UDC 616-006(05)(497.1) GODEN RDIUA 4 YU ISSN 0485-893X RADIOLOGIA IUGOSLA VICA ANNO 25 1991 FASC 4 PROPRIETARII IDEMQUE EDITORES: SOCIETAS RADIOLOGORUM IUGOSLAVIAE AC SOCIETAS MEDICINAE NUCLEARIS IN FOEDERATIONE SOCIALISTICA REI PUBLICAE IUGOSLAVIAE LJUBLJANA 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 shern (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 1 O let: 20 µ,g proteina površinskega antigena v 1 ml suspenzije. Novorojencki in otroci do 1 O let: 10 µ,g proteina površinskega antigena v 0,5 ml suspenzije. Podrobnejše informacije in literaturo dobite pri proizvajalcu. ... KRK. tovarna zdravil, p. o., Novo mesto YU ISSN 0485-893X GODEN RDIUA 4 UDC 616-006(05)(497.1) RADIOLOGIA IUGOSLA VICA PROPRIETARII IDEMQUE EDITORES: SOCIETAS RADIOLOGORUM IUGOSLAVIAE AC SOCIETAS MEDICINAE NUCLEARIS IN FOEDERATIONE SOCIALISTICA REI PUBLICAE IUGOSLAVIAE LJUBLJANA FASC 4 ANNO 25 1991 Editorial Board Avcin J, Ljubljana -Benulic T, Ljubljana -Bicaku E, Priština -Borata R, Novi Sad -Fettich J, Ljubljana -Ivancevi<': D, Zagreb -Jamakoski B, Skopje -Jev1ic V, Ljubljana -Karanfilski B, Skopje -Kosti<': K, Beograd -Ledic S, 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 October -December 1991; 25:283-376 RADIOLOGIA IUGOSL/1.VICA The review for radiology, nuclear n,od1dne, rad,otl,erapy, cncology_ radiopl1ysics, radiobiology and rndiation protection. P!Jhlishe, s: 1_1,jruženje z::i radioiogiju .Jugosl;:i.vije and Udružen1e 7a nuldoarnu medicinu .Jugoslavije :·dv1sory 8oard: Lovrincevic; A, Sarajevo (pres,rJent) •-Boschi S, Split -Dakic D. Novi Sad -Dimitrova A, Skopje -Dujrnovic M Rijeka -Goldner B, Beograd -Guna F, Ljubljana -Hebrang A, Zagreb -lvkovic T, Niš -Jevti(; V, Ljubljar,a --Kamenica S, Beograd --Lišanin Lj, Beograd -Lc1asic l. Rijeka --Mine S, Sarajevo -Milutinovic P, f'pograd •-Mi!rovic N, Beograd -Plesnicar S, Ljub:jana -Porenta M, Ljubljana --Radojevic M, Skopje --f1ajicevic M, fitograd -Ristic S, Novi Sad -Ristov N, Skopie -Stankovic R. Priština --Šimonovic 1, Zagreb --Širn,Jnic S. Z:,greb ··· Šurlan M. Ljubljana -ladžer l. Sl(OPjP Re:,der tor English language: Shre5tha Olga UDC and Key words: mag. dr. Klemencic Eva, Institute tor Biomedical lnformatics, Faculty ot Medicine, University ot Ljubljana Secretary: Harisch Milica Address of Editorial Board: Radiologia lugoslav1ca The Institute ot Oncology, Zaloška cesta 2, 61000 Ljubljana, Slovenia P11one: 061;110-165, Fax 38 61 329 1T/ ONK lf·IST LJB YU Pub!ished quart8rly: Subscription rate --tor institution 2300 SL T. individual 600 SL T. Subscription rate --for institution 100 US $. indiv1dual 50 US $ Single 1ssue -tor instilution 700 SL T, ind,vidual ?00 SL T. Single issue -tor instit1Jtions 30 US $, inrtividual 20 US $. 8ank account number: 50101„678-48454 Foreign currency account number: 50100-620-010-257300-5130/6 L.B ·· Gospodarska banka --Ljubljana lnrJexed anrJ/or abstractP,d by: BIOMEDICINA IUGOSLAVICA, BOWKER R.R. ULRICH'S INTERNAT. PERIOD. DIRECTORY, CHEMICAL ABSTRACTS, EXCERPTA MEDICA, MEDICO INFORMATIONDIENSTE GmbH, PHYSICS IN MEDICINE ANO BIOLOGY, SOVJETSKI.) 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UDC 616-006(05)(497.1) CODEN RDIUA 4 YU ISSN 0485-893X RADIOLOGIA IUGOSLAVICA ANNO 25 1991 FASC.4 Editorial On the Publication of the 25m Volume Benulic T 285 Diagnostic radiology Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty (orig sci paper) Dujmovic M, Lovasic 1 287 Superior mesenteric artery (SMA) aneurysm with a Martan syndrome -Case report (case report) Radanovic B, Šimunic S, Borcic V, Oberman B, Strozzi M, Škegro M lnterventional radiology lntraarterial digital subtaction angiography of the intracranial blood vessels -lmaging costs analysis (orig sci paper) Bošnjakovic P, lvkovic T, llic M, Milatovic S, lvkovic A 301 Digital subtraction sialography (profess paper) Borkovic Z, Katic B, Ožegovic 1 305 From practice tor practice -Cardiovascular system (case 4) Klancar J 309 Computerized tomography and ultrasound Possibilities of computed tomography in evaluation of gastric neoplasms extension (orig sci paper) Jankulov V, Lincender L, Lovrincevic A, Obradov M 311 Application of intraoperative ultrasonography in biliary surgery (orig sci paper) Drinkovic 1, Gabelica V, Makaruha B, 2upancic K, Boko H, Brkljacic B, Vidjak V 315 Nuclear medicine Values of THS receptor autoantibodies (TRAb) in patients with treated Graves' disease (orig sci paper) Paunkovic N, Paunkovic J, Pavlovic O 319 Preliminary report on radiochemical and preclinical study tor the registration of scintimun CEA in Hungary (orig sci paper) Rakias F, Szentogyorgyi P, Janoki Gy 325 Radiol lugosl October -December 1991; 25:283-376 GFR (Cr-EDTA) values in children with IDDM with respect to the disease duration (profess paper) Grujic E, Ducic V, Babovic D, Arihodžic N 331 Pentavalent technetium-99m-(V)-DMSA uptake in an occult medullary carcinoma of the thyroid (case report) Brkljacic B, Tomic-Brzac H, Halbauer M, Bence-Žigman Z, Pavlinovic ž, Kušter ž, Težak S 335 Radiotherapy -Oncology Radiotherapy of intracranial childhood tumours with 9 meV linear accelerator (NEPTUN 10-P) (orig sci paper) Koscis B, Pap L, Horvath A, Kaldau F, Gyenes G, Bajcsay A, Kontra G, Varjas G 339 The effect of new understanding of curable breast cancer and related with that changed treatment approach on five-year disease-free survival and overall survival of breast cancer patients (orig sci paper) Lindtner J, Eržen D 345 Experimental oncology Local treatment of fibrosarcoma SA-1 and malignant melanoma B-16 solid tumors in mice by electrical direct current: A preliminary report (prelim report) Miklavcic D, Serša G, Vodovnik L, Novakovic S, Bobanovic F, Reberšek S 351 Letter to Editor Kontrastna sredstva pri slikanju z magnetno resonaco Contrast agents in MR imaging Kristl V 355 Reports Dose in radiotherapy -ESTRO-IAEA Seminar, Leuven, September 1991 Umek B 361 ESTRO teaching course 9f basic clinical radiobiology, Athene, October 1991 Jancar B 362 Book review Cancer in organ transplant recipients. Schmahl D, Penn l. eds, 1991 Kovac V 363 Appendix Author's index 367 Subject index 369 Reviewers in 1991 370 Radiol lugosl October -December 1991 ; 25 :283-376 On the Publication of the 25th Volume As the present No.4/91 of RADIOLOGIA IUGOSLAVICA actually represents the 25th volume of our journal, and thus symbolises its successful continuation, it seems right that we say a few words about its beginnings and development till now. The start of our activity reaches back to the year 1964. At that tirne, on the occasion of the IVth Yugoslav Congress of Radiology, a decision on the foundation of a radiological journal was taken at the initiative of Prof. Dr. Božena Ravnihar. From the very beginning till now, the seat, i.e. editorial office of this newly established journal has been situated at the Institute of Oncology in Ljubljana. The first and many following issues were edited and prepared by Prof. Dr. Stojan Plesnicar, in collaboration with one of the pioneering edi­tors and coworkers of our journal, Prof. Dr. Ivo Obrez. Thus, after several years, RADIOLOGIA IUGOSLAVICA successfully filled the gap left behind after discontinuation of »Radiološki glasnik« that had been appearing in the period between 1935-1940 in Zagreb. Let us hope that the recent war entailed by the disintegration processes in Yugoslavia will not in a similar way interfere with the publica­tion of our journal. In the past 25 years there were over 12000 pages of scientific and professional papers as well as other contributions perti­nent to the fields of x-ray diagnostics, nuclear medicine, oncology, radiobiology, radiophy­sics, radiation protection and allied subjects published by our journal. By the development of new, specially technical, subfields in medi­cine, contributions covering the topics of ultra­sonography, computed tomography and mag­netic resonance etc. have been gradually included in our journal. From the very beginning the journal has been appearing regularly on the quarterly basis; apart from these regular numbers, there were also occasional supplements pu­blished which were dedicated to particular topics of medicine. Our tendency to favour English over national languages was based on the idea that in this way the journal could surpass the borders of a national publication and enable a more efficient flow of scientific information. Among the authors are many renowned national and international professionals and scientists, as well as numerous promising young research workers. Thus our journal has been playing an important role in the professional education in the field of scientific publishing, and for this important mission deservedly received a number of awards from Yugoslav federal and national institu­tions. Without exaggeration we can say that, due to its permanent development in the design and context, our journal is abreast of other similar publications abroad. On the occasion of our 25th anniversary, the editorial board has decided to publish a book entitled »Advances in Radiology and Oncology«. The publication is being prepa­red in collaboration with many prominent national and foreign authors, and will com­prise a number of outstanding original scienti­fic papers and review articles in the fields covered by our journal. It is hoped that the book will be well accepted by the worldwide scientific community. On the other hand, the experience gained through its editing and publication will prove invaluable for our future development and will influence the editorial board's policy in preparing further regular numbers of the journal. On this occasion our due thanks should be given to the authors and coworkers whose collaboration enabled the continuation and development of our activity despite the pre­sent difficult situation that we tace nowadays. lf our mutual efforts and dedication have in any way contributed to the promotion of medical science and related to it improved quality of patients' life, this would be the best reward tor the staff as well as tor ali the coworkers of our journal. Tomaž Benulic, MD, Editor-in-Chief !!i a::I L U Ei L J U B L J A N A d.d. 61000 LJUBLJANA, MAŠERA-SPASICEVA ul. 10 T.lefoni: n.c. (061) 371-744-direktor: 371 689 prodaja: 374 436, 374 809, 374 981, 372 219 Fax: 371 568 OSKRBUJE lekarne, bolnišcice, zdravstvene do­move ter druge ustanove in podjetja s farmacevt­skimi, medicinskimi in drugimi proizvodi domacih proizvajalcev, s proizvodi tujih proizvajalcev pa s pomocjo lastne zunanjetrgovinske službe! Proizvaja ALLIVIT PLUS® Kapsule cesna z dodatkom zdravilnih zelišc. Prodajna in dostavna služba posluje vsak dan neprekinjeno od 7. do 16. ure, razen sobote. UNIVERSITY OF RIJEKA, MEDICAL FACULTY, DEPARTMENT OF ANATOMY CLINICAL HOSPITAL CENTER RIJEKA, DEPARTMENT OF RADIOLOGY RADIOLOGICAL ANATOMY OF THE STOMACH AND DUODENUM FOLLOWING VAGOTOMY AND PYLOROPLASTY Dujmovic M, Lovasic 1 Abstract -The study comprises 1358 patients who have undergone total vagotomy (TV) selective vagotomy (SV) with sec. Finney or sec. Heineke-Mikulicz. Our descriptions of gastric morphology following TV and SV deviate from those reported in literature. Hypertonic wedgelike or horn -like forms dominate in a definite postoperative picture of the stomach. Otherwise, this shape is typical tor SSV. The appearance of pylorobulbar area corresponds to the one reported in literature with remark !hal pseudodiver­ticular protrusions of contours were represented to a much lesser ectent. Hypotonia or spasm is found in the changed from of duodenal curve in 50% of the patients. UDC: 616.33-006.6-089:616.33-073.75 Key words: vagotomy; pylorus-surgery, duodenum-radiography Orig sci paper Radiol lugosl 1991; 25:287-96. lntroduction -Vagus resection and its in­fluence on secretion and motility of the stomach have been known long ago. The surgical method in duodenal ulcer disease treatment by vagotomy combined with pyloroplasty as a drainage met­hod is based on this cognition. During radiological stomach and duodenum examination following vagotomy and pyloropla­sty, the changed anatomical appearance can be the cause of difficulties in interpretion of the occurred morphological changes. It represents a great diagnostic problem not only tor the less experienced radiologist, but even tor the one with long roentgenologic experience if he is not familiar with the changes of anatomical relation­ships entailed by this drainage method. At pre­sent, we can look back at the analysis of definite X-ray changes of the stomach and duodenum from a longer tirne period. Material and methods -During a 20-year period from 1965 to the end of 1984, 1358 patients with ulcer disease underwent vagotomy using one of drainage methods at the Surgical Clinic, Clinical Hospital Centre Rijeka. Selective anterior and complete posterior va­gotomies, combined with Finney's pyloroplasty, were carried out most frequently. This combina­tion was applied in 974 examined patients (72%). Total anterior and posterior vagotomy with Fin­ney's drainage method was performed 249 times and the Heineke-Mikulicz pyloroplasty 105 times. Other combinations were carried out in a lesser number of cases. Radiological-anatomical appearance of the stomach has been conditioned by complex of symptoms as a whole, occurring in various com­binations. The following was estimated: gastric shape and size, appearance of fundal gas bub­ble, secretion on an empty stomach, gastric emptying, tonus and gastric wall peristalsis. The first (early) postoperative examination was performed in all the patients as a rule between the eighth and the tenth day following after surgery, after the nasogastric probe had been removed. Gastric and duodenal examination was managed in standing position of the patient. Examination of the complete gastric emptying was carried out between the fifth and the sixth hour after a contrast intake. Not all the operated patients underwent the second (late) routine postoperative examination, but only those who appeared tor a check up tor some disturbances and those randomly called . Dujmovic M, Lovasic l. Radiological anatomy of the stomach and duodenum following ·vagotomy and pyloroplasty because of verification of the appearance and function following gastric vagotomy and pyloro­bulbar area. It was done within a long-time interval rangins from two months up to ten and more years. Results -The dominance of symptoms on the first (early) control examination was as follows: a reduced tonus of the gastric wall, a stomach enlarging and on increased secretion on the empty stomach. Taking into consideration the expressive stage of the aforementioned sym­ptoms all the examined patients were divided into two groups (Table 1 ). The first group comprised the patients with less expressed symptoms. No retention of gastric contrast medium was observed during the se­cond phase of the examination (60% of the operated examined cases). Table 1 -Gastric form at the first (early) postoperative examination. OPERATED PAT IENTS Group I Type •t .form!:. 1 w1thin the No. '/, Type 1 -characterized by a lesser curvature broken at a right angle in the angulus area. Vertical segment is usually narrower related to the wider horizontal one. No peristaltic waves are discerned along the lesser curvature. Fundal gas bubble is slightly enlarged (Fig. 1 a). Type 2 -a hook-like shape with clearly expres­sed longer and wider descending part and shor­ter and narrower ascending part. Small peristaltic waves of a dissimilar amplitude are better obser­ved along the greater than the lesser curvature. Enlarged gastric fundal gas bubble is limited at the lower part by an ample level of liquid content being of greater horizontal than vertical diameter, just the same as in the remaining three gastric forms (Fig. 1 b). Type 3 -a horn-like shape with strong wall tonus. small fundal gas bubble, and the lower­ >---·-l·----jr------,---t------+=. 1. -.11 ___ _'3.-.--45,1 - i ---11 160 32,J 59,2 1 · C'W111-.... 1 9,7 2,9 i.,,_-11_,. __ 1 Fc.,_ ­..... ;, [f .. -15': 1 ·Q8T 1358 The patients with strong retention and few cases of gastroplegia were included in the se­cond group with markedly expressed symptom triad described. A high secretion column was above the contrast medium (40% of the operated examined patients (Fig. 2). According to our experience four gastric types Fig. 1 a -The stomach with broken lesser curvature at are distinguished in the first group. a right angle Radiol lugosl 1991; 25:287-96. Dujmovic M, Lovasic l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty Fig. 1 b -A hook-like stomach most placed pylorobulbar part. This form was found less frequently and the contrast medium evacuation was accelerated (Fig. 1 c). Type 4 -a wedge-like shape with formed cascade in the area of relatively larger fundal gas bubble (Fig. 1d). Estimation of secretion is possible on basis of secretion height column measuring and the leve! extension. Stimating the stage of secretion for the whole first group we are satisfied with conclu­sion it varies from completely empty stomach to hypersecretion of a medium degree. We didn't get involved in more accurate estimations for the quantity of secretion often increased in front of us during diascopy. A great amount of secretion was evident in the second group on an empty stomach, being often increased in the course of examination. Taken barium suspension decrea- #)> ' Fig. 1 c -A horn-like stomach sed in the secretion like a »snow drop«, and the secretion was often mixed with food residues (alimentary retention). The second (late) postoperative examination is characterized by regression of ali radiological simptoms established during the first control examination. Hypersecretion and hypotonia gra­dually disappear to the end of the third and the fourth week after operation. Peristalsis becomes normal in this period. Those few cases of hyper­secretion and hypotonia after this period comple­tely vanish, according to our experience, to the end of the eighth week. Namely, radiological picture stabilizes, being definite from the sixth month onwards. A turnabout of radiological picture, concerning the tonus, secretion and peristalsis is evident (Table 2). In ali the examined cases wall tonus Dujmovic M. Lovasic l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty Table 2 -Definite gastric form following vagotomy and pyloroplasty expressed on the sample of 120 examined patients. Comparison with control group of 120 inopera- ted examined patients without ulcus. I! ,7 39,6 1,0 ril 1 ! 2. •• 1 1 o o 1 1 08 ' ___ !!_ ' j 1 OPF.RAlED PAllENTS CONI RCJL GROUP 1 Group :10 r-.;------.;-. 22 1 18,2 1 1 . --; ----.;;7 1 22 1 18. 2 1 85-W ' 1 · was re-established and the increased secretio, disappeared. Dividion into the first and the se­cond group, as it happened during the first control examination, became unnecessary. Here all the examined operated patients who under­went follow-up were ranged into the first group. There is also a complete turnabout of radiologi­cal gastric feature within the first group. AII the examined patients display normal or increased wall tonus, regular rhythmical and symmetrical peristalsis, there is no secretion on the empty stomach at all, and the size of stomach is normal. Four gastric types described earlier in the first group are now represented in quite inverted numerical relationship. A wedge-shaped stomach with formed cascade or without it is most frequently found (39.6%), (Fig. 1d). Other­wise, this form is characteristic tor the suprase­lective vagotomy (SSV). A horn-like stomach is in the second place (23.2%), (Fig. 1c). Both shapes are characterized by the lowermost pla­ced part corresponding to plastic area. The lu­men is gradually spread from this place to the fundus where the stomach is mostly extended, and the fundal gas bubble is more or less enlarged. This gas bubble is larger in the wedge­like stomach. A hook-like shape (Fig. 1 b) and the from of a lesser curvature broken to a right angle (Fig. 1a) are equally represented (18.2%), but to a lesser extent, compared to the first two forms. The sinus is their lower-most part of the stomach. The stomach is empty before taking food in all the forms and the peristalsis is regular and Fig. 1 d -A wedge-like stomach symmetrical. Peristalsis is absent or it is discerni­bly smaller only in a stomach with lesser curva­ture broken at a right angle. Therefore, such a form of gastric lesser curvature and the form of the stomach as a whole are thought to be caused because of the tonus difference alongside its one and other side as a consequence of the surgical treatment. We had a good display of pylorobulbar area during the first control examination in approxima­tely 60% of the examined patients. Some featu­res, becoming typical during the second exami­nation and later controls, appeared only indivi­dually. It was not possible to distinguish one type of the drainage operation from the other. We always had good display of the whole duodenal curve including pylorobulbar area at the second control examination. OujmoviC M, LovasiC l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty Fig. 2 -Ectatic, atonic ventriculus tuli of secretion on an empty stomach. A weak display of pylorobulbar area At the Finney's drainage operation pylorobul­bar area is characterized by a wide canal the gastric contrast medium is continuously moving through (Fig. 1 b, 1 d). Occasionally, there was an impression of passage discontinuity due to a gastric wall peristalsis and the position of the patient. Bulges of irregular and unusual shape can be observed on contours of both sides (Fig. 3a), and pseudodiverticulous formations are ra­rely found (Fig. 3b). Characteristic sign is more or less caused by the expressed ridge at the site of plastic, being visible as an impression of sharply bordered contour (Fig. 3c) and as a linear illuminated contrast shadow thrusting into the lumen from the side of greater curvature at the site of plastic. These both signs should be typical far the Finney's operation. Using a dou­ble-contrast technique the border of gastric and duodenal mucoust membrane can be often well observed. Spherical appearance of the outer contour of the upper and the descending duode­nal part represents the third typical sign of this operation. Decrement of the duodenal curve t Fig. 3a,b,c,d -Typical changes of the form of pylorobul­bar area and duodenal curve appears as a result of wide junction between the stomach and duodenum (Fig. 1,2,3,4). Wide junction between the stomach and duo­denum with continuous passage of contrast me­dium have also been found at Heineke-Mikulicz operation. Contour at the site of plastic is usually protruded (Fig. 3d), while so many times mentio­ned and described pseudodiverticula (»Heineke­Mikulicz« diverticula or »dachshund ears«) (1,2,3,4,5,6) are not so much represented in our report (Fig. 4). Spherical outer contours of duode­nal curve are expressed to a much lesser extent than at Finney's operation (Fig. 4). The remaining part of duodenal curve is of equal appearance regardless whether it is a question of one or another type of pyloroplasty. Continuous filling of the whole duodenal curve is Dujmovic M, Lovasic l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty Fig. 3b found in approximately 50% of the patients by demonstration of mucosal configuration (the pic­ture of »watering-can«) (Fig. 1 b). Narrower lu­men accompanied with lesser ar stronger expres­sed spasm is present in 25% of the patients. Often findings are edematous, inflammatory changed mucosal folds (Fig. 5a). Pronounced hypotonia with occasionally visible antiperistaltic waves is present in the remaining one fourth (Fig. 5b). Discussion -Without getting into details, Bee­ger and Vogel (1) report stomach enlarging, reduced peristalsis with uncoordinated contrac­tions and slow evacuation in the truncal vago­tomy (TV). Changes in the selective vagotomy (SV) are identical to those in TV, but with earlier regression. It primarily aplies to re-establishment Fig. 3c of tonus, following in the third ar the fourth week, but not later than the third month. Sapounov (3) reports in detail the gastric pic­ture following vagotomy (SV) based on 400 operated and examined patients. He describes normal appearance of the stomach and neat emptying in 56% of patients. A wedge-like form of corpus and fornix, typical far SSV, with neat emptying is found in 25% of patients. 18% of patients developed ectasy with slow evacuation. Gastroplegia is observed in 2.5% of patients. Comparison of the forms found, and general appearance of the stomach is neither possible nor authoritative at the first examination because of various types of vagotomy and pyloroplasty and their mutual combinations (1,2,4,5,6,7,8). According to the description of the stomach appearance our finding are more similar to those Dujmovic M, Lovasic l. Aadiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty r J Fig. 3d described by Sapounov (3), being essentially dissimilar in the number of particular findings. »Normal finding« and marked ectasies and hy­persecretions with normal evacuation are much more represented in his findings (80%). The difference in the appearance of the antral part of the stomach is even greater. Relatively narrow antrum has been found by Sapounov in the equal percentage (80%). Namely, he considers the patient with ulcus to have dysfunction of antral wall and the pyloric canal caused by fibromuscular hypertrophy, inflammatory infiltra­tion and degenrative nervous changes. Vago­tomy is followed by more or less expressed muscular decompensation of other parts of the gastric wall. We should also favour this explana­tion since we found such findings in those pa- Fig. 4a -Spastic form of the duodenal curve tients who had undergone bilateral TV. In addi­tion, such appearance of the stomach in patients who underwent SV could be caused by a higher rate of innervation coming sometimes from ga­stric collaterals of the hepatic vagal branch. Some authors try to judge the achieved suc­cess in vagotorny even in the early phase of examination based on the assessment of picture elements and gastric function (1,4). We do not agree with it because we noticed many turna­bouts concerning the form and function, espe­cially in the control abdominal picture six hours later. Those, being engaged in these problems (1,2,3,4) usually speak about the postoperative normalization from one to two months without getting into a more detailed description of mor­ OujmoviC M, LovasiC l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty -A ' Fig. 4b -Hypotonic form of the duodenal curve phological changes. We should not agree with general statement that the stomach assumes its typical preoperative shape. Table 2 lists numeri­cal relationships among gastric types in inopera­ted persons. Percentage differences in represen­tation of particular types of the stomach in com­parison to their representation following vago­tomy and pyloroplasty are obvious. Greater representation of hypotomic gastric shape (type 3 and type 4) certainly results from changed innervation. Residual vagal branches after incomplete vagotomy can explain hyperto­nia in the early postoperative phase. Later, a certain role is likely to play in it by intramural nerve plexuses. From our experience, no definite assessment about efficiency of a drainage operation can be made in either type of pyloroplasty according to Fig. 5a -Markedly expressed postbulbar stenosis the appearance of pylorobulbar area during the first follow-up examination, because of accompa­nying symptoms conditioned by oedema, spasm, hypotonia and secretion. AII the morphological and functional changes ·in the whole duodenal area are of temporary character, being essentially changes as the tirne passes on after the operation. These changes result from the wall consolidation at the site of sutures, oedema disappearance and cicatrical changes during tonus re-establishment in the wall. Šepic (9) and Zaninovic (10) report sec. Finney to give better technical possibilities for lumen distension (Fig. 5a, 5b), especially in the case of very strait lumen owing to cicatrical changes. Sapounov (3) quotes that finding of normal or slightly ectatic pylorus with normal bulbar basis means unsuccessful pyloroplasty. We had seve­ral finding of a kind and decided to support the statement reported (Fig. 6). Radiol lugosl 1991; 25:287-96. Oujmovic M, Lovasic l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty Fig. 5b -The same patient following Finney's pyloro­plasty. Wide gastroduodenal canal at the site of steno­sis. AII the gastric and duodenal examinations after 11agotomy and pyloroplasty are easy to carry out, and do not require special technical conditions. Making comparisons of the reports by various authors is very difficult or not practical at ali. The reason for this is diversity of methods of vagotomy and pyloroplasty and their all possi­ble mutual combinations. lnvestigation of radiological anatomy of the stomach and duodenum after truncal and selec­tive vagotomy with pyloroplasty, regardless the recently more and more applied proximal selec­tive vagotomy, is of great importance. It is a fact that the operated in such a way are among our patients, and there is always a risk for a radiolo­gist, who is not experienced enough, to interprete radiological-anatomical picture in a wrong way. Fig. 6 -Preserved form of the bulbus and pylorus as a sign of inadequate pyloroplasty. The sign of ridge is placed aborally to the bulbus. Sažetak RADIOLOŠKA ANATOMIJA 2ELUCA 1 DVANAESNIKA POSUJE VAGOTOMIJE 1 PILOROPLASTIKE U studiji je ukljuceno 1358 pacijenata u kojih je ucinjena TV il SV uz sec. Finney ili sec. Heineke-Miku­licz. Naši opisi morfologije želuca nakan trunkalne ili selektivne vagotomije odstupaju od opisa u literaturi. U definitivnoj slici želuca poslije operacije dominira hiper­tonicna forma u obliku klina ili roga. Ovaj oblik je inace tipican za SSV. lzgled pilorobulbarnog podrucja odgovara opisima u literaturi uz napomenu da su mnogo manje zastupljena pseudodivertikulozna izbocenja kontura. U promijenjenoj formi duodenalnog zavoja kod polo­vice slucajeva nalazimo hipotoniju ili spazam. Uocene su razlike forme kod istih drenažnih metoda a razlicitih timova operatera. References 1. Beeger F, Vogel H. Rdntgenmorphologie nach Vagotomie, Rdntgen BI 1983; 36 :403-6. ,Dujmovic M, Lovasic l. Radiological anatomy of the stomach and duodenum following vagotomy and pyloroplasty 2. Maas R, Vogel H. Die Rontgenmorphologie des Magenausgangs nach Pyloroplastikoperationen. Fortschr Rontgenstr 1982; 137(4):428-33. 3. Sapounov S. Das Rontgenbild von Speiserohre, Magen und Zwolffingerdarm nach selektiver gastraler Vagotomie und Pyloromyoplastik. Fortschr Rontgenstr 1971 ; 115 :423-32. 4. Stauch G, Lohr E, Boettcher 1, Beersiek F, Eigler FW, Das Rontgenbild des Magens und Zwolffingerdar­mes nach organschonender Operationen beim Gastro­duodenalulkus. Fortschr Rontgenstr 197 4; 120 :31-41. 5. Dihlmann W, Cen M. Zur Kennthis und rontgenol­gischen Beurteilung der Drainageoperationen am Ma­gen. Der Radiologe 1969; 6:196-200. 6. Jamakoski B, Novak J, Peev A, Serafimov K, Ivanov A. Rentgenološki, morfološki i funkcionalni ka­rakteristiki na gastroduodenumot posle proksimalna gastricna vagotomija. In: Zbornik radova l. naucnog sastanka, Vagotomija u lijecenju gastroduodenalnog ulkusa, Opatija 1978; 297-305. 7. Eideshem D, Otteni F, Hollender LF, Bloch P. Etude des aspects radiologiques de l'estomac dans le decours immediat d'une vagotomie supra-selective. J Radio! Electrol 1975: 56(12):841-6. 8. Zeitler R. Rontgendiagnostik des operierten Ma­gens. Der Radiologe 1969; 173-86. 9. Šepic A. Vrijednost vagotomije i piloroplastike u lijecenju perforiranog duodenalnog ulkusa. Disertacija. Rijeka 1974. 10. Zaninovic N, švalba N, Komljenovic B, Gudovic A, Zelic A, Franciškovic V. Analiza i rezultati vagotomije i piloroplastike u lijecenju ulkusne bolesti. In: Zbornik radova I naucnog sastanka Vagotomija u lijecenju gastroduodenalnog ulkusa Opatija 1978;31-9. Author's address: Milivoj Dujmovic MD, Clinical Ho­spital Centre Rijeka, Department of Radiology, Borisa Kidrica 42, 51000 Rijeka, Croatia TOS-AMA 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 111 Zdravniške maske in kape Sanitetne torbice in omarice Avtomobilske apoteke CLINICAL HOSPITAL CENTER, 1INSTITUTE OF RADIOLOGY, 2CLINIC OF SURGERY 3INSTITUTE OF CARDIOVASCULAR DISEASES, MEDICAL FACULTY, UNIVERSITY OF ZAGREB SUPERIOR MESENTERIC ARTERV (SMA) ANEURVSM WITH A MARFAN SVNDROME -CASE REPORT Radanovic B.1, Šimunic S.1, Borcic V.2, Oberman B.1, Strozzi M. 3, Škegro M.2 Abstract -A case of an aneurysm of the superior mesenteric artery trunk with a Martan syndrome suggested by real-tirne ultrasound and CT confirmed by angiography is presented. Surgical resection of the aneurysm was successfully pertormed. UDC: 616.136.44-007.64:616.71-007.152 Key words: mesenteric arteries; aneurysm; Martan syndrome Case report Radiol lugosl 1991; 25:297-9. lntroduction -Aneurysms of superior mesen­teric artery (SMA) trunk and its branches are very rare. In surgical and radiological literature they are described as sporadic cases or only in smaller series (1,2,3,4). Etiological factors causing the SMA aneurysms are arteriosclerosis, trauma, inflammation, me­dial cystic necrosis, collagen vascular diseases, arteritis, hepatic, lesions and congenital anoma­lies (3,4,5). Their frequencies are best illustrated by works of Lucke & Rea and McNamara (1,4). Most often asymptomatic, in case of rupture, they are followed by bleeding into the gastrointe­stinal or peritoneal tracts. Non-invasive radiologi­cal diagnostic methods (US, CT, MRI) reveal the SMA aneurysms most often as an expansive process in the irrigational part of SMA, with stronger or slighter suspicion for aneurysm. Only the angiographic examination -conventional or digital subtraction angiography (OSA) -provides a complete morphological and hemodynamic di­splay of aneurysm. Angiographic finding of aneu­rysm with its relation to the trunk, a display of peripheral ramification and possible collateral are the basic conditions for a successful surgical intervention (4,5,6,7). Case report -A 22-year old woman was treated from her earliest childhood for a mitral orifice insufficiency caused by a prolapse of mitral valve. The patient was extremely high (194 cm), a Martan constitution with dolichostenomelia and arachnodactilia and with a high gothic palate. Ophthalmologic report was in order. Six months earlier she was treated for endocarditis with bacterial vegetations on both mitral cusps and positive hemocultures (alpha-hemolytic strepto­coccus). A month later, she developed waist epigastric pains with no nausea or vomiting. Pain decreased in a bent sitting position. Laboratory findings were within normal range. Arterial blood pressure was normal. Palpation of the umbilical region discovered a well formed, smooth round pulsatory formation 7-8 cm of size. Ultrasound examination revealed a cystic mass of 5.0 x 7.0 cm in para-aortal abdomen. Systolic flow from the aorta was evident by Doppler method. CT examination showed a mas­sive round expansive formation fo fresh blood absorption values. The abdominal aortography established a good state of celiac, renal and inferior mesenteric arteries. However, a clear survey of SMA and its RadanoviC B et al. Superior mesenteric artery (SMA) aneurysm with a Martan syndrome -case report ,'", -:.:;. Fig. 1 -Abdominal aortography: the absence of SMA picture, pale contrast opacity right para-aorta! branches was m1ssmg. In later stage, a pale contrast opacity about 7-8 cm on the right side was observed causing the impression of subrenal part of the abdominal aorta. Only the selective angiogram of SMA offered a clear picture of SMA trunk with its branches and a huge aneurysm of about 8.0 cm in approximately 1 O.O cm of SMA from the aorta. Jejunal branches appeared to be normal. Collaterals from jejunal branches and mesenteric arcades also showed a post-aneury­smal part of SMA and its branches. In later stage, the mesenteric-portal vein system was neatly presented (Figs. 1 and 2). lmmediately after the angiographical diagno­stic examination, a surgery followed with extirpa­tion of the aneurysm (Fig. 3). lnitial and subsequent post-operative recovery was normal. Histological finding revealed a gra­nulated tissue and smaller formations of lympho­cytes and macrophages in arterial and aneury­smal walls. Three months later, control OSA was perfor­med. The abdominal aortography did not show the SMA trunk, and left colic artery and inferior mesenteric artery (IMA) formed a hypertrophic Riolan arch. On selective celiac trunk angiogram a hypertrophic gastroduodenal artery and broad pancreatic duodenal arcades were found, over which the postocclusal SMA segment was vascu­larized (Figs. 4 and 5). The patient has been, without subjective or objective difficulties. Discussion -First successful resection of SMA aneurysm was performed by DeBakey and Cooley (1949) and marked the turn in surgical treatment of this disease (3). Fig. 3 -lntraoperative display of SMA aneurysrn Radiol lugosl 1991, 25:297-9. RadanoviC B et al. Superior mesenteric artery (SMA) aneurysm with a Marfan syndrome -case report , .. ,it ' «._,.; ,,,. II; ' ,! \J .,,. ,! Fig. 4 -Post-operative OSA of the abdominal aorta: SMA trunk display missing, hypertrophic gastroduode­nal arcades, Riolan arch. _.,••· ""'f ·,·•. " w ··•i, , '1., --. I .;= .. r'' \. Fig. 5 -Post-operative selective OSA of the common hepatic artery: hypertrophic gastroduodenal artery and pancreatic duodenal arcades: revascularization of a postocclusive SMA segment. Precise pre-operative diagnostic examination stands as a basic condition of a well planned and performed surgical treatment. The most impor­tant pari in a diagnostic algorithm of this disease is attributed to the angiographic examination (3, 4, 5). Arteriosclerosis participates as the most fre­quent factor in the etiopathogenesis of SMA aneurysms. Other factors are rare (3, 4, 5). In our case, we had a young patient with a Martan syndrome and a predominant cause of huge aneurysm was most probably due to a congenital disorder of connective tissue, yet su­bacute bacterial endocarditis the patient under­went could not be disregarded. Surgical resection of the aneurysm was suc­cessfully performed. Post-operative DSA showed significantly changed hemodynamic situation in the irrigating part of SMA (the occlusion of the starting segment with hypertrophic pancreatic duodenal arcades and Riolan arch), but without clinical signs of mesenteric ischemia. Sažetak ANEURIZMA GORNJE MEZENTERICNE ARTERIJE SA MARFANOVIM SINDROMOM-PRIKAZ SLUCAJA Prikazan je slucaj bolesnice s Martanovim sindro­mom i aneurizmom gornje mezentericne arterije, koja je dijagnosticirana ultrazvukom, kompjutoriziranom to­mografijom i angiografijom. Kod bolesnice je uspješno izvedena kirurška resekcija aneurizme. References 1. Lucke B and Rea MH. Studies on aneurysm: general statistical dala on aneurysm. JAMA 1921 ; 77:935-40. 2. Graham JM, McCollum CH, DeBakey ME. Aneu­rysms of the splanhnic arteries. Am J Surg 1980; 140:797-801. 3. DeBakey ME, Cooley DA. Successful resection of mycotic aneurysm of superior mesenteric artery: case repo rt and review of literature. Am Surg 1953; 19 :202­12. 4. McNamara MF, Bakshi KR. Mesenteric aneu­rysms. In: Bergan JJ, Yao JST, eds. Aneurysms: diagnosis and treatment. New York: Grune & Stratton, 1982 :385-403. 5. Knox M, Chuang VP, Stewart MT. Superior me­senteric aneurysm and arteriovenous fistula: angio­graphic and CT features. AJR 1985; 145:383-4. 6. Baker KS, Tisnado J, Cho SR, Beachley. Splanh­nic artery aneurysms and pseudoaneurysms: transcat­heter embolization. Radiology 1987; 163:135-9. 7. Mourad K, Guggiana P, Minasian H. Superior mesenteric artery aneurysm diagnosed by ultrasound. Br J Radiol 1987; 60:287-8. Author's address: Branko Radanovic MD, Institute of Radiology, Clinical Hospital Center »Rebro«, Kišpati­ceva 12, 41000 Zagreb, Croatia SIEMENS SOMATOM AR.T SIC 212 Ganzkorper-Computertomograph . l. .i INSTITUTE OF RADIOLOGY UMC NIŠ INTRAARTERIAL DIGITAL SUBTRACTION ANGIOGRAPHY OF THE INTRACRANIAL BLOOD VESSELS -IMAGING COSTS ANAL YSIS Bošnjakovic P, lvkovic T, llic M, Milatovic S, lvkovic A Abstract -We compared the costs of standard neuroangiographic procedures with the costs entailed by digital arteriographic imaging. A prospective study was performed in 1989, including 50 patients with subarachnoidal hemorrhage in each group. The study resulted in 29.8% cest reduction in catheterization and filming material in favour of digital subtraction angiography (DSA). The procedure with DSA lasted significantly shorter. More projections were required with DSA because of flexibility and simplicity of the method. It connected with two angiographic machines, DSA would be completely payed back in 1 year. UDC: 616.831 .94-002.252 :616.133.33-073. 75 Key words: subarachnoid hemorrhage; angiography, digital subtraction Orig sci paper P.adiol lugosl 1991 ; 25 :301-3. f ntroduction -The method of Digital Subtrac­tion Angiography (OSA) has been developed for visualization of the arterial side of circulation after intravenous injection of contrast medium in bolus, but the full application in neuroradiology was achieved with intraarterial injections after selective catheterization (1, 2, 3, 4). Beside the parameters related to the quality of the picture and diagnostic value of the study, those that show the costs of application method, compared with the costs of standard angiographic techni­que, are of importance (9, 7). In order to deter­mine these factors we performed a prospective study comparing the imaging costs in groups of patients examined with OSA and conventional angiography. Based on the results of the study, we estimated the tirne necessary for the OSA unit to pay back. Material and methods -The study was per­formed in the Institute of radiology UMC Niš, Yugoslavia between January and December 1989. Fifty patients with clinical and computer tomo­graphic signs of subarachnoidal hemorrhage were examined by means of OSA whereas 50 others with the same symptoms were examined by automatic puck film changer. In both groups, we were measuring duration of the intervention, number of projections obtained, necessary mate­rial for catheterization and filming. Afterwards we compared the values. AII the examinations were performed on an Angioscop C X-ray unit (Siemens) with Coordinat 11ID table, puck film changer which accepted the 24 x 30 size of films. The OSA group was examined using the Angiotron CMP (Siemens) which started to function in our institution in June, 15th, 1985. The matrix size was 512 x 512 and image intensifier diameter 33 cm. The docu­mentation of the angiographic findings was achieved on single-emulsion films using multifor­mat camera. lnterventional procedures were not analyzed. The costs were calculated considering the number of films used per patient, the amount and concentration of contrast medium and necessary catheterization material. On the basis of the number of examined patients during 12 months and knowing price of a OSA unit, the tirne necessary for the machine to pay back was calculated. Bošnjakovi(; P et al. 1ntraarterial digital subtraction angiography of the intracranial blood vessels -immaging costs analysis Results -Examination tirne necessary far the visualization of both carotid and vertebrobasilar artery arborization, measured from the puncture of the femoral artery to catheter evacuation, was significantly shorter with OSA (50, 14 minutes) compared with conventional angiography (89,56 minutes) owing to the elimination of the tirne necessary far the photographic film processing. This fact opens the possibility of examining more patients during the daily work. The number of obtained projections was higher in the group of patients examined with OSA (7,80 : 7, 12). The reason is flexibility and rapidness of aquiring the additional projections with OSA. The structure of catheterization material and contrast media is shown on table 1 (prices in DEM). Table 1 -Costs of the examination per patient (DEM) Material OSA PUCK - catheter 42 42 quidewire 29 29 Tota! 202 287,7 The costs far guide wires and catheters in both groups were the same. The film costs in OSA group comprised 12 single-emulsion films (24 x 30). This number of films was used with only one OSA picture per film which was besi accepted by neurosurgeons. Far contrast medium cost analy­sis, the mean price of 50 ml of nonionic contrast medium, at a concentration of 300 mg/ml was calculated. In the group of patients examined with stan­dard angiographic technique, beside guide wire and catheter, we calculated the costs of 30 films (24 x 30) and 80 ml of nonionic contrast medium at a concentration of 30 mg/ml or higher. The application of OSA resulted in 29.80% cost reduction per patient. Taking in account the price of the unit of 250 000 DEM and the price of automatic puck film changer, with supposed frequency of 1000 patients per year, the unit would pay back in less Ihan two years. The units of latest generations are more expensive so, with the price of 750 000 DEM per unit, pay back tirne would be 7,5 years, amortization and interests not included. The pay-back tirne could be reduced to half the tirne if the unit is connected with two angio­graphic machines. It should be pointed out that the greatest cost reduction could be achieved in interventional procedures which are not included in this study. Discussion -By means of OSA the intracra­nial vasculature might be visualized in three ways: after intravenous injection of contrast me­dium in bolus (with central or peripheral injec­tion), after semiselective injection in the aortic arch and after selective catheterization of the vessel (5). Each of the methods mentioned above has advantages and disadvantages, bul intraarterial injection after the selective catheteri­zation is widely accepted because of image quality, absence of artefacts, and superposition and dependance on the cardiac function (6). The main drawback of the OSA image achie­ved with intraarterial injection is less spatial resolution if compared with conventional angio­graphic films. This is more obvious in visualiza­tion of the small vessels (smaller Ihan 0.5 mm in diameter). Using matrix size 1024 x 1024 and TV 51,6 film systems with 1000 lines on the monitors and 141,7 contrast medium cameras, the spatial resolution will be significan­ tly improved and new fields far the application of OSA technique opened. The machines with such characteristics are more expensive compared to the machines of the first and the second genera­tion (7). Because of the differences in duration of the procedure, speed of image acquisition and used material, literature dala show cost reduction in favor of OSA between 1 O and 30 percent (7). Cost reduction is estimated to be 200 USD per patient by Brandt-Zawadzki et al. (8). It should be emphasized that our study showed the expenses in a single X-ray tube unit. The biplane unit, in our oppinion, would not result in significant shortage of neuroangiographic proce­dure. The amount of contrast medium would be reduced, bul in other parameters (including the unit price) there would not be any important difference. Conclusion -lntraarterial OSA, after selective catheterization, is very important in neuroradio­logy and can almost completely (except neova­sculature assesment) replace conventional an­giography. Beside the advantages in manipula­tion with the unit and image quality, important factor is the cost reduction which is aproximately 30 percent in favor of OSA. Radiol lugosl 1991. 25:301-3. BošnjakoviC P et al. lntraarterial digital subtraction angiography of the intracranial blood vesse1s -immaging costs analysis Sažetak INTRAARTERIJSKA DIGITALNA SUPTRAKCIONA ANGIOGRAFIJA INTRAKRANIALNIH KRVNIH SUDOVA-ANALIZA TROŠKOVA PRIMENE METODE Uporedili smo troškove primene standardnih neu­roangiografskih procedeura sa troškovima pregleda uz primenu digitalne suptrakcione angiografije (OSA). Pro­spektivna studija izvedena je 1989, godine sa po 50 bolesnika sa znacima subarahnoidalne hemoragije u svakoj grupi. Rezultati su pokazali sniženje troškova kateterizacionog i filmskog materijala za 29.80% uz primenu OSA. Ušteda u vremenu uz OSA je znacajna. Uz OSA bio je korišcen veci broj projekcija po bolesniku zbog fleksibilnosti i lakoce primene. Ukoliko je pove­zana sa dva angiografska aparata OSA ce se kom­pletno isplatiti za godinu dana. References 1. Robb GP and Steinberg l. Visualization of the chamber of the heart, the pulmonary circulation and great blood vessel in man. AJR 1939; 41 :1 '-, 2. Bannister RG, Leslise M. Venoangiography in the study of cerebrovascular diseases. Brain 1963; 86: 161 . 3. Kruger RA, Mistreta CA, Houk TL et al. Compute­rized fluoroscopy techniques tor intravenous study of cardiac chamber dynamics. lnvest Radiol 1979; 14:279. 4. Bošnjakovic P. OSA in diagnosis of intracranial aneurysms and arteriovenous malformations (doctoral thesis). University in Niš 1990; 68-79. 5. Zimmerman RA, Grossman RI, Goldberg HI et al. Comparation of digital subtraction angiography with conventional film screen subtraction arteriography tor neuroradiology. Neuroradiology 1984; 26:457-2. 6. Nakstad D, Bakke SJ, Kjartansson O. lntra-arte­rial digital subtraction angiography of carotid arteries. Special refference to contrast media. Neuroradiology 1986; 28:195-8. 7. Norman D, Ulloa N, Brandt-Zawadzki M. lntraarte­rial Digital Subtraction. lmaging costs consideration. Radiology 1985; 156 :33-5. 8. Brandt-Zawadzki M, Gould R, Norman D. Digital subtraction Cerebral angiography by intraarterial injec­tion: comparation with conventional angiography. AJNR 1983; 347-53. 9. Modic MT, Weinstein MA, Chilcote WA et al. Digital subtraction angiography of intracranial vascular system: comparative study in 55 patients. AJR 1982; 138 :299-306. Author's address: As dr sci Petar Bošnjakovic, Insti­tute of Radiology UMC Niš, Brace Taskovica 48, 18000 Niš SLOVENE NUCLEAR MEDICINE SOCIETY SLOVENE MEDICAL ASSOCIATION President: dr. Jurij Avcin, MD Vicepresident: dr. Janez Šuštaršic, MD Secretary: dr. Metka Milcinski, MD Administrative secretariat: University Medical Centre Nuclear Medicine Department Zaloška 7 61000 LJUBLJANA SLOVENIA T elephone: *38-61-316855 T elefax: *38-61-127272 The traditional Austrian-Hungarian-Slovene Nuclear Medicine Meeting will take place this year in Slovenia, in Bled on 21 t h and 22th May 1992. The following scientific programme is proposed: News in nuclear medicine diagnostics Thyroid carcinomas Free presentations MILITARY HOSPITAL ZAGREB, DEPARTMENT OF RADIOLOGY DEPARTMENT OF OTORHINOLARYNGOLOGY DIGITAL SUBTRACTION SIALOGRAPHY Borkovic z, Katic B, Ožegovic 1 Abstract -The technique of sialography of the parotid gland by means of digital subtraction has been applied in 19 patients. We have done both sides in 2 patients, so the total number of investigations performed was 21. The diagnoses were confirmed by clinical, cytological aspiration biopsy or also by histological findings after surgery. Sialography by means of digital subtraction is a diagnostic improvement in comparison with classical sialography because of its higher resolution and the ability to show details. The subtraction of bone structures, as well as of air in the pharynx and sinuses, enables clearer imaging of the salivary gland duet and the gland itself. Using this method, a large number of recordings can be obtained, and the images improved by digital processing; it is most important, though, that the dose of radiation is significantly reduced. UDC: 616.316.5-073.755 Key words: sialography-methods; parotid gland Profess paper Radiol lugosl 1991; 25:305-7. lntroduction -The method of digital subtrac­tion angiography is applied for review of nonvas­cular structures of the parotid gland. This method for visualisation of the parotid gland, parotid duet, intraductal changes and a review of the salivary gland tissue by application of digital technique has been developed to make the diagnosis by means of digital subtraction sialography more simple and useful (1-4). With the diagnostic methods of CT, CT-sialo­graphy, MR, US and digital subtraction sialogr.ľp­hy, the latter method opens new possibilitie.;; in the diagnosis of pathological changes ir, the imaged structures (4-9). Because of the large number of recordings, arithmetical processing and the applied techni­que of subtraction reinforcement of signal, redu­ced tirne needed for examination and a reduced dose of radiation, this method has proved to be superior in comparison with classical film method (3). Materials and methods -During our three year study of digital subrraction sialography, 19 pa­tients were examined: one 47-year old woman and 18 men 19-62 years of age. The proportion of examined salivary glands on the left and on the right side was the same. Bilateral examina­tion of the parotid glands was performed in 2 patients; there was a pause of one day between both examinations. Ali the examinations were done by means of a Philips DVI-CV machine with application of an electronic amplifier 6 and 1 O in. of size. Sideways recordings were taken in ali patients. We perfor­med 21 recordings for each patient with the application of contrast medium and the patient in lying position; the speed was 1.9 recordings per second. This examination requires a good coope­ration of the patient as he has to stay calm for 15 seconds. The contrast medium was applied manualiy, using a needle with rounded tip or a catheter SIA-30 (Angoimed). Non-ionic contrast medium lohexol (Omnipaque 180-Nycomed) in a quantity of 2-6 ml was used. The application of contrast medium during the recording was foliowed on the monitor tili the review of glandular phase. BorkoviC Z et al. Oigital subtraction sialography Fig. 1 -Chronical sialadenitis of the parotid gland Results -The method of digital subtraction sialography was applied in 19 patients. Two od them had bilateral examination which gave a total of 21 digital subtraction sialographies. The results are shown in Table 1. There were 7 patients whose findings were within the limits of normal values. In 5 patients chronic inflamma­tory changes were found which were expressed as obvious dilatation and rough contours of the parotid duet, but at its narrow elongated end it was tortuous, displaced or bowed (Fig. 1 ). Bran­ches were considerably reduced and irregularly formed. Glandular phase showed a reduction of glandular tissue. Benign lipoma showed a shar­ply delineated defect in the glandular tissue. We found a central or peripheral defect in the glandular tissue in malignant lymphoma and malignant epithelioma which had wavy polycyclic contours (Fig. 2). In ali patients the diagnosis was established by cytological aspiration biopsy and pathohistological examination of surgical specimens (Table 1 ). Table 1 -Digital sialography, clinical and pathologic diagnosis Diagnosis No. of patients Normal glands 7 Chronic sialoadenitis 5 Abscess 2 Lipoma 1 Lymphoma 2 Epithelioma 2 Total 19 Fig. 2 -lnfiltration of the proximal part of the parotid gland with a malignant tumor (arrow) Discussion -The ditital subtraction sialo­graphy represents a new technique for extravas­cular review of the parotid duet and the parotid gland. The method can be regarded as a consi­derable improvement because of its ability to show even very srna!! structures and intraductal changes better than the classical sialography. In the latter method, the intensity of bone shadows and air in the pharynx substantially interfere with correct interpretation of the findings. By using the non-ionic contrast lohexol (Om­nipaque 180) in a srna!! quantity and by following the contrast medium til! the optimal review, we get a high quality image on the monitor and we also avoid striking sensations in the area of the facial nerve. The method of digital subtraction sialography represents a considerable diagnostic improve­ment in comparison with the classical sialograp­hy. The examination has severa! advantages: it does not require much tirne, the image obtained is better, a lesser quantity of contrast medium is needed, and, as the most important, the dose of radiation received by the patient during examina­tion is reduced. References 1. Dawson P. Digital Subtraction Angiogprahy-A Critical Analysis. Clinical Radiology 1988;39:474-7. 2. Lightfoote JB, Friedenberg RM, Smolin MF. Digi­tal Subtraction Ductography. AJR 1985;144:635-8. 3. Gmelin E, Rinast E, Bastian GO, Hollands ­Thorn B, Weiss HO. Dakryzystographie und Sialograp­hie in digitaler Subtraction. Fortschr. Rbntgenstr 1987;147:643-6. BorkoviC Z et al. Digital subtraction sialography 4. Cizmeli E, llgit ET. The technique and advantages 7. Eviolfsson O, Nordshust T, Dahi T. Sialography of digital subtraction sialography. European Congres of and CT Sialography in the Diagnosis of Parotid Mas­Radiology, Vienna 15-20 sept. 1991 p. 291. ses. Acta Radiol (Diagn) 1984;25:361-4. 5. lko BO. Computed Tomography and_ Sialography of Chronic Pyogenic Parotitis. Br J Radio! 1984 ;57 :1083-90. 6. Me Gahan JP, Walter JP, Bernstein L. Evaluation of the Parotid Gland: Comparison of Sialography, Non-contrast Computed Tomography and CT sialo­graphy. Radiology 1984;152 :453-8. 8. Gritzman N. Sonography of the Salivary Glands. AJR 1989;153:161-6. 9. Bohnodorf K, Lbnnecken 1, Zanella F, Lanfermann L. Der Wert von Sonographie und Sialographie in der Diagnostic von speicheldrusenerkrankungen. Fortschr. Rbtgenstr. 1987; 14 7 :288-93. Author's address: Zdravko Borkovic, MD, Cvijete Zvoric 53/V, 41000 Zagreb, Croatia EUROPEAN ASSOCIATION CANCER RESEARCH CIILI, FOR l. ,-,.-, ,-,, 26th to 29th February 1992 St. Gallen, Switzerland. 4th lnt. Conferenc. on Adjuvant Therapy of Primary Breast Cancer. Details from: Mrs. Beatrice Nair, Dept of Medicine, Kantonsspital, CH-9007 St. Gallen, Switzerland. 17th to 20th March 1992 Amsterdam, The Netherlands. 7th NCI-EORTC symposium on new drugs in cancer therapy: Cancer treatment. Details from: EORTC New Drug Development Office (EORTC-NDDO), Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Dear Colleagues, By the beginning of 1992, a special book dedicated to the 25th anniversary of our journal RADIOLOGIA IUGOSLAVICA will be published. The book entitled ADVANCES IN RADIOLOGY AND ONCOLOGY has been prepared in collaboration with over 150 authors and coauthors contributing papers on the topics covered by our journal: interventional radiology, computer tomography, magnetic resonance, ultrasono­graphy, nuclear medicine, clinical oncology, experimental oncology, radiophysics, and radiation protection. The authors are renowned professionals from our country and abroad. Most part of the material consists of review articles, and therefore the publication can be regarded as a valuable handbook tor all young as well as senior specialists in the appointed branches of medicine. Hereby we invite you to order book by filling-in the enclosed form. The ordered sample(s) will be sent to you upon the remittance of 50.-DEM or counter-value to the following bank account: LB 50101--678-48454 (when paid in SL T) or LB 50100--620-010-257300-5130/6 (when paid in foreign currency), with a remark »Advan­ces in Radiology and Oncology«. Please send your filled-in order form together with a copy of the bank draft to the following address: RADIOLOGIA IUGOSLAVICA Redaction The Institute of Oncology Zaloška 2 61105 Ljubljana / Slovenia Tei: (38 61) 110 165 Fax: (38 61) 329 177 --x ------­--------­---cul here - ---------- ------- ----- ORDER FO RM Ordering individual/institution: Address: (street) (city) (code) (stale) 1/We wish to order _ __ _samples of ADVANCES IN RADIOLOGY AND ONCOLOGY Dale:-----Signature: __________ _ Fram practice far practice FROM PRACTICE FOR PRACTICE CARDIOVASCULAR SYSTEM Case 4 This 35-year-old patient presented with severe haemoptysis which required ventilation and blood transfusion prior to this investigation. What is this investigation and what does it show? What are the possible therapeutic options? Figure 1 a Figure 1 b (For answers see page 318) 1 st. EUROPEAN SYMPOSIUM ON PEDIATRIC NUCLEAR MEDICINE IV JORNADES DE LA SOCIETAT CATALANA DE MEDICINA NUCLEAR MARCH 20-21, 1992 AUDITORIUM -PAVELLO DE GOVERN CIUTAT SANITARIA VALL D'HEBRON BARCELONA ORGANIZATION: Pediatric Task Group of the European Association of Nuclear Medicine. Societat Catalana de Medicina Nuclear. ORGANIZING AND SCIENTIFIC SECRETARIAT: Adress: 1 st. EUROPEAN SYMPOSIUM ON PEDIATRIC NUCLEAR MEDICINE Servei de Medicina Nuclear Hospital General Vali d'Hebron BARCELONA-08035 Phone : 343-4286042, 10:00-12:00 a.m. Fax 343-4280371 UNIVERSITY MEDICAL CENTER SARAJEVO INSTITUTE OF RADIOLOGY ANO ONCOLOGY POSSIBILITIES OF COMPUTED TOMOGRAPHY IN EVALULATION OF GASTRIC NEOPLASMS EXTENSION Jankulov V, Lincender L, Lovrincevic A, Obradov M Abstract -During the period from January to December 1988, the computed tomography (CT) findings were evaluated in 30 patients with the diagnosis of neoplastic gastric process (double contrast X-ray imaging of the gastroduodenum and/or endoscopy). The following parameters were evaluated: the gastric wall thickness exceeding 1 cm, infiltration of the surrounding structures, adenopathy, metastases in the parenchymal organs. The results show !hal the most frequent finding was wall thickness (70% of cases) infiltration (50%), adenopathy (30%), metastases (16,7%). According to the results, it can be concluded that CT is not the primary diagnostic procedure in the gastric malignomas, bul it can improve the »staging« and, suggest to the surgeons the resectability of the stomach. UDC: 616.33-006.6--073. 756.8 Key words: stomach neoplasms; tomography, x-ray computed Orig sci paper Radiol lugosl 1991 ; 25 :311-4. lntroduction -Gastric neopolasms are the most frequent the gastrointestinal tract tumors. Although the incidence of gastric tumors has been decreasing, especially in the USA, this disease presents a great health and social pro­blem in our country (1 ). In some countries the incidence of this disease is extremely high (Ja­pan, Chile, lsland, Austria). In Japan, more than 50% of males affected by malignant diesease die of gastric malignoma (2). Members of the yellow race, males and the carriers of the blood group »A« have greater chances to develop gastric malignoma. The relation between males and females is 2:1 (2). The most frequent patho­histologic type is adenocarcinoma (95%), then lymphoma 3%) and leiomyosarcoma (2%) (2, 3). lntroducing the computed tomography (CT) in the '70s, the primary interest of the clinicians focused on the evaluation of solid, parenchyma­tous abdominal organs. Relating to the level of CT technique development at that tirne, the information about the condition of digestive tract were inaccurate. lntroducing the tast scanners with the technique of dynamic scanning, it was concluded that CT provides valuable data on extraluminal extension of gastric neoplasm (4, 5, 6, 7). Patients and methods -CT findings of 30 patients, obtained during the period from January to December 1988, were evaluated. Out of the primary diagnostic procedure in 9 patients, X-ray of gastroduodenum was applied in 13 patients and both diagnostic procedures in 8 patients. Of 17 patients who underwent endoscopy, pathohi­stologic finding was obtained in 14 patients. In the cases diagnosed by X-ray examinations of the stomach, we strictly followed the radiologic criteria for the diagnosis of gastric malignomas. The patients were prepared fot the examination in the same way as for X-ray of gastroduodenum; 600 ml of the diluted water-soluble contrast medium Telebrix 300 per os was administered. At the table, prior to the scanning the etferves­cent powder Visogas (Pliva)per os and Buscopan (2 mil i.v.) were applied. CT seans were obtained on either Somatom SF of Somatom DRH (Sie­mens), with 4-8 mm thick slices; the stomach was scanned from the level of esophagogastric junction to the level of pylorus. The following parameters, showing the signs of neoplastic process, and its extragastric propa­gation were evaluated on the images: -gastric wall thickness exceeding 1 cm, Jankulov V et al. Possibilities of computed tomography in evaluation of gastric neoplasnis extension infiltration of perivisceral fat tissue and sur­ rounding organs, -adenopathy, -metastases in the parenchymatous abdomi­ nal organs. Results -Our series of 30 examined patients showed the greatest incidence of gastric mali­gnomas in a group of male patients aged 51-60 years (Table 1 and 2); the rate of male VS. temale patients is similar to the data from litera­ture (2). Table 3 shows the distribution of patients according to diagnostic procedures. Of the ex­pected 17 pathohistologic findingš, only 14 were obtained; there were 13 adenocarcinomas and one gastric lymphoma. The most frequent finding on CT was gastric wall thickening exceeding 1 cm without signs of invasion of the surrounding structures, sugge­stive of tumor resectability (Table 4). ' Discussion -In spite of the fact that the incidence of gastric malignomas has been de­creasing in the developed as well as in our country (1, 2), this disease presents a serious problem from the point of early detection as well as therapy. Till the introduction of endoscopy in the ga­stroenterological practice, the only method tor diagnosis of gastric malignoma was X-ray of the stomach. Despite the relevant advances in the technique of investigation, early types of maligno­mas frequently remain undiagnosed. Our cases had two or more main radiologic signs of neo­plasm. lntroducing fast CT scanners, radiologic dia­gnosis of gastric tumors has been significantly improved because of the possibility to evaluate the extraluminal progression of the process (4). The most frequent change noticed in those conditions, confirmed also by our findings, was the decrease of wall thickness tor more than 1 cm in the tumor area (4, 7) (Fig. 1 a, 1 b, 2a, 2b). Besides this parameter, the signs of the sur­rounding organs invastion (6) Fig. 1 c), adeno­pathy (4) (Fig. 1 b), as well as the lesions in parenchymatous organs in the form of metasta­ses (Fig. 2b) were noticed. During the evaluation of the examined group of patients, we did not search tor the metastatic lesions outside the digestive system. The liver was evaluated as the primary site of neoplastic process disemination. For the optimal presentation of the stornach, the optimal preparation of the patient is neccessary, Table 1 -Sex distribution of patients 0 19 63,4% 9 11 36,6% Table 2 -Age distribution according to groups Age distribution % 21 -30 o 31 -40 6,7 41 -50 20 51 -60 33,3 61 -70 23,3 71 -80 16,7 Table 3 -Distribution of patients according to diagnostic procedures Diagnostic procedures No of patients Endoscopy 9 Endoscopy and X-ray of gastroduodenum 8 X-ray of gastroduodenum 13 Table 4 -Evaluated parameters Wall thickness 21/30 (70%) exceeding 1 cm lnfiltration 15/30 (50%) Adenopathy 9/30 (30%) Metastases 5/30 (16,7%) which is the »condition sine qua non« tor an adequate analysis of the seans. CT of the sto­mach is not the primary diagnostic procedure in this group of patients, but it has the place in the algorithm of investigations. Other authors expe­riences are different; from those ignoring the possibilities of CT (8), to those who base the pathohistologic diagnosis on findings of this exa­mination (5). According to our experience, based on the series of 30 patients, CT is the most adequate non-invasive method tor »staging« of patients with gastric malignomas. According to the American authors (6), patients are classified in three groups. The first group comprised patients without signs of surrounding structure invasion, who were candidates tor sur­gery. The second group consisted of patients with signs of invasion and metastases, who would undergo palliative surgical interventions. In third group there were patients with undefined Radiol lugosl 1991; 25:311-4. Jankulov V et al. Possibilities of computed tomography in evaluation of gastric neoplasms extension Fig. 1 a -X-ray ot gastroduodenum: subcardial infiltra­tion of the stomach corpus CT findings, who would undergo further diagno­stic procedures. CT of the stomach has its plase also in surgically treated cases (8), although our experiences are too modest to form our own attitudes. Conclusion -CT is not the primary diagnostic procedure in gastric malignomas, but on the basis of some parameters, disease staging and suggestions to the surgeon about resectability can be defined. Adequate preparation of the patient and ima­ging conditions are neccessary for the analysis. At this level of CT development, pathohistologic diagnosis of gastric malignoma can not be defi­ned. Sažetak MOGUCNOSTI KOMPJUTORIZIRANE TOMOGRA­FIJE U PROCJENI EKSTENZIJE NEOPLAZME 2E­LUCA U periodu od januara 1988. do decembra 1988. godine vršena je evaluacija CT nalaza kod 30 pacije­nata sa postavljenom dijagnozom neoplasticnog pro­cesa na želucu (rtg. gastroduodenuma sa dvostrukim kontrastnim sredstvom i/ili endoskopija). Fig. 1 c -CT ot the same patient three seans more caudally: the signs of retrogastric space infiltration Endoskopske i konvencionalne radiološke metode pregleda gastroduodenuma nam pružaju uvid u endolu­minalni stepen ekstenzije procesa dok nam kompjuter­ska tomografija pruža odlican uvid u stepen ekstralumi­nalne ekstenzije u okolne strukture kao i postojanjf metastatskih lezija. Uvodenjem CT-a olakšan je »sta­ging« bolesnika kao i operativni plan. Jankulov V et al. Possibilities of computed tomography in evaluation of gastric neoplasms extension Fig. 2b -CT (same patient): an expressed thickening of the gastric wall with metastases in the left liver lobe (arrow) 5. Bruneton JN, Caramella E, Cazenave P, Birtwisle Y, Hericord P, Drovillard J. Gastric leiomyosarcoma. Eur J Radiol 1987; 7 :160-2. 6. Halversen RA, Thompson WM. Computed tomo­graphic staging of gastrointestinal tract malignancies. lnvestigative Radiology 1987; 22 :2-16. 7. Catic Dž. Kompjutorska tomografija digestivnog trakta. Doktorska disertacija, Sarajevo 1984; 1-162. 8. Sussman KS, Halvorsen RA Jr, lllescas FF et al. Gastric adenocarcinoma: CT versus surgical staging. Radiology 1988; 167 :335-40. 9. Hammerman AM, Mirowitz SA, Susman N. The gastric air-fluid sign: Aid in CT assessment of gastric y.,all thickening. Gastrointest Radiol 1989; 14 :109-12. 1 O. Lee KR, Levine F, Moffrat RE, Bigongiari LR, Hermreck AS. Computed tomographic staging of malig­nant gastric neoplasm. Radiology 1979; 133:151-5. 11. Balte DM, Mauro MA, Koehler RE, et al. Gastro­hepatic ligament. Normal and pathologic CT anatomy. Radiology 1984; 150:485-90. 12. Komaiko MS. Gastric neoplasm: Ultrasound and CT evaluation. Gastrointest. Radiol 1979; 4:131-7. Author's address: Jankulov dr Vladislav, Institute of Radiology and Oncology, University Medical Center, Moše Pijade 25, 71000 Sarajevo ....... Jku::.;;,;.;:. Fig. 2 -X-ray of gastroduodenum: 1nf1ltrat1ve process of the cardia and fornix of the stomach Cilj našeg rada je da odredi mjesto i ulogu kompjutor­ske tomografije kod bolesnika sa neoplazmom želuca. References 1. Glavaš 2, Dugalic O, Jankovic A, Parunovic M, Jovanovic R. Carcinoma ventriculi. U: Markovic T. Strucno medicinski kriteriji za dijagnostiku i terapiju malignih tumora. Beograd: RSIZZZ, 1987: 137-50. 2. Kucišec A. 2eludac. In: Piljac G. Rak (Klinicka onkologija). Cakovec: TIZ „zrinski«, 1977; 280-96. 3. Robbins LS. Stomach. In: Robbins LS, Cotran SR, Kumar V. Pathologic basis of disease. Philadel­phia: W. B. Saunders Go., 1984: 806-27. 4. Balte DM, Koehler RE, Karstaldt N, Stanley RJ, Sagel SS. Computed Tomography of gastric neo­plasms. Radiology 1981 ; 140: 431-6. UNIVERSITY HOSPITAL »DR O. NOVOSEL« ZAGREB APPLICATION OF INTRAOPERATIVE UL TRASONOGRAPHY IN BILIARY SURGERY Drinkovic 1, Gabelica V, Makaruha B, L'.upancic K, Boko H, Brkljacic B, Vidjak V Abstract -In surgical practice billiary tract diseases are quite common. A whole range of preoperative diagnostic procedures has been developed in order to discover them: ultrasonography, cholangilography, retrograde cholangiography, computed tomography and magnetic resonance imaging. Despite of their high accuracy, obstructive icterus in many patients stili remains of vague genesis. With 57 patients, suspected to have jaundice caused by choledocholithiasis or suspected to have choledocholit­hiasis, intraoperative sonography proved satisfactory in 90% of patients. The accuracy of the findings, absence of radiological exposure and the opportunity to plan surgical treatment are advantages of this technique. UDC: 616.361-089:616.361-073:534-8 Key words: biliary surgery; ultrasonography, intraoperative period Orig sci paper Radiol lugosl 1991; 25:315-7. lntroduction -In biliary surgery, intraoperative ultrasonography is believed to be one of the most important diagnostic imaging methods in an adequate surgical treatment of hepatic and biliar tract diseases. By additional improvement of machines, the accuracy of intraoperative ultra­sonography in detecting biliary tract diseases has highly increased. Surgeons are provided with a sate, accurate and less invastive method for discovering· and localization of common bile duet diseases. In our surgical practice a whole range of diagnostic procedures has been used: intraoperative cholangiography, cholangiomano­metry and choledoscopy. During the last seven years, intraoperative ultrasonography has been applied as a method which enables direct visualization of biliary tree and choledochus. Material and methods -In our surgical prac­tice during the last four years, intraoperative ultrasonography was carried out in 57 patients suspected of having choledocholithiasis. At the same tirne, examination results were checked by using intraoperative cholangiography through the resected cystic duet. For that purpose we have been using a special ultrasonic machine, type Scanel 300, with image memory, linear 7 MHz probe, dimension 4x1 x1 cm, and focal distance of 2.5 cm. It enables a valuable ultrasonic imaging of the liver and the common bile duet. Mechanically well cleaned, non-sterile probe is placed into a disposable sterile plastic bag before being used by the sur­geon directly in the operative field. Transmission cable is put into a sterile linen cover. The sterile plstic bag has to be filled with paraffine oil in advance in order to achieve valuable conductivity of US signal. In order to improve the acoustic contact, a warm (37°) physiological Na CI) solu­tion is introduced into the operative field. The probe is placed under the tissue to be scanned, approximately 0.5 to 1.5 cm away from the surface of structures. Compression of the scanned structures by the probe is not allowed, because clear visualization of the surface of the tissue could be !ost. In our surgical practice we have usually been using the right subcostal section to reach the common bile duet before ultrasound examination is performed. Gallblad­der is scanned from fundus via istmus to the mouth of the cystic duet into the common bile duet. The common bile duet should be examined Drinkovic I et al. Application of intraoperative ultrasonography in billiary surgery by both longitudinal seanning and transverse seanning. Papila Vateri should also be examined. After extensive mobilization of the duodenum aeeording to Koeher's method is performed, we start examining the retropanereatie part of the bile duet and papila vateri. Furthermore, we measured the diameter of the eommon bile duet and thiekness of the wall and examined a possi­ble presenee of pathologieal masses or neopla­stie lesions in the common bile duet. We identi­fied the anatomie relationship between the eom­mon bile duet and the surrounding big vessels. Our next step will be determined by the exami­nation results. Results -lntraoperative US and intraoperative eholangiography were performed in 57 eases with suspeeted eholedoeholithiasis or obstruetive jaundiee. In 37 eases both methods indieated eholedo­eholithiasis. In 20 eases eholedoeholithiasis was not eonfirmed by any of the methods, or we found other benign or malignant lesions. Among 37 patients with positive findins, US and eolan­giography indieated the same result in 33 pa­tients. In 4 patients the results were different. With 3 patients the eholangiographie examina­tion was positive and the US examination was negative. In one ease the US examination was positive and the eholangiographie examination was negative. After surgieal treatment, we obtained the follo­wing results: eholangiography was false positive in three patients, false negative in two patients (true positive 34 patients, true negative 22 pa­tients). US was false positive in one patient, and false negative in one patient (true positive 36 patients, true negative 21 patients). By eholangiographie examination, sensitivity was 94%, speeifity 88% and aeeuraey 91 %. By US examination, sensitivity was 97%, spe­eifity 95% and aeeuraey 96%. Discussion -lntraoperative ultrasonography is a relatively simple teehnique and provides surgeons with a number of valuable information. Besides, the use of ultrasonography in surgery avoids exposing the patient and the surgieal team to radiation, whieh seems to be inevitable during intraoperative radiologieal examinations. Furthermore, the possibility of an allergie reae­tion to a eontrast material is highly redueed. Considering the tirne duration, the applieation of ultrasonography in biliary surgery is unlimited and ean be repeated severa! times in the eourse Fig. 1 -Choledochus and lumen stricture caused by tumor of operation. It enables an insight into the ealiber of eommon bile duet and the demonstration of the relation of biliary duet to surrounding organs, espeeially to the vaseular ones. Further advanta­ges inelude more image information on eaneer masses and their metastases (Figure 1 ). Consi­dering the ehoiee of surgieal methods, this kind of examination w1II provide us with more optimal deeisions. Aeeording to the data from (seeonda­ry) literature, the exaetly performed intraoperative biliary ultrasonography in deteeting biliary ealeuli, espeeially within the lumen of the eommon bile duet, proved to be satisfaetory with over 96% of patients (1-8). Therefore the high aeeuraey of intraoperative ultrasonography proved to be more advanta­geous than intraoperative radiologieal methods, espeeially in diseovering small ealeuli (Figure 2). DrinkoviC I et al. Application of intraoperative ultrasonography in billiary surgery •Hn'V .•-. •;N',Ľ·' .. . .. •, ,"«<,,>.-• .,., , .1 Fig. 2 -Small calculi in choledochus (size 2 to 3 mm) Our experience with intraoperative ultrasono­graphy in biliary surgery has enabled us to define intraoperative radiographic cholangiography as a complementary method in the case we miss relevant information. Conclusions -Based on the results of our clinical experience, we conclude that application of ultrasonography in biliary surgery is a new contribution to the intraoperative localization of common bile duet calculi. Furthermore, intraope­rative ultrasonography provides biliary surgeons with a new, safer and more accurate screening procedure for common duet calculi. References 1. Sigel B, Coelho JC, Spigos DG, Donahue PE, Wood DK, Nyhus LM. Ultrasonic imaging during biliary and pancreatic surgery. Am J Surg, 1981; 141 :84-9. 2. Rifkin MD, Rosato FE, Branch HM, Foster J, Shuin-Lin Yang, Barbot DJ, Marks GJ. lntraoperative ultrasound of the liver. Ann Surg 1987; 205(5% :466-72. 3. Chardavoyne R, Kumary-Subhaya S, Auguste LJ, Philips G, Stein TA, Wise L. Comparasion of intraoperative ultrasonography and cholangiography in detection of small common bile duet stenos. Ann Surg 1987; 206(1) :53-5. 4. Jakomowicz JJ, Rutten H, Jurgens PJ, Carol EL. Comparasion of operative ultrasonography and the radiography in screening of the common bile duet. World J Surg 1987; 11(5):628-34. 5. Klotter HJ, Rockert K, Kummerle P, Rothmund M. The use of intraoperative sonography in endocrine tumors of the pancreas. World J Surg 1987; 11 (5) :634­41. 6. Sigel B, Machi J, Kikuchi T, Anderson KW, Horrow M, Zaren HA. The use of ultrasound during surgery tor complications of pancreatitis. World Surg 1987; 11 (5) :659-63. 7. štulhofer M. et al. lntraoperativna ultrasonografija hepatoholedohusa. Digestivna kirurgija 1985; 361. 8. Yiengpruksawan A, Genepola P. Extended appli­cations of ultrasonography by the surgeon. Am J Surg, 1987; 153 :221-5. Author's address: Prof. dr. l. Drinkovic, University Hospital »Dr O. Novosel«, Zajecka 19, 41000 Zagreb, Croatia Fram practice for practice FROM PRACTICE FOR PRACTICE CARIDIOVASCULAR SYSTEM Case 4 Answer: This is a selective bronchial arteriogram which shows multiple abnormal vessels in the left upper zone. In the midst of these vessels is an area of density which represents extravasa contrast medium which indicates active Bleeding from the Bronchial Artery. The bronchial bleeding is likely to be arising in an area of bronchiectasis ar scarring left by the patients previous tuberculo­sis. This type of bleeding is difficult to control and requires either surgical ar radiological treatment. In that case the patient had very poor respiratory function and was not fit far thoracotomy. The bleeding artery was embolized with immediate control of the haemorrhage and rapid and sustai­ned recovery. Severe bronchial artery bleeding of this type can also complicate bronchiectasis (particulary complicating cystic fibrosis), carcino­ma, micetoma, pulmonary abscess, idiopathic pulmonary haemorrhage and various other chro­nic fibritic lung diseases and is often amenable to treatment by embolization (Figure 1 b). Author's address: Janez Klancar, MD, Institute of Diagnostic and lnterventional Radiology, University Me­dica! Center Ljubljana, Zaloška 7, 61000 Ljubljana, Slovenia III .lF.(Q)ITT1 Corso ltalia 112 ft (0481) 32073 SIRION s.r.1. 34170 Gorizia -ITALY . Fax (0481) 534753 P. Iva 00380480319 medlcal supplles Tx 461240 -SIRION ­ January 1989 BALT offer tor 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 MEDICAL CENTRE ZAJECAR, SERVICE OF NUCLEAR MEDICINE VALUES OF TSH RECEPTOR AUTOANTIBODIES (TRAb) IN PATIENTS WITH TREATED GRAVES' DISEASE Paunkovic N, Paunkovic J, Pavlovic O Abstract -Serum levels of TRAb, thyroid hormones and thyrotropin and clinical status were investigated in 114 patients with treated Graves disease. The following results were obtained: of 66 patients treated with methimazole (follow-up 18 months during treatment and 12 months after), 47 had normalized values of TRAb and thyroid hormones and eumetabolic clinical stale. After 6 to 1 O months 7 of them developed relapse of disease. In 19 with persistently high TRAb levels under treatment, 12 were continously hyperthyroid (in all of them relapse occured up to 3 months after cessation of treatment) and 7 patients had periodical episodes of hypothyroidism. Of 25 patients treated with radioiodine 1 to 12 years ago, TRAb levels normalized in 20 (17 euthyroid, 3 hypothyroid), and remained elevated in 5 (4 hyperthyroid and 1 hypothyroid) during 1-2 years after treatment. Of 23 surgically treated patients TRAb serum levels normalized in 16 (6 euthyroid, 1 hyperthyroid) tor 12-24 months. These findings support observations on TRAb significance in pathogenesis and evolution of Graves' disease. UDC: 616.441-008.61-074 Key words: Graves' disease; autoantibodies; receptors, thyrotropin Orig sci paper Radiol lugosl 1991; 25:319-23. lntroduction -Thyrotropin receptor autoanti­bodies (TRAb) are the most frequent thyroid stimulatory immunoglobulins (TSI, TSAb) al­though they (TSAb) sometimes coexist with thy­roid-blocking antibodies (TSBAb) or change into them during hyperthyroidism (1-4). Treatment of Graves' disease (antithyroid drugs, thyroidecto­my, radioactive iodine) should influence TRAb circulatory levels (5,6). Follow-up of TRAb in 114 treated patients and comparison of findings with thyroid hormone levels and clinical status are presented. Patients and methods -The investigation was conducted in 114 patients with Graves' disease divided into three groups, based on type of treatment. Group I consisted of 66 patients treated with methimazole (Favistan, Bosnalijek). Duration of treatment was 18-21 months. Star­ting dose was usualy 60 mg daily and was diminished during treatment according to meta­bolic state of patient. Thyroid hormones were not added. Follow-up of patients was performed du­ring the whole treatment and at least months after that. Group II consisted of 25 patients treated with radioactive iodine (131-1). Therapeu­tic dose was applied once in 16 patients, twice in 8 and three times in 1 patient). In 9 patients of this group, follow-up was performed from the application of radioactive iodine up to 12 to 60 months. In 16 patients check up was performed only once (last application of radioiodine was more than 5 years ago). Group III consisted of 23 patients with bilateral subtotal thyroidectomy. In 11 patients follow-up began right after surgery and lasted 12 to 36 months, while in 12 patients check up was done only once (patients operated on more than five years ago.) Thyroid metabolic status of patients was eva­luated by two independent experienced endocri­nologists. Serum levels of thyroid hormones were determined by routine RIA, and receptor-TSH autoantibodies were determined by radioreceptor assay (TRAK-assay, Henning). Results -The obtained results are presented in Tables 1, 2 and 3. Serum levels of TRAb in follow-up studies are indicated by arrows: with decreasing magnitude to normalization, or conti­nously elevated in patients with permanent high TRAb. Results are illustrated in four cases (2 treated with methimazole and 2 surgically) (graph 1-4). Paunkovic N et al. Values of TSH receptor autoantibodies (TRAb) in patients with treated Graves· disease Table 1 -Graves' disease, 66 patients, methimazole follow -up during treatment (18-21 months) and at least 6 months after cesation TRAb -t-il,,,, total n 47 19 66 eu hiper hypo trans total issue 47 12 7 66 relapse 7 12 3 22 Table 2 -Graves' disease, 25 patients, 131 1 therapy follow -up (12 -60 months) TRAb total t • i t f l+l+i+ll n 5 4 9 eu hypo hyper (12 months) total issue 4 1 4 9 Testing in remission (over 5 years) TRAb normal high total n 15 1 16 eu hypo hypo total issue 13 2 1 16 Table 3 -Graves' disease, 23 operated patients follow -up (12 -36 months) TRAb +-t-1 total t • H n 5 6 11 eu hypo eu hyper total issue 4 1 5 1 11 Testing in remision (over 5 years) TRAb normal high total n 11 1 12 eu hypo eu total issue 8 3 1 12 Discussion -Of 66 patients treated with methimazole more than 70% (47 patients) were good responders (reestablishment of remission, TRAb normalization). These findings are slightly better than some recently reported data (7). There is an attractive hypothesis that methima­zole has an immunosupressive effect which re­sults in diminished TRAb serum levels and con­sequent normalization of thyroid metabolic and hormona! state (4,8). It should also be considered that TRAb normalization could be a consequence of decrease in thyroid hormones levels as a result of direct thyrostatic action of methimazole (9). In 12 patients in spite of high doses of methimazole hyperthyroidism was persistent with elevated TRAb levels (nonresponders). In 7 pa­tients despite high TRAb concentrations, transi­tory hypothyroidism was observed. We have not tested TRAb activity by postreceptor effects (cAMP generation), but we assume that the high TRAb concentrations accompanying hypothyroi­dism point out their thyroblocking effect (4.1 O). Patients with persistently elevated TRAb le­vels, several months after 131-1 therapy, remai­ned hyperthyroid (all of them required additional therapeutic dose). Patients in longer remission after radioiodine therapy had normal TRAb le­vels. These findings are not in accordance with Paunkovic N et al. Values of TSH receptor autoantibodies (TRAb) in patients with treated Graves' disease TRAbT4 l U/ 1 nrnol / l 300 o------o TR A b ' T4 200 \ ,, -------­ -\ \ -r . T4 100 \ , ...... __ _._ -----.----. ---norma range _ _l 50 TRAb 10 normal range ­ t (monlhs) S 10 -L-. ..-..-..._..____.__._...J...._ l > Graph 1 -Case report: concordant normalization of T4 and TRAb under mathimazole treatment T4 TRAb lVI 300 . "-----o------o TRAb . T·---1 200 - \ \ 100 normal __ \ 1 ______ --,0 -c -s: .--,,-_ -.,,":: __ _ :r -_o_50 \ -:r ' , ' / ',,' \ I \ I \ / 1 I \ \ I 1 / . TRAb 10 nor mul ran(Je -MElHIM--,I t {month:i 1 G Graph 2 -Case report: persistence of high TRAb levels and low T 4 after a short methimasole therapy (TBAb ?) Radiol lugosl 1991; 25:319-23, Paunkovic N et al. Values of TSH receptor autoantibodies (TRAb) in patients with treated Graves' disease TAAb l T4 U/1 nmol/1 300 200 ', . --'>,_-------i1 -\-, ---­ 1 \ \ ,,,,_ ' / T4 ­ 100 \ norm rur,g• : '/ \ 1 ; -­ ----\ .--r­ ----------------­------­ 1 1 1 1 \ 1 I 1 11 \1 ij TnAb 10 norm rangC!i 0PEnATI0 METHIMAZ0LE---, w 20 30 t lmonthsl Graph 3 -Case report: persistence of TRAb few months after subtotal thyroidectomy with euthyroidism TnAb T4 U/ 1 r nmol / 1 300 200 r T4 100 normal range I ---t 50 1 ,, 1, 1 1 1 / 1 / 1 / TnAb 10 normal 0PERATI0 range 1 nELAPSf: --SUBSTITUTIO . l t I months) lo -.--. ..-..-L.___....___. Graph 4 -Case report: early postoperative hypothyroidism and rapid TRAb decrease Paunkovic N et al. Values of TSH receptor autoantibodies (TRAb) in patients with treated Graves' disease some reports in which patients in remIssIon exhibit high TRAb levels (11 ), but are similar to others (12). Low incidence of hypothyroidism in our group of treated patients is probably due to application of low doses of 131-1 (3MBq/g). These low doses have effect on the lymphocytes of the thyroid responsible tor TRAb production, and have not enormous thyreonecrotic ef­fect.(13). After bilateral subtotal thyreoidectomy, functio­nal thyroid status is normalized prior to TRAb levels (in 6 of 11 patients in early follow-up study). In one patient with early postoperative hypothyroidism rapid TRAb decrease was regi­strated. Patients in longer remission had normal TRAb levels. Our results support opinions that TRAb (TSAb) have important role in pathogenesis of immuno­genic hyperthyroidism. However, some observa­tions must be supplemented by following investi­gations (distinguishing thyrostimualting from thy­roblocking antibodies) or by testing some immu­nologic factors other than TRAb (thyroid microso­mal antibodies etc). References 1. McKenzie JM, Zakarija M, Salo A. Humoral immu­nity in Graves' disease. Ciin Endocrinol Metab 1978; 7:31-46. 2. Orgiazzi J, Madec AM. Le recepteur de la TSH. Annales d'Endocrinologie (Paris) 1989; 50 :418-24. 3. Endo K, Kasaga T, Konishi J et al. Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto-s thyroi­ditis. J Ciin Endocirnol Metab 1978; 46:734-39. 4. Fenzi GF, Hashizume K, Roudebush CB, De­Groot LJ. Changes in thyroid stimulating immunoglobu­lin during antithyroid therapy. J Ciin Endocrinol Metab 1979; 48 :572-6. 5. Rapaport B, Greenspan S, Foletti S, Pepitone M. Clinical experience with a human thyroid celi bioassay tor thyroid stimulating immunoglobulin. J Ciin Endocri­nol Metab 1984; 58:332-8. 6. McGregor AM, Peterson MM, Capiferri R et al. Effects of radioiodine on thyrotropin-binding inhibitory immunoglobulins in Graves' disease. Ciin Endocrinol 1079; 11 :437-44. 7. Budihna N, Pavlin K. TSH-receptor antibodies in the sera of patients with immunogenic hypethyroidism (Graves' disease) during antithyroid therapy. Eur Nucl Med Congress, Goslar, 1986. 8. McGregor AM, Ress-Smith B, Hall R. Specificity of the immunosupresive action of carbimazole in Gra­ves' disease. Brit. Med J 1982; 284 :1750-1. 9. Volpe R. lmmunoregulation in autoimmune thy­roid disease. N Eng J Med 1987;316:44-6. 1 O. Botger IG, Pabst HW. Clinical value of TSH receptor autoantibodies (TRAb) by radioreceptorassay (ARA). Eur Nucl Med Congress, London, 1985. 11. Marana G, Marin MC, Haro J et al. TSH receptor autoantibody measurement in clinical; evolution of thy­rotoxicosis. lbidem. 12. Kozak B, Lauterbach W, Ledda R et al. Sono­graphic patterns and TSH-receptor autoantibody titers in immunogenic and non-immunogenic thyrotoxicosis before and after radioiodine therapy. lbidem. 13. Goolden AWG. Treatment of hyperthyroidism with radioiodine. IV jugoslovenski kongres nuklearne medicine, Beograd, 1986. Author's address: Prim. dr. Nebojša Paunkovic MC Zajecar, Department of Nuclear Medicine, 19000 Zaje­car PROIZVODNI PROGRAM ZA MEDICINU - r.p.que generalni zastupnik za Jugosiaviju tvrtke Nicholas Kiwi, Geneva Medicinski rendgen filmovi (proizvedeni u suradnji F0T0KEM I KA -KODAK): SANIX RF-4 SANIX 0RTH0-4 Film za mamografiju: SANIX Zubni rendgen filmovi: SANIX DENT -20 STATUS-d Film za nuklearnu medicinu, CT i ultrazvuk: SANIX FNM -4 Filmovi za koronarografiju -35mm: SANIX K0R-17 SANIX KOR -21 Micropaque KEMIKALIJE ZA STR0JNU I RUCNU H. D. oral • ® 0BRADU MEDICINSKIH M1cropaque F0T0MATERIJALA suspenzija Efke EKG papir: -001 • @ -002 M1cropaque -003 Colon P0LAR0ID: -crno-bijeli 667 -kolor 339 [F(Q)lf (Q).. [M{] o. Poduzece za proizvodnju i promet fotografskih materijala i opreme s p.o. ZAGREB, Hondlova 2, TEL. 041/231-833, Telex: 22-214 YU FOKEM, Telefax: 041/232-653 NATIONAL INSTITUTE OF PHARMACY1 »FJC« NATIONAL RESEARCH INSTITUTE FOR RAOIOBIOLOGY ANO RADIOHYGIENE2 BUOAPEST,HUNGARY PRELIMINARY REPORT ON RADIOCHEMICAL AND PRECLINICAL STUDY FOR THE REGISTRATION OF SCINTIMUN CEA IN HUNGARY Rakias F1 , Szentgyorgy P1 , Janoki Gy2 Abstract -The radiochemical purity of Scintimun CEA was determined by rapid chromatographic method on ITLC Gelman SG layers. Three types of developing solution were used: methylethylketone, 0,9% (isotonic) sodium chloride solution and sodium carbonate solution of 3 mol/1 concentration. The most significant results were obtained by developing with the sodium carbonate solution. In this case the distribution of the radioactivity along the chromatographic layers indicated that about 94% of the total amount of the labelling Te was found at the start point (as bound to Mab), 3% migrated together with the front of the developing solution (free pertechnetate ions as radiochemical impurity). The remaining 3% were distributed along the chromatographic layer (as other bound radioactive impurities). The stability tests of the labelled solution were performed after 3 hours. No significant differencies could be evidenced by these measurements. The preclinical testing consisted of the activity distribution measuerements between different mouse organs including malignant tumour. It has been shown that the besi distribution tirne is 24 hours after the administration of the diagnostics. UDC: 616-006.6-097 Key words: carcinoembryonic antigen; antibodies, monoclonal; technetium, radiochemical purity, radiopharma­ceuticals, diagnostics, distribution in organs, malignant tumour Orig sci paper Radiol lugosl 1991; 25:325-9. lntroduction -A large number of monoclonal antibodies labelled with different radionuclides such as 131-1, 111-ln, 125-1 have been described in the litereture for scintigraphic diagnosis of cancerous tumours (1-8). A relatively new one is the medicina! product SCINTIMUN CEA (monoc­lonal Carcino-Embryonic Antigen) produced by Behring -Werke, F.R. Germany, labelled with 99mTc. We have examined such kits for registra­tion purpose. Radiochemical purity examinations and preclinical tests were carried out to prove the diagnosis. Materials and methods -AII reagents used for ITL chromatography were of analytical grade. The biological tests were made with five groups of four OBA respectively CBA mice. The immunsuppression was achieved as follows: the thymus of mice aged 3--4 weeks was extirped. A week later the mice were irradiated with gamma rays (8.5 Gy per whole body), followed by bone marrow transplantation. After another week hu­man tumour was xenografted. The biological tests referring to the technetium distribution in various mouse organs were made 2-3 weeks after an injection of the labelled (22--44 MBq) antibody (0.04-0,08 mg). 99 m Te /abelling of SCINTIMUN CEA -The kit to be examined consisted of two sterile vials. One of them contained the lyophilized monoclo­nal antibody 431/26 (the active component) to­gether with sodium phosphate (buffering agent) and 0-Glucitol (anticoagulant). The content of the other vial was the following: tin (II) chloride dihadrate (for reducing pertechnetate ions to technetium ions), tetrasodium 1, 1,3,3, propane­tetraphosphonate dihidrate (PTP, complexing agent) and sodium chloride (agent to form isoto­nic solution). The active component of the kit was lebelled with 99mTc eluated from the technetium generator AMERTEC II, supplied by Amersham lnternatio­nal England. The labelling was performed accor­ding to the directions for use. Five ml of isotonic sodium chloride solution was introduced by a syringe into the vial containing the tin(II) chloride. After dissolving the dry substance contained in this vial, one ml of the obtained solution was injected into the vial which contained the monoc­lonal antibody, dissolving the dry content in the vial. By interaction mainly between the antibody and the tetrasodium 1 , 1 ,3,3, propane-phospho­nate, reactive sites have been created tor com­plexing metal ions such as technetium(IV). An Rakias F et al. Preliminary·report on radiochemical and preclinical study for the reg(stration of scintimun CEA in Hungary adequate aliquot of technetium generator eluate containing pertechnetate ions of 540 -1230 MBq activity was added to the previously obtai­ned solution. Tin chloride reduced the pertechne­tate ions to technetium ions mal10 No ot patients 20 23 24 23 22 Sex (f/m) 18/8 11/12 8/16 10/13 13/9 Age (years) 11.3(3.5) 9.4(3.87) 13.1(3.73) 13.2(3.82) 17.5(3.46) GFR (Cr-EDTA) (ml/min/1. 73m2) 109(13) 186.18(64.22) 176.53(34.48) 139.17(31.65) 146.12(34.95) % pat.with 65.27% 41.67% 39.13% 45.45% elevated GFR (15/23) (10/24) (9/23) (10/22) p· NS Control/lV group p">.05 Control/1/11/111 group. GFR (Cr-EDTA): glomerular filtration rate with chromium edetics acid. Grujic E et al. GFR (Cr-EDT A) values in children with IDDM with respect to the disease duration Brate of GFR -% elevated GFR >10 years GFR (Cr-EDTA) ml/min/1.73m2 Fig. 1 -Relation ra\3 of GFR and percentage elevated GFR Conclusion -During the first year of the disease in children and adolescents with insulin -dependent diabetes increased glomerular filtra­tion appears. High values of glomerular filtration are apparent at the tirne of diagnosis and during the first two years of the disease. With further duration of the disease the glomerular filtration level decreases, which is also described by some other authors (4, 10, 11, 12). Mogensen (1 ), describing developing stages od diabetic nephro­pathy, also quotes an increased GFR rate even up to the fifth year of diabetes duration during the stages of hyperfiltration, neprhomegalia and clini­cally manifest stage, after which the GFR rate gradually decreases. The markers of affected renal function were of transitory character and mostly disappeared after the stabilisation of the basic disease. On the basis of current knowledge and possibilities of research, future development of diabetic nephro­pathy cannot be precisely predicted, but we believe their longitudinal observation in diabetic patients necessary. References 1 . Mogensen CE, Christiansen CK, Vitinghus E. The stages in diabetic nephropathy: with emphasis on the stage if incipient diabetic nephropathy. Diabetes 32 (suppl 2): 1983; 64-78. 2. Chantler C, Barrett T. Estimation of glomerular filtration rale from plasma clearence of 51-chromium edatic acid. Arch is Child 1972; 47 :613. 3. Kroustroup JP, Gundersen HJG, Osterby R. Glo­merular size and structure in diabetes mellitus. Early enlargement of the capillary surface. Diabetologia 1977; 13:207-10. 4. Chavers BM, Bilous RW, Ellis EN, Ste/fes MW, Mauer SM, Hostetter Th, Troy JC, Brener BM. Glome­rular haemodinamics in experimental diabetes mellitus. Kidney lntern 1981 ; 19 :410-15. 5. Hosetetter TH, Troy JC, Brener BM. Glomerular haemodynamics in experimental diabetes mellitus. Kid­ney lntern 1981; 19:410-15. 6. Viberti GC, Bilous R, Mackintosh D. Monitoring glomerular function in diabetic nephropathy; a prospec­tive study. Am J Med 1983; 74:256-64. 7. Viberty GC, Bending JJ. Early diabetic nephropat­hy. Adv Nephrol 1988; 17:101-2. 8. Viberty GC, Haycock G, Pickup J, Jarrett R, Keen H. Early functional and morphologic vascular renal consequences of the diabetic stale. Diabetologia 1980; 18:173-5. Grujic E et al. GFR (Cr-EOTA) values in children with IDDM with respect to the disease duralion 9. Brochner-Mortensen J, Ditzel J, Mogensen CE, Robro P. Microvascular permeability to albumin and glomerular filtration rate plasma clearence of 51-chro­mium edetic acid. Arch Dis Child 1972; 47:613. 1 O. Krolewski AS, Warrm JH, Chistielb AR, Busick EJ, Kahn CR. The changing natural history of nephro­pathy in type I diabetes. AM J Med 1985; 78:785-94. 11. Selby JV, Fitzsimmons SC, Newman JM, Katz PP, Sepe S, Showstack J. The natural history and epidemiology of diabetic nephropathy. lmplications tor prevention and control, JAMA 263 1990; (14) :1954-60. 12. Steffes MW, Osterby R, Chavers B, Mauer SM. Mesangial expansion as a central mechanism tor loss of kidney function in diabetic patients. Diabetes 1989; 38:1077-81. Author's address: Dr. Edina Grujic, Pediatric Glinic and Polyclinic »Prof. dr M. Sarvan«, Department of Endocrinology and Juvenile Diabetes, Hasana Brkica 81, 71000 Sarajevo. The British Nuclear Medicine Society ANNUAL MEETING Date: 6th -8th APRIL, 1992 Place:IMPERIAL COLLEGE, LONDON lnformations Mrs. S. Hatchard, BNMS Conference Secretary 157 Auckland Road, London SE19 2RH. UNIVERSITY HOSPITAL CENTER »REBRO«, DEPARTMENT OF NUCLEAR MEDICINE, ZAGREB, CROATIA PENT AVALENT TECHNETIUM-99m-(V)-DMSA UPT AKE IN AN OCCUL T MEDULLARY CARCI­ NOMA OF THE THYROID Brkljacic B, Tomic-Brzac H, Halbauer M, Bence-Žigman Z, Pavlinovic ž, Kušter ž, Težak S Abstract -This case report describes preoperative 99m-Tc-(V)-DMSA accumulation in a small, nonpalpable, occult medullary carcinoma of the thyroid gland, measuring only 8 x 5 mm. Complete preoperative, as well as postoperative examination showed no evidence of either intraglandular dissemination. or local or distant metastases. The authors believe that this is the first reported case of positive uptake of 99m-Tc-(V)-DMSA in such a small, occult primary medullary carcinoma of the thyroid. UDC: 616.441-006.6:615.849.2 Key words: thyroid neoplasms; technetium Case report Radiol lugosl 1991; 25:335-38. lntroduction -Medullary carcinoma of the thy­roid (MCT) is a tumor of the parafollicular (C­cells) of the thyroid gland, that secrete calcitonin (CT) . Almost ninety percent of the cases appear sporadically, with the resi occurring in families as a pari of multiple endocrine neoplasia (MEN tla and MEN llb), with autosomal dominant inheri­tance, high penetrance and variable expression (1, 2, 3). The diagnosis of MCT is not difficult in patients with clinical signs of thyroid tumor growth or symptomatic metastases. It is supported by pla­sma calcitonin assays combined with provocative tests, sonographic examination, fine needle aspi­ration biopsy (FNAB), and pathohistologic exami­nation. However, for curative therapy (total thyroidec­tomy), it is desirable to diagnose the disease early, during nonmetastasized, and if possible, occult tumor stage (1, 2, 3). Technetium -99m dimercaptosuccinic acid (DMSA) scintigraphy has been used for the diagnosis of MCT as well as for the localization of metastatic sites and residual tumor (4, 5, 6, 7, 8). Ohta et al. have shown DMSA uptake in a variety of benign and malignant soft tissue and bone tumors (7). Materials and methods -Technetium-99m­(V)-DMSA was prepared applying a slightly modi­fied procedure, proposed by Jovanovic et al. (9). To a vial of commercially available Tc-99m-(V)­DMSA kit (Boris Kidric Institute of Nuclear Scien­ces, Vinca, Yugoslavia) containing 1.0 mg DMSA, 0.12 mg SnCl2 x 2H2O, 0.5 mg ascorbic acid and 9 mg NaCl, 1.1 ml of fresh, sterile solution of 0.5% NaHCO3 was added. lmmediately after shaking the vial, 30 mCi of 99mTc pertechnetate in 2.9 ml of physiological saline was added, the total volume being thus adjusted to 4.0 ml. The vial was shaken again and left standing free for 20 minutes at room temperature. A dose of 15 mCi of Tc-99m-(V)­DMSA was administered intravenously to the patient. The radiochemical purity of the final product (in terms of the fraction of 99m-Tc0'4) was asses­sed by paper chromatography on Whatman No. 1, using acetone as a mobile phase (9). The radiopharmaceutical was found to be of appro­priate radiochemical purity (99mTc04 < 1 %). . Brkljacic B et al. Pentavalent technetium-99m-(V)-DMSA uptake in an occult medullary carcinoma of the thyroid Anterior and posterior images over the whole body were taken 2 hours postinjection of Tc-99m­(V)-DMSA, using a large field-of-view gamma camera, equipped with a low-energy all-purpose parallel collimator. The calcitonin level in the patient serum was determined by standard radioimmunoassay (RIA­mat Calcitonin II, Mallinckrodt Diagnostics GmbH, Dietzenbach, Germany). Sonographic examination was performed using a standard real-tirne machine (Aloka SSD­ 256) with 5 MHz and 7.5 MHz probes. Ultrasonically guided fine needle aspiration biopsy was performed using a 22 gauge needle. Fresh, air-dried smears were stained by the Papenheim (May-Gruenwald-Giemsa) method. For MCT celi identification we utilized the Grime­lius silver stain (10). Case report -A 49-year-old woman was under surveillance in our department for five years, because of euthyroid nodular goitre. She had a palpable solitary node, echographically isoechogenic, with small cystic changes, 4 x 1 .6 x 2.3 cm large, in the right lobe. Two FNAB's of this nodule showed benign findings. The patient came for control sonographic exa­mination of the thyroid, when in addition to previously described node, small, hypoechoic, clearly delineated nodule, measuring 8 x 5 mm, in the upper pole of the left lobe of the thyroid was found (Figure 1 ). Ultrasonically guided FNAB was performed, and cytologic examination revealed MCT cells. The reaction according to Grimelius was positive and manifested itself by brown-black granules in the cytoplasm of MCT cells (1 O). Pathohystologic diagnosis confirmed this finding. The patient was euthyroid with negative thyroid antibodies. Tc-99m pertechnetate and J-131 seans displayed non-homogenous distribution of radiotracers in both lobes of the thyroid. Biochemical investigations revealed normal basal serum CT levels -92.2 pg/ml (normal range: 0-150 pg/ml) and 1 O minutes after ethanol provocation CT level was elevated in excess of 176.6 pg/ml. We found normal parathormon, prolactin and ACTH serum levels and normal vanil-mandelic acid urinary level. Ultrasonography of the upper abdomen was normal, and detailed sonographic examination of neck region was normal, except for changes in the thyroid gland. + = cursors on the nodule edges. N = nodule TH = thyroid lobe Fig. 1 -longitudinal ultrasonic scan of the left thyroid lobe (LD), showing hypoechoic, clearly delineated no­ dule, measuring 8 x 5 mm, in the upper pole. Medullary carcinoma of the thyroid at histopathology. 99m-Tc-(V)-DMSA scintigraphy of the neck, thorax and abdomen was performed and showed accumulation in small area in projection of the upper half of the left thyroid lobe, corresponding to the area in which MCT was situated (Figure 2). Total thyreoidectomy was performed, and pat­hohystologic examination in multiple slices confir­med the diagnosis of medullary carcinoma. There was no evidence of tumor cells in thyroid paren­chima outside of small nodule. Postoperative 99m-Tc-(V)-DMSA scintigraphy, as well as neck region sonographic examination failed to reveal any evidence of residual tumor or dissemination. Postoperative basal and provocation CT levels were normal. Discussion -There is almost general agree­ment that in patients with hereditary and sporadic MCT, total thyroidectomy with removal of lymph nodes in the primary lymphatic drainage area of the gland is required (11 ). To achieve complete removal of tumor it is important to discover disease in early, nonmetastasized, preferably occult stage (1, 2, 3). Radiol lugosl 1991, 25:335-8. Brkliacic B et al. Pentavalent technetium-99m-(V)-DMSA uptake in an occult medullary carcinoma of the \hyroid Fig. 2 -99m-Tc-(V)-DMSA anterior scan of head and neck, with tracer uptake in the upper pole of the left thyroid lobe (arrow), corresponding to area where medullary thyroid cancer is situated. Role of screening of the patient's relatives by assesment of basal and levels of calcitonin after provocation, sonographic examination and FNAB under ultrasonic guidance is substantial (1, 2). Up to now, several authors reported more than 50 patients with primary or metastatic MCT who were submitted to 99m-Tc-(V)-DMSA scinti­graphy (4, 5, 6, 7, 8, 12, 13, 14, 15). It is considered that convenience and high-image quality make 99m-Tc-(V)-DMSA a valuable adjunct to the currently accepted biochemical method of follow up of MCT patients after thyroi­dectomy (16). As far as preoperative accumulation of 99m­Tc-(V)-DMSA in MCT is concerned, Ohta et al., described four MCT patients with hypercalcitoni­nemia and significant tracer uptake in palpable cervical tumor and metastatic sites (4). Although encouraging, ali of these patients had bulk di­sease that was evident on clinical examination or conventional radiographic studies. Subsequently, Hilditch et al., reported no up­take in five patients with hypercalcitoninemia (15). These patients were thought to have early disease with only modest calcitonin levels -the subset of patients in whom a sensitive early scintigraphic technique would have the greatest impact. More recent reports by Ramamoorthy et al. ( 17), and Clarke et al. ( 16), have been more favourable. However, ali Ramamoorthy's pa­tients appeared to have had known metastases, while Clarke's patients were symptomatic at the tirne of the study, suggesting advanced disease. In this report we present a case of occult medullary carcinoma of the thyroid. that was diagnosed preoperatively, using ultrasonically guided fine needle aspiration biopsy, cytochemi­stry analysis, as well as 99m-Tc-(V)-DMSA scin­tigraphy. Tumor was limited solely to a small, nonpalpa­ble nodule, measuring only 8x5 mm, with no evidence of either intraglandular dissemination of local or distant metastasis, in course of preo­perative, as well as postoperative management. Since we found positive uptake in such a small tumor preoperatively, we believe that this report could contribute to further evaluation of 99m-Tc­(V)-DMSA scintigraphy as a complementary preoperative diagnostic method in management of medullary carcinoma of the thyroid. Sažetak NAKUPLJANJE 99m-Tc(V)-DMSA U OKUL TNOM ME­DULARNOM KARCINOMU ŠTITNJACE Ovaj prikaz slucaja opisuje preoperativno nakupljanje 99m-Tc-(V)-DMSA u malom, nepalpabilnom, okultnom medularnom karcinomu štitnjace, dimenzija 8 x 5 mm. Temeljite preoperativne, kao i postoperativne pre­trage nisu pokazale znakova postajanja intraglandu­larne diseminacije, kao niti lokalnih ili udaljenih mesta­staza. Autori vjeruju da je ovo prvi opisani slucaj pozitivnog nakupljanja 99m-Tc-(V)-DMSA u tako ma­lom okultnom, primarnom, medularnom karcinomu štit­njace. References 1. Saad MF, Ordonez NG, Rashid KR, et al. Medul­lary Carcinoma of the Thyroid. A Study of the Clinical Features and Prognostic Factors in 161 Patients. Medi­cine 1984: 63(6):319-42. 2. Gershengorn MC, Robbins J. Thyroid Neoplasia. In: Green WL ed. The Thyroid. New York: Elsevier, 1987: 325-6. 3. Schwerk WB, Gruen R, Wahl R. Ultrasound Diag­nosis of C-celi Carcinoma of the Thyroid. Cancer 1985; 55:624-30. 4. Ohta H, Yamamtoto K, Endo K, et al. A New lmaging Agent for Medullary Carcinoma of the Thyroid. J Nucl Med 1984; 25:223-5. Brkljacic B et al. Pentavarent technetium-99m-(V)-DMSA uptake in an occult medullary carcinoma of the thyroid 5. Ohia H, Endo K, Fujila T, el al. Sipple's syndrome wilh liver lumors examined by iodine -131 MIBG and lechnelium -99m-(V)-DMSA. J Nucl Med 1988; 29 :33­8. 6. Clarke SEM, Lazarus CR, Wraighl P, Sampson C, Maisey MN. Penlavalenl 99mTc-DMSA, 131-J­MIBG, and 99mTc-MDP -an evalualion of lhree imaging lechniques in palienls wilh medullary carci­noma of lhe lhyroid. J Nucl Med 1988; 29:33-8. 7. Ohia H, Endo K, Fujila T, el al. Clinical evalualion of lumour imaging using 99 m Tc-(V) -dimercaplosuc­cinic acid, a new lumour-seeking agent. Nucl Med Commun 1988; 9:105-6. 8. Palel MC, Palel RB, Ramanalhan P, et al. Clinical evaluation of 99 m-Tc (V) dimercaptosuccinic acid (DMSA), tor imaging medullary carcinoma of thyroid and its metastasis. Eur J Nucl Med 1988; 13:507-10. 9. Jovanovic MS, Zmbova B, Maksin T, et al. Com­parative radiochemical and kinetic study of tumorotro­pic and renal 99m Tc-DMSA. J Radoanal Nucl Chem 1990; 141 :91-9. 10. Halbauer M, crepinko 1, Tomic Brzac H, Šimono­vic l. Fine needle aspiration cytology in the preoperative diagnosis of ultrasonically enlarged parathyroid glands. (In press in Acla Cytologica). 11. Bruni LM, Wells SA Jr. Advances in lhe diagno­sis and trealment of medullary lhyroid carcinoma. Surg Ciin Norih Am 1987; 67:263-79. 12. Udelsman R, Mojiminiyi OA, Soper NDW, Buley 10, Shepstone BJ, Dudley NE. Medullary Carcinoma of lhe lhyroid: managemenl of persislenl hypercalcilonae­mia utilizing 99 m-Tc-(V) dimercaplosuccinic acid scin­ligraphy. Br J Surg 1989; 76(12):1278-81. 13. Endo K, Ohia H, Torizuka K, Horiuchi K, Yomoda 1, Yokoyama A. Technetium-99m(V)-DMSA in the imaging of medullary thyroid carcinoma. J Nucl Med 1987; 28: 252-3. 14. Adams BK, Falaar A, Byrne MJ, Leviti NS, Magley PJ. Pentavalent technetium-99M-(V)-DMSA uptake in a pheochromocytoma in a patient with Sip­ple's syndrome. J Nucl Med 1990; 31(1):106-8. 15. Hilditch TE, Connell JMC, Elliott AT, Hurray T, Reed NS. Poor Results with Technetium-99M-(V)­DMS and iodine-131 MIBG in the lmaging of Medullary Carcinoma. J Nucl Med 1986; 27-1150-3. 16. Clarke SEM, Lazarus C, Mistry R, Maisey MN. The role of technelium-99m pentavalent DMSA in the management of patients with medullary carcinoma of the thyroid. Br J Radio! 1987; 60:1089-92. 17. Ramamoorthy N, Shetye SV, Pandey PM, et al. Preparation and evaluation of 99m TC-(V)-DMSA complex: studies in medullary carcinoma of thyroid. Eur J Nuci Med 1987; 12 :623-8. Author's address: Dr. Boris Brkljacic, M. Sci Zavod za radiologiju, KB »Or O. Novosel«, Zajceva 19, 41000 Zagreb, Croatia. CHAIR OF RADIOTHERAPY, POSTGRADUATE MEDICAL UNIVERS!TY, BUDAPEST,HUNGARY RADIOTHERAPY OF INTRACRANIAL CHILDHOOD TUMOURS WITH 9 MV LINEAR ACCELERATOR (NEPTUN 10-P) Kocsis B, Pap L, Horvath A, Kaldau F, Gyenes G, Bajcsay A, Kontra G; Varjas G Abstract -The authors have investigated the possible ways of radiotherapy in childhood tor malignant CNS tumours, emphasizing the significance of postoperative radiotherapy. The presentation of their practical work is based on their own patient groups. Between 1986 and 1990 altogether 30 patients, under the age of 15 years, were treated tor CNS primary malignancies. The crude survival rale of the patients was 24.5 months. UDC: 616.831-006.6:615.849.12 Key words: brain neoplasms; radiotherapy Orig sci paper Radiol lugosl 1991; 25:339-44. lntroduction -The tumours of the central nervous system are the most frequent solid tumours of childhood. However, this statement is true only in general -analyses based on age, sex and histology give different results. The frequency of these tumours among childhood malignancies is 20-25 percent (1, 2, 3). Accor­ding to British and US registrations, out of one million children under the age of fifteen years approximately 100 develop new malignant tu­mours per year, with 20-25 tumours of the central nervous system (4). A majority of the cases occur in the second part of the first decade of life. Considering the frequency of these tumours, radiotherapists are constantly challenged by the task of applying the appropriate irradiation treat­ment. The aim of the paper is to provide a survey of the medical activity at the Chair of Radiothera­py, Postgraduate Medical University. We exa­mine the mode of postoperative radiotherapy of solid tumours, moreover, the radiotherapy of recurrences and inoperable tumours excluding the manifestations of systemic diseases in the central nervous system, metastatic brain tu­mours, and spinal cord tumours. Material and methods -The Neptun 1 0p linear accelerator has been used in the National Insti­tute of Oncology (Chair of Radiotherapy, Post­graduate Medical University) since October 1985. This equipment was used far the treatment of children far the first tirne in 1986 (Figure 1 ). The accelerator produces a 9 MV X-ray and 6, 8 and 10 MeV energy electron beams. By means of a continuously adjustable diaphragm-system optional size fields can be applied ranging from 3x3 cm to 40x40 cm by X-rays, and from 3x3 cm to 25x25 cm by electron beam. The 9 MV energy X-ray beam is suitable far the treatment of intra­cranial childhood tumours. Altogether 30 children suffering from intracra­nial primary malignant tumours were treated with the Neptun 1 0p linear accelerator between 1986 and December 31, 1990. The youngest patient was nine months old and the oldest 14 years, the mean age was 8.1 years. Twenty-one of them were males and nine females -ratio 2.3 :1. Table 1 shows the localization and histology of the tumours. Treatment planning was performed in all chil­dren. The real anatomic situation was reprodu­ced by the help of a CT scan. The target volume Kocsis 13 et al. Radiotherapy of intracranial childhood tumours with 9 MV linear accelerator (Neptun 1 O·P) can be determined by the CT scan and by -....:.;;""; knowledge of all clinical data, i.e. localization, extent, previous status in case of an earlier operation, preoperative CT picture, surgical data as well as histology. The area to be protected has to be defined for optimal beam direction, number and size of the fields. The application of two or more fields, with ·:),. ·[ I . different beam directions for the target area ' .L ; usually provides optimal dose distribution (Figure 2a-b). By irregular geometry of the tumour the optimal dose distribution can be assured by wedged fields. Rotation of the irradiating head between O and 365 degrees in both directions \:an be carried out by Neptun 1 Op. This has two . practical advantages: the first one is that the patient can be treated in a horizontal position, on his back and in this way the precision and Fig. 1 -The Neptun 1 0p linear accelerator of the reproductivity of the irradiation can be assu­ National Institute of Oncology red. Table 1 -Histology and localization PNET medullobl. astrocyt. glioma ependym. small No data celi. tu Post. scala 13 1 2 Cerebrum 3 2 Chiasma/n. opt. 1 2 Cranio-spinalis 1 Total 13 6 2 6 Furtheremore, the danger of the patient move­ment during irradiation is the smallest in this horizontal position. The second advantage is the possibility of isocenter technology application, i.e. the geometrical center of the velurne to be irradiated is the axis of rotation, and by the rotation of the irradiating head around this axis we can adjust the desired directions of the beam (Figure 3a-b)­ Out of the children treated in our Institute, radiotherapy was applied in 19 postoperative, 9 inoperable and 3 relapsing cases. One patient received preoperative radiotherapy. Thirty-two series of treatment were given to 30 patients. In one patient the reason for this was a recurrence that developed four months after radiotherapy, so complementary irradiation had to be applied ­thus, this patient has been included in both the postoperative and the recurrent tumour groups (Gy. L. age: six years, ependymoma papillare). In the case of another patient repeated manife­station developed over the area of the medulla oblongata after 30 Gy of postoperative irradia­tion. Thus, the therapy was continued as the radiotherapy far an inoperable tumour. We did not apply any chemotherapy in our Institute. The doses delivered in postoperative and ino­perable cases ranged from 44 to 60 Gy -average. 52 Gy (Fig. 4a, b, c). The maximal dose of preoperative radiotherapy was set at 30 Gy. It is impossible to determine the exact dose far recur­ring tumours because of some other influencing factors, the most important being the previously irradiated velurne and the total dose. The daily fractions were 1.5 or 1.8 Gy. The distribution of tumours according to age is shown in Table 2. Results -Our results can be summarized as followas: The average rough survival rate was 24.5 months, with the average of those living 25. 3 months (16 patients), and the average of those deceased 23.3 months (1 O patients). Altogether Radiol lugosl 1991; 25:339-44. Kocsis 8 et al. Radiotherapy of intracranial childhood tumours with 9 MV linear accelerator (Neptun 10-P) r-I"<: Vf"i 1 atl't , 89XE:, 0004 Fig. 2a -CT-topometry. D.F., male, six years old. Dg: glioma cerebri • IZULE:fvT.R 9MV-X FD 1 T 2;,< 1_yx2 F81,92,3c.n-, 'CT Fig. 2b -lrradiation plan, two opposing fields, weight factor 2:1, linear accelerator 9 MV. Field size 1 0x8 cm. we were able to follow 26 patients, 4 patients were lost to follow-up. A longer survival rate -31.8 months -in the case of medulloblastomas implies a favourable prognosis as the average survival rate of the deceased is only 27.8 months. However, this difference is not a significant point (5). This statement is also true of the group without histo- Radiol lugosl 1991; 25 :339-44. .!R:' ./ Fig. 3a -A.K. 7-year old child. Preoperative CT scan of the child who was operated on for medulloblastoma. The treatment plan was made on the basis of a preoperative CT scan. 12ocENTS\)._ 9M\'-,X KA FG1ii = '31 = .)_8.. R lL I --;--,-. ­ 1_8x12 . \ llC ]x: 6 IxC CT Y.TlxG Fig. 3b -CT-based treatment planning. lrradiation to five fields with isocenter technology. Three 7x6 cm and two 18x18 cm fields. logical diagnosis, both with regard to expected survival as well as to its statistical significance. We were unable to evaluate other histological groups because of the low number of patients. Kocsis B et al. Radiotherapy of intracranial childhood tumours with 9 MV linear accelerator (Neptun 10-P) \ ,,. .. -··_ .. ;?t_.. .f:-.. ·. : - Fig. 4a -lnoperable tumour of the posterior scala, unknown histology. CT-based treatment planning M.B. 3-year old boy mance status, age, etc. -should also be conside­red. In favourable cases, originally inoperable 120CENfER BM. '3Mv·-X FeiT . '30,t cm R F [',/" 9)/iu,,flt 7x6 Zx6 .,II< fBf='j\,cn-. Fig. 4c -Regression is observable on the follow-up CT scan, six weeks after completed irradiation who were treated by operation alone was 24 percent, while the application of postoperative radiotherapy increased this rate to 60 percent. Sheline and his associates (7) found the 5-, 1 O-, and 20-year survival trates to be 18, 1 O and O percent, respectively in patients treated by opera­tion alone. However, this rate could be increased to 46, 25 and 23 percent, respectively with postoperative radiotherapy. These data prove the effectiveness of postoperative radiotherapy, especially in radiosensitive neoplasms. 2. Radiotherapy of inoperable intra­c rani a I tu m o ur s -Regarding operability, the primary factors are the size and/or localization of tumour although other clinical aspects -perfor­ Fig. 4b -lrradiat1on treatment plan Discussion -Radiotherapy of the primary CNS tumours in childhood can be indicated as follows: 1. Postoperative radiotherapy -the most common form. Following radical extirpation of the tumour, the application of radiotherapy signi­ficantly increases the chances of survival. Accor­ding to the data of Mork and Locken (6) the five-year survival of children with ependymoma tumours were rendered operable by the applica­tion of an appropriate total dose, this form of treatment becoming recognized preoperative 1radiotherapy. 3. Radiotherapy of recurrent tu­m o ur s is indicated according to the localization, size and histology of tumour, and the previous radiation dose. This form of treatment is applied generally with palliative intent both in the case of single or multifocal recurrences. Kocsis Bet al. Radiotherapy of intracranial childhood tumours with 9 MV linear accelerator (Neptun 10-P) Table 2 -Age distribution 2 o 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 o No ft/.:1 age/years Whatever the indication may be, the irradiation of primary childhood tumours of the central ner­vous system must be carried out by supervoltage radiation: X-ray and electron radiation of circular or linear accelerators, particularly by cobalt -or caesium teletherapy. According to the young age of the patients the selection of an appropriate radiation source and a proper treatment planning are necessary, with special emphasis on some unique aspects: a. The area to be irradiated is located in a bone-surrounded cavity. In that case radiation has to penetrate through a number of different­density substances. As it is well known from radiation physics, critical zones develop on the borders of the substances with different density -first of all as a result of secondary electron rays. Another point of consideration is that the absorption of the ionizing radiation depends on the Ca content of the bones. The younger the patient, the smaller the rate of calcium in the bones. Thus, the absorbed radiation dose is also smaller than by adults. Further differences can be observed in certain age groups. b. The cellular radiosensitivity of growing chil­dren's tissues -including the nerve cells -differs from the radiosensitivity of the mature cells of adults. This has to be taken into consideration with regard to the degree of the acute radiation reaction during and after treatment, and later on in the development of late side effect evaluation. c. As a result of the unique circumstances, radiotherapy necessitates higher technological :1Y1 ,,,.··· ./ '."cl-'..-0,??":W.&.Wffe'J 3 4 5 and personnel conditions. More advantageous applications are, for instance, the multiple direc­tion radiation treatments, the use of wedged fields, and isocenter technology. d. The improving results and increasing num­ber of cured children raise the question of late, frequently permanent radiation effects. Their inci­dence must be followed for prophylaxis and rehabilitation. Both radiation therapy and cytosta­tic treatment can cause the development of damage such as somatic mutations, genetic di­sorders, disturbances of the endocrine system, growth disturbances, and the decrease in the intelligence quotient (8, 9). Conclusion -We have investigated the possible ways of radiotherapy in childhood for malignant CNS tumours, emphasizing the significance of postoperative radiotherapy. Between 1986 and 1990 we treated altogether 30 patients under the age of 15 years, for CNS primary malignancies. The crude survival rate of our patients was 24.5 months. Refe rences 1. Farwell IR, Dohrmann GH, Flannery JT. Cancer 1977;40:3123. 2. Gyenes G. Magyar Onkol6gia 1981; 25:235. 3. Gyenes G, Nemeth Gy. Sugartherapia -Medici­na. Budapest, 1986. 4. Gyenes G. Magyar Onkol6gia 1977;21 :231. 5. Juvancz 1, Paksy A. Orvosi biometria, Medicina BP, 1982. 6. M\f)rk SJ, L:.cken AC. Cancer 1977;50:907. 7. Scheline GE. Cancer 1977;39:873. Kocsis B et al. Radiotherapy of intracranial childhood tumours with 9 MV linear accelerator (Neptun 10-P) • 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. 8. Sasaki U, Haru M, Watanabe S. JP H Ciin Oncol 1988;18:84, 9. Schuler D. Orvostudomany 1982;33:445. 1 O. Fritz P, Becker F, Kuttig H, Winkel K. Strahlen­ther, Onkologie 1989;165:571. 11. Goldwein JW, Glauser TA, Packer RJ et al. Cancer 1990 ;66 :557. 12. Gyenes G. Radiobiol Radiother 1980 ;21 :208. 13. Jones, P.M. The Practitioner 1979;222:221. 14. Kocsis B, Pap L, Soml6 P, Gyenes G, Kontra G. Magyar Onkol6gia 1989;33:173. 15. Lanering B, Marky J, Nordborg C. Cancer 1990;66:604. 16. Lindgren M. Strahlentherapie 1974;147:109. 17. Scherer E. Strahlentherapie, Springer Verlag, 1989 . 18. Suc E, Pons A, Roche H et al. Acta Neurochir 1989;97:19. 19. Veath JM. Childhood Cancer Triumph over Tra­gedy. Basel, Miinchen, Paris, London, New York: S. Karger 1982. Author's address: Dr Bela Kocsis, Orrostovabbkepzo 20 lntezet, Sugartherapieas Tanszek, Budapest XII, Rath Gyorgy utca 7-9, P.F. 21, 1525 Budapest, Hungary THE INSTITUTE OF ONCOLOGY, LJUBLJANA THE EFFECT OF NEW UNDERSTANDING OF CURABLE BREAST CANCER AND RELATED WITH THAT CHANGED TREATMENT APPROACH ON FIVE-YEAR DISEASE-FREE SURVIVAL AND OVERALL SURVIVAL OF BREAST CANCER PATIENTS Lindtner J, Eržen D Abstract -A comparison of 5--year disease-free survival and overall survival in two groups of breast cancer patients treated at the Institute of Oncology in Ljubljana in the years 1976-1977 (287 pts) by surgery and irradiation, and in the years 1982-1985 (318 pts) by surgery, chemotherapy and irradiation, has pointed out a favourable effect of adjuvant systemic treatment on the survival of patients with unfavourable prognostic factors. UDC: 616.19-006.6:615.849.5 Key words: breast neoplasms; survival analysis Orig sci paper Radiol lugosl 1991 ; 25 :345-9. lntroduction -Breast cancer st. 1 and II is generally believed to be a surgically curable disease if diagnosed on tirne and treated by an adequate intervention. This is almost a century old belief which can hardly be shattered by more recent knowledge on curable cancer as a syste­mic disease which, however, fails to be detected by the existing diagnostic methods (1 ). As a result of these discoveries, in the last two deca­des new treatment approaches have been intro­duced in oncology, in the first place additional systemic treatment, i.e. the so--called adjuvant cytostatic and hormona! therapy. At the Institute of Oncology, the results of such changed attitude became apparent in the decade between 1976-1985: thus, by 1975, adjuvant systemic treatment would have been regareded as a hardly acceptable novelty whereas in 1985 it was vitium artis if at least certain patients with operable breast cancer were not treated by adjuvant chemotherapy. ls it therefore exaggera­ted to call that decade, at least with reference to the treatment in breast cancer st. 1 and 11, »a decade of changes«? The aim of the present study is to point out how the mentioned changed understanding of curable breast cancer and accordingly changed approach to its treatment reflects on the 5-year disease-free survival and overall 5-year survival of these patients. Material -The research was based on historic data of 605 patients with breast cancer stage 1 and II, treated at the Institute of Oncology in Ljubljana from January 1, 1976 to December 31, 1985. Patients over 70 years of age, as well as pregnani, breast-feeding and those in whom breast cancer treated during the appointed tirne period was not a primary malignancy, were exclu­ded. The selected patients were distributed into two groups that could be compared to each other in order to provide an answer to the question defined in the aim of this study: G r o u p A comprised 287 patients treated in the years 1976 and 1977, whereas G r o u p B consisted of 318 patients treated dUTing the period 1982-1985. The comparability of both groups by specified prognostic factors is given in Tables 1 and 2. Differences in treatment approach are evident from Table 3. Lindtner J, Eržen D. The effect of new understanding of curable cancer and related with that changed treatment approach on five-year disease-free survival and overall survival of breast cancer patients Table 1 -Comparability of the observed groups of Table 4 -5-year cure of observed patients distributed patients into prognostic classes Observed parameter Group A Group B (Na = 287) (Nb =318) Class 1976-1977 No. of %of 1982-1985 No.o! %of patients cure patients cure 1) Mean age 51yra .. 87 2) Menopause .% .% 1) N0G1 3) Primary tumor size 2) No G2 70 84 38 87 3) N0G3 28 75 upto20 mm .% .% 4) N1 G1,2 Po 48 65 over 50 mm 0% 3% 4) Rate of poorly differentiated 5) N1 G1,2 P1 26 58 58 66 primary tumors 6) N1G3 Po 29 41 21 58 (grade III) .% ..7% 7) N1 G3 P1 29 45 5) Rate of patients with negative lymph nodes ..5% .% Legend: N -lymph nodes G -grade of malignancy P -l.n. capsule invasion Table 2 -Comparability of patients with histologically positive lymph nodes Table 5 -5-year survival of observed patients distribu­ ted into prognostic classes GroupA GroupB Observed parameter (Na1 = 142) (Nb1 = 181) 1976-1977 1982-1985 Class No.of %of No. of %of lymph nodes 1-3 59.8% 54.6% 1) Number of positiye patients survival patients survival 10 or more 12.6% 20.9% 98 1) N0G1 2) lnvasion through 2) N0 G2 70 84 38 87 lymph node capsule 45.7% 58.6% 3) No G3 28 82 78 81 4) N1 G1 ,2 Po 48 Table 3 -Treatment methods in A and B groups of 5) N1 G1 .2 Po 26 77 58 66 patients 6) N1 G3 Po 29 48 21 76 Treatment Group A Group B 7) N1 G3 P1 44 57 1 ) Mastectomy 100% ..7% Legend: N -lymph nodes 2) Breast resection o 17.3% 3) Postoperative irradiation 30.6% .4% 4) Adjuvant chemotherapy o ..2% 5) Perioperative chemotherapy o M.4% Results -Five-year disease-free survival and overall survival of patients in the observed groups is graphically presented in Figure 1. Five-year disease-free survival and overall survival of patients with negative axillary lymph nodes is presented in Figure 2. -Five-years disease-free survival of patients distributed according to prognostic categories is given in Table 4. Discussion -Here it should be pointed out again that this study was not aimed to evaluate the effect of one or the other treatment modality on disease-free survival or overall survival, but rather to present how the changed approach to the treatment of patients with curable breast cancer reflected on the course of disease during the first five years since the beginning of therapy. This is most evident from Table 3 and the respective totals of percentages in the 1 st and G -grade of malignancy P -l.n. capsule invasion 2nd columns: thus the former presents what happened with the patients, whereas the latter specifies the method of treatment which was obviously different. The present work actually conveys just this message and nothing more. The decision to define the period between 1976-1985 as »the decade of changes« has been made for technical reasons: In that period, diagnostic workup and conse­quential follow up of patients with curable breast cancer treated at the Institute of Oncology in Ljubljana was improved in accordance with the recommendations of SASIB research group (Scando--Afro--Swiss lnternational Breast Cancer Study, Lausanne, Switzerland) which was joined also by our Institute. The comparison presented in Tables 1 and 2 is not possible for older patients. Also, the apparently small number of patients included in group B during the years 1982-1985 requres an explanation: though the number of patients with curable breast cancer treated yearly at the Institute of Oncology did not significantly change, the patients from other Yu­goslav republics had to be excluded from the Lindtner J Eržen D. The effect of new understanding of curable cancer and related with that changed treatment approach o n five-year disease-free survival and overall of survival cancer patients study as their regular follow up was practically axillary lymph nodes. Though we cannot explain not possible. this difference, it does not seem to be of rele­ As to the comparability ot our groups ot pa­vance tor the message conveyed by our report, tients under investigation, the only statistically as each group was represented independently. significant difference was tound between the With regard to the tumour volume, it should be patients with positive and those with negative pointed out that in group A, the criteria tor tumour 1001 -..:"S-,-----:,,,___ ..• OOI························. .. c,n A,B rt! > OO•································································· .•­ > s... :::::, Vl <40 (lJ 20 s... :::::, u 01----r-----.----r-----.------,.---. o 10 20 .30 -40 50 ro Legend: A -cure rale in 287 palienls lrealed in lhe years C -survival of 287 palienls lrealed in lhe years 1976--77 1976--77 B -cure rale in 318 palienls lrealed in lhe years O -survival of 318 palienls lrealed in lhe years 1982-85 1982-85 Fig. 1 -Five-year disease-free survival and overall survival in 605 patients with breast cancer St I and II, treated in the years 1976-1985 at the Institute of Oncology in Ljubljana 100 . 80 --==-.-,-_ .-----------_ ..=.-= QD BA ';;j > > s... ::, v, EO 4(J ::, u 20 o o 10 20 .30 40 50 EO Months of observation Legend: A -cure rale in 142 palienls lreated in lhe years C -survival of 142 patienls lrealed in lhe years 1976--77 1976--77 B -cure rale in 182 palienls lrealed in lhe years O -survival of 182 palienls lrealed in lhe years 1982-85 1982-85 Fig. 2 -Five-year disease-free survival and overall survival in 282 patients with breast cancer St I and II and negative axillary lymph nodes, treated in the years 1976-1985 at the Institute of Oncology in Ljubljana. Lindtner J Eržen D. The effect of new understanding of curable breast cancer and related with that changed treatment approach on five-year disease-free survival and overall survival of breast cancer patients '00i ..----. "" 80 "' > > '-­::, v, •·· w ---.=d . 40 a., '-­ ::, u or--,---,----,-----..---------,---.j o I O .'(1 .:{1 40 :(J ED Months o f observa ti on Legend: A -cure rale in 145 palienls lrealed in lhe years C -survival of 145 palienls lrealed in lhe years 1976-77 1976-77 B -cure rale in 137 palienls lrealed in lhe years D -survival of 137 palienls lrealed in lhe years 1982-85 1982-85 Fig. 3 -Five-year disease-free survival and overall survival in 323 patients with breast cancer SI I and II and positive axillary lymph nodes, treated in the years 1976-1985 at the Institute of Oncology in Ljubljana. operability determination were strictly defined by T-symbol, whereas in group B also breast cancer classified as T3a were considered curable. Though in our discussion we try to avoid drawing conclusions on the relevance of particu­lar treatment approaches, Table 3 stili calis for some further explanation: Evidently, the patients in group A did not receive any primary systemic therapy; these were the patients with negative axiliary lymph nodes and tumours in the anterior median third of the breast, who received postope­rative irradiation. This treatment, however, was not applied invariably, but depended rather on the decision of individual physicians. Even grea­ter diversity of opinions was seen with reference to the need of postoperative irradiation in patients with positive lymph nodes. Therefore, our Insti­tute decided to join the aformentioned internatio­nal prospective randomized study according to which every other patient with positive lymph nodes was subjected to postoperative irradiation. Likewise, every other patient with negative lymph nodes from group B underwent additional systemic therapy: thus 69 of 137 received a perioperative dose of CMF chemotherapy accor­ding to our prospective randomised clinical study (LBCS V) (2). As a rule, group B patients with positive lymph nodes were invariably subjected to either hormona! or cytostatic chemotherapy. As to the latter treatment modality, in some patients cytotoxic drugs were applied perioperati­vely, whereas others received classical postope­rative chemotherapy or a combination of both regimens. Figures presenting the data on disease-free and overali survival do not require any further comment. The noticeable differences are without statistical significance. In an attempt to present possible differences, ali the patients were further distributed into different prognostic subgroups. Thus, the patients with negative lymph nodes are divided into three classes according to mali­gnancy grade of the primary tumour (in this distribution, also the tumours which are generaliy not classified according to their malignancy grade were included in grade III subgroup). The pa­tients with positive lymph nodes were distributed int0 4 prognostic classes according to the criteria co. ,didered in the randomization by SASIB group. Some positive differences have been observed in prognosticaliy unfavourable subgroups, though the differences were not statisticaliy significant owing to a smali number of cases. Our study supports the weli known (3) and subsequently confirmed opinion on the value of adjuvant syste­mic treatment in patients with early breast can­cer. It further points out that an objective asses­sment of the significance of individual treatment approaches requires a substantialiy larger num- lindtner J Eržen D. The eflect of new understanding of curable breast cancer and related with that changed treat'!lent approach of five-year disease-free survival and overall survival of breast cancer patients ber of patients than can be collected within a reasonable period of tirne by a single oncological center, and therefore, multicentric collaboration between different oncological institutions in this field is of essential importance. References 1. Fisher B, Redmond C, Fisher ER, NSABP investi­gators. The contribution of recent NSABP clinical trials of primary breast cancer therapy to an undertanding of tumour biology -an overview of findings. Cancer 1980; 46:1009-25. 2. Ludwig Breast Cancer Study Group: Randomized perioperative in operable breast cancer: The Ludwig trial V. Recent Results Cancer Res 1989; 115:43-53. 3. UK-BCTSC/UICC/WHO (1984) Review of morta­lity results in randomized trials in early breast cancer. Lancet II: 1205. 4. Adjuvant Systemic Treatment tor Breast Cancer Metaanalysed, LANCET 1989;1 :30-84. Author's address: Doc. Dr. Jurij Lindtner, The Insti­tute of Oncology, Zaloška 2, 61105 Ljubljana, Slovenia Najnovejše v zdravljenju ulkusne bolezni UL TOP@ (omeprazol) kapsule 20 mg prvi selektivni inhibitor protonske crpalke nova ucinkovina z bistveno drugacnim nacinom delovanja od vseh doslej znanih antiulkusnih zdravil • hitrejša zacelitev ulkusa dvanajstnika, želodca in požiralnika • hitrejše prenehanje bolecin • ucinkovit tudi pri bolnikih rezistentnih proti dosedanjemu zdravljenju • zdravilo izbire za bolnike s Zollinger-Ellisonovim sindromom Indikacije Duodenalni ulkus, želodcni ulkus, refluksni ezofagitis, Zollinger-Ellisonov sindrom. Doziranje Duodenalni ulkus 1 kapsula (20 mg) Ultopa 1-krat dnevno pred zajtrkom; ce ulkus ne zaceli v 2 tednih, zdravljenje podaljšamo še za 2 tedna. Zelodcni ulkus in refluksni ezofagitis 1 kapsula (20 mg) Ultopa 1-krat dnevno pred zajtrkom 4 tedne; ce ulkus ne zaceli, zdravljenje podaljšamo še za 4 tedne. Bolnikom, ki ne reagirajo na druga zdravila, priporocamo 40 mg (2 kapsuli Ultopa) na dan, 4 tedne pri duodenalnem ulkusu, oz. 8 tednov pri želodcnem ulkusu ali refluksnem ezofagitisu. Zollinger-Ellisonov sindrom Priporocamo zacetno dozo 60 mg (3 kapsule Ultopa) dnevno. Nadaljnje doziranje je indiv,tlualno, zdravljenje pa traja, dokler je indicirano. Ce je dnevna doza višja od 80 mg, jo razdelimo v dve posamezni dozi. Kontraindikacije Niso znane. Oprema 14 kapsul po 20 mg Podrobnejše informacije in literaturo dobite pri proizvajalcu. . .. KRK. tovarna zdravil, p. o., Novo Mesto 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, zalim 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 EIIIII Beograd, Kosovska 17/VI Beograd, Svetog Save 2 telefoni: 321-440 i 321-791 (i) tel. 434-712 fax. 431-517 FACUL TY OF ELECTRICAL ANO COMPUTER ENGINEERING 1, UNIVERSITY OF LJUBLJANA, INSTITUTE OF ONCOLOGY2 , LJUBLJANA LOCAL TREATMENT OF FIBROSARCOMA SA-1 ANO MALIGNANT MELANOMA B-16 SOLID TUMORS IN MICE BY ELECTRICAL DIRECT CURRENT: A PRELIMINARY REPORT Miklavcic D1 . Serša G2, Vodovnik L 1 . Novakovi<': S2, Bobanovic F1 . Reberšek S1 Abstract -Low level direct current (1.0 to 1.8 mA) was employed as an antitumor agent in two different murine tumor models, fibrosarcoma Sa-1 in A/J mice and malignant melanoma B-16 in C57 BI/6 mice. Single shot treatment with direct current (1.0, 1.4 and 1.8 mA) of one hour duration was performed after tumors reached initial tumor volume (V0) 48.2±7.9 (n=53) and 45.2±7.5 (64) in Sa-1 and B-16 model respectively (AM±STD). Direct current was deliverad via multiple needle electrode array (Pt-lr alloy, 90-10%), where three electrodes (cathodes) were inserted directly into the tumor and two electrodes (anodes) were placed subcutaneously in tumor vicinity. Escalating doses of electrotherapy resulted in both tumor models with proportional increase in achieved growth delay which was 4.1 ±0.8 (n=19) days at 1.0 mA and 11.8±0.9 (n=1 O) days at 1.8 mA in fibrosarcoma SA-1 and 8.6±0.6 (n=23) days at 1.0 mA and 16.8±0.8 (n=6) in melanoma B-16. In the later tumor model also 4%, 10% and 40% cures were achieved by electrotherapy with 1.0, 1.4 and 1.8 mA of one hour duration respectively. After ET in both tumor models temporal tumor remission was obtained at higher current levels but in most cases tumor regrowth occurred. Fram the results obtained it is evident that ET as described is a potential regional cancer treatment modality. UDC: 616-006.327.04:615.84 Key words: fibrosarcoma; melanoma; electromagnetic fields-therapeutic use Prelim report Radiol lugosl 1991; 25:351-3. lntroduction -Although cancer is a very old disease known already in ancient cultures, there is stili need to search new cancer treatment modalities since many clinical cases do not respond to established approaches. There has been few reports describing low leve! direct current (DC) as a possible antitumor agent on different murine tumor models (1-3) and in clinic (4). The objective of our study was to investigate the effect of electrotherapy (ET) on two new murine tumor models. The protocol was based on our previous research where the effects of DC polarity, current level, ET duration and the num­ber of electrodes were studied (5,6). Materials and methods -lnbred A/J and C57 Bl/6 animals of both sex were purchased from the Institute Rudjer Boškovic, Zagreb, Croatia and were eight to twelve weeks old at the start of experiment. Animals were kept in groups of five to eight in plastic cages at natura! day/light cycle, constant room temperture 24 ° C and were fed ad libitum. Subcutaneous solid tumors fibrosarcoma (Sa-1) syngeneic to A/J and malignant melanoma (B-16) syngeneic to C57 Bl/6 were initiated by subcutaneous injection of 5. 105 and 7. 105 tumor cells dorsolaterally respectively. Single celi su­spension was obtained from ascitic fluid of tumor bearing animals tor Sa-1 and by gentle mechani­cal disaggregation from viable tumor parts for B-16. Celi viability was determined by trypan blue exclusion test and was more than 90%. After the tumors reached initial tumor volume (V0), 48.2±7.5 (n=53) in Sa-1 and 45.2±7.5 (64) B-16 tumor model, they were subjected to single­shot electrotherapy. DC was delivered through Pt-lr needle electrodes (0=0.7 mm) inserted (three electrodes, 18 mm long, insulated except 3 mm tip) directly into tumor and (two electrodes, 20 mm long) subcutaneously in tumor vicinity (5 mm medialiy and lateraliy from tumor edge). Electrodes inserted into tumor were connected with single lead to negative terminal and those inserted subcutaneously in tumor vicinity to posi­tive terminal of constant current source designed and manufactured at Faculty of Electrical and Computer Engineering, Ljubljana, Slovenia. Total DC of 1 .O mA, 1 .4 mA, and 1.8 mA was passed through tissue for one hour. Control group was treated in the same way except for the current flow. During ET, animals were firmly fixed and they showed no obvious discomfort, therefore no anasthesia was used. Therapy effect was asses- Miklavcic O et al. Local treatment of fibrosarcoma SA-1 and malignant melanoma 8-16----solid tumors in mice by electrical direct current: a preliminary report sed by measuring three mutually orthogonal tu­mor diameters (ee1 , e2, e3) on each day tollowing ET, and the tumor volume was calculated (eq.1 ). From tumor growth curves the tirne needed to double initial tumor volume (TD) was determined tor each tumor individualy, and growth delay (GO) was calculated (eq. 2) V = . . ·e1 ·e2·e3 6 GDx . LTDxj : LTDci 2 j ·where c is index ot control and x ot specitic ETegroup, i and j are indexes ot animals within both groups running from 1 to m and 1 to n in controland ET group respectively. Corresponding stan­dard deviation a was calculated (eq. 3) with v degrees ot freedom (eq. 4)e (n-1)·a/+(m-1)a/(_2_+_2_) 02= 3e n+m-2 m n v=en+m-2 4 where CTx and CTc are experimental standard de­viations in experimental and control groups. Results were statistically evaluated employing non-parametric Mann-Whitney Rank-Sum testeon each day tollowing ET, comparing the me­dians ot tumor volumes in control and specitic ET group. Results and discussion -Time from inocula­tion to performance ot ET was 7 and 1 O days in Sa-1 and B-16 respectively. Tumor volume dou­bling tirne (TD) in control groups was 1.8±0.6 days (n=15) in Sa-1 and 2.5±0.7 days (20) inB-16 tumor model. At 'doses' 1.4 mA and 1.8 mA temporal tumor remission was obtained. In most ot the cases tumor regrowth occurred within tew days. Tumor growth curves are presented in Figure tor Sa-1 (left) and tor B-16 model (right).Tumor growth delay was statistically highly signi­ticant on each day tollowing the ET (p<0.0001tor six days after ET). Animals, in which no tumorregrowth occurred within 30 days after ET, were pronounced as tumor free (S) and accordingly,the percentage ot cures (C) was calculated (eq.5). number of tumor free animals C= number of all animals in specific ET group . 1 OO% 5e Different susceptibility ot Sa-1 and B-16 was evident from GO and C and it remains to beeexplained whether it is a result ot different struc­ture ot Sa-1 and B-16 tumors, or is it due to the differences between tumor celi strains. At least partially the difference in tumor response to ET between both models employed may be explai­ned by the difference in initial tumor volumesbetween Sa-1 and B-16 models (p<0.01 : single tailed Student t-test). From the results obtained in our study it is evident (Table, Figure) that ET as performed, although stili in its intancy, is an effective poten­tial regional cancer treatment modality compara­ble to other established approaches. We have observed no_ side effects such as tissue burnsnor any obvious discomtort in animals during ET. Acknowledgements -This research was sup­ported by The Ministry ot Science and Technolo­gy, Slovenia. Authors wish to express their ap­preciation to M. Kogovšek, Eng., and J. Rozman, M.eSe. tor their valuable assistance.e Refereences 1. Humphrey CE and Seal EH. Biophysical approachtoward tumor regression in mice. Science 1959; 130:388-90. 2. David SL, Absolom DR, Smith CR. Effect of lowlevel direct current on in vivo tumor growth in hamsters.Cancer Res 1985; 45: 5625-31 . 3. Marino AA, Morris O and Arnold T. Electricaltreatment of Lewis lung carcinoma in mice. J Surg Res 1986; 41: 198-201. Table 1 -Single-shot electrotherapy effect on tumor growth by growth delay (GO), number of tumor free animals (S) and percentage of cures (C) for each specific ET group together with number of animals (n) included in groups. Sa-1 B-16e GO (days) n C GO (days) n C ET 1.0 mA 4.1 ±0.8e19e0% 8.6±0.6e23+1S 4% ET 1.4 mA 7.2±0.7 9 0% 11.5±1.1 9+1S 10% ET 1.8 mA 11.8±0.9 10 0% 16.8±0.8 6+4S 40% Miklavcic O et al. Local treatment of fibrosarcoma SA-1 and malignant melanoma 8-16-solid tumors in mice by electrical direct current: a preliminary report Fibrosarcoma Sa-1 Malignant melanoma B-16 1000 -.-----------------, .--------------......-1000 500 300 Q) 100 o f> 1-. o . 50 30 J-11 /1tf}ttI if -t1 .,rt ft fl ttf • control 'f-tf' ¦ ET 1.0mA .t. ET 1.4mA "" ET 1.BmA • control ¦ ET 1.0mA .t. ET 1.4mA "" ET 1.BmA (n=20) (n=23) (n=9) (n6) = 10 -t-,.........,.....-,--..-,--,--,,--,-..,.....-,--..-,--,--,--,--r-r-r-.-r-rl 1 10 o 5 10 16 20 25 O 5 10 15 20 25 days after electrotherapy Fig. 1 -Tumor growth curves after single-shot electrotherapy with 1.0, 1.4 and 1.8 mA, one hour duration, for fibrosarcoma Sa-1 (left) and malignant melanoma B-16 (right) murine tumor models. Vertical bars: standard error of the mean. J f (n=15)(n= 19) = (n9) (n= lO) 4. Nordenstrom BEW. Electrochemical treatment of cancer. 1: Variable response to anodic and cathodic fields. Am J Ciin Oncol (CCT) 1989; 12: 530-6. 5. Miklavcic D, Serša G, Novakovic S, Jercinovic A. Electrical current in treatment of malignant tumors. Trans BRAGS 1990; 10: 55. 6. Miklavcic D, Serša G, Novakovic S, Reberšek S. Non-thermal antitumor effect of electrical direct current on murine tibrosarcoma Sa-1 tumor model. In: Brighton CT and Pollack SR eds. Electromagnetics in Biology and Medicine. San Francisco: San Francisco Press, 1991 ; 222-4. Author's address: Damijan Miklavcic MSc, Tržaška 25, Faculty of Electrical and Computer Engineering, University of Ljubljana, Slovenia Ranital ® i {"o ­ .) ,,.,;.f ' 0" 1.Y' §i o e lillllltmlllli= ::. l\ !l : : : : : : : : : : : : : : : : : : : : : : : : : : : : :. illilii:1:::1 :t, l :ill i il ·. @ lek tovarna farmacevtskih in : kemicnih izdelkov, n.sol.o, Ljubljana UNIVERZITETNI KLINICNI CENTER, INŠTITUT ZA DIAGNOSTICNO IN INTERVENTNO RADIOLOGIJO KONTRASTNA SREDSTVA PRI SLIKANJU Z MAGNETNO RESONANCO CONTRASt AGENTS IN MR IMAGING Kristl V Abstract -Basic mechanisms of contrast agents enhancement in MR imaging are presented. The most important chemical compounds, which are contrast carriers such as paramagnetic ions, nitroxides, superparamagnetic and ferromagnetic particles, are described. Their proton relaxivity, stability, toxicity and usability are given. UDC: 539.143.43 Key words: magnetic resonance imaging; contrast media Letter to editor Radiol lu9osl 1991; 25:355-9. Uvod -Kvaliteta slike je pri slikanju z mag­netno resonanco (MR) odvisna od intenzitete merjenega signala. Signal je soodvisen od števila protonov (1 H) in hitrosti relaksacije. Osnovni vir kontrasta v MR sta razlicna relaksacijska casa posameznih tkiv in razlike v gostoti vode (proto­nov H). MR sliko dobimo tako, da v mocno magnetno polje postavimo vzorec in ga obse­vamo z radiofrekvencnimi (RF) pulzi. Protoni z magnetnimi lastnostmi se v polju usmerijo, RF pulzi pa jih izmaknejo iz ravnovesne lege. T1 ali longitudinalni oz. spin -mrežni relaksacijski cas je interval, ki ga skupina protonov potrebuje, da se ponovno uredi z magnetnim poljem in se vzpostavi longitudinalna (vzdolžna) magnetizaci­ja. T 2 ali transverzalni oz. spin-spinski relaksacij­ski cas pove, kako dolgo tkivo zadrži zacasno pravokotno magnetizacijo, ki smo jo inducirali z RF pulzom. To je torej cas, ki je potreben, da izgine pravokotna magnetizacija na osnovno zu­nanje magnetno polje (1 ). Kontrast slike lahko teoreticno spreminjamo s: l. variacijo parametrov snemanja (poseg v ra­cunalniški program) II. poseganjem v tkiva (v pacienta{ -spreminjanje gostote protonov H (uporaba diuretikov, alkohol, hormoni, dehidracija, veliko vode v GIT...) -spreminjanje temperature (T 1 je odvisen od temperature zato lahko spreminjamo kontrast­nost z ogrevanjem ali ohlajevanjem posame­znega dela telesa ali vzorca) -spreminjanje mangetnega polja (kar dose­žemo s kontrastnimi sredstvi (KS). S KS v MR skrajšamo T 1 in T 2. Kontrasta na sliki dejansko ne vidimo, pac pa je viden le njegov ucinek oziroma vpliv KS na magnetno polje vode. V tem se MR KS locijo od rentgen­skih. Tudi uporabne doze so razlicne. Doze pri MR so od 10-5 do 10-3 mol/kg, pri rentgenskih jodnih KS pa so doze 10-3 do 1 o-mol/kg. Tkiva,ki so brez notranjega MR signala ali je šibak, so neprimerna za prikazovanje s KS. To so tkiva z nizko spinsko gostoto, zaradi majhne gostote protonov, kratek T 2 (skelet) ali premikajoci deli (tekoca kri). S povecevanjem koncentracije KS se MR signal ne spreminja linearno in pri vecjih koncentracijah KS MR signal povsem izgine (slika 1 ). Najpomembnejša fizikalna lastnost KS je pozitivna magnetna dovzetnost (magnetna susceptibilnost) (2), ki predstavlja razmerje indu­cirane magnetizacije proti uporabljenemu polju. Kristl V. Kontrastna sredstva pri slikanju z magnetno resonancos N a ru ­ b C (Gd DTPA) Slika 1 -Vpliv koncentracije Gd-DTPA na spremembe T 1 ali T 2 (a-cerebrospinalna tekocina, b-mišica, c-je­tra) (2) Fig. 1 -Effect of Gd-DTPA concentration on changes in T 1 or T 2 (a-cerebrospinal fluid, b-muscle, c-liver) (2). Ta vrednost podaja sprejemljivost dolocene snovi za magnetizacijo z zunanjim magnetnim poljem. Odvisna je od atomske zgradbe in porazdelitve elektronov na orbitalah. Snovi delimo v diamagnetne, paramagnetne, superparamagnetne in feromagnetne. Diamag­netne snovi imajo negativno magnetno dovzet­nost in zato se v njih inducira negativna magneti­zacija. Ta efekt je zelo šibak. Vecina organskih in anorganskih spojin kaže le diamagnetne las­tnosti in so kot take nezanimive kot KS za slikanje z MR. Princip delovanja kontrastnih sredstev -Znacilen za paramagnetne, superparamagnetne in feromagnetne snovi je magnetni ucinek ne­sparjenih elektronskih spinov. Te snovi imajo pozitivno magnetno dovzetnost in zato povzro­cajo pozitivno inducirano magnetizacijo v mag­netnem polju. Magnetni tok okrepi v teh snoveh magnetno polje. Povišana temperatura kvari magnetno urejenost snovi in manjša magnetno dovzetnost. Pri doloceni temperaturi (Neelova temperatura) je magnetna dovzetnost enaka nic. Pri spreminjanju magnetnega polja kažejo fero­magnetni materiali lastno magnetizacijo, ki ostane tudi po njegovi odstranitvi. Tak magnetni »spomin« se med drugim uporablja za magnetne zapise in za stalne magnete. Superparamag­netne snovi obravnavamo kot termodinamsko neodvisne delce. Njihova magnetna dovzetnost (po atomu ali molu npr. železa) dalec presega odgovarjajoce paramagnetne snovi. Superpara­magnetna dovzetnost se linearno veca z mocjo polja pri šibkih jakostih in se nasiti (doseže maksimum) pri zadostni jakosti magnetnega pol­ja. Po odstranitivi zunanjega magnetnega polja se inducirana magnetizacija izgubi. Paramag­netna KS vnašamo v organizem kot vodne razto­pine, superparamagnetna pa suspendirana. Prva imajo široko uporabnost, druga pa le pri prikazo­vanju retikuloendotelialnega sistema (RES), kjer izkorišcajo fagocitozo. Relaksacijski vplivi paramagnetnih snovi so bili prvic opisani leta 1946 (3). Paramagnetizem izhaja iz nesparjenega elektrona, ki tvori mag­netno polje in spremeni relaksacijo. Pozitivna magnetna dovzetnost je potrebna, ni pa zadostna za povecanje relaksacije. Vecanje relaksacije je odvisno od bližine jedrskih in elektronskih spinov in casa medsebojnega delovanja. Molekuli vode in paramagnetnega KS morata biti zelo blizu, da se prva hitreje relaksira. Razlicen vpliv na T 1 in T 2 lahko razumemo kot posledico neravnotežja magnetnih momentov, bližine razlicnih spinov in vpliva faktorja spin/cas. Dogajanja niso popol­noma razjasnjena, ceprav opisujeta naslednji enacbi približne osnove za oblikovanje paramag­netnih KS (4). + T1opazovan T 1 paramagneten T 1 diamagneten 1 + T 2opazovan T 2paramagneten T 2diamagneten 1 /T 1 in 1 IT 2 sta relaksacijski razmerji, opazo­vani v prisotnosti paramagnetnih molekul. So le vsota proton relaksacijskih razmerij' ki bi se pokazala brez paramagnetne snovi in razmerij, ki so povzrocena z vnašanjem le teh. Paramag­netne snovi znižajo T 1 in T 2. Relaksivnost pomeni relativno spremembo relaksacije merjenega vzorca ali tkiva glede na koncentracijo KS (npr. relaksivnost 8 pomeni, da se ob uporabi 1 mmol KS poveca relaksacija tkiva za 8-krat). Kot prva KS v MA poglejmo topne para­magnetne snovi (5,6). Doloceni kovinski ka­tioni Gd +3, Mn +2 , Fe +3 in cr +3 so paramagnetni zaradi nesparjenih elektronskih spinov v 3d (pre­hodne kovine) ali 4f (lantanidi) atomskih orbita­lah. Število nesparjenih elektronov je lahko od O do 7. Neto molekularni magnetni moment je odvisen od orbitalnega gibanja elektronov in zašcitnega vpliva, ki ga povzroca elektronska vezava v molekularnem povezovanju. Druga bi­ Kristl V. Kontrastna sredstva pri slikanju z magnetno resonancos Tabela 1 -Toksicnost razlicnih paramagnetnih kontras­tnih spojin, ki so potencialno zanimive za MR slikanje Table 2 -Toxicity of several paramagnetic contrast agents which are of potential interesi in MR imaging Spojina Toksicnost Compound Toxicity (mM/kg) MnCl 2 0,22 Na3MnDTPA 1,9 Na2MnEDTA 7,0 GdCl3 0,26 Na2GdDTPA 20,0 stvena zahteva za KS je visoka toleranca /Tabela 1). Slabo prenašanje Gd+3 , cr +3 , Mn +2 , Fe +3 prostih kovinskih ionov je bil vzrok, da so jih izlocili iz proucevanj, ceprav imajo izrazito relak­sirajoce delovanje. Ucinkovita strategija za zmanjšanje toksicnosti, pri tem pa se ohrani paramagnetni ucinek, je keliranje ionov z makro­ciklicnimi ligandi (slika 2). S tem se onemogoci možnost vezave ionov na biološka vezna mesta. Keliranje zmanjša toksicnost, vpliva na biodistri­bucijo, stabilnost in izlocanje. Stabilnost kom­pleksov predstavlja kriticen podatek za toksicno delovanje. Gd+3-ion je v Gd-DTPA tesno pripet s termodinamsko stabilnostno konstanto K5 = 1023, v DOTA pa še mocneje, K5 = 1028, kar rezultira v višji letalni dozi. Keliranje kovine spre­meni njeno obnašanje. Pristop molekul topila do kovinskega iona je zmanjšan, upocasni se nje­govo gibanje, cuti se vpliv liganda na relaksacijo. ·ooc ·ooc coo· coo· ) o,·•· sicnost. Lantanidi imajo veliko afiniteto vezave z poliaminopolikarboksilnimi kislinami. Testirajo dietilentriaminpentaocetno kislino (DTPA), ki se je že uporabljala kot antidot pri zastrupitvah z lantanidi. Gd+3 kaže najvecjo protonsko relaksa­cijo pri vezavi v makromolekularne komplekse z aminokarboksilnimi kislinami, derivati albumina, imunoglobulini ali biokompatibilnimi polimeri. Lantanidov v telesu sesalcev normalno ni. Prosti lantanidi so v dozah od 1 O do 20 µmol/kg mocno hepatotoksicni. Pojavijo se mašcobne degenera­cije jeter in lokalne nekroze že po 12 urah. Pri poskusih in vitro povzroce nizke doze lantanidov precipitacijo nukleinskih kislin, inhibirajo RNA polimerazo, jetrno lipoproteinsko mobilizacijo, glukoneogenezo, tvorijo efekte kalcijevega anta­gonizma, stimYlirajo sprošcanje nadledvicnih ka­teholaminov in nadomešcajo kalcij v encimih, ki vsebujejo kovino (metaloencimi) in s tem spre­mene njihovo aktivnost. Znanih je nekaj Gd+3 izredno stabilnih kompleksov, ki se tudi zadovo­ljivo izlocajo iz organizma: Gd-DTPA, Gd-CDTA (cikloheksandiamintetraocetna kislina) in Gd­DOTA (tetraciklododekantetraocetna kislina). So anionski kelati, ki se nespecificno porazdelijo ekstracelularno in izlocijo z glomerularno filtraci­jo. Normalno ne prestopijo hemato-encefalne bariere. Za razliko od prostih kovin in manj stabilnih kelatov se v uporabljanih dozah dobro prenašajo. Gd-DTPA dimeglumin je prvo klinicno testirano parenteralno KS za MR (7) in junija 1988 registrirano pri Food and Drug Administra­tion (FDA) v ZDA. Dosegljiv je pod zašcitenim imenom MagnevistR (Schering). Reverzibilni stranski ucinki Gd-DTPA so hipotenzija, dvig serumskega železa (pri 15 do 30% pacientih, HOOCV< N Gtl'" > < N N "--v N . v e oo-vzrok je neznan) in pojav nenormalnih jetrnih funkcijskih dvigom bilirubina (pri 2% testov z Gd-EDTA \ COoH ·ooc coo· pacientov, mehanizem neznan). -:-'·1 r. "7 \..____/ COOH Druge spojine gadolinija kažejo predvsem afi­niteto do RES in hepatobiliarnega sistema. Gd­" "'" oksidi in hidroksidi so pri fiziološkem pH-ju ne­ ," ·ooc topni in se lahko oblikujejo kot suspenzije. Neka­teri Gd-kompleksi kot npr. Gd-iminodiacetati se vecinoma pojavijo v hepatobiliarnem sistemu in izlocijo preko biliarnih poti (8). Ostali lantanidi so bili zaradi izredne toksicnosti manj testirani, ce­prav imajo nekateri vecji magnetni moment. Prehodne kovine -so mocno relaksiraJoci elementi. Sem sodijo posebno Mn + 2, er+ in Fe+3 z nesparjenimi elektroni. Omenjeni elementiso prisotni tudi v biomolekulah. Mn +2 je odlicen relaksirajoc element z najdaljšim elektronspin­skim relaksacijskim casom med prehodnimi kovi- Gd·DOTA Slika 2 -Strukturne formule Gd-kelatov Fig. 2 -Structural formules of Gd-chelates Lantanidi -Uporabnost lantanidov se je poka­zala šele pri razvoju MR KS. Mocno skrajšajo relaksacijske case. Gd+ 3 in Eu+ 2 imata sedem nesparjenih elektronov in najvišje spinsko kvan­tno število. Gd+ 3 ima od vseh proucevanih para­magnetnih snovi najvecji relaksacijski ucinek. Keliranje lantanidov spremeni relaksivnost in tok- Kristl V. Kontrastna sredstva pri slikanju z magnetno resonancos nami. MnCl2 povzroci takojšnjo hepatobiliarno relaksacijo, ki pojenja šele po vec urah. Mehani­zem te nenavadne poti izlocanja je neznan. Nekateri Mn-kelati kot npr Mn-PDT A (mangan­propanodiaminotetraocetna "kislina) in Mn-EGTA (mangan-etilenglikolaminoetiletertetraocetna ki­slina) kažejo podobno afiniteto do hepatobiliar­nega sistema (9).Vnešeni manganovi kompleksi se v telesu metabolizirajo, metaboliti še niso popolnoma znani. Verjetno se Mn + 2 v krvnem obtoku veže z makromolekulami. Prost Mn + 2 je strupen. MnCl2 v vecjih dozah kot 1 O µmol/kg je kardiovaskularno toksicen zaradi blokade kalcija. Pojavijo se spremembe v EKG zapisu (QT in PR interval se podaljšata), pojavi se povišan krvni tlak in lahko tudi ventrikularna fibrilacija, tahikar­dija ali bradikardija pri dozi 0,2 mmol/kg. cr + 3 so proucevali v kompleksu z EDTA, kot prost pa je strupen. V skupini prehodnih kovin so obetavni kontrasti z železom. L'.elezove spojine vsebujejo nevrtralno železo (Fe), ione v feri (Fe +3) ali fero (Fe +2) obliki. Feri in fero spojine vsebujejo štiri ali pet 3d orbitalnih elektronov, ki se obnašajo paramagnetno ali superparamag­netno. L'.elezo je normalno prisotno v telesu (1 mmol/kg), njegov metabolizem je dobro poznan. Nahaja se v eritrocitih, kostnem mozgu, RES-u in mišicah, kjer je vezano na funkcionalne pro­teine (hemoglobin, mioglobin, hem-ali nehem­encime, transport.e proteine -transferin, ... ). Glavna biološka naloga železa so redoks reakcije· v transportu kisika in elektronov. Znane so tudi zastrupitve z železom. Posebno so pogoste akutne zastrupitve pri otrocih pri peroralnem vnosu vecjih kolicin zdravil z železom. Pojavijo se gastrointestinalne (GIT) motnje, hepaticna in srcna nekroza. Opisana je celo smrt že pri nizki peroralni dozi (2 'mmol/kg). Parenteralno vne­šeno prosto železo je toksicno še v nižjih koncen­tracijah. Doze parenteralno vnešenega železa 2 mmol Fe/dan kot železo z dekstranom lahko povzroce lokalno bolecino, limfadenitis, glavobol, slabost, vrocino, urtikarijo, artralgijo, mialgijo, hi­potenzijo in redko anafilaksijo. KS v MR vsebu­jejo železo v obliki soli za peroralno uporabo (za prikaz GIT) in v obliki stabilnih kelatov za paren­teralno. Prva uporabljena Fe-sol je bil FeCI3, vendar ni ustrezal, ker draži GIT, boljši je železo­amonijevcitrat. Lepo prikaže proksimalni del GIT, v distalnem pa je efekt slabši, ker verjetno pride do razredcitve in redukcije spojine (1 O). L'.elezov kompleks Ferrioxamin B uporabljajo za prikazovanje secnih poti, je pa kardiovaskularno toksicen in kot tak nevaren. Obetavna sta železova fenolata, Fe-EHPG (etilenhidroksifenilglicin) in Fe-HBED (hidroksibenziletilendiamin), ki se izlocata hepa­tobiliarno (11, 12). Fe-HBED je najstabilnejši že­lezov kelat, ki povzroci takojšnje hepatobiliarno obarvanje in obarvanje secnih poti pri T 1 obteže­nih slikah MR. Superparamagnetni železov oksid apliciran subkutano se zbira v bezgavkah in predstavlja KS za MR limfografijo (13). Nitroksili -Nitroksili so organski radikali z vsaj enim nesparjenim elektronom. Pred razvo­jem MR so jih uporabljali kot paramagnetne snovi v biokemiji. Organski prosti radikali so relativno malo toksicni. V organizmu se metabo­lizirajo po oksidacijsko-redukcijskem encimskem mehanizmu v hidroksilamine, ki pa niso para­magnetni. Hitrost redukcije je višja v hipoksicnih celicah, kar se lahko izkorišca za merjenje intra­celularnega nivoja kisika (14). Farmakološka proucevanja vkljucujejo vrednotenje farmakoki­neticnih parametrov. Možno jih je modificirati s kemijsko sintezo. Relaksacijski ucinki nitroksilov se povecajo s povecanjem molekulske mase, s proteinsko bogatim okoljem, šibkejšim magnet­nim poljem, z uvedbo alkoholnih ali amidnih skupin. Vecji efekt imajo nitroksili piridinskega tipa, piperidinski pa so v organizmu stabilnejši. V primerjavi s kovinskimi paramagnetnimi spoji­nami so nitroksili znatno šibkejši, vendar imajo najdaljši elektron-spinski relaksacijski cas. Iz tega sledi, da imajo makromolekulami konjugati nitroksilov s proteini, mašcobnimi kislinami ali aminokislinami upocasnjeno molekularno gibanje in s tem izboljšano relaksivnost (ca. 1 O-krat) (15, 16). Za povecanje ucinkovitosti in varnosti nitroksilov kot KS v MR potekajo intenzivne raziskave. Posebno pozornost zasluži dejstvo, da bi nitroksile potencialno lahko uporabili kot indikatorje metabolicne aktivnosti organizma (14). Jasno je, da prosti radikali okvarjajo DNA, ni pa podatkov, ki bi pripisovali nitroksilom muta­geno ali kancerogeno delovanje. Tehnološke možnosti -Oblikovanje KS za MR vkljucuje vgrajevanje paramagnetnih (Gd­DTPA, Mn + 2-kelatov, ... ), superparamagnetnih ali feromagnetnih spojin v liposome ali koloidno disperzne sisteme (17). Ti so se izkazali zelo uporabni za prikazovanje RES-a, ker se liposomi z vgrajenim manganom kopicijo izkljucno v RES s fago_s;itozo. Hkrati se pokažejo tudi jetra (Kupferjeve celice). Uporaba gadolinijevega ok­sida je v teh oblikah omejena zaradi njegovega hepatotoksicnega delovanja (subakutni multifo­kalni hepatitis). Superparamagnetne in feromag­netne spojine v RES-u zmanjšajo intenzivnost Kristl V. Kontrastna sredstva pri slikanju z magnetno resonancos signala, kar privede do bistvenega skrajšanja T 2 in se tako razlikujejo od ucinkovanja topnih para­magnetnih snovi. Zaradi zmanjšanja signala or­gan na sliki ni vec viden. Patološko spremenjeno tkivo obdrži svoj signal in je zaradi vecje kontrast­nosti bistveno bolj vidno. Glavni problem je dolgo zadrževanje teh oblik kontrasta v RES, za kar so potrebna dodatna klinicna testiranja. Ciljana kontrastna sredstva -Ciljana kontras­tna sredstva predstavljajo KS za specificno pod­rocje organizma. Pristop je podoben kot pri proti­telesih oznacenih z radioindikatorjem v scintigra­fiji. Poslužujejo se konjugiranja specificnih protei­nov z DTPA in paramagnetnim ionom. Zaradi upocasnjega rotacijskega gibanja kompleksa se poveca relaksivnost in obdrži imunoreaktivnost (18). Pri biološkem testiranju so dokazali pojav preobcutljivosti, kar omejuje uporabnost teh kom­pleksov. Pri oznacevanju protiteles z železom nastopi prevelika obremenitev organizma z žele­zom. Raziskujejo tudi druge snovi kot so iskalci tumorjev (porfirini) in intravaskularni oznacevalci. Pomanjkljivosti le teh je njihova akutna toksic­nost. Zakljucek -V clanku je opisan osnovni meha­nizem delovanja KS v MR. Povdarjene so najvaž­nejše kemicne skupine, ki so nosilci kontrasta: paramagnetni ioni, nitroksili, superparamagnetni in feromagnetni delci. Predstavljene so glede na protonsko relaksivnost, stabilnost, toksicnost in uporabnost v MR slikanju. Literatura 1. Schild HH. MRI made easy. Berlin: Schering AG, 1990. 2. Stark OD, Bradley WG. Magnetic resonance ima­ging. New York: Mosbey Company, 1988. 3. Bloch F, Hansen WW, Packard P. The nuclear induction experiment. Physiol Rev 1946; 70: 4 7 4-85. 4. Bertini 1, Luchinat JO. NMR ot paramagnetic molecules. Menic Park. CA: Benjamin/cammings, 1986. 5. Lauterbur PC, Menodsa-Dias RH, Rudin AM. Augmentation ot tissue water proton spin lattice relaxa­ti_on rates ty in vivo addition ot paramagnetic ions. In: Dutton PL, Leigh JS, Scarpa A. Frontiers ot biological energetics. New York: 1978. 6. Bacic G. MRI kontrasti: mehanizam dejstva i primena. Farm vestn 1990;41 :280-85. 7. Brasch RC. Principles ot MRI contrast enhance­ment. In: Budinger TF, Margulis AR. Medical Magnetic Resonance. Society ot Magnetic Resonance in Medici­ne, 1988, 121-8. 8. Lauffer RB. Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem Rev 1987;87:901-27. 9. Spiller M, Browen RD, Koening SH et al. The stale ot Mn + 2 in liver bile and blood after iv injection or intusion ot Mn+2 chelates in rabbits investigated using the tield dependence ot 1 /T 1. Soc Magn Res Med 1986;25-6. 10. Wesbey GE, Brasch RC, Goldberg HI et al. Clinical experience with dilute oral iron solutions used for GIT contrast emhancement in abdominal NMR imaging. Mag Reson lmaging 1958;3:57-64. 11 . Engelstad BL, Ramos EC, Macapinlac HA et al. Fe--HBED and Fe--EHPG iron complexes exhibiting hepatobiliary enhancement in MRI. Ciin Nucl Med 1986:11 :19. 12. Renshaw PF, Owen CS, Me Laughline AC et al. Feromagnetic contrast agents: a new approach. Magn Reson Med 1986;3:217-25. 13. Saini S, Modic MT, Hamm B, Hahn PF. Advan­ces in contrast-enhanced MR imaging. AJR 1991 ; 156:235-9. 14. Demšar F, Kveder M, Rugelj S et al. Hydroxyla­mines as oxygensensitive procontrast agents tor in vivo MRI. J Magn Reson 1991 ;95: in press. 15. Lovin JO, Wesbey GE, Engelstad BL et al. Structure--relaxivity relationships tor sixteen nitroxide spin labels potentially suit able as NMR contrast agents. Magn Reson lmaging 1985;3:73-81. 16. Ehman LR, Brasch RC, McNamara MT et al. Diradical nitroxyl spin label contrast agents tor magne­tic resonance imaging. A comparison ot relaxation effectiveness. lnvest Radiol 1986; 21 :125-31. 17. Unger E, Needleman P, Cullis P, Tilcock C. Gadolinium-DTPA liposo mes as a potential MRI con­trast agent. lnvest Radiol 1988; 23 :928-32. 18. Schrere P, Aisen AM. Monoclonal antibodies labeled with polymeric paramagnetic ion chelates. Magn Reson Med 1986; 34:336-40. Zahvala Dr. Franciju Demšarju, Institut Jožef Stefan, Ljubljana, se iskreno zahvaljujemo za strokovne nasvete in pomoc. Naslov avtorja: Dr. Vinko Kristl, IDIR, UKC Ljubljana, Zaloška 7, 61000 Ljubljana, Slovenia General Bectric a-1 ---------------------l , " R E PRESEN TA T.f V E O FF I C E GunduHceva 23/ff -4100. o,zagre. -C.R.· . o. ,A. T. IA Tet: +38 41 437159 -Fax: +38 :41.2t.1-2 , - .,,,•. 1 f ·. l. G v., .. Reports DOSE IN RADIOTHERAPY ESTRO-IAEA SEMINAR, SEPTEMBER 16-21, 1991, LEUVEN In September 1991 a semin2r on »Radiation Dose in Radiotherapy: from Prescription to Deli­very« was organized in Leuven /Belgium by ESTRO (European Society for Therapeutic Ra­diology and Oncology) under the auspices of IAEA (lnternational Agency for Atomic Energy) from Vienna. The seminar was aimed to analyse all the steps taken in radiation treeatment procedures, and thus ensure that the prescribed doses are delivered to irradiation field as scheduled. Among the participants there were over 90 radiophysi­cists from Europe, U.S.A., Middle East and Afri­ca, and a few invited speakers whose lectures represented the basis of the seminar. Day 1 program comprised a series of presenta­tions on general questions such as e.g. the degree of accuracy required in radiotherapy, the need for Quality Assurance Program etc. lndivi­dual stages in a radiation procedure that contri­bute to dosimetric and geometric were grouped as follows: 1. dosimetry 2. patient's data and parameters 3. dose planning 4. beam set-up 5. patient set-up 6. irradiation The degree of accuracy in dosimetry should be determined by SD (standard deviation) for the probability of tumour control, which should not exceed 10% (H.K. Awwad, Cairo). lf all the steps in treatment procedure are carried out correctly, 5% accuracy in dose determination with 3% SD can be achieved. A high SD in the dose distribu­tion in target volume is believed to be less dangerous that a high SD in the mean tumour dose. The ICRU Report No. 29 standardizing the reports on dose determination in radiotherapy was discussed in detail. As the document dates back to the year 1978, it needs to be updated in accordance with progress in dosimetry, expan­ding use at computers in radiotherapy and some other comments concerning its contents (T. Landberg, Malmo). Day 2 of the seminar was dedicated to the calibration of dosimeters and radiation as well as to radiation beam characteristics. E. Swensson (IAEA, Vienna) represented a net of substandard laboratories which would enable users to have their dosimeters calibration with the referential standard in Paris. IAEA Proto­col (Technical Report No. 277) should be accep­ted as a uniform standard for the determination of photon and electron doses worldwide. Special attention has been paid to the quality assurance (QA). Thus every radiotherapy center should have a QA program adjusted to their own needs. K.A. Johansson reported on the study results obtained by a group of radiophysicists from Gothenburg. Within the program of this study, TLD dosimeters were sent to several radiothe­rapy centers in Europe and elsewhere in order to be irradiated under referential conditions with a dose of 100 cGy. Afterwards, actual doses recei­ved by dosimeters were determined. In the period from 1968 to 1984, the measurements were repeated three times and 330 sources of X-rays, Co-60 and electrons were compared. It has been established that during the investigation period the number of measured x-ray and elec­tron doses deviating from the referential values for less than 3% increased from 50% to 98%. Far Co-60 photon beam this rate was 100% throughout the observation period. Among the participating institutions was also the Institute of Oncology in Ljubljana, where a sufficiently accu­rate calibration of machines has been establi­shed (<3% deviation). One of the two main topics that were discussed on Day 3 were patient's data and parameters needed in treatment planning. In her excellent lecture J. Dobbs (London) pointed out the advan­tages and drawback of individual methods for data collecting, i.e. mechanical plotters of countu- Reports res radiological examinations, computed tomo­graphy (CT) and magnetic resonance (MR). In the view of accurate treatment planning, CT has become practically indispensable as it provides reliable data on the exact position and density of individual body structures. though diagnostic va­lue of MR images is indisputable, the method has proved useless in dosimetry since it does not give data on tissue density, and the obtained images are geometrically distorted. A. Dutreix held an interesting lecture on the importance of tissue heterogeneity consideration in treatment planning. The second topic dealt with dusimetry in vivo. There, termoluminiscent dosimetry and semiconductor diodes were pre­sented in detail. Two novelties in this field, i.e. dose determination from portal images and dosi­metry by means of alanine were mentioned. Alanine uptake in the cells occurs under the influence of and it's concentration in the celi is dose dependent. It can be determined by ESR (electron spin resonance), thus providing the data on cumulative dose received by the irradia­ted tissue before measurement. The guideline of the seminar was OA in radio­ therapy at ali stages of the procedure, and there­ fore the whole Day 4 program was dedicated to this topic. Quality audit is performed by different study groups of radiophysicists as well as by institutions. As the basic dosimetry in radiothe­ rapy is relatively advanced, they also test the quality of other factors such as e.g. treatment planning systems. For this purpose, different phantoms with built-in heterogeneities, breast phantom, RANDO phantom etc., intended for in vivo quality testing of dosimetric procedures, are used. According to the results of these studies, inaccuracy of the dose in the reference point of irradiated volu me is relatively small ( < 1-2% ), whereas outside that point it can increase signifi­cantly in certain cases (in breast irradiation to > 10% ). This error is further enhanced by compu­ted treatment planning programs where the hete­rogeneity of structures is frequently corisidered incorrectly in dose calculating. The last day was dedicated to portal imaging. S. Faermann and Y. Krutman developed a physi­cal model of a cassette for gammagraphy. B.J. Mijnheer (Amsterdam) presented a series of new portal imaging techniques where image is crea­ted on a matrix-ionization chamber or on a fluorescent screen placed underneath the patient during irradiation. The image is available on computer screen only a few seconds after the procedure. Recently, new systems are being developed which provide real tirne images that can be compared with simulator images of the same irradiation field on the screen. This repre­sents one of the greatest achievements in the endeavours for radiotherapy improvement. The seminar was characterised by relaxed atmosphere and lively discussion. The partici­pants from developing countries showed unex­pectedly sound knowledge and ambition to solve problems in radiotherapy. Though QA in this field of medicine largely depends on the available material basis, knowledge, accuracy and expe­rience as well as the supervision of equipment and procedures are believed to be of major importance. Bogdan Umek, M.Se. The Institute of Oncology Ljubljana ESTRO TEACHING COURSE OF BASIC CLINICAL RADIOBIOLOGY October 5-9, 1991, Athens ESTRO in collaboration with the University of Athens organized and successfully performed a 5-day course on clinical aspects of radiobiology. Lectures were held in the outskirts of Athens, in Vouliagmeni, which provided stimulating environ­ment for work. The list of teaching staff (G.G. Steel, A.C. Begg, M.C. Joiner, J. Overgaard, A. van den Kogel) promised a high level of lectures, and these expectations have been completely fulfil­led. In the series of lectures which lasted throug­hout the working day »classical« radiobiological topics such as 5-R, celi kinetics and proliferation, radiobiology of tissues etc. were discussed first. There were tutorials held between the lectures, which offered excellent opportunities for informal chat with lecturers by the pool with a cup of coffee. More »recent« topics such as LQ moqel, unconventional fractionation, hyperthermia, pho­todynamic therapy, flow cytometry, interaction of radiation with chemotherapy etc., were also co­vered in sufficient detail, so the course can be regarded as an excellent »high school« of radio­biology for clinicians. The organization and especially the academic level of lecturers and their presentations were of the highest standard. Boris Jancar, MD The Institute of Oncology, Ljubljana Book review CANCER IN ORGAN TRANSPLANT RECIPIENTS Edited by Dietrich Schmahl and lsrael Penn. 183 pp., illustrated, 21 figures. Springer-Ver­lag, Berlin Heidelberg New York, 1991. The book presents a detailed analysis of the problem of cancers that occur before and after organ transplantation. As noted in the preface, in 1968 T.E. Starzl and 1. Penn from Denver recognized that a cancer de novo could develop after transplanta­tions. They observed two lymphomas: one was a non-Hodgkin lymphoma involving the stomach and other organs, and the second a multifocal non-Hodgkin lymphoma of the brain. This expe­rience stimulated inquiries at other transplant centers and resulted in reports of another three cases. That was the beginning and reason tor studying of cancer after organ transplantation. At the 1968 Summer Meeting of the Trans­plantation Society in New York it was suggested that Dr. Penn should start a registry to collect data on post-transplant malignancies. This led to the establishment of Denver (now Cincinnati) Transplant Tumor Registry, which collected data from transplant centers throughout the world, and which has provided numerous publications on the subject. Many investigators at other trans­plant centers have also published data concer­ning experience with these tumors, gained at their own centers, or gleaned from regional regi­stries. Some of them are contributors in the debated book. Another group of tumors occurring in trans­plant patients, that is discussed in this book too, comprises neoplasms that involve a vital organ; the only effective treatment is removal of the entire organ and its replacement with a healthy one, in other words, transplantation. But a funda­mental question that arises is: it any residual tumor cells are left behind, how do they behave when the patient's immune defenses are impai­red by immunosuppressive therapy? These are some of the questions discussed in this book. In the summer of 1989 Prof. D. Schmahl conceived the idea of inviting a small group of experts in various fields -basic cancer research, molecular biology, epidemiology, oncology, viro­logy, nephrology, immunology, pathology, and transplantation surgery -to meet for two days tor a »brainstorming« session to discuss in depth the field of (1) de novo malignancies after transplantations, and (2) the treatment of pre-exi­sting cancers by organ transplantations. Toget­her with Dr. l. Penn they prepared the program and list of invited speakers. The brain storming session was held in May, 1990 in Heidelberg in the Federal Republic of Germany. This book is the outcome of the presentations and discus­sions of ali the papers. This would be ali, as to a brief history of the book. The book is undoubtedly impressive in contents and scope. D.Schmahl 1.Penn (Eds.) ancer c in Organ Transplant Recipients r:1, Springer-Ver1ag W Book review The list of contributors comprises authors from around the world; they have published a number of articles in the world literature in the past years, thus, the book is quite up to date. The publication is well organized and distri­ buted in four sections: The first one is centred on the analysis of de novo cancer in organ transplant patients. It has been pointed out that differences in tumor incidences and tumor patterns in post-transplant patiE:mts between various transplantation centers depend on the degree of immunosuppression, the combination of immunosuppressive agent with other drugs, the kind of organ transplanta­ tion, as well as on the treatment and diseases that the patients had before transplantation. Pari two addresses The treatment of can­cer by organ transplantation and comprehends Liver transplantation far malignant disease, Bone marrow transplantation, and Transplantation of the upper gastrointestinal organs. Within the above field of problems it has been marked that · tor symptomatic kidney cancers tumor recur­ rence rates indicate that it is advisable to wait at least 24 months after primary therapy before performing the transplantation, otherwise a dra­ matic increase in tumor recurrence rates can be expected. For incidentally discovered renal tu­ mors the prognosis is much better. In these cases, it is not necessary to wait until two years have passed, transplantation may be performed as soon as possible. Part three focuses on Possible causes of cancer in transplant patients. It has been emphasized that multiple factors probably play a role in the etiology of the various cancers that occur post-transplantation. lmmunodeficiency per se and infection with oncogenic viruses are probably the major influences. There was discus­ SE!d their role and also those of the underlying diseases requiring transplantations; direct da­mage to DNA by various immunosuppressive treatments; possible synergistic effect of these treatments with various carcinogens; and genetic factors influencing susceptibility or resistance to the development of malignancy. - Part four reviews A possible prevention of de novo cancer in transplant patients. It has been stated that clinical measures such as main­taining immunosuppressive levels as low as is possibly compatible with graft survival, reducing exposure to sunlight, and ensuring antiviral prop­hylaxis have limited value. Apart from the vaccine against hepatitis B, it seems to be far away from developing effective vaccines against other po­tentially oncogenic viruses. The impeding intro­duction of variety of new immunosuppressive agents and a host of new monoclonal antibodies is unlikely to reduce the incidence of post-trans­plant malignancies as long as their effects involve suppression of the host's immune defences. The authors believe our research must becentred on inducing specific immunologic unresponsiveness directed only against the foreign antigens of the graft, but leaving intact immune responses to ali types of infectious agents and to nascent malig­nancies. The most relevant chapters of this book are Discussions at the end of each section of the book. The pointing out and accents in these chapters are the most interesting. The figures and tables in each chapter are well done and helpful. Unlike most multiauthored works, it has sur­prisingly little variation in the excellent quality and clarity of its writing. The book can be recommended unequivo­cally as a thoughtful and stimulating appraisal of de novo cancer in transplant patients. Viljem Kovac, M.D. The Institute of Oncology Ljubljana UDC 616-006(05)(497.1) CODEN RDIUA 4 YU ISSN 0485-893X R.ADIOLOGIA Il1G.OSLAVICA PROPRIETARII IDEMQUE EDITORES: SOCIETAS RADIOLOGORUM IUGOSLAVIAE AC SOCIETAS MEDICINAE NUCLEARIS IN FOEDERATIONE SOCIALISTICA REI PUBLICAE IUGOSLAVIAE LJUBLJANA ANNO 25 1991 Editorial Board Avcin J, Ljubljana -Benulic T, Ljubljana -Bicaku E, Priština -Borota R, Novi Sad -Fettich J, Ljubljana -lvancevic D, Zagreb -Jamakoski B, Skopje -Jevtic V, Ljubljana -Karanfilski B, Skopje -Kostic K, Beograd -Ledic S, 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 1991; 25 (1-4): 1-376 ® 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 informacile in literaturo dobite pri proizvajalcu. ... KRK. tovarna zdravil, p. o., Novo mesto Author's lndex 1991 AUTHOR'S INDEX Ajdinovic B: 1/47-50 Anticevic D: 1 /35-8 Arifhodžic N: 4/331-4 Arnež Z: 3/219-24 Babovic D: 4/331-4 Bajcsay A: 4/339-44 Bajgoric M : 1 /69-70 Banic D: 2/125-8 Barmeir E: 2/129-32 Bedek D: 1/15-7 Beketic-Oreškovic L: 3/235-9 Bence-L'.igman Z: 4/335-8 Benulic T: 1/1-11; 2/95-6; 3/183; 3/255-8; 4/286 Bešlic Š: 3/197-200 Biukovic M: 2/133-5 Bobanovic F: 4/351-3 Boka H: 4/315-7 Borcic V: 4/297-9 Borkovic Z: 2/119-21; 4/305-7 Boschi S: 2/97-101 Bošnjakovic P: 4/301-3 Bracic 1 : 1 /35-8 Bradic 1: 2/103-8; 3/193-6 Brencic E: 3/229-34 Brkljacic 8: 4/315-7; 4/335-8 Budihna M: 2/137-41 Bulajic M: 1 /11-4 Cengic F: 1/69-70 Cengic-Hukovic F: 1/69-70 Cohar F: 3/201-4 Dalagija F: 3/197-200 Dangubic V: 3/225-8 Dizdarevic Z: 3/197-200 E>ordevic-Laloševic BV: 1/39-42 E>ordevic 2M: 1 /39-42 E>urkovic P: 3/197-200 Dodic M: 1/11-4 Dodig D: 1/35-8 Drinkovic 1: 4/315-7 Donati D: 2/129-32 Ducic V: 4/331-4 Dujmovic M: 4/287-96 Dujšin M: 2/103-8 Eržen D: 4/345-9 Fedel 1 : 3/185-92 Fedel V: 3/185-92 Filakovic z: 3/205-9 Frimo O: 1/51-6 Frkovic M: 2/103-8; 3/193-6 Fuckar 2: 3/201-4 Gabelica V: 4/315-7 Gacina M: 2/97-101 Gacina P: 2/97-101 Gadžijev E: 3/229-34 Gašparovic S: 2/115-8 Goldner 8: 1/11-4 Golubovic N: 2/133-5 Radiol lugosl 1991 , 25 :365-70. Graf D: 1/57-61 Grujic E: 4/331-4 Gyenes Gy: 4/339-44 Halbauer M: 4/335-8 HatJ: 1/21-5 Hebrang A: 2/97-101 Horvath A: 4/339-44 Huljev D: 1/57-61; 2/163-5 llic M: 4/301-3 lvaniš N: 2/125-8 lvanovic V: 1/63-7 lvkovic A: 4/301-3 lvkovic T: 4/301-3 Jancar 8: 3/255-8; 4/362 Jankulov V: 4/311-4 Janoki Gy: 4/325-9 Jerin L: 3/185-92 Kacic M: 2/103-8 Kaldau F: 4/339-44 Kasal B: 3/245-9; 3/251"4 Katic B: 4/305-7 Kauzlaric D: 2/129-32 Kenda M: 1/72-72 Klancar J: 1/19 + 1/61; 2/123 + 2/148; 3/211 + 3/240; 4/309 + 318 Klanfar Z: 1/21-5 Kocsis B: 4/339-44 Koljevic A: 3/225-8 Kontra G : 4/339-44 Kovac v: 2/167-7; 3/263-4; 4/363-4 Kraus 1: 2/125-8 Kristl V: 4/355-9 Krošl G: 2/157-62 Kurbel S: 3/205-9 Kušter 2: 4/335-8 Lazarov A: 3/225-8 Lincender L: 4/311-4 Lindtner J: 4/345-9 Lakner V: 2/143-8; 3/213-8 Loncaric S: 1 /35-8 Lovasic 1 : 4/287-96 Lovrincevic A: 4/311-4 Makaruha B: 4/315-7 Mandic A: 2/103-8; 3/193-6 Markovi{; S: 1 /11-4; 3/229-34 Marolt-Ferlan V: 3/229-34 Miklavcic D: 4/351-3 Milatovic S: 4/301-3 Miloševi{; D: 1/57-61 Mozetic V: 3/201-4 Musafija A: 2/133-5 Novak E>: 3/235-9 Novakovi{; S: 2/157-62; 4/351-3 Oberman B: 1/5-9; 44297-9 Oberman BB: 2/115-8 Author's lndex 1991 Obradov M: 4/311-4 Odavic M: 3/225-8 Osmak M: 2/149-55 Ožegovic 1 : 4/305-7 Pap L: 4/339-44 Paunkovic DN: 1/39-42 Paunkovic J: 1 /43-6: 4/319-23 Paunkovic N: 1/43-6; 4/319-23 Paunkovic SJ: 1 /39-42 Pavlinovic Z: 4/335-8 Pavlovic O: 1/43-6; 4/319-23 Peric R: 2/125-8 Perovic A V: 3/229-34 Petrovic J: 1/47-50 Petrovic M: 1 /63-7 Petrovic V: 1 /63-7 Pikat D: 3/185-92 Pinter 2: 3/225-8 Plavec G : 3/225-8 Plesnicar A: 1/71-1 Plesnicar S: 1/75-6; 2/157-62 Pocajt M : 3/255-8 Pompe Kirn V: 3/259-62 Popovic s: 3/251-4 Poropat M: 1 /35-8 Praprotnik T: 2/97-101 Prosen M: 2/157-62 Radanovic B: 1/5-9; 2/115-8; 4/297-9 Radiologia lugoslavica: 1/77-82; 4/365-70 Rajkovic-Huljev Z: 1/57-61 Rakias F: 4/325-9 Rastovac M: 1/47-50 Reberšek S: 4/351-3 Rog lic MM: 2/115-8 Rubin O: 3/205-9 Rubinic M: 2/125-8 Schustar N: 2/129-32 Serša G: 2/157-62; 4/351-3 Skrobic M: 2/133-5 Smolcic S: 1/15-7 Stanojevic-Bakic N: 1 /51-6 Starcevic-Božovic A: 1 /63-7 Strinovic B: 2/109-13 Strozzi M: 4/297-9 Szenzgyorgyi P: 4/325-9 Šeric M: 1 /11-4 Šimunic S: 1/5-9; 2/103-8; 2/115-8; 4/297-9 Škegro M: 4/297-9 Škugor M : 1 /35-8 Šlakovic Š: 1/27-34 Šmid L: 2/137-41; 3/219-24 štabuc B: 3/229-34 Šurlan M: 3/229-34 šustic A: 3/201-4 Šušnjar S: 1/51-6 Težak S: 1 /35-8; 4/335-8 Tkalec V: 3/185-92 Tomic-Brzac H: 4/335-8 Tomic M: 1/47-50 Umek B: 4/361-2 Us J: 1/1-4 Vanlic-Razumenic N: 1/47-50 Varjas G: 4/339-44 Vidakovic Z: 2/109-13 Vidak V: 4/315-7 Vodovnik L: 4/351-3 Vuckovic-Dekic Lj: 1/51-6 Vuckovic R: 2/103-8 Zakotnik B: 2/137-41 Zamberlin R: 1/15-7 Zovko E: 3/241-4 Zubovic 1 : 2/133-5 Zupancic B: 3/193-6 2argi M: 3/219-24 2upancic K: 4/315-7 2upevc A: 3/219-24 Subject lndex 1991 SUBJECT INDEX abnormalities: 3/193-6 aneurysm: 4/297-9 angiography: 4/301-3 angioplasty: 1 /21-5; 3/185-92 antibodies: 3/235-9; 4/325-9 -antibodies monoclonal: 1 /63-7 arteriovenous fistula: 3/185-92 autoantibodies: 2/133-5; 4/319-23 bile duet ·neoplasms -therapy: 3/229-34 biliary surgery: 4/315-7 biological: 3/225-8 blood proteins: 1/47-50 brachytherapy: 2/143-8 brain contusion: 1 /27-34 brain neoplasms: 4/339-44 breast neoplasms: 1/1-4; 4/345-9 -breast neoplasms -therapy: 3/235-9 carcinoma: 3/205-9 -carcinoma non-small celi lung-radiotherapy: 1 /51-6 carcinoembryonic antigen: 4/325-9 cardiovascular system: 1/19 + 61; 2/123+148; 3/211+240; 4/309 + 318 carebral ischaemia: 2/97-101 chromium: 4/331-4 collateral circulation: 1 /5-9 colon -abnormalities: 3/193-6 colorectal neoplasms: 2/125-8 computer -assisted: 3/213-8 contrast media: 4/355-9 dacarbazine: 2/157-62 densitometry: 3/245-9 diabetes mellitus: 4/331-4 diagnosis: 1/27-34 diagnostics: 4/325-9 digital subtraction: 4/301-3 distribution in organs: 4/325-9 dose-response relationship: 2/149-55 drainage: 1/69-70 duodenal diseases: radiography: 1 /11-4 duodenum -radiography: 4/287-96 dura mater: 1/21-5 electromagnetic fields -therapeutic use: 4/351-3 electrotherapy: 4/351-3 elements: 1/57-61 enteritis -radiography: 1 /15-7 esophageal neoplasms -surgery: 3/255-8 fibrosarcoma: 4/351-3 fulvic acids: 2/163-5 gamma cameras: 3/251-4 ganglioneuroma: 2/129-32 gastrointestinal system -radiography: 1/103-8 glioblastoma -analysis: 1/57-61 glomerular filtration rale: 4/331-4 gold radioisotopes 3/241-4 <;:,raves'disease: 1/43-6; 4/319-23 Radiol lugosl 1991; 25:365-70. head and neck neoplasms -surgery: 3/219-24 heard-radionuclide imaging: 3/213-8 hemodialysis: 1 /39-42 -hemodialysis -adverse effects: 3/185-92 hig count rate: 3/251-4 hip: 1/109-13 -hip joint-radiography: 1/109-13 hyperthyroidism: 2/135-5 image processing: 3/213-8 immunity cellular: 1/51-6 index 1991: -author's index: 4/367 -subject index: 4/369 insulin dependent: 4/331-4 interleukin: 2/157-62 intestines -abnormalities: 1/103-8 intraoperative period: 4/315-7 iohexol : 2/115-8 iridium radioisotopes: 2/143-8 ischemia: 1/15-7 kidney neoplasms -radiography 3/205-9 laser surgery: 3/255-8 Legg-Perthes disease -radionuclide imaging: 1/35-8 leukocyte -drug effects: 2/157-62 liver abscess: 1/69-70 lung diseases: 3/225-8 magnetic resonance imaging: 4/355-9 malignant tumour: 4/325-9 mammography: 1 /1-4 Martan syndrome: 4/297-9 melanoma: 4/351-3 mesenteric arteries: 4/297-9 metabolic clearance rate: 3/241-4 mice: 2/157-62 microscopy: 3/245-9 monoclonal: 3/235-9; 4/325-9 multiple: 3/193-6 neoplasms -epidemiology: 3/259-62 nephritis -therapy: 3/201-4 paranasal sinus neoplasms -therapy: 2/137-41 parotid gland: 4/305-7 pelvic veins: 2/119-21 phlebography: 2/119-21 prolapse: 1 /11-4 prostatic neoplasms -diagnosis: 1/63-7 protein binding: 1/47-50 pylorus -surgery: 4/287-96 radiation: 2/149-55 -radiation dosage: 2/143-8 -radiation tolerance: 2/149-55 radiochemical purity: 4/325-9 radiologist: 1 /1-4 radionuclide imaging: 3/245-9 radiopharmaceuticals: 4/325-9 radiotherapy: 4/339-44 receptors: 4/319-23 Subject lndex 1991 renal artery -radiography: 2/115-8 renal celi: 3/205:9 retroperitoneal neoplasms: 2/129-32 rheumatic fever -drug therapy: 3/241-4 quality control: 3/251-4 sialography -methods: 4/305-7 sinus thrombosis: 1 /21-5 Slovenia: 3/259-60 spine abnormalities: 3/193-6 stomach neoplasms: 4/311-4 subarachnoid hemorrhage: 4/301-3 subtraction technic: 2/119-21 surgical flaps: 3/219.24 survival: 3/229-34 -survival analysis: 4/345-9 technetium: 1/47-50; 4/325-9, 4/335-8 -technetium -diagnostic use: 1/43-6 thyroid function tests: 1 /39-42, 1 /43-6 thyroid hormones: 1 /39-42 thyroid neoplasms: 4/335-8 thyrotropin: 4/319-23 thyroxine: 2/133-5 tomography: 1/21-5, 1/27-34;4/311-4 -tomography X-ray computed: 1/21-5, 1/27-34 !race elements: 2/163-5 tracheobronchomegaly: 3/197-200 transluminal: 3/185-92 triiodothyronine: 2/133-5 trypsin inhibitors: 3/225-8 tumor markers: 3/225-8 tumor models: 4/351-2 ultrasonic diagnosis: 1 /69-70; 2/125-8, 2/129-32 ultrasonic therapy: 3/201-4 ultrasonography: 4/315-7 uniformity: 3/251-4 vagotomy: 4/267-96 vena cava inferior obstruction: 1 /5-9 vertebral artery -radiography: 2/97-101 water pollutants: 2/163-5 X-ray computed: 1/21-5, 1/27-34; 4/311-4 X-ry film: 3/245-9 REVIEWERS IN 1991 Benulic T, Ljubljana -Bilic A, Zagreb-Brencic E, Ljubljana-Budihna N, Ljubljana -Burger J, Ljubljana -Cvetnic V, Zagreb -Debevec M, Ljubljana -Demšar F, Ljubljana -Drinovec J, Ljubljana -Fettich J, Ljubljana -Fidler V, Ljubljana -Grivceva-Janoševic N, Skopje -Guna F, Ljubljana -Jakša 1, Ljubljana -Jamar -Škrbec B, Ljubljana -Jancar B, Ljubljana -Jereb B, Ljubljana -Klancar J, Ljubljana -Kovac V, Ljubljana -Kovacevic D, Zagreb -Kregar T, Ljubljana -Kurbus-Verk J, Ljubljana -Ledic S, Beograd -Lešnicar H, Ljubljana -Lišanin B, Beograd -Lovasic 1, Rijeka -Malenica B, Zagreb -Maricic 2, Zagreb -Maškovic J, Split -Miklavcic L, Valdoltra -Milcinski M, Ljubljana -Miric S, Saraievo -Novak O, Zagreb -Osmak M, Zagreb -Pichler E, Zagreb -Porenta M, Ljubljana -Serša G, Ljubljana -Simunic S, Zagreb -Škrk J, Ljubljana -Štrukelj M, Ljubljana -šurlan M, Ljubljana -Šuštaršic J, Ljubljana -Us J, Ljubljana -Vidakovic Z, Zagreb -Zupancic 2, Ljubljana Editors greatly appreciate the work of the reviewers which significantly contributed to the improved quality of our journal. INTERTRADE PRAVA POT DO VAŠIH REŠITEV I N TE RT RAD E • ITS S Y S T E M S Podjetje za proizvodnjo, informatiko in zastopanje IBM d.d. I:-:..1 0PERATIONS a ' CURRENT PERSPECTIVES: FUTURE HORIZONS A MAJOR INTERNA TIONAL CANCER CONFERENCE AND EXHIBITION ORGANISED BY THE ROYAL M.ARSDEN HOSPITAL IN ASSOCIATION WITH BRITISHJOURNAL OF HOSPITAL MEDICINE KENSINGTON NEW TOWN HALL, HORTON STREET, LONDON W8 M.ARCH 2, 3 AND 4 1992 • Visoko ucinkovit selektivni virostatik v obliki injekcij za infuzijo, mazila za oci in kreme VI RQLEX® (aciklovir) za zdravljenje in preprecevanje infekcij, ki jih povzrocajo virusi herpes simplex tipa 1 in tipa 2 ter varicella zoster • visoko selektivno deluje na viruse • hitro zaustavi razmnoževanje virusov • hitro odpravi simptome infekcije • bolniki ga dobro prenašajo VIROLEX® -injekcije za infuzijo za zdravljenje infekcij s herpesom simplexom pri bolnikih z oslabljeno imunostjo hudih oblik primarnega genitalnega herpesa simplexa -primarnih in rekurentnih infekcij z varicello zoster pri osebah z normalno in oslabljeno imunostjo -herpes simplex encefalitisa (fokalnega in difuznega) -za preporecevanje infekcij s herpesom simplexom pri bolnikih z zelo oslabljenim imunskim sistemom (transplantacije, zdravljenje s citostatiki) VIROLEX® -mazilo za oci za zdravljenje -keratitisa, ki ga povzroca herpes simplex VIROLEX® -krema za zdravljenje -infekcij s herpesom simplex na koži in sluznicah Podrobnejše informacije in literaturo dobite pri proizvajalcu. . KRKA, tovarna zdravil, n. sol. o., Novo mesto KRKA European School of Haematology The European School of Haematology (ESH) is a postgraduate institution tor medica:I specialists and researchers who are interested in updating their knowledge through close scientific contact with internationally respected experts in the fields of haematology, immunology, oncology, genetics, molecular biology, etc. To register, an applicant should send: • a curriculum vitae • a letter, vritten in the language of the cour.se, explaining why the applicant wishes to attend • a list of his/her recent publications • an identity photograph ESH Classical Study Sessions is held in English Methodology of Clinical Trials 24th -26th February, 1992 Venue: Chateau de Maffliers, France Chairperson: C. 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Number the references in the order in which they appear in the text and quote their corresponding numbers in the text. The authors names are followed by the title of the article and the title of the journal abbreviated according to the style of the lndex Medicus. Following are some examples of references from articles, books and book chapters. 1. Deni RG, Cole P. In vitro maturation of mono­cytes in squamous carcinoma of the lung. Br J Cancer 1981; 43:486-95. 2. Chapman S, Nakielny R. A guide to radiologi­cal procedures. London: Bailliere Tindall, 1986. 3. Evans R, Alexander P. Mechanisms of extra­cellular kiling of nucleated mammalian celis by macrophages. In: Nelson DS ed. lmmunobiology of macrophage. New York: Academic Press, 1976; 45-74. Author's address should be written following the References. The publication of the journal is subsidized by the Ministry of Science and Technology of the Republic of Slovenia Contributions of lnstitutions: -Institut za radiologiju i onkologiju, Beograd -Institut za radiologiju i onkologiju UMC-a Sarajevo -Inštitut za diagnosticno in intervencijsko radiologijo, UKC Ljubljana -KB »Dr Mladen Stojanovi<':«, Zagreb -Klinika za nuklearno medicino, UKC Ljubljana -Medicinski centar »Zajecar«, Zajecar -Onkološki inštitut, Ljubljana -Zavod za onkološku zaštitu, Kladovo Donators and Advertisers: -ANGIOMED, Karlsruhe, Germany -BA VER PHARMA, Ljubljana -BYK GULDEN, Konstanz, Germany, Representative Office, Beograd -CIS BIO lnternational, Paris, Representative Otlice Ferimport, Zagreb -FOTOKEMIKA, Zagreb -GENERAL ELECTRIC, Representative Office, Zagreb -INTERTRADE ITS, Ljubljana -KODAK, Representative Otlice MEDITRADE, Austria -KRKA, Novo Mesto -LEK, Ljubljana -NYCOMED A/S Oslo, Norway, Representative Otlice Schaffhausen, Switzerland, -PHILIPS, Representative Office AVTOTEHNA, Ljubljana -RO INSTITUT ZA NUKLEARNE NAUKE »BORIS KIDRIC«, Vinca -SALUS, Ljubljana -SANOLABOR, Ljubljana -SIEMENS, Erlangen, Germany, Representative Office BANEX, Zagreb -SIRION, Gorizia, ltaly -SKB Banka, Ljubljana -SLOVIN IBP, Ljubljana -TOSAMA, Domžale -ZAVAROVALNA SKUPNOST IMOVINE IN OSEB »CROATIA«, Zagreb, Department Nova Gorica -»ZORKA« Šabac -FARMACIJA, MEDICINSKI SEKTOR, Novi Beograd e (\. avtotehna d.d. 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