ADIOLOGY ,.,.11 NCOLOGY March 2001 Vol. 35 No. 1 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 AND NCOLOGY Editorial office Radiologij and Oncology Institute oj Oncologtj Zaloška 2 SI-1000 Ljubljana Slovenia Plwne: +386 1 4320 068 Phone/Fax: +386 1 4337 410 E-mail: gsersa@onko-i.si Aims and scope Mnrch 2001 Vol. 35 No. 1 Pages 1-82 JSSN 1318-2099 UDC 616-006 CODEN: RONCEM Radiology and Oncology is a journal devoted to publicntion oj original contributions in diagnostic and interventional radiology, computerized tomography, ultrasound, nrngnetic resonance, nuclear medicine, radiotherapy, clinicnl and experimental oncologtj, radiobiologtj, radiophysics and radia/ion protection. Editor-in-Chief Gregor Serša Ljubljana, Slovenia Executive Edi tor Viljem Kovac Ljubljana, Slovenia Editorial board Marija Auersperg Ljubljana, Slovenia Nada Bešenski Zagreb, Croatia Karl H. Bolmslavizki Hamburg, Gennnny Haris Boka Zagreb, Croatia Nataša V. Budihna Ljubljana, Slovenia Marjan Budihna Ljubljana, Slovenia Malte Clausen Hamburg, Gennany Christoph Clemm Miinchen, Germany Mario Corsi Udine, ltaly Christian Dittrich Vienna, Austria Ivan Drin/covic Zagreb, Croatia Gillian Duchesne Melbourne, Australia Editor-in-Chief Emeritus Tomaž Benulic Ljubljana, Slovenia Edi tor Uroš Smrdel Ljubljana, Slovenia Bela Fornet Budapest, Hungary Tullio Giraldi Trieste, Jtaly Andrija Hebrang Zagreb, Croatia Laszl6 Horvath Pecs, Hungary Berta Jereb Ljubljana, Slovenia Vladimir Jevtic Ljubljana, Slovenia H. Dieter Kogelnik Salzburg, Austrin Jurij Lindtner Ljubljana, Slovenia Ivan Lovasic Rijeka, Cron tia Marijan Lovrencic Zagreb, Croatia Luka Milas Houston, USA Metka Milcinski Ljubljana, Slovenia Maja Osmak Zagreb, Croatia Branico Palcic Vancouver, Canada Jurica Papa Zagreb, Croatia Dušan Pavcnik Portland, USA Stojan Plesnicar Ljubljana, Slovenia Ervin B. Podgorša/c Montreal, Canada Jan C. Roos Amsterdam, Netherlands Slavko Šimunic Zagreb, Croatia Lojze Šmid Ljubljana,Slovenia Borut Štabuc Ljubljana, Slovenia Andrea Veronesi Aviano, Italy Živa Zupancic Ljubljana, Slovenia Publisher Association of Radiologij and Oncology Affiliated with Slovenian Medica/ Association -Slovenian Association of Radiology, Nuclear Medicine Society, Slovenian Society far Radiotherapy and Oncology, and Slovenian Cancer Society Croatian Medica/ Association -Croatian Society of Radiologij Societas Radiologorun1 Hungarorum Friuli-Venezia Giulia regional groups of S.I.R.M. (Italian Society of Medica/ Radiology) Copyright © Radiology and Oncology. 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]BAS12X Subscription fee far institutions $ 100 (16000 SIT), individuals $ 50 (5000 SIT) The pub/ication of this joumal is subsidized by the Ministry of Science nnd Technology 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 March 2001 UDC 616-006 Vol. 35 No. 1 CODEN: RONCEM CONTENTS INTERVENTIONAL RADIOLOGY Biliary small intestinal submucosa covered Z-stents: Preliminary results in an animal model Yamakado K, Pavcnik D, Uchida BT, Timmermans H, Corless CL, Park JW, Yamada K, Keller FS, Rosch J 1 RADIOLOGY AND SONOGRAPHY Diagnostic imaging of hypertrophic pyloric stenosis (HPS) Frkovic M, Šeronja Kuhar M, Perhoc Ž, Barbaric-Babic V, Molnar M, Vukovic J 11 Computer system for determination of pressure distribution in the hip joint articular surface: validation and results Stankovski V, Smrke S 17 NUCLEAR MEDICINE Bone scintigraphy in clinical routine Miiller V, Steinhagen ], de Wit M, Bohuslavizki KH SONOGRAPHY Ultrasonography of pleural effusion: the quantification of rninimal detectable volume Šuštic A, Medved I, Kovac D, Ivaniš N, Ekl D, Šimic O ONCOLOGY Intraoperative radiation therapy (IORT) of the tumor bed only for breast cancer: technique and outcome Proulx CM, Hurd T, Lee RJ, Stomper PC, Podgorsa/c MB, Edge SB 35 Sentinel lymph node identification in early breast cancer -peritumoral or subareolar injection of lymphotropic blue dye? Baichev G, Sergieva S, Gorchev G 43 What is current practice in soft tissue sarcoma grading? Golouh R, Braclco M 47 RADIOPHYSICS Upgrading of gamma cameras for developing countries Fidler V, Prepadnik M, Xie Y 53 Design considerations for direct and indirect active matrix fiat-panel portal images Lachaine M, Fallone BG 63 SLOVENIAN ABSTRACTS 73 NOTICES Biliary small intestinal submucosa covered Z-stents: preliminary results in an animal model Koichiro Yamakado 1,3, Duäan Pav‰nik 1, Barry T Uchida 1, Hans Timmermans 1, Christopher L. Corless 2, Joong Wha Park 1, Katsuyuki Yamada 1, Frederic S. Keller 1, Josef Risch1 1 Dotter Interventional Institute, Oregon Health Science University, Portland, Oregon, 2 Department of Pathology, Oregon Health Science University and Portland Veterans Administration Medical Center, Portland, Oregon, USA, 3 Mie University School of Medicine, Japan Background. Purpose of the study was to test the function and biological response of metallic stents cov­ered with small intestinal submucosa (SIS) in the swine biliary system. Materials and methods. A total of 9 SIS-covered single Z-stents were placed in the common bile duct (CBD) in 6 pigs. Stents were delivered into the CBD at laparotomy via the gall bladder and the cystic duct. Animals were sacrificed or died at 2 weeks (n=1), 4 weeks (n=1), 8 weeks (n=2), and 10 weeks (n=2) after stenting and histological studies were performed. Results. Nine stents were deployed in 6 animals. During follow-up, 3 stents in 3 animals (2, 4, and 10 weeks) remained stable, while one stent shifted distally in CBD and 5 of them turned sideways. All stents remained patent. Duct dilatation and bile slugging were noted at 10 weeks. The SIS-membrane was present at 2 weeks, but was not histologically distinct at 4 weeks and later. Histological study showed no significant inflammatory changes in the bile duct in any pig. Mucosal hyperplasia was absent in 2 of 3 stable stents at 2 and 10 weeks, and 1 distally shifted stent at 10 weeks. Mild mucosal hyperplasia was seen at the distal stent end in 1 stable stent at 4 weeks and in 5 dislodged stents at 8 and 10 weeks. Conclusions. Even when the study is limited by dislodgment of high percentage of placed stents, the results in stable stents conducting the bile flow suggest that SIS helps to prevent bile duct inflammation and mu-cosal hyperplasia typical for uncoated stents. Further studies, particularly with improved wet SIS are war­ranted. Key words: bile ducts, stents; intestinal mucosa Correspondence to: Duäan Pav‰nik, MD, Ph.D., Dotter Interventional Institute, Oregon Health Science University, L342, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97201, USA. Phone: (503) 494 8396, Fax: (503) 494 4258, E-mail: pavcnikd@ohsu.edu Received 13 November 2000 Accepted 7 December 2000 Introduction Expandable metallic stents have been estab­lished as useful devices for the treatment of large bile duct obstructions whether caused by benign or malignant processes.1-7 Their long-term patency, however, remains a major problem. Mucosal hyperplasia, bile sludging and stone formation resulting from signifi­cant foreign body-type inflammatory reaction often block expandable stents.1-4 In malig­nancies, direct tumor ingrowth or overgrowth also obstructs stents.8-10 Stents coated or covered with synthetic polymer material have been explored experi­mentally for potential improvement in a long­term biliary stent patency.11-15 Generally, stent coated or covered with polyester, polyurethane or polycaprolectone resulted in lesser degree of mucosal hyperplasia and re­active inflammatory or dysplastic changes than with bare stents.11-13 The results with stents coated or covered with silicone were less uniform showing a decrease of reactive changes in some experiments 11,12,14, while leading to stent occlusion in others.15 A few clinical studies with prototype stents coated or covered with polyurethane showed prom­ise in prevention of tumor ingrowth into the stent and all investigators called for an im­provement of stent covering.16-18 We explored a biomaterial- small intestin­al submucosa (SIS) as stent cover for poten­tial biliary use. SIS is a relatively acellular, collagen-rich, degradable biomaterial harvest­ed from pig small intestines. It is resistant to infection, does not produce an adverse im­munologic response and is remodeled and re­placed by host tissue.19-26 SIS has been suc­cessfully used on grafting arteries19-21, veins22, and in the defects of the urinary blad­der23,24, diaphragm25, tendon26, fascia27, and abdominal wall.28 Material and methods Animals Six young domestic swine weighing from 26 Kg to 28 Kg underwent SIS covered stent placement into the common bile duct. The study was approved by the institutional ani­mal care and use committee of Oregon Health Science University in accordance with the guideline established by the Animal Welfare Act. Covered stents Single Gianturco-Rish type Z-stents were used (Figure 1). They were hand-made in our research laboratory of 0.075-inch stainless steel wire and consisted of six legs. They were Figure 2a-b. Placement of SIS endograft in the common bile duct. (a) Cholangiography immediately after endo-graft placement. (b) Cholangiography at 8 weeks before sacrifice shows slightly dilated common bile duct. The stent turned sideways (arrow), and a defect corresponding to mucosal hyperplasia is seen in the bile duct wall where the stent end was located (arrow head). 11 mm long and 6 or 7 mm in diameter, de­pending on the size of the swine common bile duct. The stent cover was cut out of a 0.1 mm thick, dry SIS-sheet (Cook, Biotech Inc, Lafayette, IN). The sheet was cut to match the stent length and diameter and was rolled into a tube that was wrapped around the outside of the stent and attached to it at both ends with 7-0 polypropylene (Prolene, Ethicon Inc, Somerville, NJ). Stent placement Each animal was tranquilized with 1.5mL tile-tamine hydrochloride, intubated and main­tained with 2% isoflurane and 2L/min O2. After a small central incision of the abdomi­nal wall just below the sternum, the gallblad­der was mobilized with forceps, and the tip of its fundus was pulled up to the central inci­sion. There, it was punctured with an 18G needle, and a 0.035-inch guidewire (Roadrunner, Cook Inc, Bloomington, IN) was advanced through the cystic duct into the common bile duct. A 4-F catheter was then advanced over the guidewire into the com­mon bile duct. After the Roadrunner guidewire was exchanged for a 0.035-inch Super-Stiff guide wire (Medi-Tech/Boston Scientific, Watertown, MA), a 5-F vascular sheath was inserted over the wire deep in the common bile duct. Cholangiography was per­formed using the sheath for injection. The 5­F sheath was also used for stent placement in­to the common bile duct between the ampulla and entrance of the cystic duct. The stent di­ameter was selected to be about 1-1.5 mm larger than the diameter of the common bile duct. Altogether 9 single stents were implant­ed in 6 animals. Four animals received six stents of 6 mm in diameter, two receiving one stent and two receiving two stents. The other two animals received three stents with the di­ameter of 7 mm, one receiving one stent and the other two stents. When two stents were placed into the common bile duct, they were separated only by a few millimeters. After the placement of stents, a cholan­giogram was repeated and the sheath was re­moved (Figure2a). After the puncture site in the gallbladder was sutured, the gallbladder fundus was pulled up to the incision and se­cured to the inner abdominal wall. A metallic ring was then sutured together with the se­cured gallbladder fundus. This ring facilitated the identification of the fixation area for fluo­roscopically guided percutaneous puncture for follow-up cholangiography. Follow-up Animals were followed up for a maximum pe­riod of 10 weeks with a plan to sacrifice two animals at each 4, 8 and 10 weeks after stent-ing. Cholangiography was obtained at the second weeks of follow-up and at the sacri­fice or immediately after death. The two-week cholangiography was performed percuta­neously using a 21-G needle. The terminal cholangiogram was performed by the same method as during the original stent place­ment. A 4-F catheter was inserted into the common bile duct through the gallbladder and cystic duct under general anesthesia. Cholangiography was then performed (Figure 2b). Euthanasia was carried out with a solu­tion of pentobarbital and phenytoin sodium (Euthasol, Delmarva Lab, Inc., Midlothian, VA). Histology Segments of the bile duct proximal and distal to the stent, as well as at the center of the stent were placed in neutral-buffered zinc for­malin. After a minimum of 24 h of fixation, the specimens were further sectioned into tis­sue cassettes, processed through alcohol and xylene, and embedded in paraffin. Five-mi­cron paraffin sections were cut and stained with hematoxylin and eosin, or with Masson's trichrome stain. Results Stent deployment and clinical course Stents were successfully placed in the com­mon bile duct in all animals. The diameter of the stented common bile ducts ranged from 5.0 mm to 5.5 mm (mean, 5.3 mm) before stent placement. Stents with a diameter 1­1.5mm larger than the common bile duct re­mained in place during the initial study. During the follow-up, none of the animals de­veloped jaundice. One animal developed ileus caused by a gauze pad left in the peri­toneal cavity during initial laparotomy and died 16 days after stenting. Five animals were doing well, eating and gaining weight, and were sacrificed at the planned intervals of 4 weeks (n=1), 8 weeks (n=2), and 10 weeks (n=2) after stenting. Cholangiography The two-week percutaneous cholangiography was successfully performed in 4 out of 6 ani­mals. In the other two animals, it was aban­doned because of the failure to enter the gall­bladder. One of these two animals, however, died 2 days later and cholangiography was performed immediately after death. Therefore, cholangiograms were obtained at approximately 2 weeks in five animals with 7 stents. They showed good patency and nor­mal size of the stented common bile duct. Three stents remained in their original site of placement. Four stents slipped distally. There was no defect suggesting mucosal hyperpla­sia in any stent. Two stents in one animal could not be evaluated. Figure 2c-d. (c) Explanted bile duct after 8 weeks after stenting. The stent ends of the sideways turned stent are embedded in the bile duct wall. (d) Photomicrograph of common bile duct wall in area of the stent. The defect in the wall was caused by two stent struts (arrow). Their mucosal hyperplasia and the adjacent wall show slight com­pression atrophy. [Masson Trichrome, 25x original magnification] The four week follow up cholangiogram done in one animal showed well patent nor­mal sized common bile duct with stent re­maining in its original place. A smooth small defect suggesting mucosal hyperplasia was found at the distal end of the stent. The eight-week cholangiograms done in 2 animals showed slightly enlarged and well patent common bile ducts. All three stents were found dislodged from their original place, turned sideways and laying across the com­mon bile duct. There were defects, which were considered to be mucosal hyperplasia at the bile duct wall where stents turned side­ways (Figure 2b). The ten-week cholan- Figure 3a-b. Biliary endograft ex-vivo 4 weeks after placement in the common bile duct. (a) Dissected bile duct specimen shows partially embedded distal end of the Z-stent without SIS-cover in the bile duct wall. (b) The defect at the base of the mucosa corresponds to the location of a stent strut. There is mild inflamma­tion and hyperplasia of the overlying biliary mucosa. [Hematoxylin & eosin, 25x original magnification] giograms in two animals showed common bile duct dilation and some defects from sludge formation around the stents. Two stents in one animal were turned sideways. In the other animal, one stent stayed in its orig­inal position while the other was dislodged distally from the original site of placement. Mucosal hyperplasia was not evaluated cholangiographically because of associated bile sludge. Histological study Macroscopically, the SIS sheet covering the stent was identifiable at 2 weeks. Its color turned from white to blackish green, consis­tent with bile staining. After 4 weeks, the SIS-sheets were not grossly nor microscopically detectable (Figure 3a,b). The two stents, which did not dislodge at 2 and 10 weeks, had intact bile duct mucosa with no apparent hyperplasia (Figure 4a). In the third stent, which had not dislodged for 4 weeks, there was mild mucosal hyperplasia at the distal end (Figure 3a). Beneath this mucosa, there was a localized foreign body-type inflamma­tory reaction to the stent strut (Figure 3B). Mucosal proliferation was observed adjacent to the stents that had turned sideways (Figure 2c,d); in no case did the hyperplasia signifi­cantly narrow the duct lumen. In the stent dislodged distally, the bile duct wall was nor­mal and no mucosal hyperplasia was seen. (Figure 4a,b). Discussion For the evaluation of the function and biolog­ical response of SIS covered metallic stents in the swine biliary system, only the data from four (45%) stents which remained in the lon­gitudinal position in the common bile duct can be used. Three of them remained in the original position and one slipped distally from the original position. Their average im­plantation time in the common bile duct was 6.5 weeks with the range from 2 to 10 weeks. Only in these 4 stents, SIS cover was contin­uously in contact with the common bile duct mucosa and exposed to bile flow. SIS cover prevented focal denudation and reactive pro­liferation of the mucosa, inflammation in the submucosa, and narrowing of the bile duct lu­men often seen after the placement of bare, non-covered stents.15,29 SIS cover helped to decrease the foreign body-type inflammatory response to Z-stents and, of these four stents, only one showed mild inflammation and mild mucosal hyperplasia of overlying mucosa in a focal area of distal struts. There was no nar­rowing of common bile duct lumen; on the contrary, a slight, common bile duct dilata­tion developed at 10 weeks. At four weeks and later, the SIS cover was not microscopi­cally detectable. Whether the membrane sim­ply dissolved or was incorporated into the duct wall as a result of tissue remodeling re­mains unclear. It is interesting that even after 10 weeks of stenting when SIS membrane was no longer detectable the Z-stent wires did not cause a significant reaction. Whether hyperplasia and obstruction develop at a lat­er time remains to be tested. Five stents (55%) which dislodged from their original position and turned sideways across the common bile duct caused mucosal proliferation in the wall adjacent to the struts at their ends. This mucosal proliferation, however, was only mild and did not cause sig­nificant narrowing of the common bile duct lumen. The type, size, and smooth surface of SIS covered stents, absence of reactive changes in common bile duct wall together with rapid growth of animals must be consid­ered as the main causes of frequent stent dis-lodgment found in our animals. Single Z-stents used in our animals have a tendency to jump off of the catheter during delivery and remain unstable after their placement, unless their diameter is significantly larger than the lumen of the stented structure. We selected only the stents that were about 15% larger Figure 4a-b. Specimen and low power photomicrograph of common duct wall after 10 weeks of stenting. (a) Dissected bile duct after stent removal demonstrates intact mucosa. (b) The biliary mucosa is intact and shows on­ly mild chronic inflammation. [Masson Trichrome, 200x original magnification] than the common bile duct diameter. Yet, that was not sufficient in the fast growing an­imals. For future work, we plan to use larger double body Z-stents which are more stable at the delivery and after the placement. Tendency for migration of covered or coated stents with their minimized surface friction and minimal reactive changes in the duct mu­cosa, however, will be always a problem, par­ticularly with their use in a nonstenotic duct. Even when our study is limited in scope, it showed promise of SIS cover for biliary stent-ing. It showed that SIS is biocompatible and helps to decrease the foreign body-type in­flammatory reaction to metallic stents. Further detailed study will be necessary to confirm our initial results and particularly evaluate long term effect of SIS covered stents. For our study we used a dry form of SIS which has several disadvantages, particu­larly difficulty in attachment and suturing to the stent base. It is also fragile and may break during catheter delivery. For future work we plan to use most recently available and im­proved wet form of SIS which can be easily and safely attached to the stent, does not leak and can be easily introduced through a catheter. References 1. Coons H. Metallic stents for the treatment of bil­iary obstruction: a report of 100 cases. Cardiovasc Intervent Radiol 1992; 15: 367-74. 2. Yoon HK, Sung KB, Song HY, Kang SG, Kim MH, Lee SG, Lee SK, Auh YH. Benign biliary strictures associated with recurrent pyogenic cholangitis: treatment with expandable metallic stents. Am J Roentgenol 1997; 169: 1523-7. 3. Hausegger KA, Kugler C, Uggowitzer M, Lammer J, Karaic R, Klein GE, Maurer M. Benign biliary ob­struction: is treatment with the Wallstent advis­able? Radiology 1996; 200: 437-41. 4. O'Brien SM, Hatfield AR, Craig PI, Williams SP. A 5-year follow-up of self-expanding metal stents in the endoscopic management of patients with be­nign bile duct strictures. Eur J Gastroenterol Hepatol 1998; 10: 141-5. 5. Rossi P, Bezzi M, Rossi M, Adam A, Chetty N, Roddie ME, Iacari V, Cwikiel W, Zollikofer CL, Antonucci F. Metallic stents in malignant biliary obstruction: results of multicenter European study of 240 patients. J Vasc Interv Radiol 1994; 5: 279-85. 6. Gordon RL, Ring EJ, LaBerge JM, Doherty MM. Malignant biliary obstruction: treatment with ex­pandable metallic stents-follow-up of 50 consecu­tive patients. Radiology 1992; 182: 697-701. 7. Lammer J, Hausegger KA, Fluckiger F, Winkelbauer FW, Wildling R, Klein GE, Thurnher SA, Havelec L. Common bile duct obstruction due to malignancy: treatment with plastic versus met­al stents. Radiology 1996; 201: 167-72. 8. Hausegger KA, Mischinger HJ, Karaic R, Klein GE, Kugler C, Kern R, Uggowitzer M, Szolar D. Percutaneous cholangioscopy in obstructed biliary metal stents. Cardiovasc Intervent Radiol 1997; 20: 191-6. 9. Hausegger KA, Kleinert R, Lammer J, Klein GE, Fl.ckiger F. Malignant biliary obstruction: histo-logic findings after treatment with self-expandable stents. Radiology 1992; 185: 461-4. 10. Boguth L, Tatalovic S, Antonucci F, Heer M, Sulser H, Zollikofer CL. Malignant biliary obstruction: clinical and histopathologic correlation after treat­ment with self-expanding metal prostheses. Radiology 1994; 192: 669-74. 11. Alvarado R, Palmaz JC, Garcia OJ, Tio FO, Rees CR. Evaluation of polymer-coated balloon-expand­able stents in bile ducts. Radiology 1998; 170: 975­8. 12. Yasumori K, Mahmoudi N, Wright KC, Wallace S, Gianturco C. Placement of covered self-expanding metallic stents in the common bile duct: a feasibil­ity study. J Vasc Interv Radiol 1993; 4: 773-8. 13. Severini A, Mantero S, Tanzi MC, Cigada A, Salvetti M, Cozzi G, Motta A. Polyurethane-coat­ed, self-expandable biliary stent: an experimental study. Acad Radiol 1995; 2: 1078-81. 14. Silvis SE, Sievert CE Jr, Vennes JA, Abeyta BK, Brennecke LH. Comparison of covered versus un­ covered wire mesh stents in the canine biliary tract. Gastrointest Endosc 1994; 40: 17-21. 15. Vorwerk D, Kissinger G, Handt S, Gunther RW. Long-term patency of Wallstent endoprostheses in benign biliary obstructions: experimental results. J Vasc Interv Radiol 1993; 4: 625-34. 16. Born P, Neuhaus H, Rosch T, Ott R, Allescher H, Frimberger E, Classen M. Initial experience with a new, partially covered Wallstent for malignant bil­iary obstruction. Endoscopy 1996; 28: 699-702. 17. Rossi P, Bezzi M, Salvatori FM, Panzetti C, Rossi M, Pavia G. Clinical experiences with covered wallstents for biliary malignancies: 23-month fol­low-up. Cardiovasc Intervent Radiol 1997; 20: 441-7. 18. Hausegger KA, Thurnher S, Bodendorfer G, Zollikofer CL, Uggowitzer M, Kugler C, Lammer J. Treatment of malignant biliary obstruction with polyurethane-covered Wallstents. Am J Roentgenol 1998; 170: 403-8. 19. Badylak SF, Lantz GC, Coffey A, Geddes LA. Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res 1998; 47: 74-80. 20. Sandusky GE Jr, Badylak SF, Morff RJ, Johnson WD, Lantz G. Histologic findings after in vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid ar­tery in dogs. Am J Pathol 1992; 140: 317-24. 21. Badylak SF, Coffey AC, Lantz GC, Tacker WA, Geddes LA. Comparison of the resistance to in­fection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model. J Vasc Surg 1994; 19: 465-72. 22. Lantz GC, Badylak SF, Coffey AC, Geddes LA, Sandusky GE. Small intestinal submucosa as a su­perior vena cava graft in the dog. J Surg Res 1992; 53: 175-81. 23. Kropp BP, Badylak S, Thor KB. Regenerative blad­der augmentation: a review of the initial preclini-cal studies with porcine small intestinal submu­cosa. Adv Exp Med Biol 1995; 385: 229-35. 24.Kropp BP. Small-intestinal submucosa for bladder augmentation: a review of preclinical studies. World J Urol 1998; 16: 262-7. 25. Dalla Vecchia L, Engum S, Kogon B, Jensen E, Davis M, Grosfeld J. Evaluation of small intestine submucosa and acellular dermis as diaphragmatic prostheses. J Pediatr Surg 1999; 34: 167-71. 26. Badylak SF, Tullius R, Kokini K, Shelbourne KD, Klootwyk T, Voytik SL, Kraine MR, Simmons C. The use of xenogenic small intestinal submucosa as a biomaterial for Achilles tendon repair in a dog model. J Biomed Mater Res 1995; 29: 977-85. 27. Dejardin LM, Arnoczky SP, Clarke RB. Use of small intestinal submucosal implants for regener­ation of large fascial defects: an experimental study in dogs. J Biomed Mater Res 1999; 46: 203-11. 28. Clarke KM, Lantz GC, Salisbury SK, Badylak SF, Hiles MC, Voytik SL. Intestine submucosa and polypropylene mesh for abdominal wall repair in dogs. J Surg Res 1996; 60: 107-14. 29. Carrasco CH, Wallace S, Charnsangavej C, Richli W, Wright KC, Fanning T, Gianturco C. Expandable biliary endoprosthesis: an experimen­tal study. Am J Roentgenol 1985; 145: 1279-81. Diagnostic imaging of hypertrophic pyloric stenosis (HPS) Marija Frkovi“, Marina áeronja Kuhar, ëeljka Perho‰, Vinka Barbari“-Babi“, Melita Molnar, Jurica Vukovi“ Clinical Institute for Diagnostic and Interventional Radiology, Clinical Hospital Centre Zagreb - Rebro, Croatia Background. Imaging of the abdomen in children with suspected hypertrophic pyloric stenosis has been tra­ditionally performed by plain film radiography and upper gastrointestinal contrast studies. In many clinical situations, this approach has been modified or replaced by ultrasound examination. The authors aimed to analyse the value of diagnostic algorithm in children with hypertrophic pyloric stenosis confirmed at sur­gery in our hospital. Patients and methods. The authors made a five year retrospective review of hospital records of all chil­dren operated on for HPS in Clinical Hospital Centre Zagreb - Rebro and found out that 14 boys, between 2 (17 days) and 10 weeks of life (75 days) underwent surgery due to HPS. Results. Specific radiographic signs were: string sign, double track sign, elongation and narrowing of pyloric canal, mushroom sign, gastric distension with fluid and beak sign. Ultrasound was performed in 9 patients, one of them was false negative (sonographer admitted that he had no experience), the rest were positive. Conclusions. If the physical examination is negative or equivocal, sonography by an experienced sonogra­pher must be performed. If the ultrasound finding is negative, than the infant should undergo to barium up­per gastrointestinal studies (UGI). If HPS isn't a primary diagnostic question, it's better to perform UGI first in order to make a correct diagnosis. Key words: pyloric stenosis - radiography - surgery; hyperthrophy; child Received 20 October 2000 Accepted 7 November 2000 Correspondence to: Marija Frkovi“, M.D., Ph.D. radi­ologist, Clinical Institute for Diagnostic and Interventional Radiology, Clinical Hospital Centre Zagreb - Rebro, Kiäpati“eva 12, 10000 Zagreb, Croatia; Phone: +385 1 238 84 54; Fax.: +385 1 233 37 25; e-mail: marijan.frkovic@zg.tel.hr Introduction Hypertrophic pyloric stenosis (HPS) is actual­ly idiopathic hypertrophy and hyperplasia of the circular muscle fibers of the pylorus with proximal extension into the gastric antrum.1 The cause of HPS remains un­known. HPS is inherited as a dominant poly­genic trait. Some authors reported even fa­milial occurrence of HPS in twins.2 This, however, was rather an acquired than con­genital condition.1 Others presented an ex­ample of ÓsecondaryÓ HPS in a patient with prostaglandin - induced foveolar hyperplasia of antrum.3 Recently, it has assumed that, in some cas­es, HPS is caused by Helicobacter pylori.4 The latest research supports the hypothesis of a selective immaturity of the enteric glia in the muscular layers of infantile HPS.5 Hypertrophic pyloric stenosis is the most common acquired obstruction of the young infant. It is more common in boys than girls, by a 5:1 ratio and develops usually between the second and eighth weeks of life. The clinical features of bile-free progres­sive projectile vomiting, visible gastric peri­staltic waves, and an olive shaped palpable abdominal mass in the right upper quadrant are frequently diagnostic. Depending on how long symptoms have been present, little pa­tients may present with dehydration and hy­pokalemic alkalosis, irritability, weight loss, and failure to thrive. Plain film radiography has no role in the di­agnosis of pyloric stenosis. Massive gastric distension (>7 cm diameter) is seen common­ly in other conditions and is not at all specif­ic. If the child vomits before the filming, the gastric distension may be relieved. For barium upper gastrointestinal studies (UGI), we must empty gastric contents via na­sogastric tube before and after the study due to a high incidence of reflux in these patients. Positive fluoroscopic and radiographic signs include elongated pyloric canal (string sign), antral beaking, pyloric teat, flattening of the prepyloric area of the lesser curvature (shoul­der sign), and usually active gastric hyper-peristalsis (caterpillar sign). Sometimes a double or triple column of barium is present as two or three parallel lines (double/triple track sign) caused by the crowding of mucos­al folds in the pyloric canal. The base of the bulb can be indented by thickened shoulder of pyloric muscle (mushroom sign). Delayed gastric emptying is the least reliable indicator of HPS and can be seen with pylorospasm, gastric hypotonia, sepsis and ileus. The ultrasound (US) examination is per­formed with the patient in the supine, and later, in the right lateral decubitus position. Overlying bowel gas or gastric distension may occasionally hinder the sonographic di­agnosis of HPS. To resolve this problem, a novel approach for obtaining posterior views of the pylorus was reported.6 Ultrasound examination of the pyloric re­gion includes both transverse and longitudi­nal images of the pylorus. The most common measurement used is pyloric muscle thickness obtained with transverse scanning of the py­lorus. The muscle is usually hypoechoic, but it can have a nonuniform pattern.7 The mus­cle appeared to be more echogenic in its near and far fields and less echogenic on its sides due to anisotropic effect which is related to the orientation of the ultrasound beam with respect to the circular fibbers of the pyloric muscle. The transverse pyloric diameter, includ­ing the lumen and both walls of the pylorus, is less frequently measured. The pyloric canal length (echogenic) may be measured, and is shorter than the surrounding pyloric muscle length (hypoechoic structures). Several differ­ent pyloric muscle indices also have been used to detect HPS.8-10 There has been disagreement as to the ex­act measurements to be used for pyloric ste­nosis. Authors have published different num­bers for these different measurements.11-13 D-hnert 1 suggested, that pyloric muscle thickness >=3 mm, transverse pyloric diame­ter >=13 mm with pyloric canal closed and py­loric canal length >=17 mm are diagnostic of HPS. Other sonographic signs are: "target sign" (hypoechoic ring of the hypertrophied pyloric muscle around echogenic mucosa centrally on cross-section), "cervix sign" (in­dentation of the muscle mass on the fluid-filled antrum on longitudinal section), "antral nipple sign"14 (redundant pyloric canal mu­cosa protruding into the gastric antrum), ex­aggerated retrograde peristaltic waves and delayed gastric emptying of fluid into the duodenum. The authors aimed to analyse the value of diagnostic algorithm in children with hyper-trophic pyloric stenosis confirmed at surgery in Clinical Hospital Rebro. Patients and method This is a retrospective review of hospital records of all children operated on for pyloric stenosis in Clinical Hospital Centre Zagreb -Rebro from 1st January 1995 to 31st December 1999. Fourteen infants underwent surgery due to hypertrophic pyloric stenosis during the period in question. They were all boys, between 2 (17 days) and 10 weeks of life (75 days). UGI study was performed with 5-10 ml of diluted barium on Siemens Sireskop 3. Sonographic examination was performed in the standard supine and right lateral decubi­tus position, using a GE Logiq 400 scanner and 5.0-MHz convex traducer and 6.6-MHz linear traducer. Results Clinical findings in our patients are presented in Table 1. In all infants, the radiological diagnosis was made on the basis of upper gastrointesti­nal series (Table 2). Specific radiographic signs were: string sign, double track sign, elongation and nar­rowing of pyloric canal, mushroom sign, gas- Table 1. Clinical symptoms and laboratory data Clinical symptoms and laboratory data No. Bile-free projectile vomiting 14 Olive shaped muscular mass 2 Dehydration and hypokalemic alkalosis 9 Weight loss, failure to thrive 3 Table 2. Methods of imaging No. UGI US 14 14 (100%) 9 (64%) UGI= barium upper gastrointestinal studies; US= ul­trasound examination tric distension with fluid and beak sign. Ultrasound was performed in 9 patients, one of them was false negative (the sonographer admitted that he has no experience), the rest were positive. Ultrasound signs and measure­ments were: target sign, transverse pyloric di­ameter, pyloric muscle wall thickness and py­loric canal length. All measurements were consistent with the diagnosis of HPS. Discussion Nowadays, the reliance on diagnostic imag­ing has been increasing.15 During palpation performed by paediatrician or surgeon the in­fant must be calm; this is time consuming, and may even be impossible, if the stomach is distended. Some authors stated that the tech­nique of palpating a pyloric mass became Óa declining artÓ.16 Many publications on this subject stressed that the diagnosis often can be made by physical examination and that imaging procedures don't need to be routine­ly performed.17-20 Only children with a nega­tive or equivocal physical examination should go to ultrasonography. Currently, ultrasonog­raphy has replaced the upper gastrointestinal (UGI) examination as the method of choice for establishing the diagnosis.21-23 US is more economical, there is no exposure to ionising radiation such as in UGI studies, and allows to follow up the patients, but it demands a highly experienced sonographer. It has also been reported that over-reliance on ultra­sound scans only lead to negative explo­rations.24 There are also other opinions: that the UGI is less expensive than the US as the first strat­egy in the evaluation of the infant with sus-pected HPS.25, 26 An advantage of the UGI is that it has slightly higher sensitivity for py­loric stenosis than does US scan. UGI also provides definitive information in the evalua­tion of the vomiting infant regarding other potential diagnoses such as gastroesophageal reflux, malrotation and intestinal obstruction. If the clinical findings are doubtful, it is justi­fied to perform UGI because of concomitant pathology. One of the papers presented the cases of pyloric stenosis associated with mal­rotation.27 In a recent publication, reporting of the at­tempts to develop a cost- and time-effective algorithm for differentiating HPS from other medical causes of emesis in infants, it is rec­ommended that the child is given nothing by mouth for 3 to 4 hours before gastric aspira­tion. The aspirated volume >= 5ml implicated gastric outlet obstruction and ultrasonogra­phy was performed. If this examination was positive for HPS, the child was referred for surgery. If US was negative, upper gastroin­testinal series were performed. The aspirated stomach contents volume <5ml suggested an­other medical cause of emesis; therefore UGI was performed.28, 29 In our hospital UGI was performed always on surgeon's request, even clinical and US findings were positive. Surgeon's trust and confidence in UGI versus US is changing very. They sometimes neglect the ionising ra­diation during UGI studies. On the other hand, because US is very operator -depend­ent imaging modality, false positive and false negative results can compromise this me­thod. This is no wonder because HPS is rare pathology. An additional problem is that, in large centres like our hospital, we have no de­partment of paediatric radiology. Differential diagnosis of HPS after the imag­ing includes infantile pylorospasm in which the muscle thickness is between 1.5 and 3 mm. In this condition, antral narrowing is of variable calibre, gastric emptying is delayed, the pylorus is elongated, antral peristalsis is functioning. Muscle thickness or pyloric length measurements may overlap those ac­cepted as positive for HPS. Image or meas­urement variability is an important clue for diagnosing pylorospasm.30 Milk allergy and eosinophilic gastroenteritis can also mimic the clinical symptoms and US appearance of idiopathic HPS.31 Eosinophilic gastro-enteri­tis is characterised by hypertrophy of the hy­poechoic muscular layer and also thickening of the mucosal and submucosal layers of the pylorus. It is also helpful to search for thick­ening of the antral wall. The differential diag­nosis for possible HPS encompasses several other gastrointestinal tract abnormalities, in­cluding gastroesophageal reflux, duodenal obstruction, and pyloric membrane, or webs. After the imaging we didn't have any differ­ential diagnostic difficulties. Treatment is surgical (pyloromyotomy). We follow up the operated children with US. Recently, some attempts have been made in the treatment with atropine sulfate; all in­fants were followed by sonography to ob­serve the anatomical changes (shortening of the pyloric canal, followed by thinning of the muscular layer).32, 33 We have no experience in such treatment. Our review of the litera­ture suggests that this kind of treatment has­n't found general clinical acceptance. The infant with symptoms that clearly sug­gests pyloric stenosis must be examined by an experienced physician prior to imaging. If the physical examination is negative or equiv­ocal, sonography by an experienced sonogra­pher must be performed. If the US is negative, than the infant should go to UGI. If HPS isn't primary diagnostic question, it's better to perform UGI first to establish the correct diagnosis. References 1. D-hnert W. Radiology Review Manual. 4th ed. Baltimore: Williams&Wilkins; 1999. p. 692-3. 2. Zajadacz B, Baraniak A, Juszkiewicz A. Hypertrophic pyloric stenosis in twins. Wiad Lek 1999; 52: 616-8. 3. Callahan MJ, McCauley RG, Patel H, Hijazi ZM. The development of hypertrophic pyloric stenosis in a patient with prostaglandin - induced foveolar hyperplasia. Pediatr Radiol 1999; 29: 748-51. 4. Paulozzi LJ. Is helicobacter pylori a cause of infan­tile hypertrophic pyloric stenosis? Med Hypotheses 2000; 55: 119-25. 5. Guarino N, Shima H, Oue T, Puri P. Glial-derived growth factor signalling pathway in infantile hy­pertrophic pyloric stenosis. J Pediatr Surg 2000; 35: 835-9. 6. Sargent SK, Foote SL, Mooney DP, Shorter NA. The posterior approach to pyloric sonography. Pediatr Radiol 2000; 30: 256-7. 7. Spevak MR, Ahmadjian JM, Kleinman PK, Henriquez G, Hirsh MP, Cohen IT. Sonography of hypertrophic pyloric stenosis: frequency and cause of nonuniform echogenicity of the thick­ened pyloric muscle. Am J Roentgenol 1992; 158: 129-32. 8. Davies RP, Linke RJ, Robinson RG, Smart JA, Hargreaves C. Sonographic diagnosis of infantile hypertrophic pyloric stenosis. J Ultrasound Med 1992; 11: 603-5. 9. Ozsvath RR, Poustchi-Amin M, Leonidas JC, Elkowitz SS. Pyloric volume: an important factor in the surgeon's ability to palpate the pyloric "olive" in hypertrophic pyloric stenosis. Pediatr Radiol 1997; 27: 175-7. 10. Lowe LH, Banks WJ, Shyr Y. Pyloric ratio: efficacy in the diagnosis of hypertrophic pyloric stenosis. J Ultrasound Med 1999; 18: 773-7. 11. Rohrschneider WK, Mittnacht H, Darge K, Troger J. Pyloric muscle in asymptomatic infants: sono-graphic evaluation and discrimination from idio­pathic hypertrophic pyloric stenosis. Pediatr Radiol 1998; 28: 429-34. 12. O'Keeffe FN, Stansberry SD, Swischuk Le, Hayden CK Jr. Antropyloric muscle thickness at US in infants: what is normal? Radiology 1991; 178: 827-30. 13. Hallam D, Hansen B, Bodker B, Klintorp S, Pedersen JF. Pyloric size in normal infants and in infants suspected of having hypertrophic pyloric stenosis. Acta Radiol 1995; 36: 261-4. 14. Hernanz-Schulman M, Dinauer P, Ambrosino MM, Polk DB, Neblett WW 3rd. The antral nipple sign of pyloric mucosal prolapse: endoscopic find­ings correlation of a new sonographic observation in patients with hypertrophic pyloric stenosis. J Ultrasound Med 1995; 14: 283-7. 15. Morrison SC. Controversies in abdominal imag­ing. Pediatr Radiol 1997; 44: 555-74. 16. Macdessi J, Oates RK. Clinical diagnosis of pyloric stenosis: a declining art. BMJ 1993; 306: 553-5. 17. Aronson DC, van Oostayen JA, Kievit J. When is echography necessary in the diagnosis of pylorus hypertrophy in young children. Ned Tijdschr Geneeska 1994; 138: 1622-5. 18. Godbole P, Sprigg A, Dickson JA, Lin PC. Ultrasound compared with clinical examination in infantile hypertrophic pyloric stenosis. Arch Dis Child 1996; 75: 335-7. 19. Deluca SA. Hypertrophic pyloric stenosis. Am Fam Physician 1993; 47: 1771-3. 20. Huddy SP. Investigation and diagnosis of hyper-trophic pyloric stenosis. J R Coll Surg Edinb 1991; 36: 91-3. 21. Hernanz-Schulman M, Sells LL, Ambrosino MM, 3rd Heller RM, Stein SM, Neblett WW . Hypertrophic pyloric stenosis in the infant with­out a palpable olive: accuracy of sonographic diag­nosis. Radiology 1994; 193: 771-6. 22. Neilson D, Hollman AS. The ultrasonic diagnosis of infantile hypertrophic pyloric stenosis-tech­nique and accuracy. Clin Radiol 1994; 49: 246-7. 23. Van der Schouw YT, van der Velden MT, Hitge-Boetes C, Verbeek A. Diagnosis of hypertrophic pyloric stenosis: value of sonography when used in conjunction with clinical findings and laborato­ry data. Am J Roentgenol 1994; 163: 905-9. 24. Misra D, Akhter A, Potts SR, Brown S, Boston VE. Pyloric stenosis: is over reliance on US scans lead­ing to negative explorations? Eur J Pediatr Surg 1997; 7: 328-30. 25. Olson D.A, Hernandez R, Hirschl BA. The role of ultrasonography in the diagnosis of pyloric steno-sis: a decision analysis. J Pediatr Surg 1998; 33: 676­81. 26. Emmink B, Hadley GP, Wiersma R. Infantile hy­pertrophic pyloric stenosis in a Third -World envi­ronment. S Afr Med J 1992; 82: 168-70. 27. Croitoru D, Neilson I, Guttman FM. Pyloric steno-sis associated with malrotation. J Pediatr Surg 1991; 26: 1276-8. 28. Finkelstein MS, Mandell GA, Tarbell KV. Hypertrophic pyloric stenosis: volumetric meas­urement of nasogastric aspirate to determine the imaging modality. Radiology 1990; 177: 759-61. 29. Mandell GA, Wolfson PJ, Adkins ES, Caro PA, Cassell I, Finkelstein MS, et al. Cost -effective im­aging approach to the nonbilious vomiting infant. Pediatrics 1999; 103(6 Pt 1): 1198-202. 30. Cohen HL, Zinn HL, Haller JO, Homel PJ, Stoane JM. Ultrasonography of pylorospasm: findings may simulate hypertrophic pyloric stenosis. J Ultrasound Med 1998; 17: 705-11. 31. Hummer-Ehret BH, Rohrschneider WK, Oleszczuk-Raschke K, Darge K, Nutzenadel W, Troger J. Eosinophilic gastroenteritis mimicking idiopathic hypertrophic pyloric stenosis. Pediatr Radiol 1998; 28: 711-3. 32. Yamamoto A, Kino M, Sasaki T, Kobayashi Y. Ultrasonographic follow-up of the healing process of medically treated hypertrophic pyloric stenosis. Pediatr Radiol 1998; 28: 177-8. 33. Yamataka A, Tsukada K, Yokoyama Laws Y, Murata M, Lane GJ, Osawa M, et al. Pyloromyotomy versus atropine sulfate for infan­tile hypertrophic pyloric stenosis. J Pediatr Surg 2000; 35: 338-41. Computer systems for determination of pressure distribution in the hip joint articular surface: validation and results Vlado Stankovski and Dragica Smrke Department of Surgery, University Medical Centre, Ljubljana, Slovenia Background. In this work, we describe the computer systems Viprecox and Active Contours that are used in the process of realistic estimation of some biomechanical parameters of the hip joint, including the maxi­mal value of the stress in the hip joint p. The computer system Active Contours uses standard antero- max posterior radiographs of the whole pelvis and both hips for its calculations and Viprecox in its kernel uses a relatively simple three-dimensional mathematical model of stress distribution in the hip-joint articular sur­face which has been extensively described elsewhere (e.g. Igli‰ 1996). Material and methods. Both state-of-the-art computer systems were tested by analysing the calculated val­ues of pfor 81 patients (37 males and 44 females). max Conclusions. In this way we prove that the described computer systems can be used for the determination of the contact stress distribution from standard AP radiographs. Key words: hip joint; biomechanics; computer systems; weight bearing Introduction Higher and unevenly distributed contact stress in the hip-joint is a risk factor for the development of arthrosis.1,2,3 There are sever­al biomechanical parameters that describe the distribution and the peak value of the stress in the hip joint, such as the gradient of the stress at different positions of the articu­lar surface or the maximal value of the pres­sure on the articular surface of the hip joint Received 5 February 2001 Accepted 12 February 2001 Correspondence to: Assist. Prof. Dragica Smrke, Ph.D., M.D., Department of Surgery, Zaloäka 2, SI­1000 Ljubljana, Slovenia; Phone: +386 1 543 1419; Fax: +386 1 231 6889; E-mail: dsmrke@hotmail.com p. The realistic measurement or the esti- max mation of these parameters would be helpful in exploring the incidence of degenerative joint diseases. In this work, we describe the computer systems Viprecox and Active Contours that are used in the process of a realistic estimation of some biomechanical parameters of the hip joint including the value of the parameter p. Our additional purpose is to test these max state-of-the-art computer systems by analysing the calculated values of pfor 81 patients max (37 males and 44 females). Materials and methods The computer system Active Contours uses standard antero-posterior radiographs of the whole pelvis and the both hips for its calcula­tions (Figure1) and Viprecox in its kernel uses a relatively simple three-dimensional mathe­matical model of stress distribution in the hip-joint articular surface, which has been ex­tensively described elsewhere.4 The system Viprecox was developed as a 100% pure Java application, which enables the compatibility with any platform that uses the Java Virtual Machine. In the process of design and application development the ob-ject-oriented paradigm was used. The use of the object-oriented programming technique will allow the system easy maintenance and upgrades, but it will also allow a conversion to other platforms. The system Active Contours uses digitised profiles of standard antero-posterior radi­ographs of the pelvis and the both hips in or­der to extract the important data about the geometry of the both hips and the pelvis (Figure 1). These data are then transformed by using a non-homogeneous tailoring proce­dure5 in order to prepare the input data for the three-dimensional mathematical model of stress distribution in the hip-joint articular surface.4 For this purpose a reference model of the hip-joint musculature is used.6 As a result of the non-homogeneous tailor­ing procedure certain muscles' origin and in-sertion points are estimated. The reference muscles' origin points6 on the pelvis and the reference insertion points on the femur were not corrected in the antero-posterior direction because of the lack of data. All other coordi­nates are corrected as follows: The reference origin points on the pelvis for all muscles were corrected in the medio-lateral direction by using the ratio C/Cref, where C is the distance between the sagital plane passing through the femoral head cen­tre and the most lateral point on the pelvis. The system Viprecox automatically measures this point. Cref is the corresponding distance in the model of Dostal and Andrews6 Cref=(Bref-Lref)/2. The insertion points on the femur are divided into three groups: 1. m. gluteus medius and m. gluteus minimus, 2. the lateral point of m. piriformis and 3. the in­ferior points of m. tensor fasciae latae and m. rectus femoris. The system Viprecox automat­ically measures the Cartesian coordinates of the insertion points of the gluteus muscles in the frontal plane from the digitised antero-posterior radiographs. The insertion point of m. piriformis lies laterally and was therefore corrected only its medio-lateral coordinate by using the ratio between the already corrected medio-lateral coordinates of the gluteus mus­cles and the corresponding reference values. The distance L between the two centres of ro­tation of both hips was taken as automatical­ly measured by the system Viprecox. After such non-homogeneous tailoring procedure the prepared data are presented to the mathematical model of the hip-joint.4 In this way the maximal pressure on the hip joint articular surface pis calculated. max Results and conclusions Figure 2 shows the calculated hip joint con­tact stress for a patient with implanted hip endoprosthesis (for the other healthy side). In order to establish the clinical relevance of the parameter pthe computer system should max be applied to various populations of patients where the correlation between the clinical status and the hip stress may be studied. Recently, these systems have been used in or­der to determine the peak contact stress in the articular surface of the hip joint from standard AP radiographs for 37 male and 44 female healthy hips of patients subject to trauma of the other hip (Figure 2). It was shown that the peak contact stress is consid­erably higher (cca 20%) (p<0.00005) in the fe­male population (1.99 MPa) than in the male population (1.63 MPa). These results are in favour of the hypothesis that the increased hip joint contact stress in the female popula­tion could contribute to the greater incidence of arthrosis in the female population relative to the male population. To conclude, the described computer sys­tems Active Contours and Viprecox can be used for the determination of the contact stress distribution from standard AP radiographs. The systems can be applied in the clinical practice to predict an optimal stress distribu­tion in different operative interventions in the hip and to analyse the short and long term outcome of the treatment of various con­ditions of the hip. References 1. Hadley NA, Brown TD, Weinstein SL. The effects of contact pressure elevations and aseptic necrosis on the long-term clinical outcome of congenital hip dislocation. J Orthop Res 1990; 8: 504-13. 2. Maxian TA, Brown TD, Weinstein SL. Chronic stress tolerance levels for human articular carti­lage: two nonuniform contact models applied to long term follow-up of CDH. J Biomech 1995; 28: 159-66. 3. Brand RA. Hip osteotomies. A biomechanical con­sideration. J Am Acad Orthop Surg 1997; 5: 282-91. 4. Igli‰ A. Matemati‰no modeliranje operativnih posegov v kolku. Univerza v Ljubljani: doktorska disertaci­ja; 1996. 5. Stankovski V, Igli‰ A, Kralj-Igli‰ V, Kersni‰ B. The hip-joint resultant force in healthy male and fe­male population: a comparative study. Acta Chir Orthop Trauma ›ech 1996; 63: 211-3. 6. Dostal WF, Andrews JG. A three-dimensional bio-mechanical model of the hip musculature. J Biomech 1981; 14: 149-56. Ultrasonography of pleural effusion: the quantification of minimal detectable volume Alan áusti“1, Igor Medved2, Draěen Kova‰3, Nikola Ivaniä4, Darko Ekl2, Ognjen áimi“2 1Dept. of Anaesthesiology and ICU, 2Dept. of Surgery, 3Dept. of Pathology, University Hospital Rijeka, Croatia, 4Private ultrasound laboratory, Rijeka, Croatia Background. The aim of this study was to establish a minimal volume of free thoracic fluid in the pleural space of the supine cadaver detectable by ultrasonography. Material and methods. A prospective study with an experimental model on 20 cadavers (10 male, 10 fe­male; age 66 ±11 yr.; height 172 ±9 cm; weight 75 ±12.6 kg; body surface area (BSA) 1.87 ±0.2 m2) was used. Each cadaver was punctured bilaterally in 5th or 6th intercostal space at the medioclavicular line with venous cannula infusing in NaCl 0,9% solution at randomised speed in the chest. During the procedure the laterodorsal part of the thoracic wall next to the pulmonal base and phrenicocostal sinus was ultrasono-graphically scanned. At the moment of the visualisation of anechogenic line pertaining to the free fluid be­tween dorsal thoracic wall and lungs, the installation was stopped and the amount of injected fluid verified. Results. Minimal, by ultrasonography detectable amount of free fluid in the right pleural space was 223±52 ml with the significant positive correlation to height (r = 0.69; p < 0.001), weight (r = 0.68; p < 0.01) and the BSA (r = 0.71; p < 0.001) of cadaver. Detectable volume in the left pleural space was notably small­er than contra lateral, namely 172±53 ml also with a significant correlation to the cadaver's height (r = 0.55; p < 0.05), weight (r = 0.59; p < 0.01) and BSA (r = 0.60; p < 0.01). Conclusions. The authors affirm that ultrasonographically detectable quantity of free fluid in the chest pos­itively correlates with height, weight and BSA of cadavers, and that the measured amount in the supine po­sition is approximately 223 ml for the right space versus 172 ml for the left pleural space. Key words: pleural effusion, ultrasonography, quantification. Received 23 December 1999 Accepted 28 August 2000 Correspondence to: Alan áusti“, M.D., Ph.D., Dept. of Anaesthesiology and ICU, Clinical Hospital Rijeka, T. Striěi“a 3, Rijeka 51000, Croatia. Phone: + 385 51 21 84 07; Fax: + 385 51 21 84 07, E-mail: alan.sustic@ mamed.medri.hr Introduction The diagnosis of pleural effusion in critically ill patients frequently presents a serious problem. Transportation risks, the uncoordi­nated co-operation and difficulties in ade­quate positioning of those patients in the in­tensive care unit (ICU) make radiological methods often inadequate or unperforma­ble.1,2 Ultrasonography provides a rapid, con­venient, economic and bedside method for detecting pleural effusion in supine pa­tients.3-6 Meanwhile, there are no data in the pertinent literature, which could suggest what the minimal is, by ultrasonography de­tectable fluid volume in the pleural space. The aim of our study was to establish the smallest, by ultrasonography visible amounts of fluid in the cadaver (human body) in the supine position. Materials and methods An experimental model with 20 cadavers (10 male and 10 female; age 66 ±11 yr.; height 172 ±9 cm; weight 75 ±12.6 kg; body surface area (BSA) 1.87 ± 0.2 m2) was used. Each cadaver was punctured bilaterally in 5th or 6th inter-costal space at the medioclavicular line with venous cannula (1.5 mm x 44 mm; maximal possible flow of 142 ml/min) infusing in the pleural space NaCl 0.9% solution at ran-domised speed. During the whole procedure the laterodorsal part of the thoracic wall next to the pulmonal base and phrenicocostal si­nus was ultrasonographically scanned. The lungs of the cadavers were not insuflated. At the moment of the first visualisation of ane­chogenic line pertaining to the free fluid be­tween the dorsal thoracic wall and lungs, the installation was stopped and the amount of injected fluid verified. All cadavers were ex­amined in the supine position by the same physician using portable scanner Hitachi 405 EUB with a 3.5/5 MHz narrow convex trans­ducer (Hitachi Medical Corporation, Tokyo, Japan). The ultrasonographer was not previ­ously informed about the chosen velocity of infusion flow and the volume infused. Average minimal detectable quantity of fluid in the left and right hemi thorax was com­pared and correlated with height, weight and BSA of each cadaver. A statistical method was Mann-Whitney U test and Pearson's mo­ment of correlation. Results Minimal, by ultrasonography detectable amount of free fluid in the right pleural space was 223 ± 52 ml (range: 105 - 295 ml) with significant positive correlation to height (r = 0. 6849; p < 0.001), weight (r = 0.6799; p < 0.01) and the BSA (Figure 1) of cadaver (r = 0.7075; p < 0.001). Minimal detected volume in the left pleural space was notably smaller (p < 0.001) than contra lateral, namely 172 ±53 ml (range: 80 - 240 ml) also with a signif­icant correlation to the cadaver's height (r = 0.5532; p < 0.05), weight (r = 0.5886; p < 0.01) and BSA (r = 0.6042; p < 0.01) (Figure 2). Discussion The clinical routine in the diagnosis of pleural effusions uses a conventional posterior to an­terior (PA) chest radiography in the erect or high sitting position (ł45°) or a lateral decu­bitus radiography (LDR) where patients are in lying position. Both radiographic methods in standard hospital conditions have satisfac-tory accuracy, however, in the ICU setting where the quality of radiograph is sub opti­mal and where adequate positioning of the patient is impossible, the sensitivity of those methods in the detection of minor effusions is not convincing.1,2 A computed tomography is often used in the diagnosis of pleural effu­sions (quantitative and qualitative), but it is connected with the transport of patients from ICU and is not always available in all hospi­tals.1,2 Recently, ultrasonography has been recog­nised as a superior method in the diagnostics of pleural effusions in the supine position, particularly in critically ill ICU or trauma pa­tients.4-6 In the presented study, average minimal, by ultrasonography detectable, fluid volume in the right pleural space was 223 ml, while the mean volume of fluid in the left pleural space was 172 ml. Such discrepancy is proba­bly due to the position of cardiac massive, which is situated predominately in the left hemithorax. Classic anatomical studies con­firm that the transversal diameter of the lung base is significantly smaller on the left side (7­9 cm left vs. 10-13 cm right); that the left lung is smaller than the right and consequently, the overall volume of the left hemithorax is smaller than the overall volume of the right hemithorax.7 It follows that the required quantity of pleural fluid necessary for the ul­trasonographic visualisation in the left thorax is much smaller than on the right side. In the study a statistically significant cor­relation between the minimal detectable vol­ume of pleural effusion and cadaver's height, weight and BSA was demonstrated. It is logical to presume that in more corpu­lent patients with greater BSA more liquid will be needed to diagnosticate pleural effu­sion by ultrasonography. It is important to point out the great variability in the amount of minimal detectable fluid in the thorax be­tween cadavers varying from 160 ml on the left side to over 190 ml on the right side. Such large range together with a significant corre­lation between a minimal detectable volume of fluid in the thorax and cadaver's height, weight and BSA, shows that in clinical pre­conditions negative ultrasound findings do not exclude the presence of a small pleural ef­fusion. Such findings should be interpreted in the context of all available information about the patient's habitus. However, this study has an important defi­ciency. First, data of a cadaver study cannot be quite transferable to the clinical examina­tion of patients (respiratory effects, lung compliance, etc.). Furthermore, in clinical conditions it is usually possible to position a patient to a half-sitting position. It is presum­able that such movement, difficult to perform on cadavers, could influence on the delec­tability of fluids. On the basis of the results from the exper­imental, cadaveric model it can be concluded that ultrasonography enables the visualisa­tion of relatively small amount of pleural flu­id in patients in the supine position, but neg­ative finding does not exclude minimal effusion. References 1. Cascade PN, Kazerooni EA. Aspects of chest im­aging in the intensive care unit. Crit Care Clin 1994; 10: 247-65. 2. Tarver RD. Intensive care unit chest radiology. In: Newell JD, Tarver RD, editors. Thoracic radiology. New York: Raven Press Ltd.; 1993. p. 131-46. 3. Lomas DJ, Padley SG, Flower CDR. The sono-graphic appearances of pleural fluid. Brit J Radiol 1993; 66: 619-24. 4. Eibenberger KL, Dock WI, Ammann ME, Dorffner R, Hmann MF, Grabenwiger F. Quantification of pleural effusions: sonography versus radiogra­phy. Radiology 1994; 191: 681-4. 5. Sisley AC, Rozycki GS, Ballard RB, Namias N, Salomone JP, Feliciano DV. Rapid detection of traumatic effusion using surgeon-performed ultra-sonography. J Trauma 1998; 44: 291-6. 6. Mathis G. Thoraxsonography - Part I: Chest wall and pleura. Ultrasound Med Biol 1997; 23: 1131-9. 7. Warwick R, Williams PL. Gray's anatomy, 35th edn. Edinburg: Longman Group Ltd.; 1973. p. 1190-9. review Bone scintigraphy in clinical routine Vika M.ller1, Jirn Steinhagen2, Maike de Wit3, Karl H. Bohuslavizki1 Departments of 1Nuclear Medicine, 2Orthopedic Surgery and 3Hematology and Oncology, University Hospital Eppendorf, 20246 Hamburg, Germany Background. In 1971, bone scintigraphy was performed the first time using 99mTc-labeled polyphospho­nates. Since that time, bone scintigraphy has become one of the most frequent diagnostic procedures in nu­clear medicine departments. However, in the last decade, indications for this skeletal imaging procedure have been changing continuously. This paper, therefore gives a concise review of the current spectrum of indica­tions for bone scintigraphy and its realization. Conclusions. Just as many other nuclear medicine procedures, the bone scintigraphy has a high sensitivi­ty, and the changes of the bone metabolism are seen often earlier than the changes in bone structure devel­oping after x-ray. Therefore, occult lesions in the whole skeleton might be detected early by bone scintigra­phy. On the other hand, bone turnover is increased in various bone diseases. Consequently, bone scintigraphy usually has a low specificity, and differential diagnosis of the underlying etiology is often not feasible. However, three-phase bone scintigraphy and SPECT can significantly increase the specificity in some skeletal areas. Key words: Bone diseases-radionuclide imaging; technetium; diphosphonates; bone neoplasms; bone scintigraphy, 99mTc-diphosphonates, indications Introduction Since 1961 bone turnover has been examined using various radio-labeled substances. In 1971 bone scintigraphy was performed the first time using modern 99mTc-labeled polyphosphonates, e.g. 99mTc-hydroxyethyl- Received: 28 September 2000 Accepted: 16 October 2000 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 enephosphonate(HDP) or 99mTc-methoxyeth­ylenephosphonate (MDP). After intravenous injection, these radiopharmaceuticals are ad­sorbed at the bone surface within some hours. The amount of adsorption depends both on the perfusion of the bones and the in­tensity of bone metabolism. Moreover, bone-seeking radiopharmaceuticals are excreted by the kidneys, and the kidneys and bladder can be seen routinely on a bone scan. Thus, total bone uptake depends not only on the perfu­sion and metabolic turnover, but also on re­nal function. In regions with a high bone me­tabolism, e.g. epiphyseal plates of children or mechanically stressed regions, e.g. ileosacral joints, the radiopharmaceutical uptake is in­creased physiologically. Additionally, in sev­eral pathophysiological conditions, even ex-traskeletal accumulation of tracer can be seen, e.g. in scars, myositis ossificans, liver metastases or tumors.1-3 On the other hand, fat patients (high absorption of radiation) and patients with renal failure show a reduced bone-to-background contrast resulting in de­graded images. Since the first bone scans using 99mTc-la­beled polyphosphonates by Subramanian and Mc Affee4 in 1971, the radioactive load has decreased continuously for the patient due to radiopharmaceutical and technological ad­vantages, and bone scintigraphy has become a routine method in clinical nuclear medicine. However, in the last decade, the indications for bone scanning have changed dramatically. Therefore, the current spectrum of indica­tions for bone scintigraphy and its realization are reviewed concisely in this paper. Indications in benign bone diseases In inflammatory joint diseases, both soft tis­sue and bone metabolism can be affected. The three-phase bone scintigraphy can image the activity of both processes. Increased per­fusion, higher blood pool and raised activity of osteoblasts may be demonstrated by bone scan. Moreover, bone scan may contribute to the differential diagnosis of rheumatical joint diseases due to specific distribution patterns of several joint affections. Fractures are seen primarily in radiograph­ic images. Nevertheless, fractures in radi­ographically unclear regions can be excluded sufficiently by bone scintigraphy, and bone scanning also allows establishing the vitality of bone grafts or the loosening and infections of prostheses. Current clinical indications for bone scintigraphy in benign bone diseases are list­ed in Table 1. Table 1. Bone scanning in benign bone diseases Disease To be mentioned Osteomyelitis In 3-phase bone scintigraphy, the activity of the process and other bone lesions can be seen early in acuteosteomyelitis.9-11In newborn the sensitivity is as low as 50 %.1,2 In children with acute osteomyelitis MRI has the highestsensitivity (90%).12In diabetic foot, 3-phase bone scintigraphy should be first in the diagnostic cascade.13 However, 3-phase bonescintigraphy is sensitive but not specific in osteomyelitis of diabetic foot.14 Evaluation of prostheses Normal 3-phase bone scintigraphy excludes infection or loosening of hip prostheses.1,2 Sensitivity of 3-phase bone scintigraphy in knee prostheses is low.15 Arthritis or rheumatoid diseases Bone scintigraphy can be used to confirm arthritis if x-ray is normal. Scintigraphy may show arthritis earlier,Psoriatic arthritis may explore the severity of arthritis and may be used for evaluation of therapy.2,16-18 Ankylosing spondylitis Distribution of joint diseases may allow differential diagnosis.16,19 3-phase bone scintigraphy can be usedReiter's syndrome to evaluate the therapeutic success after radiosynoviorthesis.20 Degenerative joint diseases Bone scintigraphy is uncommon- osteoarthroses Avascular necrosis 3-phase bone scintigraphy may help, if MRI is not predicative.1,2,21 MRI is the method of choice for avascularPerthe's disease necrosis of the hip.22 Osteonecrosis Bone fractures and stress fractures Normal bone scan can exclude bone fractures after distinct time intervals,1,2,23 especially in carpal bones24,25 and tarsal bones, in scapula, vertebrae, proximal femur, sternum, pelvic bones,26 sacrum.27 Reflex sympathetic dystrophy 3-phase bone scan is of major importance for establishing the diagnosis, in staging and to control results oftherapy.28 Child abuse Bone scan provides an overview over the whole skeleton, and periostal lesions can be seen.1,2,29 Metaphyseallesions in younger children, multiple fractures in different stages of healing, posterior rib fractures, long-bone fractures in younger children are typical signs. Frostbite and ischemic injuries Bone scan may help to specify the need and the line of amputation.2,30 Paget's disease Normal 3-phase bone scintigraphy excludes dedifferentiation, helps to screen both regions and extent of boneinvolvement.2,11 Plantar fasciitis, archilles tendinitis, Normal 3-phase bone scan excludes inflammation in patients with clinical symptoms andosteitis pubis negative x-ray.2 Heterotopic ossification Bone scan is abnormal before radiographic lesions show up.2 Osteoporosis Bone scan is usually used to exclude stress and compression fractures.2,31 Osteomalacia Bone scan excludes pseudofractures earlier than x-ray.2 Benign bone tumors (enchondroma, Normal 3-phase bone scintigraphy excludes any bone involvement if radiographically no lesion is shown.chondroblastoma, giant cell tumors, However, bone scan has low specifity since most lesions will accumulate radioactive tracer. Characteristiceosinophilic granuloma, fibrous findings are rare, e.g. in osteoid osteoma.11 Usually, vertebral hemangioma show normal uptake in planar dysplasia, brown tumors of scintigraphy.32 hyperparathyroidism, osteoid Malignancy cannot be excluded by bone scintigraphy.2 osteoma, aneurysmal bone cyst,vertebral hemangioma) Bone infarction Bone scan has a high sensitivity but is less specific.Erdheim-Chester disease Scintigraphic patterns of involved skeletal sites may lead to the diagnosis.33 "Bone" pain of unknown origin Bone scan allows the differential diagnosis between soft tissue and bone lesion.2 In patients older than 50 yearsa bone scan is useful to exclude occult malignancy or metastases.34 Myositis ossificans 3-phase bone scan may demonstrate the activity of the process. Figure 1. Recurrent osteosarcoma in the right femur in a 17-year-old boy and metastatic disease in the right tibia (arrows). Indications in malignant bone diseases In primary bone tumors, the three-phase bone scintigraphy is often used to evaluate the primary lesion and to search for other oc­cult bone lesions. In oncology, bone scintigra­phy is used to exclude bone metastases of various malignancies. Current recommenda­tions for bone scanning in daily clinical nu­clear medicine are given in Table 2. Bone scanning The injected activity of 99mTc-polyphospho­nates varies from 700 to 800 MBq. In chil­dren, the activity is adapted to body weight, with a minimum of 80 MBq. Younger chil­dren should get a sedative during image ac­quisition in order to reduce movement arti- Table 2. Bone scnanning in malignant bone diseases Disease To be mentioned Primary bone tumors (Osteosarcoma, Bone scan is not useful to exclude primary bone malignancies.Ewing's Sarcoma, Chondrosarcoma) Bone scan is helpful to search for bone metastases or to exclude a local recurrence after treatment.2,35,36 3-phase bone scan is useful to evaluate treatment efficacy37 or viability of bone grafts. Screening for metastases Bone scan allows screening of the whole skeleton with a high sensitivity.38,39 Prostate cancer Bone scan is useful in preoperative staging when PSA is increasing ł30 ng/ml or in patients with clinicalevidence of bone metastases. Control of progression of known bone metastases with scintigraphy.40-42 Evaluation of therapeutic effects in bone metastases following endocrine therapy.43 Breast cancer Bone scan is indicated in primary staging of high-risk patients (axillary lymph nodes positive), clinical evidenceof bone metastases or if CA 15-3 is elevated.44,45 In known skeletal metastases bone scan allows to look forpotential pathological fractures.3 Treatment control is also possible by bone scan, if flare phenomenon is takeninto account.46About 5% of metastases are missed due to pure osteolyses.1 Lung cancer Bone scan in primary staging only in resectable tumors47,48 or in clinical evidence.46,49 About 10% of metastases are missed due to pure osteolyses.1 Renal cell or bladder carcinoma Bone scan should be done in patients with clinical evidence of bone metastases only.2,50 Differentiated thyroid cancer In advanced follicular thyroid tumors or increasing Tg-levels without any correlates in 131I-scan or in bone pain.About 30-50% of metastases may be missed due to pure osteolyses.1Patients with elevated serum calcitonin and patients with medullary thyroid carcinoma should undergo bonescintigraphy.2 Gastrointestinal cancer Only in patients with advanced regional tumors and clinical evidence of bone metastases or in patients inwhom an infiltration of sacrum is possible. Malignant Melanoma In patients with clinical evidence of bone metastases or in patients with advanced regional tumors orhistological positive lymph nodes. Bone scan cannot exclude bone metastases.2 Squamous-cell carcinoma of the Only in patients with an advanced-stage disease, local and regional recurrences, and in second primariesupper aerodigestive tract located below the clavicle.51 Cervical carcinoma, endometrial Only in patients with clinical evidence of bone metastases or with advanced regional or histologically poorlycarcinoma, ovarian carcinoma differentiated tumors.2 Testicular carcinoma Only in patients with stage IV seminoma with bone pain.2 Neuroblastoma 123I-MIBG-scintigraphy is more sensitive.2 Bone scan can show MIBG-negative metastases.52 Lymphoma Useful in primary lymphoma of the bone and in reticulum cell sarcoma.3 Multiple Myeloma Not useful since metastases are missed in 60-80% due to pure osteolyses.1 Systemic Mastocytosis Bone marrow scintigraphy is more sensitive.2 The degree of uptake and progress in serial scans marks moreaggressive bone marrow disease.53 Langerhans cell histiocytosis Bone scan may detect additional regions of bone involvement.54 Palliative pain-therapy with Bone scan is a prerequisite for palliative pain-treatment with 186Re-HEDP or 153Sm-HDTMP osteotrope radiopharmaceuticals. Soft tissue tumors Bone scintigraphy can establish the activity and perfusion of soft tissue processes. Screening for bonemetastases or postoperative recurrences is also possible. Anterior Posterior Anterior Posterior Figure 2. Bloodpool and late whole body images in a 75-year-old women with diabetes. Images show active os­teomyelitis of the talus (arrows) and degenerative disease in the lumbar spine due to scoliosis. Artificial photope­ nia in the left thorax is caused by a pacemaker. facts. In standard bone scintigraphy, images are acquired approximately 3 hours after in­jection. In the interim period, the patients should drink at least 1 liter of fluid. Immediately before image acquisition, the pa­tients are asked to empty their bladder. In or­der to reduce the radiation burden of physi­cians and nurses, bone scintigraphy should be performed directly after dialysis of the pa­tients with renal failure. In several focused problems, the three-phase bone scintigrams may give an overview of perfusion, blood pool, and bone mineral­ization. Dynamic image acquisition is started directly after intravenous injection of 99mTc­polyphosphonates (perfusion phase). After the first minute, a static image is acquired for 5 minutes (blood pool phase). Late static im­ages (mineralization phase) are performed at least after three hours. Usually, whole-body images are acquired at a double-headed gam­ma camera with large field-of-view. The quantification of images may help to establish specific diagnoses, e.g. in sacro-ileitis, or may help to monitor treatment regi­men, e.g. during chemotherapy of primary bone tumors. Additional images may be ac­quired from unusual angles optimized for best views of distinct bone areas. The images with a pinhole collimator permit clear identi­fications of small lesions, e.g. of bone infarc­tion in the femoral head of children. Add­itionally, tomographic image acquisition using single photon emission computed to­mography (SPECT) allows to separate over­lapping bone structures, e.g. in pelvic, verte­brae, or in hip joints in transaxial, coronal and sagittal projections. Figure 3. 61-year-old women with radiological obscure findings in the sacrum. Bone scintigraphy performed 6 days after trauma revealed sacrum fracture (arrows). Additionally, hip prosthesis on the right side without any signs of loosening or infection and degenerative changes of bone metabolism in the left hip, both shoulders and in the left big toe can be seen. Contraindications Bone scintigraphy will usually not be per­formed during pregnancy, and only life-threatening indications will lead to bone scanning in breast-feeding women. In these patients, breast-feeding should be discontin­ued for 48 hours after injection. In children, repeated imaging need rigorous indication, particularly because of the higher radioactive load in their epiphyseal plates. Radiation load The effective dose in normal bone metabo­lism and regular renal function amounts to Figure 4. Multilocalar bone metastases in a 73-year-old woman with breast cancer. 0.008 mSv/MBq, which is equivalent to 6 mSv per study.5 Conclusion Just as many other nuclear medicine proce­dures, the bone scintigraphy has a high sensi­tivity, and changes of the bone metabolism are often seen earlier than the subsequent changes in bone structure in x-ray. Therefore, occult lesions in the whole skeleton might be detected early by bone scintigraphy.6 On the other hand, bone turnover is increased in var­ious bone diseases. Consequently, bone scintigraphy usually has a low specificity, and the differential diagnosis of the underlying etiology is often not feasible. However, three-phase bone scintigraphy and SPECT7,8 can significantly increase the specificity in some skeletal areas. Anterior Posterior Anterior Posterior Figure 5. Bloodpool and late whole body images of 67-years-old man with Paget's disease in the pelvis (arrows). References 1. Schicha H, Schober O. Nuklearmedizin: CompactLehrbuch. 3 ed. Stuttgart: Schattauer Verlag; 1997. 2. Habert JC. The Musculoskeletal System. In: Habert JC, Eckelman WC, Neumann MD, editors. Nuclear Medicine: Diagnosis and therapy. New York: Thieme; 1996. p. 801-63. 3. Murray IPC. Nuclear medicine in disorders of bones and joints. In: Murray IPC, Ell PJ, editors. Nuclear medicine in clinical diagnosis and treatment. Livingstone: Churchill; 1998. p. 1123-303. 4. Subramanian G, McAfee JG. A new complex of 99mTc for skeletal imaging. Radiology 1971; 99: 192-6. 5. Bares R. Leitlinie f.r Skelettszintigraphie. Nuklearmedizin 1999; 38: 251-3. 6. Scharf S, Zhao QH. Radionuclide bone scanning in routine clinical practice. Lippincotts Prim Care Pract 1999; 3: 521-8. 7. Reinhartz P, Schaffeldt J, Sabri O, Zimny M, Nowak B, Ostwald E, et al. Benign versus malig­nant osseous lesions in the lumbar vertebrae: dif­ferentiation by means of bone SPET. Eur J Nucl Med 2000; 27: 721-6. 8. Savelli G, Chiti A, Grasselli G, Maccauro M, Rodari M, Bombardieri E. The role of bone SPET study in diagnosis of single vertebral metastases. Anticancer Res 2000; 20(2B): 1115-20. 9. Leitha T. Nuclear medicine procedures for diagno­sis of osteomyelitis. Der Radiologe 1996; 36: 813-22. 10. Sammak B, Abd El Bagi M, Al Ahahed M, Hamilton D, Al Nabulsi J, Youssef B, et al. Osteomyelitis: a review of currently used imaging techniques. Eur Radiol 1999; 9: 894-900. 11. Hendler A, Hershkop M. When to use bone scintigraphy. It can reveal things other studies cannot. Postgrad Med 1998; 104: 54-66. 12. Reinher T, B.rk G, Berger T, Schl.ter B, Andler W. Acute osteomyelitis in childhood. Comparison of sonography, scintigraphy and magnetic reso­nance tomography at onset of disease. Monatsschrift Kinderheilkunde 1998; 146: 1181-5. 13. Becker W. Imaging osteomyelitis and the diabetic foot. Q J Nucl Med 1999; 43: 9-20. 14. Tomas MB, Patel M, Marwin SE, Palestro CJ. The diabetic foot. Br J Radiol 2000; 73: 443-50. 15. Hogerle S, Nizsche E, Bonnaire F, Otte A, Kuner EH, Moser E. Indications for nuclear medicine di­agnosis in trauma surgery. Unfallchirurgie 1997; 23: 252-61. 16. Holzmann H, Krause BJ, Kaltwasser JP, Werner RJ. Psoriatische Osteoarthropathie und Skele­ttszintigraphie. Der Hautarzt 1996; 47: 427-31. 17. Klett R, Grau K, Puille M, Matter HP, Lange U, Steiner D, et al. Comparison of HIG scintigraphy and blood pool scintigraphy using HDP in arthrit­ic joint disease. Nuklearmedizin 2000; 39: 33-7. 18. Olejarova M, Kupka K, Pavelka K, Gatterova J, Stolfa J. Comparison of clinical laboratory, radi­ographic, and scintigraphic findings in erosive and nonerosive hand osteoarthritis. Results of a two-year study. Joint Bone Spine 2000; 67: 107-12. 19. Freyschmidt J. The bullhead sign: scintigraphic pattern of sternoclavicular hyperostosis and pus-tulotic arthroosteitis. Eur Radiol 1998; 8: 807-12. 20. Gratz S, Gobel D, Becker W. Radiosynoviorthesis in inflammatory joint disease. Orthop-de 2000; 29: 164-70. 21. Stuckey SL, Kalff V, Hoy G. Bone scan findings in Kienbick's disease. A case report with atypical findings and literature review. Clin Nucl Med 1997; 22: 481-3. 22. Kramer J, Breitenseher M, Imhof H, Urban M, Plenk H, Hofmann S. Imaging modalities in avas­cular necrosis of the hip. Orthop-de 2000; 29: 380-8. 23. Reeder MT, Dick BH, Atkins JK, Pribis AB, Martinez JM. Stress fractures. Current concepts of diagnosis and treatment. Sports Med 1996; 22: 198­212. 24. Roolker W, Maas M, Broekhuizen AH. Diagnosis and treatment of scaphoid fractures, can non­union be prevented? Arch Orthop Trauma Surg 1999; 119: 428-31. 25. Bayer LR, Widding A, Diemer H. Fifteen minutes bone scintigraphy in patients with clinically sus­pected scaphoid fracture and normal x-rays. Injury 2000; 31: 243-8. 26. Stevens SC, Male TA, Turner JH. Pelvic fractures diagnosed by bone scintigraphy in patients with normal radiographs after a fall. Med J Aust 1999; 171: 476-8. 27. Major NM, Helms CA. Sacral stress fractures in long-distance runners. Am J Roentgenol 2000; 174: 727-9. 28. Driessens M, Dijs H, Verheyen G, Blockx P. What is reflex sympathetic dystrophy? Acta Orthop Belg 1999; 65: 202-17. 29. Kocher MS, Kasser JR. Orthopaedic aspects of child abuse. J Am Acad Orthop Surg 2000; 8: 10-20. 30. Cauchy E, Chetaille E, Lefevre M, Kerelou E, Marsigny B. The role of bone scanning in severe frostbite of the extremities: a retrospective study of 88 cases. Eur J Nucl Med 2000; 27: 497-502. 31. Gasser RW, Finkenstedt G. Systemic diagnostic workup: differential diagnosis of various forms of osteoporosis. Wien Med Wochenschr 1999; 149: 479-84. 32. Han BK, Ryu J, Moon DH, Shin MJ, Kim YT, Lee HK. Bone SPECT imaging of vertebral haeman­gioma. Correlation with MR imaging and symp­toms. Clin Nucl Med 1995; 20: 916-21. 33. Gotthardt M, Welcke U, Brandt D, Tontsch D, Barth PJ, Schaefer J, et al. The role of bone scintig­raphy in patients with Erdheim-Chester disease. Clin Nucl Med 2000; 25: 414-20. 34. Jacobson AF. Musculoskeletal pain as an indicator of occult malignancy. Yield of bone scintigraphy. Arch Intern Med 1997; 157: 105-9. 35. Davies AM. Bildgebung beim prim-ren Osteosarkom. Der Radiologe 1998; 38: 492-501. 36. Henk CB, Grampp S, Wiesbauer P, Zoubek A, Kainberger F, Breitenseher M, et al. Ewing sarcoma. Diagnostic imaging. Radiologe 1998; 38: 509-22. 37. Focacci C, Lattanzi R, Iadeluca ML, Campioni P. Nuclear medicine in primary bone tumors. Eur J Radiol 1998; 27 (Suppl 1): 123-31. 38. Hansmann H, Wunsch C, Schneider B, Brado M, Flesch M, Richter GM, et al. Radiologische Diagnostik von Knochenmetastasen. Der Orthop-de 1998; 27: 224-30. 39. Howman-Giles R, Bernard E, Uren R. Pediatric nu­clear oncology. Q J Nucl Med 1997; 41: 321-35. 40. Ornstein DK, Oh J, Herschman JD, Andriole GL. Evaluation and management of the man who has failed primary curative therapy for prostate can­cer. Urol Clin North Am 1998; 25: 591-601. 41. Jhaveri FM. How to explore the patient with a ris­ing PSA after radical prostatectomy: defining local versus systemic failure. Semin Urol Oncol 1999; 17: 130-4. 42. Schmid H, Oberpenning F, Pummer K. Diagnosis and staging of prostatic carcinoma: what is really necessary? Urol Int 1999; 63: 57-61. 43. Rydh A, Ahlstrom KR, Larsson A, Johansson L, Damber JE, Tomic R, et al. Quantitative bone scintigraphy. A methodological evaluation in prostate cancer. Acta Radiol 2000; 41: 183-8. 44. Younsi N, Montravers F, Philippe C, Seddiki M, Uzan S, Izrael V, et al. CA 15-3 and bone scintig­raphy in the follow-up of breast cancer. Int J Biol Markers 1997; 12: 154-7. 45. Bares R. Skeletal scintigraphy in breast cancer managment. Q J Nucl Med 1998; 42: 43-8. 46. Becker W. A changing role for bone scintigraphy in oncology: the road from routine imaging screen­ing to patient-based screening. Eur J Nucl Med 1998; 25: 1359-61. 47. Prauer HW, Helmberger H, Weber W. Diagnostik des Bronchialkarzinoms. Radiologe 1998; 38: 256­62. 48. Wundbaldinger P, Bankier AA, Strasser G, Hoffmann U, Sch-fer-Prokop C, Herold CJ. Staging des Bronchialkarzinoms. Der Radiologe 1999; 39: 525-37. 49. Michel F, Soler M, Imhof E, Perruchoud AP. Initial staging of non small cell lung cancer: value of rou­tine radioisotope bone scanning. Thorax 1991; 46: 469-73. 50. Staudenherz A, Steiner B, Puig S, Kainberger F, Leitha T. Is there a diagnostic role for bone scan­ning of patients with a high pretest probability for metastatic renal cell carcinoma? J Nucl Med 1999; 40: 1623-9. 51. J-ckel MC, Rausch H. Fernmetastasierung von Plattenepithelkarzinomen des oberen Aerodigestivtrakts. Der Einfluss klinischer Tumorparameter und des Krankheitsverlaufs. HNO 1999; 47: 38-44. 52. Gordon I, Peters AM, Gutmann A, Morony S, Dicks-Mireaux C, Pritchard J. Skeletal assessment in neuroblastoma - the pitfalls of iodine-123-MIBG scans. J Nucl Med 1990; 31: 129-34. 53. Chen CC, Andrich MP, Mican J, Metcalfe DD. A retrospective analysis of bone scan abnormalities in mastocytosis: correlation with disease category and prognosis. J Nucl Med 1994; 35: 1471-5. 54. Meyer JS, De Camargo B. The role of radiology in the diagnosis and follow-up of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998; 12: 307-26. Intraoperative radiation therapy (IORT) to the tumor bed only for breast cancer: technique and outcome Gary M. Proulx1, Thelma Hurd2, R. Jeffrey Lee1, Paul C. Stomper3, Matthew B. Podgorsak1, Stephen B. Edge2 1Radiation Oncology, 2Surgical Oncology, 3Diagnostic Imaging-Mammography, State University of New York at Buffalo, Roswell Park Cancer Institute, Buffalo, NY 14263 Background. Recent published reports have demonstrated that not all patients with early stage breast can­cer need the entire breast irradiated for local control of their disease. To address the difficulties of several weeks of irradiation treatment, investigators have utilized different radiation techniques and treatment schedules that reduce the overall treatment time without compromising outcome. Patients and methods. An analysis was made of 7 patients treated on protocol with local intraoperative radiation (IORT) alone to the lumpectomy site after surgery with or without axillary dissection. All patients received IORT with 120 kV x-rays to the tumor bed at the time of resection. Doses ranged from 1500 cGy to 2000 cGy. Three patients were stage I, two stage IIA, and two stage IIB. Results. With a mean follow up of 123 months (range 86 to 139 months), two of seven patients developed a local recurrence which were treated with mastectomy. The disease specific survival is 100% and overall survival is 86% with one patient being dead without disease. The cosmetic outcome of the 5 patients with their treated breast remaining have expressed satisfaction with the results. No treatment related complica­tions have occurred. Conclusions. The results of our pilot study support the findings that not all patients with early stage breast cancer need the entire breast irradiated for durable local control of their disease. However, patient numbers in this study are low and any conclusions need further evaluation with larger trials. Key words: breast neoplasms-radiotherapy; intraoperative radiation, breast cancer, breast conservation therapy Received 25 September 2000 Accepted 4 October 2000 Correspondence to: Gary M. Proulx, MD, Roswell Park Cancer Institute, Department of Radiation Oncology, Elm & Carlton Streets, Buffalo, NY 14263. Phone: +1 716 845 3172; Fax: +1 716 845-7616; E-mail: gary.proulx@RoswellPark.org Introduction Breast conserving therapy (BCT) is a well es­tablished mode of treating early stage breast cancer. Several prospective randomized stud­ies have demonstrated equivalent efficacy in overall and disease-free survival in patients undergoing either BCT or mastectomy.1-8 Furthermore, BCT eliminates the emotional and psychological stress associated with re­moval of the breast. Currently, standard radi­ation treatment after lumpectomy involves treating the entire breast with external beam irradiation often followed by a local boost to the tumor bed. The rationale for the boost is that most recurrences involve the tumor site or near it.9,10 Radiation treatment generally involves 6-7 weeks of once-a-day treatment. The difficulties to patients with such lengthy treatment involve transportation issues, em­ployment issues and physical limitations of the patient. These difficulties may be a major reason why many eligible patients for BCT do not receive it. These factors have led to the hypothesis that radiation alone to the primary tumor bed may be enough for local control of disease with BCT. We report here on the long-term outcome of seven patients treated on a pilot study at Roswell Park Cancer Institute for their breast cancer with local radiation alone using intraoperative irradiation (IORT) to the tumor bed after lumpectomy with or without axillary dissection. Patients and methods Seven patients with breast carcinomas were treated with adjuvant radiation using IORT alone to the surgical bed after lumpectomy with or without axillary dissection. Patients were assessed for age, race, meno­pausal status, family history, T-stage, nodal status, hormone receptor status, margin sta­tus, and grade. Details of patient and tumor characteristics are outlined in Tables 1 and 2. The mean age of the patients treated was 58 years (range 43-70 years). Six of the seven patients were Caucasian and one patient was Hispanic. Two of the seven were pre-menopausal defined by cessation of menses at the time of treatment. Two patients had a positive family history of breast cancer with having one or more members of the immedi­ate family diagnosed with breast cancer. Patients were staged according to the American Joint Committee on Cancer (AJCC). Three patients had stage I and four stage II disease. Tumor staging include T1c (3), T1b (1), T2 (2), and T3 (1). Axillary nodal status was assessed in six of seven patients. One pa­tient did not have the axilla surgically as­sessed because of medical reasons and was clinically negative. Four of the six were node negative and two were positive, one with 4/37 nodes positive and one with 3/13 nodes posi­tive. Five of seven patients were hormone re­ceptor positive. Margins were negative in all patients. All of the patients had serial post-treat­ment mammograms at Roswell Park Cancer Institute (RPCI). These were reviewed in-house with specific attention to any alteration of the appearance of the surgical excision site or changes associated with whole breast irra­diation (i.e., increased parenchymal density and/or skin thickening ).11 All patients were treated with intraopera­tive radiation using orthovoltage 120 kVp x-rays to the tumor bed at the time of resection. A Picker Zephyr 120 machine was rebuilt in­to a compact portable unit for use in a desig­nated operating suite. The applicator size and prescribed dose were selected at the time of surgery following lumpectomy with or with­out axillary node dissection. Five of the seven patients received a dose of 1500 cGy to the tu­mor bed and two patients received 2000 cGy. All patients have been followed closely since completion of treatment with physical examinations, mammograms, chest x-rays, and standard laboratory studies. Cosmetics has been assessed by both the patient and physician by expression of either satisfaction or dissatisfaction with the appearance of their breast. This included shape and texture of the breast as well as the skin color. A retrospective review of the medical records was made to determine treatment Table 1. Patient characteristics Patient Age Race Stage Menopausal Status Fm Hx Birth Control Use 1 70 Caucasian IIA (T1cN1) Post no no 2 43 Caucasian IIA (T2N0) Pre yes no 3 51 Caucasian I (T1cN0) Pre no no 4 62 Hispanic IIB (T2N1) Post no no 5 56 Caucasian I (T1bN0) Post no no 6 63 Caucasian I (T1bN0) Post no no 7 60 Caucasian IIB (T3N0) Post yes no Fm Hx = positive family history of breast cancer Table 2. Tumor characteristics Patient Pathology Quadrant Margins Grading T Stage Nodal Status ECE ER/PR 1 IDC UOQ ( - ) high Tic pN1(4/37) (+) (+)/(+) 2 IDC UIQ ( - ) high T2 pN0(0/9) (-) (+)/(-) 3 IDC LOQ ( - )* high T1c pN0(0/29) (-) (+)/(-) 4 IDC UOQ ( - ) high T2 pN1(3/13) (-) (-)/(-) 5 IDC UOQ ( - ) inter T1c pN0(0/15) (-) (-)/(-) 6 IDC UOQ ( - ) high T1b pN0(0/25) (-) (+)/(+) 7 ILC UOQ ( - ) inter T3 not assessed (-) (+)/(+) * Close: < 2 mm IDC = Invasive ductal carcinoma; ILC = Invasive lobular carcinoma; UOQ = upper-outer quadrant; UIQ = upper-inner quadrant; LOQ = lower-outer quadrant; ECE = Extra capsular extension; ER/PR = estrogen and progesterone receptors rendered and the events of local control, dis­tant failure, disease-specific survival, overall survival, cosmetic outcome, and complica­tions (Table 3). Results Serial post-treatment mammograms were available for review on each patient and showed no alteration of the post-excision mammographic appearance for a median fol­low-up of 6 years (range 2-10 years). Five of 7 (71%) patients had mammographic evidence of post-surgical scarring consisting of archi­tectural distortion and focal skin thickening. There was no short or long-term alteration of the appearance of the primary excision site after intraoperative radiation treatment. There was no identifiable skin thickening or increased mammographic parenchymal den­sity attributable to IORT. After a mean follow-up of 123 months (range of 86 to 139 months), 6 of 7 patients were free of disease. Two of seven patients re­curred locally. One patient with stage I, T1cN0M0 recurred in the surgical scar 36 months after local treatment, while the sec­ond patient with local recurrence, stage IIB, T2N1, recurred within the treatment bed at 120 months. These patients both underwent mastectomy and remain disease-free 70 months later and 12 months respectively. Therefore, the disease-specific survival is 100%. One patient died of other causes with­out evidence of disease. Regarding cosmetic outcome, the 5 patients who have successful­ly preserved their affected breast have ex­pressed personal satisfaction with the results, as had the two patients with local failures up Table 3. Treatment given and outcome Patient Surgery TAM Surface Dose Follow Up (month) Local Failure Distant Failure Status 1 Lump + Ax + 1500 cGy 139 no no ANED 2 Lump + Ax - 1500 cGy 132 no no ANED 3 Lump + Ax + 1500 cGy 133 yes no ANED 4 Lump + Ax + 1500 cGy 135 yes no ANED 5 Lump + Ax - 2000 cGy 137 no no ANED 6 Lump + Ax + 2000 cGy 132 no no ANED 7 Lump + 1500 cGy 86 no no DNED TAM = tamoxifen; Lump = lumpectomy; Ax = axillary dissection; ANED = alive, no evidence of disease; DNED = died of other causes, no evidence of disease until the time of their mastectomy. No treat­ment related complications have occurred. Discussion To address the difficulties of several weeks of irradiation treatment, investigators have uti­lized different radiation techniques and treat­ment schedules that reduce the overall treat­ment time without compromising outcome. By reducing the overall treatment time, many patients could potentially be able to receive BCT who might not otherwise because of dif­ficulties related to a several week course of ra­diation. One technique employs the use of hypofractionated external beam radiation treatment (EBRT) of the entire breast with the number of treatments reduced by delivering higher doses per fraction.12 Another tech­nique combines whole breast EBRT with in-traoperative electrons to boost the surgical bed, thereby reducing the number of boost treatments by giving only one treatment at the time of surgery.13 In addition to different techniques and treatment schedules to re­duce the overall treatment time, the possibili­ty of treating only the tumor bed and not the entire breast is currently under investigation. The rationale for giving only local irradia­tion to the tumor bed region is supported by both pathologic data from mastectomy speci­mens and patients treated with tumorectomy alone that has shown a relatively low risk of tumor burden and failure rate distant from the primary tumor site. In evaluating over 200 mastectomy specimens, Holland et al. found 32% of patients with extensive intraductal component (EIC) and only 12% of patients without EIC had residual disease greater than 4 cm from the cancer removed by surgery.14 In another report as high as 36% of mastecto­my specimens had either in-situ disease or in­vasive disease between 2 and 4 cm from the tumor site.15 In addition several reports of patients treated with local surgery alone have identi­fied subsets of patients that have the tumor bed quadrant as the predominate site of re­currence and are consequently at a very low risk of recurrence elsewhere within the breast. Fisher et al. found that of 1108 patho­logically patients able to be evaluated and treated with lumpectomy (9.9%) from the NS­ABP protocol 6, 110 patients developed a lo­cal breast recurrence. All 110 patients had their recurrence within or close to the quad­rant of the initial or index cancer.9 In another series, Liljegren et al. had 33/36 (77%) of all lo­cal recurrences within the surgical field after wide excision alone.10 Since the risk of recurrence appears to be low outside a margin around the surgical re­section, can irradiation of the surgical bed achieve the same local control as irradiating the entire breast with a boost to the tumor bed? The use of local irradiation alone to the surgical bed with radioactive implants or IORT electrons would significantly reduce the number of treatments that patients would receive from several weeks of once-a-day treatment to only a single day of treatment. The use of IORT with electrons is not a new concept with its benefits having been report­ed for solid tumors, most notably for intraab­dominal or pelvic tumors;16,17 however, its use in breast cancer, however, has mainly been limited to boosting after external beam radiation treatment (EBRT) to the entire breast.14 Furthermore, IORT with orthovoltage has been successfully utilized for other sites in­cluding the treatment of rectal, gynecologic, and pancreatic malignancies.18-20 In our se­ries, orthovoltage was selected over the use of electrons at the time because of difficulties with transporting the patient to the radiation department where electrons could be deliv­ered. Other advantages of using the 120 kVp machine included low cost, ease of radiation protection, and direct observation of the pa­tient 5 ft away from the anesthetist with im­mediate access to the patient if needed. Disadvantages of the system included a shal­low fall-off of dose, and a relatively low out­put of 100 cGy per minute. Orthovoltage x-ray beams can potentially offer a simple, generally applicable, alternative treatment modality for intraoperative radiotherapy. The limited choice of x-ray energy, however, re­quires that a compromise be made between providing an adequate depth of penetration to cover the tumor volume while minimizing the dose to underlying tissues. The use of local irradiation alone after tu­morectomy in early stage breast cancer is cur­rently being explored in subsets of patients felt to be at low risk for a recurrence outside of the surgical bed. Recent reports using brachytherapy alone to the tumor bed have encouraging results. Perera et al. reported on­ly 1 infield recurrence out of 39 patients treat­ed with high dose rate brachytherapy (HDR) to the primary tumor bed at a median time of 20 months.21 Similarly a pilot study using low dose rate brachytherapy (LDR) by Vincini et al. demonstrated no local recurrences for 51 women at a median of 20 months follow-up. Selection criteria required tumors to be 3 cm or less, margins greater than or equal to 2 mm, no extensive intraductal component (EIC), a level I and II axillary dissection with up to 3 lymph nodes positive, pre- and post­operative mammograms, breast technically suitable for implant, implant performed with­in 8 weeks of last breast surgery, and patients at least 40 years of age.22 Additionally, Kuske et al. have had no local breast recurrences involving 51 patients treated with either LDR or HDR brachythera­py with a four year median follow-up. Cosmetics was good to excellent in 78% treat­ed with LDR and 67% for HDR.23 The GuyŐs Hospital experience using local LDR brachytherapy reports only two isolated local regional recurrences (7.5%) and a 96% good to excellent outcome.24 In contrast, Ribeiro et al. had inferior results when local radiation to the involved quadrant using 10 MeV elec­trons was utilized vs treating the entire breast with tangent fields. At six years follow-up, both axillary and breast reccurrence were higher for the local radiation treatment arm. A 20% recurrence rate in the breast for lobu­lar carcinomas in the quadrant - radiation arm was felt to contribute to this difference.25 A current phase II Radiation Therapy Oncology Group (RTOG) trial is ongoing comparing low dose rate (LDR) with 45Gy vs high dose rate (HDR) with 34 Gy brachyther­apy in patients meeting criteria for low risk for recurrence outside of the surgical bed. Our observation that intraoperative radia­tion treatment does not alter the mammo-graphic appearance of the primary excision site is important because a majority of early local recurrences after breast-conserving therapies occur at or near the primary exci-sion site. Stability or resolution of the mam-mographic post-surgical changes on serial mammograms is an essential component of the mammographic analysis in the follow-up of these patients.11 The lack of any apprecia­ble mammographic changes often associated with whole breast irradiation may improve the sensitivity for detection of recurrence for some patients. Our study and the brachytherapy studies suggest that tumor bed irradiation alone can be effective in controlling disease within the breast for selected early-stage patients and provide good to excellent cosmetics as judged by both patient and physician. In our series, despite not all of the patients fitting the strict criteria of more modern studies exploring the use local radiation alone (e.g., no lobular his­tologies, no tumors larger than 3 cm, no asso­ciated extensive intraductal component), five of seven have achieved local control with the two local failures occurring at very long inter­vals after treatment (Table 3). The optimal treatment for breast cancer patients desiring breast preservation is in evolution. In our pilot study, two patients have failed locally within the treatment site at long intervals from treatment, which indi­cates that patients may require lifetime fol­low-up and perhaps higher local doses to the local field than were given in this study. The benefits of treating locally with IORT with one treatment include more convenience to the patient, lower treatment costs, and less volume of normal tissue irradiated. Our re­sults would seem to suggest that not all pa­tients with breast cancer need the entire breast irradiated to obtain local control of their disease. However, patient numbers in this study are low and any conclusions need further evaluation with larger patient num­bers using prospective studies. Acknowledgements We would like to thank S Kishel, R. Russo, RTT and F Wojtas, RTT, RN for the excellent patient care given to these patients and for technical support in their treatment. Also we are grateful to Dr. Remedios B. Penetrante for review of the pathologic specimens. References 1. Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and re­sults after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1995; 333: 1456-61. 2. Veronesi U, Luini A, Galimberti V, Zurrida S. Conservative approaches for the management of stage I/II carcinoma of the breast: Milan Cancer Institute Trials. World J Surg 1994;18: 70-5. 3. van Dongen JA, Bartelink H, Fentiman IS, Lerut T, Mignolet F, Olthuis G, et al. Factors influencing lo­cal relapse and survival and results of salvage treatment after breast-conserving therapy in oper­able breast cancer: EORTC trial 10801, breast con­servation compared with mastectomy in TNM stage I and II breast cancer. Eur J Cancer 1992; 28A: 801-5. 4. Morris AD, Morris RD, Wilson JF, White J, Steinberg S, Okunieff P, et al. Breast-conserving therapy vs mastectomy in early-stage breast can­cer: a meta-analysis of 10-year survival. Cancer J Sci Am 1997 Jan-Feb; 3: 6-12. 5. Blichert-Toft M, Rose C, Anderson JA, Overgaard M, Axelsson CK, Andersen KW, et al. Danish ran­domized trial comparing breast conservation ther­apy with mastectomy: Six years of life-table analy­sis. J Natl Cancer Inst Monogr 1992; 11: 19-25. 6. Sarrazin D, Le MG, Arriagada R, Contesso G, Fontaine F, Spielmann M, et al. Ten-year results of a randomized trial comparing a conservative treat­ment to mastectomy in early breast cancer. Radiother Oncol 1989; 14: 177-84. 7. Jacobson JA, Danforth DN, Cowan K, dŐAngelo T, Steinberg SM, Pierce L, et al. Ten-year results ofthe National Cancer InstituteŐs randomized trial of breast conservation versus mastectomy for stage I and II breast cancer. N Engl J Med 1995; 332: 907­11. 8. Atkins H, Hayward JL, Klugman DJ, Wayte AB. Treatment of early breast cancer: A report after 10 years of a clinical trial. Br Med J 1072; 2: 423-9. 9. Fisher ER, Sass R, Fisher B, Gregorio R, Brown R, Wickerham L. Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol 6): II. Relation of local breast recurrence to multicentricity. Cancer 1986; 57: 1717-24. 10. Liljegren G, Holmberg L, Adami HO, Westman G, Graffman S, Bergh J. Sector resection with or without postoperative radiotherapy for Stage I breast cancer: five-year results of a randomized tri­al. J Natl CA Inst 1994; 86: 717-22. 11. Stomper PC, Recht A, Berenberg AL, Jochelson MS, Harris JR. Mammorgraphic detection of re­current cancer in the irradiated breast. AJR 1987; 48: 39-42. 12. Maher M, Campana F, Mosseri V, Dreyfus H, Vilcoq JR, Gautier C, et al. Breast Cancer in Elderly Women: A Retrospective Analysis of Combined Treatment with Tamoxifen and Once-Weekly Irradiation. Int J Radiat Oncol Biol Phys 1995; 31: 783-9. 13. Merrick HW 3rd, Battle JA, Padgett BJ, Dobelbower RR Jr. IORT for early breast cancer: a report on long-term results. Front Radiat Ther Oncol 1997; 31: 126-30. 14. Holland R, Connolly JL, Gelman R, Mravunac M, Hendriks JH, Verbeek AL, et al. The presence of an extensive intraductal component residual (EIC) following a limited excision predicts for promi­nent residual disease in the remainder of the breast. J Clin Oncol 1990; 8: 113-8. 15. Rosen PP, Fracchia AA, Urban JA, Schottenfeld D, Robbins GF. ÓResidualÓ mammary carcinoma fol­lowing simulated partial mastectomy. Cancer 1975; 35: 739-47. 16. Willett CG, Shellito PC, Tepper JE, Eliseo R, Convery K, Wood WC. Intraoperative electron beam radiation therapy for primary locally ad­vanced rectal and rectosigmoid carcinoma. J Clin Oncol 1991; 9: 843-9. 17. Gunderson LL, Willett CG, Harrison LB, Petersen IA, Haddock MG. Intraoperative irradiation: cur­rent and future status. Semin Oncol 1997; 24: 715­31. 18. Kim HK, Jessup JM, Beard CJ, Bornstein B, Cady B, Stone MD, et al. Locally advanced rectal carcino­ma: pelvic control and morbidity following preop­erative radiation therapy, resection, and intraoper­ative radiation therapy. Int J Radiat Oncol Biol Phys 1997; 38: 777-83. 19. Hicks ML, Piver MS, Mas E, Hempling RE, Mcauley M, Walsh DL. Intraoperative orthovolt-age radiation therapy in the treatment of recurrent gynecologic malignancies. Am J Clin Oncol 1993; 16: 497-500. 20. Rich TA. Radiation therapy for pancreatic cancer: eleven year experience at the JCRT. Int J Radiat Oncol Biol Phys 1985; 11: 759-63. 21. Perera F, Engel J, Holliday R, Scott L, Girotti M, Girvan D, et al. Local resection and brachytherapy confined to the lumpectomy site for early breast cancer: a pilot study. J Surg Oncol 1997; 65: 263-7. 22. Vincini FA, Chen PY, Fralle M, Gustafson GS, Edmundson GK, Jaffray DA, et al. Low-dose rate brachytherapy as the sole radiation modality in the management of patients with early-stage breast cancer treatment with breast-conserving therapy: preliminary results of a pilot trial. Int J Radiat Oncol Biol Phys 1997; 38: 301-10. 23. Kuske RR, Bolton JS, Wilenzick RM, McKinnon WMP, Pullen B, Scroggins TG, et al. Brachytherapy As the Sole Method of Breast Irradiation in TIS, T1,T2, N0-1 Breast Cancer. Int J Radiat Oncol Biol Phys 1994; 30(S1): 245. 24. Fentiman IS, Poole C, Tong D, Winter PJ, Mayles HM, Turner P, et al. Iridium implant treatment without external radiotherapy for operable breast cancer: a pilot study. Eur J Cancer 1991; 27: 447-50. 25. Ribeiro GG, Dunn G, Swindell R, Harris M, Banerjee SS. Conservation of the breast using two different radiotherapy techniques: interim report of a clinical trial. Clin Oncol 1990; 2: 27-34. Sentinel lymph nodes identification in early breast cancer - peritumoral or subareolar injection of lymphotropic blue dye? George Baichev1, Sonia Sergieva2, Grigor Gorchev1 1Dept. of Surgical Oncology, University Centre of Oncology, Pleven, Bulgaria 2Dept. of Nuclear Medicine, National Centre of Oncology, Sofia, Bulgaria Background. The sentinel lymph node (SLN) biopsy is a recently developed, minimally invasive method for staging the axilla in patients with early breast cancer. The authors investigated the optimal technique -peritumoral versus subareolar injection for the localization of the SLN. Patients and methods. 192 procedures out of 238 ones were performed using a blue dye peritumoral in­jection at the early breast cancer site against 46, with a subareolar technique. All patients underwent sen­tinel node biopsy, followed by an axillary lymph node dissection. Results. The SLN were metastatic in 69 out of 80 axillary positive patients that accounted for 86,3%. The sentinel node histology correctly predicted the axillary disease in 90,6% with a peritumoral injection versus 68,8 % with a subareolar lymphatic mapping. Conclusions. This experience indicates that the peritumoral injection of blue dye is a more accurate than the subareolar one for axillary staging. Key words: breast neoplasms; lymphatic metastasis; axilla; lymph nodes-pathology; biopsy; early breast cancer; sentinel lymph node biopsy Introduction Axillary staging operations in patients with breast cancer range from sampling with a blind biopsy alone to complete or with a total Received: 18 July 2000 Accepted 20 September 200 Correspondence to: George Baitchev, MD, Dept. of Surgical Oncology, Centre of Oncology, Medical University, 1stKl. Ohridsky str., 5800 Pleven, Bulgaria. Phone: +359 64 427245; Fax: 359 64 801603; E-mail: oncology@el-soft.com lymph node dissection. The concept of the sentinel lymph node (SLN) has profound consequences for our understanding of the process of tumour cell spread. The sentinel lymphadenectomy has been shown as an attractive technique in multiple studies, carried out recently as a part of on­going effort to find a less invasive and still ad­equate method for axillary staging (N+ or N-) in the cases of early breast cancer. The first SLN or SLNs along the lymphatic pathways have never before been traced by the preop­erative instillation, both of the blue dye1 or ra­dioactive nanocolloid2 peritumorally. The his­tological assessment of this "strategic spot" after the biopsy was compared with the re­sults of the axillary dissection. The accuracy is reported to be up to 87-100%.1-3 The extensive research of the lymphatic drainage and metastatic mapping led some authors up to the idea of employing the alter­native approach, namely - the subareolar in­jection of radiocolloids, aiming the indication of the SLN.4,5 There is no sufficient data in the literature related to subareolar mapping of SLN. Hence, the purpose of the current study was to examine the both methods comparatively and to submit the results of the analyses. Patients and methods During the period from February 1995 through June 2000, 238 women with primary early invasive, unilateral breast carcinoma (T1-2, N0-1, M0) scheduled for the surgical treatment at our department were enrolled in this study. The median age of the group was 56.1 years (range 24 to 75). We excluded pregnant or lactating women, those who had previously undergone biopsy or received radiotherapy to the axilla. Patients with multicentrical or multiphocal breast carcinoma, mammographically con­firmed, were also excluded. Informed con­sent was obtained in all cases. The technique of lymphatic mapping and sentinel node biopsy included the following: in 192 patients, 2 ml of lymphotropic blue dye were injected immediately before the in­troduction of anaesthesia with a fine needle (21-22 G) around the tumour. In the majority of cases - 147 (76.6 %), Patent blue V (BYK Gulden) was applied, and 19 patients re­ceived Drimaren Brilliant blue (Fluka). The study also included 26 females with breast cancer in whom locoregional perioperative chemotherapy with Mitoxantrone (Novan­trone, Wyeth-Lederle) was carried out. Two sites around the tumour were injected with 0.5 ml (1 mg) Mitoxantrone. It was estab­lished that Mitoxantrone dyes the lymphatic system very well, so this drug was used as a dye occasionally. The rest 46 patients received the subareo­lar injections into two different zones by 0,5 ­1,5 ml each, into the respective quadrant where the carcinoma had been localized. Preoperative lymphoscintigraphy was per­formed in 9 patients. 99mTc - sulphur colloid (Solco Lymphoscint, Sorin) with the particle average diameter of 50 nm was injected in the subareolar area in volume of 0,2 - 0,3 ml. The specific radioactivity of the injection zone was 20 mBq. Planar images - in frontal and in­clined positions were obtained by rotative ­gamma camera (Diacam, Siemens). The visu­alization achieved: the early one - at the 20-th minute and the late one - at the 120 to180-th minute after the application, respectively. In most of the cases - 201 (84,5%) a modi­fied radical mastectomy was performed and in 37 (15,5%) - quadrantectomy with axillary dissection. Lymphadenectomy in 215 cases (90,3%) includes I, II and III axillary anatomic levels and in 23 cases (9,7%) with minimal size of the tumour (<1cm) - I and II levels. All nodes in the axillary dissection specimen were processed for histologic examination us­ing hematoxylin and eosin (H&E). Immunohistochemical techniques to identify micrometastases were not performed. Results The median amount of the removed and ex­amined lymph nodes is 12,6 (range 10-21). The identified blue-stained SLNs ranged 1 to 3, i.e. 1,5 per case at the average. Sentinel nodes were located on level I in 193 cases, in 34 cases - on level I and II, and in 11 cases SLN mapped only on level II. Lymph node metastases had been found in 80 patients that accounted for 33,6% of the background - 64 of them from the group with peritumoral application of blue dye and 16 belonged to the group with subareolar appli­cation. Sixty-nine women (86,3%) had posi­tive SLNs (Table 1). Table 1. The axillary status of the two groups of pa­tients studied Lymph dissection SLN (+) (-) Total Peritumoral (+) (-) 58 6 -128 58 134 Subareolar (+) 11 - 11 (-) 5 30 35 Total 80 158 238 SLN= sentinel lymph node In most cases with mapped metastatic SLN the primary tumour is located in the lat­eral quadrants (53 cases). In 16 patients the carcinoma is localized centrally and in the rest 11 cases the tumour had medial location (Table 2). After the preoperative lymphoscintigraphy hot spots were identified in 7 cases. In five women one SLN in each case were scanned in the axilla site zone on level I - as at the ear­ly so at the late stage of scanning. In other two patients with medial location of the tu­mour 1 sentinel node in each case was visual­ized in the area of ipsilateral lymphatic parasternal chain. With only two patients none SLN was visualized neither at the early nor at the late stage of the study most likely due to microembolies in the lymphatic ves­sels, draining the tumour-bearing breast. Discussion Metastatic lymph nodes involvement proved to be the basic principal in the clinical strate­gic assignment and prognostication in cases of early breast cancer. The removal of the nodes from the levels I and II is a routine sur­gery operation when the primary breast can­cer is diagnosed and thus, up to 98 % of the cases with positive axilla are identified.6 At the same time, the relatively high percentage (67-80%) with early disease with tested nega­tive lymph nodes, as well as possible postop­erative complications (lymphoedema), ap­proved the necessity of a sentinel lymphadenectomy as an alternative to the lymph node dissection over the last decade. The accuracy of this procedure is con­firmed in numerous studies. There is a prob­ability of only 0-6% of detecting false negative SLNs after the peritumoral application of blue dye or radiocolloids.1-3,6 According to the results of the two studies of Klimberg et al. and Mertz et al., published so far, the exactness of 100% was reported to be achieved with 68 and 47 patients, respec­tively, who had received 99mTc sulfocolloid subareolar injection.4,5 As to the accuracy after the peritumoral mapping, our results (90,6% of background) concur with those, performed by the other au­thors employing this method. Simultaneously, some differences are ob- Table 2. Location of the primary tumour in the cases with metastatic SLN Localization Peritumoral Subareolar Axilla (+) SLN (+) Axilla (+) SLN (+) Lateral 44 42 9 5 Central 12 11 4 4 Medial 8 5 3 2 Total 64 58 (90,6%) 16 11 (68,8%) served between our results and figures, given in the literature, regarding the subareolar technique. We achieved 68,8% of diagnostic precision, using this method that appears to be much lower, in comparison to the percent­age, presented in the other two studies, men­tioned above. These results may be explained as follows: Ń The subareolar technique, being new and at its first stages, may give the accuracy which still remains debatable. Ń The investigation was conducted up to now on an insufficient number of patients; Ń Lymphatic drainage might be traced incom­pletely and further combination of blue dye and radiocolloids may raise the rate of strictness of this method; Ń Metastatic SLN are not localized precisely by a microscope examination. We assume that in an additional immunohistochemical investigation micrometastases might be found. In conclusion, the authors of the current study state that the peritumoral application of blue dye or radiocolloids technique is con­sidered to be a reliable tool in determination of axillary status, verified histologically, whereas subareolar SLN mapping is still dis­putable and only further extending research would correctly evaluate its efficiency and positive/negative predictive values. References 1. Giunliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lym­phadenectomy for breast cancer. Ann Surg 1994; 220: 391-401. 2. Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg V, Shriver C, et al. The sentinel node in breast cancer. N Engl J Med 1998: 339: 941-6. 3. Bass SS, Cox CE, Ku NN, Berman C, Rentgen DS. The role of sentinel lymph node biopsy in breast cancer. J Am Coll Surg 1999; 189: 183-94. 4. Klimberg VS, Rubio T, Henry R, Cowan C, Colvert M, Korourian, S. Subareolar versus peritumoral in­jection for localisation on the sentinel lymph node. Ann Surg 1999; 229: 860-5. 5. Mertz L, Mathelin C, Marin C, Gairard B, Chenard M, Brettes J, et al. Subareolar injection of 99 Tc-sulfur colloid for sentinel nodes identification in multifocal invasive breast cancer. Bull Cancer 1999; 86: 939-45. 6. Rubio IT, Korourian S, Cowan C, Crag DE, Colvert M, Klimberg VS. Sentinel lymph node biopsy for staging breast cancer. Am. J Surg 1998; 176: 532-7. What is current practice in soft tissue sarcoma grading? Rastko Golouh, Matej Bra‰ko Department of Pathology, Institute of Oncology, Ljubljana, Slovenia Purpose. Most published grading systems of soft tissue sarcomas (STS) are somewhat subjective and it seems that there is no definite consensus among experts which of them is the most effective. The aim of this study was to collect data from practicing pathologists and to get some insight in the practice of STS grading. Subjects. A questionnaire was sent to 135 pathologists chosen randomly. Results. There were 88 responders from 30 countries from 5 continents. Most responders (85%) grade STS, more frequently in Europe than in non-European countries. Three-grade system is preferred by both European and non-European pathologists, who use it in almost 77% and 67%, respectively. They apply the criteria set by FNCLCC in 37.3%, by NCI in 24%, by Broders in 12% and by Markhede in 1.4%. In Europe, FNCLCC system is the most widely used. Beside classical histological criteria, other modern methods are ap­plied by more than one half of the responders. Immunohistochemical evaluation of proliferation markers is the method most widely used, followed by molecular markers and DNA flow cytometry. Conclusion. The results of our study indicate that most pathologists consider histologic grade of STS as a valuable, however not completely satisfactory predictor of a patient's survival. Key words: soft tissue neoplasms; sarcoma pathology; neoplasms staging; prognosis Introduction No other variable seems to work better in the prediction of the behavior of soft tissue sar­comas (STS) than histological grade, but at the same time, no other prognostic factor has been responsible for so much controversy and debate. Soft tissue sarcomas are a large group of approximately 50 different nosolog- Received 23 November 2000 Accepted 5 January 2001 Correspondence to: Rastko Golouh, MD, PhD, Dept. of Pathology, Institute of Oncology, Zaloäka 2, SI-1000 Ljubljana, Slovenia. Fax: +386 1 43 14 180; E-mail: rgolouh@onko-i.si ic entities that, despite sharing common clin­ical features such as blood-borne metastatic spread, also present significant clinical differ­ences. The value of histopathological grading should, therefore, be balanced against the predictive significance of other morphologic and clinical parameters that vary according to the specific type of sarcoma. In most sarcoma grading systems, the de­gree of histological differentiation, cellularity, pleomorphism, mitotic activity, necrosis and vascular invasion are taken into account. In addition, some schemes take the pathological diagnosis of the tumor as a dominant compo­nent for grading as it is well known that cer­tain sarcomas have a specific biological be­havior that is defined mostly by their line of differentiation. However, many grading systems applied to STS have not been completely satisfactory in terms of predicting prognosis. Therefore, attempts to identify potentially more aggres­sive sarcomas have been made using addi­tional quantitative methods such as flow cy­tometry, markers for assessment of proliferative activity as well as molecular techniques looking for oncogenes, suppres­sor genes and gene product expression. Although most published grading systems may provide valuable prognostic information, an international consensus on STS grading has not been reached. One may, therefore, suppose that grading of STS varies consider­ably among different places and even among experts in the field. The historical and practical aspects of his-tologic grading of STS have recently been ex­tensively reviewed.1 In addition, some guide­lines regarding STS grading have been proposed in the recently published recom­mendations for the reporting of soft tissue sarcoma.2 The aim of the present study was to collect data from practicing pathologists and to get some insight in the current practice of STS grading in different institutions of differ­ent countries. Material and methods To obtain first-hand information, a question­naire was sent to 135 pathologists who were chosen at random from the list of participants of the 15th European Congress of Pathology. They were asked to answer to four specific questions, as follows: 1. Do you grade STS (yes, no)? 2. How many grades do you use (two, three, four)? 3. Which grading system do you use (Broders, NCI, Jensen, FNCLCC, other-specify)? 4. Do you use other methods to assess STS prognosis (no, yes - DNA ploidy, S-phase fraction, proliferation markers, molecular markers, other - specify)? Finally, all potential responders were asked for their comments. Results All the data were processed anonymously. In total, there were 88 responders from 30 coun­tries of 5 continents (Table 1). Most of them (74%) were from Europe. Their answers are shown in Table 2. Table 1. Geographical distribution of the responding pathologists Australia 2 Iceland 1 Austria 2 Italy 6 Brasil 1 Japan 5 Canada 1 Macedonia 2 Croatia 1 Norway 5 Czech Republic 2 Poland 1 Denmark 3 Portugal 2 Finland 3 Slovenia 1 France 5 Spain 7 Germany 5 Sweden 2 Great Britain 4 Switzerland 3 Greece 2 Turkey 2 The Netherlands 3 Ukraine 1 Hong Kong 2 USA 12 Hungary 1 Yugoslavia 1 Most responders (85%) grade STS. Among them, however, certain geographical differ­ences became evident. Pathologist in Europe use gradation of STS more frequently (in nearly 88%), compared to the pathologists in non-European countries, who grade STS in 78%. Similarly, number of grades used, namely 2, 3 or 4, also varies considerably - 11%, 74%, and 15%, respectively. Three-grade system is preferred by both European and non-European pathologists, who use it in almost 77% and 67%, respectively. Table 2. Answers provided by the participating pathologists All (n=88) European (n=65) non-European (n=23) grading used 75 (85.2%) 57 (87.7%) 18 (78.3%) number of grades 2 8 (9.1%) 5 ( 8.9%) 3 (16.7%) 3 55 (62.5%) 43 (76.8%) 12 (66.7%) 4 11 (12.5%) 8 (14.3%) 3 (16.7%) grading system Broders 9 (12.0%) 6 (10.5%) 3 (16.7%) NCI 18 (24.0%) 13 (22.8%) 5 (27.8%) FNCLCC 28 (37.3%) 26 (45.6%) 2 (11.1%) other/not specified 20 (26.7%) 12 (21.1%) 8 (44.4%) other methods used 47 (53.4%) 38 (58.5%) 9 (39.1%) proliferation markers 38 (43.2%) 31 (47.7%) 7 (30.4%) SPF and/or DNA ploidy 12 (13.6%) 11 (16.9%) 1 (4.3%) molecular 15 (17.0%) 12 (18.5%) 3 (13.0%) other/not specified 10 (11.4%) 8 (12.3%) 2 ( 8.7%) Of the 75 individuals who systematically grade STS, only 56 specified the system used. Pathologists apply the criteria set by FN­CLCC in 37.3%, by NCI in 24%, by Broders in 12%, and by Markhede in 1.3%; the remaining 25.3% did not specify the system they use. Again the analysis disclosed some differences between the regions studied. While FNCLCC system is the most widely used in Europe (46%), non-European pathologists seem to prefer other systems. Rather surprisingly, of the 56 pathologists who specified the grading system they use, 11 (19.6%) stated that they use a number of grades different to that applied in the original published grading scheme. Beside classical histological criteria to as­sess soft tissue sarcoma prognosis, other modern methods are applied by more than one half of the responders. In Europe, these are used in 59%, compared to 30% in non-European countries. Immunohistochemical evaluation of proliferation markers is the method most widely used, followed by mo­lecular methods and flow-cytometric determi­nation of DNA ploidy and/or S-phase frac­tion. Discussion The results of our study show that the large majority of pathologists apply grading to the diagnosis of soft tissue sarcoma. On the oth­er hand, they also indicate that, in practice, this is done rather inconsistently, that various grading schemes are in use, and that the guidelines set forth by the published grading systems are often only loosely applied. One of the reasons for this, as well as for the fact that as many as 15% of pathologists do not use STS grading, might be the lack of inter­national consensus. Despite the validation of many histologic grading systems for STS, none have been uni­versally accepted. Because of the overall rari­ty of specific sarcoma subtypes, the evalua­tion of grading systems and their prognostic significance have tended to be based on sar­comas as a general group, diminishing the value and significance of histologic subtyp­ing. The same histological criteria have been applied to 50 different types of sarcomas, de­spite the fact that some behave as borderline or low-grade malignant tumors (dermatofi­brosarcoma protuberans, retiform heman-gioendothelioma) and others are uniformly high grade (clear cell sarcoma, desmoplastic small cell tumor). It has been pointed out that histologic grading may overestimate or un­derestimate the biological potential of some STS. Therefore, it has been suggested that the grading criteria should be revised for each type of soft tissue tumor. Moreover, the study of each specific type of STS should be sub­jected to multivariate statistical analysis with simultaneous consideration of histological, clinical and treatment factors.3 If histologic grading is to be applied to cer­tain types of STS, which grading should be used and what is the current grading prac­tice? Most grading systems incorporate similar histologic parameters, namely histologic type, cellularity, tumor necrosis, and mitotic activity. The parameters by which these crite­ria are applied tend to be less defined in sys­tems of Broders4 and Markhede5 both of which use a four-grade scale. The more recent systems, preferred by our responders, the National Cancer Institute (NCI) system as proposed by Costa6 and the system of Federation Nationale des Centres de la Lutte Contre le Cancer (FNCLCC),7,8 appear far less subjective than its predecessors and provide specific guidelines for applying tumor grade. They both are 3-tiered. The NCI largely incor­porates histologic subtype and extent of necrosis, whereas FNCLCC uses tumor dif­ferentiation, mitotic count and volume of tu­mor necrosis. Although both systems have predictive value for metastatic development and tumor mortality, the FNCLCC system ap­pears to be slightly superior to the NCI sys­tem, both in the ability to predict a patient's survival and in the reproducibility of the scor­ing system among pathologists.7,9 In contrast to most previous attempts that tried to evaluate STS as an entire group, pre­dictive value for metastatic disease has re­cently been specifically assessed for the main histologic types of adult STS.10 The results of a study of 1240 patients, assessed by FN­CLCC system, confirmed the impression that histologic grade is the most important predic­tor of metastasis development in several ma­lignant soft tissue tumors. In order of impor­tance, the following parameters were reported to have independent predictive val­ue: (1) grade, neurovascular or bone involve­ment (NBI), tumor size and depth for the whole group; (2) grade and tumor size for li­posarcoma (n=188); (3) NBI, grade and tumor size for leiomyosarcoma (n=148); (4) grade and NBI for synovial sarcoma (n=125); (5) grade for unclassified sarcomas (n=140) and sarcomas of other types (n=158). Interestingly, the authors could not identify any prognostic parameter for malignant schwannoma (n=72) and for rhabdomyosar-coma (n=60). It should be pointed out that both NCI and FNCLCC systems are best applied to adult soft tissue sarcomas. Recognizing the differ­ences between children and adults, Parham et al. reported the criteria of Pediatric Oncology group (POG) for nonrhabdomyomatous sar­comas in children.11 POG system is similar to NCI grading scheme, but takes into account more adequately the unique clinico-patholog­ic features of children and therefore better suits this age group. On the other hand, for childhood rhabdomyosarcoma the Intergroup Rhabdomyosarcoma Study Group have pro­posed a grading system which better corre­lates with prognosis of this specific group of STS.12 The classification, specifically desig­nated as the International Classification of Rhabdomyosarcoma (IRC), divides RMS in three groups - tumors with superior, interme­diate and poor prognosis. Arguably, the classification, histological subtyping, and grading systems of STS are mostly based on classical, morphologic fea­tures. Recent advances in our understanding of the cytogenetic and molecular features of STS have yielded significant insight into STS pathogenesis.13 It is not surprising that, ac-cording to our study, more than one half of pathologists apply additional methods, al­though their value in predicting behavior of STS is not entirely clear at present. Markers such as MIB1 to more accurately assess pro­liferative activity are most commonly used. They are followed by molecular methods to evaluate the expression of p53, MDM2, RB and other gene products, and flow cytometry to separate diploid from aneuploid tumors and to determine S-phase fraction. Again, it has to be stressed that additional studies of these and many other modern methods are needed to evaluate their specific prognostic significance for each type of STS. Although the data gathered in this study suggest that certain differences exist in the practice of STS prognostication between European and non-European pathologists, none of this differences proved to be statisti­cally significant. It should be noted, however, that the number of responders from non-European countries was far too small to draw any firm conclusion. In conclusion, the results of our study in­dicate that most pathologists are aware of the fact that histologic grade of STS appears to be a valuable, however not completely satisfac­tory predictor of a patient's survival. Despite the impressive advances in our understand­ing of STS and high level of expertise in stat­ing accurate diagnosis of common and many recently described entities, there are still many problems that account for the failure of most grading schemes to consistently func­tion well. Acknowledgement This study was supported by the Ministry of Science and Technology of Slovenia (J3-7953). References 1. Kilpatrick SE. Histologic prognostication in soft tissue sarcomas: Grading versus subtyping or both? A comprehensive review of the literature with proposed practical guidelines. Ann Diagn Pathol 1999; 3: 48-61. 2. Association of Directors of Anatomic and Surgical Pathology. Recommendations for the reporting of soft tissue sarcoma. Virchows Arch 1999; 434: 187­91. 3. Meis-Kindblom JM. On the comparison of apples, oranges and sundry fruit: problems with grading and prognostication in soft tissue tumors. Patologia 1999; 32: 426-7. 4. Pritchard DJ, Soule EH, Taylor WF, Ivins JC. Fibrosarcoma. A clinicopathologic and statistical study of 199 tumors of soft tissues of the extremi­ties and trunk. Cancer 1974; 33: 888-97. 5. Markhede G, Angervall L, Stener B. A multivariate analysis of the prognosis after surgical treatment of malignant soft-tissue tumors. Cancer 1984; 49: 1721-33. 6. Costa J, Wesley RA, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas: Results of a clinicopahological correlation in a series of 163 cases. Cancer 1984; 53: 530-41. 7. Guillou L, Coindre JM, Bonichon F, Nguyen BB, Terrier P, Collin F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers sarcoma group grading systems in a population of 410 adult patients with soft tis­sue sarcomas. J Clin Oncol 1997; 15: 350-62. 8. Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, de Mascarel A, et al. Soft tissue sarcomas of adults: Study of pathological prognostic variables and definition of a histopathologic grading sys­tem. Int J Cancer 1984; 33: 37-42. 9. Coindre JM, Trojani M, Contesso G, David M, Rouesse J, Bui NB, et al. Reproducibility of histopathologic grading system for adult soft tis­sue sarcoma. Cancer 1986; 58: 306-9. 10. Coindre JM, Terrier P, Collin F, le Doussal V, Guillou L, Ranchere D, et al. Predictive factors for metastasis development in main histologic types of adult soft tissue sarcomas. United States and Canadian Academy of Pathology. Annual Meeting, San Francisco, 1999. Abstract 9A. 11. Parham DM, Webber BL, Jenkins JJ 3rd, Cantor AB, Maurer HM. Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: Formulation of a simplified system for grading. Mod Pathol 1995; 8: 705-10. 12. Newton WA Jr, Gehan EA, Webber BL, Marsden HB, van Unnik AJ, et al. Classification of rhab­domyomatous and related sarcomas; pathologic aspects and proposal for a new classification - an Intergroup Rhabdomyosarcoma Study. Cancer 1995; 76: 1073-85. 13. Ladanyi M. The emerging molecular genetics of sarcoma translocation. Diagn Mol Pathol 1995; 4: 162-73. Upgrading of gamma cameras for developing countries Valentin Fidler1, Milan Prepadnik1, Yanfen Xie2 1Nuclear Medicine Department, University Medical Centre, Ljubljana, Slovenia 2Nuclear Medicine Section, Division of Human Health, International Atomic Energy Agency, Vienna, Austria Background. The project of upgrading the analog gamma cameras with PC based systems from International Atomic Energy Agency (IAEA) and the Ministry of Science and Technology of RS is present­ed from the initial basic demands to the final developments. Several national research groups (from China, India, Cuba and Slovenia) were involved in the IAEA development project for the acquisition card with soft­ware and the standard set of clinical protocols. Conclusions. The most functionally stable acquisition system tested on several international workshops and in university clinics was the Slovenian one with a complete set of nuclear medicine clinical protocols, documenting, networking and archiving solutions for simple MS Network or server oriented network sys­tems (NT server, etc). More than 300 gamma cameras in 52 countries all over the world were digitized and put in routine clinical work. Key words: gamma cameras; computer systems; upgrading of analogue gamma cameras; acquisition card; PIP-GAMMA-PF system. Introduction In the last ten years, IAEA put considerable efforts to help developing countries in renew­ing old gamma cameras and nuclear medicine computer systems. It was high time to take this step because many gamma cameras were already out of function for different reasons. Most of them got broken or computers were Received 25 May 2000 Accepted 28 June 2000 Correspondence to: Valentin Fidler, PhD, Nuclear Medicine Department, University Medical Centre, Zaloäka 7, 1000 Ljubljana, Slovenia. Phone: +386 01 5431486; E-mail: Valentin.Fidler@kclj.si too old to suit technologically to new nuclear medicine methods, radiopharmaceuticals and information technology. In many countries, the old analogue gamma cameras (20 years or more) were put out of operation and, as a con­sequence, the nuclear medicine departments were being closed. Nuclear medicine, though a relatively young medical branch, started to "die away". At the same time, the nuclear medicine staff also started to leave the field for other fields, mostly imaging ones. For these reasons, the IAEA measures re­lated to the upgrading of analogue gamma cameras have been initiated to help develop­ing countries to revive nuclear medicine or extend its life. Because of high costs of new equipment, the idea of the IAEA was to up­grade the old analog and semi-digital gamma cameras and computer systems with low cost interfacing cards, developed under the agency support, and the PC based computer systems with acquisition and processing soft­ware, ink-jet or laser printers, CD archive and network. The whole cost per system was lim­ited to 5.000 US $, what is just a small frac­tion of the price of new commercial systems. Concurrently with upgrading the equipment, the training courses for this technology and validation seminars took place in all the re­gions of the developing world. Methods IAEA established a group of experts for defin­ing the upgrading objectives, criteria for se­lecting the research institutions for the devel­opment of acquisition hardware and software, defining the procedures for follow­ing the results of development and creating the final report of the project. The expert group defined the following demands for the upgrading system of analogue gamma cam­eras. Basic demands for development of acquisition cards: Ń single ISA format acquisition card, Ń solution for adjusting amplitude and tim­ings for input signals from a variety of gam­ma cameras, Ń simple installation and setup of X, Y (posi­tional), Z (strobe), E (energy) and G (gated) signals; such that most of the end users can install the system by themselves, Ń matrix size up to 256x256, Ń acquisition driver incorporated in PIP (Portable Image Processing), Ń on-line energy and count correction of im­age data, Ń negligible count loss, Ń stable function of the system for all kinds of possible clinical studies (fast and slow dy­namic, static, gated and combined studies), Ń continuous upgrading, Ń low price (less than 3.000 US $), Ń 4 years for development and validation. Basic demands for software development Ń MS-DOS operating system in WINDOWS (3.1, 95, 98), Ń PIP system for patient database and general data processing, Ń tools for end-user development of clinical protocols (C++ library, macro functions), Ń algorithms for automatic analysis of clinical data with possible manual intervention, Ń tools for image, dynamic curves and ROI processing, Ń images from study analysis in standard pic­ture formats (i.e. PCX, BMP), Ń set of gamma camera quality control func­tions (NEMA tests), Ń converter to and from "Interfile" format, Ń SVGA colour scale for display, Ń results of analysis on one page, Ń printing of documents in high spatial resolu­tion (1200x1200 dots/inch) and on low cost high quality media (paper, transparencies), Ń archiving the original image data and re­porting documents on low cost CD as "soft" copy, Ń network support, Ń user-friendly system, Ń clinically validated software. Three experienced research institutions from developing countries were selected for building the upgrading system: Ljubljana University Medical Center,1,2 Bombay Nuclear Research Institute3 and Havana University Institute,4 Acquisition system Basically two different approaches were used in the development: 1. The acquisition card from Bombay Nuclear Research Institute3 with the signalŐs gain and offset control, AD conversion, energy correc­tion, creating images and gate control. Communication with computer is triggered by interrupt service. ComputerŐs time control is used. Setup of gamma camera signalŐs gain and offset is performed manually (Figure 1). Figure 1. Principle of the Indian acquisition system. Positional (X and Y), strobe (Z), energy (E) and gate (G) signals are converted into digital form in the ac­quisition card, which also creates image and send it to the computer by applying the interrupt service. 2. The acquisition card from Havana University Institute4 with the signalŐs gain and offset control, AD conversion with sav­ing the position, energy and other control da­ta (i.e. gate signal, signal for gantry control) are transferred to the computerŐs memory us­ing PORT transfer. The interrupt service is used for triggering the data transfer (Figure 2). Gain and offset adjustment is performed manually. PC Interrupt service Figure 2. Principle of the Cuban acquisition system. Positional, strobe, energy and gate signals are con­verted into digital form in the acquisition card, which sends them to the computer by applying the interrupt service. 3. The acquisition card from Ljubljana University Medical Centre2 with the signalŐs gain and offset and time control, AD conver­sion, saving of position, energy and all other control data for each detected gamma event by computerŐs PORT transfer to the comput­er memory, software control of analogue sig­nals for zooming, gain, offset and orientation settings. Computer has complete control on the acquisition at every moment. Interrupt pulse is not used for triggering the communi­cation between the acquisition card and com­puter (Figure 3). The setup of signalŐs gain and offset (for X, Y and E) is performed auto­matically through "computer - acquisition card" feedback control (Figure 5) by appropri­ate software1 algorithm (Figure 4). PC PORT transfer Figure 3. Principle of the Slovenian acquisition sys­tem. Positional, strobe, energy and gate signals are converted into digital form in the acquisition card, which sends them to the computer through PORTs without interrupt service. 4a. Initial gain and offset settings: X, Y range: ±0.5V to ±3V, GAIN = 50, OFFSET=128 matrix 2r Gain = 50 Offset 4b. Gain and offset settings at the end of au­tomatic adjustment: GAIN=200, OFFSET=90, matrix X Y Z E G ADC Control logic X Y Z E G ADC Control logic 4c. Iterative loop for gain adjustment. By in­creasing the gain of positional signals the im­age diameter is proportionally increased. gain ­Ţ2r ­ Figure 4. Algorithm for automatic adjustment of inter­facing card's gain and offset settings for positional sig­nals X and Y. All manipulations with the data on image creation, time, count and gate control are per­formed by PC. a) Offset adjustment X, Y input X, Y output Offset voltage D0 . . . D7 from PC I/O port b) Gain adjustment X, Y signal input X, Y output D A C from PC I/O port Figure 5. Digital control of offset (a) and gain (b) for analogue positional (X and Y) signals. By reverse con­trol from the computer to the acquisition card, the analogue signals are appropriately adjusted: a definite constant voltage is added for offset adjustment (a) and part of the signal is taken for gain adjustment (b). Results Acquisition cards All three research institutions developed a few prototypes in the project time. The last and the final version was evaluated in details by several institutions: Institute of Biome­dical Techniques and Physics, AKH, Vienna, Turkey Atomic Energy Commission, Argen­tina National Atomic Energy Commission, and at three expert meetings (in Ljubljana, Ankara and Santiago de Chile). The conclu­sion from all involved testing institutions and experts was that all acquisition cards fulfill most of the required features. The final con­clusion of the testing was:5 "The Slovenian system GAMMA-PF is the most adequate, due to better technical performance, stability of functioning, facility of installation, techni­cal support, lower price, accomplishing in de­livery time schedules and professionalism of the involved team". The most probable cause of instability of Indian and Cuban cards is the interrupt service for communication between acquisition card and PC. Slovenian acquisition and processing system GAMMA-PF In the following, the features of Slovenian acquisition card are presented: Ń standard PC hardware, Ń acquisition can not run simultaneously with processing, Ń one 16-bit PC AT professionally designed card in four layers, Ń range of X and Y analogue bipolar signals from ±0.5 V to ±10 V, Ń alternative software or manual adjustment of GAIN and OFFSET settings for X, Y and E signals, Ń software adjustment of ZOOM (1.0, 1.5, 2.0 and 2.5) to analogue positional signals and image ORIENTATION, Ń matrix sizes from 32 x 32 to 256 x 256 in words, Ń all standard acquisitions (static, dynamic, gated and combined static-dynamic) with on-line energy and count correction, Ń stopping condition: by time, counts or time/counts (which is reached the first), Ń persistence scope function for gamma cam­era tuning with continuous computation of regional count density, Ń count loss: < 1 % without energy correction, < 10 % with energy correction measured at count-rate of 50 K c/s, Ń energy correction is performed by the ac­ceptance of current pixelŐs energy from the look-up matrixes of low and high photo-peak limits, Ń energy correction: integral uniformity index is lowered by factor 2, Ń count correction: integral uniformity index is lowered by factor 3 - 5. One of the most important results of test­ing the effect of uniformity and energy cor­rection was that the count correction decreas­es much more (by factor 3-5) the integral uniformity index than the energy correction (by factor 2). This study was performed on GE 300A gamma camera with artificially sup­pressed one of the PMTs for approximately 60 % (Table 1 and Figure 6). Another important result is the recom­mendation that the count correction should be applied only for images from gamma cam­eras which have integral uniformity index less than 30 %. At higher values the noise am­plification overcomes the signal and the false positive spots become visible in the corrected scans at low count images.2 Clinical software Besides the basic tools for image, region of interest and dynamic curves processing func­tions, the set of most important clinical pro­tocols was developed. Ń Heart: Gated ventriculography: ejection fraction, amplitude and phase images, phase his­togram, contraction images, movie display, Shunt: gamma-variate fit, left-right shunt ratio. Ń Kidneys: Renography (MAG3, DTPA): relative func­tion, Tmax, T1/2, deconvolution analysis. DMSA: relative function with attenuation correction. Ń Lung perfusion: relative function with at­tenuation correction. Ń Salivaries: pertechnetate uptake, excretion after ascorbic acid stimulation. Ń Thyroid: pertechnetate uptake in 15 min­utes. Ń For all other studies the basic tools for im­age processing is available (contrasting, movie display, different colour scales, ROI selection, dynamic curves, etc). Analysis is nearly completely automated with possible quality assurance interven­tions: correction of automatically determined ROI, manual correction of time intervals for relative function computation in dynamic curves, movie display of sequential images with plotted ROIs, manual correction of auto­matic selection of end-systolic image, manual correction of time intervals for "shunt" analy­sis, etc. Most of the patient studies can be Table 1. Analysis of scan uniformity by NEMA standards Figure 6. Effect of on-line energy and count correction on gamma camera (GE 300A) image with 60% suppressed one PMT. 6a. Original image. 6b. Only count corrected. 6c. Only energy corrected. 6d. Energy and count corrected. SCAN Integral uniformity (%) Differential uniformity (%) UFOV CFOV UFOV CFOV Original 49.8 49.2 23.2 23.2 Energy corrected 23.6 23.6 9.6 9.6 Count corrected 6.7 6.6 3.4 3.4 Energy and count corrected 4.7 4.6 2.4 2.4 processed in less than 2 minutes. An example of MAG3 analysis is shown in Figure 7. Networking Setup of network with GAMMA-PF system (Figure 8) can be done either by NOVELL, Microsoft Network or WINDOWS NT net­work software. The acquired studies, images from analysis and documents are stored on common server's disk, archived on CD or oth­er large scale storage media, printed on high quality ink-jet or laser-jet printers and com­munication performed through hospital to external lines. Distribution of acquisition cards with software In 1998, there were 2689 gamma cameras in the developing world. This is nearly the same as in Japan. In the past 15 years 48 planar and SPECT gamma cameras were donated to 39 Figure 7. Example of the final results from MAG3 study analysis. AA P PR Figure 8. Functional schema of GAMMA-PF network. A: acquisition; P: processing; R: reporting PC; S: server; D: common hard disk; CD: compact disk (read/write); PR: printer member states. Along with the donated cam- Ń significant improvement of old gamma eras, IAEA distributed 234 PC gamma inter- camera images (uniformity from 20 % to 5 % face cards to 52 member states. Main after both on-line energy and count correc- achievements of the IAEA projects on up- tions), grading are the following:6 Ń life prolongation of old gamma camera for Ń low cost (about 5.000 US $ including a about 5 - 10 years, Pentium PC, gamma camera interfacing Ń increment of diagnosis throughput by esti- card and PIP software), mated 30 - 40 %, Ń high quality black and white or colour im­ ages with new low cost generation of print­ ers instead of film, Ń knowledge improvement in nuclear medi­ cine technology for engineers, physicians and technologists on training courses in all regions of the developing world. Discussion The IAEA project of upgrading analogue gam­ma cameras in the developing world gained some important results: prolongation of old analogue planar gamma cameras, improve­ment of quality assurance of images by on-line count and energy correction, replacing old computer technology with new PC, intro­ducing computer network, archiving of stud­ies, communication inside nuclear medicine departments and improvement of the techno­logical knowledge of nuclear medicine stuff. These results have a definite limited value. Upgrading project should be implemented al­so to other nuclear medicine equipment, i.e. thyroid uptake system, gamma counters for RIA, multi-probe systems and monitors. There are also some other detector systems that should be included in the future devel­opment, i.e.: radio-chromatograph, whole-body scanning bed (bones, white cells, metas­tases), monitor for patient whole body radioactivity (for checking patient activity be­fore dismissing form hospital), etc. Also the energy and count correction should be im­proved in the future by physically more feasi­ble method - equalizing the PMT output (ei­ther changing the high voltage setting or changing the PMT gain). This should improve the gamma camera spatial uniformity as well as linearity. But to achieve this the electronics of the gamma camera head and the electronic console should be replaced completely by the digital system. Conclusions The IAEA project of upgrading the old ana­logue gamma cameras by PC based acquisi­tion and processing systems yielded a high promotion of nuclear medicine in the devel­oping world. Besides the immediate help to 52 member states in the life prolongation of old gamma cameras, somewhere also reviving the nuclear medicine, it also improved the technological knowledge of nuclear medicine stuff on several training courses on upgrad­ing and quality assurance of planar and SPECT gamma cameras and programming of clinical protocols. Among the three financial­ly supported projects for development of ac­quisition system the Slovenian one was as­sessed by expert testing and end-user evaluation as technically the most advanced, functionally stable, user-friendly concerning the installation with setup of image size, off­set and energy settings, simplicity of clinical protocols with quality assurance functions, delivery time, with smallest price and was mostly distributed. References 1. Fidler V, Prepadnik M, Fettich J, Hojker S. Nuclear Medicine IBM-GAMMA-PF Computer System. Radiol Oncol 1997; 31: 27-32. 2. Fidler V. Validation of IBM PC interfacing with gamma camera and appropriate application soft­ware for data processing of clinical software. Coordinated research program. IAEA, report for 1995-1998. 3. Singh B. Validation of IBM PC interfacing with gamma camera and appropriate application soft­ware for data processing of clinical software. Coordinated research program. IAEA, report for 1995-1998. 4. Boron M. Validation of IBM PC interfacing with gamma camera and appropriate application soft­ware for data processing of clinical software). Coordinated research program. IAEA, report for 1995-1998. 5. ARCAL XXIII project (RLA/6/027). Report of the expert meeting on evaluation of gamma cameras upgrading systems, Santiago de Chile, Chile, 21­25th September 1998. 6. Groth S, Padhy A, Xie Y. Promotion of Nuclear Medicine by IAEA. Coordinated research Program, IAEA. Report on Joint WFNM&B and EANM Congress in Berlin 1998. Design considerations for direct and indirect active matrix flat-panel portal imagers Martin Lachaine and Biagio Gino Fallone Department of Medical Physics, Cross Cancer Institute, University of Alberta, Alberta, Canada Department of Physics, McGill University, Montreal, Canada Background. Recent advances in thin film transistor (TFT) technology have allowed the construction of ac­tive matrix flat-panel imagers (AMFPI) for various medical imaging modalities. Since the design of such sys­tems is still in the development stage, it is unclear what detector characteristics are required in order to op­timize these detectors for portal imaging. Material and methods. In this work, we used cascade analysis and Monte Carlo techniques to calculate the DQE for both direct and indirect AMFPIs for portal imaging, and use these calculations to study the op­timal detector characteristics. We validate our calculations with existing experimental data. Results. We show that the for ideal flat-panel characteristics the direct and indirect detection methods have the same DQE for a given mass thickness. Conclusions. We generate graphs which may be helpful in the design of future megavoltage AMFPIs. Key words: portal imaging, Monte Carlo method; DQE, AMFPI, EPID; amorphous selenium Introduction During a radiation therapy treatment, many factors may influence the proper delivery of a calculated dose distribution. Some of these factors include misalignment of the treatment beam with respect to the patient, external or Received 20 October 2000 Accepted 20 November 2000 Correspondence to: Prof. B. Gino Fallone, PhD, FC­CPM, ABMP, Medical Physics, Cross Cancer Institute and University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada. Phone: +1 780 432-8750; Fax: +1 780 432-8615; E-mail: Gino.fallone @cancerboard.ab.ca internal patient motion, or inaccurate posi­tioning of beam-modifying devices.1 In order to quantify these geometric inaccuracies dur­ing treatment, a portal image is typically ex­tracted from the megavoltage treatment beam with a radiation-sensitive detector. In this manner it is possible to verify the position of the radiation field relative to the bony anato­my. Portal imaging has also been studied with varying success for use in exit dosime­try, where the images are used to verify the dose distributions delivered to the patient.2,3 Traditionally, film has been used as the portal imaging detector. Over the past decade, several electronic portal imaging de­vices (EPIDs) have been developed for the purpose of replacing film.4 The inherent ad­vantages of such inherently digital detectors include immediate viewing and the ability to use contrast-enhancing algorithms to im­prove image quality. Despite these advan­tages, however, EPIDs have not widely re­placed portal films. This has been attributed to poor image quality, limited field of view, and bulkiness.5 In recent years, thin film transistor (TFT) technology has lead to the development of a new category of digital x-ray detectors.6-8 Such detectors, often called active-matrix flat panel imagers (AMFPIs), may use either the in­direct or the direct detection of x-rays to form the digital image. The indirect method typi­cally uses a phosphor to convert the incident x-rays into visible light, which are then con­verted into electron-hole pairs by an array of photodiodes. The charge is collected in the photodiodes during the image formation, and subsequently read out electronically. The di­rect method, on the other hand, uses a photo-conductor such as amorphous selenium (a-Se) to directly convert the x-rays into elec-tron-hole pairs, which are collected at pixel electrodes through the use of an applied elec­tric field. The charges are stored in the capac­itors of the active matrix during irradiation and subsequently read out. Characteristics which must be considered when designing AMFPI detectors include the detection method (indirect or direct), detector thickness, pixel size, fill factor, and electron­ic noise characteristics. Some of these are dif­ficult to quantify experimentally, since con­struction of AMFPIs is expensive. For this reason, it is useful to use theoretical tech­niques to describe AMFPI image quality, which is often quantified in terms of the de­tective quantum efficiency (DQE). Cascaded systems analysis9 has success­fully been applied to calculate the DQE of AMFPI detectors in the diagnostic energy range.10,11 These analyses have been useful in studying detector designs for various modali­ties such as mammography, chest radiogra­phy and fluoroscopy. At the energies used in these modalities, there is little spread of the ionizing radiation within the detector and thus this spreading is not taken into account in the analysis. At megavoltage energies, however, x-rays produce high energy elec­trons within a metal build-up layer (conver­sion plate) which is placed above the sensi­tive volume of the detector. These high energy electrons scatter within the detector, resulting in an additional loss of resolution. Bissonnette et al.12,13 have taken this addi­tional process into account to model both video-based and indirect AMFPI portal im-agers. Their analysis, however, did not agree with data measured by Munro and Bouius.14 This disagreement was attributed to the fact that it is impossible to experimentally sepa­rate the spread of high-energy radiation from the spread of the visible light within the phos­phor. In our work, we use Monte Carlo meth­ods to investigate this particular problem for both direct and indirect portal AMFPIs. The design constraints for portal AMFPIs are different than for diagnostic AMFPIs, and have to date not been studied. We thus use the cascade analysis formalism to explore po­tential benefits of the direct versus the indi­rect detection methods for portal imaging, and to explore the effects of detector thick­ness, pixel size, fill factor and electronic noise on the DQE at megavoltage energies for both indirect and direct detection techniques. Materials and methods We first consider the interaction of quanta with the detector, which are referred to as analog processes. We make the approxima­tion that these can be divided into elementary amplification stages (which includes binary se­lection as a special case) and dislocation stages according to cascade analysis.9,15 We neglect depth-dependent quantities (i.e. the Lubberts effect).16 In order to include both direct and indirect detection, we use the term secondary quanta to refer to optical quanta or electron-hole pairs for the case of indirect and direct detection, respectively. Similarly to Bissonnette et al.,12 we use the following stages: 1) interaction of x-rays with the detec­tor, which is a binary selection stage with probability equal to the x-ray quantum effi­ciency of the detector h; 2) spread of ionizing x radiation within the detector, a dislocation stage which has a Modulation Transfer Function (MTF) equal to Trad(¦); 3) creation of secondary quanta; an amplification stage Ń2 with average gain gand variance s; 4) sec sec spread of secondary quanta, a dislocation stage which has an MTF equal to T(¦); and sec 5) loss of secondary quanta, a binary selection stage with probability hloss. Following these stages, the analog DQE becomes which simplifies to (2) Ń in the limit g>>1 which is the case for a-Se sec and Gd2O2S:Tb detectors where typically 104 secondary quanta are created per inter­ ~acting x-ray. The analog DQE of Eq. (2) repre­sents the intrinsic DQE of a metal/phosphor or metal/photoconductor detector at mega-voltage energies. In the approximation of the cascade analysis we have used, this DQE is thus seen to be degraded only by the x-ray 2 quantum efficiency h, the variance sand xsec the spread of ionizing radiation Trad(¦), but not the spread of secondary quanta T(¦) or secthe loss of secondary quanta hloss. In an AMFPI, the analog signal is first inte­grated over the active matrix pixels, and then sampled to create a digital signal. An elec­tronic noise component Sis then added to e the noise power spectrum (NPS) by the flat panel, leading to a digital DQE for a direct or indirect AMFPI: where Ń gis the incident fluence, a is the pixel size 0 and d is the pixel pitch. For perfect flat-panel characteristics, i.e. infinitesimally small pixels and no electronic noise, the digital DQE re­duces to the analog DQE. We refer to this as the ideal DQE for an AMFPI detector. In order to calculate the DQE for both di­rect and indirect detectors at megavoltage en­ Ń2 ergies, we need the quantities, i.e. h, g, s, xsecsecand Trad(¦). These quantities depend on the incident energy spectrum, and the densities, atomic numbers, and thicknesses of the front plate and sensitive layers. We determined these quantities for metal/phosphor and met-al/a-Se detectors by Monte Carlo methods us­ing EGSnrc.17 The technical details have been previously described.18 Briefly, two different types of simulations are used. The first type of simulation scores the energy absorbed in the sensitive region of the detector in order to determine the absorbed energy distribution (AED).19 The quantum efficiency is then giv­en by the zeroth-moment of the AED, and the Ń2 quantities gand scan be calculated using sec sec the first and second moments, respectively. The second set of simulations determine the spatial distribution of energy deposited in the sensitive region of the detector due to an in­finitesimally thin line of incident x-rays. The resulting distribution corresponds to the LSF, from which we calculate Trad(¦) using Fourier analysis. In our calculations, we use an incident 6 MV spectrum as given by Kubsad et al.20 The detectors for the indirect detection AMFPIs are modeled with a Cu front plate and a gadolinium oxysulfide Gd2O2S:Tb phosphor screen with a reduced density of 3.67 g/cm3 as described by Jaffray et al.19 For direct de-tection, the front plate is modeled in the same fashion but the phosphor layer is replaced by atomic Se with a reduced density of 4.27 g/cm3 to match that of the amorphous state. Describing a-Se in this fashion is an excellent approximation for studying macroscopic en­ergy deposition only.21 For the case of direct detection, we use T(¦)=1. For indirect detection, we need the sec MTF describing the spread of visible light. For this purpose, we use the experimental MTFs for phosphor screens measured by Bissonnette et al.13 These total MTFs T(¦) are tot equivalent to the product T(¦)T(¦). (3) tot(¦)=TradsecTo calculate T(¦), we therefore divide the sec total experimental MTF by the MTF due to the spread of high energy radiation obtained by Monte Carlo techniques. We first investigate what we have defined as the ideal DQE, i.e. the intrinsic DQE of met-al/phosphor or metal/a-Se, given by Eq. (2). We calculate the ideal DQE as a function of spatial frequency for a 1 mm Cu front plate coupled with the following sensitive detec­tors: four phosphors of different mass thick­nesses, namely 67 mg/cm2 (Lanex Regular), 134 mg/cm2 (Lanex Fast Back), 358 mg/cm2, and 721 mg/cm2; and four a-Se thicknesses, namely 46 mg/cm2 (0.2 mm), 92 mg/cm2 (0.4 mm), 138 mg/cm2 (0.6 mm), and 184 mg/cm2 (0.8 mm). Once we have explored the ideal DQE, we use the results to explore the effects of the ac­tive matrix, i.e. pixel size, fill factor and elec­tronic noise, using Eq. (3). In our calculations, for a-Se we assume that hloss is governed only by recombination and assume a recombina­tion fraction of 0.25.22 For the case of phos­phor we assume that hloss is governed only by the absorption of visible light within the phosphor, and use the values tabulated by Bissonnette et al.13 We assume that there are no further losses in the coupling of the sec­ondary quanta to the active matrix array. In order to validate our cascade analysis for AMFPI detectors, we calculate the DQE for the indirect AMFPI detector described by Munro and Bouius,14 which consists of a 1.5 mm Cu front plate followed by a Lanex Fast Back phosphor screen (134 mg/cm2 Gd2O2S4:Tb). Their detector is placed on top a glass substrate which we include in our EGSnrc simulations. This glass substrate in­creases the energy deposited in the phosphor due to backscatter. Their active matrix is comprised of 0.75 mm pixels with a fill factor of 54%. They have determined that their de­tector is quantum limited at the exposures and spatial frequencies described in their pa­per, and we can thus neglect electronic noise in Eq. (3) for this case (for spatial frequencies below 1 cycle/mm). To investigate the effects of aliasing and electronic noise, we calculate the DQE as a function of pixel size and electronic noise for two fill factors: 50% and 90%, for both direct and indirect detection techniques and with the same thicknesses described above for the case of the ideal DQE (the fill factor is defined as F= a2/d2). p Results In Figure 1 we show the digital DQE we have calculated for the detector described by Munro and Bouius. We show excellent agree­ment to their data, which shows that the ap­proximations we have used in the calculation of the DQE are justifiable. In Figure 2 we show the ideal DQE(f) for indirect and direct detection methods respec­tively. The DQE(0) for each case can be seen to increase with mass thickness. The ideal DQE for both indirect and direct detection methods are degraded with spatial frequency only by the square of the MTF due to the spread of high energy radiation. This degra­dation is more pronounced as the mass thick­ness increases, but over the spatial frequency range shown, the ideal DQE(f) is superior for a larger mass thickness. In order to show the effect of system noise and pixel size on the various detectors, we present our results as contour plots of the DQE normalized as a percentage of the ideal DQE. In this fashion, one can pick the appro­priate design characteristics for a given detec­tor, and visualize the corresponding degrada­tion of the ideal DQE. The contour plots are shown at two reference spatial frequencies (0 and 1 cycles/mm) and for two fill factors (50% and 90%), for indirect detection and for direct detection AMFPIs in Figure 3 and Figure 4, re­spectively. Discussion For a given mass thickness, the ideal DQE is approximately the same for the direct and in­direct methods, because as previously dis­cussed, the NPS compensates for the degra­dation of the MTF. Since present practical phosphors generally have larger mass thick­nesses than a-Se, the ideal DQEs shown are slightly greater for the indirect method. This can be overcome by increasing the thickness of a-Se to over 1 mm, which may however be technically difficult to attain while maintain­ing adequate uniformity of the a-Se. By inspection of Figure 4, it can be seen that for indirect detection AMFPIs, the pixel size should be kept below about 0.3 mm and the electronic noise per incident fluence be­low about 105 mm2 in order to ensure that the DQE is not significantly degraded. The fill factor is seen not to be an important factor for indirect detection detectors, as expected from the previous discussions. For direct detection AMFPIs, the con­straint on the pixel size is approximately the same as for indirect detection, but the elec­tronic noise per incident fluence can be about Figure 3. Contour plots of DQE at 0 and 1 cycles/mm, normalized as a percentage of the ideal DQE, for indirect AMFPIs as a function of pixel size and system noise per incident fluence. Plots are shown for both 50% and 90% fill factors, and for various phosphor thicknesses (a 1 mm Cu front plate and 6 MV photon beam are used). two orders of magnitude greater than that for indirect detection, i.e. about 107 mm2, before significantly degrading the DQE. It can also be seen, however, that the fill factor must be maximized for a-Se detectors. Several tech­niques have been discussed by Pang et al.23 in order to increase the effective fill-factor. The constraints on pixel size and electron­ic noise have been achieved in prototype de­tectors for diagnostic radiology, indicating that AMFPIs for portal imaging with DQEs equal to their ideal DQE can be manufac­tured. The AMFPI described by Munro et al. has been shown to be quantum limited, but Figure 4. Contour plots of DQE at 0 and 1 cycles/mm, normalized as a percentage of the ideal DQE, for direct AMFPIs as a function of pixel size and system noise per incident fluence. Plots are shown for both 50% and 90% fill factors, and for various a-Se thicknesses (a 1 mm Cu front plate and 6 MV photon beam are used). we have shown that its DQE could be im-or indirect detection methods for megavolt-proved if the pixel size were reduced from age imaging. The main difference will likely 0.75 mm to below 0.3 mm. be related to the manufacturing costs of We have calculated the constraints on pix-building active matrices with specific pixel el size and electronic noise for both indirect sizes, fill factors, and electronic noise. The and direct detection AMFPIs. In essence, if cost and ease of manufacturing uniformly these constraints are satisfied, there is no sig-sensitive phosphors and a-Se layers must also nificant advantage in using either the direct be explored. Conclusions We have presented an approximation which describes the DQE of AMFPI detectors for portal imaging, for both direct and indirect detection methods. We validate our approxi­mation with existing measurements of a pro­totype indirect-detection AMFPI and a met-al/phosphor detector. We calculate the ideal DQE for both direct and indirect detection AMFPIs for portal im­aging. We show that although the resolution of the indirect detection method is superior to that of direct detection, the decrease in NPS compensates for this decrease in resolution. We explore the effects of electronic noise, pixel size and fill factor for direct and indirect AMFPI detectors. We show that aliasing ef­fects are more serious using the direct method, but that requirements on the elec­tronic noise of the active matrix are more stringent for the indirect method. We show plots of the DQE as a function of system noise and pixel size for various detector thicknesses which should prove helpful in the design of future AMFPI detectors for por­tal imaging. References 1. Kutcher GJ, Mageras GS, Leibel SA. Control, cor­rection and modeling of setup errors and organ motion. Semin Radiat Oncol 1995; 5: 143-5. 2. Essers M, Boellaard R, Van Herk M, Lanson H, Mijnheer B. Transmission dosimetry with a liquid-filled electronic portal imaging device. Int J Radiat Oncol Biol Phys 1996; 34: 931-41. 3. Boellaard R, Herk Mv, Uiterwaal H, Mijnheer B. Two-dimensional exit dosimetry using a liquid-filled electronic portal imaging device and a con­volution model. Radiother Oncol 1997; 44: 149-157. 4. Boyer AL, Antonuk L, Fenster A, Van Herk M, Meertens H, Munro P, et al. A review of electron­ic portal imaging devices (EPIDs). Med Phys 1992; 19: 1-16. 5. Munro P. Portal imaging technology: Past, present and future. Semin Radiat Oncol 1995; 5: 115-33. 6. Antonuk LE, El-Mohri Y, Huang W, Jee K-W, Siewerdsen J, Maolinbay M, et al. Initial perform­ance evaluation of an indirect-detection, active matrix flat-panel imager (AMFPI) prototype for megavoltage imaging. 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Radio/ Oncol 2001; 35(1): 1-10. Stenti Z, oplašceni s submukozo tankega crevesa v žolcnem sistemu: Rezultati preliminarne raziskave na živalskem modelu Yamakado K, Pavcnik D, Uchida BT, Timmermans H, Corless CL, Park JW, Yamada K, Keller FS, Rosch J Namen. Z raziskavo na svinjah smo testirali uporabnost in biološki odgovor kovinskih stentov v žolcnem sistemu, oplašcenih z submukozo tankega crevesa (SIS). Materiali in metode. V skupni žolcevod 6 svinj smo vstavili 9 enojnih stentov Z, oplašcenih s submukozo tankega crevesa. Stente smo vstavili z laparatomijo skozi žolcni mehur in žolcnikov = vod. Živali smo žrtvovali ali usmrtili 2 tedna (n=l), 4 tedne (n2) in 10 tednov (n=2) po vstavitvi stentov. Hkrati smo izvedli tudi histološke preiskave. Rezultati. Šestim živalim smo vgradili 9 stentov. Med pregledi po 2, 4 in 10 tednih so 3 stenti v 3 živalih ostali na svojem mestu, medtem ko se je 1 v skupnem žolcniku distalno premaknil, 5 pa se jih je obrnilo postrani. Vseh 9 stentov je bilo prehodnih. Po 10 tednih smo opazili, da se je žolcevod razširil, pretakanje žolca pa se je upocasnilo. Submukoza v tankem crevesu je ostala tu­di po dveh tednih in se niti po 4 tednih niti kasneje ni histološko spremenila. Histološka preiska­va ni odkrila nobenih vnetnih sprememb v žolcevodih preizkusnih živali. V 2 od 3 nepremakn­jenih stentov niti po 2 niti po 10 tednih nismo opazili hiperplazije mukoze, v enem distalno premaknjenem stentu pa se je pojavila po 10 tednih. Zmerno hiperplazijo mukoze smo po 4 ted­nih opazili na distalnem delu nepremaknjenega stenta in po 8 in 10 tednih pri 5 premaknjenih stentih. Zakljucek. Cetudi je zaradi visokega odstotka premaknjenih stentov raziskava omejena, so rezultati nepremaknjenih stentov, ki urejajo pretok žolca, potrjujejo, da stenti v tankem crevesu, oplašceni s submukozo preprecujejo vnetje žolcevoda in hiperplazijo mukoze, ki sta pogosti pri neoplašcenih stentih. Raziskave bomo nadaljevali in jih še posebej izboljšali na stentih z ovlaženo submukozo tankega crevesa. Radio/ Oncol 2001; 35(1): 11-6. Slikovna diagnostika hipertroficne piloricne zožitve Frkovic M, Šeronja Kuhar M, Perhoc Ž, Barbaric-Babic V, Molnar M, Vukovic J Izhodišce. Rentgensko slikanje trebuha in kontrastna preiskava zgornjih prebavil sta obicajni pri otrocih, kjer sumimo na hipertroficno piloricno zožitev. V zadnjem casu ju dopolnjuje oziroma zamenjuje ultrazvocna preiskava. Avtorji v prispevku ocenjujejo vrednost diagnosticnega postopka pri otrocih s kirurško potrjeno hipetroficno piloricno zožitvijo. Bolniki in metode. Avtorji so retrospektivno pregledali popise bolnikov, ki so se zdravili v zad­njih petih letih v bolnišnici Rebro zaradi hipertroficne piloricne zožitve in ugotovili, da je bilo zaradi te bolezni operiranih 14 fantov, starih od 2 (17 dni) do 10 tednov (75 dni). Rezultati. Znak strune (string sign), znak dvojne sledi (double track sign) zdaljšanje in zožitev piloricnega kanala, znak gobe (mushroom sign), s tekocino izpolnjen želodec ter znak kljuna (beak sign) so se izkazali za znacilne dignosticne znake. Devet bolnkov je bilo pregledanih z ul­trazvokom; pri enem je bila diagnoza napacno negativna (razlog je bila neizkušenost preisko­valca), vse ostale pa so bile pozitivne. Zakljucek. Ce je klinicni pregled negativen ali nejasen, je nujno potrebna še ultrazvocna preiska­va, ki jo mora opraviti izkušen radiolog -specialist za ultrazvok. V primerih, ko je izvid ultra­zvocne preiskave negativen, je potrebno opraviti še kontrastno preiskavo zgornjih prebavil. Kadar pa je diagnosticnih možnosti vec, je kot prva na mestu kontrastna preiskava, ki opredeli bolezensko stanje. Radio/ Oncol 2001; 35(1): 17-9. Racunalniška sistema za opredeljevanje porazdelitve tlaka na kolcni sklepni površini: preizkus in rezultati Stankovski V, Smrke D Izhodišca. V delu sta opisana racunalniška sistema Viprecox in Active Contours, ki ju uporabljamo v procesu ocenjevanja nekaterih biomehanskih parametrov kolcnega sklepa vkljucno z najvecjo vrednostjo tlaka v kolcnem sklepu Pmax· Racunalniški sistem Active Contours za svoje izracune uporablja standardne antero-posteriorne rentgenograme cele medenice in obeh kolkov. Aplikacija Viprecox v svojem jedru uporablja relativno enostaven tridimenzionalen matematicni model porazdelitve tlaka na kolcni sklepni površini, ki je podrobno predstavljen drugje (npr. Iglic 1996). Material in metode. Oba racunalniška sistema smo preizkusili tako, da smo analizirali izracu­nane vrednosti Pmax za 81 bolnikov (37 moških in 44 žensk). Zakljucki. Pokazali smo, da sta opisana sistema uporabna pri dolocanju porazdelitve kolcnega sklepnega tlaka iz standardnih anteroposteriornih AP rentgenogramov. Radio/ Oncol 2001; 35(1): 21-30. Scintigrafija skeleta v klinicni praksi Miiller V, Steinhagen J, de Wit M, Bohuslavizki KH Izhodišca. Leta 1971 so prvic izvedli scintigrafijo skeleta z 99111Tc oznacenimi polifosfati. Od takrat je ta preiskava postala ena od najpogosteje izvajanih v nuklearni medicini. Zadnjih deset let pa so se neprestano spreminjale indikacije za obravnavano slikovno skeletno preiskavo. Predstavljamo razlicne indikacije, predvsem tiste, ki jih danes upoštevamo. Zakljucki. Tako kot v mnogih drugih nuklearnomedicinskih preiskavah s skeletno scintifgrafijo dosežemo veliko senzitivnost sprememb. Cesto ugotovimo spremembo kostnega metabolizma, preden se posledicno spremeni kostna struktura, ki jo zaznamo z rentgenskim slikanjem. Na ta nacin lahko ugotovimo skrite kostne lezije v celotnem skeletu. Seveda pa so tako ugotovljene kostne spremembe lahko posledica zelo razlicnih kostnih bolezni. Kostna scintigrafija ima nizko specificnost, zato pogosto ne moramo dolociti etiologije scintigrafsko ugotovljenih kostnih spre­memb. Specificnost preiskave znatno povecamo s trifazno kostno scintigrafijo in SPECT-om. Radio/ Oncol 2001; 35(1): 31-4. Ultrazvocno ugotavljanje pleuralnega izliva: kako majhen volumen še lahko zaznamo Šustic A, Medved I, Kovac D, Ivaniš N, Ekl D, Šimic O Izhodišca. Namen naše raziskave je bil dolociti minimalni volumen proste tekocine v pleural­nem prostoru, ki ga je še moc ugotoviti z ultrazvokom pri kadavrih, ki so ležali vznak. Material in metode. Raziskavo smo izvajali na 20 kadavrih (10 moških, 10 ženskih, starost 66 ±11 let; višina 172 ±9 cm; teža 75 ±12,6 kg; telesna površina 1,87 (0,2 m2). Vsak kadaver smo punktirali obojestransko v petem ali šestem interkostalnem prostoru v medioklavikularni crti. Z venozno infuzijsko iglo smo dovajali 9% raztopino NaCl. Medtem ko je s poljubno hitrostjo vtekala tekocina, smo izvajali ultrazvocno preiskavo v predelu laterodorzalne torakalne stene tik nad pljucno bazo oz. frenikokostalnim sinusom. Ko smo zaznali tekocino med dorzalno torakalno steno in pljuci, smo prekinili dovod tekocine in ugotovili njeno kolicino. Rezultati. Minimalna z ultrazvokom zaznavna tekocina v desnem pleuralnem prostoru je bila 223±52 ml in je statisticno znacilno korelirala s kadavrovo višino (r = 0,69; p < 0,001), težo (r = 0,68; p < 0,01) in telesno površino (r = 0,71; p < 0,001). Volumen zaznavne tekocine v levem pleuralnem prostoru je bil manjši kot na desni strani, znašal je 172±53 ml in je pravtako statis­ticno znacilno koreliral s kadavrovo višino (r = 0,55; p < 0,05), težo (r = 0,59; p < 0,01) in telesno površino (r = 0.60; p < 0.01). Zakljucki. Ugotovili smo, da najmanjši ultrazvocno zaznavni volumen intrapleuralne tekocine premosorazmerno korelira z višino, težo in telesno površino kadavrov. Izmerjena kolicina in­traplevlarne tekocine je 223 ml na desni strani in 172 na levi. Radio/ Oncol 2001; 35(1): 35-41. Intraoperativno obsevanje (IORT) ležišca tumorja pri karcinomu dojke Proulx GM, Hurd T, Lee RJ, Stomper PC, Podgorsak MB, Edge SB Izhodišca. Bolnice z zgodnjo obliko raka dojke imajo manj ponovitev bolezni, ce jih postopera­tivno obsevamo. Takšno zdravljenje pa je dolgotrajno, zato novejše raziskave išcejo tiste skupine bolnic, ki ne bodo potrebovale postoperativnega obsevanja celotne dojke, ampak bi jih zdravili drugace. Razvili so razlicne oblike obsevanja, ki omogocijo enako dobre lokalne kontrole bolezni. Bolniki in metode. Avtorji so analizirali 7 bolnic, ki so bile zdravljene z lokalnim intraopera­tivnim obsevanjem (IORT) ob lumpektomiji. Pri vecini so tudi operativno odstranili aksilarne bezgavke. Vse bolnice so bile obsevane v casu operacije na ležišce tumorja s 120 kV rentgenski­mi žarki. Tumorska doza je bila od 1500 cGy do 2000 cGy. Tri bolnice so imele stadij I bolezni, dve stadij IIA in dve stadij IIB. Rezultati. Srednja doba sledenja je bila 123 mesecev (od 86 do 139 mesecev), pri dveh od sed­mih bolnic se je pojavil lokalni recidiv, ki je bil zdravljen z mastektomijo. Preživetje, ki je bilo povezano z osnovno boleznijo, je bilo 100%, celokupno preživetje pa 86%, ker je ena bolnica um­rla, vendar brez zankov malignoma. Pet bolnic je bilo zadovolnjih s kozmeticnim ucinkom takšnega zdravljenja. Niso zasledili zapletov, ki bi bili povezani z IORT. Zakljucki. Tudi rezultati te pilotske študije kažejo, da ni potrebno vsem bolnicam z zgodnjo ob­liko raka dojke postoperativno obsevati celotne dojke. Zaradi majhnega števila bolnic pa ni moc narediti zakljuckov, za to so potrebne klinicne študije na vecjem številu bolnic. Radio/ Oncol 2001; 35(1): 43-6, Ali naj pri ugotavljanju varovalnih bezgavk pri bolnicah z zgodnjim rakom dojke uporabljamo peritumorsko ali subareolarno iniciranje limfotropnega modrila? Baichev G, Sergieva S, Gorchev G Izhodišca. Biobsija varovalnih bezgavk, ki so jo razvili v novejšem casu, je minimalna invazivna metoda, s katero lahko ugotovimo prizadetost aksilarnih bezgavk pri bolnicah z zgodnješo ob­liko raka dojke, Da bi ugotovili optimalno tehniko za lokalizacijo varovalnih bezgavk, so avtorji primerjali peritumorsko in subareolarno injiciranje modrila, Bolniki in metode. Pri 192 od 238 bolnicah, ki so imele zgodnejšo obliko raka dojke, so upora­bili peritumorsko iniciranje modrila, pri 46 pa subaereolarno iniciranje, Pri vseh je bila nato narejena biopsija varovalne bezgavke po predhodni kirurški odstranitvi aksilarnih bezgavk Rezultati. 80 bolnic je imelo metastatsko spremenjene aksilarne bezgavke, 69 bolnic pa je ime­lo metastatsko prizadete varovalne bezgavke, kar predstavlja 86,3%_ Patohistološki pregled varovalne bezgavke je pravilno ocenil prizadetost aksilarnih bezgavk v 90,6%, ce je bilo barvilo inicirano peritumorsko, ce je bilo inicirano subareolarno, pa le v 68,8 %, Zakljucki. Izkušnje avtorjev kažejo, da je za ocenitev prizadetosti aksilarnih bezgavk primer­nejša peritumorska aplikacija modrila kot pa subareolarna, Radio/ Oncol 2001; 35(1): 47-52_ Kako danes gradiramo sarkome mehkih tkiv? Golouh R, Bracko M Namen. Vecina objavljenih sistemov gradiranja sarkomov mehkih tkiv (SMT) je vsaj delno sub­jektivnih, Zdi se, da med strokovnjaki ni popolnega soglasja o tem, kateri od njih je najboljši, Z raziskavo smo skušali zbrati podatke med patologi iz prakse in tako vsaj delno ugotoviti, kakšna je praksa gradiranja SMT_ Anketiranci. Nakljucno izbranim 135 patologom smo poslali posebej prirejen vprašalnik Rezultati. Dobili smo 88 odgovorov patologov iz 30 dežel iz vseh petih kontinentov, Vecina pa­tologov (85%) gradira SMT, pogosteje v Evropi kot v neevropskih deželah, Oboji uporabljajo na­jpogosteje sistem treh stopenj, prvi v 77%, drugi 67%, V praksi so najpogostejši kriteriji FNCLCC (37.3%), NCI (24%), Brodersa (12%) in Markhedeja (1-4%)_ V Evropi je najbolj popularen sistem FNCLCC Vec kot pol anketirancev uporablja poleg klasicnih histoloških kriterijev tudi moderne metode, Najpogostejša je imunohistokemija, sledijo molekularni markerji in DNA pretocna cit­ometrija, Razprava. Rezulati raziskave kažejo, da imajo patologi histološko gradiranje SMT za koristen, ceprav ne povsem zadovoljiv kazalec bolnikovega preživetja, Radio/ Oncol 2001; 35(1): 53-61. Nadgradnja kamer gama za države v razvoju Fidler V, Prepadnik M, Xie Y Izhodišca. Naredili smo nadgradnjo analognih kamer gama s sistemom osebnega racunalnika. Raziskovalni projekt sta finansirala Mednarodna agencija za atomsko energijo (IAEA) in Ministrstvo za znanost in tehnologijo republike Slovenije. Projekt predstavljamo od izhodišcnih razvojnih zahtev do koncnega sistema. Pri izgradnji zajemalnega vezja ter programske opreme za zajemanje in obdelavo klinicnih preiskav v nuklearni medicini je sodelovalo vec nacionalnih raziskovalnih skupin (iz Kitajske, Indije, Kube ter Slovenije). Zakljucki. Kot najstabilnejši zajemalni sistem mnogih testov na mednarodnih delavnicah in na univerzitetnih klinikah se je izkazal slovensko-angleški PIP -GAMMA-PF. IAEA ga je tudi najštevilcneje dodeljevala kot tehnicno pomoc državam v razvoju. V okviru projekta smo po­magali 52 državam s preko 300 kamer gama. Slovenski GAMMA-PF vsebuje izjemno stabilno rešitev za zajemanje, obdelavo preiskav s celostnim klinicnim paketom, dokumentiranjem, arhiviranjem in komuniciranjem po mrežah (MS Network, NT server, itd). Radio/ Oncol 2001; 35(1): 63-71. Premisleki pri nacrtovanju neposrednih in posrednih ravnih prikazovalnikov z aktivno matriko za portalno slikanje Lachaine M, Fallone BG Izhodišca. Napredek v tehnologiji tankih tranzistorskih plasti je omogocil izdelavo ravnih slikovnih prikazovalnikov z aktivno matriko, ki jih uporabljamo na razlicnih podrocjih medi­cinskega slikanja. Ker je nacrtovanje teh prikazovalnikov še zmeraj v razvojni fazi, ni jasno, kakšne morajo biti njihove detektorske karakteristike za optimalno uporabo v portalnem slikan­ju. Material in metode. Za izracun kvantnega izkoristka detektorja za neposredne in posredne prikazovalnike z aktivno matriko smo uporabili kaskadno analizo in tehnike Monte Carlo. Rezultate izracunov smo uporabili za študij optimalnih karakteristik detektorja. Svoje izracune smo potrdili z rezultati obstojecih meritev. Rezultati. Pokazali smo, da imajo neposredne in posredne metode detekcije enak kvantni izko­ristek za ravni prikazovalnik z idealnimi karakteristikami pri dani masni debelini detektorja. Zakljucki. Ustvarili smo grafe, koristne pri nacrtovanju prihodnjih megavoltnih ravnih prikazo­valnikov z aktivno matriko. Notices Notices submitted for publication should contain a mailing address, phone and/or fax number and/ or e-mail of a Contact person or department. Colorectal cancer March 8-9, 2001 The ESO conference will take place in Milan, Ttaly. 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 Radiotherapy March 11-14, 2001 The "European Conference on Cancer Strategy and Outcomes" will take place in Edinburg, U.K. Contact ECSO 2001, ICM Conference Associates, 4 Cavendish Square, London WiM OBX, U.K.; or call +44 207 499 0900; or fax +44 207 629 3233; or e-mail boa@icmgb.com Laryngeal cancer Mnrch 12-14, 2001 The master course "Endoscopic Treatment of Laryngeal Cancer" 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 Chemotherapy March 22-24, 2001 The ESO training course "New Fluoropyrimidines in Cancer Chemotherapy" will be offered in Thessaloniki, 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 Radiotherapy Mnrch 25-29, 2001 The ESTRO teaching course "Radiotherapy Treatment Planning: Principles & Practice" will take place in Dublin, Ireland. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Brachyradiotherapy March 25-29, 2001 The ESTRO teaching course "Modem Brachytherapy Techniques" will take place in Paris, France. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Urological malignancies Mnrch 30-31, 2001 The ESO training course will be offered in Athens, Greece. 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 Gynecological cancer April, 2001 The ESO training course "New Developments in the Treatment of Gynecological Cancers" will be offered in Oradea, Romania. 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 April, 2001 The ESO advanced course "Breast Conserving Surgery and Breast Reconstruction" 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 Oncology April 1-5, 2001 The ESTRO teaching course "Molecular Oncology for Radiotherapy" will take place in Venezia, Italy. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Rectal Cancer April 6-7, 2001 "2nd The International Symposium on Sphincter Saving Treatment in Rectal Cancer" will take place in Lyon, France. Contact FCSANTE@rockefeller. univ-lyonl .fr Clinical research April 22-26, 2001 The ESTRO teaching course "Clinical Research in Radiation Oncology" will take place in Izmir, Turkey. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Malignant mesothelioma April 20-21, 2001 The meeting "Malignant Mesothelioma -Thera­peutic Options and Role of SV40: An Update" will take place in Chicago, USA. Contact Conference Secretariat, S.G. Madison, 8445 Freeport Parkway, Suite 680, Irving, TX 75063, USA; or call +1 972 929 1900; or fax +1 972 929 1901; or e-mail kimp@sgmadison.com Lung Cancer April 26-30, 2001 The "4th International Congress on Lung Cancer" will take place in Halkidiki, Greece. Contact FORUM Internati ona! Congress Organisers, 18 Mitropoleos str., GR-54624 Thessa­loniki, Greece; or call +30 31 257 128; or fax +30 31 231 849; or e-mail forup@otenet.gr; or see Internet http://www.forumcongress.gr Cancer in elderly April 2 7-30, 2001 The ESO training course "Cancer in the Elderly: New Advances and Perspectives" will be offered in St. Petersburg and 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. Oncology May, 2001 The ESO training course "Influence of Psycholo­gical Factors in the Cancer Process" 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 Prostate cancer Mny 13-14, 2001 The ESTRO teaching course "Brachytherapy for Prostate Cancer" will take place in Leeds, United Kingdom. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiophysics May 20-24, 2001 The ESTRO teaching course "Dose and Monitor Unit Calculations for High Energy Photon Beams: Basic Princi ples & Application to Modem Techniques" will take place in Coimbra, Portugal. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call + 32 7759340; or fax + 32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Notices 81 Radiology May 22-24, 2001 The ESO training course "Interventional and Diag­nostic Radiology in Clinical Oncology" 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. Oncology May 27-29, 2001 The ESO training course "Therapeutic Advances in Oncology" will be offered in Teheran, Iran. 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 Hypertherrnic Oncology May 31 -June 2, 2001 The "19th Annual Meeting of the European Society of Hyperthermic Oncology" (Joint with the "12th European BSD Users Conference") will take place in Verona, Italy. Contact elmaluta@tin.it; or see Internet http://www.esho2001.com Lung Cancer June 3-6, 2001 "7th The Central European Lung Cancer Conference" will take place in Prague, Czech Re­public. Contact 7th CELCC, Conference Partners, Sokolska 10, 120 00 Prague 2, Czech Republic; or call/fax +420 2 2426 1371; or e-mail info@conference.cz Radiosurgery June 4-7, 2001 The "5th International Stereotactic Radiosurgery Society Congress" will be offered in Jerusalem, Israel Republic. Contact 7ISRS Secretariat, c/o International Trave! & Congresses Ltd., 20 Rothschild Boulevard, POB 29313, Tei Aviv 61292, Israel; or phone +972 3 795 1444; or fax +972 3 510 7716; or email congs@interna­tionaltc.co.il; or see http://www.isrs-jerusalem.com. Radiotherapy June 7-9, 2001 The Annual Brachytherapy Meeting GEC/ESTRO will take place in Stresa, Italy. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiobiology June 10-12, 2001 The "1'' ESTRO Workshop on Biology in Radiation Oncology" will take place in Fuglso (Aarhus), Denmark. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Breast cancer June 11-13, 2001 The ESO advanced course "Breast Cancer: Oncologic and Reconstructive Surgery" will be offered in Milan, Italy. 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 Breast cancer June 13-15, 2001 The ESO conference will take place in Milan, Italy. 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 Chemotherapy June 16-17, 2001 The ESO multiprofessional course "High Dose Chemotherapy with Haematological Support" will be offered in Milan, Italy. 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 Oncology June 26-28, 2001 The ESO training course "Prevention and Screening of Cancer" 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. Leukemia and Iymphoma June 24-27, 2001 The ESO advanced course "Molecular Biology of Acute Leukemia and Malignant Lymphoma" will be offered in Ascona , Swi-tzerland. 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 Racliotherapy ]une 24-28, 2001 The ESTRO teaching course "IMRT and Other Conformal Techniques in Practice" will take place in Amsterdam, The Netherlands. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Radiotherapy June 24-28, 2001 The ESTRO teaching course "Imaging for Target Volume Determination in Radiotherapy" will take place in Krakow, Poland. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Obstetrics and gynaecology July 10-13, 2001 The "29th British Congress of Obstetrics and Gynaecology (BCOG)" will take place in Birmingham, U.K. Contact info@conforg.com Radiophysics August 26-30, 2001 The ESTRO teaching course "Physics for Clinical Radiotherapy" will take place in Leuven, Belgium. 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 Brachytherapy August 29 -September 2, 2001 The ESTRO teaching course "Modem Brachy­therapy" will take place in Bratislava, Slovakia. Contact ESTRO office, Av. E. Mounier, 83/4, B-1200 Brussels, Belgium; or call +32 7759340; or fax +32 2 7795494; or e-mail info@estro.be; or see Internet http://www.estro.be Pathology September, 2001 The ESO training course "Hot Topics in Pathology" will be offered in Alexandroupolis, 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 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, Zaloška 2, SI-1000 Ljubljana, Slovenia. FONDACIJA DR. J. CHOLEWA 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 0 1 51 9 1 2 77 FAKS 01 251 81 13 ŽR: 501 00-620-1 33-05-1 0331 1 5-2 1 4 779 FONDACIJA DR.JCHOLEWA Activity of "Dr. J. Cholewa" Foundation for Cancer Research and Education -A Report for the Fourth Quarter of 2000 The activity of the Foundation in the year 2000 and in the earlier part of 2001 represented the con­tinuation of its well established previous pursuits. It was also agreed that it is unfortunately becoming increasingly difficult to entice individuals and other business subjects to contribute to the special type of charities, as is the activity of the "Dr. J. Cholewa" Foundation, as it was possible even some months ago. Fortunately, there are some of the donors from Slovenia and abroad who tirelessly continue to try to support it, and the members of the Foundation and its Executive and Supervisory Committees feel obliged to express their gratitude to ali who understand the importance of its goals and activities to reach them. The summary of the activities of the Foundation in the year 2000 and in the earlier part of 2001 makes a complex and interesting reading. It is planned that the Foundation will help to finance as many scientific and education events in Slovenia as possible and within its reach. Furthermore, a pub­lic invitation for research grants in the field of oncology was published in "Dnevnik" and "Vecer" dai­ly newspapers in Slovenia, in "Radiology and Oncology" international oncology journal, published in Ljubljana, Slovenia, and in "ISIS", the journal of the Medica! Chamber of Slovenia, Ljubljana, Slovenia. It is planned the invitation will be publicly issued again this year with the aim to provide grants for MSc, PhD and post-doctoral studies. In addition, severa! grants for participation on various interna­tional congresses and symposia are to be provided for the applicants from Ljubljana and different re­gions of Slovenia. The Foundation has continued to support the regular publication of "Radiology and Oncology" in­ternational scientific journal, and the regular publication of the "Challenge ESO Newsletter" in 1999, in the year 2000 and in the earlier part of 2001. Both medica! journals are edited, published and print­ed in Ljubljana, Slovenia. In the years 1999 and 2000 the Foundation also contributed support for the publication of the Slovenian Dictionary of Medica! Terminology, and for the Proceedings of two meet­ings organised by the Nursing Association of Slovenia, and dedicated to the problems in oncology. The Foundation will in the year 2001 continue to strive to concentrate its activities to facilitate the ac­cess to oncology research and education to as many interested individuals and institutions in the re­gions of Slovenia as possible. Severa! new approaches and ways to achieve the enhancement of the knowledge in cancer prevention and early detection ali over the country will have to be evaluated. As mentioned earlier, special attention will be given to the requests coming from the regions of Slovenia outside Ljubljana to provide grants for the participation of Slovenian oncologists and others on vari­ous educational meetings in the country and abroad. The Foundation therefore continues to follow its objectives, as was stated before in these reports, and as was decided and outlined by its members participating in the meetings of its General assembly, its Supervisory and Executive Boards. Borut Štabuc, MD, PhD Andrej Plesnicar, MD Tomaž Benulic, MD THE LITTLE KNIGHT, FOUNDATION FOR ASSISTENCE TO YOUNG CANCER SURVIVORS Zarnikova 3, 1000 LJUBLJANA, SLOVENJA Phone: +386 01/306-15-87 Fax:+ 386 01/306-15-87 Bank Accaunt: 50100-678-705843 THE LITTLE KNIGHT, FOUNDATION FOR ASSISTENCE TO YOUNG CANCER SURVIVORS INTRODUCTION The treatment of childhood cancer has markedly improved during the last three decades. We know more about the disease as well as about the damage caused by the treatment. With increased knowledge we can modify treatment in order to minimize its harmful consequences. The number of cures is increas­ing, from 10% to 60%. This growing group of survivors are more or less special individuals with special problems, but with common experience and memory of their fight far survival in early life. The damage is psychological, in our own studies mainly emotional, as well as somatic. These young, cured, farmer patients are less competitive, less ambitious and have lower self-esteem compared with their contemporaries. They have bul few friends and tend to be loners. On the other hand, they appear more adult, are clearly more symphatetic and tolerant of those who differ. In Slovenia each year about 60 children get cancer. Each year the group of survivors, with all their problems, grows by about 40. THE AIM OF THE FOUNDATION IS: -to stimulate research of the late effects of cancer treatment in childhood in order to minimize these ef­fects by better treatment, -to treat and palliate the damage done, to offer technical help, to help to adequate education, -to offer psychological and medica! help and rehabilitation, also in groups, occasionally in a sanatorium, a spa and similar. THE ORGANIZATIONAL SCHEME: The Foundation "The little knight" is a humanitarian faundation and is a legal person according to civil law. The faundation has been faunded by prof. Berta Jereb on 8.10.1996 with a legal act according to the law on Foundations (Legal Journal Slov. Rep. 60/95). The Foundation is administered by a board, whose concern is the achieving of the aims of the faunda­tion, all according to the law and the statute of the faundation enacted 22.1.1997. The board consists of eight members who from among them elect a president. The Foundation has a Board of control with three members, one of them elected as president. The Board of control concerns itself mainly with the economic side of the management. The Foundation is funded by the management of the faunding property, by gifts and other donations, by income from activities and by the stale, through subventions. In order to infarm the society about childhood cancer and its consequences the Foundation is organizing humanitarien concerts and perfarmances. The aim is further to stimulate the young survivors to appear in public to socialize and also but not mainly colect some mony. We have 3-4 concerts per year get support from financial different institutions and have f.i. in 1999 spend more then Sit 3,000.000.-far rehabilitation of 12 survivors in a spa and 30 in the mountains or at the beach. The right and duties of members of the Foundation are a matter of honor. Members do not receive any compensation far their participation in the activity of the Foundation. Berta Jereb, M.D. @ Sanolabor sg zastopa naslednja podjetja Kottermann (Nemcija): INTEGRA BIOSCIENCES (Švica): laboratorijsko pohištvo, laboratorijska oprema za mikrobiologijo, varnostne omare za kisline, biologijo celic, molekularno biologijo luge, topila, pline in strupe, in biotehnologijo ventilacijska tehnika in digest0rji CORNING (ZDA): DAKO (Danska): specialna laboratorijska plastika testi za aplikacijo v imunohistokel'ililidi, za aplikacijo v imunologiji, mikro­patologiji, mikrobiologiji, virologiji, biologiji-virologiji, ipd., mehanske eno­mono-in poliklonalna protitelesa in veckanalne pipete in nastavki SVANOVA Biotech (Švedska): EVL (Nizozemska): Elisa testi za diagnostiko v veterini diagnosticni testi za uporabo v veterinarski medicini NOVODIRECT BIOBLOCK (Francija): kompletna oprema in pripomocki HURNER (Nemcija): za delo v laboratoriju ventilacijska tehnika GFL (Nemcija): CSL -Biosciences: laboratorijski aparati, omare in diagnosticni testi za uporabo skrinje za globoko zamrzovanje v veterinarski medicini ANGELANTONI SCIENTIFliC:. (Italija): BIOMERICA (ZDA): hladilna tehnika in aparati za laborat©liije, hitri testi ka diagnostiko, transfuzijo, patologijo in sodrno medicino EIA /RIA testi EHRET (Nemcija): CHARLES ISCHI (Švica): laminar flow tehnika, inkubatorji, specialna oprema za testiranje izdelkov sušilniki, suhi sterilizatorji in oprema v farmacevtski industriji;aparati za za laboratorijsko vzrejo živali -kletke procesno kontrolo in kontrolo kvalitete ROSYS -ANTHOS (Avstrija): fotometri, avtomatski pralni sistem za mikrotitrine plošce LABORMED d.o.o. Zg. Pirnice 96/c SI -1215 Medvode Tel.: (O) 1 362 14 14 Fax: (0)1 362 14 15 LABORMED, razstavni salon Bežigrajski dvor Periceva 29, Ljubljana Tel.: (0)1 436 49 01 i n f o @ 1 a bo r m e d . si Fax: (0)1 436 49 05 w w w abormed . s Are your radiographers' hands tied by equipment that slows them down' And whar can you do abour it? Nearly 70% of X-rays are made ar a Bucky. A facr that has influenced the design of Philips' Bucl.-y sysrems. lt's led to rechnology without gadgetry, for uncomplicared, speedy work. Control unirs operated one-handed. A display thar diminates rrips to rhe generator. Tomography funcrions activared via a single button. Ali to speed pacient throughput, for improved cosr-efficiency. lr's one way in which Philips Medica! Sysrems is working with you to meet roday's changing healthca.re needs. For more information call 061 177 88 50. website: www.phllips.com/ms - - - - - - - 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 dan Najvecji dnevni odmerek je 800 mg. preprecevanje kandidoze 50 do 400 mg na dan kriptokokni meningitis prvi dan 400 mg, nato od 200 do 400 mg na dan vzdrževalno zdravljenje 200 mg na dan Kontraindikacije: Preobcutljivost za zdravilo ali sestavine zdravila. Interakcije: Pri enkratnem odmerku flukonazola za zdravljenje vaginalne kandidoze klinicno pomembnih interakcij ni. Pri veckratnih in vecjih odmerkih so možne interakcije s terfenadinom, cisapridom, astemizolom, varfarinom, derivati sulfonilureje, hidroklorotiazidom, fenitoinom, rlfampiclnom, ciklosporinom, teofilinom, indinavirom in midazolamom. Nosecnost In dojenje: Nosecnica lahko jemlje zdravilo le, ce je korist zdravljenja za mater vecja od tveganja za plod. Dojece matere naj med zdravljenjem s flukonazolom ne dojijo. Stranski ucinki: Povezani so predvsem s prebavnim traktom: slabost, napenjanje, bolecine v trebuhu, driska, zelo redko se pojavijo preobcutljivostne kožne reakcije, anafilaksija in angioedem -v tem primeru takoj prenehamo jemati zdravilo. Pri bolnikih s hudimi glivicnimi obolenji lahko pride do levkopenije in trombocitopenije in do povecane aktivnosti jetrnih encimov. Oprema in nacin izdajanja: 7 kapsul po 50 mg, 28 kapsul po 100 mg, 1 kapsula po 150 mg. Na zdravniški recept. 1/99. Podrobnejše informacije so na voljo pri proizvajalcu. Krka. d. d„ Novo mesto šmorješko cesta 6 8501 Novo mesta SIEMENS Rešitve po meri Mammomat 3000 modular Mammomat 3000 modular • univerzalni sistem za vse vrste mamografije • optimizacija doze in kompresije z OPDOSE in OPCOMP sistema • modularna zgradba zagotavlja posodabljanje sistema • servis v Sloveniji z zagotovljenimi rezervnimi deli in garancijo • izobraževanje za uporabnike SIEMENS d.o.o. Dunajska 22 1511 Ljubljana Telefon 01 / 474 61 00 Telefaks 01 / 474 61 35 ,---& lzdellje:Bayar Pharma d.o.o. ljubljana. Celovška 135, Ljubljana po liceoci Grilnen1hal GmbH, NemQja lram81 Tramadol analgetik • 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 Roche H'e lnnovate Healthcare Roche Diagnostics 1000 Ljubljana, Slovenia Diagnostics Promotional Office Tei: 080 12 32 PE: Stritarjeva 5, 4000 Kranj, Slovenija tel.: (0)4/ 2015 050, fax: (0)4/ 2015 055 e-mail: kemomed@siol.net KEMOME0 Promega IZDELKI ZA MOLEKULARNO BIOLOGIJO PLASTIKA ZA CELICNE KULTURE SANYO llFE.T'EO-NOLOGIES ,.. CISTA VODA ZA LABORATORIJ SKRINJE CELICNE KULTURE IN HLADILNIKI BIOHIT ELEKTRONSKE IN MEHANSKE AVTOMATSKE PIPETE RadiologtJ and Oncology 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 infarmation, 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 far publica­tion elsewhere: the authors are responsible far ali statements in their papers. Accepted arti­cles become the property of the journal and therefare cannot be published elsewhere with­out written permission from the editorial board. 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Manuscripts which do not comply with the technical requirements stated herein will be returned to the authors far cor­rection befare peer-review. Rejected manu­scripts are generally returned to authors, how­ever, the journal cannot be held responsible far their loss. The editorial board reserves the right to ask authors to make appropriate changes in the contents as well as grammatical and stylistic corrections when necessary. The expenses of additional editorial work and re­quests far reprints will be charged to the au­thors. General instructions• Radiology and Onco­logy will consider manuscripts prepared accor­ding to the Vancouver Agreement (N Engl J Med 1991; 324: 424-8, BM] 1991; 302: 6772; JA­MA 1997; 277: 927-34.). Type the manuscript double spaced on one side with a 4 cm margin at the top and left hand side of the sheet. Write the paper in grammatically and stylisti­cally correct language. Avoid abbreviations unless previously explained. 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In vitro maturation of monocytes in squamous carcinoma of the lung. Br J Cancer 1981; 43: 486-95. Chapman S, Nakielny R. A guide to radiolog­ical procedures. London: Bailliere Tindall; 1986. Evans R, Alexander P. Mechanisms of ex­tracellular killing of nucleated mammalian cells by macrophages. In: Nelson DS, editor. Immunobiology of macrophage. New York: Academic Press; 1976. p. 45-74. Page proofs will be faxed to the correspon­ding author whenever possible. It is their re­sponsibility to check the proofs carefully and fax a list of essential corrections to the editori­al office within 48 hours of receipt. If correc­tions are not received by the stated deadline, proof-reading will be carried out by the edi­tors. Reprints: Fifty reprints are free of charge, for more contact editorial board. Far reprint information in North America Contact: International Reprint Corporation 968 Admiral Callaghan Lane, It 268 P.O. Box 12004, Vallejo; CA 94590, Tei: (707) 553 92 30, Fax: (707) 552 95 24. Nycomed Imaging is proud oj its role in providing jor the early, accurate diagnosis oj disease, thus improving patients' quality oj life and prospect jor effective treatment. The company is commited to the continuous development oj inovative imaging product to enhance diagnostic procedures. ZASTOPA DISTRIBUCIJA HIGIEA d.o.o., Trzin Nycomed SALUS d.d. Ljubljana tel.: (01) 589 72 25 tel.: (01) 589 91 00