reconstruction of extensive defects after ablative surgery of head and neck carcinomas by means of microvascular free flap (MFF) was performed in 28 patients treated at the University Depar­tment of Otorhinolaryngology and Cervicofacial Surgery in Ljubljana. Selection of MFF tor various recipient areas is presented in Table 1. Received: June 5, 1991 -Accepted: June 14, 1991 Šmid L et al. Microvascular free fl<1ps in reconstruction afler ablative surgery of head and neck tumors Table 1 -Selection of flaps for reconstruction of deffects after ablative cancer surgery in patients, trea­ted at University Department of Otorhinolaryngology and Cervico-Facial Surgery in Ljubljana in the years 1986-1990 Recipient area Facial Oral Pharynx Tota! Selected skin cavity flaps Radia! forearm flap 7 7 5 days respectively. Lateral upper arm flap 3 4 Latissimus dorsi flap 2 2 lliac osteocutaneous 2 2 flap Scapular osteocutaneous ­flap TOTAL 10 11 7 28 Ali 1 O patients with facial skin carcinoma had recurrent disease after previous unsuccessful surgery and/or radio-therapy performed in other institutions. Besides an extensive cutaneous and subcutaneous tissue excision, 4 patients also underwent exenteration of the orbit, whereas 2 had simultaneous ethmoidectomy and 3 patients had partial resection of the nose due to tumor invasion into the nasal cavity. Facial artery and vein were used as recipient vessels in 7 cases, and· in 3 flaps the anastomoses were performed with superficial temporal vessels. AII except four patients with carcinoma of the oral cavity and oropharynx, in whom the treat­ment was a primary one, had recurrent disease after previous surgery and/or radio-therapy. The decision for reconstruction of the mandible with an osteomyocutaneous flap was made in 5 pa­tients with carcinoma of the floor of the mouth. Osteocutaneous flap of the iliac crest was used in two cases, a radial forearm flap in another two, and a scapular flap in one case. For microvascu­lar anastomoses the superior thyroid artery, lin­gual artery, facial artery, and the external or common carotid arteries were used as donor vessels; in the latter cases end-to-side technique was performed. Each surgery required cooperation of two teams: one for ablative head and neck procedure and the other for reconstructive plastic surgery. The duration of surgery ranged from 5 to 13 hours, mean 7.5 hours. The patients were hospi­talized for 17-64 days, mean duration of hospita­lization being 37 days. Flap necrosis occurred in two cases: in one patient with MFF of the iliac crest the non-viable transplant was removed after three weeks, whe­reas in the other one necrosis of the radial forearm flap used for pharyngeal reconstruction occurred on the second day after surgery; the defect was subsequently covered using a pedic­led pectoral myocutaneous flap. There were 2 miner oro-or pharyngocutaneous fistulas; these, however, healed spontaneously after 14 and 21 Discussion -The use of MFF in reconstruc­tion following ablative surgery of head and neck tumors has a considerable advantage over pedic­led flaps. Namely, the length and the width of the latter flap are limited, and its tip is frequently insufficiently vascularized since the distal part of a pedicled fl.p often reaches beyond the natural margins which stili receive satisfactory blood supply from the pertinent blood vessels. In con­trasi with that, MFF represents a central area of arterial and venous blood supply. MFF provides a sufficient amount of well vascularized tissue which renders reconstruction of practically every defect feasible. The very size of MFF frees ablative surgeons of the eternal dilemma how to remove the whole tumor with sufficient safety margin, i.e. in accordance with oncological princi­ples, and at the same tirne maintain the possibi­lity of having the deteci satisfactorily reconstruc­ted from both functional and aesthetic point of view. MFF also meets the most essential require­ment of presen! oncological surgery according to which the final reconstruction should be immedia­te, with a relatively short hospitalization tirne; ali this is of particular importance for patients with extensive malignomas of the head & neck region. The hospitalization tirne of our patients does not differ from that reported in the literature (4). On the other hand, we should be aware of certain drawbacks of MFF reconstruction. The surgical procedure is longlasting and requires specially skilled surgeons. In our interventions, generally, both surgical teams performed their work simultaneously, which explains shorter du­ration of surgery in c0.·:1parison with those repor­ted by other authors (8,9, 1 O, 11 ). It should be stressed that these operations require a micro­vascular surgeon who handles free-flap transfers in his routine clinical work to minimize the rate of complications and to shorten the duration of surgery (12). In the case of unsuccessful flap transplantation, the loss of MFF is complete in contrast to a pedic!ed flap where only its distal Radio! lugosl 1991 ; 25 :219-24. Šmid L et aL Microvascular free flaps in reconstruction after ablative surgery of head and neck tumors part is lost. Theretore the flap should be monito­red every hour during the first postoperative days to allow for immediate revision in case of throm­bosis of the vessels (7, 12). In our patients revi­sions were required in 4 cases of which 3 were successful. The decision which of the available MFF variants will be selected in a particular case depends on whether only a thin layer of lining is needed, or the flap should replace a bulk of tissue or even reconstruct a missing part of the bone. Last but not least, this decision is influen­ced also by the microsurgeon's skill and his preference for a particular flap type. It was mainly for the latter reason that of 21 flaps needed tor reconstruction of facial skin defect, part of the oral cavity and pharynx, in as many as 17 cases we chose the radial forearm flap instead of the lateral upper arm flap which is equally suitable tor reconstruction, but entails significantly less apparent mutilation of the donor site. We rarely performed reconstruction after seg­menta! mandibulectomy, believing that only re­section of the front part of the mandible repre­sents an absolute indication for reconstruction, due to the entailed surgery-related difficulties at swallowing and articulation as well as severe aesthetic sequels which the patient might find unacceptable. Namely, our experience, as well as that of other authors, show that the resection of the mandibular ramus in comparison with the resection of its frontal part does not cause exces­sive functional and cosmetic defects (11 ). Among the available combined osteomyocutaneous flaps those taken from the iliac crest, torearm and scapula were selected. Of the three, the latter flap appears most suitable due to excellent vascularization of the skin and bone, as well as due to great mobility of the skin from the related bone, which has given a very good result also in our patient (Fig. 1 ). The only drawback of this reconstruction method is in the long duration of surgery. Particularly in reconstruction of the man­dible, the technique of microvascular transfer proved most suitable since the percentage of successful reconstruction outcomes using osteo­myocutaneous pedicled flaps had not been satis­factory. Also the use of alloplastic implants has generally been disappointing; this applies spe­cially to irradiated tumor beds where sufficient vascularization of the transplant is of particular importance (9, 13, 14). Fig. 1 a -Patient with advanced carcinoma of the floor of the mouth infiltrating through the mandible into the skin End-to-end and end-to-side techniques tor anastomoses were used in almost equal propor­tion. Although, by some authors, the end-to-side technique is used only in exceptional cases when there are no branches of the carotid artery available, we have found this technique even more successful and by all means safer (12, 15). Our series of recurrent skin carcinomas points out again that, regardless seemingly limi­ted extent of tumor, the primary treatment of such malignomas should be carried out in accor­dance with all principles of oncological surgery. This is particularly true of prognostically unfavou­rable sites such as the nasal canthus and nasola­bial sulcus. Namely, the very recurrences of these sites, particularly in the cases of basocellu­lar carcinomas, may entail such severe mutila­tions as in our cases when exenteration of the orbit or removal of a large part of the nose was required (Fig. 2). The defect after excision is regularly larger than expected. Considering their atorementioned properties, this is also why mi­crovascular flaps in such reconstructions have significant advantages over other methods. Veri­fication of resection margins by frozen section method, which is routinely used in oncological surgery, should become part of regular practice not only in the surgery of extensive malignomas, Radiol lugosl 1991 ; 25 :219-24. Šmid L et al. Microvascular free flaps in reconstruction after ablative surgery of head and neck tumors Fig. 1 b -Deteci after excision of the anterior part of the Fig. 1 c -Dissected scapular osteocutaneous flap floor of the_ mouth together with symphysal segment of providing bone and the lining tor bolh, floor of the the mandible and adjacent skin mouth and skin // / /, : Fig. 1 d -Reconstruction of the anterior part of the floor of the mouth and mandible is followed by reconstruction of skin defect. Fig. 1 e -Patient one year after reconstruction with good cosmetic and functional result. 222 Radiol lugosl 1991: 25:219-24. Šmid L et al. Microvascular free flaps in reconstruction atter ablative surgery of head and neck tumors Fig. 2b -Extensive deteci after tumor excision after previous excision and radiotherapy. Fig. 2d -After completition of the vascular anastomosis to the facial artery and vein the flap is sutured into the deteci Conclusions -In the reconstruction surgery after ablation of head and neck malignomas MFF have proved to have so many advantages over Šmid L et al. Microvascular free flaps in reconstruction after ablative surgery of head and neck tumors Fig. 2e -Patient one year atter reconstruction pedicled flaps that they should be regarded as the method of choice in such surgical interven­tions. This applies particularly to recurrences after previous unsuccessful treatment, which re­quire reconstruction with an extremel1 well vas­cularized flap, and specially to bone nsplants in reconstruction of the mandible. Double-team approach using highly qualified surgeons shortens the duration of operations and results in a decreased rate of complications. References 1. Carrel A. Results of transplantation of blood vessels, organs and limbs. JAMA 1908; 5:1662-7. 2. Taylor GI, Daniel RK. The tace flap: composite tissue transfer by vascular anastomoses. Aust N Z J Surg 1973; 43:1-9. 3. Panje WR, Bardach J, Krause CJ. Reconstruc­tion of the oral cavity with a free flap. Plast Reconstr Surg 1976 ;58 :415-8. 4. Ackland RD, Flynn MB. l01mediate reconstruc­tion of oral cavity defects using microvascular free flaps. Am J Surg 1978;136:419-23. 5. Serafin D, Villareal-Rios A, Georgiade NG. A rib-containing free flap to reconstruct mandibular def­fects. Br J Plast Surg 1977; 30:263-6. 6. Soutar OS, Scheker LR, Tanner NSB, McGre­gor IA. The radial forearm flap:a versatile for intraoral reconstruction. Br J Plast Surg 1983; 36 :1-8. 7. Godina M. Preferential use of end to side arterial anastomoses in free flap transfer. Plast Re­constr Surg 1979; 64:673-82. 8. Ackland RD. Microvascular surgery for recons­truction of the head and neck. In: Ariyan S, ed. Cancer of the head and neck. St. Louis: The C V Mosby Company, 1987; 513-34. 9. Silverberg B, Banis JC, Ackland RD. Mandibu­lar reconstruction with microvascular bone transfer series of 10 patients. Am J Surg 1985; 150:440-6. 10. Soutar OS, McGregor IA. The radial forearm flap in intraoral reconstruction: The experience of 60 consecutive cases. Plast Reconstr Surg 1986;78:1-8. 11. Pech A, Zanaret M, Bardot J, Tort C, Cannoni M. Le transfer! osseux vascularise libre de crete iliaque dans la reconstruction mandibulaire. Rev Soc Fr ORL 1991 ;7:9-13. 12. Kambic V, Godina M, 2upevc A. Epithelialized microvascular iliac crest flap for reconstruction of sub­glottic and upper tracheal stenosis. A preliminary re­port. Am J Otolaryngol 1986; 7:157-62. 13. Sullivan MJ, Baker SR, Crompton R, Smith­Wheelock M. Free scapular osteocutaneous flap for mandibular reconstruction. Arch Otolaryngol Head Neck Surg 1989; 115:1334-40. 14. 2argi M. The radial forearm flap in mandibular reconstruction. In: Proceedings of 1 er Congres Euro­peen d'Oto-Rhino-Laryngologie et de Chirurgie Cer­vico-Faciale. Paris 1988:331. 15. Tomljanovic 2, Kovacevic M, Tic A, et al. Slobodni podlakticni režanj u rekonstrukciji defekata sluznice nosne šupljine i ždrijela nakon radikalnih odstranjenja tu mora. Chir Maxilofac Plast 1989; 19 :91­6. 16. Kambic V, Gale N, 2argi M. Pomen zaledene­lega reza za kirurško zdravljenje malignomov v otorino­laringologiji. Zdrav Vesin 1981; 50:83-6. Author's address: Dr Šmid L, Univerzitetna klinika za otorinolaringologijo UKC Ljubljana, Zaloška c. 2, 61105 Ljubljana. Radiol lugosl 1991 ; 25 :219-24. MILITARY MEDICAL ACADEMY INSTITUTE OF NUCLEAR MEDICINE1 , LUNG CLINIC2, BELGRADE COMPARISON OF TUMOR-ASSOCIATED TRVPSIN INHIBITOR (TATI) AND TISSUI! POLVPEPTIDE ANTIGEN (TPA) IN SERUM AND PLEURAL EFFUSION IN PATIENTS WITH LUNG DISEASES Lazarov A 1. Plavec G2, Odavic M1 . Dangubic V2, Koljevic A 1 Abstract -The concentration of tumor-associated trypsin inhibitor (TATI) was measured in serum and pleural effusion -in 70 patients wilh malignant and nonmalignant lung diseases. The levels of TATI were compared with serum leve! of TPA in the same groups. Serum and pleural effusion TATI levels were determined by the immunoradiometric assay, using a commercial kit SPECTRIA TATI (Farmos Diagnostica). The·levels of TPA were measured using the PROLIFIGEN TPA two-site immunoradiometric assay. Serum TATI and TPA levels were higher in malignanl Ihan in nonmalignant diseases. Concentrations of TATI in serum and pleural effusion showed a high correlation. Pleural effusion TPA was about 10-fold higher Ihan serum TPA in lhe same patients. Sensitivity, specificity and accuracy were satisfaclory tor both TATI and TPA. UDC: 616.24-006.6-079-097 Key words: lung diseases; tumor markers, biological; trypsin inhibitors Orig sci paper Radiol lugosl 1991; 25:225-8. lntroduction -Tumor markers are used to help in the diagnosis and monitoring of tumors. No marker with defined specificity and sensitivity for early prediction of metastases at a subclinical stage has been identified. A new marker which has been introduced recently, is tumor-associa­ted trypsin inhibitor (TATI). TATI is a small peptide (6000 dalton) which consists of 56 aminoacids and no carbohydrates. It has been isolated for the first tirne in the urine of women with ovarian carcinoma (1 ). High concentrations of TATI have been found in the urine of patients with gynaecological cancers (2), in the serum of patients with cancer of the pancreas and in those with chronic pancreatitis (3). High levels have been found in patients with cancer of the stomach and hepatoma (4). Very high levels of TATI also occured in the cyst fluid of patients with mucinous ovarian tumors (5). Tissue polypeptide antigen (TPA) is another potential marker in lung cancer. High sensitivity and specificity were obtained in 44 patients with tung cancer (6). TATI was compared with other tumors mar­kers (CEA, CA 19-9, CA 50 and elastase) in patients with various gastrointestinal disorders and elevated levels of those markers were reported (7). TATI was also compared with other tumor markers such as CA 15-3, CA 125 and CA 19-9 (5, 8) in ovarian cancer. 1 n this study the concentrations of TA TI were studied in serum and pleural effusion of patients with malignant and nonmalignant lung diseases. The levels of TATI were compared with serum levels of TPA in the same group of patients. Materials and methods -The study compri­sed 70 patients; 51 of them were with malignant and 19 with nonmalignant lung diseases (table 1 ). Their age ranged from 37 to 80 years, mean age being 58.8 years. Forty-two healthy blood donors served as a control group. AII patients with malignant and nonmalignant diseases were hospitalised in the Lung Glinic of the Military Medical Academy, Belgrade, Yugoslavia, during the 12-month period from January to December 1989. Sera obtained from blood samples of 70 patients were stored at -20°C until use. Spice­ments of pleural effusion from 27 patients were obtained by thoracocentesis. Serum and pleural-effusion TATI levels were determined by the immuno radiometric assay, using a commercial kit SPECTRIA TATI (Farmos Diagnostica, OULUNSALO, Finland). AII measu- Received: November 21, 1990 -Accepted: July 8, 1991. Lazarov A et al. Comparison of tumor-associated trypsin inhibitor (TATI) and lissue polypeptide antigen (TPA) in serum and pleural effusion in patients Table 1 -Distribution of malignant and nonmalignant lung diseases Ma lignant: No nmalignant: bronchogenic carcinoma planocellular microcellular adenocarcinoma 15 13 9 tuberculosis bronchopneumonia and pleuropneumonia fibrosis 10 5 2 bronchoalveolar 3 sarcoidosis 2 nondiferentiated 11 Total 51 Tota! 19 1500 800 ] • • 1 1000 700 • 600 1 • • 1 500 ...:1 ...... ::i ::;: ::i c.i:: ri:l C/) z H ,:t: ll, E-< 400 200 100 • • • •• • •• ••• ... ·:•:· ••• •••• •­ • • • •• •• ...:1 ....... o, :;!, ::;: ::i c.i:: ri:l U) z H E-< ,:t: E-< 300 100 50 1 1 J 1 - - • • • • • • 1 1 • •• 1 : • • • • • • - - 22 85 . ,. • • • • • 50 1 • • NON NON MALIGNANT MALIGNANT MALIGNANT MALIGNANT Fig. 1 -Concentration of TPA and TATI in serum of patients with malignant and nonmalignant lung diseases. rements were performed in duplicate. The results were expressed in µ,g/L based on a reference standard. The results of measurements in 42 healthy subjects showed that the normal range of TATI was up to 22 µ,g/L. The intraassay and interaassay coefficients of variation (CV) were measured. The intraassay CV tor TATI level was 8.1-%. The interaassay CV from 11 assay perfor­med with different lots of the kit was 9.3%. Serum TPA level was measured in duplicate using the PROLIFIGENR TPA two-site immuno­radiometric assay (IRMA). A commercial kit sup­plied by Sangtec Medical (Bromma, Sweden) with 85 U/L as the upper normal value was used. Radiol lugosl 1991 ; 25 :225-8. Lazarov A et al. Comparison of tumor-associated trypsin inhibitor (TATI) and tissue polypeptide antigen (TPA) in serum and pleural ettusion in patients Data were expressed statisticaly as the stan­dard error of mean and were compared using Student' s t test. Results -Serum levels of TATI and TPA are presented in Figure 1. Apparently mean TATI concentration was higher in patients with malig­nant than in those with nonmalignant lung disea­se, but the difference was non significant (p > 0.1 ). Serum TPA concentrations were more ele­vated in patients with malignant than with non malignant diseases (p < 0.01 ). Pleural effusion concentrations of TATI and TPA in patients with malignant and nonmalignant lung diseases are presented in Table 2. Table 2 -Pleural effusion levels of TATI and TPA in patients with malignant and nonmalignant lung disea­ses Group n TATl/µ.g/L±SE TPA U/L±SE malignant 13 72.7±48 4020.0±384 non-malignant 14 51.31 ±20 3091.5±427 Concentrations of TATI were not significantly different (p = 0.347). Serum levels of TPA were higher in patients with malignant than in those with nonmalignant diseases. Levels of TPA in pleural effusion were extremly high (it was about 10-fold higher), but difference between two groups (malignant and nonmalignant) were bor­derly nonsignificant (p = 0.0590). As shown in table 3, the analysis of both markers regarding sensitivity, specificity and accu­racy showed that TPA had better characteristics. TATI had satisfactory performance characteri­stics being higher that 50%. The best results in cancer detection were obtained by simmulta­neous measurements of TATI and TPA. Table 3 -Sensitivity, specificity and accuracy of two markers rnnsitivity specificity accuracy (%) (%) (%) TATI 54.9 68.4 57.3 TPA 78.4 63.2 72.8 Radiol lugosl 1991 ; 25 :225-8. In our series 47 (92%) of 51 patients with malignant lung diseases had high TATI or TPA concentrations. Therefore, both markers reached normal range in four cases only. Discussion -TATI and TPA have clearly shown their clinical usefulness as tumor markers in malignant pulmonary disease. Of 51 patients with malignant lung disease TATI levels were elevated in 27 (52.9%) and TPA in 42 (82.3%). Both TATI and TPA showed good sensitivity, but a rather low specificity (57% for TATI and 65% for TPA), which reflected that TATI and TPA concentrations were high, i.e. 43% and 35%, respectively. No significant difference was found between serum and pleural effusion TATI concentrations in malignant or nonmalignant disease but pleural effusion concentration of TP A was higher than serum TPA concentration (4020.0 U/L versus 294.5 U/L in malignant and 3091.5 U/L versus 66-1 U/L in nonmalignant duseases). Our results differred from those reported by Larbre et al. (8) who found higher serum TATI levels in 35.5% patients with lung cancer. This difference may be due to the different stages of disease in compara­ble in both groups. As far as we-know, pleural effusion TATI levels have not been reported TPA concentrations were in malignant effusion signifi­cantly higher than in r;ionmalignant effusion. It is non clear why TPA concentrations in effusion were more than 10-fold higher than in serum. Perhaps an inflammatory process in the pleura could be involved. Conclusion -TATI and TPA seem to be good markers in pulmonary diseases, but neither of them showed sufficient sensitivity. The asso­ciation of TATI with TPA allows greater precision in predicting the course of disease. In our series, 47 (92%) of 51 patients with malignant lung diseases had high TATI or TPA concentrations. Therefore, both markers reached normal range in four cases only. A combination of TATI with other serum markers, which are more specific for lung cancer as TPA, may be helpful in tumor detection and also contribute to better manage­ment of the patients throughout the course of disease. Concentrations of TATI is significantly higher in malignant than in nonmalignant disea­ses, but differences in the levels between serum and pleural effusions have been found. Pleural effusion TPA level were extremely high. lazarov A et al. Comparison of tumor-associated trypsin inhibitor (TATI) and tissue polypeptide antigen (TPA) in serum and pleural effusion in patients Sažetak UPOREDNO ODRE0IVANJE TRIPSINSKOG INHfBI­TORA (TATI) 1 TKIVNOG POLIPEPTIDSKOG ANTI­GENA (TPA) U SERUMU I PLEURALNOM IZLIVU U BOLESNIKA SA OBOLJENJIMA PLUCA Koncentracija tripsinskog in hibi tora (TATI) merena je u serumu i pleuralnom izlivu . u 70 bolesnika sa malignim i nemalignim oboljenjima pluca. Vrednosti koncentracije TATI uporedene su sa vrednostima TPA uradenim iz istog uzorka krvi. Merenje koncentracije TATI u serumu i pleuralnom izlivu izvedena je radioimu­nometrijskom metodam primenom tržišnog kompleta SPECTRIA TATI, firme Farmos Diagnostica. Nivo TPA odreden je dvostranom radioimunometrijskom anali­zam primenom gotovog trzinskog kompleta PROLIFI­GEN TPA firme Byk-Sangtec. Rezultati pokazuju da je koncentracija TATI i TPA u serumu znacajno povecana u bolesnika sa malignim oboljenjima u odnosu na bolesnika sa ne malignim oboljenjima pluca. Koncen­tracija TATI u serumu i pleuralnom izlivu pokazuje visoku korelaciju, dok je koncentracija TPA u pleural­nom izlivu oko 1 O puta veca u odnosu na koncentraciju u serumu. Osefljivost, specificnost i lacnost zadovolja­vaju za oba markera (TATI i TPA). References 1. Huhtala ML, Kahampa K, Seppala M, Hallila H, Stenman UH. Excretion of a tumor-associated trypsin inhibitor (TATI) in urine of patients with gynecological malignancy. lnt J Cancer 1983; 31 :711-4. 2. Hallila H, Lehtovirta P, Stenman UH. Tumor-as­sociated trypsin inhibitor (TATI) in ovarian cancer. Br J Cancer 1988; 57:304-7. 3. Haglund C, Hallila H, Nordling S, Roberts P, Sheinin T, Stenman UH. Tumor-associated trypsin inhibitor, TATI in patients with pancreatic cancer, pan­creatitis and benign biliary disease. Br J Cancer 1986 ;54 :297-303. 4. Mastuda K, Ogawa M, Murata A, Kitahara T, Kosaki G. Elevation of serum immunoradioactive tryp­sin inhibitor contens in various malignant diseases. Res Comm Chem Pathol 1983; 40 :301-5. 5. Hallila H, Huhtala ML, Haglund C, Nordling S, Stenman UH. Tumor-associated trypsin inhibitor (TA­TI) in human ovarian cyst fluid. Comparisan with CA 125 and CEA. Br J Cancer 1987; 56:153-6. 6. Falcone F, Subbatani S. Fini A, Turba E, Magrei P, D'ales A. Combination of tissue polypeptide antigen (TPA) and carcinoembrionic antigen (CEA) in differente type of cancer. Nucl Med Commun 1985;6:299-304. 7. Stenman UH. Tumor-associated trypsin inhibi­tor, TATI. Farmos Diagnostica, Newsletters no 7, 1986. 8. Larbre H, Marechal F, Deltour G. Tumor-asso­ciated trypsin inhinitor (TATI): A new marker of cancer patients, in: H.A.E. Shmidt, J. Chambron ed. Nuclear medicine Quantitative Analysis in imagining and fun­ction. Stuttgart -New York: Shattauer, 1990:123-5. Author's address: Dr sci. med. Angel Lazarov, Institute of Nuclear Medicine MMA, 11 000 Belgrade Radio! lugosl 1991 ; 25 :225-8. THE INSTITUTE OF ONCOLOGY1 , LJUBLJANA UNIVERSITY CLINICAL CENTER2, LJUBLJANA FACUL TY OF MEDICINE3, UNIVERSITY OF LJUBLJANA THERAPY OF BILE DUCT TUMORS WITH A COMBINATION OF RESECTION AND INTRAARTE­ RIAL INTRAHEPATIC CHEMOTHERAiJY štabue 81 , Markovic S1 , Gadžijev E2, šurlan M2, Brencic E2, Perovic AV2, Marolt -Ferlan V3 Abstract -Klatskin's tumors, (i.e. tumors of the upper third of the bile ducts) are rare. The survival of patients with operable and inoperable tumors is short. Considering that radical resections are often non feasibile and that microscopically evident residual disease is generally found even after presumably radical surgeries, such P.atients require an adjuvant chemotherapy or irradiation. Regional intraarterial chemotherapy and intraoperative irradiation have proved to be the most effective therapeutic methods. In our randomized clinical study, 8/23 patients with Klatskin's tumor after radical or nonradical surgery were treated by intraarterial intrahepatic chemotherapy (IAIHCT) with 5-Fluorouracil (5-FU) in the dose of 1000 mg/m2. The mean observation period was 9 months (range 2-20 months). In the group of patients treated by chemotherapy 2 died 13 mohths after surgery on average. In the control group, 3 patients died directly after surgeI,, and another 3 on average 7 months after the procedure. The probability of 2-year survival in radically operated patients was 78% arid in non-radically operated 40% (p<0.1 ), whereas in the patients treated by IAIHCT this probability was 72% regardless the radicality of previpus surgical treatment, in contrast to 42% calculated in the control group Without IAIHCT p<0.1 ). Based on our preliminary results and the data from literature, we belive that intaarterial chemotherapy can prolong the survival of patients with this disease. UDC: 616.361-006.6-08 i > ,5 s.. ::, .... v, o .n "' .n o s.. P < 0.1 C.. 12 24 mos ---------9 patients with radical surgery 14 patients with non-radical surgery Fig. 1 -Survival of patients with Klatskin's tumor after radical and non-radical surgery 1 "" 7 ro > • s. > ::, v, .... o 1 .n "' P< 0.1 l .n o C.. 24 12 mos 8 patients with IAIHCT 15 patients without IAIHCT Fig. 2 -Survival of patients with Klatskin's tumor with or without IAIHCT Radio! lugosl 1991 ; 25 :229·34. Štabuc B et al. Therapy of bile duet tumors with a combination of resection and intraarterial intrahepatic chemotherapy Discussion -So far, the role of radiotherapy in the treatment of bile duet tumors has not been clearly defined. The results of a retrospective study on the use of percutaneous irradiation with 24000-5000 cGy indicate that 6-month survival achieved in non-irradiated patients could be prolonged to 19 months in the irradiated group (1 O). Fogel reports on 11 month mean survival and 6% 5-year survival achieved in a group of 35 nonresectable irradiated patients (11 ). Nowadays many authors believe that in locally advanced tumors a curative dose of percutaneous irradia­tion ranges between 6000 -7000 cGy delivered in 6 to 8 weeks. With microscop\cally evident residual disease after resection, however, a dose between 4500 -5000 cGy is recommended (1, 12, 13). Nevertheless, in percutaneous irradiation the treatment with cytotoxic agents unfeasible, and therefore only few patients with tumors of the bile ducts are treated by chemotherapy. According to the results of some more relevant clinical studies, a short-lasting partial response can be achieved in only 1 /4 of these patients (Table 2). In tumors of the bile ducts a systemic polyche­motherapy according to the FAM schedule (5­FU, Doxorubicine, Mitomycin-C) is stili believed to be the most effective (19). Thought the results of many studies indicate that systemic chemothe­rapy may prolong the survival of patients for 6-11 months on aver.age, the real value of this Table 2 -Systemie ehemotherapy tor bile duet eaneer a tumoricidal dose is difficult to achieve, despite Drug the small irradiation fields, owing to the risk of patients No. (%) damage to the surrounding tissue. This can be avoided by using brachytherapy and a lower cumulative dose of percutaneous irradiation (13). 5-FU (14) 17 4 (24) Mitomyein C (14) 15 7 As to the intraoperative irradiation of nonre­ sectable tumors with a single dose of 3000 cGy, FAM(15) 14 4 (29) this method is reported to have resulted in reca­ FAM(16) 13 4 (31) nalization of obstructed bile ducts and a prolon­5-FU (17) 12 1 (8) ged survival. Abe and Takahashi (12) claimed 5-FU + MeCCNU (17) 12 2 (17) such an effect, i.e. recanalization of obstructed Ftorafur + adriamyein bile ducts, being achieved in 90% od 59 patients +BCNU(18) 7 3 (43) treated by intraoperative irradiation with a single dose of 2500-4000 cGy. The patient tolerated Tota 1 90 25 (26) the treatment well. The analysis of autopsied patients revealed that a single dose of 3500 cGy 5-FU = 5-fluorouraeil, FAM = 5-FU + adriamyein + coU1d be regarded as potentially curative. mitomyein C, MeCCNU= 1-(2-ehlorethyl)-3(4-methyl- Low incidence and frequent occurrence of eyclohexyl)-1-nitrosourea, BCNU = 1.3-bis (2-ehloroet-liver damage or hiperbilJirubinemia often render hyl)-3-eyelohexyl-1-nitrosourea. Table 1 -Charaeteristies of patients with Klatskin's tumor Primary tumor site No. of pts Radieal surgery Nonradieal surgery IAIHCT after non-radieal Adjuvant IAIHCT Regional metastases surgery Common bile duet 4 3 1 o 2 o B-1 Confluenee II 6 3 3 1 o 4 L. hepatie duet III b 9 3 6 3 1 5 R. hepatie duet III a 1 o 1 1 o o Central tiepatie duet-IV 3 o 3 o o 3 11 To tal 25 9 14 5 3 IAIHCT -intraarterial intrahepatie ehemotherapy Aadiol lugosl 1991 ; 25 :229-34. štabuc B et al. Therapy of bile duet tumors with a combination of resection and intraarterial intrahepatic chemotherapy treatrnent is questionable, taking into account the lowered quality ot lite and chemotherapy-re­lated side effects. A majority ot patients with bile duet cancer die ot locoregional disease and not because ot distant metastases. Considering negligible et­tects ot systemic chemotherapy and hardly feasi­ble intraoperative irradiation, as well as a small tumor volume, the regional or intraarterial che­motherapy is frequently believed to be the treat­ment ot choice. In the last 20 years there were many reports published on the use ot chemotherapy in patients with primary tumors ot the liver or hepatic meta­stases, particularly those originating from colo­rectal cancer. A majority ot authors claim that intraarterial chemotherapy by means ot a percu­taneous or surgically inserted catheter has the potential ot increasing the rate ot objective re­sponses, prolonging the survival and improving the quality ot patient's lite (20, 21 ). Unfortunately, during ali these years there has been only one randomized clinical study carried out where a group ot untreated patients was compared with a group treated by intraarte­rial chemotherapy. According to the obtained results, patients in the latter group survived 375 days whereas the survival in the untreated con­trols was only 55 days. However, in the control group there were also some patients who did not meet the requirements tor i.a. therapy (22). Apart trom the above, no other such randomized clini­cal study comparing the results ot i.a. therapy with systemic treatrnent or untreated patients has been performed so far. Theretore, also the supposition that i.a. ChT may prolong the survival is not based on reliable evidence. The encoura­ging results (approximately 50% ot objective responses) could be due to patient selection. Namely, such clinical studies generally comprise patients in good general condition which permits tor surgery or percutaneous insertion of catheters and chemotherapy. These patients do not have distant metastases, and present with satistactory hepatic tunction; they are also free ot hypoprotei­nemia, jaundice and ascites. These prognostic tactors alone may indicate that the patient has 50% chances ot surviving one year (1 ). The number of patients with tumors of the upper two thirds of the bile ducts, treated by i.a. chemotherapy and included • in a randomized clinical study is 2 -15. The small number ot patients as well as the scarcity ot such studies render a reliable assessment of the true value ot i.a. chemotherapy difficult. Radiol lugosl 1991 ; 25 :229-34. Warren et al. (23) report on a group ot 41 patients with non-resectable tumors ot the bile ducts, 15 ot which received i.a„ chemotherapy with FUDR. Sixteen ot these patients survived longer than 1 year. Of these, 9 (60%) were treated by i.a. chemotherapy. One patient survi­ved over 3 years. In other three studies (24, 2., 26) where 8, 11 , and 1 O patients respectively were treated with FUDR (tloxuridine), the rate ot objective responses (partial responses) ranged between 20-50%. As reported by Smith et al. (27), two partial responses were achieved in 4 patients treated with i.a. applications of Mitomycin-C and 5-FU, whereas Garnick et al. (28) and Messney et al. report on one partial remission achieved in 2 patients treated with doxorubycin, and 32 pa­tients receiving 5-FU respectively. The number ot IAIHCT treated patients with Klatskin's tumor included in our study is relatively small, and the observation period is short as well. At that, 3 patients received adjuvant IAIHCT. Despite the longer survival observed in the treated patients, the efficacy ot such therapy cannot be statistically contirmed. 5-FU is metabolically processed in the !iver, and afterwards excreted through the bile ducts. A high concentration ot medication in the bile ducts and liver probably has a very positive effect on the remaining tumorous tissue. On the tirst passage ot medication through the liver a part ot the substance undergoes detoxitication. This may explain why, despite its higher regional concentration ot the drug, the presented treat­ment entails less side ettects than systemic therapy. Regional toxicity ot i.a. chemotherapy, howe­ver, is associated with severe problems. Among these, drug-induced sclerosant cholangitis, in­creased aminotransterases, toxic hepatitis, bi­liary stasis, focal necroses of the liver and chemi­cal cholecystitis are observed most frequently. According to the report by Hohn et al. (30), in a group ot 55 patients treated with FUDR, drug-in­duced sclerosant cholangitis was observed in 56%, chemical cholecystitis in 9%, and increa­sed aminotransferase immediately after comple­ted treatment in 96% ot the patients. In our group a transitional increase in aminotransferase levels immediately after 5-FU application was noted in only 30% of patients. None of them presented with sclerosant cholangitis. There were no treat­ment-related deaths. 233 štabuc B et al. Therapy o! bile duet tumors with a combination o! resection and intraarterial intrahepatic chemotherapy Conclusion -The existing experience with regional chemothera,py in patients with Klatskin's tumor is stili scarce. Frequent, microscopically evident nonradical surgeries and poor prognosis of the patients render an adjuvant treatment necessary. When comparing the regional che­motherapy with the systemic one, the former approach has the following advantages: lesser side effects, short hospitalization period, and a better quality of life. Based on our experience, we believe that the regional chemotherapy has the potential of improving the prognosis in pa­tients with Klatskin's tumor. References 1. Wanebo HJ, Falkson G, Order SE. Cancer of the hematobiliary system. In: De Vita VT, Hellman S, Rosenberg SA, eds. Cancer -principles and practice of oncology. Philadelphia: Lippincott JB, 1980:836-74. 2. lncidenca raka v Sloveniji 1986. Onkološki inšti­tut, Register raka za R Slovenijo, 1990. 3. Longmire J, McArthur MS, Bastounis EA, Hiatt J. Carcinoma ot the extrahepatic biliary tract. Ann Surg 1973;178:333-7. 4. ·Rossi RL, Heiss FW, Beckmann CF, Braasch JW. Management ot cancer ot the bile duet. Surg Ciin N Amer 1985;65:59-65. 5. Alexander F, Rossi RL, O'Brian M, Khettry U, Brassen JW, Watkins E Jr. Biliary carcinoma: a review of 109 cases. Am J Surg 1984 ;147 :503-9. 6. Bismuth H, Castaing D, Traynor D. Resection ot paliation; priority in surgery in the treatment ot hilar cancer. World J Surg 1988;12:29-47. 7. Bengmark S, Jeppsson B. Biliary tract cancer: treatment options. Ann Chir 1989;43:189-93. 8. Piti HA, Roslyn JJ, Tompkins RK. Surgical re­section ot bile duet cancer: the UCLA experience. In: Wanebo HJ, ed. Hepatic and biliary cancer. New York: Marcel Dekker, 1987:339-55. 9. Mizumoto R, Kawarada Y, Suzuki H. Surgical treatment ot hilar carcinoma ot the bile duet. Surg Gynecol Opstet 1986; 162: 153-8. 1 O. Lees CD, Zapolanski A, Cooperman AM. Carci­noma ot the bile ducts. Surg Gynecol Obstet 1980;151 :193-8. 11. Fogel TD, Weissberg JB. The role of radiation therapy in carcinoma ot the extrahepatic bile ducts. In! J Radia! Oncol Biol Phys 1984;10:2251-8. 12. Abe M, Takahashi M. lntraoperative radiothera­py: the Japanese experience. lnt J Radia! Oncol Biol Phys 1981 :7:863-8. 13. lwasaki Y, Todoroki T, Fukao K, Ohara K, Okamura T, Nishimura A. The role ot intraoperative radiation therapy in the treatment ot bile duet cancer. World J Surg 1988;12:91-8. 14. Ramming KP, Tesler AS, Haskell CM. Ga­strointestinal !raci neoplasms. In: Haskel CM ed. Can­cer Treatment. Philadelphia: Saunders, 1980 :231 . 15. Harvey JH, Smith FP, Schein PS. 5-tluoroura­cil, mitomycin and doxorubycin (FAM) in carcinoma ot the biliary tract. J Ciin Oncol 1984;2:1245-8. 16. Cambareri RJ, Smith FP, Kales A, Warren R, Woolley PV, Schein PS. FAM, 5-tluorouracil, aqriamy­cin, and mitomycin-C, in cholangiocarcinoma, 16th Annual meeting ot the American Society of Clinical Oncology, San Diego 1980. 17. Falkson G, Maclntyre JM, Moertel CG. Eastern Cooperative Oncology Group experience with chemot­herapy tor inoperable gallbladder and bile duet cancer. Cancer 1984 ;54 :965-9. 18. Hall SW, Benjamin RS, Murphy WK, Valdivieso M, Bodey GP. Adriamycin, BCNU, ftorafur chemothe­rapy ot pancreatic. and biliary tract cancer. Cancer 1979 ;44 :2008-13. 19. Oberfield RA, Ross AL. The role of chemothe­rapy in the treatment ot bile duet cancer. World J Surg 1988;12:105-8. 20. Kanematsu T, Furuta T, Takenaka K et al. 5-year experience of lipiodolization: selective regional chemotherapy for 200 patients with hepatocellular car­cinoma. Hepatology 1989 ;1O:98-102. 21. Lise M, Da Pian PP, Nitti S, Pilati PL, Prevaldi C. Colorectal metastases to the liver: presen! status of management. Dis Colon Rectum 1990;33:688-94. 22. Lange M, Falkson G, Geddes E. lntra-arterial chemotherapy in the treatment ot primary liver cancer. S Afr J Surg 1974;12 (Suppl 4):245. 23. Warren KW, Mountain JC, Lloyd-Jones W. Malignant tumours of the bile ducts. Br J Surg 1972 ;59 :501-8. 24. Sullivan RD, Zurek WZ. Chemotherapy tor liver cancer by protracted ambulatory intusion. JAMA 1965; 194:481-3. 25. Watkins E Jr, Oberfield RA, Cady B, Clouse ME. Arterial intusion chemotherapy of diftuse hepatic malignancies. In: Ariel IM, ed. Progress in clinical cancer. Vol 7. New York: Grune Stratton, 1978:235. 26. Reed Ml, Vaitkevisius VK, AI-Saraf M et al. The practicality of chronic hepatic artery infusion the­rapy of primary and metastatic hepatic malignancies: ten year result of 124 patients in a prospective protocol. Cancer 1981 ;47:402-7. 27. Smith SW, Bukowski RM, Hewlett JS, Groppe CW. Hepatic artery intusion ot 5-fluorouracil and mito­mycin-C in cholangiocarcinoma and gallbladder carci­noma. Cancer 1984 ;54: 1513-8. 28. Garnick MB, Ensminger WD, lsrael MA. Clinical -pharmacological evaluation of hepatic arterial infusion of adriamycin. Cancer Res 1979;39:4105-11. 29. Massey WH, Fletcher WS, Judkins MP, Dennis DL. Hepatic artery intusion tor metastatic malignancy using percutaneously placed catheters. Am J Surg 1971 ;121 :160-7. 30. Hohn D, Melnick J, Stagg R et al. Biliary sclerosis in patients receiving hepatic arterial infusions of floxorudin. J Ciin On col 1985 ;3 :98-103. Author's address: Borut štabuc, MD, MSc, The Institute of Oncology, Zaloška 2, 61105 Ljubljana Radiol lugosl 1991 ; 25 :229-34. INSTITUT »RU0ER BOŠKOVIC« OOUR EKSPERIMENTALNA BIOLOGIJA I MEDICINA, ZAGREB MONOCLONAL ANTIBODIES IN THE TREATMENT OF BREAST CAACINOMA Beketic-Oreškovic L, Novak 0 Abstract -In order to find specific reagents for the diagnosis and treatment of breast carcinoma numerous monoclonal antibodies have been produced. This review deals with the trials involving monoclonal antibodies for breast carcinoma treatment: radiolabeled monoclonal antibodies, immunotoxins, chemoimmunoconjugates and monoclonal antibodies used alone. The major obstacles to cancer therapy are discussed: the lack of specificity of monoclonal antibodies, heterogeneity and modulation of tumor antigens, and human anti-mouse immunological response. The possibilities to circumvent this obstacles are indicated: the use of the combination of monoclona:I antibodies; human, chimeric and antiidiotypic antibodies; antibody fragments instead of the whole immunoglobulin molecule etc. UDC: 618.19-006.6-08-097 Key words: breast neoplasms-therapy; antibodies, monoclonal Review paper Radiol lugosl 1991; 25:235-9. lntroduction -Carcinoma ot the breast is the most common malignant disease in women and the leading cause ot mortality among we­stern women (1,2). Numerous investigations are aimed today to find new possibilities ot breast carcinoma treatment. Monoclonal antibodies which bind to specific antigens, represent one ot these possibilities. In 1975, Kohler and Milstein made the seminal report ot production ot monoclonal antibodies by using method ot celi hybridisation, tor which they received the Nobel Prize (3). Cultures ot mye­loma cells can be tused to lymphocytes from immunised animals to form hybrid celis that grow continously in culture and secrete antibodies specitic tor the antigen against which the animal was immunised. This technology has made it possible to generate high attinity antibodies ot a required specitity and in limitless quantities (4, 5). Since then, this principle has been used tor the production ot numerous monoclonal antibo­dies to breast carcinoma antigens, and there are attempts to use some ot them tor the treatment ot this disease (6-9). culture (10, 11 ), on human carcinomas ot the breast gratted in experimental animals (12, 13), and also, monoclonal antibodies have been di­rectly applied in some patients with breast carci­noma. This was particularly the case when other modalities ot treatment were relatively inettective (9, 14, 15). Monoclonal antibodies can kili tumor celis by several mechanisms, depending on whether they are applied alone, or conjugated with different cytotoxic substances such as ra­dioisotopes, toxines, chemotherapeutic agents, etc. It monoclonal antibodies are applied alone, they can kili tumor cells indirectly by complement­dependent cytotoxicity or celi mediated cytotoxi­city (2). Growth ot human carcinoma ot the breast gratted into nude mice can be reduced by more than 80 per cent it a combination ot monoc­lonal antibodies produced to human milk tat globule membranes is given to the mouse prior to tumor implantation. The reduction in growth in less than 50 per cent it the antibodies are administered after implantation (16, 17). Accor­ding some other authors, passive immunothe­rapy with monoclonal antibodies used alone can not be succestul, because the cellular immunity plays the main role in the natural immunological detense against tumor (18, 19). There are seve- Received: July 2, 1991 -Accepted: July 15, 1991 Beketic-Oreškovic L, Novak O. Monoclonal antibodies in the treatment of breast carcinoma ral reports of trails in which monoclonal antibo­dies irnpaired the proliferation of tumor celis by inhibiting growth factors or otherwise by altering the regulation of the target celis. So, monoclonal antibodies directed against receptors for transfer­rin (20, 21 ), for interleukin-2(22, 23) and for epidermal growth factor (24, 25) could compete with the growth factors and impair the prolifera­tive capacity of tumor celis. This way of immunot­herapy seems to be more effective in leukaemias (22, 26). The basis of the therapeutic application of conjugated monoclonal antibodies is the linking of monoclonal antibodies with radioisotopes, na­tura! toxines, chemotherapeutical agents or with other substances which modify immunological response. Such »immunoconjugates« could kili tumor celis in vivo because of their selective toxicity. In mice with human breast carcinoma xenografts, monoclonal antibodies to human milk fat globule membranes (HMFGM 1 and HMFGM 2), conjugated with iodine 125, reduced the size of tumors by 60 per cent (2, 30). Monoclonal antibodies to human milk fat globule membranes were also conjugated with iodine 131 and injec­ted to the patients intracavitary, on the place from which breast aspiration with malignant celis was taken. After this treatment, by repeated breast aspirations, malignant cells were not found (31, 32). By the systemic injecting of radioiodinated monoclonal antibodies it was pos­sible to destroy the epithelial celis of human breast tumors implanted in nude mice (33). Rela­tively greater success with regional application of monoclonal antibodies could be explained by cross-reactivity with normal tissue antigens and by poor access and penetration into the tumor by systemic therapeutic application of monoclonal antibodies (9). Among toxins, the most commonly used for the conjugation with monoclonal antibodies is the A-chain of the plant toxin, ricin (34-36). In vitro and in vivo, many tumor celis have been destroyed in this way (37, 38), but 20-30% per cent of tumor celis remain viable, what is proba­bly the reflection of the heterogeneity of tumor cells (14). Different chemotherapeutic agents can also be used for the conjugation with monoclonal antibodies, and they form so calied chemoimmu­noconjugates (39). lnvestigators have explored conjugation of various agents, including anthra­cyclines such as daunorubicin (40-42), alkylating agents such as chlorambucil (43), a:nd also anti­metabolites such as methotrexate (44-46). Che-moimmunoconjugates have been studied for their effect mainly on tumor cells grown in culture, or on experimental animals, but there are only few attempts of direct application to the patients (47, 48). There a,re nurnerous factors wtiich make the applicatiori of monoclonal antibodies in the breast carcinoma treatment rather complicated. Two major obstacles are: pronounced heterogeneity and modulation of tumor antigens, and the lack of absolute specifity of monoclonal antibodies (1,8,9). Tumor celis exhibit pronounced hetero­geneity, so even in the same tumor cells differ as to their phenotypic and in genotypic characteri­stics (49). It could be the result of different celi subpopulations· from which the tumor originates, of the modulation or loss of the antigens of tumor cells, and finally, heterogeneity could also occur because the tumor ·cells were in different stages of differentiation, or in different stages of the celi cycle (50-53). Tumor celis are also genetically very instable. Constant genomic changes and selective pressure of their inviroment (immunolo­gical system or given therapy) result in heteroge­neity of the tumor cells (53). It is belived that this problem could be partly overcome by conjugation of monoclonal antibodies with isotopes. The ef­fect of radiation is carried over five celi diameters, so that not ali tumor celis need to possess the antigen to be destroyed (2). To dale, many monoclonal antibodies produced to breast carci­noma antigens have been described, but none of them is specific only for brnast carcinoma. They mostly also react with normal tissues and/or with other tumors, although generaliy to a much lesser degree Ihan with breast cancer (1 ). But, the therapeutic application of several monoclonal antibodies in combination at the same tirne, has an undoubted clinical value (7,9,54,55). One of important limitations associated with the application of monoclonal antibodies includes the developrnent of human antimouse antibody response. Human antimouse antibodies are for­med after the repeated doses of murine monoclo­nal antibodies. They can be directed towards the isotype of a constant region or towards the idiotype of a variabile · reg ion of mu rine immuno­globulines (56). These antibodies can inhibit the effect of primarily given mouse monoclonal anti­bodies (57), and also they can couse in some patients aliergic rec;1ctions; such as serum sic­kness, renal toxicity and various adverse reac­tions (56,57). Some clinical trials have led to the suggestion that an immune response against the murine immunoglobulins could be beneficial, be- Radiol lugosl 1991; 25:235-9. Beketic-Oreškovlc L, Novak D. Monoclonal antibodies in the treatment of breast carcinoma cause these secondary antibodies could additio­naly induce an immune attac. by the host against the tumor antigens (58, 59). There are some attempts of therapy whith antiidiotypic antibodies (60-62). The development of human immunological response to murine monoclonal antibodies is avoided by the therapeutic application of human monoclonal antibodies (63-66). But, great growth instability, tendency of loosing chromosomes, and weak production of monoclonal antobodies are the characteristics of human hybridomas (67). Genetic. engineering technologies have made it possible to make chimeric monoclonal antibodies (human heavy chaines and murine light chaines of immunoglobulin molecules), which are much less immunogenic (68, 69). Reports about very few clinical investigations have been published (70, 71 ). Because of the immunogenicity problems caused by the Fc por­tion of the murine immunoglobulin molecule, there are.some attempts of therapy with antibody fragments-Fab or F(ab'b where Fc portion is removed (72). Molecules, like toxines or chemot­herapeutic agents, conjugated to these frag­ments, penetrate much easier to tumor intersti­tium (73), bul rapid clearing in the kidney greatly impairs the ability to concentrate the reagent in the tumor (1 O). Conclusion -The application of monoclonal antibodies in the treatment of malignances in general, and also in the treatment of breast carcinoma, stili represents a great challange for many investigators. There are more successful results in vitro and in animal models, but exam­ples of direct clinical application are stili insuffi­cient. Obviously, more tirne is required to proove the real value of such therapeutic approach to the treatment of breast carcinoma. The progress which has been already made is the reason tor the optimistic point of view. Sažetak PRIMJENA MONOKLONSKIH PROTUTIJELA U TE· ' RAPIJI KARCINOMA DOJKE U cilju pronalaženja specificnih supstanci za dijag­nostiku i terapiju karcinoma dojke, do danas su proizve­dena brojna monoklonska protutijela. U ovom pregled­nom clanku prikazani su pokušaji primjene monoklon­skih protutijela u terapiji karcinoma dojke: primjena monoklonskih protutijela vezanih na radioaktivne ele­mente, citostatike, ili toksine, kao i primjena samih monoklonskih protutijela. Navedene su i osnovne za­preke u terapijskoj primjeni monoklonskih protutijela: heterogenost tumorskih antigena, nedostatak apso­lutne specificnosti monoklonskih protutijela, kao i imu­nološki odgovor pacijenata na unos mišjih imunoglobu­lina. Naznacene su i mogucnosti prevladavanja ovih poteškoca: terapijska primjena kombinacije monoklon­skih protutijela; humana, himericna, te antitidiotipska antitijela; primjena fragmenata antitijela umjesto cijele molekule imunoglobulina itd. References 1.Tjandra JJ, KcKenzie IFC. Murine monoclonal antibodies in breast cancer: an overview. Br J Surg 1988; 75:1067-77. 2. Sterns EE, Cochran AJ. Monoclonal antibodies an the diagnosis and treatment of carcinoma of the breast. 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Specitic targeting of chlorambucil to tumours with the use of monoclonal antibodies. J Natl Cancer lnst 1986; 75 :503-1 O. 44. Smyth MJ, Pietersz GA, McKenzie IFC. The mode of action ot methotrexate monoclonal antibody conjugates. lmmunol Celi Biol 1987; 65:189-200. 45. Kanelios J, Pietersz GA, McKenzie IFC. Stu­dies of methotrexate-monoclonal antibody conjugates tor immunotherapy. J Natl Cancer lnst 1985; 75:319­32. 46. Embleton MJ. Drug-targeling by monoclonal antibodies antibodies. Br J Cancer 1987; 55:227-31. 47. Pitersz GA, Smyth MJ, Kanellos J. Preclinical and clinical studies with a variety ot immunoconjugates. Antibody lmmunocon Radiopharm 1988; 1 :79-103. 48. Oldham RK, Lewis M, Orr DW, et al. Adriamy­cin custom-tailored immunoconjugate in the treatment of human malignancies. Molec Biother 1988; 1 :103-13. 49. Schnipper LE. Clinical implications ot tumor-celi heterogeneity. N Engl J Med 1986; 314:1423-31. 50. Nicholson GL. Tumor celi instability, diversifica­tion, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res 1987; 47:1473-87. 51. Mareel MM, Van Roy FM, De Baetselier P. The invasive phenotypes. Cancer Melasi Rev 1990; 9 :45­62. 52. Rubin H. The significance of biological hetero­geneity. Cancer Metast Rev 1990; 9:1-20. 53. Heim S, Mandahl N, Mitelman F. Genetic con­vergence and divergence in tumor progression. Cancer Res 1988; 48 :5911-6. 54. Dillman RO. Antibody therapy. In: Oldham RK ed. Principles of cancer biotherapy. New York: Raven Press, 1987 :291-318. 55. Oldham RK. Monoclonal antibodies: does suffi­cient selectivity to cancer cells exist for therapeutic aplication? J Biol response Mod 1987; 6 :227-34. Radiol lugosl 1991 ; 25 :235-9. Beketic-Oreškovic L, Novak El. Monoclonal antibodies in the treatment of breast carcinoma 56. Kroonenburgh MJPG, Panwels EKJ. Human immunological response to mouse monoclonal antibo­dies in the treatment or diagnosis of malignant disea­ses. Nucl Med Commun 1988; 9:919-30. 57. Schrott RW, Foon KA. Beatty SM, Oldham RK, Morgan AC. Human antimurine immunoglobulin re­sponses in patients receiving monoclonal antibody therapy. Cancer Res 1985; 135:1530-5. 58. Koprowski H, Herlyn D, Lubeck M, De Freitas E, Sears HF. Human antiidiotype antibodies in cancer patients: is the modulation of the immune response beneficial tor the patient? Proc Natl Acad SCI USA 1984; 81 :219-9. 59. Burdette S, Schwartz RS. Current concepts: immunology. ldiotypes and idiotypic networks. Med Intel 1987; 317:219-24. 60. Sikorska HM. Therapeutic applications of antii­diotypic antibodies. J Biol Response Mod 1988; 7 :327­58. 61. Herlyn D, Ross AH, Koprowski H. Anti-idiotypic antibodies bear the interna! image of a human tumor antigen. Science 1986; 232:100-2. 62. Raychaudhury S, Saeki Y, Fuji H, Kohler H. Tumor-specific idiotype vaccines. l. GeneraMn and characterisation of interna! image tumor antigen. J. lmmunol 1986; 137:1743-9. 65. Shoenfeld Y, Hiza A, Tal R. Human monoclona­ler antibodies derived from lymph nodes of a patient with breast carcinoma react with MuMTW polypeptides. Cancer Res 1987; 59:43-50. 66. Kjeldsen TB, Rasmussen 88, Rose C, Zeuthen J. Human-human hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocy­tes from breast cancer patients. Cancer Res. 1988; 48 :3208-14. 67. Gebauer W, Lindi T. Entwicklung humaner monoklonaler A_ntikorper. Arzneim-Forsch/Drug Res 1989; 39:287-91. 68. Brown BA, Davis GL, Saltzgaber-Muller J, et al. Tumor-specific genetically engineered murine/hu­man chimeric monoclonal antibody. Cancer Res 1987; 3577-83. 69. De Pinho RA, Feldman LB, Scharff MD. Tailor made monoclonal antibodies. Ann lntern Med 1986; 104 :225-33. 70. Liu Ay, robinson RR, Hellstrom AE, et al. Chimeric-mouse-human lgG1 antibody that can me­diate lysis of cancer cells. Proc Natl Acad Sci USA 1987; 84 :3439-43. 71. LoBuglio AF, Wheeler R, Leavitt RD, et al. Pharmacokinetics and immune response to chimeric mouse/human monoclonal antibody (CH17-1A) in man. Proc ASCO 1988; 7:111. 72. Smyth MJ, Pietersz GA, McKenzie IFC. The in vitro and in vivo antitumor activity of N-AcMEL-(Fab) 2 conjugates. Br J Cancer 1987; 55:7-11. 696-502. 73. Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res 1987; 47:3039-51. 64. Strelhaushas AJ, Taylor CL. Human monoclo­nal antibody: construction of stable clones rective with Author's address: Dr. Lidija Beketic-Oreškovic, human breast cancer. Cancer lmmunol lmmunother OOUR EBM, Institut »Ruder Boškovic«, Bijenicka 54, 1986; 23:31-40. 41000 Zagreb Radiol lugosl 1991: 25:235-9. Fram practice for practice FROM PRACTICE TO PRACTICE Case 3 Answer: This is an lntra-arterial digital sub­traction (OSA) aortogram which shows that there is occlusion of the left renal artery and a severe stenosis of the right renal artery. In addition, although the hepatic and splenic arteries are fairly well opacified there is hardly any opacifica­tion of the branches of the superior mesenteric artery (SMA), suggesting that there is significant stenosis of the origin of the SMA. This could be confirmed by a lateral aortogram, which will show stenosis or occlusion of the SMA. There is also a linear subtraction artefact to the right of the lumen of the aorta, which is caused by movement of the calcified aortic wall, indicating that there is extensive disease of the aortic wall. •' This patient has a severe renal artery steno­sis affecting his only kidney. Although there is debate about the role of other imaging studies (e.e. isotope studies) in selecting patients for renal artery angioplasty, in this situation the patient has a high risk of infarcting his remaining kidney and further imaging of the kidneys is redundant as there is no doubt that the stenosis needs treatment. In this situation angioplasty, with readily available surgical back-up and suita­ble angioplasty experience, is often the treatment of choice. In this ·patient the angioplasty was successful in relieving hypertension and impro­ving renal function (Fig. 1 b}. .t!'" '.;U'·•.t t4• 1: '­ -, e Fig. 1 b -The post-angioplasty angiogram Author's address: Klancar J, MD, Institute of Rentgenology, University Medical Center Ljubljana, Zaloška 2, 61000 Ljubljana UNIVERZITET U SARAJEVU, PAIRODNO-MATEMATICKI FAKULTET, ODSJEK ZA HEMIJU SOME APPLICATIONS OF NONDESTRUCTIVE RADIOACTIVATION ANALYSIS IN MEDICINE Zovko E Abstract -The elimination of gold in form of 198Au radioisotope from th. organi.srn of a patient, with rheumatic fever to whom myochrisine (di-natrium salt of aurithiomaleic acid) had been applied intramuscularly, was followed by means of r.dioactivated analysis, The application of gold preparations, due to possible disturbances, especially in the kidney function, requires the monitoring of gold content in urine, which was done in the first phase of the programme. In the second phase of the programme, gold from the radiated sample was separated, i.e, gold was extracted with mercury, in order to avoid disturbances from other nuclides in traces (Ag, Rb, Fe, Co, Zn) which are also presen! in the patient's urine, We can conclude from the curve of the elimination of gold by kidney function that elimination of gold by means ot urine, after intramuscular injection of myochrisine, is a relatively slow process. UDC: 616-002. 77°085:615.849.2-034.61 Key words: rheumatic fever-drug therapy; metabolic clearance rate: gold Radioisotopes Orig sci paper Radlol lugosl 1991; 25:241-4. lntroduction -In some cases of rheumatic arthritis, patients are treated with intramuscular injections of a preparation of gold called myochri­sine (di-natrium salt of aurithiomaleic acid). Since clinical practice requires following of the preparations of gold, the aim was to monitor the quantity of gold in patient's urine by means of the nondestructive radio activation analysis, and to test the possibility of extracting isotope 198Au from the mixture after neutron radiation (1,2). Based on the obtained dala, the approximate quantity of gold eliminated from patient's orga­nism through urine was estimated after an intra­muscular injection of 50 mg of myochrisine (3). Material and methods -Urine of a patients with rheumatic arthritis was used as a sample. In the first phase of the programme, the whole dry residue of urine was radiated at the Institute »Boris Kidric« in Vinca, in order to determine the complex urine spectrum and other radionuclides which are likely to be found in urine (Fig. 1). In the second phase of the programme, new series of samples were prepared for the quantita­tive determination of gold in urine, using created isotope 198Au. Samples of urine (1 O ml), with ampullated gold standard (1.2 10~5 g) were placed into the common channel of the reactor (1,5 1 O 13 n/sec cm2) and the comparison of yield of isotope 198 Au against the standard was done by means of comparativ!3 method of radioactivted analysis. Due to the possibility of disturbance of some other nuclides, in the latter phase of the pro­gramme, a simple radiochemical procedure for the separation of gold from the radiated sample was developed. The extraction of gold by means of elemen­tary mercury was applied (4). Measurment of the radiated samples was performed on a 4096 Ge-Li detector at the Institute »Boris Kidric« in Vinca and on multic­hannel y spectrometer with NaJ/T1/, at this Insti­tute. The purpose of these parallel measurments was to estimate whether bolh systems are equally worth using for determination of 198 Au in urine. Received: June 6, 1991 -Accepted: Avgust 2, 1991 Zovko E. Some applications of nondestructive radioactivation analysis in medicine "'Au .tv \l4,4 •szn 1. 1'11Au >­,.;..1·K,v lOi\­ > -.i "' \' " "'"'"' ' .lo '"'" ,,.. ·, """ . ".,,,, - llii'i·. :olff-. .--·· ;:i. .. "" -., ,. "" ,,.. .. . '. .. . channel number Fig. 1 -y spectrum of urir. 2800 2600 i400" . 200 2000 Q. ld!JO E ?: '.i.00 ­ ; ;;: 1rno· 1000·· \ .00 iOO .co 2!)Q. o ·1---.----,----,----,--------,---,---,----,--------,---,----,----. 400 420 440 460 4IO SlO S40 SIO ,oo '20 channel number 198 Au extracted from urine Radio! lugosl 1991 ; 25 :241-4. Zovko E. Some applications of nondestructive radioactivation analysis in medicine 12000­ )000 1000 400 420 • 2 1 To ... m .E ....-UFOY + CFOV oL--.----'----.L_-.==.'-., o 200 •oo eoo aoo 1000 True count rate (kcounts/sec) Fig. 1 -The indices of integral uniformity for useful and central field of view of the gamma camera as calculated for flood images taken with Tc-99m point sources giving different count rates. The dependence ot the integral unitormity for Tc-99m sources on the true count rate (not the observed one) is represented in Figure 1. The true count rate is the counting rate that would be recorded if the dead tirne ot the system was zero. Integral uniformity is getting worse both in CFOV and UFOV with high activities applied, as it can be expected from our knowledge ot pile-up ettect. But, at the same tirne, the unexpectedly high values are noticed at very low count rates. When working with the activities ot arround 100 µ,Ci, the integral unitormity indices are nearly double than those one should expect when extrapolating the curves towards the low values ot the true count rates. The results ot the same experiment, but using 1-131 point sources, are given in Figures 3 and 4. One does not notice the adverse beha­viour ot the indices at low count rates. The true count rate range is ditterent in these graphs because in the case of 1-131 the saturation starts Radiol lugosl 1991 : 25 :251-4. Kasal B, Popovic S. Effect of constant background on gamma camera uniformity at different count rates ­ :; a ·e .E e ·c ::, ai • . I+ To • ¦lhll . 2 ·+ Ro-• • CfOY i5 --Colu•n• -CFOV oL __ ,__ __ .,__ __ .==.=._, o 200 •oo eoo eoo 1000 True count rate (kcounts/sec) Fig. 2 -Differential unitormity in the CFOV vs. true count rate tor Tc-99m point sources ot different activi­ 30 -30 .26 ·e .E 20 ·c ::, 16 ai c,10[ Q) . tes. --* 1 •11t _ ll( _-C -& UFOV * CfOV 0 0 60 100 160 True count rate (kcounts/sec) .--------*---­ 12 l10 ?: e e .§ e ai . 4 ::: 2 i5 0 J , o 601 100 20 l .16 := ,o § 1: e ai . - j 6r\+ -+-+----+-----+-----· ------+ CFOY .!: -· + To•tlM (•140 MV -8-1-131 E•H-4 MV oL _ _,_ __ ,_ _ _,_.=====. o • e e 10 12 Activity (mCi) Fig. 5 -Integral unitormity in the CFOV sources ot Tc-99m and 1-131 as the tunction ot increasing activity. A strong energy dependence is evident, especially at very high radioactivities. sooner due to the lower intrinsic efficiency of the crystal tor higher energy gamma rays. Far the purpose of illustration and comparison in Figure 5, the true count rate values were recalculated back to activities. Evidently, there is strong dependence of the uniformity indices on the energy when high activities (and, consequen­tly, high count rates) are applied: the uniformity is much worse in the case of 1-131 than in the case of Tc-99m when the same activities are 200 used far point sources. Discussion and conclusion -The unifor­ Fig. 3 -Integral uniformity tor different true cour.! rates mity indices tor constant count density flood in CFOV and UFOV using 1-131 point sources. images are increasing with increasing the true count rate (or activity of the source). This effect is stronger in the region of very high count rates where saturation and mispositioning of the events happen. .Jlf For equally radioactive sources, but of diffe­rent gamma energy, worsening of uniformity with increasing the count rate (especially on its high side) will be much quicker in the case of the radionuclide emitting higher gamma energy. The extraordinary high values of the indices were calculated tor the flood images taken with '-101 I ·!" •-•-c•ov ,::::r Cohnua • CFOV 160 True count rate (kcounts/sec) Fig. 4 -Differential unit.rmity in the CFOV vs. very weak technetium sources. The unusual 1 effect was not noticed when 1-131 was used as , , a test source. The unusual effect 1s ev1dently 200 tirne dependent, beeing most markedly expres­ sed in the studies with the longest collection limes. Analysing the conditions of the experi­ ment, ali the phenomena that would not cause a true count rale tor 1-131 point sources ot different activities. tirne dependent effect were eliminated as possi- Radiol lugosl 1991 ; 25 :251-4. Kasal B, Popovic S. Effect of constant background on gamma camera uniformity at different count rates ble reasons for such a behaviour of the uniformlty indices. The contamination of the detector with 1-131 was also excluded. We suppose that the uniformity could possibly be affected by scattered radiation from 1-131 used in the same room for kidn.ey or bone seans on other two cameras of beeing stored in the small hot depository. The low level of scattered radiation, with decreased photon energy and coming all the tirne from the same direction, could affect the uniformity only in the studies of long duration. Because of its decreased energy it falls out of 1-131 energy window and produces no changes on 1-131 flood images. So, although in general the uniformity is better when measured at a low count rate, in a very busy nuclear medicine department precau­tions may also be needed when intrinsic unifor­mity tests are performed at low count rates (even not extremely low). That is why we suggest that in every busy department the uniformity indices be measured in the whole range of count rates (activities) in the standard set-up always used for intrinsic flood checks and then decide on the activity which is the most appropriate for every­day tests. This work is stili in progress. Changing the levels of constant 1-131 background by using the sources of known activities in fixed positions as well as the effect of smoothing and off-peak flood imaging is being investigated. Sažetak UTJECAJ STALNOG POZADINSKOG ZRACENJA NA UNIFORMNOST GAMA KAMERE KOD RAZLICITIH BRZINA BROJANJA Kontrola uniformnosti vidnog polja opcenito je pri­hvacena kao najvažniji test u programu kontrole kvali­tete rada gama kamera. Indeksi uniformnosti uglavnom su najbolji (najniže vrijednosti, mjereno prema NEMA protokolima) kod malih brzina brojenja gdje je, normal­no, mala razlika izmedu registrirane i stvarne brzine brojenja. U ovom radu indeksi uniformnosti mjereni su intrin­sicno u širokom rasponu brzina brojenja za dva naj­cešce korištena radionuklida tehnecij-99m i jod-131 da bi se ukljucio efekt razlicitih energija. laka je unifor­mnost lošija kod velikih brzina brojanja, u jako zaposle­nom zavodu za nuklearnu medicinu rnjere predostrož­nosti mogu biti potrebne i ortda kad se test izvodi kod malih brzina brojenja. U slucaju vrlo slabog radioaktiv­nog izvora Tc-99m izmjereni indeksi integralne i dife­rencijalne uniformnosti mnogo su viši od ocekivane vrijednosti. U isto vrijeme takav neobican efekt nije zamijecen kad je 1-131 korišten kao test izvor. Eliminirajuci druge potencijalne razloge za ovakvu pojavu, pretpostavljamo da se radi o kvarenju unifor­mnosti pod utjecajem raspršenog zracenja od 1-131 koji se u istoj prostoriji koristi za brojne dijagnosticke testove ili stoji u prirucnim »vrucim« spremištima. Utje­caj je, normalno, najevidentniji kod dugotrajnih studija. Preporucamo da se u svakom jako zaposlenom nuklearno medicinskom zavodu indeksi intrinsicne uni­formnosti izmjere za široki raspon aktivnosti izvora i onda odluci koja je aktivnost najprimjerenija za rutinski svakodnevni test. References 1. Adams R, Zimmerman D. Methods tor calcula­ting the deadtime of Anger camera systems. J Nucl Med 1973; 14:496-8. 2. Strand SE, Lamm IL. Theoretical studies of image artifacts and counting losses tor different photon fluence rates and pulse-height distributions in single­crystal Nal(TI) scintillation cameras. J Nucl Med 1980; 21 :264-75. 3. Lewellen TK, Murano R. A cornparison of count rale parameters in gamma cameras. J Nucl Med 1981; 22:161-8. 4. Hasman A, Groothedde. Gamma camera unifor­mity as a function of energy and count rale. Brit J Radiol 1976; 49:718-22. 5. Muehllehner G, Wake RH, Sano R. Standards tor performance measurements in scintillation cameras. J Nucl Med 1981; 22:72-7. 6. NEMA Standards tor performance measure­ments of scintillation cameras. NEMA Standards Publi­cation NU 1 -1986. 7. Hughes A, Sharp PF. Factors affecting gamma camera non-uniformity. Phys Med Biol 1988; 33 :259­69. 8. Hughes A, Sharp PE. The sensitivity o! objective indices to changes in gamma camera non-uniformity. Phys Med Biol 1989; 34 :885-893. 9. Grossman LW, Anderson MP, Jennings RJ, Kruger JB, Lukes SJ, Wagner RF, Warr CP. Noise analysis o! scintillation camera images: stochastic and non-stochastic effects. Phys Med Biol 1986; 31 :941-53. Author's address: B. Kasal, Department of Nuclear Medicine, Clinical Hospital Centre Rebro, 41000 Za­greb Radiol lugosl 1991; 25:251-4. SPLOŠNA BOLNIŠNICA MARIBOR, GASTROENTEROLOŠKI ODDELEK ONKOLOŠKI INŠTITUT V LJUBLJANI LASERSKO ZDRAVLJENJE STENOZANTNEGA RAKA POŽIRALNIKA LASER TREATMENT OF STENOTIC ESOPHAGEAL CANCER Pinter 2, Pocajt M, Benulic T, Jancar B Abstract -Laser treatment of stenotic cancer process in the esophagus has the potential of improving the quality of patient's lite, and also enables further irradiation and/or chemotherapy. The method has proved effective in the prevention of cachexia and elimination of esophageal pain. When performed by an experienced endoscooist, the laser procedure is a realible method which entails only few complications. As such it is suitable also tor patients in whom ot11er treatment approaches are not feasible. UDC: 616.329-006.6-089-073 Key words: esophageal neoplasms-surgery; laser surgery Letter to editor Radiol lugosl 1991 ; 25 :255-8 Uvod -Paliativni posegi pri malignih steno­zah požiralnika imajo namen izboljšati kvaliteto življenja bolnikov, ki niso sposobni za radikalni operativni poseg. Z laserskim žarkom odstranimo mehansko oviro, ki bolniku preprecuje požiranje, in s tem zmanjšamo tudi bolecino. Z uspešno rekanalizacijo požiralnika preprecimo grozeco kaheksijo in omogocimo nadaljnje zdravljenje z radioterapijo in/ali kemoterapijo (1, 2, 3). Cilj laserskega zdravljenja je odstranitev tu­morske mase v lumnu požiralnika. Za poseg z laserjem smo se odlocili pri bolnikih kjer opera­tivni poseg ni bil možen zaradi lokalne razširjeno­sti tumorja, zasevkov po telesu in zaradi drugih spremljajocih bolezni. Zdravljenje z laserjem ni možno pri visoko ležeci stenozi, to je nad 15-18 cm od zobnega roba in pri ezofagealni fistuli. Bolniki in metode dela -Od aprila 1987 do decembra 1990 je bilo na naš oddelek napotenih 40 bolnikov z napredujocim rakom požiralnika. Operativni poseg ni bil možen zaradi stenoze daljše kot 7 cm (pri 39 bolnikih), 13 bolnikov je imelo zasevke po drugih organih, 31 jih je bilo starejših od 60 let, od teh 20 starejših od 70 let. Pri 5 bolnikih je bilo prisotno še drugo, vzporedno rakavo obolenje. Starost bolnikov je bila od 37 do 82 let, med njimi je bilo 8 žensk in 32 moških (slika 1 ). Pri vseh bolnikih je bila diagnoza potrjena s histološko preiskavo biopsijskega materiala. Zaradi izbire nacina posega in orientacije v požiralniku smo pred pricetkom zdravljenja opra­vili še RTG slikanje prehodnosti požiralnika in CT zajetega podrocja. Dolžine rakaste rašce so pri­kazane na sliki 2. Stenozo v požiralniku smo opredelili glede na lego: v 1. tretjini požiralnika (1 bolnik), v 2. tretjini požiralnika {12) in v 3. tretjini požiralnika (27 bolnikov) (slika 2). Posege z laserjem smo ponavljali v razmaku 2-3 dni, tako da smo dosegli prehodnost požiral­nika za obicajen gastroskop. Pri posegih smo uporabljali gastroskop firme Olympus GIP Q 1 O in Neodym YAG laser firme MBB. Zožitev lumna smo ocenjivali pred prvim posegom in po za­kljucku zdravljenja z naslednjimi ocenami: O -lumen ni viden, 1 -lumen je viden, 2-lumen 3-4 mm (širina biopsijskih klešcic), 3 -lumen 7-8 mm (širina biopsijskih klešcic), 4 -lumen 12-14 mm, prehoden za gastro­ skop. Received: July 1 O, 1991 -Accepted: September 1 O, 1991 Pinter 2: et al. Lasersko zdravljenje stenozantnega raka požiralnika ....: >Vl -1 -12 -27 13 11 5 2 2 30 40 50 60 70 Slika 1 -Razdelitev bolnikov po starosti Fig. 1 -Distribution of patients by age - 1/3 2/3 3/3 7 80 let o N u .o . °' se- ­ rn Slika 2 -Lokalizacija raka v požiralniku po tretjinah Slika 3 -Dolžina rakov v požiralniku Fig. 2 -Localization of cancer in the esophagus by Fig. 3 -Extent (length) of esophageal cancer thirds Aadiol lugosl 1991 ; 25 :255-8. Pintar 2: et al. Lasersko zdravljenje stenozantnega raka požiralnika Ocenjevali smo tudi sposobnost požiranja pred prvim posegom in po zakljucku zdravljenja: O -ne more požirati, 1 -pije tekocino, 2 -pije brez težav, 3 -požira pasirano hrano, 4 -požira formirano hrano. Rezultati -Pri 40 bolnikih smo opravili skupno 231 posegov z laserjem, povprecno 5,7 pri posameznem bolniku (1-15) (slika 4). 14 - 11 - }l.. Prehodnost požiralnika in sposobnost požira­nja pred in po zdravljenju so prikazani na sliki 5 in 6. Preživetje bolnikov od posega z laserjem do smrti je prikazano na sliki 7. Bolniki so bili hospitalizirani na oddelku pov­precno 14 dni (4-28 dni). K o m p I i k a c i je : Komplikacije, ki jih pri po­segih z laserjem pricakujemo, so: perforacija in krvavitev pri bolniku in refleksija laserskega žarka ter fotokoagulacijski efekt na roženici ocesa pri 1 n 3X sx 7X 10X 15X Slika 4 -število posegov z laserjem pri bolniku Fig. 4 -Number of laser interventions per patient A B lumen ni viden 1 lumen je viden 2 lumen 3-4 mm 3 lumen 7-8 mm 4 lumen 12 14 mm za gastroskop Slika 5 -Prehodnost požiralnika: A -pred zdravljenjem, B -po zdravljenju Fig. 5 -Passability of esophagus: A -before treatment, B -after treatment Radiol lugosl 1991 ; 25 :255-8. .Pinter 2 et al. Lasersko zdravljenje stenozantnega raka požiralnika A B o ne more požirati -1 pije tekocino 2 pije brez težav .... . 3 pozira pas1rano 4 požira formirano hrano Slika 6 -Sposobnost požiranja: A -pred zdravljenjem, B -po zdravljenju Fig. 6 -Swallowing ability: A -before treatment, B -after treatment E -O rn -.:t N .O ....... Slika 7 -Preživetje bolnikov po laserskem zdravljenju (v mesecih) Fig. 7 -Survival of patients after laser therapy (in months) endoskopistu in asistentih. Vseh komplikacij je bilo sedem (3% od 231 posegov) in to: tri perforacije, dve fistuli ter po enkrat zastoj dihanja in zapora lumna. Ezofagealni fistuli sta nastali vec tednov po zadnjem posegu z laserjem, tako da ju težko ovrednotimo kot neposredno komplikacijo zdrav­ljenja. Do zastoja dihanja (pojavil se je enkrat in minil po ustrezni terapiji) lahko pride ob preko­ merni analgeticni terapiji, posebno pri starejših bolnikih, vendar, odkar uporabljamo preparat flu­mazelin, podobnih komplikacij ni bilo. Zakljucek -Ugotavljamo, da s paliativnim laserskim zdravljenjem izboljšamo kvaliteto živ­ljenja bolnikov z napredujocim rakom požiralnika. Ob primerni medikamentozni predpripravi bolniki dobro prenašajo zdravljenje. Laserski žarek je v rokah izkušenega zdravnika -endoskopista -varen inštrument in omogoca zanesljivo oprav­ljan endoskopskih posegov tudi pri ogroženih bolnikih. Literatura 1. Krasner N, Barr H, Skidnore C, Morris AI. Palliative laser therapy tor malignant dysphagia. Gut 1987; 28:792-8. 2. Bown SG, Hawes R, Matthewson K, Swain CP, Barr H, Boulos PB, Clark CG. Endos­copic laser palliation tor advanced malignant dysphagia. Gut 1987; 799-807. 3. Bader M, Dittler HJ, Ultsch B, Ries G, Siewert JR. Palliative Treatment of Malignant Stenoses of the Upper Gastrointestinal Tract using a Combination of Laser and Afterloading Therapy. Endoscopy 1986; 18 :27-31 . Naslov avtorja: Dr. Pinter Ž, Splošna bolni­šnica Maribor; Gastroenterološki oddelek, 62000 Maribor Radio! lugosl 1991 ; 25 :255-8. ONKOLOŠKI INŠTITUT LJUBLJANA EPIDEMIOLOŠKI POGLED NA PROBLEMATIKO RAKA V SLOVENIJI IN JUGOSLAVIJI EPIDEMIOLOGICAL ASPECT OF CANCER RELATED PROBLEMS IN SLOVENIA ANO YUGOSLAVIA Pompe Kirn V Abstract -Cancer morbidity in different republics of Yugoslavia varies according to the differences in age structure, lite habits and socio-economic conditions. Relevant dala on cancer incidence are available only tor S!ovenia, Croatia and Voivodina. In the remaining parts of Yugoslavia the registration is stili being introduced and therefore their cancer incidence could be estimated on the basis of mortality dala only. The obtained figures are, however, not representative due to the excessive load of prognostically unfavourable cancers; the dala are influenced also by the quality of death cause determination which is varying by different republics. In all republics a majority of cancer related deaths are due to lung cancer, which is followed by stomach-and breast cancers. Th_e mortality rates far lung cancer in men and breast cancer in women are. constantly increasing in all regions, and so are also the respective rates far cancers of the oral cavity, tongue, pharynx and larynx, as well as far colorectal cancer. The highest increase is observed in the incidence of cancers 70-80% of which are related to cigarette smoking. In Slovenia and Yugoslavia as well, the endeavours to achieve 15% decrease of cancer mortality should be centred on well prepared campaigns against active and passive smoking, and against alcohol abuse; apart from these, sensibly organized and to our conditions adjusted secondary prevention, i.e. screening programs far the detection of precancerous and early stages of cervical and breas! cancer are also expected to contribute to this goal. In 1991, two cancer prevention programs are under way in Slovenia: 1) Slovenia 2000 and Cancer, organized by the Slovenian Anticancer Society and the Institute of Oncology in Ljubljana, and 2) CINOI program carried out by the Health Center of Ljubljana. UDC: 616-006.6-036.2 Key words: neoplasms-epidemiology; Slovenia Letter to editor Radiol lugosl 1991 ; 25 :259-62. Uvod -Onkološka epidemiologija obravnava pojavnost raka in raziskuje vzroke njenih spre­memb in razlicnosti po svetu. S pomocjo mate­maticnih modelov napoveduje spremembe. V njeno podrocje dela sodijo tudi intervencijske populacijske in klinicne študije. Epidemiologi opazujejo bolezen kot množicen pojav, za katerega veljajo zakonitosti statistike, ki temeljijo na teoriji verjetnosti. Zaradi vkljucitve statistike v epidemiološka proucevanja se meto­dologija dela hitro razvija. Problem opazovanja redkih pojavov na majhnem populacijskem ob­mocju, npr. opazovanja posameznih primerov levkemij v okolici razlicnih virov sevanja kljub vsemu prizadevanju še ni rešen. V zadnjih letih je vse bolj prisotna težnja zlitja dognanj laboratorijske eksperimentalne onkologi­je, predvsem molekularne biologije z epidemiolo­gijo. Vecji mednarodni raziskovalni centri raka, kot je IARC (Mednarodna agencija za raziskavo raka) sodijo med njene pobudnike z organizacijo tecajev in skupnih raziskav. Zbolevanje za rakom v posameznih republikah Jugoslavije Zbolevanje za rakom v posameznih republi­kah Jugoslavije je glede na raznoliko starostno strukturo, življenske navade in razlicen socialno ekonomski razvoj, zelo razlicno. V predelih z vecjim odstotkom starejših je raka vec. Zato je pred iskanjem drugih vzrokov za razlike v obolevanju potrebno podatke najprej starostno standardizirati (1 ). Najboljša mera številcne ocene zbolevanja za rakom je incidenca. Zane­sljive podatke o incidenci pa lahko dobimo le za republiki Slovenijo in Hrvaško ter Vojvodino, kjer imajo registri raka že dolgoletno tradicijo zbiranja in obdelave podatkov. Podatke o incidenci raka v Sloveniji in na Hrvašk<:Jm lahko redno poišcemo v letnih porocilih obeh registrov. V preostalih delih Srbije in v drugih republikah je registracija raka od 1. 1. 1986. dalje z zakonom predpisana in obvezna, vendar kot lahko razberemo iz poro­cila Zveznega zavoda za zdravstveno varstvo Received: July 1, 1991 -Accepted: August 30, 1991 Pompe Kirn V. Epidemiološki pogled na problematiko raka v Sloveniji in Jugoslaviji novembra 1990 (lzveštaj o prijavi malignih neo­plazmi u SFRJ u 1988 godini) (2), je v teh predelih registracija raka nepopolna in so vredno­ sti incidence podcenjene. Zvezni zavod za zdravstveno varstvo je v letu 1990 izdal še drugo gradivo: Smrtnost od malig­nih neoplazmi u Jugoslaviji 1969-1987 (3). Ce­prav mortaliteta ni reprezentativen podatek o obolevnosti, zaradi prevelike teže prognosticno neugodnih rakov in zaradi vpliva kvalitete zdrav­stvene službe na opredeljevanje vzrokov smrti, je to edini kazalec, ki ga po priporocilih SZO zbirajo skoraj v vseh deželah sveta. Za leto 1987. navaja Zvezni zavod za zdravstveno var­stvo za Jugoslavijo kot celoto koeficient 145,3/ 100000 prebivalcev. S takšnimi vrednostmi de­janske in tudi starostno standardizirane umrljivo­sti zaradi raka se Jugoslavija uvršca skoraj na dno evropske lestvice. Od te povprecne vrednosti znacilno odstopajo Slovenija, Hrvaška in Vojvo­dina z višjimi vrednostmi (207,3-202,2/100000), in se uvršcajo v sredino evropske lestvice. Zna­cilno nižje vrednosti so na Kosovu, v Crni Gori in Makedoniji (35,8-88,3/100000). V vseh republikah je bilo najvec smrti zaradi pljucnega raka. Najvišji koeficienti so bili v Vojvo­dini, na Hrvaškem in v Sloveniji. Primerjava podatkov iz let 1969, 1973, 1979, 1983 in 1987 kaže, da povsod narašca umrljivost za pljucnim rakom. Razmerje med spoloma (moški/ženski) je bilo v Jugoslaviji povprecno 6 : 1, najvecje na Hrvaškem in v Vojvodini (9 :1 ). Želodcni rak je bil kot vzrok smrti med raki na drugem mestu, ceprav se koeficienti povsod, razen v Bosni in Hercegovini ter Crni Gori, manjšajo. Razmerje med spoloma je bilo 3 : 2 za moške. ženske v vseh predelih Jugoslavije umirajo vsevec zaradi raka dojk. Najvišja umrljivost je bila leta 1987 v Sloveniji, Vojvodini in na Hrvaškem (33,9-21,8). Povsod je narašcala umrljivost zaradi raka grla, žrela, jezika in ustne votline, rektuma in debelega crevesa. Zaskrbljujoce je, da je v Jugo­slaviji leta 1987 še vedno 737 žensk umrlo zaradi raka maternicnega vratu. Povprecni koeficient je znašal 6,2/100000, najvišji je bil v Srbiji (10,9/ 100000 na ožjem obmocju in 8,4/100000 v Vojvo­dini). Glede na leto 1979 in 1983 so koeficienti na Hrvaškem porasli, v Sloveniji so se stabilizira­li, v Srbiji so upadli. Koeficienti so nekoliko porasli v Crni Gori, v Makedoniji in na Kosovu, vendar so bile zabeležene vrednost (1-2/100000) povsod precej nižje od jugoslovanskega povprec­ja. Nižje vrednosti mortalitete, cetudi so staros­tno standardizirane, ne pomenijo dejansko nižje umrljivosti v primerih, ko je odstotek slabo opre­deljenih vzrokov smrti velik, npr. 30% na Kosovu in 25% v Crni Gori. V teh primerih je mortaliteta zaradi raka gotovo podcenjena. Možnosti primarne in sekundarne prevent ive Namen prispevka ni v povdarjanju razlik v obolevnosti in umrljivosti, ampak v iskanju skup­nih opornih tock za boljšo organizacijo primarne preventive in zgodnjega odkrivanja tistih rakavih bolezni, kjer rizicne dejavnike poznamo premalo, da bi jih lahko aktivno preprecevali. Upoštevajoc dolgo latencno dobo vecine ra­kavih bolezni, znanje o rizicnih dejavnikih in o redu velikosti njihovega vpliva, razvite dežele Severne Amerike, dežele Evropske gospodarske skupnosti in nordijske države s pomocjo vecjih raziskovalnih centrov nacrtujejo, uvajajo in merijo uspešnost primarnih preventivnih programov. Clanice Evropske gospodarske skupnosti so sestavile skupino strokovnjakov za pripravo pred­loga programa »Evropa proti raku« januarja 1986 (4). Leto 1989 so proglasile za informativno leto o raku in izdale Evropski kodeks proti raku, ki obsega deset znamenitih zapovedi. Izpolnjevanje teh zapovedi naj bi do leta 2000 zmanjšalo umrljivost za rakom za 15%. Najvec si obetajo predvsem od uspešnega boja proti aktivnemu in pasivnemu kajenju. Epi­demiološke raziskave so pokazale, da bi se s prenehanjem kajenja lahko izognili 80 -90% pljucnega raka pri moških, 60-80% pljucnega raka pri ženskah, 30-70% raka mehurja, 30-40% raka ledvic in 30% raka trebušne slinavke. Ob prenehanju kajenja in zmanjšanju uživanja alko­holnih pijac bi lahko zmanjšali obolevnost in umrljivost za rakom grla in požiralnika za 75%, za rakom jezika, ustne votline in žrela pa za 85% (5). V izogib malignemu melanomu in drugim kožnim rakom odsvetujejo pretirano soncenje. Priporocajo omejevanje števila rentgenskih pre­gledov in upoštevanje. varnostnih predpisov pri proizvodnji, skladišcenju in uporabi karcinogenih snovi. Za podrocje prehrane, kjer so dognanja epi­demiologije in bazicne onkologije še skromna, dajejo splošna navodila: priporocajo predvsem biološko polnovredno, uravnoteženo prehrano brez kaloricnih viškov, fizicno aktivnost in vzdrže­vanje ustrezne telesne teže. V vseh predelih Jugoslavije predstavljajo ka­dilski raki velik delež rakov pri moških. V Sloveniji narašca število teh rakov pri moških srednjih let, tako da v Registru raka registriramo najvec pri- Radio/ lugosl 1991 ; 25 :259-62. Pompe Kirn V. Epidemiološki pogled na problematiko raka v Sloveniji in Jugoslaviji merov pljucnega raka in rakov grla, žrela in ustne votline med 50 in 64 letom starosti. Najvecji porast incidence opažamo prav pri rakih ustne votline, jezika, žrela in grla (6). V Sloveniji boj proti kajenju še ni dovolj dobro organiziran. Ob­staja nekaj društev nekadilcev, omejitev kajenja na sestankih in v nekaterih javnih prostorih, vendar je pravica nekadilcev do cistega zraka še vse premalo spoštovana. Alkoholizem je v Slove­niji velik družbeni problem. Tudi organiziranega presejanja (screening) za zgodnje odkrivanje raka maternicnega Yratu v Sloveniji še ni. lncidenca invazijske oblike tega raka je že deset let 17/100000 žensk in umrljivost 6/1 00000 žensk. V Sloveniji so še vedno ob­mocja z incidenco okoli 30/1 00000 in umrljivostjo okoli 10/100000 (obalne obcine). V starosti 60-69 let incidenca narašca, v starosti 60-64 let je povprecni letni porast celo 5,4%. Ženske hodijo na preventivne ginekološke preglede po lastni presoji, nekatere prepogostokrat, druge, bolj ogrožene pa premalo ali nikoli. Potrebno bo uvesti presejanje v pravem pomenu besede za ženske stare 27-55 let na vsaka tri leta po dveh zaporednih negativnih brisih (7). Skrbna merjenja uspešnosti presejanja drugod po svetu so poka­zala, da lahko s takšnim pregledovanjem zni­žamo umrljivost zaradi raka maternicnega vratu do 90%. Ker je problematika raka dojk posebno v nekaterih predelih Slovenije zelo velika (inci­denca je v ljubljanskih obcinah okoli 100/100000 žensk), poteka v organizaciji Onkološkega inšti­tuta v Ljubljani od leta 1989 randomizirana pilot­ska študija v šestih obcinah. ženske stare 50-64 let so vabljene na klinicni pregled in mamografijo. Rezultati študije bodo vodilo pri morebitnem uva­janju sistematicnih pregledov v najbolj prizadetih obcinah (8). Umrljivost zaradi raka dojk se lahko zniža od 35% do 40% (5), ce je le odzivnost žensk na ponujene programe dovolj velika ­40% smrti manj pri najbolj pogostnem raku žensk v Sloveniji bi pomenilo veliko število rešenih življenj. Kaj je bilo od navedenih možnosti storjenega v Sloveniji? Zveza slovenskih društev za boj proti raku je s pomocjo zdravnikov Onkološkega inštituta preoblikovala Evropski program v pro­ gram Slovenija 2000 in rak. Izdala ga je sredi leta 1990 (9). Pri tem je deset evropskih zapovedi spremenila v Sedem dobrih nasvetov in jim dodala še Sedam znamenj, oboje v obliki licnega letaka. V letu 1991 je izšlo posebno gradivo za ucitelje osnovnih in srednjih šol. V programu so zapisali, da Zveza slovenskih društev za boj proti raku in Onkološki inštitut, pobudnika in nosilca Radiol lugosl 1991 ; 25 :259-62. programa organizirata izobraže\Lanje in vzgojo celotnega prebivalstva Slovenije, konkretno v osnovni šoli, ki jo osem do dvanajst let obiskuje vsak Slovenec. Sodeluje tudi Rdeci križ ki ima zdravstveno vzgojo predvideno v svojem pro­gramu in s svojimi· organizacijami sega skoraj. v vsako našo vas. V tednu boja proti raku so Univerzitetni zavod za zdravstveno varstvo. Za­vod RS za šolstvo, Republiški odbor Rdecega križa Slovenije, Zveza društev nekadilcev ter Onkološki inštitut podpisali dogovor o izvajanju tega programa. V aprilu so stekli prvi tecaji za zdravnike in višje medicinske sestre. Zdravniki bodo poucevali ucitelje, ki bodo, tako kot višje medicinske sestre, posredovalci programa. Štirje clani kancerološke sekcije po predahu vec kot 15 let spet obiskujejo regijska kancerološka društva in regijske podružnice SZD z izbranimi prispevki iz onkologije. Poslušavci (zdravniki) najcešce želijo odgovor na vprašanja iz njihovega vsakda­njega dela z onkološkimi bolniki in iz lokalne ekološke problematike. Lahko recemo, da je zagnanost predavateljev na tecajih in obiskov na terenu zaenkrat še dovolj velika. Sprašujemo pa se, ce smo na pravi poti in delamo casu primerno. Prav gotovo je vsak zacetek težak in upamo, da bomo speljali evropski program tudi v našem prostoru navkljub težkim casom. Pri tem ne smemo pozabiti, da je evropski program široko zasnovan in da poleg zdravstvene vzgoje prebivalstva vsebuje še: pre­precevanje raka, izobraževanje zdravstvenih de­lavcev ter raziskovalno delo. To so kompleksne naloge, ki zahtevajo timski pristop strokovnjakov razlicnih strok (4). Tudi za zdravstveno vzgojo prebivalcev in preusmerjanje njihovih življenskih navad bi bilo potrebno storiti vec; po zgledu nekaterih uspešnih reklam v vecji meri prodreti v najbolj razširjene medije obvešcanja: radio, tele­vizija, seveda ne amatersko, temvec v sodelova­nju s psihologi, novinarji in vsemi tistimi, ki obvladajo tehniko sodobnega širjenja novic. Zelo poslušane kontaktne oddaje bi morali skrbneje pripraviti. Pametneje je javno povedati, da-je danes onkologija zelo široko podrocje in da vsak zdravnik Onkološkega inštituta ne more obvladati celotne onkologije; potem se ne bi zgodilo, da bi izpadli kot nepoznavalci, ko bi hoteli povedati nekaj, kar ni vec v skladu s sodobnimi dognanji. V Ljubljani poteka program CINDI, ki ga po navodilih in metodologiji SZO izvaja Zdravstveni dom Ljubljana. To je širše zasnovan preventivni program, ki vkljucuje vse tocke programa Slove­nija 2000 in Rak. Ali smo se medsebojno dovolj povezali? Ali bomo pri vzporednih preventivnih 261 Pompe Kirn V. Epidemiološki pogled na problematiko raka v Sloveniji in Jugoslaviji akcijah v Sloveniji pametno sodelovali? Kako bomo merili uspešnost? S programom CINDI je ocenjeno izhodišcno stanje na vzorcu prebival­cev Ljubljane, Onkološki inštitut ima že rezultate raziskave javnega mnenja iz leta 1989 (1 O). Kaj bomo dosegli leta 2000? Bojim se, da glavnega kazalca zaželjenega cilja, to je zmanj­šanje umrljivosti za rakom za 15% še ne, saj tega·v tako kratkem casu tudi realno ne moremo pricakovati. Veseli bomo lahko, ce bo ponovljena raziskava javnega mnenja leta 2000 pokazala, da je v starosti 20-40 let manj kot 50% kadilcev med moškimi in manj kot 40% kadilk med žen­skami. Toliko jih je po podatkih raziskave javnega mnenja bilo leta 1989. Veseli bomo tudi, ce bomo v Registru raka za Slovenijo namerili vecjo incidenco neinvazivnih intraduktalnih rakov dojk in vec primerov intraepitelijske oblike raka mater­nicnega vratu med ženskami po 40.letu starosti. Potem bomo lahko upali, da bodo cez nekaj let tudi rezultati merjenja umrljivosti zaradi raka ugodnejši. Povzetek -Zbolevanje za rakom je v posa­meznih republikah Jugoslavije glede na razlicno starostno strukturo, razlicne življenjske navade in razlicen socialno ekonomski položaj razlicno. Reprezentativni podatki o incidenci raka so na voljo le za Slovenijo, Hrvaško in Vojvodino. V ostalih obmocjih Jugoslavije se registracija šele uvaja, zato lahko ocenjujemo incidenco le iz podatkov o umrljivosti. Te ocene zaradi prevelike teže prognosticno neugodnih rakov niso repre­zentativne; nanje vpliva tudi kvaliteta opredelje­vanja vzrokov smrti, ki je v posameznih republi­kah razlicna. V vseh republikah je najvec smrti zaradi pljucnega raka, na drugem mestu je želodcni rak, na tretjem rak dojk. Umrljivost zaradi pljucnega raka pri moških in raka dojk pri ženskah narašca povsod, enako tudi umrljivost zaradi raka ustne votline, jezika, žrela in grla ter danke in debelega crevesa. Najbolj narašcajo raki, ki jih v 70-80% pripisu­jemo kajenju. V boju za 15% zmanjšanje umrljivosti zaradi raka si tudi v Sloveniji in Jugoslaviji lahko najvec obetamo od dobro pripravljenih akcij zoper ak­tivno in pasivno kajenje in zoper alkoholizem ter v premišljeni, našim pogojem prilagojeni organi­zaciji sekundarne preventive, tj. presejanja (screening) žensk za prekancerozne spremembe in zgodnje stadije raka maternicnega vratu in dojk. V Sloveniji potekata v letu 1991 dva preven­tivna programa: Slovenija 2000 in rak, v organi­zaciji Društva za boj proti raku in Onkološkega inštituta in Program CINDI v organizaciji Zdrav­stvenega doma Ljubljana. Literatu ra 1. Pompe Kirn V, Primic L'.akelj M. Epidemiološke metode v onkologiji. Med Razgl 1988; 27:283-303. 2. lzveštaj o prijavi malignih neoplazmi u SFRJ u 1988 godini. Savezni zavod za zdravstvenu zaštitu, Beograd 1990. 3. Smrtnost od malignih neoplazmi u ,Jugoslaviji. Savezni zavod za zdravstvenu zaštitu, Beograd 1990. 4. Europe against cancer programme: proposals by the European Commission. Official journal of the European Communities 1987; 30 :1-56. 5. Cancer, Causes, Occurence and Control. Toma­tis L. ed. IARC, Lyon, 1990 (IARC Sci Pubi No 100). 6. Pompe Kirn V. lncidenca rakov ustne votline, orohipofarinksa in grla mocno narašca. Zdrav Vestn 1991 (v tisku). 7. Pompe Kirn V, Kovacic J, Primic L'.akelj M. Epidemiološka ocena zgodnjega odkrivanja raka ma­ternicnega vratu v Sloveniji v letih 1977-1986. Zdrav Vesin 1991. 8. Pompe Kirn V, Vlaisavljevic V, Kaucic M, Jelincic V, Us J, Rudolf Z, Novak F. Pilot study of breast cancer screening in six communes of Slovenia. In: Coleman M. et al(eds): Directory of on-going research in cancer epidemiology 1991. Lyon, IARC, 11 O· 1. (IARC scientific publications: 101 ). 9. Slovenija 2000 in rak. Zveza slovenskih društev za boj proti raku in Onkološki inštitut, Ljubljana 1990. 1 O. Primic L'.akelj M. Zdravstvena prosvetljenost polnoletnih Slovencev o raku. Onkološki inštitut, Ljub­ljana 1991 (specialisticna naloga). Naslov avtorja: prof. dr. Vera Pompe Kirn, Onkološ­ki inštitut, Zaloška 2, 61105 Ljubljana, Slovenija Radiol lugosl 1991; 25:259-62. Report INTERREGIONAL TRAINING COURSE ON NUCLEAR MEDICINE organized by IAEA held at the Nuklearmedizinische Klinik Klinikum Berlin Buch, Germany September 16 -October 11, 1991 The Training Course was organized and finan­ced by the lnternational Atomic Energy Agency (IAEA), Vienna in cooperation with the World Health Organization and Ministry of Research and Technology of the German government, Bonn. The program of the Course included theoretical and practical training in general clinical application of radionuclides in medicine (diagnostic and thera­peutic), safe handling of radioisotopes, data analy­sis for in vivo and in vitro in11estigations with radionuclides and organization of radiation protec­tion and radiopharmacy services in nuclear medi­cine practice. The Course also acquainted the students with some of the recent advances in nuclear medicine such as immunoscintigraphy and positron emission tomography. Prof. H. Deckart, who was the Course director and chairman of ali sessions, should be mainly credited tor the excellent perforrnance ot the cour­ se. It would be impossible to mention ali the speakers -internationally renowned protessionals -whose lectures enriched the knowledge of parti­ cipants on particular topics, and who were always ready tor discussion, additional explanations and confronting ot ideas. Nevertheless, 1 should men­ tion at least some of them. In the first part ot the Course, which was dedicated prevailingly to basic research and in vitro investigations, we had the opportunity to attend lectures on radiopharmaceuticals by Prof. G. Subramanian from New York and Dr. S. Hesslewood from Birmingham. The lectures ot Dr. R. Piyasena were centred on radioimmu­noassay, quality controls and, nevertheless, on the possibilities of progress in developing countries. The second part of the Course was more clinically oriented. There we had the opportu­ nity to enjoy the excellent lecture on investiga­tions in nephrology by Dr. K. Britton where clearly delineated principles were presented along with further perspectives ot these functional investi­gations. He also reported on their experience with radioimmunotherapy (intraabdominal applications) and the use ot MIBG in neuroblastoma therapy, with emphasis on the importance ot MIBG as a first-line therapy. Namely, chemotherapy often cau­ses dedifferentiation of tumors which renders MIBG treatment ineffective. The cases of patients with advanced disease who have been cured point out, however, that the problem of radiation protection is worth solving, and that the treatment should be started in due tirne. In his lecture Prof. J. F. Chatal from Nantes gave a clear review ot tumor markers, whereas Prof. E. Pauwels trom Leiden lectured on the diagnostics ot arthritis and on thyroid scintigrap­hy. Diagnostic procedures in thyroidology and thyroid oncology with all dilemmas were excellen­tly reviewed and summarised from other lectures by Prof. H. Deckart trom Berlin. He emphasized the importance of team work in the diagnosis and treatment of thyroid diseases, which is essential tor optimum results. Apart from his investigations in hematology, Dr. K. Buchali from Berlin had theoretical and practical presentation ot his experience with preoperative lymphscintigraphy in malignant me­lanoma; using this method, corresponding sur­gery in high risk patients (Clark III -V) resulted in a 20% irnproved disease tree survival. The analysis of their results ot double blind study with 89-strontium therapy or saline as placebo was also interesting. They have treated skeleta! meta­stases ot prostatic carcinoma and, unexpectedly, beside the effect on pain a higher survival rate was found after Sr application. Radiol lugosl 1991; 25:263·264. Report Prof. U. Buell from Aachen had an intere­sting presentation on Nuclear lmaging Techni­ques in Brain. Many speakers had lectures related to cardio­logy, among them also Prof. A. Cuaron from Vienna (IAEA) who joined us during the last week of the Course. His clearly defined stand­points on furthering nuclear medicine in develo­ping countries and final panel discussion were met with great interest. The scope of the Course covered a large variety of topics, among them also the foliowing: dosimetry, radiation protection, instrumentation in nuclear medicine, adverse reactions to radiop­harmaceuticals, quality assurance at ali levels of nuclear medicine, endocrine orbitopathy, diag­nostics in inflammatory diseases, regular aspects of drug regulations, SPECT, PET, clinical use of stable isotopes, P-32-treatment of Polycythemia vera, nuclear medicine in hepatology, radiosyno­vorthesis in rheumatoid arthritis, diagnostic pro­cedures in endocrinology, pediatric nuclear medi­cine, recommendations of IAEA, etc. As it has been impossible to mention ali the speakers, it is also far beyond the scope of this brief report to enlist ali the questions, problems and topics that have been presented and/or discussed at the Course. Every afternoon was dedicated to a labora­tory course with practical training. Here we should specialiy point out the outstanding kin­dness and hospitality of the staff of Nuclear Medicine Glinic in Berlin-Buch. They were always open tor discussion and wiliing to provide extra information when needed. They never objected when a participant would express his interest in additional training. Without their help this training would not have been possible. We were enabled to visit the Nuclear Medi­cine Department in Berlin-Zehlendorf City Hospi­tal with demonstration of pulmonary function; Nuclear Medicine Glinic of the Charite Hospital in Berlin, as weli as the Nuclear Medicine Depar­tment of Friedrichshein-Hospital, Berlin, with lecture on Nuclear Medicine Emergency Diagno­stics. We also had an interesting scientific excur­sion organized to the Reactor Center in Rossen­dorf near Dresden. The social program was very rich, despite the tough schedule. Thus we had the opportunity to MFSTIUCTUI Ol.II\UTION DkAFT V,rnM.IVY\ HANDBOOK OF NUCLEAR MEDICINE PRACTICE IN DEVELOPING COUNTRIES ® INTERNATIONAL ATOMIC ENERGV AGENCY Fig. 1 -Pari of literature which was given to the participants at the course see Potsdam with Prussian Kings' Gardens and Palaces (Sanssouci, Cecilienhof), Bernau, Dres­den with the King's palaces, galieries and Kcnig­stein, as well as Sachsische Schweiz (Elbsand­steingebirge) and Rembrandt exhibition. The participants were from 24 different coun­tries world-wide, Europe, Asia, Africa and Latin America. By the end of the Course it was our generally belief that, apart from gaining additional professional knowledge, we got useful ideas how to improve our routine diagnostic and treatment methods together with guidelines tor our further research work. The Course has confirmed that nuclear medi­cine remains an indispensable part of in vitro and in vivo diagnostics and therapy so in the develo­ped as weli as in developing countries. Undoubtedly, in organizing this Course, IAEA has not just met but actualiy surpassed the expectations of participants. Finally, thanks to the Agency, almost all participants received fel­lowships which enabled them to attend this va­luable professional training. Viljem Kovac, MD Radiol lugosl 1991; 25:263-264. EUROPEAN SCHOOL OF ONCOLOGY The Institute of Oncology and the Faculty of Medicine Ljubljana, Slovenia, Yugoslavia Preliminary Announcement 2nd Rare Tumor Symposium MALIGNANT MELANOMA AND PREGNANCY Thursday 26 -Friday 27 March, 1992 in Ljubljana, Slovenia, Yugoslavia The Symposium will consist of a series of invited lectures dealing with the immunological and hormona! changes in pregnancy, the incidence of this condition, natural course of the disease as well as its diagnpsis and treatment. The lectures will be followed by a poster sessioi1 and oral presentations. A conference planned for the end of the Symposium is intended to produce guidelines for the diagnosis, treatment and prevention of this rare condition. For more detailed information please contact: Symposium Secretariat Ms. Olga Shrestha The Institute of Oncology Zaloska 2, 61105 Ljubljana Slovenia, Yugoslavia Tel.: +38 61 327 955 Fax: +38 61 329 177 ,; I r .< ,../ ...> SEKCIJA ZA RADIOLOGIJU HRVATSKOG LIJECNICKOG ZBORA ODJEL ZA RADIOLOGIJU MEDICINSKOG CENTRA VARAŽDIN JUEIILARNI DESETI ZNANSTVENI SKUP RADIOLOGA HRVATSKE Varaždin, 4. -7. prosinca 1991. godine. DRUGA OBAVIJEST Teme: 1. Dijagnosticka i intervencijska radiologija probavnog sustavaa 2.a Dijagnostici e\­ \'<>'O\ ·e, () \('<>0\ i oi, \ {'" .§-f,0s oo •e0\ . e . \ .o \ : :::: : ......:::::::•· @ lek tovarna farmacevtskih in : , L kemicnih izdelkov, n.sol.o, Ljubljana danes najuspešnejši kinolonski preparat Cenin® / Ciprobay® ciprofloksacin širokospektralni kemoterapevtik • hitro baktericidno delovanje na gram pozitivne in gram negativne mikroorganizme kakor tudi na problemske klice • izrazito delovanje na psevdomonas • hiter terapevtski uspeh zaradi visoke ucinkovitosti • dobra prenosljivost • samo dvakratna dnevna uporaba, kar pomeni veliko olajšanje v klinicni in splošni praksi • prednost tudi zaradi oralnega zdravljenja na domu Kontraindikacije: preobcutljivost za ciprofloksacin; otroci in mladi v dobi rasti; nosecnost, dojenje; previdnost pri starejših bolnikih in poškodbah osrednjega živcevja. Bayer-Pharma Jugoslavija Ljubljana ,. 11111 Byk Gulden Konstanz/SR Nemacka RENTGENSKA KONTRASTNA SREDSTVA: HEXABRIX -kontrastno sredstvo niskog osmoaliteta, smanjene toksicnosti i gotovo bezbolan u primeni. INDIKACIJE: Sva arteriografska ispitivanja, zatim cerebralna angiografija, i flebografija, kao i selektivna koronarografija. PAKOVANJA: Hexabrix amp. (5 amp. x 10 ml) Hexabrix amp. (20 amp. x 20 ml) Hexabrix boc. (2 boc. x 50 ml) Hexabrix boc. (1 boc. x 100 ml) Hexabrix inf. (1 boc. x 200 ml bez pribora za infuziju) DIMER X ampule 5 x 5 ml -kontrast za lumbosakralnu mielografiju TELEBRIX -kontrast za urografije, angiografije, periferne i selektivne arteriografije. PAKOVANJA: Telebrix 300 amp. (20 amp. x 30 ml sa špricom) Telebrix 300 amp. (20 amp. x 30 ml bez šprica) Telebrix 380 amp. (20 amp. x 30 ml sa špricom) Telebrix 380 amp. (20 amp. x 30 ml bez šprica) Telebrix 380 za inf. (2 boc. x 50 ml) Telebrix 300 za inf. (2 boc. x 50 ml) Telebrix 30 za inf. (1 boca x 100 ml) Telebrix 45 za inf. (1 boca x 250 ml) Byk Gulden FABEG Predstavništvo: lnostrana zastupstva Hotel »Slavija lux« A-158 .11111 Beograd, Kosovska 17/VI Beograd, Svetog Save 2 telefoni: 321-440 i 321-791 @) tel. 434-712 fax. 431-517 •' -J /l -r'/ '/._. SIEMENS SOMATOM AR.T SIC 212 Ganzkorper-Computertomograph (IJ ) , J 00 rnrnrnu.m Medicinski rendgen film Podrucje primene • Opšti rendgenski pregledi • Specijalni pregledi sa automatskim transportom ili s tehnikom uskladištenje Svojstva • Srednje brzinski i visoko kontrastni film, osetljivosti prilagodene univerzalnoj upotrebi • Sjajne slike s visokem sposobnošcu dijagnostickog opažanja • Robustna površina filma s niskim koeficijentom trenja. Narocita podesno za zamene filma i tehniku uskladištenja • Prikladan za upotrebu sa svim folijama (CaWO4 i retke zemlje) • Harmonicno plava obojena Gevar -Polyester podloga, obostrano obložena Obrada • Podesan za mašinsku i rucnu obradu 1 'ZIll..HA\.. §AUBA\