ADIOLOGY 11111 NCOLOGY June 2001 Vol. 35 No. 2 Ljubljana ISSN 1318-2099 Ni pomembno zgolj preživetje Lilly Onkologija Eli Li lly (Suisse) S. A .. Podružnica v Ljubljani WTC. Dunajska 156. 1113 Ljubljana Telefon, (01) 5688 280. faks, (01) 5691 705 www.lilly.com Dodatne informacije o zdravilu so na voljo v strokovnih publikacijah, ki jih dobite na našem naslovu. ADIOLOGY ANO NCOLOGY Editorial office Radiologij and Oncology June 2001 Institute of Oncology Vol. 35 No. 2 Zaloška 2 Pages 83-159 SI-1000 Ljubljana ISSN 1318-2099 Slovenia UDC 616-006 Phone: +386 1 4320 068 CODEN: RONCEM Phone/Fax: +386 1 4337 410 E-mail: gsersa@onko-i.si Aims and scope Radiologij and Oncologij is a journal devoted to publication of original contributions in diagnostic and interventional radiologij, computerized tonwgraphy, ultrasound, magnetic resonance, nuclear medicine, radiotherapy, clinical and experimental oncologi;, radiobiology, radiophysics and radiation protection. Editor-in-Chief Editor-in-Chief Emeritus Gregor Serša Tomaž Benulic Ljubljana, Slovenia Ljubljana, Slovenia Executive Editor Editor Viljem Kovac Uroš Smrdel Ljubljana, Slovenia Ljubljana, Slovenia Editorial board Marija Auersperg Be1a Fornet MajaOsmak Ljubljana, Slovenia Budapest, Hungary Zagreb, Croatia Nada Bešenski Tullio Giraldi Branko Palcic Zagreb, Croatia Trieste, Italy Vancouver, Canada Karl H. Bohuslavizki Andrija Hebrang JuricaPapa Hamburg, Germany Zagreb, Croatia Zagreb, Croatia Haris Boko Laszl6 Horvath Dušan Pavcnik Zagreb, Croatia Pecs, Hungary Portland, USA Nataša V. Budihna Berta Jereb Stojan Plesnicar Ljubljana, Slovenia Ljubljana, Slovenia Ljubljana, Slovenia Marjan Budihna Vladimir Jevtic Ervin B. Podgoršak Ljubljana, Slovenia Ljubljana, Slovenia Montreal, Canada Malte Clausen H. Dieter Kogelnik Jan C. Roos Hamburg, Germany Salzburg, Austria Amsterdam, Netherlands Christoph Clemm Jurij Lindtner Slavko Šimunic Munchen, Gennany Ljubljana, Slovenia Zagreb, Croatia Mario Corsi Ivan Lovasic Lojze Šmid Udine, Italy Rijeka, Croatia Ljubljm.a,Slovenia Christian Dittrich Marijan Lovrencic Borut Stabuc Vienna, Austria Zagreb, Croatia Ljubljana, Slovenia Ivan Drinkovic Luka Mi/as Andrea Veronesi Zagreb, Croatia Houston, USA l;viano, Italy Gillian Duchesne Metka Milcinski Ziva Zupancic Melbourne, Australia Ljubljana, Slovenia Ljubljana, Slovenia Publisher Association of Radiology and Oncologi; Affiliated with Slovenian Medica/ Association -Slovenian Association of Radiologi;, Nuclear Medicine Society, Slovenian Society far Radiotherapy and Oncologi;, and Slovenian Cancer SociehJ Croatian Medica/ Association -Croatian Society of Radiologij Societas Radiologorum Hungarorum Friuli-Venezia Giulia regional groups of S.I.R.M. (Italian Society of Medica/ Radiologi;) Copyright © Radiologi; and Oncologif Ali rights reserved. Reader for English Mojca Cakš Key words Eva Klemencic Secretaries Milica Harisch Mira Klemencic Design Monika Fink-Serša Printed by Imprint d.o.o., Ljubljana, Slovenia Published quarterly in 700 copies Bank account number 02010-0090006751 Foreign currency account number 010-7100-900067 /4 NLB d.d., Podružnica Ljubljana Center, Ljubljana S. W.I.F. T. Code L]BASI2X Subscription fee far institutions $ 100 (16000 SIT), individuals $ 50 (5000 SIT) The publication of this journal is subsidized by the Ministry of Science and Technologi; of the Republic of Slovenia. Indexed and abstracted by: BIOMEDICINA SLOVENICA CHEMICAL ABSTRACTS EMBASE / Excerpta Medica Sci Base This journal is printed on acid-free paper Radiology and Oncology is available on the internet at: http://www.onko-i.si/radiolog/rno.html COLOGY Ljubljana, Slovenia ISSN 1318-2099 June 2001 UDC 616-006 Vol. 35 No. 2 CODEN: RONCEM CONTENTS SONOGRAPHY Color duplex-Doppler ultrasonography of lower extremities veins -types of findings Brkijacic B, Šebecic B, Grga A, Patrlj L, Hebrang A 83 Sigmoid diverticulitis: A case report Niyyati M, Varga G, M6r6 Z 89 NUCLEAR MEDICINE Conventional staging and 18F-FDG-PET staging of malignant melanoma Jenicke L, Klutmann S, Bohuslavizki KH, Neuber K, Altenhoff J, Wedler J, Buchert R, Nebeling B, Clausen M COMPUTERIZED TOMOGRAPHY Comparison of CT analyses of primary renal cell carcinoma and of metastatic neoplasms of the kidney Ingrid Prkacin I, Naumovski-Mihalic S, Dabo N, Palcic I, Vujanic S, Babic Z ONCOLOGY Opportunities for up to date treatment of the colorectal cancer Yovtchev Y, Nikolov S Radical irradiation of the prostate. Combination of percutaneous irradiation and irradiation with LDR Ir-192 implants Kragelj B, Guna F, Burger J 117 Dividing patients with brain metastases into classes derived from the RTOG recursive partitioning analysis (RP A) with emphasis on prognostic poorer patient groups Willfurth P, Mayer R, Stranzl H, Prettenhofer U, Genserc B, Hackl Arnulf B 127 Predictors of recurrence in stage I invasive breast carcinoma Baitchev G, Gortchev G, Ve/kova A, Deliisky T 133 MRI macromolecular contrast agents as indicators of changed tumor blood flow Ivanuša T, Beravs K, Cemažar M, Jevtic V, Demšar F, Serša G 139 SLOVENIAN ABSTRACTS 149 NOTICES 157 Color duplex-Doppler ultrasonography of lower extremities veins - types of findings Boris Brklja‰i“1, Boěidar áebe‰i“2, Ante Grga2, Leonardo Patrlj2, Andrija Hebrang1 1Department of Radiology and 2Department of Surgery, University Hospital ŇMerkurÓ, Zagreb, Croatia Background. The types of ultrasonographic findings observed in patients referred for color duplex Doppler ultrasonography (CDD-US) of veins of lower extremities are presented in this paper. Patients and methods. During 27 months, 934 patients were examined. Among these, 663 were women (71 %) and 271 men (29 %), with the age range 19-86 (mean 58.4) years. Color Doppler scanners Acuson 128 XP 10, ATL HDI 5000 and Siemens Sonoline Elegra were used, with the transducers in the frequency range from 2.5-12 MHz. The types of findings were classified as: (a) deep venous thrombosis (DVT), (b) pathology related to veins without DVT, (c) pathology of adjacent structures, (d) normal findings. Results. DVT was observed in 210 patients (22.5 %) - acute or chronic in 129 patients, and 81 patients were examined in the follow-up of the DVT treatment. Postthrombotic syndrome, varicose veins, superficial thrombophlebitis and popliteal venous aneurysms were seen in 415 patients (44.4 %). The pathology unre­lated to veins was observed in 117 patients (12.5 %). Muscular hematomas and popliteal cysts were most common in this group, but very rare pathology was noted, as well. In 192 patients (20.6 %) CDD-US was normal. Conclusions. In patients referred for CDD-US examination of lower extremities veins, a high number of findings unrelated to veins, in addition to well-known findings of various venous pathologies, can be ob­served on CDD-US. The lesions that clinically mimic DVT should be recognized with US in order to avoid erroneous medical treatment. Key words: peripheral vascular diseases - ultrasonography, veins; ultrasonography, Doppler, duplex Correspondence to: Assist. Prof.Boris Brklja‰i“, MD, PhD, Department of Radiology, University HospitalŇMerkurÓ; Zaj‰eva 19, HR-10000 Zagreb, Croatia. Received 29 December 2000 Phone: +385 1 2431 421; Fax: +385 1 2431 397; E-mail: Accepted 29 January 2001 boris.brkljacic@zg.tel.hr Introduction In the last decade, ultrasonography (US) has become a primary and routine imaging method for the diagnosis of venous pathology of lower extremities.1 It is most important and the most commonly used in diagnosing deep venous thrombosis (DVT).1,2 Color du­plex-Doppler ultrasonography (CDD US) has very high accuracy in the detection DVT in the illiac region and in the lower extremities and has almost completely replaced contrast venography in diagnostic algorithm of DVT.1-3 The advantages of US over venography were well documented in several studies during the last decade.4-6 CDD US is also routinely used for preoperative visualization of superfi­cial veins, diagnosis and grading of saphe­nofemoral and saphenopopliteal insufficien­cy; it enables visualization of changes in postthrombotic syndrome, and it is useful for presurgical mapping of superficial veins used for bypasses.1-3,7 The purpose of this article is to present the types of findings observed in patients re­ferred for CDD-US examination of lower ex­tremities veins. Patients and methods Between October 20, 1997 and March 31, 2000, 934 patients were referred for CDD-US of lower extremities veins. Among these pa­tients, 663 were women (71 %), and 271 men (29 %). The age range was 19-86 (mean 58.4 years). The two most common reasons for re­ferral of patients were to rule out DVT in clin­ically suspected cases, or to evaluate deep, su­perficial and perforant veins prior to the surgery of superficial veins. Patients were al­so referred for CDD-US follow-up of antico­agulant treatment of the DVT. The most com­mon clinical findings in the patients with suspected DVT were the following: unilateral swelling of the leg, direct trauma of the leg, postoperative state, postthrombotic syn­drome with suspected rethrombosis, erysi­pelas Klippel-Trennaunay syndrome, heman­gioma. CDD-US was performed using state-of-the-art color Doppler scanners Acuson 128 XP 10, ATL-HDI 5000, and Siemens Sonoline Elegra, with the variety of transducers in the fre­quency range of 2.5-12 MHz. Mostly, trans­ducers in the frequency range from 7,5 to 10 MHz were used. Routine examination consisted of the com­pression of the deep veins with the transduc­er to evaluate venous compressibility, and to rule out DVT. Illiac veins, common femoral veins (CFV), superficial femoral veins (SFV), deep femoral veins, popliteal veins, and all three groups of crural deep veins were exam­ined. Color duplex-Doppler evaluation was always performed. Normal spectra were ob­tained and tests of distal compression and flow augmentation were performed on the level of CFV, SFV and popliteal veins. Moreover, the superficial veins were exam­ined also for saphenofemoral and saphenopopliteal insufficiency and for the presence of varices and superficial throm­bophlebitis. The soft tissue of lower extremi­ties was evaluated for the presence of edema, hematoma, or other pathology. Contrast venography was not performed in these patients. The medical treatment of DVT was introduced on the basis of CDD-US findings, and was also used in follow-up. The types of ultrasonographic findings were classified as: (a) deep venous thrombo­sis (DVT), (b) pathology related to the veins without DVT, (c) pathology of adjacent struc­tures, (d) normal findings. Results The types of ultrasonographic findings cla­ssified into four groups are presented in Table 1. Table 1. Types of ultrasonographic findings in all ex­amined patients Deep venous thrombosis 210 22.5 % Venous pathology without DVT 415 44.4 % Pathology of adjacent structures 117 12.5 % Normal findings 192 20.6 % Total number of findings 934 100.0 % Among 934 examined patients, DVT was found in 210 (22.5 %). Acute complete DVT of the leg was found in 97 patients, and acute isolated DVT in 26 patients (crural DVT in 17, CFV DVT in one, popliteal vein DVT in four, illiac vein DVT in four patients). Chronic DVT was found in six patients. Eighty-one patients were referred for the follow-up of DVT during the medical treatment; partial recanalization of DVT was found in 45 patients, and com­plete recanalization was found in 36 patients. Types of findings in this group are presented in Table 2. Table 2. Findings in patients with deep venous throm­bosis (DVT) Acute complete DVT 97 Acute isolated DVT 26 Chronic DVT 6 Partial recanalization 45 Complete recanalization 36 Total number of findings 210 Of 934 examined patients, 415 patients (44.4 %), who did not have acute or chronic DVT, were diagnosed with pathology related to veins. In 143 of these patients, the post-thrombotic syndrome without signs of DVT was observed, with edema, swelling, insuffi­cient perforate veins and varicose veins. Patients with crural ulcerations were includ­ed in this group. In 245 patients, we detected varicose veins, but no significant oedema or ulceration. Twenty-five patients had superfi­cial thrombophlebitis. Popliteal venous ane­urysm was observed in one male patient and the aneurysm of the gastrocnemic vein (part of the deep venous system) was observed in one female patient. Types of findings in this group are presented in Table 3. Table 3. Findings in patients with pathology related to veins, who did not have acute or chronic DVT Postthrombotic syndrome 143 Varicose veins 245 Superficial thrombophlebitis 25 Venous aneurysms 2 Total number of findings 415 The pathology unrelated to veins was ob­served in as many as 117 patients (12,5 % of all examined patients). In 27 patients, popliteal cyst was observed; ruptured cyst was seen in 11 cases, inflamed cyst in 2, and hemorrhagic cyst in two. In 34 patients, hematoma was observed in the musculature of lower extremities; the hematoma in the gastrocnemius muscle was seen in 24 pa­tients, in the quadriceps muscle of the thigh in 5 patients, in the soleus muscle in three pa­tients, and two hematomas were adjacent to ruptured Achilles tendons. Iliopsoas bursitis was observed in 10 patients with the enlarged bursa between the trochanter minor, com­mon femoral artery and common femoral vein. Pronounced inguinal lymphadenopathy with swelling of the leg was observed in eight patients with normally patent deep veins. Diffuse phlegmonous inflammation of crural soft tissue was seen in three patients. Six pa­tients had swelling with the clinical signs of erysipelas. Five patients had Klippel-Trennaunay syndrome, though with no evi­dence of venous thrombosis or A-V fistulas. Two patients had cavernous hemangiomas, one adjacent to the knee, and the other in the femoral region. In one patient with acute myeloic leukaemia, multiple abscesses in muscles of both legs were seen. One patient had a large sarcoma of the gastrocnemius and soleus muscles, misdiagnosed clinically as DVT. One patient had iatrogenic pseudoa­neurysm (PSAN) of the peroneal artery; it oc­curred after the orthopaedic surgery (patellar ventralization) with traumatic injury of the peroneal artery with a screw during the sur­gery. One patient had partially thrombosed aneurysm of the popliteal artery. In one pa­tient with Von RecklingshausenŐs disease, multiple nodules were found in the soft tissue of lower extremities. In a small group of patients without DVT, the anticoagulant therapy was erroneously in­troduced prior to the CDD-US examination, based only on clinical symptoms of leg swelling. The patients in whom DVT was misdiagnosed and mistreated with anticoagu­lant therapy had several underlying diseases: three patients had hematomas in the gastroc­nemic muscle, and one in quadriceps muscle of the thigh; two patients had inflamed popliteal cysts; two patients had diffuse phlegmonous inflammation of the crural soft tissue; one patient had a large sarcoma of the gastrocnemius and soleus muscles. In one pa­tient with iatrogenic PSAN of the peroneal ar­tery, the anticoagulant medications were be­ing administered for three months; actually, a large hematoma and swelling compromised arterial perfusion of the limb. The immuno­compromized patient with acute myeloic leukaemia, who had multiple abscesses in the soft tissue of both legs, had a typical clinical manifestation of DVT. Luckily, unnecessary anticoagualant therapy was avoided with the CDD-US examination. In addition to that, in seventeen patients, isolated edema of the superficial tissues was observed that could not be related to venous pathology. In seven of these patients, car­diac pulsatility was transmitted to the pe­ripheral veins, with bilateral swelling, indi­cating that the edema was of cardiogenic origin. Table 4. Findings in patients with pathology of adja­cent structures unrelated to veins muscular hematomas 34 popliteal cysts 27 isolated edema of soft tissues 17 illiopsoas bursitis 10 marked inguinal lymphadenopathy 8 erysipelas 6 Klippel-TrennaunayŐs syndrome 5 diffuse inflammation of the soft tissue 3 cavernous hemangiomas 2 very rare pathologies 5 Total number of findings 117 In 192 patients (20.6 %) CDD-US of lower extremities veins was completely normal, and no pathology was found in the soft tissue as well. Discussion In our practice, most common referrals for ve­nous CDD-US are to rule out DVT, to follow­up the effects of anticoagulant therapy in es­tablished DVT, and to evaluate venous system prior to surgery of superficial veins. Groups of patients with the high risk of de­veloping DVT are the patients after a major trauma, bone fractures, surgery, especially or­thopedic surgery (e.g. hip replacement), pa­tients with coagulopathies, pregnant and puerperal women, and all patients who are bed-ridden for longer period of time.1-3,7,8 The risk increases with obesity and previous thromboembolic episodes. The risk of DVT is higher with aging; in old people, after long surgery, the risk of DVT is 40-70 %, whereas pulmonary embolia occurs in 1-5 % of pa­tients.1,2,8 The accuracy of CDD-US in the di­agnosis of DVT above the knee is 99 %, and below the knee 81 %.1-3,9-11 It is well-known that the clinical diagnosis of DVT is not very accurate. Classical clinical symptoms, like positive HomanŐs sign, local swelling and ten-derness, are not reliable, and DVT is often overcalled, based on these findings. The same clinical symptoms can be caused by a variety of other conditions: abscesses, muscle hema­toma, ruptured popliteal cyst, etc. Also, DVT is often clinically silent, with absent local symptoms.1-7,11 The results of the present study show that various pathology was found in almost 80 % of patients referred for CDD-US examination of lower extremities veins. The accuracy of CDD-US in diagnosis and follow-up of the therapy of DVT is well established, as well as in the diagnosis of the postthrombotic syn­drome, varicose veins and superficial throm­bophlebitis.1-11 Contrast phlebography can be safely omitted in the diagnosis of these cases. In our study, US findings were normal only in 20.6 % of the referred patients. These data in­dicate the high clinical yield of US examina­tion of lower-extremity veins. However, the referral of patients for US examination is not the responsibility of radiologist, but of the general practitioner and/or various clinicians (surgeons, specialists in internal medicine, oncologists, etc.). A well-established capacity of US to visu­alize DVT, changes of postthrombotic syn­drome, and changes of superficial veins was confirmed in the present study. Nevertheless, the reported results indicate that unexpected pathology, or pathology unrelated to veins was found in as many as 12.5 % of patients. This, we believe, may have important clinical consequences. Popliteal cysts, especially in cases of rupture, hemorrhage or inflamma­tion, are known to be the causes of the leg swelling. The same applies to iliopsoas bursi­tis, traumatic muscular hematomas, and in­guinal lymphadenopathy.1-3 Such changes cannot be seen with contrast venography, while ultrasonography enables their visuali­zation with very high accuracy. We believe that, for an effective manage­ment of patients, it is important to emphasize relatively rare, and unexpected changes as observed by CDD-US in our patients. This refers especially to those patients who were misdiagnosed to have DVT on the basis of clinical symptoms, and who were conse­quently mistreated with anticoagulant thera­py. These patients were not initially referred to CDD-US examination, and received thera­py without US confirmation of the diagnosis of DVT. Among these patients, we found muscular hematomas, inflamed popliteal cysts, diffuse phlegmonous inflammation of the soft tissue, rare tumors, and even more rare iatrogenic pseudoanerysm of the per-oneal artery. It should also be kept in mind that abscesses in the soft tissue can be seen in immunocompromized patients. Ultrasonography is nowadays the main di­agnostic modality in cases of venous patholo­gy and ultrasonologists should be familiar with all the presented types of findings. There is no doubt that the erroneous diagno­sis of DVT has serious clinical implications, as unnecessary administration of anticoagu­lant medications can result in life-threatening complications. All physicians included in di­agnosis and treatment of the diseases related to the peripheral veins have to be aware of the high diagnostic accuracy of US in visuali­zation of both, venous pathology and the pathology of adjacent structures that is unre­lated to veins, but that can mimic venous dis­eases. Therefore, we believe that the antico­agulant therapy for DVT should not be introduced prior to US examination of lower extremities veins, even if all typical clinical symptoms of DVT are present. References 1. Brklja‰i“ B. Doppler of peripheral veins. In: Brklja‰i“ B, editor. Doppler of blood vessels. [Croatian]. Zagreb: Medicinska naklada; 2000. p. 57-77. 2. Gooding GAW. Ultrasound of deep venous throm­bosis. In: Goldberg BB, Pettersson H, editors. Ultrasonography. Oslo: NICER; 1996. p. 583-611. 3. Cronan JJ. Controversies in venous ultrasound. Semin Ultrasound CT MR 1997; 18: 33-8. 4. Rosner NH, Doris PE. Diagnosis of femoro­popliteal venous thrombosis: comparison of du­plex sonography and plethysmography. Am J Roentgenol 1988; 150: 623-7. 5. Lewis BD, James EM, Welch TJ, Joyce JW, Hallett JW, Weaver AL. Diagnosis of acute deep venous thrombosis of the lower extremities: prospective evaluation of color Doppler flow imaging versus venography. Radiology 1994; 192: 651-55. 6. Rose SC, Zwiebel WJ, Nelson BD, Priest DL, Knighton RA, Brown JW, et al. Symptomatic low­er extremity deep venous thrombosis: accuracy, limitations, and role of color duplex flow imaging in diagnosis. Radiology 1990; 175: 639-44. 7. Jaeger K, Frauchiger B, Eichlisberger R. Vascular ultrasound In: Tooke JE, Lowe GDO, editors. A textbook of vascular medicine. London: Arnold; 1996. 8. Weinmann EE, Salzman EW. Deep-vein thrombo­sis. N Engl J Med 1994; 331: 1630-41. 9. Rose SC, Zwiebel WJ, Miller FJ. Distribution of acute lower extremity deep venous thrombosis in symptomatic and asymptomatic patients: Imaging implications. J Ultrasound Med 1994; 13: 243-50. 10. van Bemmelen PS, Bedford G, Strandness DE. Visualization of calf veins by color flow imaging. Ultrasound Med Biol 1990; 16: 15-7. 11. Effeney DJ, Friedman MB, Gooding GAW. Iliofemoral venous thrombosis: real-time ultra­sound in the diagnosis of iliofemoral venous thrombosis: real-time ultrasound diagnosis, nor­mal criteria and clinical application. Radiology 1984; 150: 787-92. Sigmoid diverticulitis: A case report Mahtab Niyyati, Gyula Varga, Zsuzsanna MŠrŠ Department of Radiology, P”cs Medical University, P”cs, Hungary Background. Diverticulitis could be a challenging diagnosis in a patient presenting with acute abdomen. Case report. Our case presents a patient with acute abdomen in whom an abdominal ultrasound examina­tion showed a mass with internal reflexes continued to the sigmoid colon and a diagnosis of diverticulitis was suspected. Later abdominal helical CT proved it to be diverticulitis. Conclusions. The case emphasises the importance of ultrasound as a first line imaging modality for detect­ing bowel pathology. Key words: sigmoid diseases; diverticulitis, diverticulosis, colonic; acute-ultrasonography, abdominal ul­trasound Case report A 56 year old woman who complained of fever, left lower quadrant pain which wors­ened, frequent urination without dysuria, on­set of mild non bloody diarrhoea. On physical examination a mass was palpable under the umbilicus, which was mobile and very ten­der. WBC count was elevated (18000). Gynaecologic examination: Just beside the uterus a very painful mass was palpable. Douglas pouch was empty of fluid. Uterus, ovaries were intact. So a gynaecological cause was ruled out. Received 18 December 2000 Accepted 27 December 2000 Correspondence to: Mahtab Niyyati M.D., Department of Radiology, P”cs Medical University, Ifjus/g utca 13, P”cs, Hungary. Phone: +36 70213 7621; Fax: +36 7233 0335; Email: mahtabn@ hotmail.com Abdominal ultrasound (US) examination: beside the uterus, above the bladder a big ho-mogenous, hypoechogenic mass was seen. On suspicion of an abscess formation, an US-guided fine needle aspiration was attempted, but no fluid was aspirated. Next day on admission fillowing control ultrasound examination the mass was seen as a continuation of the sigmoid colon with in­ternal reflex representing the lumen and sym­metrically thickened bowel wall (Figure 1). A diagnosis of sigmoid diverticulitis was highly suspected. Abdominal and pelvic CT scan: thick walled sigmoid colon with diverticula outpou­ching from its surface, surrounded by an area of paracolic inflammation (Figure 2). Diagno­sis: Sigmoid diverticulitis, diverticulosis. Colonoscopy: The mucosa of the sigmoid colon was oedematous and rigid. On the oedematous mucosa an almost closed diver-ticular opening was seen, in addition to two Figure 1. Abdominal ultrasound showing a mass in left lower quadrant in the continuation of sigmoid colon with central reflex representing bowel lumen and symmetrically thickened bowel wall. other diverticulas. Diagnosis: Sigmoid diveri­culitis, diverticulosis. The patient was treated with broad-spec­trum antibiotics (cefriakson) along with ap­propriate diet and fluids. The patient did not need any surgery or drainage. Ten days later a control abdominal ultrasound was negative and a double contrast barium enema study showed free bowel lumen with small filling surpluses representing diverticulosis (Figure 3). The patient was discharged. Introduction Diverticulitis is among the first line in the list of differential diagnosis of acute abdomen, most frequently presenting as left lower quadrant pain and tenderness, leukocytosis, fever. Ultrasound is nowadays becoming the cheapest and easiest way in the diagnosis of the cause of acute abdomen, especially in places where access to CT is limited. The purpose of our case report was to show the possible difficulties that can arise in the diagnosis of diverticulitis, and to show the use of ultrasound as a cheap and available method in reaching the diagnosis. Discussion The interesting point in this case is the mis­leading appearance of diverticulitis in the first ultrasound examination. The reasons could be: absence of the midline reflex repre­senting the bowel gas and inability to follow the mass to the intestine. Figure 2. Abdominal CT showing a thick walled sigmoid surrounded by an area of paracolic inflammation and out-pouchings representing diverticuli. The approach to diverticulitis starts from a plain abdominal x-ray, which is normally used for ruling in or out perforation, obstruc­tion. Traditionally barium enema examina­tion had been the mainstay in the evaluation of patients suspected of having acute diverti­culitis, but its sensitivity did not exceed 77 %­86 %. The signs could be localised extravasa­tion of contrast material, colonic fold thickening and distortion, localised mass ef­fect.1 Many believe that this procedure is con­traindicated in acute cases; if done, water-sol­uble contrast material should be employed.2 Ultrasound has gained a lot of popularity due to its high degree of accuracy; its wide­spread availability, relatively low cost, and no need for patient preparation and contrast agents. It can have a sensitivity of 84 %-100 % especially with graded compression tech­nique.1 The use of intravaginal ultrasound gives a higher sensitivity for evaluation of gut pathology and ruling out gynaecological caus­es of acute abdomen.3 CT has made a significant impact on the diagnosis of gastrointestinal disorders associ­ated with perienteric inflammatory exten­sion.4 CT is becoming the primary imaging modality for evaluation of patients with clini­cal symptoms of acute abdomen and a con­fusing clinical picture.1 According to a study, a very accurate method for ruling in or out acute diverticuli­tis is spiral CT after contrast material administered only through colon (99% accu-racy).5 Two sets of criteria should be used for a di­agnosis of diverticulitis to be established: 1. Mural changes: 1a- bowel wall thickening 1b- presence of diverticula Figure 3. Double contrast barium enema study showing a free lumen and diverticulosis. The examination was done after receiving treatment and regression of symptoms. 2. Extramural changes: 2a- paracolic fat inflammation 2b- paracolic abscess formation For a definite diagnosis of diverticulitis one from each group should be present. Several studies show that the sensitivity and specificity of ultrasound and CT in de­tecting the above mentioned signs is almost the same, except that CT is more sensitive for detecting the extramural changes and di­vertivula. A problem, which exists, is that none of these signs are specific for divertic­ulitis, but could also be seen in other tumoral, inflammatory, ischemic conditions and fur­ther research should be done for finding spe­cific signs. According to some authors, the Ňarrow-head signÓ in CT could be specific for diverti­culitis (contrast material or gas seen pointing towards the opening of a diverticulum). Another helpful sign, but not specific, is the increasing width of right anterior extrarenal space, which is seen in inflammatory and tu-moral conditions of the abdomen. There are other conditions mimicking acute divericulitis e.g. appendicitis, pelvic in­flammatory disease, ectopic pregnancy, oophoritis, renal colic, ischemic colitis, bowel obstruction, colon cancer.1 Cancer of the sig­moid colon appears as the main differential diagnosis6, so it is wise to rule out carcinoma after resolution of the acute event with the follow-up colonoscopy-barium enema study. Appearance of lymph nodes along with thick­ened bowel wall also speaks in favor of can­cer rather than of a chronic inflammatory process.8 Conclusions Ultrasound is the first line imaging modal­ity in ruling in or out acute diverticulitis or other similar conditions mimicking acute di­verticulitis clinically. In cases of critically ill patients presenting with an acute abdomen, CT should be con­sidered as the first line modality. Patients should be followed up by barium enema study for ruling out cancer after reso­lution of the acute event. References 1. Pradel JA, Adell JF, Taourel P, Djafari M, Monnin-Delhom E, Bruel JM. Acute colonic diverticulitis: prospective comparitive evaluation with ultra­sound and CT. Radiology 1997; 205: 503-12. 2. Gillessen A, Domschke W. Acute sigmoid diverti-culitis-current diagnosis. Chirurg 1995; 66: 1177­81. 3. Schiller VL, Schreiber L, Seaton C, Sarti DA. Transvaginal sonographic diagnosis of sigmoid di­verticulitis. Abdom Imaging 1995; 20: 253-5. 4. Birnbaum BA, Balthazar EJ. CT of appendicitis and diverticulitis. Radiol Clin North Am 1994; 32: 885­98. 5. Rao PM, Rhea JT, Novelline RA, Dobbins JM, Lawrason JN, Sacknoff R, et al. Helical CT with only colonic contrast material for diagnosing di­verticulitis: Prospective evaluation of 150 patients. Am J Roentgenol 1998; 170: 1445-9. 6. Chen JJ, Changchier CS, Kuo CH. Causes of in­creased width of right anterior extrarenal space seen in ultrasonographic examinations. Journal of Clinical Ultrasound 1995; 23: 287-92. 7. Moreaux J, Mombet J, Mal F. Diagnostic pitfalls of complicated colonic diverticulosis. Rev Prat 1995; 45: 990-3. 8. Chintapalli KN, Chopra S, Ghiatas AA, Esola CC, Fields SF, Dodd GD. Diverticulitis versus colon cancer: differentiation with helical CT findings. Radiology 1999; 210: 429-35. Conventional staging and 18F-FDG-PET staging of malignant melanoma Lars Jenicke1, Susanne Klutmann1, Karl H. Bohuslavizki1, Karsten Neuber2, J.rgen Altenhoff2, Juliane Wedler2, Ralph Buchert1, Bruno Nebeling1, Malte Clausen1 1Departments of 1Nuclear Medicine and 2Dermatology, University Hospital Eppendorf, Hamburg, Germany Background. Preliminary reports suggest that PET using 18F-FDG may be a valuable diagnostic tool in pa­tients with advanced malignant melanoma. Therefore, the aim of this study was to compare the findings of 18F-FDG-PET and those of conventional imaging including physical examination for both primary and fol­low-up staging of patients with malignant melanoma. Patients and methods. Thirty-five patients with histologically proven malignant melanoma underwent 61 PET examinations. After an intravenous injection of 370 MBq 18F-FDG, whole-body images were acquired on an ECAT EXACT 47 (921) with an axial field-of-view of 16.2 cm. Moreover, all patients underwent physical examination and conventional imaging, i.e. ultrasound, CT, and MRI within a two-week interval after 18F-FDG-PET. Based on the findings of both staging procedures, the patients were classified according to UICC. Results. In primary staging or follow-up, 5 out of 35 patients were classified as stage I by conventional stag­ing. Seven out of 35 patients were classified as stage II. The remaining 23 patients were initially classified as stage III. In the follow-up, two out of the latter 23 patients were upstaged to stage IV. However, none of these patients was classified as stage IV in primary staging by conventional diagnostic procedures. According to the results of 18F-FDG-PET, 9 out of 35 patients revealed neither evidence for distant metas­tases nor presence of lymph node metastases in primary staging (stage I/II). However, initially 21 out of 35 patients were suspected for lymph node metastases but no distant metastases (stage III). Moreover, 18F­FDG-PET suspected 5 patients, initially classified as stage IV, for distant metastases. However, in the fol­low-up, 18F-FDG-PET turned out to be false-positive for distant metastases in one out of the latter 5 patients; therefore, this patient was staged down to stage III. As compared to conventional diagnostic work-up, 18F-FDG-PET revealed the corresponding tumor stage in 17 out of 35 patients (49 %). However, 14 patients (40 %) were staged up by 18F-FDG-PET and 4 patients (11 %) were staged down by 18F-FDG-PET in primary staging or follow-up investigations. With respect to anatomical localization, the majority of false-negative PET lesions were lymph node metastases close to the skin area. Conclusions. Our results underline the added value of 18F-FDG-PET in staging of malignant melanoma. Since further treatment mainly depends on the clinical stage, 18F-FDG-PET might help to select the appro­priate treatment protocol for each individual patient. Key words: melanoma; neoplasms staging; tomography, emission-computed, 18F-FDG-PET; morphological imaging; treatment strategy Introduction Cutaneous malignant melanoma is one of the most common malignancies with a twofold to threefold increasing incidence over the last 40 years.1 The most important prognostic fac­tor is tumor staging at the time of diagnosis.2 According to the recommendations of the American Joint Commission on Cancer (AJCC), the clinical stage is divided into four groups. Clinical stages I and II are defined for primary malignant melanomas limited to the site of the origin without any evidence of a tu­mor spread elsewhere. In case of palpable lo­cal lymph node involvement or a disseminat­ed disease, patients are classified as clinical stage III and IV, respectively. At the time of the first presentation, nearly 80 % of all pa­tients are noted in clinical stage I or II with a mean 5-year survival rate of 85 %.2 However, one third of the latter patients will have clini­cally undetectable lymph node metastases which, if left untreated, will significantly worsen the survival rate.3,4 Thus, an accurate tumor staging is a prerequisite for selecting the adequate treatment protocol. Conventional imaging, i.e. computed to­mography, magnet resonance imaging, and ultrasound are valuable and well-established diagnostic tools in pretherapeutic staging.5-8 However, these imaging modalities allow an identification of morphologic changes only, whereas the tumor tissue in normal-sized lymph nodes cannot be detected by defini­tion.9 Moreover, the morphologically orien­tated imaging permits a screening of a pre-se­lected body area only. Since malignant Received 6 February 2001 Accepted 14 February 2001 Correspondence to: Karl H. Bohuslavizki, MD, PhD, Department of Nuclear Medicine, University Hospital Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. Phone: +49 40 42803 4047; Fax: +49 40 42803 6775; E-mail: bohu@uke.uni-hamburg.de melanomas are known for their aggressive lymphatic and hematogenic spread potency 3,7, one single non-invasive imaging modality with simultaneous imaging of the whole-body would significantly facilitates pretherapeutic management of these patients. Thus, a num­ber of radiotracers have been suggested for 1 this purpose, i.e. 67Ga-citrate , 123I-benza­mide, 123IŃaŃmethyltyrosine 9, and 99mTc-la-belled antimelanoma-antibodies.11 A great number of false-negative findings were re­ported for all of these radiotracers.9,12 In con­trast, initial experiences demonstrated the clinical potency of positron emission tomog­raphy (PET) using 18F-fluoro-2-deoxy-D-glu­cose (18F-FDG) for the detection of both local and systemic spread of metastatic malignant melanoma.1,13-22 Within its geometric resolu­tion of about 4-6 mm (FWHM), PET is able to detect tumor tissue independent of morpho­logical changes due to an increased rate of glycolysis in malignant transformed cells. Since the early detection of malignant melanoma metastases increases the patientsŐ survival rate, 18F-FDG-PET might be a valu­able diagnostic tool in detecting melanoma metastases.23,24 The aim of this study was to compare the findings of 18F-FDG-PET and those of con­ventional imaging including physical exa­mination for both, the primary and follow-up staging of patients with malignant me­lanoma. Patients and methods Patients Thirty-five patients (13 female, 22 male) aged from 31 to 81 years with histologically proven malignant melanoma were investigated. The primary tumors were located in the skin area of the head and neck region in 5 patients, of the upper extremities in 4, of the lower ex­tremities in 6, on the chest wall in 3, on the back in 15, and on the abdominal wall in 1 pa-tients. The anatomic site of the primary tu-Breslow scheme 26 are listed in Table 1. In mor was unknown in one patient. short, the following distribution was ob- Clark levels (CL)25 and classification of the served: CL I, no patient; CL II, 1 patient; CL thickness of the primary lesions according to III, 8 patients; CL IV, 18 patients; CL V, 1 pa- Table 1. Staging of all melanoma patients, according to the findings of conventional imaging and 18F-FDG-PET, re­spectively. Demographic data, Clark level (CL) and Breslow scheme (BS) are shown in detail as well as a compar­ison of both staging procedures, respectively. ­: up-staging by PET; Ż: down-staging by PET; =: staging unchanged, D Staging: staging changed by PET with respect to conventional staging, NA: data not available Suspicious depth Conventional staging PET-staging Patient CL BS Primary Follow-up Primary Follow-up D Staging M/74 IV 0.7 I III ­ M/64 NA 3.7 III III III III = M/41 III 0.4 III III I/II I/II Ż F/71 IV 3.3 II I/II = M/48 II 0.5 III III = F/61 IV >6 III III = F/66 IV/V 8.3 III III = M/81 IV >4 III III = M/74 IV 1.0 III III III III = M/71 NA >8 III III III IV Ż M/61 IV 1.2 III III = F/69 III 0.8 I I I/II IV ­ F/44 III 1.2 I I III III ­ M/56 IV 4.5 III I/II Ż M/59 IV 1.3 II II I/II I/II = M/49 IV 2.1 II IV ­ M/43 IV 1.9 III III = F/53 III 1.7 III III IV IV ­ M/63 NA NA II I/II = F/79 IV 1.6 III III, III III III, III = M/53 IV 3.0 III III I/II I/II Ż M/45 IV 3.5 III III III IV ­ M/62 IV 2.6 III III III III = M/58 IV 1.1 II II III IV ­ M/81 NA NA II I/II = F/55 III NA III III I/II I/II Ż F/46 IV 1.9 III III, III III III, III = F/66 II/III 0.6 I III ­ F/60 IV 1.4 III III, IV, IV IV III, IV, IV ­ F/47 III 1.0 I III ­ M/31 IV 2.1 III IV III IV = M/66 II/IV 1.9 II IV IV IV ­ M/43 III 1.6 III III, III III III, III = F/52 V 7.0 III IV ­ M/57 III 0.4 III III III IV ­ tient, and 1 patient in each of the following levels: CL II/III, CL III/IV, and CL IV/V. Five patients presented with thin lesions (0.75 mm or less), 21 intermediate lesions (0.76­ 3.99 mm), and 6 patients thick lesion (4 mm or more). Clark levels and Breslow scheme were not available in four and three patients, respectively, due to the localization of the pri­mary tumor and initial resection. For the primary staging (n = 35) or follow­up study (n = 26), all patients underwent con­ventional staging consisting of physical ex­amination as well as of morphological imaging, i.e. chest x-ray, CT scans of the chest, brain and abdomen or MRI. A total of 61 18F-FDG-PET examinations were per­formed on these patients. According to the criteria of the UICC 27, (Table 2), the patients were staged both conventionally and by the findings of 18F-FDG-PET, and both results were compared. All tumor-suspicious find­ings were evaluated by histopathology as a golden standard. PET scanning The patients fastened for at least 12 hours pri­or to PET-scanning in order to minimize blood insulin levels and glucose utilization of normal tissue.28 Whole-body emission im­ages were acquired without attenuation cor­rection 60 min after i.v. injection of 370 MBq 18F-FDG using an ECAT EXACT 47 (921) scanner (Siemens/CTI, Knoxville, TN, USA) with an axial field-of-view of 16.2 cm. Table 2. Staging of the cutaneous malignant melanoma according to the criteria of the UICC from 1997 Tumour stage T N M Stage I PT1, pT2 N0 M0 Stage II PT3 N0 M0 Stage III PT4 N0 M0 Any pT N1, N2 M0 Stage IV Any pT Any N M1 Patients were laid in the PET gantry feet first with both arms folded over the ab­domen. Images were acquired for 4 min per bed position covering the feet up to the mid­dle of the femurs. Then, the patients were repositioned in the gantry head first, and the second set of images was acquired from the brain down to the waist. Prior to the third ac­quisition set from the waist down to the low­er extremities, the patients were asked to empty the bladder in order to decrease urine activity. Emission data were reconstructed by filtered back projection using a Hanning filter with a cut-off frequency of 0.4 of the Nyquist frequency. PET images were printed on trans­parency film (Helios 810, Sterling) using a lin­ear gray scale with the highest activity dis­played in black. Images were displayed with an upper threshold of five times of the mean activity in the lung. Standardized documenta­tion included both 20 transversal and 20 coro­nal slices, and maximum-intensity-projec­tions (MIPs) in the anterior, left lateral, right-anterior-oblique, and left-anterior-obli­que view as published previously.29 Two independent nuclear medicine physi­cians, blinded to the results of conventional staging, interpreted PET images visually. Results Conventional staging The results of conventional diagnostic proce­dures are listed in detail in Table 1. According to the results of conventional imaging and clinical examination, 5 out of 35 patients were classified as stage I in primary staging or follow-up, and 7 out of 35 patients as stage II in primary staging. One out of these 7 pa­tients was initially classified as stage II but was then staged up to stage IV at the first fol­low-up. The remaining 23 patients were ini­tially classified as stage III. In the follow-up investigations, 13 out of these 23 patients re­mained stage III, whereas two patients were upstaged to stage IV. However, none of the patients was classified as stage IV in primary staging by conventional diagnostic proce­dures. 18F-FDG-PET staging Results of 18F-FDG-PET are listed in detail in Table 1 as well. According to the results of 18F-FDG-PET, nine out of 35 patients had nei­ther evidence of distant metastases nor pres­ence of lymph node metastases at primary staging. These patients were initially classi­fied as stage I to II since 18F-FDG-PET allows in principle no differentiation between pT1, pT2 or pT3. In further follow-up staging, this initial tumor stage was changed in one pa­tient to stage IV malignant melanoma. In pri­mary staging, 21 out of 35 patients were sus­pected for lymph node metastases, but not for distant metastases; therefore, these pa­tients were classified as stage III by 18F-FDG­PET. In the follow-up investigations, this ini­tial stage was changed in five patients due to distant metastases seen by 18F-FDG-PET. These patients were classified as stage IV. As far as primary staging is concerned, 18F-FDG­PET suspected five patients for distant metas­tases, classifying these patients as initial stage IV. However, in the follow-up, 18F-FDG­PET turned out to be false-positive for distant metastases in one out of the latter patients; therefore, this patient was staged down to stage III. Comparison of conventional diagnostic work-up and 18F-FDG-PET As compared to the conventional diagnostic work-up, 18F-FDG-PET revealed the corre­sponding tumor stage in 17 out of 35 patients (49 %), whereas 14 patients (40 %) were staged up by 18F-FDG-PET and 4 patients (11 %) were staged down by 18F-FDG-PET at primary stag­ing or follow-up investigations. Discussion Initial studies assessed the clinical utility of 18F-FDG-PET for the detection of metastatic malignant melanoma. Gritters and cowork­ers3 studied 12 patients with a total of 52 biopsy- or CT-diagnosed melanoma lesions. All patients underwent additional 18F-FDG­PET. Their initial data demonstrated the po­tential role of 18F-FDG-PET for the detection of metastatic malignant melanoma, especially in untreated extrathoracic lesions. Steinert and coworkers21 examined 33 patients with the primary diagnosis or known relapse of malignant melanoma. In their patients, 18F­FDG-PET showed a sensitivity of 92 % for the detection of malignant melanoma lesions. Moreover, the specificity was 77 % without further clinical information and 100 % with clinical information. Corresponding findings were demonstrated by Holder and cowork­ers16 who recommended 18F-FDG-PET as a primary strategy imaging modality in the staging of melanoma patients. In this study, a total of 35 patients with malignant melanoma underwent 61 18F-FDG­PET examinations. In nine of these patients, initial tumor staging revealed a stage I/II dis­ease with no evidence of lymph node metas­tases or distant metastatic spread. However, in four of these nine patients, morphological imaging and physical examination revealed lymph node metastases and, due to the find­ings of conventional imaging, these patients were classified as stage III. Thus, 18F-FDG­PET initially led to down-stage these patients. However, in the great majority of the pa­tients, a stage III malignant melanoma was detected both by conventional diagnostic pro­cedures and by 18F-FDG-PET. Thus, 23 and 21 patients were initially classified as stage III melanoma by conventional diagnostic proce­dures and by 18F-FDG-PET, respectively. However, a detailed comparison of primary staging by 18F-FDG-PET and by conventional imaging showed that only 13 out of 21 pa-tients, classified as stage III by 18F-FDG-PET, were staged equivalently also by convention­al imaging. Yet, in 8 of these patients, con­ventional imaging and physical examination were false-negative concerning the detection of lymph node metastases. In these 8 pa­tients, 18F-FDG-PET required an up staging. Moreover, 18F-FDG-PET was not able to de­tect the presence of lymph node metastases only in 4 of 23 patients initially classified as a stage III malignant melanoma by convention­al diagnostics. In six of these 23 patients, 18F­FDG-PET not only detected lymph node metastases, but was also suspicious of distant metastatic spread. These patients were there­fore classified by 18F-FDG-PET as stage IV. In all patients but one mentioned before, 18F­FDG-PET was true-positive concerning the presence of distant metastases at primary staging. Comparing the results of both staging methods, it is remarkable that none of the pa­tients was initially classified as stage IV by conventional staging at primary staging. In contrast, 18F-FDG-PET showed suspicious-suspicious tracer accumulations, which aroused suspicion of stage IV. The histologi­cal evaluation of the detected lesions con­firmed the stage IV in all these patients but one. Thus, concerning the detection of dis­tant metastases at primary staging, 18F-FDG­PET was true-positive in a total of 4 out of 35 patients. With regard to the findings of convention­al diagnostic work-up and those of 18F-FDG­PET, corresponding results were seen in about half of the patients investigated. In 11 % of all patients, conventional diagnostic work-up staged-up the patients comparably to 18F-FDG-PET. Surprisingly, in the patients in whom 18F­FDG-PET was not able to detect the presence of lymph node metastases, it is remarkable that most of these lesions were found in the inguinal area close to the skin. Thus, the skin might be problematic for the detection of ma­lignant melanoma metastases by 18F-FDG­PET. One potential cause of false-negative re­sults is the fact that 18F-FDG is excreted via the urine. Thus, suspicious lesions of the skin, predominantly on the lower extremities and in the inguinal area, might be interpreted as contaminations. Moreover, it is also known that the patients treated with interfer­on alpha and interleukin-2 exhibit cutaneous inflammatory infiltrations at the injection site24 which may be difficult to be differenti­ated from a metastastic spread. The limited impact of 18F-FDG-PET for the detection of metastases close to the skin might be ex­plained for physiological and technological reasons. First, suspicious lesions located within the regions of high physiological 18F­FDG uptake, i.e. the brain or the kidneys, might not be identified by 18F-FDG-PET imag­ing. Second, the detection of small lesions with diameters of less than 5 mm might be limited by geometrical resolution of 18F-FDG­PET. Moreover, PET-images in this study were reconstructed by filtered back-projec­tion. As a consequence, melanoma metas­tases in borderline areas, i.e. the skin, can hardly be differentiated from non-malignant tissue. This problem might be overcome by time-consuming iterative reconstruction algo­rithms. With these limitations in mind, whole-body 18F-FDG-PET is a suitable imag­ing modality in order to prove suspicious le­sions in malignant melanoma. However, for the exclusion of skin metastases, an accurate and careful physical examination by a derma­tologist is still indispensable in daily clinical patient management. Any diagnostic test should, in principle, not only be judged with respect to its statistic data, but rather in the light of its effect on a treatment strategy. The therapeutic approach in malignant melanoma mainly depends on the extent of the disease. In clinical stages I and II, the excision of the primary malignan­cy has always been the golden standard. In the last few years, elective lymphadenectomy was abandoned because its additional value in improving the patientsŐ survival rate was demonstrated only in retrospective30,31 but not in randomized prospective studies of pa­tients.31 If patients present with regional lymph node metastases (stage III), the thera­peutic approach includes therapeutic lym­phadenectomy. However, 10-year-survival-rate decreases from 97 % in patients staged pT1N0M0 to 19 % in patients staged N1 or N2 and M0 melanoma.32 The primary treatment goal in patients with M1 malignant me­lanoma (stage IV) is the reduction of tumoral masses in order to prolong the patientsŐ life expectancy as well as to improve the quality of life.33 In principle, there are three thera­peutic options: surgery, external radiothera­py, and chemotherapy. In case of isolated metastases, surgical operative treatment has appeared to be helpful in the prolongation of patients life expectancy. In most studies, life prolongation was demonstrated only in cases of total resection of all tumoral masses.34 Thus, a 10-year-survival-rate was expected to be as low as 3 % in the patients with advanced malignant melanoma.32 Unfortunately, there is no well-established, standardized systemic treatment protocol for managing the patients with distant metastases. The treatment strat­egy itself is still under clinical investigation and the subject of several patients studies. It is now evident that the patients with stage IV malignant melanoma benefit from an aggres­sive chemotherapy consisting of the applica­tion of interleukin-2 and interferon alpha. These authors report 5-year-survival-rate of up to 10 %.24,35 In addition to sensitivity and specificity of high-resolution ultrasonography of 70 % and 90 %,36 respectively, even the patients with advanced malignant melanoma may benefit from the detection of metastases by 18F-FDG­PET due to several reasons. First, patientsŐ survival rate decreases with an increasing number of involved lymph node regions.37 Second, the prognosis of patients is better with an early detection of metastases and with less suspicious masses at the time of de­tection.37 Third, in the detection of lung metastases 18F-FDG-PET has been proven su­perior as compared to conventional, well-es­tablished computed tomography.38,39 And last, 18F-FDG-PET offers the advantage to im­age the whole body in one single procedure which is especially important since in malig­nant melanoma often unexpected, aberrant metastatic spread is found. Thus, 18F-FDG­PET has already been suggested as a tool for staging malignant melanomas.21 Conclusion Our results underline the added value of 18F­FDG-PET in the staging of malignant melanomas. Since further treatment mainly depends on the clinical stage, 18F-FDG-PET might help to select the appropriate treat­ment protocol for each individual patient. However, for the exclusion of metastases, physical examination by a dermatologist and conventional imaging are indispensable. References 1. Macfarlane DJ, Sondak V, Johnson T, Wahl RL. Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of re­gional lymph nodes in patients with cutaneous ma­lignant melanoma. J Clin Oncol 1998; 16: 1770-6. 2. Sober AJ, Koh HK. Melanoma and other pigment­ed skin lesions. In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci, A.S, Kasper DL, edi­tors. HarrisonŐs principles of internal medicine. 13 ed. New Yoork: McGraw-Hill, Inc; 1994. p. 1867-71. 3. Gritters LS, Francis IR, Zasadny KR, Wahl RL. Initial assessment of positron emission tomogra­phy using 2-fluorine-18-fluoro-2-deoxy-D-glucose in the imaging of malignant melanoma. J Nucl Med 1993; 34: 1420-7. 4. Zartman GM, Thomas MR, Robinson WA. Metastatic disease in patients with newly diag­nosed malignant melanoma. N Nucl Med 1987; 35: 163-4. 5. Ginaldi S, Wallace S, Shalen P, Luna M, Handel S. Cranial computed tomography of malignant melanoma. AJR 1981; 136: 145-9. 6. Shirkhoda A, Albin J. Malignant melanoma: corre­lating abdominal and pelvic CT with clinical stag­ing. Radiology 1987; 165: 75-8. 7. Silverman PM, Heaston DK, Korobkin M, Seigler HF. Computed tomography in the detection of ab­dominal metastases from malignant melanoma. Invest Radiol 1984; 19: 309-12. 8. Patten RM, Shuman WP, Teefey S. Metastases from malignant melanoma to the axial skeleton: a CT study of frequency and appearance. AJR 1990; 155: 109-12. 9. Steinert H, Boni R, Huch-Boni RA, Capaul R, von Schulthess GK, Westera G. 123I-alpha-methyltyro-sine scintigraphy in malignant melanoma. Nuklearmedizin 1997; 36: 36-41. 10. Bekerman C, Hoffer PB, Bitran JD. The role of Gallium-67 in the clinical evaluation of cancer. Sem Nucl Med 1985; 15: 72-103. 11. Bockisch A, Oehr P, Biltz H, Hotze A, Kreysel HW, Biersack HJ. The clinical value of radioimmunode­tection (RID) using antimelanoma antibodies. Tumordiag und Ther 1991; 12: 112-6. 12. Boni R, Steinert H, Huch Boni R, Von Schulthess GK, Meyer J, Dummer R, et al. Radioiodine-la-belled alpha-methyl-tyrosine in malignant melanoma: cell culture studies and results in pa­tients. Br J Dermatol 1997; 137: 96-100. 13. Damian DL, Fulham MJ, Thompson E, Thompson JF. Positron emission tomography in the detection and management of metastatic melanoma. Melanoma Res 1996; 6: 325-9. 14. Boni R. Whole-body positron emission tomogra­phy: an accurate staging modality for metastatic melanoma. Arch Dermatol 1996; 132: 833-4. 15. Hsueh EC, Gupta RK, Glass EC, Yee R, Qi K, Morton DL. Positron emission tomography plus serum TA90 immune complex assay for detection of occult metastatic melanoma. J Am Coll Surg 1998; 187: 191-7. 16. Holder WD Jr, White RL Jr, Zuger JH, Easton EJ Jr, Greene FL. Effectiveness of positron emission to­mography for the detection of melanoma metas­tases. Ann Surg 1998; 227: 764-71. 17. Engel H, Steinert H, Buck A, Berthold T, Huch Boni RA, von Schulthess GK. Whole-body PET: physiological and artifactual fluorodeoxyglucose accumulations. J Nucl Med 1996; 37: 441-6. 18. Kern KA. [14C]deoxyglucose uptake and imaging in malignant melanoma. J Surg Res 1991; 50: 643-7. 19. Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high risk melanoma pa­tients with whole- body 18F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients. Cancer 1998; 82: 1664-71. 20. Paquet P, Hustinx R, Rigo P, Pierard GE. Malignant melanoma staging using whole-body positron emission tomography. Melanoma Res 1998; 8: 59-62. 21. Steinert HC, Huch Boni RA, Buck A, Boni R, Berthold T, Marincek B, et al. Malignant melanoma: staging with whole-body positron emission tomography and 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1995; 195: 705-9. 22. Reske SN, Bares R, B.ll U, Guhlmann A, Moser E, Wannenmacher MF. Clinical value of positron emission tomography (PET) in oncologic ques­tions: results of an interdisciplinary consensus conference. Nuklearmedizin 1996; 35: 42-52. 23. Reintgen DR, Balch CM, Kirkwood J, Ross M. Recent advances in the care of the patient with malignant melanoma. Ann Surg 1997; 225: 1-14. 24. Richards JM, Gale D, Mehta N, Lestingi T. Combination of chemotherapy with interleukin-2 and interferon alfa for the treatment of metastatic melanoma. J Clin Oncol 1999; 17: 651-7. 25. Clark WHJ, From L, Bernandino E, Mihm M. The histogenesis and biologic behaviour of primary malignant melanomas of the skin. Cancer 1969; 29: 705-26. 26. Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970; 172: 902-8. 27. UICC. TNM classification of malignant tumors. 5 ed. New York: John Wiley & Sons; 1997. 28. Minn H, Leskinen-Kallio S, Lindholm P, Bergman J, Ruotsalainen U, Teras M, et al. (18-F)fluo­rodeoxyglucose uptake in tumors: kinetic vs. stady-state methods with reference to plasma in­sulin. J Comput Assist Tomogr 1993; 17: 115-23. 29. Bleckmann C, Buchert R, Schulte U, Lorenzen J, Bohuslavizki KH, Mester J, et al. Onko-PET: lesion detection by computer display versus standard­ized documentation on film. Nuklearmedizin 1999; 38: 56-60. 30. Kaufmann R. Operative Therapie des prim-ren Melanoms. Onkologe 1996; 2: 449-52. 31. Balch CM, Milton GW, Cascinelli N, Sim HF. Elective lymph node dissection: pros and cons. In: Balch CM, Houghton AN, Milton GW, Sober AJ, Soong SJ, editors. Cutaneous melanoma. Philadelphia: Lippincott, J. B.; 1992. p. 345-66. 32. H-ffner AC, Garbe C, B.ttner P, Orfanos CE, Rassner G, Burg G. The prognosis of primary and metastasizing melanoma. An evaluation of the TNM classificationin 2495 patients and proposals for their revision. Br J Cancer 1992; 66: 856-61. 33. Garbe C. Malignes Melanom. In: Seeber S, Sch.tte J, editors. Therapiekonzepte Onkologie. 3 ed. Berlin: Springer; 1998. p. 799-829. 34. Gihl J, Meyer T, Haas C, Altendorf Hofman A, Hohenberger W. Ist die chirurgsche Therapie von Fernmetastasen maligner Melanome sinnvoll? Langenbecks Arch Chir Suppl Kongressbd 1996; 113: 122-6. 35. Hoffmann R, M.ller I, Neuber K, Lassmann S, Buer J, Probst M, et al. Risk and outcome in metastatic malignant melanoma patients receiving DTIC, cisplatin, BCNU and tamoxifen followed by immuntherapy with interleukin 2 and interferon alpha2a. Br J Cancer 1998; 78: 1076-1080. 36. Blessing C, Feine U, Geiger L, Carl M, Rassner G, Fierlbeck G. Positron emission tomography and ultrasonography. A comparative retrospective study assessing the diagnostic validity in lymph node metastases of malignant melanoma. Arch Dermatol 1995; 131: 1394-8. 37. Hoh CK, Hawkins RA, Glaspy JA, Dahlbom M, Tse NY, Hoffman EJ, et al. Cancer detection with whole-body PET using 2-[18F]fluoro-2-deoxy-D-glu­cose. J Comput Assist Tomogr 1993; 17: 582-9. 38. Hoh CK, Schiepers C, Seltzer MA, Gambhir SS, Silverman DH, Czernin J, et al. PET in oncology: will it replace the other modalities? Semin Nucl Med 1997; 27: 94-106. Comparison of CT analyses of primary renal cell carcinoma and of metastatic neoplasms of the kidney Ingrid Prka‰in, Slavica Naumovski-Mihali“, Nives Dabo, Iva Pal‰i“, Svetozar Vujani“, Zdravko Babi“ Department of Internal Medicine, Merkur University Hospital, Zagreb, Croatia Background and purpose. We compared the computed tomography (CT) findings in 25 patients, in 10 with pathologically proven metastases in the kidney and in 15 with renal cell carcinoma to establish the dif­ference on CT scan. Patients and methods. All 25 patients with kidney neoplasm were analysed by the conventional contrast-enhanced CT criteria. Imaging initiated 2 min after intravenous contrast injection. Results. The sensitivity of CT to discriminate renal cell carcinoma from renal metastases and to discrimi­nate renal metastases from renal cell carcinoma were 98 % and 70 %, respectively. Conclusions. This study indicates that CT could be useful in clinical practice for distinguishing renal cell carcinoma and metastatic neoplasms of the kidney. Key words: tomography, x-ray computer; carcinoma, renal cell; kidney neoplasm-secondary Introduction In order to decide on the type of therapy it is necessary to differentiate between renal car­cinoma and renal metastases. If the renal cell carcinoma is diagnosed, nephrectomy is indicated (in more than 95 %), but in the case of renal metastases, nephrec­tomy is not the best possible therapy. Received 9 March 2000 Accepted 18 February 2001 Correspondence to: Ingrid Prka‰in, M.D., Ph.D., De­partment of Internal Medicine, Merkur University Hospital, I. Zajca 19, 10000 Zagreb, Croatia. Phone: +385 1 24 31 390 / 454; Fax: +385 1 24 31 393. The most common origin of kidney meta­stases is the carcinoma of the lung.1 Other primary malignancies are the carcinomas of the colon, breast, stomach, ovaria, uterus and prostate.2-5 Although CT is more sensitive than ultra­sound and urography in the differentiation of the renal metastases from the renal cell carci­noma, there is only one report comparing CT findings of renal cell carcinoma and of renal metastases.3 We report here on CT findings of renal me­tastases and renal cell carcinoma in order to establish the criteria for the differentiation of these two forms of kidney malignancies. Patients and methods CT examination was performed in 25 patients with kidney neoplasms, using a Shimatzu 4500 T with scan times of 2 to 3 seconds. Con­ventional contrast-enhanced computed tomo­graphy studies were perfomed by using intra­venous 60 % iodinated contrast medium administered by bolus injection or drip infu­sion technique. In 15 out of 25 patients (me­an age 58 years, range 21-89 years) renal me­tastases were found. The most common origin of the metastases was the carcinoma of the lung (n = 4), followed by the carcinomas of the colon (n = 3), ovaria, pancreas and a lymphoma, each in one patient. The interval between the initial diagnosis of the primary malignancy and the occurrence of renal meta­stases was 1 to 5 years (mean 1.9 years). The diagnoses were pathologically confir­med by surgery in 19 patients (renal cell carci­noma 18, renal metastases 1), by biopsy in 4 patients (renal metastases 4), and by autopsy in 2 patients (renal metastases 2). When multi­ple tumours existed in one or both kidneys, the largest tumours were chosen for evaluation be­cause they were the most frequently biopsied. Renal function was normal except in one patient with lymphoma and acute renal failu­re, successfully treated by haemodialysis. There were no patients with acquired renal cystic disease or patients with Von Hippel-Lindau disease. Results We retrospectively reviewed 25 cases of ki­dney neoplasms diagnosed during the past 5 years. Fourteen CT criteria were chosen to cha­racterise the tumours: bilateralism, number, location, size, shape, margin, calcification, in­volvement of the renal vein, involvement of collecting system, hydronephrosis, perirenal extension, attenuation, thickening of GerotaŐs fascia and lymphadenopathy. Table 1 presents the result concerning individual predictors of renal cell carcinoma and renal metastasis. Criterion location included 2 categories: type I - tumour located entirely within the re­nal parenchyma and capsule, less than 50 % of the tumour has an exophytic pattern; type II - more than 50 % of the tumour demonstra­ted an exophytic pattern. The largest axis was used as an expression of the tumour size. The lesionŐs shapes were divided into round or wedge-shaped. The tumour margin was cha­racterised as well or poorly demarcated, and the attenuation (density) as homogenous or inhomogeneous. The lymph nodes were mea­sured by the length of their longest axis and those that were more than 10 mm long were diagnosed as positive. The calcification, renal vein involvement, collecting system involve­ment, hydronephrosis, perirenal extension and Gerota involvement were descirbed as yes or no. All patients with renal cell carcino­ma had solitary tumours (100 %). Five pati­ents (50 %) with renal metastasis had solitary tumours, 3 patients (30 %) 2 unilateral tumo­urs, and 2 (20 %) patients had more than 2 bi­lateral tumours. Renal metastases were smaller (mean 3.1 cm) than renal cell carcinoma (mean 8 cm). A round shape was found in 80 % of patients with renal cell carcinoma, and in 70 % of pati­ents with metastases. Renal cell carcinoma were of exophytic pattern in 60 % of patients, with the size of 6­9 cm in 53 % of patients, well demarcated tu­mour margin in 66 % of patients, calcification in 33 % of patients, renal vein involvement in 20 % of patients, collecting system involve­ment in 73 % of patients, with hydronephro-sis in 36 % of patients, perirenal extension in 60 % of patients, and lymph node metastasis in 53 % of patients. Renal metastases were located within the kidney parenchyma in 80 % of patients; their size ranged 0-3 cm in 60 % of patients. The metastases had smooth margins and were wi­thout calcification in 80 % of patients; in 10 % Table1. Individual predictors between renal cell carcinoma and renal metastasis in our patients (I part) Predictors Renal cell carconoma Renal metastases Laterally Unilateral 15 8 Bilateral 0 2 Number One 15 6 Two 0 3 >=3 0 1 Location a) within parenchyma 6 8 and capsule, less than 50 % of tumour is exophytic b) more than 50 % 9 2 of tumour is exophytic Size 0-3 cm 2 6 3.1-6 cm 5 3 6.1-9 cm8 1 > 9.1 cm 0 0 Table 2. Individual predictors between renal cell carcinoma and renal metastasis in our patients (II part) Predictors Renal cell carcinoma Renal metastases Shape round 12 7 irregular 3 3 Margin smooth 10 3 irregular 5 8 Attenuation inhomogeneous 6 8 homogenous 4 6 Calcification no 10 10 yes 5 0 Renal vein involvement no 12 0 yes 3 9 Collecting system no 4 7 involvement yes 11 3 Table 3. Individual predictors between renal cell carcinoma and renal metastasis in our patients (III part) Predictors Renal cell carcinoma Renal metastses Hydronephrosis no 10 9 yes 5 1 Perirenal no 6 7 extension yes 9 3 Gerota no 8 8 involvement yes 7 7 Lymph node no 7 7 metastases yes 8 8 of patients, renal vein involvement and in 30 % of patients collecting system involve­ment were observed; 80 % patients had lymph node metastasis. The stepwise discriminant analysis sho­wed that number (N), laterality (L), location (LO), perirenal involvement (P) and calcifica­tions were the strongest predictors. The pri­mary and secondary scores were calculated according to Honda et al. as follows: Primary score = (L x 3.63) + (N x 0.85) + + (P x 0.83) + (LO x 4.29) ­- 9.65. Secondary score = (L x 5.01) + (N x 2.67) - (P x 1.27) + (LO x 3.33) - - 11.60. The radiologic variables were defined as follows: L = laterality; 0 = unilateral, 1 = bilateral N = number; actual number of the tumours P = perirenal involvement; 0 = yes, 1 = no LO = location: 0 = a, 1 = b. Using these primary and secondary scores the posterior probabilities (PP) of primary versus secondary tumour were computed as follows: Posterior probability (primary) = = exp(primary score) / exp(primary score) + exp(secondary score) Posterior probability (secondary)= = exp(secondary score) / exp(primary score) + exp(secondary score) The PP (primary) + PP (secondary) = 1. When PP (primary) > PP (secondary) the number can be diagnosed as primary tumour. When PP (primary) < PP (secondary) it can be diagnosed as secondary tumour. The classification functions detected 98 % of primary renal cell carcinoma and 70 % of metastases. Discussion The kidney is a common site of metastases, with reported incidence of 2 to 20 % at au­topsy.6-9 The tumour that most commonly metastasises to the kidney is the lung carcino­ma1, followed by the tumours of the breast and stomach, melanoma and contralateral re­nal cell carcinoma.5 Most renal metastases are less than 3 cm in diameter, whereas more than 50 % of renal cell carcinomas are more than 6 cm long.6 Bilateral, multiple, small lesions without an exophytic appearance may be seen in mul­tiple areas of renal inflammation, renal in­farction and multiple renal cysts.10 It is well known that renal cell carcinoma can also occur bilaterally or multifocally, es­pecially in the patients with predisposing conditions (i.e. in the patients with acquired renal cystic disease or patients with Von Hip-pel-Lindau disease).11,12 This study did not in­clude any patients with acquired renal cystic disease or patients with Von Hippel-Lindau disease. In recent years, more and more small renal masses have been reported (usually inciden­tally) due to the widespread use of cross-sec­tional imaging modalities (especially ultraso­und and computed tomography) as well as other reasons.13,14 Most of these masses are low stage renal cell carcinomas. The problem is that the growth rate of small renal tumours is variable; the tumours that are destined to grow and possibly metastasise do so early. So, bilateral or multifocal involvement do-esnŐt exclude renal cell carcinoma as the dia­gnosis.14 The size Ňper seÓ cannot be a strong predic­tor for the metastases.15,16 The indication for surgery in renal cell carcinoma is under di­scussion in the urologic literature.12 The main problem of nephron-sparing surgery is the multifocality of renal cell carcinoma. Modern double-phase helical CT can distinguish among the subtypes of renal cell carcinoma (clear, chromophobe, papillary), and correla­tes with microvessel density or the existence of intratumoral necrosis or haemorrhage. Ho­wever, it does not differentiate between renal cell carcinoma and other solid tumors.17 In the preparation for nephron-sparing surgery of renal cell carcinoma, preoperative routine imaging cannot safely predict multi-focal lesions of renal cell carcinoma.12 In this study, tumour calcification was a di­agnostically strong predictor for the renal cell carcinoma. Calcifications were present in five cases of renal cell carcinoma and in none of the cases of renal metastases. Metastases we­re more frequently bilateral or multifocal, and smaller than renal cell carcinoma. Stepwise, discriminant analysis showed that the useful radiologic predictors were the number, laterality, location and perirenal ex­tension. The sensitivity of CT to discriminate renal cell carcinoma from renal metastasis was 98 %, and to discriminate renal metasta­ses from renal cell carcinoma was 70 %. In contrast to the investigation of Honda et al., the margin of the lesion, the involvement of the renal vein and collecting system, existen­ce of hydronephrosis, thickening of GerotaŐs fascia and lymphadenopathy were not dia­gnostically strong predictors, like in.3 Conclusions Using the stepwise discriminant analysis and posterior probabilities of primary versus se­condary tumour, computed tomography co­uld be useful to differentiate between non-multifocal renal cell carcinoma and renal metastasis. In patients with a single, exophytic, large and perirenally extending lesions with calcifi­cations, renal cell carcinoma is more likely than renal metastasis. In patients with multiple, less exophytic, small renal lesions with or without wedge shaped appearance, the renal metastasis is more likely than the renal cell carcinoma. The biopsy of tumour lesions is restricted to cases with discrepancy between clinical manifestation and computed tomography fin­dings. References 1. Becker WE, Schellhammer PF. Renal metastases from carcinoma of the lung. Br J Urol 1986; 58: 494-7. 2. Hietala SO, Wahlqvist L. Metastatic tumors to the kidney. A postmortem, radiologic and clinical in­vestigation. Acta Radiol Diagnosis 1982; 23: 585-8. 3. Honda H, Coffman CE, Berbaum KS, Barloon TJ, Mausa K. CT analysis of metastatic neoplasm of the kidney. Acta Radiol 1992; 33: 39-44. 4. Lindell OI, Grein HU, Schreiter FJ. Opposite renal pelvic metastasis of renal adenocarcinoma. Scan J Urol Nephrol 1991; 25: 165-7. 5. Muller-Mattheis V, Hagen M, Frenzel H, Acker­mann R. Seltene Metastasierungsform des Nieren­zellkarzinoms. Urology 1989; 28: 355-8. 6. Pagani JJ. Solid renal mass in the cancer patients. Second primary renal cell carcinoma versus renal metastasis. J Comput Assist Tomogr 1983; 7: 444-8. 7. Peterson RO. Renal neoplasm. In: Dial DH, editor. Hammar Speeds. Pulmonary pathology. New York: Springer-Verlag 1988. p. 973-1028. 8. Prkacin I, Malcic I, Ivancevic D, Hebrang A. Ratio­nal choice of diagnostic medical test in patients with renal tumors. Lijec Vjesn 1995; 117: 209-15. 9. Fielding JR, Aliabadi N, Renshaw AA, Silverman SG. Staging of 119 patients with renal cell carcino­ma: the yield and cost-effective of pelvic CT. AJR 1999; 172: 23-5. 10. Voci SL, Gottlieb RH, Fultz PJ, Mehta A, Parthasa­rathy R, Rubens DJ, et al. Delayed computed to­mographic characterization of renal masses: preli­minary experience. Abdominal Imaging 2000; 25: 317-21. 11. Yip SK, Chee C. Clinics in diagnostic imaging. Re­nal cell carcinoma in acquired cystic kidney disea­se. Singapore Med J 2000; 41: 89-91. 12. Koga S, Nishikido M, Inuzuka S, Sakamato I, Ha-yashi T, Hayashi K, et al. An evaluation of Bosni­akŐs radiological classification of cystic renal mas­ses. BJU Int 2000; 86: 607-9. 13. Mitchell TL, Pippin JJ, Devers SM, Kimball TE, Gibbons LW, Cooper LL, et al. Incidental detecti­on of preclinical renal tumors with electron beam computed tomography: report of 26 consecutive operated patients. J Comp Assist Tomogr 2000; 24: 843-5. 14. Schlichter A, Schubert R, Werner W, Zermann DH, Schubert J. How accurate is diagnostic ima­ging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery? Urol Intern 2000; 64: 192-7. 15. Zagoria RJ. Imaging of small renal masses: a medi­cal success story. AJR 2000: 175: 945-55. 16. Rendom RA, Stanietzky N, Panzarella T, Robinet­te M, Klotz LH, Thurston W, et al. The natural hi­story of small renal masses. J Urol 2000; 164: 1143­7. 17. Jinzaki M, Tanimoto A, Mukai M, Ikeda E, Koba­yashi S, Yuasa Y, et al. Double-phase helical CT of small renal parenchymal neoplasm: correlation with pathologic findings and tumor angiogenesis. J Comp Assist Tomogr 2000; 24: 835-42. Review Opportunities for up to date treatment of the colorectal cancer Yovtcho Yovtchev, Stoian Nikolov Department of Surgical Diseases, Medical Faculty, Thracian University, Stara Zagora, Bulgaria Background. Up to now the basic methods in the treatment of colorectal cancer are surgery, chemo- and ra­diotherapy. Throughout current years new methods were developed and successfully used in oncology; they consist of application of specific antibodies, the antibody driven enzyme pro-drug treatment, the application of radioimmunoconjugates and the radioimmunoguided surgery. Conclusions. With the applied methods for the treatment of colorectal cancer we prolong a disease-free sur­viving period, reduce subjective complaints and decrease mortality. Key words: colorectal neoplasms-therapy Introduction The colorectal cancer (CRC) provides great op­portunities for challenging the surgeonŐs skills, as well as for the application of the modern molecular biological and radioimmune meth­ods for its diagnosis and treatment. The presented review aims to introduce the contemporary state of the problem and the possibilities for the application of some new methods for treatment into the surgical society. Despite the achievements of the modern clinical oncology the colorectal cancer is diag- Received 15 March 2000 Accepted 14 May 2000 Correspondence to: Yovtcho Yovtchev, M.D., Department of Surgical Diseases, Medical Faculty, Thoracian University, Armeiska Str. 11, Stara Zagora, Bulgaria. E-mail: yovtchev@abv.bg nosed relatively late, i.e. in the advanced cli­nical stage. The treatment is unsatisfactory. The mortality is high. The annual mortality in the United Kingdom in 1995 was about 20 000; Italy 7000; in Bulgaria 1400. The most frequent localisation of the col-orectal cancer is the rectal cancer. Its inci­dence in the Western European countries is 70 / 100 000 population. Many people could be protected from the colorectal cancer by in­troducing accessible screening methods. Many of the complications of the traditional surgery can be avoided by improving the technical abilities for the operative treatment. In about 50 % of the patients suffered from the rectal cancer the definitive colostomy is unavoidable. In 2/3 of them it could be avoid­ed by applying the so-called total mesenteric excision (TME) with a modern stapling tech­nology. The early diagnosis, the accurate pre­operative staging, the radical surgical inter­vention and the subsequent postoperative chemo- and radiotherapy are of great impor­tance for the complex treatment of the col-orectal cancer. Up to now the literature does not comment the issues about the functional disorders of the reservoir functions and the disturbances of the sexual function and the socialisation of the person.1 At present the main methods for the treat­ment of the colorectal cancer are: Ń Surgery Ń Chemotherapy Ń Radiotherapy In the recent years the following new tech­nologies and methods are applied for the treatment of the colorectal cancer: Ń Application of specific antibodies; Ń Creation and application of radioimmuno- conjugates; Ń Radioimmunoguided surgery (RIGS); Ń Antibody driven enzyme pro-drug treat­ ment (ADEPT).2 Application of specific antibodies The development of immunology and im­munotherapy as a branch of the oncology originates from the works of Cooley who es­tablished that in patients with the advanced sarcoma the same has a regressive course af­ter a severe infection. There were hopes due to some medicines, like BCG vaccine, levamisol (Lev), interferon, interlevkin -2 (IL-2). There are several ran-domised studies for the effect of BCG-vaccine application in patients with CRC but none of them has proved some advantage regarding the total or the disease-free surviving period. Levamisol increases the immune response by stimulating the T-lymphocytes, the macrophages and the neutrophils. The simul­taneous application of Lev+5 Fluorouracil (5­FU) to the patients in stage C, according to Dukes, decreased mortality in 1/3 of the cas­es. The single use of Levamisol does not cause changes in the percentage of the sur­vival rate compared with the other group of patients who do not receive the medicine. Another study of the application of IL-2 has found higher percentage of the survival of patients who have received this medicine be­fore the operation, followed by the postoper­ative application of 5-Fu and Folic acid. There was found that this medicine increased the ability of patients to tolerate easier the post­operatively developed lymphocytopenia.2,3 The works of Leonard P.C. (1999) and Brivio et al. (1996) claim that the medicines stimu­lating the humoral immunity do not meet the hopes reposed on them. That is why in the clinical practice the antitumor antibodies (Ab2) were established and introduced. The works in this field are directed to: Ń Manipulation of antigen presenting cells; Ń Use of co-stimulating molecules for facili­ tating the specific cell activation; Ń Use of double specific antibodies by T-cell targeting to the tumour. Monoclonal antibodies The designing and introducing first in the ex­periment and later in the clinical practice of monoclonal antibodies is related with the in­vention of CEA. Its relation with the cancer of the colon has encouraged studies using radio-labelled anti-CEA monoclonal antibodies. Other two classes with even higher specifici­ty are TAG-72 and 17-1A. In a randomised study on 189 patients with CRC, stage C ac­cording to Dukes, who have been treated by the resection received either 500 mg 17-1A antibody, followed by 4 x 100mg infusions every month or have been just followed up for 5 years. In the treated group it was found 27 % decrease of the relapses and 30 % of the mortality.2,4 High affinity single-chain Fv antibodies loaded with radioisotope and CEA were cre-ated in the last 2 - 3 years. They, with high tu­mour affinity and their sensitivity, signifi­cantly exceed this of the up to now used com­puter tomography (CT).5 Radioimmunoconjugates The radioimmunotherapy was developed as a type of treatment due to the ability for the successful targeting of radiolabeled antibod­ies to the tumour antigens (e.g. radioactive CEA antibodies for the treatment of CRC).2 They are high - energy beta-particles, emitted from Radionuclide, such as 131I, 90Yt, 111 In, accumulating in the tumour, characterised with high efficiency in experimental models and for 131I and 111In in patients. Radioimmunoguided surgery The implementation of the above-mentioned radioimmunoconjugates in the medical prac­tice contributed to the development and ap­plication in the surgical diagnosis of the so-called radioimmunoguided surgery. The postoperatively applied radioimmuno-anti­bodies are targeted against the tumour tissue. By the aid of a gamma-detector in the partic­ular time interval and even intraoperatively the tumour process can be exactly located and staged. The implementation of the method will facilitate: Ń Finding metastases in hepatogastric liga­ ment Ń More comprehensive and exact staging of the tumour process. A problem for the intraoperative staging is whether there are metastatic lymph nodes in hepatogastric ligament or not. The applica­tion of anti -TAG - MoAbs changed the deci­sion making for the surgical treatment and staging of patients with primary or relapsing colorectal tumour. There can be concluded that TAG - MoAbs can be used for the intra-operative detection of the tumour even when there are no significant levels of the serum TAG- 72 and /or CEA.6 In the study of Filez L. (1999), carried out on 26 patients with CRC, the application of RIGS has led to the change of the operative technique in 16 patients.6 At present in USA and Europe a multicen­ter clinical trial for the evaluation of the pos­sible benefits of RIGS is going on in patients with the primary colorectal tumour as well as with its relapses.7 Chemotherapy of CRC Already for several decades 5-Fu the main stream of the treatment of advanced colorec­tal cancer and of some other solid tissue ma­lignancies is obvious, despite that its success in patients with the advanced colorectal can­cer is low (incidence of effectiveness 10-15 % when using bolus injections). The application of 5-Fu by the infusion has a better effect than the bolus injection due to the route of administration or to the dose in­tensity achieved or as a combination of both factors.8-10 The presence of some new drugs including biochemical modulators of 5-Fu, increasing its cytotoxicity, has renewed the interest to these agents in the recent years. Some of them are other fluoro-pyrimidins, new modulators of 5-FU or new ingredients, activated in a different way. 5-Etinoluracil. At present a clinical trial of this agent in combination with 5-Fu is carried out. Trimetrexat. It is considered as a more po­tent modulator of 5-Fu than metotrexate. One recently completed phase III clinical trial has found good results in the treatment of pa­tients with CRC.11-12 Thymidilat - syntetase (TS) inhibitors The TS inhibitors catalyse the uridin mono-phosphate (UMP) methilation to the timidi­latmonophosphate (TMP), which is after that metabolised to the timidilatmonophosphate (TTP). At present 6 TS inhibitors are included in the clinical practice as pre-clinical or early clinical trials. Tomudex (ZD 1694 or raltritrexed) is a specif­ic TS inhibitor in the advanced stage of a clinical trial. In a large phase II study 187 pa­tients with the untreated colorectal cancer were included. An objective effect is found in 26 %. In a completed randomised phase III clinical trial comparing Tomudex with 5­Fu+Lev. (bolus injections) the identical sur­vival and degree of effectiveness has been found. Tomudex was been applied in a dose of 3 mg/m2 as an infusion in every three weeks. Other drugs Irinotecan is a topoisomerase I inhibitor and it is created for the treatment of the advanced CRC. The DNA-synthetase inhibition leads to a retention of S-phase of the cell cycle. In a trial with the agent on 455 patients with the advanced CRC there was found the stabilisa­tion of the disease in 42 %, benefit incidence of 13 % and symptoms suppression in 62 %.13,14 Oxaliplatin. This is a diamonohexan plat­inum complex with an alkylating agent. There was found the benefit incidence of 10 % and in combination with 5-Fu+Lev.of 20-40 %. Prevention of the relapsing CRC The incidence of relapse after the radical re­section in patients with CRC varies from 2,6 up to 32 %. The time for the local relapse is various but in 55 to 80 % it occurs in the first 2 years following to the operation.15 The incomplete tumour resection is one of the causes, as according to different authors it varies from 4 to 27 % as 85 % of the patients have tumour invasion of the lateral resection lines and develop a relapse in a term of 23 months.15 According to the data of Burkhardt et al., cited from other authors too15 by the aid of the conventional histology bone marrow metastases in 17 % of patients with the intes­tinal cancer without any evidence of the sys­temic problems were diagnosed. Except these two widely accepted methods in the recent years there were accepted me­thods for: Ń Intralumen tumour sterilisation by Povido­ ne iodine 10 % or 5 % solution, iertimide, chlorhexidine and DakinŐs solution which were assessed as more cytotoxic and can- cericide than some other agents.15 Ń Systemic chemotherapy Ń Intraportal chemotherapy Their implementation immediately after the operation causes the destruction of the tumour cells, which could disseminate in the portal circulation at the time of the surgical intervention. The analysis based on the data upon 3824 patients and consistent with the aim of the treatment showed a reduction of the risk for relapse with 14 ± 5 % (p = 0,007) and for death with 13 ± 6 % (p = 0,007) after median 5 year follow up.16 Ń Intraperitoneal chemotherapy. There is no available data about performed controlled trials. Conclusions Reaching high incidence of surgical healing is the most important aim in the present time. Instead of being considered as ŇharmlessÓ the abdomino-perineal extirpation should be applied only for the highest situated can­cers. The high specificity of imunotherapy will lead to the effective treatment but will create an immune memory providing a defence against relapses. References 1. Heald RJ. Colorectal cancer - a surgeonŐs view. OIP 1997; 2: 3-5. 2. Leonard PC, Begent HRJ. Immunotherapy options for colorectal cancer. OIP 1999; 1: 8-10. 3. Brivio F, Lissoni P, Alderi G, Barni S, Lavorato F, Fumagalli L. Preoperative IL-2 subcutaneos im­munotherapy may prolong survival time in ad­vanced colorectal cancer patients, Oncology; 1996; 53: 263-8. 4. Rietmuller G, Schneider-Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, et al. Randomised trial of monoclonal antibody for ad-juvant therapy of resected Dukes C colorectal car­cinoma. German Cancer Aid 17-1A Study Group. Lancet 1994; 343: 1177-83. 5. Lane DM, Eagle KE, Begent RHJ, Hope-Stone LD, Green AJ, Casey JL, et al. Radioimmunotherapy of metastatic colorectal tumours with iodine-131-la-belled antibody to carcinoembrionic antigen. Phase I-II study with comparative biostrillution of intact and F(ab2) antibodies. Br J Cancer 1994; 70: 521-23. 6. Filez L, Penninckx F, Ectors N, Van Cutsem E, Geboes K, et al. Radioimmunoguided surgery for colorectal carcinoma. Hepatogastroenterology 1999; 46: 691-700. 7. Scott KW, Grace RH. Detection of lymph node metastases in colorectal carcinoma before and af­ter fat clearance. Br J Surg 1989; 76: 1165-7. 8. Rougier P, Paillot B, LaPlanche A, Morvan F, Seitz JF, Rekacewicz C, et al. 5-Fluorouracil (5-FU) con­tinuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer. Eur J Cancer 1997; 33: 1789-9. 9. de Gramout A, Bosset JF, Milan C, Rougier P, Bouche O, Etienne PL, et al. Randomized trial comparing monthly low-dose leucovorin and fluo­rouracil bolus with bimonthly high-dose leucov­orin and fluorouracil bolus plus continuous infu­sion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997; 15: 808-15. 10. Caudry M, Bonnel C, Floquet A, Marsault C, Quetin P, Pujol J, et al. A randomized study of bo­lus fluorouracil plus folic acid versus 21-day fluo­rouracil infusion alone in association with cyclo­fosphamide and mytomicin C in advanced colorectal carcinoma. Am J Clin Oncol 1995; 18: 118-25. 11. Wils JA. New drugs for colorectal cancer. OIP 1997; 2: 6-7. 12. Bajetta E, Colleoni M, Rosso R, Sobrero A, Amadori D, Comella G, et al. Prospective random­ized trial comparing fluorouracil versus doxifluri-dine for the treatment of advanced colorectal can­cer. Eur J Cancer 1993; 29A: 1658-63. 13. Blanke CD, Kasimis B, Schein P, Capizzi R, Kurman M. Phase II study of trimetraxate, fluo­rouracil and leucovorin for advanced colorectal cancer. J Clin Oncol 1997; 15: 915-20. 14. Creemers GJ, Lund B, Verweij J. Topoisomerase I inhibitors: topotecan and irinotecan. Cancer Treat Rev 1994; 20: 73-96. 15. Diaz-Rubio E, Marty M, Extra JM. Multicenter phase II study with oxaliplatin (L-OHP) in 5-Fu re­fractory patients with advanced colorectal cancer (ACC) [Abstract]. Proc Am Soc Onc 1995; 14: 514. 16. Topal B, Basha G, Penninckx F. Mechanisms and prevention of recurrent colorectal cancer. Hepatogastroenterology 1999, 46: 701-8. Radical irradiation of the prostate. Combination of percutaneous irradiation and irradiation with LDR Ir-192 implants Borut Kragelj, France Guna, Janez Burger Institute of Oncology, Ljubljana Background. The irradiation of the carcinomas of the prostate with the doses above the tolerable ones of standard radiotherapy improves the local control of the disease. The aim of this study is to determine the acute toxicity and tolerability of the high-dose prostate irradiation combining external beam radiotherapy (EBRT) and interstitial low dose rate (LDR) brachyradiotherapy (BRT) with Ir-192 of the prostate. Material and methods. We examined medical records of 8 patients with localized carcinoma of the pro­state (T2-T3 No-x Mo) treated from August 1999 until February 2000. The initial PSA was 2.7-37.5 ng/ml (median 13.7) and Gleason score 4-9 (median 7). Radiotherapy consisted of 48.6 - 50.4 Gy of EBRT to the prostate and seminal vesicles (4 patients) or the whole pelvis (4 patients) and 20.0-28.0 Gy of interstitial LDR Ir-192 BRT given as a single fraction, fluoroscopic guided transperineal implantation of the prostate. The cumulative doses of percutaneous and interstitial irraditations to the prostate were 68.6 - 79.1 Gy. Results. Acute toxic effects of irradiation though observed in all patients were of only mild intensity. Ac­cording to the RTOG criteria, 20/30 toxicities were assessed as grade 1, 9/30 as grade 2, and 1/30 as gra­de 3. In none of the patients, toxic effects required any specific modification of the treatment regimen. Conclusions. The very first experiences indicate moderate toxicity and optimal tolerance of the treatment by patients. An improvement of implantation techniques may be expected with regular CT controls of the implants and extra attentive care of the implants in the urethra region. Key words: prostatic neoplasms - radiotherapy; radiotherapy dosage; brachytherapy; radiotherapy ­adverse effects Received 10 April 2001 Accepted 24 April 2001 Correspondence to: Borut Kragelj, MD, MSc, Institute of Oncology, Zaloäka 2, 1000 Ljubljana, Slovenia; Pho­ne: +386 01 323063 Fax: +386 01 4314180; E-mail. bkragelj@onko-i.si Introduction The aim of any local therapy has always been to obtain local control of the disease. A better local control over the localized carcinomas of the prostate and the locally advanced tumors invading to the seminal vesicles, periprostatic tissue or urinary bladder can improve also the systemic control of the disease - better local control is associated with better biochemical, distant metastasis-free and cancer specific survival rates.1-3 The probability of local recurrence after standard irradiation with the doses not exce­eding 70 Gy is 20-60 % in locally advanced tu­mors (T3,T4),4 and 8-27 % in T1 and T2 tu-mors.2,5-7 However, the effectiveness of standard radiation in terms of local disease control might be even lower. As suggested by the PSA-based follow-up, the rate of local di­sease control assumed from the digitorectal and imaging examinations of the prostate is perhaps overestimated.6 One of the factors that influence local dise­ase control is the radiation dose. Even within the range of conventional external beam radi­otherapy (EBRT), the dose increase improves the local control of disease. In conformal radi­otherapy; a better biochemical control of dise­ase, at least temporarily, within five-year pro­jection, is obtained with a dose increase up to 81 Gy. In view of the treatment modality, this is due to a better local control. The effective­ness of conformal radiotherapy may be obser­ved in particular in the group of patients with the initial PSA between 10 and 20 ng/ml or with high tumor grade (Gleason score 8-10) in whom standard radiation is often unsucces­sful.8,9 Tumor dose depends upon the tolerance of surrounding organs to radiation. In confor­mal radiotherapy, higher tolerance may be obtained with a more precise adjustment of radiation fields to target volume, thereby re­ducing the involvement of the surrounding organs that are not affected with tumor mass.9-11 Similarly, the increase of a tumor dose not exceeding the level of admissible im­pairment of the surrounding organs can be obtained with the combination of percutane­ous radiation and brachyradiotherapy (BRT) using J-131, Pd-10312,13 seeds or Ir-192 wi­res14-17 as permanent or temporary implants, respectively. The article describes our experi­ences with the combination of percutaneous irradiation and interstitial low dose rate (LDR) BRT with Ir-192. Material and methods From August 1999 to February 2000, 8 pati­ents with localized carcinoma of the prostate received combined therapy of percutaneous irradiation and interstitial brachyradiothe­rapy with Ir-192. In all patients, transrectal ultrasonography was carried out before treatment. In seven pa­tients, the US guided biopsy from six typical sites was performed, whereas in 1 patient on­ly the biopsy of tumor mass was made. In all patients, the PSA concentration in the serum was measured. In all of them, the carcinoma of the prostate was histologically confirmed and its grade assessed according to Gleason score. They also underwent the CT scan of the pelvis, bone scintigraphy, X-ray of the thorax and renography. The treatment indications were given with the histological confirmation of the adenocar­cinoma of the prostate, stage T1-T3 No Mo, while the contraindication was earlier transu­rethral resection of the prostate. Some restric­tions were imposed by the expected survival rate - 5 years in patents with high tumor gra­des (Gleason over 7), and 10 years in the rest of the patients, all with PSA concentration in the serum not exceeding 30 ng/ml. The recruitment of the patients was based on negative selection, i.e. unsuitability of the patients for a radical surgery due to the risk factors, such as high tumor grade, tumor spread into seminal vesicles, tumor overlap­ping the capsule, PSA over 10 ng/ml, or ac­companying diseases that may add on doubts to the fitness of the patients for surgical trea­tment. The patientsŐ characteristics are presented in Table 1. The preparations for brachytherapy star­ted with the US-guided insertion of 3 to 4 per­manent metal implants into the prostate (Fi­gure 1). CT scans were used for the planning of radiation delivery and metal implants ser­ved as markers. The location of markers in the prostate, especially with respect to the prostate margins, was determined from the CT scans (Figure 2). The planned target volu­me encompassed at least 0.5 cm margin aro­und the outer border of prostate or any extra-capsular tumor extension. The needles were implanted under digital and fluoroscopic con­trol using metal implants as orienters. A pro­per needle positioning was achieved by a template with 1 to 1.5 cm spacing between the needles. The contrast in the urinary blad­der served for a proper positioning of nee­dlesŐ points into the bladder wall in order to assure a satisfactory radiation of the base of the prostate. In planning the implantation as well as carrying it out, we were careful to avo­id the urethra. During the implantation, the Table 1. A survey of patients with regard to their age, tumor stage, initial PSA concentration and tumor grade (Gle­ason score) No. of patients Age (years) T stage PSA (ng/ml) Grade 1 68 T2c 24.4 7 2 68 T3 7,2 4 3 71 T2a 18,9 7 4 68 T3 37,5 7 5 72 T2b 12,5 5 6 72 T3 14,3 9 7 73 T3 2,7 5 8 68 T3 13,2 7 position of the urethra was marked by the contrast contained in the urinary catheter. With regard to the size of the prostate and ac­tivity of Ir wires, the number of implanted ne­edles varied from 11 to 16. Following the tra­dition of the house, we applied, in 7 patients, metal needles, which were later replaced by plastic ones, to provide higher comfort to pa­tients and also to facilitate the subsequent de­termination of the location of the needles with CT scan. We used 20 cm long needles with a diameter of 1.9 mm. A single implantation was planned before starting with of EBRT. The prescribed dose was defined as the dose applied to the peri­pheral isodose area involving the planned tar­get volume and, at the same time, assuring a minimal exposure of the rectal wall and ure­thra (the so-called 100 % isodose) (Figure 3). The dose calculation was made according to the Paris dosimetry system. The reference do­se was 15 % lower than the minimum dose wi­thin the implant. The calculations of the pre­scribed dose also took account of biological correction factor with respect to the dose ra­te. The so-calculated radiation dose ranged from 2000 cGy to 2800 cGy. Brachyradiotherapy was followed by EBRT. The patients were irradiated with the linear accelerator of the energy of 10 MV us­ing the technique of four fields and individu­al shieldings. The standard fractionation was applied. The prescribed target dose was 50.4 Gy given in daily doses of 1.8 Gy. With re­gard to the probability of lymphogenic spread that was calculated from RoachŐs equation, the radiation was targeted exclusively to the prostate and seminal vesicles if the estimated risk was lower than 15 %; otherwise the regio­nal lymph nodes were also involved.17 In the­se cases, standard, pelvic fields were applied. In EBRT, limited to the prostate and seminal vesicles, target volume included also a 2.5 cm wide surrounding margin. The details of radiation therapy are presen­ted in Table 2. All patients received complete androgen Table 2. A survey of patients with regard to the external beam radiotherapy (EBRT) field and dose, dose delivered by brachiradiotherapy, total dose delivered to the prostate and treatment time No. of EBRT field EBRT EBRT dose (cGy) Dose to (Gy) Treatment ) patients dose (Gy) dose (cGy) the prostate time (days 1 pelvis 48,6 2000 68,6-78,6 54 2 P+SV 48,6 2000 68,6-72,3 48 3 P+SV 48,6 2000 68,6-69,5 42 4 pelvis 48,6 2500 73,6-78,9 47 5 P+SV 50,4 2500 75,4-80,6 53 6 pelvis 50,4 2000 70,4-74,4 48 7 P+ SV 50,4 2400 74,4-79,6 45 8 pelvis 50,4 2800 79,1-84,1 56 P+SV: prostate and seminal vesicles; Dose to the prostate: total dose including the mean minimal dose within the implant. Radiol Oncol 2001; 35(2): 117-26. blockade for a period of at least three months before irradiation. Toxic effects of irradiation were evaluated according to the RTOG criteria. Results In all patients, the treatment was completed within the expected period. The treatment ti­me ranged from 42 to 56 days (median 48 days). The differences in treatment time are due to different time intervals between brachy- and teleradiotherapy, which could not be avoided because the treatment faciliti­es are overcrowded. In no one of the patients, the toxic effects of radiation were so severe that they would require discontinuation of the therapy. In most patients (7/8 patients) the trea­tment was completed without major compli­cations. In one patient, the position of the im­plant changed. The implant was therefore prematurely removed and reimplanted after the completed percutaneous irradiation. The toxic side effects of the irradiation of the urinary bladder, urethra and rectum oc­curred in all patients. They were generally mild and did not radically affect the quality of life. According to the RTOG criteria, 20/30 si­de effects were categorized as morbidity gra­de 1, 9/30 as grade 2, and 1/30 as morbidity grade 3. The side effects arising from the radiation toxic effects on the urinary organs were evalu­ated in 6 patients. In one patient, this evalua­tion could not be made because the urinary catheter had been inserted permanently befo­re treatment. The most often side effects were more frequent urinations, urge to urinate (7/7 patients), stranguria (6/7 patients), dysuria (4/7 patients), and hematuria (1/7 patient). This single case of hematuria, which occurred immediately after the removal of the implant and required the whole day rinsing of the bladder, was the only morbidity grade 3. Table 3. Acute toxic effects of percutaneous irradiation combined with low dose rate brachyradiotherapy (LDR BRT) Ir-192: urinary toxicity with regard to the pain, frequency of mictions, decreased stream, and hematuria. The grade of these complications is evaluated according to RTOG criteria No of Pain Frequency Decreased Hematuria patients (grade) (grade) stream (grade) (grade) 1 2 1 + 0 2 2 1 0 0 3 1 1 + 0 4 0 1 + 3 5 0 1 + 0 6 7 1 1 + 0 8 0 1 + 0 Table 4. Acute toxic effects of percutaneous irradiation combined with LDR BRT Ir-192: intestinal toxicity with re­gard to stool frequency, painful defecation, tenesmuses and bleeding. The grade of these complications is evalu-ted according to RTOG criteria No. of Stool frequency Pain Tenesmuses Bleeding patients (grade) (grade) (grade) (grade) 12 1 0 0 20 0 0 0 30 1 0 0 4 1 1 2(*) 0 5 0 0 2(*) 0 62 2 0 0 7 1 0 2(*) 0 80 2 0 0 (*) concurrent miction, evacuation of winds and mucinous rectal discharge Painful defecation was the most often to­xic effect of the rectal irradiation (5/8 pati­ents), followed by more frequent defecation (4/8 patients), and tenesmuses (3/8 patients). No hemorrhage from the colon was observed. The complications in the urinary organs occurred in all patients immediately after the completion of BRT. During percutaneous irra­diation, these complications were intensified in 3/7 patients: in 2 patients, the urge of fre­quent urination further increased, whereas in one patient, stuttering urination became mo­re disturbing. Radiation proctitis was noted in 3/8 patients after the removal of the im­plant: in one patient, it was manifested as more frequent tenesmuses, in the second as tenesmuses and more frequent defecations, and in the third as painful defecations. The occurrence of side effects was higher with higher BRT doses. They were mostly re­lated to more intensive proctitic complicati­ons. All patients who had proctitic complica­tions after brachyradiotherapy received a dose exceeding 2000 cGy. In all these pati­ents, the complications persisted also during the percutaneous irradiation. The cystitic symptoms were also more pronounced and long lasting in the treatment with higher do­ses, while with lower doses, this complicati­ons disappeared in the first two or three we­eks of percutaneous irradiation. Within the short follow up, no biochemical recurrence was observed in the patients with the PSA concentration that was at the begin­ning of radiotherapy lower than 1 ng/ml. Discussion The technique of transperineal biopsy of the prostate with the US-guided needle was intro­duced by Holm in the 1980s. The technique was then used primarily for diagnostic purpo­ses, and after unsuccessful retropubic im­plantations of J-125 seeds into the prostate, also for therapeutic purposes in the treatment of the carcinoma of the prostate. The findings of some radiobiological facts on the unsuita­bility of the treatment with J-125 and the de­velopment of high dose rate (HDR) BRT ur­ged the application of permanent Pd-103 implants and temporary HDR Ir-192 implants in the treatment of the carcinoma of the pro­state. At the same time, new data and kno­wledge on the value of particular tumor cha­racteristics in prognosticating the natural progression of very different tumor types we­re being gathered. The prognostic factors, such as PSA con­centration, local spread of the disease, and hi­stological tumor grade, allow the categorizati­on of the patients with localized disease into the groups with respect to the assumed dise­ase progress. This also facilitates a better ana­logy of different treatment modalities and, consequently, also the selection of the most suitable one. In view of radical radiotherapy, the patients may be classified into three gro­ups; the first group, termed as Ôprognostically favorableŐ, includes the patients with the tu­mor stages T1 and T2, PSA level below 10 ng/ml and Gleason score grade lower than 8. In this group, the conventional teleradiothe­rapy, implantation of J-125 or Pd-103 seeds 8,18-20 and radical prostatectomy18 are all con­sidered as effective treatment modalities. The second group comprises the patients in whom high dose radiation therapy,8,9 eventu­ally with the irradiation of the regional lymph nodes,13,20 seemed to be more effective than standard radiotherapy. The patients falling into this group have the serum PSA levels ranging between 10 and 20 ng/ml,8,9,13,21 tu­mor stage T3,8,14 and Gleason score grade above 78 or 8.22 The patients with more of the above mentioned unfavorable prognostic fac­ tors8,23,24 or PSA level exceeding 20 ng/ml8,9,13,22 may be defined as Ôhigh risk gro­upŐ, at least in view of the curability with on­ly local or locoregional treatment - however, in these patients the local control, relapse-free and overall survivals25,26 can be impro­ved by an adjuvant hormonal therapy. With regard to the above prognostic factors, our patients were consistent with the mean and the high-risk group. The decision on trea­tment modality was therefore focused on three main issues: the use of high dose irradi­ation of the prostate,8,9,14-17 elective irradiati­on of the seminal vesicles27 or regional lymph nodes24 and instantaneous medicamentous androgen blockade.25,26 These issues were re­solved by applying the combination of EBRT to the prostate and seminal vesicles or to the pelvic region and the LDR Ir-192 BRT to the prostate, together with an instantaneous ap­plication of LH-RH agonists and blockers of androgen receptors. Our brachyradiotherapy technique was ba­sed on the CT and transrectal ultrasound (TRUS) determinations of the target volume, the introduction of the needles with respect to the position of implanted metal markers, fluoroscopic control of the position of the ne­edles, and choice of LDR Ir-192 as the radiati­on source. The main reasons for this specific technique were the in-house experiences with LDR BRT Ir-192 method, limited possibilities of US-guided implantation of the needles and unavailability of technical devices for HDR. These are also the basic differences between our technique and more advanced ones. The advantage of the HDR BRT Ir-192 te­chnique is the possibility of more accurate adjustment of irradiated field to the prostate, thereby reducing the exposure of the surro­unding tissue to irradiation; it is also possible to avoid hot spots that may occur because of the improper geometry of the implant. This may be obtained by planning the treatment after the needles have been in place, and by precise placing of a single movable high in­tensity Ir-192 source anywhere in a after loa­ding needle, and by varying the time spent at a particular location to control the dose depo­sition. By choosing different lengths of active Ir-192 wires and by varying the time of inser­tion of a particular active wire into the after loading needle it is possible to adjust to a cer­tain point also the dose in LDR BRT; but this is only a rough approximation to the possibi­lities of HDR BRT. An important advantage of the US-guided implantation is higher accuracy in positio­ning the needles. Besides, in the determinati­on of target volume, our technique can hard­ly assure the same accuracy as that achieved in TRUS-guided implantation.15 However, the accuracy of TRUS has certain limitations: the accuracy of the TRUS measurements of the tumor volume is 62-92 %.28 Moreover, in the determination of the prostate volume, there is a discrepancy between CT scan and TRUS ­the target volume determined by CT scan may exceed the volume determined by TRUS by 25-40 %.17 TRUS is also unreliable in pre­dicting the invasion into the capsule and pe­riprostatic tissue. This is particularly impor­tant in bilateral tumors in which as high as 72 % probability of the invasion into the ca­psule has been recorded. In view of the possi­bility of underestimation of the tumor volume by TRUS, especially in T2B, T3 tumors, a lar­ger treatment volume determined by CT scan from the target volume and wider safety mar­gin, due to a lesser accuracy of needle place­ment, may contribute to a more reliable im­plantation. The limited follow-up of our patients has not allowed any comparison of the late sequ­els of the LDR and HDR BRT Ir-192 treatment modalities. The only components of the two modalities that could be compared were acu­te toxicity of the treatment and tolerance of the patients to the treatment. Both treatment modalities are comparable as regards the non-occurrence of serious toxicity and 100 % tolerance of the patients to the planned the­rapy. Perhaps, an exception was a patient with hematuria. It was classified as RTOG to­xicity grade 3, but it was short and transitory and did not affect the physical condition of the patient. Similar complications were ob­served also in US-guided implantations and were classified as low degree toxic effects (15). A higher toxicity, due in particular to proctitic complications, was observed with the doses escalating up to 2500 cGy. Never­theless, even in these dose ranges, the toxi­city remained within low to median limits. The factors that may influence the toxicity, such as the accuracy of irradiated volume to fit the prostate, and the quality of treatment planning are not in favor of our technique ­the main advantages of more accurate adju­stment of irradiated to the target volume by US-guided HDR BRT Ir-192 are lower exposu­re of the surrounding organs to radiation and lesser possibilities of hot spots inducing acu­te and late sequels of treatment. The dose, another factor influencing the occurrence of toxic effects is, at least nominally, compara­ble or even higher than 36-50 Gy of EBRT and 12- 30 Gy of BRT in HDR 192-Ir treatments (14,15,22). Hence, one can speculate that the comparability of the least acute toxicity may be due to better biologic tolerance of LDR BRT. The possibilities to improve our technique lie in the use of TRUS during the implantati­on without the help of a fixed template, and in the routine use of CT scan after the implan­tation. The determination of the actual positi­on of needles allows more adequate calculati­on of the dose. Another advantage is the possibility to irradiate different areas of the implant with different doses, i.e. increasing the dose in the tumor area and decreasing it in the area of the urethra and of the wall of the rectum - i.e. the organs most at risk for the development of late irradiation injury.21 With further technical improvements, we ex­pect to decrease toxicity or, at least, preserve the existing tolerance with increasing the tu­mor dose. References 1. Sands SA, Pollack A, Zagars GK. Influence of ra­diotherapy on node-positive prostate cancer trea­ted with androgen blocking. Int J Radiat Oncol Biol Phys 1995; 31: 13-9. 2. Zagars GK, von Eschenbach AC, Ayala AG, Schul­theiss TE, Sherman NE. The influence of local con­trol on metastatic dissemination of prostate cancer treated by external beam megavoltage radiation therapy. Cancer 1991; 68: 2370-7. 3. Zietman AL. The role of radiation as adjuvant or salvage therapy following radical prostatectomy. In: Vogelzang NJ, Scardino PT, Shipley WU, Cof­fey DS, editors. Comprehensive textbook of genitouri­nary oncology. Baltimore: Williams & Wilkins; 1996. p. 782-90. 4. Lee WR, Hanks GE, Schultheiss TE. The role of ra­diation therapy of stage T3-T4 prostate cancer: ra­tionale, technique, and results with standard radi­ation, conformal therapy, proton and neutron beam therapy. In: Vogelzang NJ, Scardino PT, Shi­pley WU, Coffey DS, editors. Comprehensive textbo­ok of genitourinary oncology. Baltimore: Williams & Wilkins; 1996. p. 790-8. 5. Hanks GE, Perez CA, Kozar M, Asbell SO, Pile-pich MV, Pajak TF. PSA confirmation of cure at 10 years of T1b T2 N0 M0 prostate cancer patients treated in RTOG protocol 7706 with external beam radiation. Int J Radiat Oncol Biol Phys 1994; 30: 289­92. 6. Shipley WU, Prout GR, Couchron VM, Mc Manus PL, Healey EA, Althausen AF, et al. Radiation the­rapy for localized prostate carcinoma: experience of the Massachusetts general hospital. NCI mono­graphs 1988; 7: 1973-84. 7. Asbell SO, Martz KL, Shin KH, Sause WT, Doggett RL, Perez CA, et al. Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG # 77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma. Int J Radiat Oncol Biol Phys 1998; 40: 769-82. 8. Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Ventkatramen ES, et al. Dose escala­tion with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998; 41: 491-500. 9. Hanks GE, Hanlon AL, Schultheiss TE, Pinover WH, Movsas B, Epstein BE, et al. Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions. Int J Radiat Oncol Biol Phys 1998; 41: 501-10. 10. Dearnaley DP, Khoo VS, Norman AR, Meyer L, Nahum A, Tait A, et al. Comparison of radiation side-effects of conformal and conventional radio­therapy in prostate cancer: a randomised trial. Lancet 1999; 353: 267-72. 11. Boersma LJ, van den Brink M, Bruce AM, Shou-man T, Gras L, Velde A, et al. Estimation of the in­cidence of late bladder and rectum complications after high dose (70-78 Gy) conformal radiotherapy for prostate cancer, using dose-volume histo­grams. Int J Radiat Oncol Biol Phys 1998; 41: 83-92. 12. Kuban DA, Schellhamer PS, El-Mahdi AM. Radia­tion therapy for stage T1 and T2 prostate cancer. In: Vogelzang NJ, Scardino PT, Shipley WU, Cof­fey DS, editors. Comprehensive textbook of genitouri­nary oncology. Baltimore: Williams & Wilkins; 1996. p. 759-80. 13. Blasko J, Ragde H, Cavanagh W, Sylvester J, Grimm P. Long term outcomes of external beam irradiation and J 125/ Pd 103 brachytherapy boost for prostate cancer. [Abstract] Int J Radiat Oncol Bi­ol Phy 1996; 36(Supp 1): 79. 14. Kovacs G, Wirth B, Berterman H, Galalalae R, Kohr P, Wilhelm R, et al. Prostate preservation by com­bined external beam and HDR brachytherapy at nodal negative prostate cancer patients-an interme­diate analysis after ten years experience. [Abstract] Int J Radiat Oncol Biol Phy 1996; 36(Supp 1): 80. 15. Borghede G, Hadelin H, Holmang S, Johansson KA, Aldenborg F, Petterson S, et al. Combined tre­atment with temporary short-term highdose rate Iridium-192 brachytherapy and external beam ra­diotherapy for irradiation of localized prostatic carcinoma. Radioth Oncol 44: 237-44. 16. Hoskin PJ. HDR brachytherapy as a boost in loca­lised prostate cancer. In: Prostate brachytherapy workshop. Zeist: 1999. p. 33-4. 17. Mate TP, Gottesman JE, Eulau SM. CT based HDR IR-192 for prostate implantation. In: Prostate brach­ytherapy workshop. Zeist: 1999. p. 29-31. 18. DŐAmico AV, Whittington R, Malkowitz SB, Schultz D, Renshaw AA, Tomaszewski JE, et al. Optimizing patient selection for dose escalation techniques using the prostate-specific antigen le­vel, biopsy Gleason score, and clinical T stage. Int J Radiat Oncol Biol Phy 1999; 45: 1227-33. 19. Batterman JJ. Iodine-125 implantation for localised prostate cancer, the Utrecht University experien­ce. In: Prostate brachytherapy workshop. Zeist: 1999. p. 15-8. 20. Beyer DC, Brachman DG, Thomas T, Hilbe J. Fai­lure free survival following brachytherapy alone or external beam irradiation alone for T1/T2 prostate tumors in 2222 patients: results from a single prac­tice. In: Prostate brachytherapy workshop. Zeist: 1999. p. 7-13. 21. Mate TP, Gottesman JE, Hatton J, Gribble M, Van Hollebeke. High dose-rate afterloading 192 Iridi­um prostate brachytherapy: feasibility report. Int J Radiat Oncol Biol Phys 1998; 41: 525-33. 22. Roach M III, Meehan S, Kroll S, Weil M, Ryu J, Small EJ, et al. Radiotherapy for high grade clini­cally localized carcinoma of the prostate. J Urol 1996; 156: 1719-23. 23. Roach M. The role of PSA in the radiotherapy of prostate cancer. Oncology 1996; 10: 1143-53. 24. Seaward SA, Weinberg V, Lewis P, Leigh B, Phil­lips TL, Roach M III. Identification of a high-risk clinically localized prostate cancer subgroup rece­iving maximum benefit from whole-pelvic irradia­tion. Cancer J Sci Am 1998; 4: 370-7. 25. Bolla M, Gonzalez D, Warde P, Dubois JB, Mirima­noff RO, Storme G, et al. Improved survival in pa­tients with locally advanced prostate cancer trea­ted with radiotherapy and goserelin. N Engl J Med 1997; 337: 295-300. 26. Pilepich MV, Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, et al. Phase III trial of an­drogen suppression using goserelin in unfavora-ble-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of radiation therapy oncology group protocol 85-13. J Clin On-col 1997; 15: 1013-21. 27. Diaz A, Roach M, Marquez C, Coleman L, Pickett B, Wolfe S, et al. Indications for and the significan­ce of seminal vesicle irradiation during 3D confor­mal radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 1994; 30: 323-9. 28. Narayan P, Hricak H. Imaging in prostate cancer 726-33 In: Vogelzang NJ, Scardino PT, Shipley WU, Coffey DS, editors. Comprehensive textbook of genitourinary oncology. Baltimore: Williams & Wil­kins; 1996. p. 726-33. 29. Montie JA, Pienta K, Pontes JE. Staging systems and prognostic factors for prostate cancer In: Vo­gelzang NJ, Scardino PT, Shipley WU, Coffey DS, editors. Comprehensive textbook of genitourinary on­cology. Baltimore: Williams & Wilkins; 1996. p. 712-22. Dividing patients with brain metastases into classes derived from the RTOG recursive partitioning analysis (RPA) with emphasis on prognostic poorer patient groups Peter Willfurth1, Ramona Mayer1, Heidi Stranzl1, Ulrike Prettenhofer1, Bernd Genser2, Hackl Arnulf1 1University Clinic of Radiation Oncology, 2Department of Laboratory Diagnosis (BL II) University Hospital Graz, Graz, Austria Background. The aim of our study was to investigate whether selecting the patients with brain metastases by classifying them into three classes according to the results of the recursive partitioning analysis (RPA) of the Radiation Therapy Oncology Group (RTOG) is useful or not for further decision concerning altered treatment schedules in patients. Patients and methods. The investigated group included 57 male and 48 female patients having received whole brain radiotherapy in a total dose of 30 Gy / 3 Gy daily / 5 days a week. Patients who had surgical excision of brain metastases or had radiosurgical intervention were excluded. All patients were stratified ac­cording to the findings of RPA (Class I: Karnofsky Performance Status (KPS) =70, age <65, controlled pri­mary tumour, no other metastases; Class II: not Class I or III; Class III KPS <70). Results. The six/twelve months survival probability for classes I to III was 80 %/44 %, 43 %/17 % and 6 %/0 %, respectively. KPS and extracerebral tumour activity, but not age (<>65) had an impact on sur­vival according to multivariate analysis. Conclusions. Selecting the patients by dividing them into the three RPA classes seems to be useful. Considering the short survival time in RPA Class III, those patients might be well treated with a shorter treatment course. Keywords: brain neoplasms-secondary-radiotherapy, brain metastases; survival analysis; Karnofsky per­formance status; recursive-partitioning analysis, prognostic groups Received 23 January 2001 Accepted 15 February 2001 Correspondence to: Peter Willfurth, Klinik f.r Radioonkologie und Strahlentherapie, LKH Graz, Auenbruggerpl. 32, A-8036 Graz. Phone: +43 316 385 2639; Fax: +43 316 385 3426; E-mail: peter.will­furth@kfunigraz.ac.at Introduction The Radiation Therapy Oncology Group (RTOG) performed a recursive partitioning analysis on 1200 patients from three consecu­tive RTOG trials which tested different dose fractionation schemes and radiation sensitiz­ers.1 The goals of this analysis were a) to analyse the relative contributions of pre-treat­ment variables to the survival of patients with brain metastases using an interactive, non­parametric statistical technique known as re­cursive partitioning analysis; b) to define the influence of treatment variations on survival among patients enrolled on three consecutive RTOG randomised trials and c) to identify pa­tient subgroups or stages.1 Based on this analysis, a classification in three classes was suggested to test new treat­ment techniques on homogeneous patient groups. To learn more about the survival charac­teristics, we retrospectively analysed a ho-mogenous group of 105 patients with brain metastases treated by whole brain radiothera­py. The highest emphasis was placed on the prognostically poorer groups to find out if it might be reasonable to enter these patients into shorter treatment courses with higher single doses and a higher probability of late toxicity reactions. Methods and materials To gain a homogenous patient group, only pa­tients without previous treatment, like surgi­cal resection or radiosurgical intervention, were accepted. The investigated group in­cluded 57 (54.2 %) male and 48 (45.8 %) fe­male patients, who were irradiated at our Department between 1987 and 1997. All pa­tients had received whole brain radiotherapy of 30 Gy in ten fractions within two weeks. Following CT-assisted treatment planning, ir­radiation was administered using a linear ac­celerator with 18 MV photon beams. Reproducible patient positioning was achieved by using a thermoplastic mask sys­tem. During irradiation, all patients received corticosteroids as prophylaxis of cerebral oedema. All patients were stratified into three classes according to the findings of Gaspar et al.: Class 1: Karnofsky Performan­ce Status (KPS) = 70, age < 65 years with con­trolled primary and no evidence of extracra­nial metastases (16 pts, 15.2 %), class 3: KPS < 70 (37 pts, 35.2 %) and class 2: all remaining patients (52 pts, 49.5%). PatientsŐ characteristics and class charac­teristics are provided in Table 1. Statistics The survival curves were calculated using the Kaplan Meier method and the log rank test was used for univariate comparison. Prognostic factors were analysed using CoxŐs regression model. Results The mean follow up time of the whole group was 6.9 months (0.4-53.3). The median sur­vival of all 105 patients was 3.2 (95 % confi­dence interval (CI), ±0.98) months. The medi­an survival of the classes one to three was 10.7 (95 % CI, ±1.6), 4.7 (95 % CI, ±1.2) and 2 (95 % CI, ±0.79) months, respectively. The six/twelve months survival probability of classes one to three was 80 %/44 %, 43 %/17 % and 6 %/0 %, respectively. Comparing the sur­vival times of the three classes, a distinct dif­ference was seen (p < 0.0001) Univariate analysis of the whole group showed significant differences in the survival of patients with a Karnofsky Performance Status = 70 or < 70 (p < 0.001), of the patients with or without extracerebral tumour activity (p < 0.001) and of the patients with or without Table 1. Patient characteristics according to classes resulting from recursive partitioning analysis (RPA) Class 1 Class 2 Class 3 Total n % n % n % n % Gender Female 8 50 20 39 20 54 48 46 Male 8 50 32 61 17 46 57 54 Age < 65 16 100 35 67 17 46 67 64 > 65 0 0 17 33 20 54 38 36 Performance Status < 70 0 0 0 0 37 100 37 35 > 70 16 100 52 100 0 0 68 65 Neurological symptoms No 13 81 34 65 12 32 59 56 Yes 3 19 18 35 25 68 46 44 Number of brain lesions < 3 8 50 24 46 18 49 50 48 > 3 8 50 28 54 19 51 55 52 Primary tumour Lung cancer 6 38 28 54 15 40 49 47 Breast cancer 5 31 14 27 12 32 31 30 Melanoma 3 19 3 6 4 11 10 9 Renal cancer 0 6 1 2 1 3 3 3 Gynaecological cancer 1 0 0 0 1 3 1 1 Unknown primary 0 0 0 0 1 3 1 1 Others 1 6 6 11 3 8 10 9 Active primary tumour Yes 16 100 35 67 23 62 74 71 No 0 0 17 33 14 38 31 29 Extracerebral metastases No 16 100 24 46 15 40 54 51 Yes 0 0 28 54 22 60 51 49 neurological symptoms stage 3 and 4 (p = 0.01). Details of neurological function sta­tus are given in Table 2. Age did not seem to have an effect on survival with a p-value of 0.8. A multivariate Cox regression model re­vealed the Karnofsky Performance Status (p < 0.001, relative risk (RR), 3.2) and extrac­erebral tumour activity (p = 0.004; RR, 2.4) as significant prognostic factors. Discussion According to the findings of the RTOG1 and validating studies 2,3, we saw a distinct and significant (p < 0.0001) difference in the sur­vival of the three prognostic classes. Age, however, did not show statistically significant impact on survival. Selecting patients accord­ing to the parameters derived from the RPA analysis might be a good way of predicting Table 2. Neurological function status1 Stage Symptoms 0 No neurological symptoms; fully active at home/work without assistance 1 Minor neurological symptoms; fully ac­ tive at home/ work without assistance 3 Moderate neurological symptoms; less than fully active at home/work and re­ quires assistance 4 Severe neurological symptoms; totally inactive requiring complete assistance at home or in institution. Unable to work the survival time not only for the patients with favourable prognosis but also for those with poor prognosis. Identifying this group of patients gives the possibility to adept the treatment to their needs. In Table 3, the sur­vival times of four studies on the RPA find­ings are shown. The six/twelve months sur­vival ranged between 6-20 % and 0-6 %, respectively for patients of the RPA class III. The median survival ranged between 2 to 2.3 months. Considering these short survival times we should apply the shortest and least demanding scheme of therapy possible. Table 3. Survival in different studies on RPA classification Haie-Meder et al.4 performed a ran-domised trial on two radiation schedules comparing 18 Gy in 3 fractions versus the same fractionation followed by a second course of radiotherapy with a one-month time interval. The second course was identical to the first one or delivered 25 Gy/10 frac­tions/14 days. The neurological improvement was similar in both treatment arms; no neu­rological complications were observed. Concerning the survival, the two treatment arms were equivalent with 4 to 5 months of median survival. The authors conclude, that a radiation schedule as short as 18 Gy in 3 frac­tions can provide good palliation with the ad­vantage of saving time spent by the patient in the hospital and smaller cost and the mainte­nance of the same level of palliation. It has al­so been indicated that the patients might not have lived long enough to experience serious complications. Short fractionation programs have also been tested by the RTOG.5-7 The investigation on 10 Gy in one fraction or 12 Gy in two frac­tions showed comparable results with those of the patients receiving 20 to 40 Gy, single fraction 2-4 Gy, concerning response rates, promptness of neurological improvement, treatment morbidity and median survival. However, the duration of improvement, time to progression of neurological status and rate of complete disappearance of neurological symptoms were generally less for those pa­tients who received 10 or 12 Gy, suggesting that ultra rapid high dose irradiation sched­ules might not be as effective as higher-dose schedules in the palliation of patients with brain metastases.5 RPA Classes I II III Gaspar et al. 19961 6 mo (%) 59 36 ~16 12 mo (%) 32 16 ~6 median (mo) 7.1 4.2 2.3 Nieder et al. 19993 6 mo (%) ~70 ~30 ~20 12 mo (%) ~38 ~16 ~5 median (mo) 10.5 3.5 2 Gaspar et al. 20002 6 mo (%) 51 33 - 12 mo (%) 29 12 - median (mo) 6.2 3.8 - Present study 6 mo (%) 80 43 6 12 mo (%) 44 17 0 median (mo) 10.7 4.7 2 Conclusion It still has to be considered, that there are long time survivors among the patients with brain metastases and longer schedules still should be routine. But considering the short survival times of patients in the RPA class III, the use of a short schedule might give pre­cious time at home to the patient with the same palliation and reasonable small risk of more complications than from longer schemes. References 1. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analy­sis (RPA) of prognostic factors on three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 1997; 37: 745-51. 2. Gaspar L, Scott C, Kevin M, Curran W. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 2000; 47: 1001-6. 3. Nieder C, Nestle U, Motaref B, Walter K, Niewald M, Schnabel K. Prognostic factors in brain metas­tases: Should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes? Int J Radiat Oncol Biol Phys 2000; 46: 297-302. 4. Haie-Meder C, Pellae-Cosset B, Laplanche A, Lagrange JL, Tuchais C, Nogues C, et al. Results of a randomized clinical trial comparing two radia­tion schedules in the palliative treatment of brain metastases. Radiather Oncol 1993; 26: 111-16. 5. Borgelt B, Gelber R, Larson M, Hendrickson F, Griffin T, Roth R. Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: fi­nal results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1981; 7: 1633-8. 6. Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metas­tases: final results on the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980; 6: 1-9. 7. Wright DC, Delaney TF. Treatment of metastatic cancer. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: Principles and practice of oncology. 3rd Edition. New York: J. B. Lippincott Company; 1980. Predictors of recurrence in stage I invasive breast carcinoma George Baitchev1, Grigor Gortchev1, Angelica Velkova2, Tashko Deliisky1 1Dept. of Surgical Oncology, University Centre of Oncology, Pleven, Bulgaria 2Dept. of Social Medicine & Public Health, Medical University, Pleven, Bulgaria Background. The aim of the retrospective study was to determine whether 6 classical prognostic factors might predict a disease-free survival (DSF) in stage I breast carcinoma. Patients and methods. We analysed 181 patients who were operated on from 1991 through 1995. Measurements were made to find the association between the incidence of recurrence and prognostic fea­tures (size; histological subtype; lymphatic/vascular invasion (LVI); histological grade; hormone receptor status; age). Results. There were 4 cases with locoregional recurrences (2.2 %), 6 with locoregional and distant metas­tases (3.3 %) and 13 women with distant metastases (7.2 %). In univariate analysis, the following prognos­tic factors were significantly related to DSF: tumour size, age and LVI. In the multivariate analysis age (p = 0.007) and LVI (p = 0.00001) remained firmly associated with DSF, although the tumour size (p = 0.067) lost its significance. Conclusions. Our experience indicates that the combined use of the tumour size, LVI and age may be a bet­ter predictor of recurrence in T1N0M0 breast cancer. Key words: breast neoplasms, stage I breast carcinoma; prognosis, prognostic factors; recurrence Introduction The last decade has witnessed changing trends in the presentation and primary treat­ment of, and adjuvant therapy for women with early breast carcinoma. Patient aware­ness and mammographic screening have re­sulted in earlier detection of the disease.1,2 Women with breast cancer-lacking evi­dence of regional lymph node metastases and systemic disease (stage I) fare significantly Received 13 December 2000 Accepted 14 January 2001 better than those in whom nodal but not sys­temic involvement (stage II) occurs. Disease-free survival (DFS) of the former has been es­timated to be approximately 93.8 % for 5 years and 79.3-81 % for 18-20 years following surgical treatment.3-5 The literature discussed various prognostic factors of T1 (Ł 2 cm) tumours for their asso­ciation with the likelihood of locoregional and distant recurrences. This study for stage Correspondence to: George Baitchev, MD, Dept. of Surgical Oncology, Centre of Oncology, 5800 Pleven, Bulgaria. Phone: +359 64 427 242; E-mail: oncology@el-soft.com I breast cancer was performed to determine whether 6 classical clinical and histological features might predict DSF and also be used to identify patients who have increased or de­creased risk of relapse. Patients and methods A total of 181 patients with T1 lesions were initially examined at the University Centre of Oncology in Pleven from 1991 through 1995. They all underwent axillary node dissection (complete or levels I and II) as part of their treatment for breast carcinoma and those who had an adequate follow-up were includ­ed into the study. The womenŐs age range was 24-75 years (median 58.8 years). None of them had any known regional or distant metastases at the time of initial diag­nosis and, according to the International Union Against Cancer (UICC) classification, they were presented as patients with pT1N0M0 deasise.6 Invasive carcinomas were classified using the largest dimension of the invasive component to determine the size: 5 mm or less, T1a; 6-10 mm, T1b; 11-20 mm, T1c. The axillary contents were dissected fresh; all identified lymph nodes (10-24, me­dian 12.9) were sectioned through the hilum and examined histologically. Pathologic characteristics of the primary tumour (size, histological type and grade, lymphatic/vascular channel invasion (LVI) by tumour emboli) were evaluated on the rou­tine haematoxylin and eosin slides. Oestrogen receptor (ER) and progesterone re­ceptor (PR) status were determined by ra­dioimmunoassay. The patients were treated with a modified radical mastectomy (81 %) or breast-conserv­ing surgery and radiation therapy (19 %). Of 181 patients with ER or PR positive cases, 121 women received adjuvant hormonal treat­ment with Tamoxifen for 5 years. Seven node-negative T1c patients with high risk of recurrence (age < 40 years, ER/PR negative) received six courses of cyclophosphamide, methotrexate and 5-fluorouracil (classical ad-juvant CMF), repeated every 4 weeks. The cases of recurrence were defined sep­arately as locoregional (after mastectomy) and distant metastases. The median follow­up duration of patients was 7 years (range 5­9 years). The log rank test was used to perform the univariate analyses. Multivariate analysis was based on the Cox proportional hazards regres­sion model and included any variable found to be significant in the univariate analysis. Results Table 1 illustrates the distribution of various clinical and pathologic features studied. The median tumour size was 14.8 mm. Ten pa­tients (5.5 %) were with T1a tumours, 38 (21 %) were with T1b, and 133 (73.5 %) were with T1c. The majority of tumours (80.7 %) were infiltrating ductal carcinoma, 16 (8.8 %) were of infiltrating lobular type, and 19 (10.5 %) were of ŇfavourableÓ (mucinous, tu­bular or papillary) histology. One hundred and forty-four patients (79.6 %) had positive steroid hormone receptor status - oestrogen and/or progesterone receptor positive (> 10 fmol). The majority of cases (86.8 %) had LVI (-) tumours. Within the period of 1991­1995, the histological grading was studied on 80 cases out of 181 patients. In 31 patients (38.7 %), the tumour was well differentiated, and in the remaining 49 women, the tumour was moderately or partly differentiated. Twenty-three cases (12.7 %) developed the disease recurrence; ten were with locoregion­al recurrences (5.5 %), and 19 were with dis­tant metastases (10.5 %), four women devel­oped only locoregional, and the other 6 had locoregional and distant recurrence. Thirteen patients with distant metastases (7.2 %) died of the disease. Table 1. Patients with T1N0M0 breast cancer On univariate analysis, variables signifi­cantly associated with the disease recurrence Variable N (%) were: tumour larger than 1 cm (p = 0.03), pres- Tumour size (mm) < 10 11-20 Histologic type ŇFavourableÓ ductal/lobular Histologic grade G1 GII/GIII Lymphatic/vascular invasion Absent Present Hormone receptor status (+) or (+/-) (-) Age (yr) ł 60 < 60 181 48 133 181 19 162 80 31 49 166 143 23 181 144 37 181 99 82 ence of LVI (p = 0.00001) and patientŐs age 26.5 % under 60 years (p = 0.018). 73.5 % The variables statistically significant at the univariate level entered into a multivariate lo­ 10.5 % gistic regression model with backward elimi­ 89.5 % nation. Only two variables remained statisti­cally significant as independent predictors in the final model. They were LVI (odds ratio 38.7 % 13.41; p = 0.00001) and age (odds ratio 5.21; 61.3 % p = 0.007) (Table 2). Among 77 older patients (ł 60 years) with­ 86.8 % out LVI, the incidence of disease recurrence 13.2 % was observed only in 2 cases (2.6 %). However, 4 patients out of 6 with the two risk 79.6 % factors (LVI positive; age < 60 years) had an 20.4 % incidence of relapse that accounted for 66.7 %. 51.9 % Table 3 present the relationship of various 48.1 % clinical and pathologic markers to the clinical Table 2. Statistical associations between recurrences and prognostic variables Table 3. Pathologic parameters and recurrence at 7 years Factor % Recurrences Univariate p value Multivariate p value (Odds ratio) Tumour size (mm) Ł 10 4.3 % 0.067 (4.57) 11-20 15.8 % 0.03 NS* Histological type ŇFavourableÓ 5.3 % Ductal/lobular 13.7 % 0.3 Histological grade G1 6.5 % GII/GIII 12.2 % 0.35 Lymphatic/vascular invasion Absent 7.3 % Present 43.5 % 0.00001 0.00001 (13.41) Hormone receptor status (+) or (+/-) 11.2 % (-) 18.9 % 0.15 Age (yr) ł 60 7.2 % < 60 17.1 % 0.018 0.007 (5.21) *NS: not significant Radiol Oncol 2001; 35(2): 133-7. Factor Disease free survival p value Distant disease free survival p value Tumour size (mm) Ł 10 95.8 % 97.9 % 11-20 84.2 % 0.38 86.5 % 0.026 Histological type ŇFavourableÓ 94.7 % 94.7 % Ductal/lobular 86.4 % 0.45 88.9 % 0.62 Histological grade G1 93.5 % 96.8 % GII/GIII 87.8 % 0.61 89.8 % 0.44 Lymphatic/vascular invasion Absent 92.4 % 93.8 % Present 54.5 % 0.000002 63.6 % 0.000048 Hormone receptor status (+) or (+/-) 88.9 % 91.0 % (-) 81.1 % 0.27 83.8 % 0.28 Age (yr) ł 60 92.6 % 93.6 % < 60 81.6 % 0.027 85.1 % 0.06 outcome. By univariate analysis, the tumour size, LVI and age were significant prognostic factors for disease free survival. These factors also showed a trend toward better outcome for distant relapse-free survival, although on­ly LVI and age reached statistical signifi­cance. Discussion Absence of metastases in the axillary lymph nodes has traditionally been considered as favourable biologic condition for patients with invasive breast cancer. However, all the cases with node-negative breast cancer are at risk for disease recurrence. Intensive efforts to define an individual patientŐs risk of re­lapse have produced a plethora of potential prognostic factors, from patient features to histological, biochemical and molecular char­acteristics of the tumour. The importance of these various prognostic factors has been the subject of controversies. The frequency of the reported DFS period (83.3 % for 7 years) in 181 patients with the stage I disease is close to that reported by oth­er authors.3,4 The most important predictors of DFS, out of the studied 6 ones, are LVI and the pa-tientŐs age followed by the size of the primary tumour. These results, excluding the histolog­ical grading, concur with a number of preced­ing analyses, demonstrating their extreme prognostic importance. As to the histological grading, the lack of statistic authenticity in our study (p = 0.35) can be explained by a lim­ited number of cases with a histological grad­ing defined.5,7-11 For the patients with node-negative dis­ease, International Consensus Panel (St. Gallen, 1998) recommends that the tumour size, histological and nuclear grade, steroid hormone receptor status, LVI and age are the factors considered by the Panel to define groups with differential prognosis for use in treatment selection. For women assumed to be at high risk of recurrence (T > 2 cm; hor­mone receptor status negative; Grade II-III; age < 35 years) the treatment choice follows an algorithm similar to that for node-positive disease, which has a similar prognosis.12 The current multivariate analyses aiming to define the role of the growth rate of the tu­mour, measuring in terms of S-phase frac­tion, DNA ploidy, the occurrence of oncogene amplification of the epidermal growth-factor receptor or the c-erb B-2 gene, are going to de­termine the scope of the routine clinical im­plementation of these new prognostic factors to estimate the risk of the disease recurrence with the cases of early breast cancer. References 1. Treatment of early-stage breast cancer. Curr Probl Cancer 1999; 23(4): 149-228. 2. Sirovich BE, Sox HC. Breast cancer screening. Surg Clin North Am 1999; 79: 961-90. 3. Carter CL, Allen C, Nenson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989; 63: 181-7. 4. Mansour EG, Ravdin PM, Dressler L. Prognostic factors in early breast carcinoma. Cancer 1994; 74: 381-400. 5. Rosen PP, Groshen S, Kinne DW, Norton L. Factors in fluencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow­up. J Clin Oncol 1993; 11: 2090-100. 6. Sobin LH, Wittekind Ch, editors. International Union Against Cancer. TNM classification of malig­5th nant tumors. edition. New York: John Wiley&Sons, 1997. p. 126-30. 7. Fisher ER, Redmond C, Fisher B. Prognostic fac­tors in NSABP studies of women with node-nega­tive breast cancer. J Natl Cancer Inst Monogr 1992; 11: 151-8. 8. Mann GB, Port ER, Rizza C, Tan LK, Borgen PI, Van Zee KJ. Six-year follow-up of patients with mi-croinvasive, T1a and T1b breast carcinoma. Ann Surg Oncol 1999; 6: 591-8. 9. Mouridsen HT, Andersen J, Andersen KW, Axelsson C, Blichert-Toft M, Dombernowsky P, et al. Classification prognostic factors in node-nega­tive breast cancer: the DBCG experience. J Natl Cancer Inst Monogr 1992; 11: 163-6. 10. Rosner D, Lane WW. Predicting recurrence in ax-illary-node negative breast cancer patients. Breast Cancer Res Treat 1993; 25: 127-39. 11. Saimura M, Fukutomi T, Tsuda H, Sato H, Miyamoto K, Akashi-Tanaka S, et al. Prognosis of a series of 763 consecutive node-negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor. J Surg Oncol 1999; 71: 101-5. 12. Goldhirsch A, Glick JH, Gelber RD, Senn HJ. Meeting highlights: International Consensus Panel on the treatment of primary breast cancer. J Natl Cancer Inst 1998; 90: 1601-8. MRI macromolecular contrast agents as indicators of changed tumor blood flow Teodora Ivanuäa1, Katarina Beravs2, Maja ›emaěar3, Vladimir Jevti‰4, Franci Demäar1, and Gregor Seräa3 2 ŇJozef StefanÓ Institute Ljubljana, 1 Veterinary Faculty, University of Ljubljana, 3 Institute of Oncology Ljubljana, 4 Medical Center Ljubljana, Slovenia Background. A rapid mapping technique derived from dynamic contrast enhanced MRI data was used to identify and characterize reduction of blood flow in fibrosarcoma SA-1 tumors treated either by application of electric pulses or vinblastine. Materials and methods. Tissue permeability surface area product (PS) and fractional blood volume (BV) were calculated on a pixel-by-pixel basis using dynamic MRI intensity data after administration of gadomer­17 or polylysine-Gd-DTPA; prototypic macromolecular contrast agents designed for blood pool enhance­ment. PS and BV values of untreated tumors were compared to those of tumors treated by local application of 8 electric pulses (amplitude/distance ratio, 1300 V/cm; duration, 100 ms, frequency, 1 Hz) percutaneo­usly to the tumor or by systemic administration of vinblastine (2.5 mg/kg). Results. Both treatments transiently, but significantly reduced tumor blood flow, application of electric pul­ses to the tumors being by 40% more effective in reducing tumor blood flow than systemic administration of vinblastine. PS and BV values derived with polylysine-Gd-DTPA-enhanced MRI were lower compared to those with gadomer-17, due to larger molecular size. Interestingly, Gd-DTPA-enhanced MRI did not show any significant changes of PS and BV between untreated and treated tumors. Conclusion. This study demonstrates that dynamic contrast enhanced MRI can be effectively used to qua­litatively monitor tumor blood flow, and quantitatively by means of BV and PS. Key words: sarcoma experimental - therapy - blood supply; vinblastine; electroporation; magnetic reso­nance imaging; contrast media; macromolecular systems Received 3 May 2001 Accepted 5 June 2001 Correspondence to: Katarina Beravs, Ph.D., ŇJozef Ste-fanÓ Institute, Jamova 39, SI-1000 Ljubljana, Slovenia. Phone: +386 31 313 806; Fax: +386 1 251 93 85; E-ma­il: Katarina.Beravs@ijs.si Introduction Tumors are physiologically different compa­red to normal tissues. Tumors are usually po­orly perfused, have low oxygen tension and lower pH, due to chaotic vascularization. If the blood flow is chronically impaired, a ca­scade of tumor cell death occurs due to the lack of nutrients and accumulation of catabo­lic products. Therefore, the knowledge of tu­mor physiology is important for understan­ding of tumor growth.1 Knowledge about tumor perfusion and its consequences on tumor cellsŐ oxygenation is also important for planning of different trea­tments.2 Radiation therapy requires good tu­mor oxygenation; adequate tumor perfusion is also important for successful delivery of chemotherapeutic drugs to tumor cells. Many anticancer agents and therapies in current use have been shown to have tumor blood modifying effect, and exert their antitumor action also by compromising tumor vascular function.3 In order to measure tumor blood flow se­veral techniques have been developed.2 One of imaging techniques that have already si­gnificantly contributed to better tumor visua­lization is magnetic resonance imaging (MRI). The use of contrast-enhancing agents in co­njunction with MRI provides an opportunity to non-invasively extract physiological infor­mation, in addition to anatomical data offe­red by unenhanced images.2 Contrast agents that are being developed nowadays are desi­gned to define the physiology and patho-physiology in various tissues. In general, they can be divided into two groups: low-molecu­lar-weight contrast agents and macromolecu­lar contrast agents. Low-molecular-weight contrast agents, represented in one study by Gd-DTPA, have proved to be clinically useful in detecting abnormalities in blood-brain bar­rier.4 Unfortunately their performance is limi­ted by rapid clearance from the blood into the extra-vascular compartment.5 Macromolecu­lar contrast agents are being developed to in­vestigate blood pool, to specifically enhance the blood pool and evaluate capillary inte­grity.6,7 Multiple applications of these con­trast agents have been tested, including as­sessment of relative tissue blood volume and abnormal capillary permeability.8,9 The aim of this study was to demonstrate the potential of dynamic contrast tissue-en­hanced MRI to evaluate changes in tumor perfusion by calculating permeability surface area product (PS) and fractional blood volu­me (BV) on a pixel-by-pixel basis.10,11 We hypothesized that estimates of permeability and blood volume based on dynamic contrast tissue-enhanced MRI data should reliably de­scribe the changes in tumor blood flow. For this purpose two tumor blood flow modifying approaches were used, a chemical agent gi­ven systemically, and a physical approach ap­plied locally. Vinblastine is a chemotherapeu­tic agent, used in treatment of cancer. Besides direct effect on tumor cells, it also has tumor blood flow modifying effect, inducing profo­und, but transient reduction in tumor blood flow.12,13 Local application of electric pulses to the tumors also induces transient, but even greater reduction in tumor blood flow compa­red to vinblastin.14,15 Furthermore, macromo­lecular agents gadomer-17 and the new pol-ylysine-Gd-DTPA were used to more accurately quantify the reduction of tumor blood flow due to their specific enhancement of tumor blood pool in contrast to Gd-DTPA, that readily diffuses across endothelium of normal and neoplastic microvessels. Materials and methods Animals and tumors An inbred strain of A/J mice was used. They were maintained at a constant room tempera­ture (22°C) with natural day and night light cycle in conventional animal colony. Before the experiment, the mice were subjected to Ivanuäa T et al. / MRI macromolecular contrast agents as indicators of changed tumor blood flow 141 an adaptation period of at least 10 days. Mice in good condition, without fungal or other in­fections, and 10-20 weeks of age were inclu­ded in experiment. Fibrosarcoma SA- 1 tumor (The Jackson Laboratory, Bar Harbor, ME) syngeneic to A/J mice was used as a tumor model. Tumor cells were obtained from the ascitic form of the tumors in mice serially transplanted every 7 days. Solid subcutaneo­us tumors located dorsolaterally were indu­ced by an injection of 5 ´ 105 SA-1 cells in 0.1 ml of 0.9 % NaCl solution. The viability of the cells was over 95 % as determined by trypan blue dye exclusion test. Tumors were imaged 6-8 days after implantation (app. 7 mm dia­meter). Treatment of tumors Eight square-wave electric pulses, divided in two sets of 4 pulses in opposing directions, of 1040 V amplitude (amplitude/distance ratio 1300 V/cm), with pulse width of 100 ms and repetition frequency 1 Hz were delivered by two flat, parallel stainless-steel electrodes 8 mm apart (two stainless-steel strips: length 15 mm, width 7 mm with rounded corners), which were placed percutaneously at the op­posite margins of the tumor. Good contact between the electrodes and the skin was assu­red by the means of a conductive gel. Electric pulses were generated by an electroporator Jouan GHT 1287 (Saint Herblaine, France). Treatment was performed without anesthesia and was well tolerated. Vinblastine (Lilly France S.A., Fagersheim, France) was admini­stered intraperitoneally in a dose of 2.5 mg/kg. Thereafter, animals were anesthetized with a mixture of Domitor (1.0 mg/kg body weight) (Pfizer GmbH, Karlsruhe, Germany) and 10 % ketamine (75.0 mg/kg body weight) (Veyx-Pharma GmbH, Schwartzenborn, Ger­many) administered intraperitoneally. During anesthesia, body temperature was kept at physiological values. Both treatments were applied 5-10 min prior to imaging. MRI MRI was performed on a 2.35 T Bruker Bios-pec system with horizontal bore magnet. First, a pre-contrast image (complete k-space data set) was acquired using standard spin-echo technique with the following imaging parameters: TR = 600 ms, TE = 18 ms, matrix 256 ´ 256, slice 2 mm, field of view 7 cm and acquisition time 5 min. Subsequently, con­trast agent was administered, and a small, central data subset of the k-domain (in the phase-encoding direction) with dimensions 32 ´ 256 k-space data points was acquired re­petitively for 60-100 min (80-100 ŇkeyÓ ima­ges). Each ŇkeyÓ image was acquired with 32 phase encoding steps that took 38 s. Before the reconstruction, dynamically acquired da­ta subset was first completed in remaining k-space points (which were not included in temporal acquisition) with the data from the first acquisition. This was followed by the dynamical image reconstruction with 2D in­verse Fourier transformation. MR contrast agent Clinically available Gd-DTPA (Magnevist¨, Schering AG, Berlin, Germany) was used as a small-molecular-size contrast agent, admi­nistered to a subgroup of 5 animals, in a do­se of 0.1 mmol Gd/kg. Gadomer-17 (Sche-ring AG, Berlin, Germany) was used as an intermediate molecular size contrast agent, but still macromolecular compared to Gd-DTPA. The size of the agent is approximately 30 kDa, allowing its complete renal elimina­tion. Gadomer-17 was administered to a se­cond sub-group of 5 animals. The new pol-ylysine-Gd-DTPA (Schering AG, Berlin, Germany) was used as a representative ma­cromolecular contrast agent (» 50 kDa). Simi­larly, polylysine-Gd-DTPA was administered to a third subgroup of 5 animals. Both macro­molecular agents were administered in a do­se of 0.025 mmol/kg and were well tolerated. Because of the increased relaxation potency of gadolinium in the macromolecule compa­red to that in the small-molecular contrast agent, this lower dose gives approximately equal initial blood enhancement. All three contrast agents were administered in a bolus via 23-gauge intravenous cannula (Vygon 247 Venoflux infusion set, France) that was inser­ted into a tail vein. Postprocessing Magnetic resonance signal was measured in a region of interest (tumor) in precontrast ima­ges and at least 80 postcontrast images at each timepoint. Signal was corrected for si­gnal variations against water phantom. From the measured signal, tissue contrast agent concentration (CT) was calculated with a sub­traction of precontrast signal from postcon­trast signals on a pixel-by-pixel basis. Con­trast agent concentration in a slowly flowing vessel (CB), such as inferior vena cava was ob­tained in a similar way, only within the infe­rior vena cava. The linearity of the CT / CB fit was checked for the first 30-50 points. Stati­stical analysis using a paired t-test was appli­ed to compare values and significance conclu­ded if P < 0.01. Data analysis Fractional blood volume BV and permeability surface area product PS were calculated using the method described previously.8,16-18 Bri­efly, BV is estimated as a ratio of tissue signal intensity CT at time t divided by signal inten­sity for blood CB in slowly flowing vessels such as the inferior vena cava. On a pixel-by-pixel basis, BV was calculated as: [1] where CT is tissue contrast agent concen­tration, CB blood contrast agent concentrati­on and PSŐ: [2] For the vascular permeability, a two-com­partment, one directional flow model was adopted for the movement of the macromole­cular contrast agent from the blood to the in­terstitial space.17 PS was calculated using equation: PS = PSŐ(1-Hct) [3] where Hct is the measured hematocrit of the blood (47 % for tumor in animals). Results Qualitative MRI data in Figure 1 showed that untreated tumors enhanced heterogeneously with contrast agents used; highly vascular rim enhancing more than the partly vascular, partly necrotic tumor center. Enhancement with Gd-DTPA was prompt and included the whole tumor, but tended to decline after the first minute, due to rapid transendothelial diffusion and rapid renal elimination (Fig. 1a; left column). Prompt and marked enhance­ment of the highly vascularized tumor rim was also observed with polylysine-Gd-DTPA and was less pronounced with gadomer-17 (Fig. 1 b, c; left column). The enhancement of subcutaneously implanted tumors increased gradually with both macromolecular agents, reflecting diffusion from blood into the inter­stitial space. Tumors treated with vinblastine or application of electric pulses showed little or no enhancement of the tumor within the first hour after the treatment, due to reduced blood flow (Fig. 1, middle and right column). Afterwards, enhancement started to increase since the reduction in tumor blood flow was transient. Enhancement with Gd-DTPA was not significantly affected by both treatments. Ivanuäa T et al. / MRI macromolecular contrast agents as indicators of changed tumor blood flow 143 The time course of gadomer-17 and pol-ylysine-Gd-DTPA accumulation (described as CT) in the untreated tumors and tumors trea­ted with vinblastine or application of electric pulses is shown in Figure 2. In untreated tu­mors, concentration of the gadomer-17 (CT) increased gradually over the first 10 minutes indicating microvascular leak and accumula­tion of the agent in the interstitial space of the tumor and than started to decreased at 20 min due to the clearence (Fig. 2 a). The CT da­ta for polylysine-Gd-DTPA also increased substantially over the time, again indicating microvascular leak and longer accumulation of the agent in the interstitial space of the tu­mor, due to its large molecule (Fig. 2 b). After both treatments, vinblastine or application of electric pulses, tumor blood flow was reduced and consequently also contrast agents accu­mulation. The effect of vinblastine was less pronounced than that of application of elec­tric pulses (Fig. 2) High mean BV and PS values in untreated tumors, obtained with Gd-DTPA indicated ra­pid transendothelial equilibration (Table 1). Approximately equal mean BV and PS values that were obtained with gadomer-17 and pol-ylysine-Gd-DTPA, but lower compared to Gd-DTPA, indicated slow diffusion of both agents from blood into the interstitial space due to larger molecular size. Large molecular size impairs passage through vascular endo­thelium compared to the small Gd-DTPA, ins-pite of the intercellular gaps. Within the first hour after the application of electric pulses, calculated BV and PS values from data obtai- Table 1. Fractional blood volume BV and permeability surface area product PS values of untreated and tumors tre­ated by vinblastine or application of electric pulses gadomer-17 polylysine-Gd-DTPA Gd-DTPA BV PS BV PS BV PS (%) (ml/cc/h) (%) (ml/cc/h) (%) (ml/cc/h) Untreated tumors 8.8 ± 1.3 680 ± 30.1 8.6 ± 1.1 510 ± 27.3 20 ± 2.3 4710 ± 45.8 Electric pulses 0.5 ± 0.03 72.3 ± 16.1 0.27 ( 0.06 58 ( 18.1 12.7* 4040* Vinblastine 4.0 ± 1.13 359 ± 50.4 1.37 ± 0.22 231.4 ± 60.7 19.8* 4180* * one data set only ned with both macromolecular contrast agents dropped on average to 10 % or less, compared to those of untreated tumors. After treatment with vinblastine, calculated BV and PS values of gadomer-17-enhanced MRI were higher for approximately 65 % and 35 %, res­pectively, compared to BV and PS values of polylysine-Gd-DTPA-enhanced MRI. Discussion Results of this study demonstrate that dyna­mic contrast enhanced MRI can be effectively used to qualitatively monitor tumor blood flow, and quantitatively by means of BV and PS from the gadomer-17 and polylysine-Gd-DTPA enhanced MRI. In order to determine the value of contrast enhanced MRI, two ap­proaches were used to reduce tumor blood flow, treatment with vinblastine and applica­tion of electric pulses to the tumors. Tumor blood flow in both cases rapidly decreased with a slow recovery. Relatively high BV and PS values of untreated tumors were due to microvascular abnormalities - vascular leaka­ge in the tumor region. Both treatments also resulted in reduced BV and PS values, trea­tment with vinblastine was less effective in reducing tumor blood flow than application of electric pulses. The data support the evi­dence on tumor blood flow modifying effect of these two treatments, provided with other methods.12-15 Changes in endothelial cells of microves­sels manifest as contraction of these cells, for­ming intercellular gaps, allowing intravascu­lar fluids and macromolecular solutes to leak into the interstitial space.19 Gd-DTPA in ge­neral promptly enhances tumors.20 Due to its Ivanuäa T et al. / MRI macromolecular contrast agents as indicators of changed tumor blood flow 145 rapid equilibration between intra-and extra-vascular compartments, enhanced tumor ves­sels could not be distinguished. With macro­molecular contrast agent such as gadomer-17 or polylysine-Gd-DTPA, transendothelial pas­sages depend on the size of the molecule. Lar­ger molecules stay within the vessel for a lon­ger period of time, thus enabling differentia­tion of the tumor vessels from the extravascu­lar compartments. This is shown on Figure 1, where highly vascularized tumor rim was en­hanced for a longer period due to the large molecular size of polylysine-Gd-DTPA. Tumor blood flow modifying effect of elec­tric pulses has already been described. It was shown that application of electric pulses lo­cally to the tumor reduces tumor blood flow transiently, returning to almost pretreatment value within 24 hours.14,15 The reduction in tumor blood flow was very quick, reaching 30 % pretreatment value within 1 hour after application of the same set of pulses as used in this study. These data were obtained with rubidium extraction technique, a pharmaco­logical technique measuring plasma flow through the tumor. Confirmed were the data by Patent blue staining technique, which also estimates tumor blood flow. Vinblastine also perturbs tumor blood flow.12,13 Studies de­monstrated that with the same dose of vinbla­stine as used in this study, the onset of redu­ced tumor perfusion after vinblastine was fast, maximal reduction was observed by 1 hour after the treatment, thereafter tumors gradually started to reperfuse. Reperfusion was not completed by 48 hours. The data ob­tained in the present study on tumor blood flow modifying effect of electric pulses and vinblastine are in accordance with the data in the literature.12-15 After both treatments, blo­od flow was reduced and consequently also contrast agent accumulation. The effect of vinblastine was less pronounced than that of applied electric pulses; the degree and durati­on of tumor blood flow reduction was smal­ler. Since the reduction of blood flow with vinblastine was not as severe as with electric pulses, the difference in gadomer-17- and pol-ylysine-Gd-DTPA-enhancement was not as pronounced. Besides gadomer-17- and polylysine-Gd­DTPA-enhanced MRI, Gd-DTPA was also used to evaluate tumor BV and PS in untrea­ted and tumors treated with vinblastine or ap­plication of electric pulses. In the treated tu­mors, BV and PS values failed to highlight the reduction of tumor blood flow. This is also in accordance with literature data.20,21 The accu­racy of the maps in tissues outside central nervous system is questionable because of the high and variable permeability of Gd-DT­PA even in normal tissue.20,21 Earlier reports have described the value of pixel-by-pixel mapping of parameters derived from MRI signal intensity data.8,20 Parame­ters mapped included T1, T2, proton density, diffusion coefficient22, oxygenation23, tempe­rature24, magnetization transfer25, chemical shift26, susceptibility27, electric current28, blo­od flow29, and contrast media.30,31 Our results are based on the use of macromolecular con­trast agents, gadomer-17 and polylysine-Gd-DTPA respectively, that allow quantitative estimation of PS and BV. Small paramagnetic Gd-chelate distribution (Gd-DTPA) can only give qualitative impression.21 ItŐs difficult to speculate, which macromolecular contrast would give better estimate of tumor blood flow reduction, however due to the complete renal clearance gadomer-17 might provide better basis for use in clinical practice. In conclusion, dynamic contrast enhanced MRI showed qualitatively that application of electric pulses to the tumors and systemic tre­atment of animals with vinblastine induced reduction of tumor blood flow, and quantita­tively by means of BV and PS calculations. From the enhancement curves as well as from the BV and PS values, the decrease in tumor blood flow was approximately 40 % more pro­nounced with electric pulses compared to vinblastine. Dynamic contrast enhanced MRI also showed that this reduction was transi­ent, but did not completely return to the valu­es of untreated tumors during the observati­on time. This approach could therefore be used for monitoring the time window and the extent of the tumor blood flow reduction in the tumor after tumor blood flow modifying therapies. Acknowledgement This work was supported by the Ministry of Education, Science and Sport of the Republic of Slovenia. References 1. Brown JM, Giaccia AJ. The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res 1998; 58: 1408-16. 2. Molls M, Vaupel P. Blood perfusion and microenvi­ronment of human tumors. Implications for clinical ra­diobiology. Berlin, Heidelberg, New York: Sprin­ger; 2000. 3. Chaplin DJ, Hill SA, Bell KM, Tozer GH. Modifica­tion of tumor blood flow: Current status and futu­re directions. Semin Radiat Oncol 1998; 8: 151-63. 4. Brasch RC, Weinmann HJ, Wesbey GE. Contrast-enhanced NMR imaging: animal studies using ga­dolinium-DTPA complex. Am J Roentgenol 1984; 142: 625-30. 5. Weinmann HJ, Laniado M, Mutzel W. Pharmaco-kinetics of Gd-DTPA/dimeglumine after intrave­nous injection into healthy volunteers. Physiol Chem Phys Med NMR 1984; 16: 167-73. 6. Shames D, Kuwatsuru R, Vexler V, Muehler A, Brasch R. Measurement of capillary permeability to macromolecules by dynamic magnetic resonan­ce imaging: a quantitative non-invasive technique. Magn Reson Med 1993; 29: 616-22. 7. Kuwutsuru R, Shames D, Muhler A, Mintorovich J, Vexler V, Mann JS, Cohn F, Price D, Huberty J, Brasch RC. Quantification of tissue plasma volu­me in the rat by contrast-enhanced magnetic reso­nance imaging. Magn Reson Med 1993; 30: 76-81. 8. Demäar F, Roberts TPL, Schwickert HC, Shames DM, van Dijke CF, Mann JS, Saeed M, Brasch RC. A MRI spatial mapping technique for microvascu­lar permeability and tissue blood volume based on macromolecular contrast agent distribution. Magn Reson Med 1997; 37: 236-42. 9. Gossmann A, Okuhata Y, Shames DM, Helbich TH, Roberts TPL, Wendland MF, Huber S, Brasch RC. Prostate cancer tumor grade differentiation with dynamic contrast-enhanced MR imaging in the rat: comparison of macromolecular contrast media-preliminary experience. Radiol 1999; 213: 265-72. 10. Seräa I, Medi‰ J, Beravs K, Demäar F. Fast keyhole MR imaging using optimized k-space data acquisi­tion. Electro Magnetobiol 1998; 17: 307-21. 11. Medi‰ J, Tomaěi‰ S, Seräa I, Demäar F. Contrast and resolution considerations in keyhole MRI: ap­plication to dynamic studies of contrast media ki­netics. Electro Magnetobiol 1998; 17: 323-31. 12. Hill SA, Sampson LE, Chaplin DJ. Anti-vascular approaches to solid tumour therapy: evaluation of vinblastin. Int J Cancer 1995; 63: 119-23. 13. Seräa G, Krěi‰ M, áentjurc M, Ivanuäa T, Beravs K, ›emaěar M, Auersperg M, Swartz HM. Reduced tumor oxygenation by treatment with vinblastine. Cancer Res 2001; 61: 4266-71. 14. Seräa G, ›emaěar M, Parkins CS, Chaplin DJ. Tu-mour blood flow changes induced by application of electric pulses. Eur J Cancer 1999; 35: 672-7. 15. Seräa G, ›emaěar M, Miklav‰i‰ D, Chaplin DJ. Tu­mor blood flow modifying effect of electrochemo-therapy with bleomycin. Anticancer Res 1999; 19: 4017-22. 16. Larsson HB, Stubgaard M, Frederiksen JL, Jensen M, Hensriksen O, Paulson OB. Quantification of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. Magn Reson Med 1990; 16: 117-31. 17. Patlak C, Blasberg R, Fenstermacher J. Graphical evaluation of blood-to-brain transfer constants from multiple time uptake data. J Cerebr Blood Flow Metab 1983; 3: 1-7. 18. Demäar F, Shames DM, Roberts TPL, Stiskal M, Roberts HC, Brasch RC. Kinetics of MRI contrast agents with size ranging between Gd-DTPA and albumin-Gd-DTPA: use of cascade-Gd-DTPA-25­polymer. Electro Magnetobiol 1998; 17: 283-97. Ivanuäa T et al. / MRI macromolecular contrast agents as indicators of changed tumor blood flow 147 19. Cotran PS, Kumar V, Robbins SL. Inflammation and repair. In: Robbins SL, Kumar V, eds. Patholo­gic basis of diseases. Vol. 2, 4th ed, Philadelphia: Sa­unders, 1989. 20. Raimo S, Young IR, Wesbey GM. Contrast-enhan­ced NMR imaging: animal studies using gadolini-um-DTPA complex. AJR 1984; 142: 625-30. 21. Su MY, Jao JC, Nalcioglu O. Measurements of va­scular volume fraction and blood tissue permeabi­lity constants with a pharmacokinetik model: stu­dies of rat muscle tumors with dynamic Gd-DTPA enhancement MRI. Magn Reson Med 1994; 32:, 714-24. 22. Taylor DG, Bushell MC. Spatial mapping of tran­slation diffusion coefficients by NMR technique. Phys Med Biol 1985; 30: 345. 23. Lewa CJ, Majewski Z. Temperature relationship of proton spin-latice realxation time T1 in biological tissues. Bull Cancer 1980; 67: 525. 24. Disckinson RJ, Hall AS, Hind AJ. Measurements of changes in tissue temperature using MR ima­ging. J Comput Assited Tomogr 1986; 10: 468. 25. Vahlensieck M, Dombrowski F, Leutner C, Wa­gner U. Magnetization transfer contrast (MTC) and MTC-subtraction-enhancement of cartilage le­sions and intracartilaginous degeneration in vitro. Skeletal Radiol 1994; 23: 535-39. 26. Dixon WT. Simple proton spectroscopic imaging. Radiology 1984; 153: 189. 27. Weisskoff RM, Kihne S. MRI susceptometry-ima-ge-based measurement of absolute susceptibility of MR contrast agents and human blood. Magn Re-son Med 1992; 24: 375-83. 28. Beravs K, Frangeě R, Gerkis AN, Demäar F. Radio-Frequency current density imaging of kainate evo­ked depolarization. Magn Reson Med 1999; 42: 136­40. 29. Dumoulin CL, Hart HR. Magnetic resonance angi­ography. Radiology 1986; 161: 717. 30. Hanna SL, Reddick WE, Parham DM, Groneme-yer SA. Automated pixel-by-pixel mapping of dynamic contrast enhanced MR images for evalu­ation of osteosarcoma response to chemotherapy ­preliminary results. J Magn Reson 1993; 3: 849-53. 31. Kuwatsuru R, Liu T, Cohen F, Shames DM, Osorio RW, Mann J, Rosenau W, Muhler A, Neuder MS, Roberts JP, Brasch RC. Early detection of endothe­lial leak in a rat model using magnetic resonance imaging and a macromolecular contrast medium. Invest Radiol 1994; 29: S297-S99. Rndiol Onco/ 2001; 35(2): 83-8. Preiskava ožilja spodnjih okoncin z dvojnim barvnim Dopplerjem -tipska razvrstitev rezultatov preiskave Brkljacic B, Šebecic B, Grga A, Patrlj L, Hebrang A Izhodišca. V študiji smo tipsko razvrstili rezultate ultrazvocne preiskave ožilja spodnjih okoncin z dvojnim barvnim Dopplerjem. Bolniki in metode. V 27 mesecih smo pregledali 934 bolnikov, 663 žensk (71 %) in 271 moških (29%), starih od 19 do 86 let (povprecna starost 58,4 let). Uporabili smo barvne Dopplerske ci­talnike Acuson 128 XP 10, ATL HDI 500 in Siemensov Sonoline Elegra ter transduktorje s frekvenco od 2,5-12 MHz. Rezultate preiskav smo razvrstili: (a) globoka venska tromboza, (b) pa­tološke spremembe na venah, na katerih nismo odkrili znakov globoke venske tromboze, (c) pa­tološke spremembe na sosednjih strukturah in (d) normalni rezultati. Rezultati. Globoko vensko trombozo smo odkrili pri 210 bolnikih (22,5 %). Pri 129 je bila vens­ka tromboza akutna ali kronicna, pri 81 bolnikih pa je bila prisotna tudi po zdravljenju, saj smo jo odkrili v casu kontrolnih pregledov. Pri 415 bolnikih (44,4 %) smo opazili posttromboticni sin­drom, varikozno razjedo, površinski tromboflebitis ter vensko anevrezmo pod kolenom. Patološke spremembe, ki niso nastale zaradi bolezni ožilja, smo odkrili pri 117 % bolnikih (12,5 %). Najpogostejše spremembe v tej skupini so bile mišicni hematomi in podkolenske ciste, opazili pa smo tudi nekaj zelo redkih patoloških spremmeb. Pri 192 bolnikih (20,6 %) so bili rezultati normalni. Zakljucki. Poleg že znanih in zelo razlicnih patoloških sprememb na ožilju spodnjih okoncin smo pri bolnikih, ki so prišli k nam na ultrazvocno preiskavo ožilja spodnjih okoncin z dvojnim barvnim Dopplerjem, odkrili razmeroma veliko patoloških sprememb, ki niso bile povezane z boleznimi ožilja. Ultrazvocna preiskava ožilja je nujna za prepoznavanje poškodb ožilja, ki klin­ icno spominjajo na globoko vensko trombozo, da ne bi po pomotoma napacno zdravili. Radio/ Oncol 2001; 35(2): 89-93. Sigmoidni diverticulitis: prikaz primera Niyyati M, Varga G, M6r6 Z Izhodišca. Eden od vzrokov akutnega abdomna je diverticulitis, ki ga je vcasih težko prepoznati. Prikaz primera. Predstavljamo primer bolnice z akutnim abdomnom. Ultrazvocna preiskava je pokazala mase z notranjimi odboji, ki so se širili k sigmoidnemu delu debelega crevesa. Sumili smo, da ima bolnica diverticulitis. Kasneje smo diagnozo potrdili s CT preiskavo. Zakljucki. Opisani primer poudarja pomembnost ultrazvocne preiskave, ki predstavlja zacetno slikovno metodo pri ugotavljanju crevesne patologije. Radžo/ Oncol 2001; 35(2): 95-103. Dolocanje razširjenosti bolezni pri bolnikih z melanomom na konvencionalni nacin ali z 18F-FDG-PET Jenicke L, Klutmann S, Bohuslavizki KH, Neuber K, Altenhoff J, Wedler J, Buchert R, Nebeling B, Clausen M Izhodišca. Doslej opravljene predhodne raziskav potrjujejo, da je 18F-FDG-PET (pozitronska emisijska tomografija z 18-deoksifluorglukozo) zelo koristna preiskava za dolocanje razširjnosti napredovalega malignega melanoma. Namen naše raziskave je bil primerjati rezultate slikanja s 18F-FDG-PET ter rezultate konvencionalnega slikanja in klinicnega pregleda bolnikov z malign­im melanomom tako pri primarnem ugotavljanju razširjenosti bolezni kot pri ugotavljanju njene razširjenosti na kontrolnih pregledih. Bolniki in metode. Skupini 35 bolnikov s histološko potrjenim malignim melanomom smo opravili 61 PET preiskav. Ko smo jim vbrizgali 370 MBq +F-FDG, smo poslikali celotno telo z napravo ECAT EXACT 47 (921) z aksialnim vidnim poljem 16,2 cm. Vseh 35 bolnikov smo v štirinajstih dneh po slikanju s 18F-FDG-PET tudi klinicno pregledali in opravili konvencionalne slikovne preiskave, kot so ultrazvocna preiskava, CT in MRI. Na osnovi rezultatov obeh metod za dolocanje razširjenosti bolezni smo bolnike razvrstili v skupine v skladu s klasifikacijo UJCC. Rezultati. Pri primarnem dolocanju razširjenosti bolezni in pri ugotavljanju njene razširjenosti na kontrolnih pregledih s konvencionalnimi metodami smo pri 5 od 35 bolnikov ugotovili, da je bolezen v stadiju I in pri 7 od 35 bolnikov da je v stadiju II. Pri ostalih 23 bolnikih smo sprva dolocili melanom v stadiju III. Na kontrolnih pregledih smo pri 2 od 23 bolnikov ugotovili višji stadij melanoma, in sicer stadij IV. Vsekakor pri primarnem dolocanju razširjenosti bolezni s konvencionalnimi diagnosticnimi slikovnimi metodami pri nobenem od bolnikov nismo ugo­tovili stadija IV. Pri primarnem dolocanju razširjenosti bolezni s preiskavo 18F-FDG-PET pri 9 od 35 bolnikov nis­mo odkrili niti zasevkov v bezgavakah niti oddaljenih zasevkov (stadij 1/11). Pri 21 od 35 bolnikov je obstajal sum na razširjenost zasevkov v bezgavkah, ni pa bilo suma oddaljenih zasevkov (stadij III). Maligni melanom preostalih 5 od 35 bolnikov je bilo opredeljenih kot stadij IV, ker je obstajal sum na oddaljene zasevke. Pri enem od teh bolnikov pa se je ob kontrolnih pregledih izkazalo, da je bila preiskava s 18F-FDG-PET lažno pozitivna zato smo ga razvrstili v nižji stadij (stadij III). V primerjavi s konvencionalnimi slikovnimi diagnosticnimi metodami smo s preiskavo 1 SF­FDG-PET pri primarnem dolocanju razširjenosti bolezni in pri ugotavljanju njene razširjenosti pri kontrolnih pregledih dolocili enak stadij melanoma pri 17 od 35 bolnikov (49 %), pri 14 (40 %) smo dolocili nižji stadij in pri 4 (11 %) višjega. Z oziram na anatomsko mesto metastatskega raz­soja smo s preiskavo PET najvec lažno negativnih diagnoz postavili za zasevke v tistih bez­gavkah, ki ležijo najbližje kožni površini. Zakljucki. Naši rezultati potrjujejo dodatno vrednost 18F-FDG-PET pri dolocanju razširjenosti bolezni malignega melanoma. Ker je nacin zdravljenja predvsem odvisen od klinicno ugotovjene razširjenosti bolezni, nam lahko 18F-FDG-PET odlicno pomaga pri izbiri vrste zdravljenja za posamicnega bolnika. Radio/ Oncol 2001; 35(2): 105-10. CT primerjava primarnega ledvicnega karcinoma in metastaz v ledvicah Prkacin I, Naumovski-Mihalic S, Dabo N, Palcic I, Vujanic S, Babic Z Izhodišca. Prirnejali srno rezultate preiskav z racunalniško tomografijo (CT) pri bolnikih s pri­marnim ledvicnim karcinomom z bolniki z metastazami v ledvicah, da bi ugotovili razlike, ki se kažejo na CT posnetkih. Bolniki in metode. Preiskavo srno opravili na 25 bolnikih, od katerih jih je bilo 10 s patološko potrjenimi metastazami v ledvicah in 15 s primarnim ledvicnim karcinomom. Dve minuti po in­travenoznem vbrizgu kontrasta srno zaceli s slikanjem. Pri analizi rezultatov preiskav srno upoštevali standardna merila za oceno CT posnetkov s kontrasti. Rezultati. Pri razlocevanju primarnega ledvicnega karcinoma od ledvicnih metastaz je bila obcutljivost CT preiskave 98-odstotna, pri razlocevanju ledvicnih metastaz od ledvicnega karci­no,i:na pa 70-odstotna. ·Zakljucki.V študiji srno ugotovili, da je CT preiskava v klinicni praksi lahko koristno orodje za razlikovanje med primarnim ledvicnim karcinomom in metastazami v ledvicah. Radio/ Oncol 2001; 35(2): 111-5. Možnosti sodobnega zdravljenja karcinoma debelega crevesa in danke Yovtchev Y, Nikolov S Izhodišca. Tudi danes zdravimo karcinom debelega crevesa in danke kirurško ter s kerno-in ra­dioterapijo. V zadnjih letih pa so razvili nove metode, ki jih uspešno uporabljamo v onkologiji. Te metode so uporaba specificnih protiteles, uporaba encimov in zdravil vezanih na protitelesa, uporaba radioirnunokonjugatov in radioirnuno vodena kirurgija. Zakljucki. Z novimi metodami lahko pri bolnikih s karcinomom debelega crevesa in danke po­daljšamo preživetje brez znakov bolezni, zmanjšamo umrljivost in izboljšamo kvaliteto življenja. Radio/ Oncol 2001; 35(2): 117-26. Radikalno obsevnje prostate v kombinaciji s perkutanim obsevanjem in implantacijo prostate z LDR Ir 192 Kragelj B, Guna F, Burger J Izhodišca. Obsevanje prostaticnih karcinomov z dozami višjimi od še sprejemljivih doz ob kla­sicni radioterapiji izboljša lokalno kontrolo bolezni. Namen študije je bil ugotoviti akutno to­ksicnost ter sprejemljivost visokodoznega obsevanja prostate s kombinacijo perkutanega obse­vanja in intersticijske brahiradioterapije, kjer smo implantacijo prostate izvedli z Ir 192, ki je imel nizko hitrost doze (LDR). Materija! in metode. Pregledali smo dokumentacijo 8 bolnikov z lokaliziranimi karcinomi pro­state (T2-3 NO-X M0). Izhodna vrednost PSA je bila 2,7 -37,5 (mediana 13,7) ng/ml., tockovanje po Gleasonu pa 4-9 (mediana 7). Zdravljeni so bili od avgusta 1999 do februarja 2000 s kombi­nacijo perkutanega obsevanja prostate in seminalnih vezikul (4 bolniki) oziroma mednicnega po­drocja (4 bolniki) s 48.6 -50,4 Gy ter intersicijskega obsevanja prostate LDR IR-192 z 20,0 do 28,0 Gy. Rezultati. Akutni stranski ucinki obsevnja, ki so se pojavili pri vseh bolnikih, so bili neizraziti -glede na RTOG kriterije je pri 20 od 30 bolnikov ocenjeno kot 1. stopnje, pri 9 od 30 2. stopnje in pri 1 od 30 bolnikov 3. stopnje. Pri nobenem bolniku ni bilo potrebno prilagajati zdravljenja zaradi stranskih ucinkov. Zakljucki. Zacetne izkušnje kažejo na zmerno toksicnost ter optimalno sprejemljivost kombina­cije perkutanega obsevanja in implantacije z LDR Ir 192. Tehniko implantacije bi lahko izboljšali z rednimi CT kontrolami implantata in z dodatno pozornostjo pri uvajanju igelj v podrocje ob uretri. Radio/ Oncol 2001; 35(2): 127-31. Razvrstitev bolnikov z možganskimi metastazami v skupine, ki jih priporoca RTOG analiza, s poudarkom na prognosticno slabe bolnike Willfurth P, Mayer R, Stranzl H, Prettenhofer U, Genserc B, Hackl Arnulf B Izhodišca. Namen naše raziskave je bilo ugotoviti, ali je razvršcanje bolnikov v skupine, ki jih priporoca RTOG analiza (RPA) koristno za nadaljnjo odlocanje, kako zdraviti bolnike z možgan­skimi metastastazami. Bolniki in metode. Retrospektivno smo analizirali 57 bolnikov in 48 bolnic, ki smo jim pred­hodno obsevali možgane s skupno tumorsko dozo 30 Gy / 3 Gy dnevno / 5 krat na teden. Bolnike, pri katerih smo možganske metatstaze zdravili tudi kirurško ali z radiokirurgijo, smo izkljucili iz študije. Obravnavane bolnike smo razvrstili v skupine glede na stanje splošne zmogljivosti po Karnofskem (KPS) in glede na starost (skupina I: KPS = 70, starost < 65, nad­zorovan primarni tumor, brez drugih oddaljenih metastaz; skupina II: bolniki, ki niso razvršceni v skupino I ali III; skupina III: KPS < 70). Rezultati. Verjetnost šest in dvanajstmesecnega preživetja za skupine I, II in III je bila 80 %/44 %, 43 %/17 % in 6 %/0 %. Z multivariantno analizo smo ugotovili, da sta na preživetje vplivala pred­vsem KPS in rast primarnega tumorja, ne pa starost bolnikov. Zakljucki. Menimo, da je razvršcanje bolnikov v skupine, kot ga priporoca RTOG analiza (RPA), koristno. Bolnike, ki smo jih razvrstili v skupino III, lahko zaradi kratkega preživetja casa zdrav­imo s krajšim nacinom obsevanja. Radio! Oncol 2001; 35(2): 133-7. Predvidevanje ponovitve bolezni pri bolnicah z rakom dojke, stadij I Baitchev G, Gortchev G, Velkova A, Deliisky T Izhodišca. V naši retrospektivni študiji smo želeli ugotoviti, ali lahko s šestimi klasicnimi napovednimi dejavniki predvidimo preživetje brez znakov bolezni pri bolnicah, ki smo jih zdravili zaradi raka dojke, stadij I. Bolniki in metode. Proucevali smo 181 bolnic, ki smo jih kirurško zdravili v obdobju med 1991 in 1995.Opredelili smo velikost tumorja, histološki tip, invazijo v limfne. in krvne žile, malig­nostno stopnjo tumorja, hormonske receptorje in starost bolnic. Želeli smo ugotoviti soodvis­nost med temi napovednimi dejavniki in ponovitvijo bolezni. Rezultati. Pri 4 bolnicah (2,2 %) se je bolezen ,ponovila lokoregionalno, pri 6 (3,3 %) pravtako lokoregionalno, vendar z oddaljenimi zasevki, pri 13 (7,2 %) pa z oddaljenimi zasevki. Rezulati univariatne analize so potrdili, da so statisticno znacilno povezani s preživetjem brez znakov bolezni naslednji napovedni dejavniki: veliko_st tumorja, starost bolnic ter tumorska,invazija v limfne in krvne žile. Rezultati multivariatne analize pa so pokazali statisticno zelo pomembno = soodvisnost med preživetjem brez znakov bolezni ter starostjo (p 0,007) in tumorsko ipvazija v limfne in krvne žile (p = 0,00001), medtem ko velikost tumorja ni bila vec statisticno znacilno povezana s preživetjem (p 0,067). = Zakljucki. V razsikavi smo ugotovili, da naslednji trije hkrati uporabljeni napovedni dejavniki, kot so velikost tumorja, tumorska invazija v limfne in krvne žile in starost bolnic, lahko zanesljiveje predvidijo ponovitev bolezni po zdravljenju raka dojke v stadiju TlN0M0. 155 Radio/ Oncol 2001; 35(2): 139-47. Uporaba kontrastno povdarjenega dinamicnega MR slikanja za spremljanje pretoka krvi v tumorjih Ivanuša T, Beravs K, Cemažar M, Jevtic V, Demšar F, and Serša G Izhodišce. Dinamicno slikanje z magnetno resonanco je diagnosticna metoda, ki omogoca pri­kaz in vrednotenje prekrvavljenosti tumorjev. Namen naloge je bil z makromolekularnimi kon­trastnimi sredstvi spremljati zmanjšanje pretoka krvi v mišjih fibrosarkomskih tumorjih po apli­kaciji elektricnih pulzov ali zdravljenju z vinblastinom. Materiali in metode. Permeabilnost tumorskega žilja (PS) in prekrvljenost tumorskega tkiva (BV) smo ocenjevali na nivoju tockovnih elementov MR signala po aplikaciji dveh prototipov makro­molekularnih kontrastnih sredstev: gadomer-17 in polilizin-Gd-DTP A, ki za razliko od nizko mo­lekularnega gadolinija (Gd-DTPA) omogocajo prikaz tumorskega žilja. PS in BV netretiranih tu­morjev smo primerjali z PS in BV vrednostimi tumorjev, katerim smo aplicirali elektricne pulze ali jih zdravili z vinblastinom. Rezultati. Oba nacina zdravljenja sta znacilno zmanjšala pretok krvi v tumorjih. Aplikacija elek­tricnih pulzov pa je bila za 40 % ucinkovitejša v zmanjšanju pretoka krvi v tumorjih kot sistem­ ska aplikacija vinblastina. PS in BV vrednosti za polilizin-Gd-DTPA so bile nižje kot vrednosti za gadomer-17 (30 kDa), kar pojasnjujemo z velikostjo molekul polilizina-Gd-DTPA(50 KDa). Zanimivo je, da PS in BV vrednosti kontrastno podarjenega dinamicnega MR slikanja z gadoli­nijem niso pokazale znacilne razlike med netretiranimi in zdravljenimi tumorji. Zakljucek. Rezultati raziskave utemeljujejo uporabo kontrastno povdarjenega dinamicnega MR slikanja za spremljanje pretoka krvi v tumorjih in kvantitativno dolocanje PS in BV vrednosti. Notices Notices submitted for publication should contain a mailing address, phone and/ or fax number and/or e-mail oj a Contact person or department. Radiology July 5-7, 2001 The course "Abdominal Imaging and Intervention 2001 -State of the Art and New Developments" orga­nised by John Hopkins University School of Medicine will be held in Salzburg, Austria. Contact Ms Edeltraut Treptow, Radiologische Uni­versitaetsklinik, Department of Diagnostic Radiology, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany; or call +49 7071 298 6676; or fax +49 7071 295 845; or e­mail edeltraut.treptow@med.uni-tuebingen.de Radiophysics September 17-22, 2001 The "6th Biennial ESTRO Meeting on Physics for Cli­nical Radiotherapy" and the "6th ESTRO Meeting on Radiation Technology for Clinical Radiotherapy" will be held in Sevila, Spain. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Life sciences September 22-26, 2001 The international conference "Life Science 2001" organised by Slovenian Biophisical Society will be held in Gozd Martuljek, Slovenia. Contact Dr. Marjeta Šentjurc, Laboratorij za biofizi­ko -EPR center, Institut "Jožef Štefan", Jamova 39, SI­1000 Ljubljana, Slovenia; or call +386 1 477 36 89; or fax +386 1 436 32 69; or e-mail Is2001@ijs.si; or see In­ternet http://www.drustvo-biofizikov.si/Is2001/ Gastro-intestinal malignancies October, 2001 The ESO training course will be offered in Cairo, Egypt. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 Ioannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Pediatric oncology October, 2001 The ESO training course will be offered in Trabzon, Turkey. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 Ioannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Breast cancer October 4-6, 2001 The ESO training course will be offered in Sarajevo, Bosnia and Herzegovina. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 loannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Radiotherapy October 7-11, 2001 The ESTRO teaching course "Evidence-Based Radi­a tion Oncology: Principles & Methods" will take place in Cairo, Egypt. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiotherapy October 7-11, 2001 The ESTRO teaching course "Basic Clinical Radiobi­ology" will take place in Tenerife, Spain. Contact ESTRO office, Av. E. Mounier, 83/ 4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Rena! carcinoma October 9-11, 2001 The ESO training course "Rena! Carcinoma" will be offered in Moscow, Russia. Contact M. Vukelic, CSC Ltd., Heligenstadter Stras­se 395b, 1190 Vienna, Austria; or call +43 1 369 0444; or fax +43 1 369 0444 20. Malignant lymphoma October 19-20, 2001 The ESO training course will be offered in Nicosia, Cyprus. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 Ioannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Radiation therapy October 21-25, 2001 The "20th Annual ESTRO Meeting / ECCO 11 Mee­ting" will take place in Lisbon, Portugal. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; web: http://www.es­tro.be Lymphoma October 26-28, 2001 The ESO training course "Non Hodgkin's Lympho­ma, Patho-Biology, Classification and Clinical Rele­vance" will be offered in Cairo, Egypt. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 Ioannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Clinical trials November, 2001 The ESO training course will be offered in Ioannina, Greece. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 Ioannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Psycho-oncology November, 2001 The ESO training course will be offered in Nicosia, Cyprus. Contact ESO office for Balkans and Middle East, N. Pavlidis, E. Andreopoulou Medica! School, Depar­tment of Medica! Oncology, University Hospital of Io­annina, 45110 Ioannina, Greece; or call +30 651 99394 or +30 953 91083; or fax +30 651 97505 Radiation therapy November 4-7, 2001 ASTRO Annual meeting will be held in San Franci­sco, California, USA. Contact American Society for Therapeutic Radio­logy and Oncology Office, 1891 Preston White Drive, Reston, VA 20191, USA; web site: www.astro.org Neck and thyroid surgery November 5-7, 2001 The master course will be offered in Milan, Italy. Call P. Lonati +39 (0)257 489 490; or fax +39 (0)257 489 589 491; or e-mail head&neck@ieo.it Cancer risk November 12-13, 2001 The ESO conference "Reducing Cancer Risk. Focus on the four big killers" will take place in New York, USA. Contact ESO Office, Viale Beatrice d'Este 37, 20122 Milan, Italy; or call +39 0258317850; or fax +39 0258321266; or e-mail esomi@tin.it Notices 159 Lung cancer December 6-8, 2001 The International Forum for Lung Cancer will be of­fered in Athens, Greece. Contact Congress Secretariat -Organising Bureau, "MOEL" Ltd, 36, Eleon str. -GR 14564, Nea Kifissia, Greece; or call +301 6203 614; or fax +301 8078 342; or e-mail liagramo@internet.gr Lung cancer March 14-15, 2002 The IASLC international workshop "Early Invasive Lung Cancer. New Diagnostic Tools & Treatment Stra­tegies will be offered in Turin, Italy. Contact Organising Secretariat, CCI Centra Con­gressi Internazionale srl, Via Cervino 60, 10155 Turin, Italy; or call +39 011 244 69 16; or fax +39 011 244 69 00; or -mail info@congressiefiere.com Radiotherapy May 9-11, 2002 The Annual Brachytherapy Meeting GEC/ESTRO will take place in Antalya, Turkey. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiation therapy May 15-19, 2002 The 7th International Meeting on Progress in Radio­Oncology tcRO/.;.GRO 7 will take place in Salzburg, Austria. Contact Prof. D.H. Kogelnik, Salzburg, Austria; call +43 662 44823900; or fax +43 662 4482887; or e-mail d.kogelnik@lkasbg.gv.at Radiation therapy September 15-19, 2002 The 21st Annual ESTRO Meeting will take place in Prague, Czech Republic. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; web: http://www.es­tro.be Radiation therapy October 6-9, 2002 ASTRO Annual meeting will be held in New Orle­ans, Louisiana, USA. Contact American Society for Therapeutic Radio­logy and Oncology Office, 1891 Preston White Drive, Reston, VA 20191, USA; web site: www.astro.org Radiation therapy September 21-25, 2003 The ESTRO 22 / ECCO 12 Meeting will take place in Copenhagen, Denmark. Contact FECS office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; web: http://www.fecs.be Radiation therapy October 19-23, 2003 ASTRO Annual meeting will be held in Salt Lake City, Utah, USA. Contact American Society for Therapeutic Radio­logy and Oncology Office, 1891 Preston White Drive, Reston, VA 20191, USA; web site: www.astro.org Radiation therapy September 12-16, 2004 The 23rd AnnuafESTRO Meeting will be held. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; web: http://www.es­tro.be Radiation therapy October 3-7, 2004 ASTRO Annual meeting will be held in Atlanta, USA. Contact American Society for Therapeutic Radio­logy and Oncology Office, 1891 Preston White Drive, Reston, VA 20191, USA; web site: www.astro.org As a service to our readers, notices of meetings or co­urses will be inserted free of charge. Please sent information to the Editorial office, Radio­logy and Oncology, Zaloska 2, SI-1000 Ljubljana, Slo­venia. Radio/ Oncol 2001; 35(2): 157-9. FONDACIJA "DOCENT DR. J. CHOLEWA" JE NEPROFITNO, NEINSTITUCIONALNO IN NESTRANKARSKO ZDRUŽENJE POSAMEZNIKOV, USTANOV IN ORGANIZACIJ, KI ŽELIJO MATERIALNO SPODBUJATI IN POGLABLJATI RAZISKOVALNO DEJAVNOST V ONKOLOGIJI. MESESNELOVA 9 1000 LJUBLJANA TEL O 1 51 9 1 2 77 FAKS 01 251 81 13 ŽR: 501 00-620-1 33-05-1 0331 1 5-2 14 779 FONDACIJA DR. J. CHOLEWA Activity of "Dr. J. Cholewa" f oundation f or Cancer Research and Education -A Report f or the First quarter of 2001 The activity of the Executive and Advisory Boards of thc "Dr. J Cholcwa" Foundation for cancer rcscarch and cdu­cation in the year 2000 and to the time of the present report continued to focus on the solution of financial problems connected with thc financial inflow and the usc of the funds availablc. It was noted that thc attention of possible do­nors had been directed elsewhere, especially to sponsoring various sports activities, an understandable shift in the year 2000, since many of the would-be sponsors decided to help the participants of the Olympic gamcs in Sydney that year. However, the Foundation continued to receive support from many of its long-time supporters in Slovenia, especially from Krka pharmaceutical company from Novo Mesto, Pivovarna Laško brewery from Laško, NLB bank from Ljubljana, SKB bank from Ljubljana, NKBM bank from Maribor, Sanolabor company from Ljubljana, Droga fo­od processing company from Portorož, and many others. The Foundation continues to support the regular publication of "Radiology and Oncology" international scienti­fic journal, that is edited, published and printed in Ljubljana, Slovenia. The support for the publication of the "Chal­lengc Newsletter" will be re-evaluated shortly. In the year 2000 the Foundation also contributed support to the orga­nisation of the traditional "Oncolct,,y Weekend" mectings, the annual "Plecnik Memorial Meeting", dedicated to ho­nour the anniversary of Professor Vinko Kambic, one of the Founding members of the Foundation and who among many other honours also received the Honorary Award of the Foundation at the special ceremony held at the Medi­ca! Faculty of thc University of Ljubljana. The Foundation also supported the organisation of thc congress of "Slove­nian Association of Genetics" held in Bled, Slovenia. The members Executive and Advisory Boards unanimously agreed to accept three new members into the Foun­dation. The new members are Igor Bartcnjev, MD, PhD, from thc Dermatologi, Clinic in Ljubljana, Janez @'agar, MD, MSc, from the Institute of Oncology in Ljubljana, and Rado Janša, MD, from the Gastroenterology Clinic in Ljublja­na. All three new members had their biography and scientific bibliography data presented to thc mcmbers of the Fo­undation and are welcornc to take an active part in its various activities. Thc members of thc Executive and Advisory Boards are honoured to announcc that on April 19th, 2001, the 1-lo­normy Award of thc "Dr. J. Cholcwa" Foundation for cancer rcsearch and education was presented to Mr. Anton Turnšek, in recognition of his merits associated with the activity of the l'oundation. Mr. Turnšek is a highly respec­ted businessman and an expert in food and beverages processing, and is presently thc Director of the Pivovarna Laško brewe1y, one of the most succcssful and propulsive food and bevcrages companies, and companies in gene­ral in Slovenia. He is a recipient of many prestigious awards, including those by the Chambcr of Commerce of Slo­venia. Mr. Turnšek is one of the founding members of the "Dr. J. Cholcwa" Foundation for cancer research and edu­cation, and especially in the beginning of the activity of the Foundation his experience in dealing with many of the related problcms proved to be invaluablc. The Foundation moved back to its original headquarters in Mesesnelova Street No. 9 in Ljubljana in thc begin­ning of the ycar 2001. This decision was taken to streamline thc cxpenses associated with the day to day activity of the Foundation and was also conveyed to the relevant City of Ljubljana authorities. It is one of the measures of the Foundation taken to facilitatc the access to oncology research and education support to as many interested indivi­duals and institutions in various regions of Slovenia as possible. New approachcs to achieve the enhancement of the knowledge in cancer prevention and early detection ali over the country will possibly bc evaluated. As it has been mentioned many times before, special attention will be givcn to the requests coming from the regions of Slovenia outside Ljubljana to provide grants far the participation of Slovenian oncologists and others on various educational meetings in the country and abroad. Tomaž Benulic, MD Borut Štabuc, MD, PhD Andrej Plesnicar, MD, MSc .. MEDITRADE d.o.o. Vodovodna 100 1000 Ljubljana, Slovenija Tel.: 01 5894 600 Fax: 01 5684 340 www.meditrade.si Zastopamo: Radiološki program firme Kodak Medicinsko opremo firme Marconi CT, MRI, IM Negatoskope firme Ella Roloskopi firme Planilux Mamografska oprema firme Metaltronica htrlXAGfrJST Are your radiographers' hands tied by equipment that slows them down? And what can ydu do about it? Nearly 70% of X-rays are made at a Bucky. A fact rhat has influenced rhe design of Philips' Bucky sysrems. It's led to technology without gadgetry, for uncomplicated, speedy work. Concrol units operated one-handed. A display rhat eliminates trips to rhe generator. Tomography funcrions activared via a single button. All to speed pacient throughput, for impr;wed cosr-efficiency. lt's one way in which Philips Medica! Systems is working with you to meet roday's changing healrhcare needs. For more information call 061 177 88 50. website: www.phlllps.com/ms - - 11111 kapsule v svetu najvec predpisovani sistemski( antimikotik edini peroralni sistemski antimikotik za zdravljenje vaginalne kandidoze, ki ga je odobril FDA Skrajšano navodilo Flukonazol je sistemski antimikotik iz skupine triazolov. Odmerjanje pri razlicnih indikacijah: vaginalna kandidoza 150 mg v enkratnem odmerku mukozna kandidoza 50 do 100 mg na dan dermatomikoze 50 mg na dan ali 150 mg na teden sistemska kandidoza prvi dan 400 mg, nato od 200 do 400 mg na da_n Najvecji dnevni odmerek je 800 mg. nrPnrPrPv<>niP kandidoze 50 do 400 mq na dan kriptokokni meningitis prvi dan 400 mg, nato od 200 do 400 mg na dan vzdrževalno zdravljenLe 200 mg_ na dan Kontraindikacije: Preobcutljivost za zdravilo ali sestavine zdravila. Interakcije: F'rL.;{kf;t;;. odmerku flukonazola za zdravljenje vaginalne kandidoze klinicno poinenJbnih lnte(al1o Pri veckratnih in vecjih odmerkih so možne interakcije s terfenadiqom, cisilpriddr varfarinom, derivati sulfonilureje, hidroklorotiazidom, fenitolnom, .rifainplcinom, teofilinom, indinavirom in midazolamom. Nosecnost in dojenje: NosecnicaJahk< le, ce je korist zdravljenja za mater vecja od tveganja za plod. Dojece rna\erenajm s flukonazolom ne dojijo. Stranski ucinki: Povezani so 1 napenjanje, bolecine v trebuhu, driska, zelo redko se p . . . anafilaksija in angioedem v tem primeru takoj prenehamo jemali _zdra glivicnimi obolenji lahko pride do levltr.bnO· do..o/pten,ašanje/ . . .. ·•····PtfJd predpis.vanje.i.Rrosi!11(), • preberite .. 11av<>di. · · · · · . · to za uporabo .. ;t.cirC>;b..i'še 1ht:;.ac;ij. AšfraZeneca UKL.imifed so na r'azpolago pri: . Pod(užnic.a v Slov.niji Einspielerjeva. 6 1000, Ljublj.na tet: (01) 436 97 1.3 taks: (01) 436 97 02 e-pošta: astrazeneca@siol.net 1f?o/! u/o/ ?vtd . rouf av111 a17vw?1d o CHALLENGE roNDAc1JA 1 A publication of the Slovenian "Doc. J. Cholewa" ooc.J.cHmwA Cancer Research Foundation, Ljubljana, Slovenia President: S. Fatur (Ljubljano, Slovenio) 03 {,-&l Editor: S. Plesnicar (Ljubljano, Slovenio) Editorial Board: M.S. Aopro, (Genolier, Switzerland) F. Ben Ayed, (Tunis, Tunisio) ­ F. Covolli, (Bellinzono, Switzerlond) -A. Costo, (Milano, ltaly) ­ N. Gad-EI-Movla, (Cairo, Egypt) -A. Ghawomzadeh, (Tehran,.lran) ­ C. Gupta, (Mumbai, Indic) -S. Kadare, (Tirana; Albania)-,-l. Mitra, (Mumbai, Indic) -O. Lopez Bascope, (Cochabamba, Bolivia) ­ N. Pavlidis, (lonnina, Greece) -D. Ra'ad, {Amon, Jordan) Language Reader: William Russel -Edu, (Milano, ltaly) 03 . &l Editorial Office: "Challenge" Slovenian "Doc. J. Cholewa" Cancer Foundation c/o S. Plesnicar, Tesarska Str. No. 6, 1101 Ljubljana, Slovenia. Tel./Fax: ++386.(0)1.25.18.066 Design: N. Tomažin, Ljubljana, Slovenia Printed by: PREPRESS, Ljubljana, Slovenia Printed in 1000 copies 03 . &l VOL II, N. 2, SPRING/SU/vVv\ER 2000 CONTENT: EDITORIAL: A turning Point ORIGINAL ARTICLES Time Trend of Cancer Frequency in lbadan, Nigeria (Thomas J) 5 My Work in an underprivileged Part of Nigeria. Personal Viewpoint (Geragthy JG) 9 HIV-Related Tumours in Northern Uganda (Rizzardini G, Declich S and Lukwiya M) 11 ----·----­ A Glimpse on the Cancer Problem in Latin America from a Central European Perspective. II. (Plesnicar AF) 14 ________ _ REPORTS IN BRIEF -Malignancies in HIV /Patients -Malignancies in Children with HIV / AIDS -On Cervical Cancer in Africa -Selected Summaries from African Continent ----------··--·­ ADVANCES IN RESEARCH -Translational Cancer Research -Breast Cancer in Elderly 3Q_______ -···­ HEALTH ECOLOGY -Smoli Countries and the Dioxin Scandal: How to Control lmported Food? A Summary 32 ______ _ REVIEW -OIP 3/99, Oncology in Practice -Lung cancer, Last issue 33 FORTHCOMING EVENTS AND ANNOUNCEMENTS Congresses and Meetings 36 .o 6. 1 1 1 zz >0 oz U) 8 LL u o °" z. o. C) .. uw :=; u z co z 2;5 _:, 0 1 1 1 u o 1 1 <:C I u VOL II, N. 2, SPRING/SUMlv\ER 2000 Radiology and Onco/ogy Instructions f or authors Editorial policy of the journal Radiology and Oncology is to publish original scientific pa­pers, professional papers, review articles, case reports and varia (editorials, reviews, short communications, professional information, book reviews, letters, etc.) pertinent to diag­nostic and interventional radiology, computer­ized tomography, magnetic resonance, ultra­sound, nuclear medicine, radiotherapy, clinical and experimental oncology, radiobiol­ogy, radiophysics and radiation protection. The Editorial Board requires that the paper has not been published or submitted for publica­tion elsewhere: the authors are responsible for ali statements in their papers. Accepted arti­cles become the property of the journal and therefore cannot be published elsewhere with­out written permission from the editorial board. 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