ADIOLOGY NCOLOGY December 2008 Vol. 42 No. 4 Ljubljana ISSN 1318-2099 Odobrena indikacija za prehod med adjuvantnim zdravljenjem BISTVENE INFORMACIJE IZ POVZETKA GLAVNIH ZNA^ILNOSTI ZDRAVILA AROMASIN® 25 mg oblo`ene tablete Sestava in oblika zdravila: oblo`ena tableta vsebuje 25 mg eksemestana. Indikacije: adjuvantno zdravljenje `ensk po menopavzi, ki imajo invazivnega zgodnjega raka dojke s pozitivnimi estrogenskimi receptorji in so se uvodoma vsaj 2 leti zdravile s tamoksifenom. Zdravljenje napredovalega raka dojke pri `enskah z naravno ali umetno povzro~eno menopavzo, pri katerih je bolezen napredovala po antiestrogenski terapiji. U~inkovitost {e ni bila dokazana pri bolnicah, pri katerih tumorske celice nimajo estrogenskih recep­torjev. Odmerjanje in na~in uporabe: 25 mg enkrat na dan, najbolje po jedi. Pri bolnicah z zgodnjim rakom dojke je treba zdravljenje nadaljevati do dopolnjenega petega leta adjuvantnega hormonskega zdravljenja oz. do recidiva tumorja. Pri bolnicah z napredovalim rakom dojke je treba zdravljenje nadaljevati, dokler ni razvidno napredovanje tumor-ja. Kontraindikacije: znana preob~utljivost na u~inkovino zdravila ali na katero od pomo`nih snovi, `enske pred menopavzo, nose~nice in doje~e matere. Posebna opozorila in previdnostni ukrepi: predmenopavzni endokrini status, jetrna ali ledvi~na okvara, bolniki z redkimi prirojenimi motnjami, kot so fruktozna intoleranca, malabsorpcija glukoze­galaktoze ali insuficienca saharoze-izomaltase. Lahko povzro~i alergijske reakcije ali zmanj{anje mineralne gostote kosti. @enskam z osteoporozo ali tveganjem zanjo je treba izrec-no izmeriti gostoto kosti s kostno denzitometrijo, in sicer na za~etku zdravljenja in nato redno med zdravljenjem. Medsebojno delovanje z drugimi zdravili: so~asna uporaba zdravil - npr. rifampicina, antiepileptikov (npr. fenitoina ali karbamazepina) ali zeli{~nih pripravkov s {entja`evko - ki inducirajo CYP 3A4, lahko zmanj{a u~inkovitost Aromasina. Uporabljati ga je treba previdno z zdravili, ki se presnavljajo s pomo~jo CYP 3A4 in ki imajo ozek terapevtski interval. Klini~nih izku{enj s so~asno uporabo zdravila Aromasin in drugih zdravil proti raku ni. Ne sme se jemati so~asno z zdravili, ki vsebujejo estrogen, saj bi ta izni~ila njegovo farmakolo{ko delovanje. Vpliv na sposobnost vo`nje in upravl­janja s stroji: po uporabi zdravila je lahko psihofizi~na sposobnost za upravljanje s stroji ali vo`njo avtomobila zmanj{ana. Ne`eleni u~inki: ne`eleni u~inki so bili v {tudijah pon­avadi blagi do zmerni. Zelo pogosti (> 10 %): vro~inski oblivi, bole~ine v sklepih, utrujenost, slabost, nespe~nost, glavobol, mo~nej{e znojenje, blago zvi{anje alkalne fosfataze. Na~in in re`im izdajanja: zdravilo se izdaja le na recept, uporablja pa se po navodilu in pod posebnim nadzorom zdravnika specialista ali od njega poobla{~enega zdravnika. Imetnik dovoljenja za promet: Pfizer Luksembourg SARL, 283, route d’Arlon, L-8011 Strassen, Luksemburg. Datum zadnje revizije besedila: 9.12.2005 Pred predpisovanjem se seznanite s celotnim povzetkom glavnih zna~ilnosti zdravila. Podrobnej{e informacije o zdravilu so na voljo pri: Pfizer, podru`nica za svetovanje s podro~ja farmacevtske dejavnosti, Ljubljana, Letali{ka cesta 3c, 1000 Ljubljana Editorial office Radiology and Oncology December 2008 Institute of Oncology Vol. 42 No. 4 Zaloška 2 Pages 173-239 SI-1000 Ljubljana ISSN 1318-2099 Slovenia UDC 616-006 Phone: +386 1 5879 369 CODEN: RONCEM Phone/Fax: +386 1 5879 434 E-mail: gsersa@onko-i.si Aims and scope Radiology and Oncology is a journal devoted to publication of original contributions in diagnostic and interventional radiology, computerized tomography, ultrasound, magnetic resonance, nuclear medicine, radiotherapy, clinical and experimental oncology, radiobiology, radiophysics and radiation protection. Editor-in-Chief Deputy Editors Gregor Serša Andrej Cör Ljubljana, Slovenia Ljubljana, Slovenia Executive Editor Igor Kocijancic Viljem Kovac Ljubljana, Slovenia Ljubljana, Slovenia Editorial Board Miklós Kásler Geoffrey J Pilkington Karl H. Bohuslavizki Budapest, Hungary Portsmouth, UK Hamburg, Germany Michael Kirschfink Ervin B. Podgoršak Maja Cemažar Heidelberg, Germany Montreal, Canada Ljubljana, Slovenia Janko Kos Uroš Smrdel Christian Dittrich Ljubljana, Slovenia Ljubljana, Slovenia Vienna, Austria Tamara Lah Turnšek Primož Strojan Metka Filipic Ljubljana, Slovenia Ljubljana, Slovenia Damijan Miklavcic Ljubljana, Slovenia Borut Štabuc Tullio Giraldi Trieste, Italy Ljubljana, Slovenia Luka Milas Ljubljana, Slovenia Ranka Štern-Padovan Maria Godény Houston, USA Zagreb, Croatia Budapest, Hungary Damir Miletic Justin Teissié Vassil Hadjidekov Rijeka, Croatia Tolouse, France Sofia, Bulgaria Maja Osmak Sándor Tóth Marko Hocevar Zagreb, Croatia Orosháza, Hungary Ljubljana, Slovenia Branko Palcic Gillian M. Tozer Maksimilijan Kadivec Vancouver, Canada Sheffield, UK Ljubljana, Slovenia Dušan Pavcnik Andrea Veronesi Portland, USA Aviano, Italy Branko Zakotnik Ljubljana, Slovenia Advisory Committee Marija Auersperg Ljubljana, Slovenia; Tomaž Benulic Ljubljana, Slovenia; Jure Fettich Ljubljana; Valentin Fidler Ljubljana, Slovenia; Berta Jereb Ljubljana, Slovenia; Vladimir Jevtic Ljubljana, Slovenia; Stojan Plesnicar Ljubljana, Slovenia; Živa Zupancic Ljubljana, Slovenia Publisher Association of Radiology and Oncology Affiliated with Slovenian Medical Association – Slovenian Association of Radiology, Nuclear Medicine Society, Slovenian Society for Radiotherapy and Oncology, and Slovenian Cancer Society Croatian Medical Association – Croatian Society of Radiology Societas Radiologorum Hungarorum Friuli-Venezia Giulia regional groups of S.I.R.M. (Italian Society of Medical Radiology) Copyright © Radiology and Oncology. All rights reserved. Reader for English Vida Kološa Key words Eva Klemencic Secretary Mira Klemencic Design Monika Fink-Serša Printed by Imprint d.o.o., Ljubljana, Slovenia Published quarterly in 600 copies Beneficiary name: DRUŠTVO RADIOLOGIJE IN ONKOLOGIJE Zaloška cesta 2, 1000 Ljubljana Slovenia Beneficiary bank account number: SI56 02010-0090006751 IBAN: SI56020100090006751 Our bank name: Nova Ljubljanska banka, d.d., Ljubljana, Trg republike 2, 1520 Ljubljana; Slovenia SWIFT: LJBASI2X Subscription fee for institutions EUR 100, individuals EUR 50 The publication of this journal is subsidized by the Slovenian Research Agency. Indexed and abstracted by: Science Citation Index Expanded (SciSearch®) Journal Citation Reports/Science Edition Scopus EMBASE/Excerpta Medica Open J-gate Chemical Abstracts Biomedicina Slovenica This journal is printed on acid- free paper Radiology and Oncology is available on the internet at: http://www.onko-i.si/radioloncol and http://www.versita.com ISSN 1581-3207 Ljubljana, Slovenia December 2008 Vol. 42 No. 4 CONTENTS RADIOLOGY ISSN 1318-2099 UDC 616-006 CODEN: RONCEM What is the most common mammographic appearance of T1a and T1b invasive breast cancer? Maja Podkrajšek, Janez Žgajnar, Marko Hocevar 173 Obliterative hepatocavopathy – ultrasound and cavography findings Ramazan Kutlu 181 Gastric gastrointestinal stromal tumour Ivan Žokalj, Renata Culinovic-Caic, Zvonimir Magaš, Zlatko Pavcec, Hussein Saghir, Jasminka Igrec, Miljenko Marotti 187 ONCOLOGY Time dependence of electric field effects on cell membranes. A review for a critical selection of pulse duration for therapeutical applications Justin Teissié, Jean Michel Escoffre, Marie Pierre Rols, Muriel Golzio 196 Quality of life in patients after combined modality treatment of rectal cancer: Report of a prospective phase II study Vaneja Velenik, Irena Oblak, Franc Anderluh 207 Management of cutaneous side effects of cetuximab therapy with vitamin K1 cr`eme Janja Ocvirk, Martina Rebersek Pituitary metastasis of renal cell carcinoma: a case report Vesna Bišof, Antonio Juretic, Nera Šaric, Ante Melada, Zdravko Perkovic, Marko Radoš, Ranka Padovan Štern 215 225 RADIOPHYSICS A phantom to assess the accuracy of tumor delineation using MRSI Amr A. Heikal, Keith Wachowicz, Steven D. Thomas, Biagio Gino Fallone 232 SLOVENIAN ABSTRACTS I NOTICES IX AUTHORS INDEX 2008 XVI SUBJECT INDEX 2008 XVII Radiology and Oncology is covered in Science Citation Index Expanded (SciSearch®), Journal Citation Reports/Science Edition, Scopus, EMBASE/Excerpta Medica, Open J-gate, Chemical Abstracts, Biomedicina Slovenica research article What is the most common mammographic appearance of T1a and T1b invasive breast cancer? Maja Podkrajšek1, Janez Žgajnar2, Marko Hocevar2 1Department of Radiology and 2Department of Surgical Oncology, Institute of Oncology Ljubljana, Slovenia Background. Data about the mammographic appearance of breast cancer smaller than 10 mm are very limited and different authors use different mammographic criteria. The aim of this study was to determine the most common mammographic appearance of small invasive breast cancers (T1a and T1b ). Patients and methods. The study group consisted of 100 women with 102 small (1-10 mm) invasive breast cancers detected on mammography at a single institution in 16 months period. The mammographic appear­ance of tumours was classified as: mass, mass with associated calcifications, only calcifications or others (asymmetric density and architectural distortion). Results. The most common mammographic appearance was a mass without calcifications (60/102; 59%). Additional 12/102 (11%) tumours had a mammographic appearance of a mass with associated calcifica­tions. Only microcalcifications were detected in 12 (11 %) and asymmetric density and architectural distor­tion in 18 breast cancers (18 %). Most (44/60) cancers which presented mammographically as a mass had stellate margins. The proportion of castig type calcifications was higher in women under 50 years. Conclusions: The most common mammographic finding of small breast cancer is a mass with stellate margins independent of the age of patients. Calcifications with/without mass are more common in woman under 50 years. Key words: breast cancer; mammographic appearance; microcalcifications, stellate; casting; asymmetric density Introduction Breast cancer is the most common non-cutaneous cancer in European women. In Slovenia 1020 new cases and 425 deaths from breast cancer are estimated in 2005. An average Slovenian woman has a lifetime risk of 1 in 16 for developing breast cancer.1 Received 13 October 2008 Accepted 5 November 2008 Correspondence to: Prof. Marko Hocevar, MD, PhD, Institute of Oncology Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia. Phone: +386 1 5879 534; Fax: +386 1 5879 407; E-mail: mhocevar@onko-i.si Mammography can identify breast can­cers too small to palpate on physical ex­amination. Clinical trials have established that screening with mammography may decrease breast cancer mortality, because breast cancers detected on screening mam­mography are smaller and more likely not to have spread to regional lymph nodes as compared with breast cancers detected at physical examination.2-4 Additionally, since breast cancers detected on screening mam­mography are smaller, they can be more often treated with breast conservation and with less-toxic systemic therapy.5 Table 1. Classification of mammographic findings 1 Mass without calcifications: with stellate margins round/oval mass 2 Mass with calcifications 3 Only calcifications: casting powdery crushed-stone like 4 Others: asymmetric density architectural distorsion If we want to detect with mammogra­phy small breast cancers, we have to use the accurate mammographic criteria for early (T1a and T1b) invasive breast cancers. However, there are only a few publications in the literature about the mammographic appearance of breast cancer smaller than 10 mm.6 Additionally, there is unfortunately no standardized approach - different au­thors use different mammographic criteria for breast cancers smaller than 10 mm. The aim of this study was to determine the most common mammographic findings of small invasive breast cancers (T1a and T1b). Patients and methods In the 16 months period (from September 2003 to December 2004) 100 consecutive women (aged 36-77 years; mean 59 years) with 102 pathologically proven small (pT1a and pT1b) breast cancers were treated at the Institute of Oncology in Ljubljana, Slovenia. Most of the cancers were non-palpable (80/102) and detected on screen­ing mammography. Palpable cancers were tumours which were palpable in the same quadrant as histologically proven tumours Table 2. Distribution of mammographic findings in 102 small breast cancers No % 1 Mass without calcifications 60 59 stellate 44 round or oval 16 2 Mass with calcifications 12 11 powdery 1 crushed-stone like 2 casting 9 3 Only calcifications 12 12 powdery 3 crushed-stone like 1 casting 8 4 Other 18 18 asymmetric density 14 architectural distortion 4 Total: 102 100% and which were cytologically proven for cancer (C5) without imaging modality. Mammographic lesions were classified according to BIRADS:7 4 lesions as R2, 28 lesions as R3, 66 as R4 and 4 as R5. Free hand fine needle aspiration biopsy (FNAB) was performed in all 20 patients with pal­pable tumours. Cytology was positive (C5) in 14/20 patients and non diagnostic (C1) in 6/20. In these six patients, as well as in all other cases (80/102) of non palpable tumour, image guided FNAB (58 cases) or core biopsy (28 cases) was performed. In 51 cases biopsy guidance was done by the ul­trasound (US) and in 35 by the stereotaxy. Preoperative diagnosis of breast can­cer was established in 67 patients (C5 in 48 cases and B5 in 19 cases) with nonpal­pable tumours. Occult lesion localization (40/67 by stereotaxy and 27/67 by US) with 30-60 MBq of 99m Tc labeled nanocolloid (Nanocol®) in 0.2 ml saline was performed on the morning of surgery. Tumourectomy Table 3. Distribution of mammographic findings in 28 small breast cancers in women under the age of 50 years No % 1 Mass without calcifications 11 39 stellate 10 round or oval 1 2 Mass with calcifications 6 21,5 powdery 0 crushed-stone like 2 casting 4 3 Only calcifications 6 21,5 powdery 2 crushed-stone like 1 casting 3 4 Other 5 18 asymmetric density 4 architectural distortion 1 Total: 28 100% (58/67), quadrantectomy (3/67) or mastec­tomy (6/67) were combined with a sentinel lymph node biopsy (SLNB). In 31 patients with preoperative C3/C4 (22 patients) or B2-4 (9 patients) radioguid-ed occult lesion localization (ROLL) and ex-cisional biopsy were performed. ROLL was performed in 26 cases under stereotaxic and in 5 cases under sonographic control. After the histological diagnosis of breast cancer (B5), in the second surgical procedure re-excision of the primary site (22 patients), quadrantectomy (2 patients) or mastectomy (3 patients) and SLNB was performed. In four patients only SLNB was performed because of adequate margins (more than 10 mm) after the excisional biopsy. Two patients with palpable cytologically proven breast cancers (C5) underwent tu­mourectomy and axillary dissection be­cause preoperative US examination and US guided FNAB of the axillary lymph nodes revealed metastases in lymph nodes.8 All mammographic images were re­viewed by a single radiologist (PM), who has a special interest and dedication in breast radiology. Mammographic findings were classified according to Table 2, as seen in Table 1. A mass is defined as a lesion seen in two different projections, while a density is observed only in a single projection ac­cording to Samardar.9 Pathologic characteristics of primary tumours included size, histologic type, grade (according to Bloom, Richardson and Elston), status of axillary lymph nodes, estrogen and progesteron receptors and HER2 status. The histological type of breast cancers was as follows: invasive ductal, in­vasive lobular, tubular, mucinous, medul­lary and papillary. For the statistical analysis descriptive statistical methods were used. Results The mean size of breast cancers was 8.1 mm (range 4-10 mm; pT1a in 18 and pT1b in84 cases). Histologically 86/102 (84%) were invasive ductal, 14/102 (14%) invasive lobular and 2/102 (2%) invasive tubular cancers. There were 48/102 (47%) grade I, 41/102 (40%) grade II and 13/102 (13%) grade III cancers. The great majority of pa­tients (98/100) had no metastasis in lymph nodes. Estrogen and progesteron receptors were positive in 91 patients, while there were only 8 patients with positive HER2 tumours. The most frequent mammographic find­ing was a stellate mass without calcifica­tions, which was seen in 44/102 (43%) can­cers (Table 2). Casting type calcifications were found in 17/102 (17%) cancers. There were 28 patients younger than 50 years and Table 3 shows mammographic findings in this group of patients. The most frequent mammographic finding was a stel- Radiol Oncol 2008; 42(4): 173-80. Table 4. The association between mammographic appearance and histologic type and grade of the tumor IDC ILC ITC Gradus Gradus Gradus III I 1 Mass without calcifications 51 8 1 6 32 22 stellate 40 4 4 24 16 round or oval 11 4 1 2 8 6 2 Mass with calcifications 9 2 1 5 5 2 powdery 1 1 crushed-stone like 1 1 1 1 casting 7 2 4 3 2 3 Only calcifications 12 3 3 6 powdery 3 3 crushed-stone like 1 1 casting 8 3 2 3 4 Other 14 4 8 10 asymmetric density 10 4 7 7 architectural distortion 4 1 3 Total: 8614 2 13 48 41 IDC invasive ductal carcinoma, ILC invasive lobular carcinoma, ITC invasive tubular carcinoma late mass without calcifications, which was seen in 10/28 (36%) cancers. Casting type calcifications were seen in 7/28 (25%) of these cancers. Table 4 shows the distribution of mam-mographic findings as compared to the his­tological type and histological grade of 102 small breast cancers. Invasive lobular cancers were found in 14% (14/102) of invasive small breast can­cers and were mammographically seen as a mass or asymmetric density in 12/14 (86%) cases. No invasive lobular cancer was mam-mographically seen as only calcifications. Table 5 shows the distribution of mam-mographic findings as compared to histo­logical type and histological grade of 28 small breast cancers in women under the age of 50. There were 22/28 (79%) grade II and III tumours in this group of young pa­tients. Figure 1. 48 years old women with three breast carcinomas. First stellate mass without calcifications on mammography. Histologically proven as 1cm large invasive breast carcinoma, grade 2. Second stellate mass with casting calcifications on mammography. Histologically proven as 0.9 cm large invasive breast carcinoma, grade 3. Third round mass without calcifications on mammography. Histologically proven as 0.7 cm large invasive breast carcinoma, grade 1. Figure 1 shows mammographic appear­ance of three different synchronous cancers in a single woman. Table 5. The association between mammographic appearance and histological type and grade of the tumor in women under 50 years IDC ILC ITC Gradus Gradus Gradus ll l lll 1 Mass without calcifications 10 1 1 1 9 stellate 9 1 1 1 8 round or oval 1 1 2 Mass with calcifications 5 1132 powdery crushed-stone like 1 2 casting 4 1 3 3 Only calcifications 4 2 3 1 2 powdery 2 1 1 crushed-stone like 1 l casting 2 1 2 1 4 Other 5 3 1 1 asymmetric density 4 2 1 1 architectural distortion 1 1 Total: 24 318 6 14 IDC invasive ductal carcinoma, ILC invasive lobular carcinoma, ITC invasive tubular carcinoma Discussion The most common mammographic find­ing in small breast cancers (T1a and T1b) in our study was a stellate mass without calcifications. It was found in 44/102 (43%) of small breast cancers. This is consistent with results of other published series.6-14 Additional 16/102 (16%) of small breast cancers have mammographic appearance of a round/oval mass without calcifica­tions. Calcifications with/without mass were present in 24/102 (24%) of small breast cancers. The important finding of our study was that the distribution of mammographic findings in small breast cancers varied with age. In the group of younger women (< 50 years) with higher breast density, a stellate mass without calcifications was still the most common mammographic finding. It was found in 10/28 (36%) of small breast cancers. However, the proportion of circu-lar/oval shaped tumours was much smaller in this group of women. There was only a single woman (1/28) with a mammographic finding of a circular/oval shaped tumour. On the other hand, calcifications with/with­out mass are much more common mammo-graphic findings in younger women. In our series, 12/28 (43%) of small breast cancers appeared mammographically as calcifica­tions. Half (6/12) of them with a mass and half of them without it. More importantly, the majority of calci­fications were of the casting type. Tabar6 proved by the multivariate analysis that the mammographic appearance of small breast cancers was an independent prognostic fac­tor. In his study the mammographic appear­ance of casting type calcifications was more predictive of a long-term survival than clas- Radiol Oncol 2008; 42(4): 173-80. Figure 2. Mediolateral oblique view of the right breast with BIRADS category 4. Mammographic finding of 0.8 cm large asymmetric density. Patologically proven as invasive ductal carcinoma grade 2. sic prognostic factors (tumour size, histo­logical grade and lymph node status). The 20-year survival rate was 72% for women with small breast cancers accompanied by casting – type calcifications. All other women with small breast cancers had an excellent survival regardless of lymph node status, histological grade or treatment.6 Casting type calcifications are associ­ated significantly with a positive lymph node status and poorer histological grade.6 In our series there were only two patients with lymph node metastases. Both of them had tumours accompanied by casting type calcifications. The majority of our patients with small breast cancers accompanied by casting type calcifications also had a high­er histological grade (grade III in 7/15 and grade II in 5/15). Asymmetric breast findings define as four different types: asymmetric breast tis­sue, densities seen in one projections, ar-chitectural distortion, and focal asymmetric densities.8,9 We have observed an architec­tural distortion (a focal area of breast tissue appears distorted with no definable central mass) and a focal asymmetric density also in our study. From 102 small breast cancers, 14 (14%) were seen as a focal asymmetric density and 4 as an architectural distor­tion. Interestingly, 4/14 (26%) of focal asym­metric density proved histologically to be invasive lobular cancers. Invasive lobular cancers accounts for 5-10% of all breast can­cers and can often manifest as an area of distortion or asymmetry.10 In our series we found 14% of invasive lobular cancer, that in 86% appeared as spiculated mass or fo­cal asymmetric density. There was no case of an invasive lobular cancer which would appear mammographically as calcifications only. This is in agreement with results of Tjurfjell.13 Samardar15 defined that palpable mass associated with a focal area of breast asym­metry or architectural distortion is very of­ten malignant. We found in our series only 20 palpable small breast cancers and they all appeared mammographically as a mass with/without calcifications. Conclusions Most of the T1a and T1b breast cancers are nonpalpable. The most common mammo-graphic finding in these cancers is stellate mass without calcifications. Calcifications are more frequent mammographic findings in younger patients. Fourteen % of small breast cancers appear mammographically as a focal asymmetric density. Invasive lob­ular cancer never appears mammographi­cally as calcifications only. References 1. Primic Zakelj M. Cancer incidence in Slovenia 2005. Ljubljana: Institute of Oncology Ljubljana. Cancer Registry of Slovenia; 2008. 2. Fletcher SW, Elmore JG. Clinical practice. Mammographic screening for breast cancer. N Engl J Med 2003; 348: 1672-80. 3. Leitch AM, Dodd GD, Costanza M, Linver M, Pressman P, McGinnis L, et al. American Cancer Society guidelines for the early detection of breast cancer: update 1997. CA Cancer J Clin 1997; 47: 150­3. 4. Tabar L, Vitak B, Chen HH, Prevost TC, Duffy SW. Update of the Swedish Two-County Trial of breast cancer screening: histologic grade-specific and age-specific results. Swiss Surg 1999; 5: 199-204. 5. Barth RJ, Jr., Gibson GR, Carney PA, Mott LA, Becher RD, Poplack SP. Detection of breast cancer on screening mammography allows patients to be treated with less-toxic therapy. Am J Roentgenol 2005; 184: 324-9. 6. Tabar L, Tony Chen HH, Amy Yen MF, Tot T, Tung TH, Chen LS, et al. Mammographic tumor features can predict long-term outcomes reliably in women with 1-14-mm invasive breast carcinoma. Cancer 2004; 101: 1745-59. 7. Rissanen TJ, Makarainen HP, Mattila SI, Karttunen AI, Kiviniemi HO, Kallioinen MJ, et al. Wire local­ized biopsy of breast lesions: a review of 425 cases found in screening or clinical mammography. Clin Radiol 1993; 47: 14-22. 8. Obenauer S, Hermann KP, Grabbe E. Applications and literature review of the BI-RADS classifica­tion. Eur Radiol 2005; 15: 1027-36. Radiol Oncol 2008; 42(4): 173-80. 9. Kocijancic I, Rener M, Vidmar K. Simultaneous oc­curence of fat necrosis and carcinoma after breast injury in a traffic accident. Eur J Ultrasound 2000; 11: 213-6. 10. Burrell HC, Pinder SE, Wilson AR, Evans AJ, Yeoman LJ, Elston CW, et al. The positive predic­tive value of mammographic signs: a review of 425 non-palpable breast lesions. Clin Radiol 1996; 51: 277-81. 11. Franceschi D, Crowe JP, Lie S, Duchesneau R, Zollinger R, Shenk R, et al. Not all nonpalpable breast cancers are alike. Arch Surg 1991; 126: 967­70. 12. Sickles EA. Mammographic features of 300 consec­utive nonpalpable breast cancers. Am J Roentgenol 1986; 146: 661-3. 13. Thurfjell MG, Lindgren A, Thurfjell E. Nonpalpable breast cancer: mammographic appearance as pre­dictor of histologic type. Radiology 2002; 222: 165­70. 14. Tinnemans JG, Wobbes T, Holland R, Hendriks JH, Van der Sluis RF, Lubbers EJ, et al. Mammographic and histopathologic correlation of nonpalpable lesions of the breast and the reliability of frozen section diagnosis. Surg Gynecol Obstet 1987; 165: 523-9. 15. Samardar P, de Paredes ES, Grimes MM, Wilson JD. Focal asymmetric densities seen at mammogra­phy: US and pathologic correlation. Radiographics 2002; 22: 19-33. case report Obliterative hepatocavopathy – ultrasound and cavography findings Ramazan Kutlu Department of Radiology, Inonu University School of Medicine, Malatya, Turkey Backgound. Obliterative hepatocavopathy is a relatively new term for the definition of primary inferior vena cava thrombosis and membranous obstruction of inferior vena cava that were included in Budd-Chiari syndrome. Case report. In this report, cavography and ultrasound findings of a case with a complete occlusion of inferior vena cava in a 36 year-old female patient who has been followed up with the diagnosis of hepatitis B related cirrhosis for 5 years were presented. Conclusions. Although this disease classically treated by surgery (e.g. portal or mesenteric–systemic shunt­ing, liver transplantation), also interventional radiology procedures e.g. transjugular intrahepatic portosys­temic shunting, percutaneous hepatic vein angioplasty and/or stent placement), now play an important role in the management4. Key words: obliterative hepatocavopathy; cavography; ultrasound; inferior vena cava Introduction The complete inferior vena cava (IVC) ob­struction develops as a result of primary IVC thrombosis.1 Although in the earlier literature this entity was included in Budd-Chiari syndrome, obliterative hepatocavop­athy (OH) is currently being used to define this condition.1 In this report, we present Received 20 September 2008 Accepted 28 October 2008 Correspondence to: Assoc. Prof. Ramazan Kutlu, M.D., PhD, Department of Radiology, Inonu University School of Medicine, Turgut Ozal Medical Center, 44069 Malatia, Turkey. Phone: +90 422 341 0660 (Extn: 5703); Fax: +90 422 341 0834 (Attn: Dr. Ramazan Kutlu); E-mail: rkutlu@inonu.edu.tr cavography and ultrasound features of this rare entity in a 36 year-old female patient. Case report A 36 year-old female patient who has been followed with the diagnosis of chronic liver disease (Child B, score 7) due to hepatitis B for 5 years was referred to our radiol­ogy department for portal Doppler evalua­tion. She had splenomegaly and moderate ascites. Upper gastrointestinal endoscopy revealed esophageal varices. She had been receiving beta blockers and diuretics. Her CA-125 level was found to be increased (234 U/mL). AB Figure 1. Gray scale axial (A) and sagittal (B) US images show hyperechoic, solid material at the posterolateral part of distal IVC. Gray scale (Figure 1 A,B) and Doppler (Figure 2 A-C) US examinations showed compressed hepatic veins, hepatopedal portal flow, and no blood flow into the right atrium through distal IVC which was thrombosed. The abdominal CT examina­tion revealed the absence of intrahepatic portion of IVC. The patient didn’t undergo A MR examination due to claustrophobia. Cavography was performed using right femoral vein access. Firstly, a large vein was erroneously accessed and a test injec­tion before introducer placement demon­strated that this vein was a large collateral vein extending to the right side of the body and ultimately draining to the intercostal, pericardiophrenic and right subclavian vein (Figures 3 A-E). Secondly, the right femoral vein was catheterized and inferior cavogra­phy revealed a complete occlusion of distal 4 cm of IVC connecting to the right atrium and retrograde flow into the prominent col­laterals in the late series (Figures 4 A,B). The selective catheterization of the hepat­ic veins showed hepatic vein confluence and weak filling (Figure 5A) and a small vein below hepatic confluence draining to IVC (Figure 5B). Superior vena cavography BC Figure 2. Sagittal (A, B) Doppler US images slight filling of hepatic vein and complete occlusion of distal IVC. Subcostal oblique image (C) reveals a relatively small hepatic vein below the hepatic confluence. Radiol Oncol 2008; 42(4): 181-6. Figure 4. Cavography performed with 6F pigtail catheter which could not passed into right atrium showed complete occlusion of distal IVC (A). Due to downward flow in the late series, markedly dilated and tortuous paraspinal collaterals were seen (B). stent placement were considered but the conditions were included in Budd-Chiari patient did not accept the intervention. syndrome which was defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction Discussion of the IVC and the right atrium, regardless of the cause of obstruction.2 Occlusion and OH is a relatively new term proposed to stenosis of the IVC are squeals of primary define primary IVC thrombosis and mem-IVC thrombosis.1 Although the majority of branous obstruction of the IVC.1 These two these cases are idiopathic, as in our case, Figure 5. Selective hepatic vein injection showed a part consistent with hepatic vein confluence and tangle of vessels in the area of hepatic veins (A) and a small vein that had been seen during Doppler examination (B). Figure 6. Superior venacavogram through introducer in right jugular vein shows no passage into IVC (A) and rapid filling of pulmonary arteries (B). Selective catheterization with a multipurpose catheter shows extrahepatic collaterals and filling of pulmonary arteries due to backflow (C), and in the later phases collateral connecting to occluded distal IVC appears and than IVC fills. thrombotic or hypercoagulable conditions (like coagulation factor deficiency or mu­tation, myeloproliferative disorders, oral contraceptive use, pregnancy etc) could be observed in OH.1 If all hepatic veins become occluded, blood is coming from hepatic artery drain into either portal veins or collateral vessels. Retrograde flow in the portal vein occurs and portocaval shunts develop. As the occlusion progresses, blood circulation changes appear in and around liver. Intrahepatic or subcapsular hepatic venous collaterals are a distinctive feature of Budd–Chiari syndrome.2,3 In complete IVC obstruction, large shunts form be­tween the IVC and the ascending lum­bar vein continuous with the azygos and hemiazygos veins or paravertebral veins. The increased pressure in the ascending lumbar/hemiazygos and azygos veins may result in retrograde flow in the intercostal and subcutaneous veins. Radiol Oncol 2008; 42(4): 181-6. Due to mainly difficulties in the differ­ential diagnosis of primary hepatic vein thrombosis and primary IVC thrombosis, the epidemiology of primary IVC throm­bosis is not well established and adults are affected more frequently, but OH could be seen at any age.1 The clinical presentation is acute and very serious like in the case of ve­na cava superior sindrom.1,4 Hepatomegaly, ascites, abdominal pain, fever and leg oede-ma appear quite fast, but the clinical course could be chronic with repeated acute epi­sodes characterized by ascites, hepatomeg­aly, and pain.1 Due to the circulatory distur­bances caused by IVC obstruction, patients commonly show marked venous dilatation over the body trunk.1 Our case had no vis­ible venous dilatation over the body trunk possibly due to the collateral between oc­cluded distal IVC and right atrium. The radiological imaging provides a de­finitive diagnosis of OH. In addition to dem­onstrating thrombus within the IVC and he­patic vein problems, ultrasonography also demonstrates caudate lobe enlargement, splenomegaly, ascites, stenotic veins, mem­brane, intrahepatic collateral veins con­necting with enlarged hepatic veins, vein to-vein anastomoses, a patent and enlarged inferior right hepatic vein opening into the IVC, and absence of normal respiratory changes in the IVC. Doppler US could de­lineate flow disturbances and direction. CT and MRI assess hepatomegaly, ascites, en­larged caudate lobe, splenomegaly, collater­al vessels, and the thrombus occluding the IVC. MRI depict the level of an obstructing membrane or web within the IVC.1 Hepatic venography delineates occluded veins, slow flow in attenuated venous branches, and rapid shunting into the portal vein. Additionally, wedged hepatic venography will demonstrate the “spider’s web” net­work.1 Cavography is one of the most im­portant imaging modality in the evaluation of IVC obstruction. It confirms the level of obstruction, occluding thrombus, mural thrombosis, membrane, and extrahepatic collateral vessels.1 Based on cavography findings three types of IVC obstruction were defined; type I, a thin membrane is present in the vena cava, type II, there is an absent segment of the IVC of variable length, type III, the vena cava is not visu­alized, and only dilated collateral channels are demonstrated.2 According to this clas­sification, our case appears to be type II. Although this disease classically treated by surgery (e.g. portal or mesenteric-system­ic shunting, liver transplantation), interven­tional radiology procedures e.g. transjugu­lar intrahepatic portosystemic shunting, percutaneous hepatic vein angioplasty and/ or stent placement also plays an important role in the management – like in the others severe vascular complicated cases.3,5,6 References 1. Okuda K. Inferior vena cava thrombosis at its he­patic portion (obliterative hepatocavopathy). Semin Liver Dis 2002; 22: 15-26. 2. Sakamoto N, Koizumi K, Asahina Y, Tazawa J, Maeda M, Marumo F, et al. Primary Budd-Chiari syndrome due to complex venous anomalies. Abdom Imaging 1997; 22: 499-501. 3. Janssen HL, Garcia-Pagan JC, Elias E, Mentha G, Hadengue A, Valla DC; European Group for the Study of Vascular Disorders of the Liver. Budd-Chiari syndrome: a review by an expert panel. J Hepatol 2003; 38: 364-71. 4. Vodvárka P, Števerák P. Algorithm for percutaneous stenting in patients suffering from superior vena cava syndrome. Radiol Oncol 2000; 34: 349-55. 5. Wu T, Wang L, Xiao Q, Wang B, Li S, Li X, et al. Percutaneous balloon angioplasty of inferior vena cava in Budd-Chiari syndrome-R1. Int J Cardiol 2002; 83: 175-8. 6. Gjikolli B, Hadžihasanovic B, Jaganjac S, Herceglija E, Nikšic M, Hadzimehmedagic A, et al. Treatment of complicated case with subclavia steal syndrome and stenosis of common iliac artery. Radiol Oncol 2008; 42: 1-12. case report Gastric gastrointestinal stromal tumour Ivan Žokalj1, Renata Culinovic-Caic2, Zvonimir Magaš2, Zlatko Pavcec1, Hussein Saghir1, Jasminka Igrec1, Miljenko Marotti3 1Department of Radiology and Ultrasound, County Hospital Cakovec, Croatia; 2Department of Surgery, County Hospital Cakovec, Croatia 3Department of diagnostic and interventional radiology, University Hospital “Sisters of Mercy”, Zagreb, Croatia Background. Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. These tumours can not be simply divided into benign and malignant forms. There is a continuum from benign to malignant forms. The tumour size and mitotic activity have strong influence on GISTs behaviour. Tumour behaviour also varies according to the site of the origin. The site of the tumour origin can be anywhere along the digestive tract, in the mesentery or omentum. GISTs are mainly benign tumours, about 70-80%, usually found in the gastric wall. We report a case of 70-year old female with gastric form of GIST. Case report. The patient has undergone abdominal ultrasound (US) because of a palpable lump in the epi­gastrium, which mainly revealed hyperechogenic round mass with small hypoechogenic areas in the central part. On the abdominal computed tomography (CT) a large expansive mass with heterogeneous structure was depicted in the gastric wall. The mass had higher attenuation coefficients on the periphery and lower in the central part. During the surgery the large exophytic tumour of the gastric wall has been found. The diagnosis of gastric GIST has been obtained after the patohistologic and imunohistochemical analysis. Conclusions. Gastrointestinal stromal tumours may be the statistically rare tumours (0.1%-0.3% of all gastrointestinal tumours) but when we have the patient with a round, mainly exophytic mass on the wall of the gastrointestinal tract or peritoneum, GIST must be taken into consideration. Cross-sectional imaging methods like US and CT allow the preoperative diagnosis of the tumour and staging. Key words: gastrointestinal stromal tumours; computed tomography Received 3 November 2008 Accepted 18 November 2008 Correspondence to: Ivan Žokalj, MD, Department of Radiology and Ultrasound, County Hospital Cakovec, Ivana Gorana Kovacica 1e, 40000 Cakovec, Croatia. Phone: +385 40 375 297; E-mail: ivan.zokalj@ck.t-com.hr Introduction Gastrointestinal stromal tumours (GISTs) are currently defined as mesenchymal tu­mours of the gastrointestinal tract, mainly KIT (CD117)-positive.1 These tumours usu­ally affect the population over 50 years, rarely patients younger than 40 years of age, and are extremely rare in the child­hood.1-3 The frequency of GISTs is about 10 to 20 cases per million persons, according to the Miettinen and Lasota.4 GISTs can arise anywhere through the gastrointes­tinal tract but they can also occur in the omentum, mesentery and retroperitoneum as a primary tumour. In 70% of cases GISTs arise in stomach, the second most fre­quent site is small intestine (20-30%). Other less frequent sites are anus, rectum, colon and oesophagus.4 GISTs of gastrointesti­nal tract commonly arise in the muscularis propria of the stomach or intestinal wall, usually in the outer muscular layer. That is the reason why GISTs have an exophytic growth pattern in majority of the cases and usually manifest themselves as large extraluminal abdominal masses. Clinical features of GISTs depend on the size and anatomic location of the tumour. They can be presented with mild signs and symp­toms of anaemia caused by occult bleeding in the gastrointestinal tract or they can have a dramatic picture with hematemesis, me-lena, abdominal pain and signs of intestinal obstruction.5,6 Histogenetically gastrointestinal stromal tumours probably originate from intersti­tial cells of Cajall (or the native KIT-positive gut pacemaker cell) which intermediates between the GI autonomic nervous system and smooth muscle cells regulating GI mo­tility and autonomic nerve function. This postulate is made on the expression of KIT on GISTs tumour cells.1,7 Larger forms of GISTs are usually cen­trally cystic, positioned extraluminally, while smaller GISTs are subserosal and intramural solid tumours, rarely polypod intraluminal ones.1 GISTs can generally be divided into three groups: spindle cell type (70%), epithelioid type (20%) and mixed spindle and epithelioid cel type.7 Gastric GISTs can be histologically divided into two groups, four spindle cell subtypes (scleros­ing spindle cell, palisaded-vacuolate spindle cell, hypercellular spindle cell, sarcomatous spindle cell) and four epitheloid subtypes (sclerosing epithelioid GIST with syncytitial pattern, epitheloid GIST with dyscohesive pattern, hypercellular epitheloid GIST, sar­comatous epitheloid GIST). Sarcomatous subtype is highly cellular form of GIST with a marked mitotic activity (more than 20 per 50 HPFs).9 The most important feature for immunohistochemical differentiation be­tween GISTs and other similar soft-tissue tumours are the antigens on the surface of the tumour cells, especially KIT tyrosine kinase receptor (CD117) which has been found in more than 95% of GISTs. There are other antigens which are less specific for GISTs but are commonly expressed, like CD34 and nestin. GISTs sometimes express smooth muscle cell markers (like smooth muscle cell actin-SMA), but are usually negative for desmin, the muscle type in­termediate filament protein.1 KIT imunore-activity has shown to be very useful in the treatment of GISTs with immunotherapy as well as in diagnostics. The immunotherapy of GISTs is based on targeting of tyrosine kinase receptors with a selective KIT-ty­rosine kinase inhibitor (STI-571, imatinib mesylate). The drug acts as a selective c-kit blocker.6 The contrast-enhanced computed tom­ography (CT) is currently widely available diagnostic imaging method and the imag­ing modality of choice for patients with ab­dominal mass suspected for GISTs.7 The standard initial treatment for GISTs, even in non-resectable cases, is the surgical treatment. Some authors propose the im­mediate treatment with imatinib for unre­sectable and/or metastatic disease.8 Case report A 70-year old female patient underwent abdominal ultrasound (US) because of pal- Figure 1. Abdominal ultrasound – axial plain. Large round hyperechogenic expansive mass (white arrow) with small hypoechogenic areas in the central part (white notched arrow). pable mass in the upper abdomen. The patient suffered from inapetency without vomiting and weight loss, hematemesis or melena. US revealed a large round hy­perechogenic expansive mass with small hypoechogenic areas in the central part. There were no signs of focal lesions in pa-renchymal abdominal organs or lymphad­enopathy (Figure 1). The next step in diagnostics was com­puted tomography (CT) of the abdomen, performed with three postcontrast phases and distension of gastrointestinal (G-I) tract with 1000ml of water. CT depicted a large intraperitoneal mass in the upper abdo­men, ventrally placed and sharply demar­cated from surrounding structures except from stomach. The lesion had a heteroge­neous structure on native and postcontrast scans with higher attenuation coefficients on periphery and lower in the central part (about 30HU on precontrast and 60HU on postcontrast scans). There were no sig­nificant changes in attenuation values cen­trally between precontrast and all series of postcontrast scanns. No lymphadenopathy or focal lesions in the parenchymal organs have been found. The working (imaging) diagnosis of mesenchymal tumour of the stomach wall (probably GIST) has been es­tablished (Figure 2). The upper G-I tract follow through with barium showed elongated stomach with sharply demarcated contours and concave­ly impressed lesser curvature (Figure 3). The patient has been treated surgically with a complete gross resection. During the explorative laparatomy a large tumour in the upper abdomen with origins on the lesser curvature of the stomach without lymphad­enopathy has been found (Figure 4). The material obtained during surgery has been sent to the pathohystologic analy­sis and immunochemical evaluation. The gross pathologic feature of the specimen was an encapsulated mass of medium firm consistency, measuring 18 cm in largest diameter. On cut section the tumour was whitish and greyish with dispersed areas of swirling structure. Predominant histologi­cal features were spindle shaped cells with scant cytoplasm and big nucleus without nucleolus. The tumour cells formed swirl­ing structures and tracks. Focal areas of de­generation and small areas of tumour tissue necrosis were found. Three mitoses per 50 consecutive high power fields (HPF) have been detected. The immunohistochemical analysis showed that the tumour cells were CD117(C-kit), CD 34 and BCL2 positive, SMA -/+ and S-100 negative. The diagnosis of gastroin­testinal stromal tumour was established. Discussion GIST is usually placed in the stomach and small intestine. The gastric form is especially common between other possible locations, 50 to 70% of GISTs are located in the stomach, 33% of cases in the small Radiol Oncol 2008; 42(4): 187-95. Figure 2. Abdominal CT post-contrast axial scan. Large round expansive mass in the upper abdomen with heterogeneous structure sharply demarcated from surrounding structures depicted on this scan. Higher attenuation coefficients on periphery (white arrow) and lower in the central part were detected on native and postcontrast scans (white notched arrow). intestine, 5 to 15% in rectum and colon and only 1 to 5% in oesophagus.2,10 GISTs can originate outside of the gastrointestinal wall, in mesentery or peritoneum in 10% of cases, but they are extremely rare retroperi­toneally. Both sexes are equally affected by GISTs, commonly between 40 and 70 years. The small intestine GISTs are usually more aggressive and have a more grave prognosis than GISTs which originate in other seg­ments of G-I tract.3,11 The factors that worsen the prognosis of GISTs are location (all extragastric lo­cations), size of the tumour (bigger than 5cm), advanced age of the patient, metas­tasis at the time of tumour manifestation, tumour tissue necrosis and high mitotic index (more than five mitosis per 50 high-power fields).4,10,11 In 10 to 30% of GISTs malignant forms have been diagnosed.4 The two most important factors that influ­ence GISTs prognosis are the tumour size and mitotic index. Currently it is believed that only tumours with diameter smaller than 1 cm can be considered as definitely benign on clinicopathologic features.12 The patient presented in this report has few bad prognostic factors, age of 70 years and the tumour largest diameter of 18 cm. Clinical features of GISTs depend on the tumour size and anatomic location of the tu­mour, they can be mild signs and symptoms of anaemia caused by occult bleeding in the gastrointestinal tract or dramatic picture with hematemesis, melena, abdominal pain and signs of intestinal obstruction.5 GIST of the stomach, small and large intestine and anorectum usually manifest with gas-trointestinal bleeding from mucosal ulcera­tions. The other common clinical features are abdominal pain, nausea, dysphagia, vomiting, weight loss and palpable abdomi­nal mass.13,14 The leading clinical feature of the case presented in this article was pal­pable abdominal mass in the epigastrium. G-I tract obstruction can be manifested in 10 to 30% of cases, usually in the cases of the small intestine GIST. The biliary tract and the renal obstruction may be the clini­cal feature of the duodenal GIST.13,15 The tumour is usually covered with an affected organ serosa. In the cases of the surrounding structures infiltration by the GIST the primary tumour has more often smooth and broad pushing than insinuat­ing fascicles. The typical location of the first recurrence of GIST is in the abdomen. Liver is the most common metastatic site, in 65% of cases. The lung and bone metastases usually develop later than liver metastases. Lymph node metastases are very rare for the difference to lymphoma and leiomyosar­ coma.1,12,16 Computed tomography (CT) and mag­netic resonance imaging (MRI) are used for the radiologic diagnostic evaluation of pa­tients with abdominal mass suspected for GIST. Contrast-enhanced CT is currently an imaging method of choice for diagnos­ing of GISTs, staging and surgical planning because of its wide availability. Endoscopic ultrasound can be used for the evaluation of the local extent in patients with small tumours which have been found inciden­tally during endoscopy. MRI is a better imaging method for the evaluation of pa­tients with rectal GISTs. MRI is indicated for the evaluation of liver lesions which can not be characterized definitely on CT scans and in cases of contrast-enhance CT is contraindicated.8,17,18 The factors that in­fluence CT features of GISTs are size of the tumour, aggressiveness of the tumour and time of presentation during the course of the disease.18 The typical CT finding of pri­mary GIST is a large mass with heterogene­ous structure because of usually centrally placed necrosis, haemorrhage, or cystic de­generation. In fact, the tumour can be so large that it is difficult to define its origin. On postcontrast scans the tumour is usu­ally presented as a hypervascular and well-enhancing heterogeneous mass. Ulceration and fistulisation to the lumen of GI tract are often seen in GIST patients. Small GISTs are commonly presented as homogenous masses.18 MRI can be used to follow-up the operated patients and to evaluate response in the patients on an adjuvant therapy with imatinib. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) is recommended in patients on imatinib therapy which need an early detection of tumour response to imatinib because of the possibility for the surgical resection after the cytoreduction with imatinib.17 There is no need to perform PET scan in every GIST patient after the complete surgical resec­tion of the tumour. PET can be performed Radiol Oncol 2008; 42(4): 187-95. Figure 4. Explorative laparatomy – a large tumour in the upper abdomen with origins on the lesser curvature of the stomach (white arrow). on patients with CT or /and MRI images suspected for metastases.8,17,18 The imaging diagnosis of GIST can be suggested when CT depicts a large, mainly extraluminal tumour arising from the stom­ach or small bowel wall with heterogene­ous contrast material enhancement (with higher attenuation coefficients peripherally and lower coefficients in the central part). Metastases are usually presented in the liv­er and on the peritoneum, but a lymph node enlargement is very rarely depicted.18,19,20 A triphasic CT scanning technique with scan­ning of the native scans and post-contrast scans after the intravenous injection of con­trast material in an arterial and a porto-ve­nous phase with delays of 20-30 s and 70­80 s, respectively, is preferred for baseline scans and follow-ups during and after the treatment.17,18 Unlike GISTs, lymphomas usually cause lymph node enlargement and circumferen­tial bowel wall thickening which homog­enously enhances on post-contrast scans. Carcinoid tumours commonly arise in the terminal ileum often stimulating a desmo-plastic reaction with calcifications. A local infiltration and a visceral obstruction are common radiologic features of the carcino­ma, very often in large tumours. Metastases of the bowel wall are usually multifocal masses in patients with a history of prima­ry known malignancy.18,20,21 It is still difficult to make a differentia­tion between GIST and other soft-tissue tu­mours like leiomyosarcoma, intraabdominal fibromatosis of the bowel wall, malignant tumours of nerve sheath and the tumours of vascular origin with radiological and pathological methods.21 Pathohystology accomplished with im­munohystochemistry still remain the gold standard for diagnosing of GIST. The transabdominal biopsy is not recommen­ded because of the possibility of seeding the tumour cells.16 GISTs are commonly positive for KIT (CD117), a tyrosine kinase growth factor re­ceptor. KIT positivity is usually strong and pancytoplasmic, but some epithelioid forms of GISTs of the stomach may be weakly CD117 positive or even negative.1 We must be aware and analyse the KIT positivity together with other clinical signs, imaging method findings and immunohistochemi-cal test results because there are few other tumours which are generally CD117 posi­tive like small cell carcinoma of the lung, mastocytoma, seminoma and extramedul­lary myeloid tumour. Tumours like meta­static melanoma, clear cell sarcoma, Ewing sarcoma family of tumours, childhood neu­roblastoma and angiosarcoma also some­times express CD 117.22 Among other GIST markers CD34, the hematopoetic progenitor cell antigen plays an important role because it can be found in 80 to 85% of gastric GISTs and 50% of small intestinal GISTs. CD34 is usually expressed on endothelial cells, subsets of fibroblasts and neoplasms related to these cell types.9 Small intestinal GISTs more often than gastric GISTs express muscle cell markers like SMA. Smooth muscle fibers can be interspersed with SMA and desmin positive GIST intratumoral spindle cells during the infiltration of tumour; in this situation we can have a false muscle marker positivity. The SMA positivity is a favourable prognostic factor for the gastric and small intestinal forms of GIST. The de­tection of S100 protein is relatively rare in GISTs, it seems to be an adverse prognostic factor in gastric GISTs.1,9 Nestin is a type VI intermediate filament protein typical of many stem cells which can be found in most of the cases of GISTs but also in GI schwanomas.23 The surgical resection is the standard ini­tial treatment for GISTs. Until the beginning of an application of imatinib (the specific tyrosine kinase inhibitor) in GIST therapy, surgery was the only way of the treatment because the conventional chemotherapy and the radiation therapy proved ineffi­cient. Generally speaking about 85% of pa­tients with primary localized form of GIST, they can be treated with a complete gross resection, but approximately 50% of those patients develop the tumour recurrence.12 The patient presented in this article was treated with a complete resection of the tu­mour. The application of imatinib mesylate for the GIST treatment was a successful in­troduction of molecularly targeted therapy for the treatment of solid tumours. The im­atinib therapy is used for the treatment of unresectable cases, recurrent or metastatic cases. Surgery or ablative modalities can be used when the disease becomes amenable to gross resection due to changes initiated by imatinib, or when the tumour develops resistance to imatinibe treatment.8,12 The evaluation of the GIST treatment with im­atinib mesylate is usually performed with CT, sometimes with 18FDG-PET. The prob­lem in the evaluation of the GIST treatment with imatinib mesylate is that they corre­late poorly with currently internationally agreed classifications for the evaluation of response to the treatment of solid tumours like the World Health Organization crite­ria or the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. It is sug­gested that changes in tumour density on CT scans are better modes of assessment of the response to the imatinib treatment than an internationally agreed guidelines. The minority of patients with GIST, less than 15%, have a primary resistance to imatinib mesylate. Half of the patients will develop resistance 2 years after the initiation of the Radiol Oncol 2008; 42(4): 187-95. imatinib treatment, usually because of the secondary KIT mutation.12 Generally, the median time of recurrence of GISTs after the surgery is 19 to 25 months with the 5­year survival rate about 50%.11 GIST may be statistically rare mesenchy­mal tumour of the gastrointestinal tract, but whenever the large heterogeneous, abdomi­nal mass with higher attenuation on pe­riphery and lower in the central parts is de­picted on the contrast-enhanced CT scans, GIST must be firstly put on the differential diagnosis list. That is important because the transabdominal biopsy of the tumour is not recommended because of the possibility of seeding the tumour cells.16 References 1. Miettinen M, Lasota J. Gastrontestinal stromal tumors: review on morphology, molecular pathol­ogy and differential diagnosis. Arch Pathol Lab Med 2006; 130: 1466-78. 2. Levy AD, Remotti HE, Thompson WM, Sobin LH, Miettinen M. Fronm the Archives of the AFIP Gastrointestinal stromal tumors: radiologic features with pathologic correlation. Radiographics 2003; 23: 283-304. 3. Kachanov DY, Dobrenkov KV, Shamanskaya TV, Abdullaev RT, Inushkina EV, Savkova RF, et al. Solid tumors in young children in moscow Region of Russian Federation. Radiol Oncol 2008; 42: 39-44. 4. Miettinen M, Lasota J. Gastrointestinal stromal tumors – definition, clinical, histological, immuno-histochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001; 438: 1-12. 5. Suster S. Gastrointestinal stromal tumors. Semin Diagn Pathol 1996; 13: 297-313. 6. Levy AD, Remotti HE, Thompson WM, Sobin LH, Miettien M. Gastrointestinal stromal tumors: radiologic features with pathologic correlation. Radiographics 2003; 23: 283-304. 7. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998; 152: 1259-69. 8. Blay J-Y, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol 2005; 16: 566-78. 9. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach:a clinicopatholog­ic, immunohistochemical, and molecular genetic studies of 1765 cases with long-term follow-up. Am J Surg Pathol 2005; 29: 52-68. 10. Dematteo RP, Lewis JJ, Leung D, Mudan SS, Woodruf JM, Brennan MF. Two hundred gastroin­testinal tumors: recurrence patterns and prognos­tic factors for survival. Ann Surg 200; 231: 51-8. 11. Emory TS, Sobin LH, Lukes L, Lee DH, O’Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomical site. Am J Surg Pathol 1999; 23: 82-87. 12. Gold JS, DeMatteo RP. Combined surgical and mo­lecular therapy: the gastrointestinal stromal tumor model. Ann Surg 2006; 244: 176-84. 13. Ludwig DJ, Traverso LW. Gut stromal tumors and their clinical behavior. Am J Surg 1997; 173: 390-4. 14. Sharp RM, Ansel HJ, Keel SB. Best cases from the AFIP: gastrointestinal stromal tumor. Armed Forces Institute of Pathology. Radiographics 2001; 21: 1557-60. 15. Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: current diagno­sis, biologic behavior, and management. Ann Surg Oncol 2001; 8:50-9. 16. Burkill GJ, Badran M, Al-Muderis O, Meirion Thomas J, Judson IR, Fisher C, et al. Malignant gastrointestinal stromal tumor: distribution, ima­ging features, and pattern of metastatic spread. Radiology 2003; 226: 527-32. 17. Phongkitkarun S, Phaisanphrukkun C, Jatchavala J, Sirachainan E. Assesment of gastrointestinal stromal tumors with computed tomography fol­lowing treatment with imatinib mesylate, World J Gastroenterol 2008; 14: 892-8. 18. Hong X, Choi H, Loyer EM, Benjamin RS, Trent JC, Charnsangavej C. Gastrointestinal stromal tumors: role of CT in diagnosis and response evaluation and surveillance after treatment with imatinib. Radiographics 2006; 26: 481-95. 19. Hama Y, Okizuka H, Odajima K, Hayakawa M, Kusano S. Gastrointestinal stromal tumor of the rectum. Eur Radiol 2001; 11: 216-9. 20. Ghanem N, Altehoefer C, Furtwängler A, Winterer J, Schäfer O, Springer O, et al. Computed tomogra­phy in gastrointestinal stromal tumors. Eur Radiol 2003; 13: 1669-78. 21. Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Gastrointestinal stromal tumors and leiomyosa­rcomas in the colon: a clinicopathologic, immuno-histochemical, and molecular genetic study of 44 cases. Am J Surg Pathol 2000; 24: 1339-52. 22. Miettinen M, Lasota J. KIT(CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morph 2005; 13: 205-20. 23. Sarlomo-Rikala M, Tsujimura T, Lendahl U, Miettinen M. Patterns of nestin and other inter­mediate filament expression distinguish between gastrointestinal stromal tumors, leiomioma and scwannomas. APMIS 2002; 110: 499-507. Radiol Oncol 2008; 42(4): 187-95. review Time dependence of electric field effects on cell membranes. A review for a critical selection of pulse duration for therapeutical applications Justin Teissié 1,2, Jean Michel Escoffre1,2, Marie Pierre Rols1,2, Muriel Golzio1,2 1 CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077 Toulouse, France; 2 Université de Toulouse; UPS; IPBS; F-31077 Toulouse, France Background. Electropulsation is one of the non-viral methods successfully used to transfer drugs and genes into living cells in vitro as in vivo. This approach shows promise in field of gene and cellular therapies. This presentation first describes the temporal factors controlling electropermeabilization to small molecules (< 4kDa) and then the processes supporting DNA transfer in vitro. The description of in vitro events brings our attention on the processes occurring before (s), during (ms) and after electropulsation (ms to hours) of DNA and cells. They all appear to be multistep events with well defined kinetics. They cannot be described as just punching holes in a lipid matrix in a two states process. Conclusions. The faster events (may be starting on the ns time scale) appear to be under the control of the external field while the slower ones are linked to the cell metabolism. Investigating the associated collective molecular reorganization by fast kinetics methods and molecular dynamics simulation will help in their safe developments for the in vivo processes and their present and potential clinical applications. Key words: electropulsation; electropermeabilization; electrotransfection; electroporation Introduction The application of electric field pulses to cells leads to the transient permeabilization of the membrane (electropermeabilization).1 This phenomenon brings new properties to the cell membrane: it becomes permeabi­lized, fusogenic and exogenous membrane Received 27 August 2008 Accepted 13 October 2008 Correspondence to: Dr. Justin Teissié, IPBS Université de Toulouse UMR 5089 CNRS, 205 route de Narbonne, 31077 Toulouse, France. Phonel: +33(0)5 61 17 58 12; Fax: +33(0)5 61 17 59 94; Email: justin.teissie@ipbs.fr proteins can be inserted. It has been used to introduce a large variety of molecules into many different cells in vitro.2,3 Clinical applications of the electropermeabilization are now under development as a results of the EU Cliniporator and Esope programs. A local antitumoral drug delivery to patients (a method called electrochemotherapy) is under clinical trial.4-8 Transdermal drug delivery is obtained in vivo.9.More recently, electropermeabilization has been also used to transfer DNA in vivo, into the skin, liver, melanoma and skeletal muscle cells.10-15 It has the main advantages of being easy to use, fast, reproducible and safe. While during 30 years due to technologi­cal limits, pulse duration was always larger than 1 microsecond, the recent availability of high voltage (tens of kV) nanosecond long pulse generators opens the way to a new approach. Very fast perturbations under strong fields are induced in the membrane organization.16,17 A new field of develop­ment is now present for electropermeabi­lization and promising results for clinical applications were reported. One of the limiting problems remains that very few is known on the physicochem­ical mechanisms supporting the reorganisa­tion of the cell membrane. The molecular target of the field effect remains unclear. The present review focuses on the criti­cal role played by the pulse duration in the electropermeabilization to small molecules (< 4kDa) and on its support to the processes associated to DNA transfer in vitro. Pulse du­rations are easy to adjust for an optimization of the clinical target: electrochemotherapy, irreversible electropermeabilization or gene therapy as suggested as a final conclusion. Electropermeabilization Theory of membrane potential difference modulation. An external electric field modulates the membrane potential difference.18 From the physical point of view, a cell can be de­scribed as a spherical capacitor which is charged by the external electrical field. The transmembrane potential difference in­duced by the electric field, ..i is a complex function g(.) of the specific conductivities of the membrane (.m), the pulsing buffer (.out) and the cytoplasm (.cyt), the mem­brane thickness and the cell size. Thus,1 ..i = f. g (.). r. E.cos. [1] in which . designates the angle between the direction of the normal to the membrane at the considered point on the cell surface and the field direction, E the field intensity, r the radius of the cell and f, which is a shape factor (a cell being a spheroid). Therefore, ..i is not uniform on the cell surface. It is maximum at the positions of the cell facing the electrodes. These physical predictions were checked experimentally by videomi­croscopy by using the potential difference sensitive fluorescent probes.19-21 The pulse duration plays a critical role when shorter than the capacitive loading time of the membrane. In the previous part of the paper, it was considered that the pulse was long enough to bring the poten­tial steady state value. The loading time tload brings a limit in this description.1 ..i = f. g (.). r. E.cos. ..(1 -exp (- t / tload ) .[2] Assumming that the membrane is a true dielectric with no electric leak, the loading time. tload, is given by tload = rCm (1/2.out + 1/.cyt) [3] Cm is the membrane capacitance, .out and .cyt, respectively, the conductance of the external buffer and of the cytoplasm. tload is longer for larger cells in a hetero­geneous population. Longer pulses are needed to reach the asymptotic electrically induced transmembrane voltage value (Eq. 1). A key assumption in this physical de­scription is that the electric pulse is a sharp square wave.22 This description is under the assumption that the cell is a sphere. A more complex description is needed for spheroi­dal cells and their orientation relative to the field has to be taken into account.23,24 The membrane leakiness affects the load­ing time of the membrane when the field is applied.1 Its physical definition is given in 26 by: Radiol Oncol 2008; 42(4): 196-206. t.= r Cm (.cyt+ 2.out) / (2 .cyt.out + r.m (.cyt+ 2 .out)/d) [4] As .m is dependent on the membrane leakiness, the loading time of the mem­brane will decrease with an increase in the membrane leakiness. The pulse duration plays a more critical role in such a case. But under physiological conditions, where .out is larger than 10 mS/cm, as .cyt is about 4 mS/cm, tload is always of the order of 1 µs for mammalian cells Critical parameters affecting electropermeabilization Effects of the electric field parameters. When the resulting transmembrane potential dif­ference ..(i.e. the sum between the rest­ing value of cell membrane ..o and the electroinduced value ..i) reaches thresh­old values close to 250 mV, membranes become permeable.25-26 Permeabilization is controlled by the field strength. Field intensity larger than a critical value (Ep) must be applied to the cell suspension. From Eq. [1], permeabiliza­tion is first obtained for . close to 0 or p. Ep is such that: ..perm = f g (.) r Ep [5] Parts of the cell surface facing the elec­trodes are affected. The extent of the per-meabilized surface of a spherical cell, Aperm, is given by: Aperm = Atot (1 - Ep /E)/2 [6] where Atot is the cell surface and E is the applied field intensity. Increasing the field strength (decreasing Ep/E) will increase the part of the cell surface, which is brought to the electropermeabilized state. This critical value of the transmembrane potential will be reached after a longer delay for the edges of the cap due to the loading time. But this delay remains always in the µs time scale. This will affect the mechanism of elec­tropermeabilization only for a very short pulse duration. These theoretical predictions were as­sayed on cell suspension by measuring the leakage of metabolites (ATP)27 or observed at the single cell level by digitised fluores­cence microscopy.28,29 The experimental re­sults are in agreement with the predictions. The field strength must be larger than the threshold value Ep to induce permeabili­zation. The permeabilized part of the cell surface is a linear function of the recipro­cal of the field intensity. Permeabilization, due to structural alterations of the mem­brane, remained restricted to a cap on the cell surface when short lived pulses (micro­seconds) are applied. The area affected by the electric field depends also on the shape (spheroid) and on the orientation of the cell with the electric field lines.24 If a train of 10 pulses is applied at a frequency of 1 Hz, it is observed that long pulses (more than 1 ms) slightly larger than Ep bring a permeabiliza­tion on two caps on the cell surface, each facing one electrode. Experimental results obtained either by monitoring conductance changes on cell suspension34 or by fluorescence observa­tion at the single cell level microscopy28,29 shows that the local level of permeabiliza­tion is strongly controlled by the pulse du­ration.27,28 As an electrical current is flowing, Joule heating is taking place. The temperature of the sample increases as a linear function of the pulse duration and of the square of the field intensity. In vitro, this deleterious by-effect is controlled by using a low ionic content pulsing buffer to deliver a limited amount of energy. This of course cannot be controlled by that means in vivo but the tis­sue can be considered as a heat sink. Sieving of electropermeabilization Electropermeabilization allows a post-pulse free-like diffusion of small molecules (up to 4 kDa) whatever their chemical nature. There is a size limit for permeabilization and the process for macromolecules is de­scribed in the second part of the text. Polar small compounds cross easily the elec­tropermeabilized membrane. But the most important feature is that this membrane organisation is long-lived in cells. Diffusion is observed during the seconds and min­utes following the ms pulse. Most of the exchange takes place after the pulse.28,29 Resealing of the membrane defects and of the induced permeabilization is a first order process, which appears to be control­led by protein reorganisation. For a given cell, the resealing time (reciprocal of k) is a function of the pulse duration but not of the field intensity as checked by digi­tised videomicroscopy.27 A precise analysis showes that several resealing processes are acting, two are very fast (ms, 50 yrs), SHBG 7 nmol/L (15 -100), cortisol = 13 nmol/L (138 - 690), al­dosteron = 879 pmol/L (20 - 410). A replace­ment hormone therapy was introduced to the patient. Postoperative control MRI after two months showed residual tumour 20x13x12 mm in diameter but now along with mul­tiple brain metastases. The palliative brain photon beam radiotherapy was performed, total dose 30 Gy in 10 fractions. CT scan of thorax and abdomen revealed the progres­sion of the lung metastases and the occur- Figure 2b. Disturbances in visual function presented by Goldmann test, left eye. rence of new bone metastases. Surprisingly, the patient was without respiratory distur­bances but he reported fatigue. His general appearance was Cushingoidal. He died ten months after the operation of the pituitary gland. Discussion Up to our knowledge only 24 cases of symptomatic pituitary metastasis of renal cell carcinoma has been reported in the literature (Table 1). Only six of them were female, while 18 were men. The majority i.e. 19 patients presented with hypopitui­tarism, while 17 patients presented with visual field defect like our patient. Our patient has not experienced symptoms of diabetes insipidus which is reported to be more frequent in pituitary metastasis than in pituitary adenomas.7,21 It is very difficult to differentiate pituitary metastasis from adenoma based on radiological and clinical findings.2,3,10,12,22 But Liu et al.7 found out that the strong enhancement of the tumour and the strong bone destruction without marked sellar enlargement are characteris­tic radiological features of pituitary metas­tasis. Fassett et al.2 stated that thickening of the pituitary stalk, invasion of the cavern­ous sinus and sclerosis of the surrounding sella turcica could indicate pituitary metas­tasis. Tumour invasiveness usually makes the resection difficult. There was no signifi­cant survival benefit in surgical series.2 The treatment of pituitary metastasis is multi-modal, consisting of surgery, radiotherapy and chemotherapy. The long-term benefit of postoperative radiotherapy is not known Radiol Oncol 2008; 42(4): 225-31. due to the rarity of such cases. The applied dose ranged in the literature from 9 to 60 Gy, with median dose 36 Gy.6 Our patient was treated with 30 Gy in ten fractions due to the occurrence of brain metastases although first it was intended to apply a higher dose. Stereotactic radiotherapy can be beneficial in sparing the optic nerves. The primary aim of treating pituitary me­tastasis is to improve the quality of life through symptomatic relief and to prevent the neurological deterioration. The overall median length of the patient’s survival after the diagnosis of pituitary me­tastasis is only 180 days.6 However, the paper recently published by Gopan et al.20 reported the overall survival ranging from 6 to 46 months from the initial diagnosis of pituitary metastasis. This can be explained by the application of new chemothera­peutic agents like sorafenib and sunitinib. Stereotactic radiotherapy with or without whole brain radiotherapy was performed in all five reported patients. In our case, whole brain radiotherapy was performed due to the brain dissemina­tion. Sorafenib and sunitinib were not reg­istered for the treatment of metastatic renal cell carcinoma in our country at the time. Symptomatic pituitary metastasis of re­nal cell carcinoma is a rare case, occurring usually in highly disseminated renal cell carcinoma. Palliative surgery and radiother­apy treatment can contribute essentially to the improvement of the quality of life of such patients. References 1 Yokoyama T, Yoshino A, Katayama Y, Watanabe T, Kashima Y, Yoshikawa T, et al. Metastatic pituitary tumour from renal cell carcinoma treated by frac­tionated stereotactic radiotherapy (Case report). Neurol Med Chir (Tokyo) 2004; 44: 47-52. 2 Fassett DR, Couldwell WT. Metastases to the pitui­tary gland. Neurosurg Focus 2004; 16: E8. 3 James RL Jr, Arsenis G, Stoler M, Nelson C, Baran D. Hypophyseal metastatic renal cell carcinoma and pituitary adenoma. Case report and review of the literature. Am J Med 1984; 76: 337-40. 4 Koshiyama H, Ohgaki K, Hida S, Takasu K, Yumitori K, Shimatsu A, Koh T. Metastatic renal cell carcinoma to the pituitary gland presenting with hypopituitarism. J Endocrinol Invest 1992; 15: 677-81. 5 McCormick PC, Post KD, Kandji AD, Hays AP. Metastatic carcinoma to the pituitary gland. Br J Neurosurg 1989; 3: 71-9. 6 Morita A, Meyer FB, Laws ER Jr. Symptomatic pituitary metastases. J Neurosurg 1998; 89: 69-73. 7 Liu H, Ymaki T, Oka S-I, Koyanagi I, Houkin K. Metastatic renal cell carcinoma mimicking pitui­tary adenoma: case report. Neurol Med Chir (Tokyo) 2005; 45: 418-22. 8 Anniko M, Lundquist PG, Silfversward C, Wersall J. Hypernephroma metastasis in the pituitary gland. A case report. Arch Otorhinolaryngol 1981; 232: 227-32. 9 Buonaguidi R, Ferdeghini M, Faggionato F, Tusini G. Intrasellar metastasis mimicking a pituitary adenoma. Surg Neurol 1983; 20: 373-8. 10 Eick JJ, Bell KA, Stephan MT, Fuselier HA Jr. Metastatic renal cell carcinoma presenting as an intrasellar mass on computerizes tomography. J Urol 1985; 134: 128-30. 11 Horikoshi T, Mitsuka S, Kimura R, Fukamachi A, Nukui H. Renal cell carcinoma metastatic to the hypophysis, case report. Neurol Med Chir (Tokyo) 1988; 28: 78-82. 12 Nishio S, Tsukamoto H, Fukui M, Matsubara T: Hypophyseal metastatic hypernephroma mimick­ing a pituitary adenoma. Case report. Neurosurg Rev 1992; 15: 319-22. 13 Weiss RE, Corvalan AH, Dillon RW. Metastatic renal cell carcinoma presenting as impotence. J Urol 1993; 149: 821-2; discussion 823. 14 Uchino A, Hasuo K, Mizushima A, Matsumoto S, Mihara F, Jimi M et al. Intracranial metastasis of renal cell carcinoma: MR imaging. Radiat Med 1996; 14: 71-6. 15 Beckett DJ, Gama R, Wright J, Ferns GA. Renal carcinoma presenting with adrenocortical insuf­ficiency due to a pituitary metastasis. Ann Clin Biochem 1998; 35(Pt 4): 542-4. 16 Marar IE, Kandil H, Kanal E, Marion D, Inman M, Amico JA. Renal cell carcinoma metastatic to the pituitary gland: clinical manifestations and suc­cessful treatment with transsphenoidal resection. Endocr Pract 1998; 4: 204-7. 17 Weber J, Gassel AM, Hoch A, Spring A. Concomitant renal cell carcinoma with pituitary adenoma. Acta Neurochir (Wein) 2003; 145: 227-31. 18 Basaria S, Westra WH, Brem H, Salvatori R. Metastatic renal cell carcinoma to the pituitary presenting with hyperprolactinemia. J Endocrinol Invest 2004; 27: 471-4. 19 Pallud J, Nataf F, Roujeau T, Roux FX. Intraventricular haemorrhage from a renal cell carcinoma pituitary metastasis. Acta Neurochir (Wein) 2005; 147: 1003-4. 20 Gopan T, Toms SA, Prayson RA, Suh JH, Hamrahian AH, Weil RJ. Symptomatic pituitary metastases from renal cell carcinoma. Pituitary 2007; 10: 251-9. 21 Mäurer J, Busch M, Matthaei D, Helwig A, Dühmke E. Diabetes insipidus and breast carci­noma – the importance of NMR tomography plan­ning. Strahelenther Onkol 1993; 169: 126-8. 22 Sioutos P, Yen V, Arbit E. Pituitary gland metas­tases. Ann Surg Oncol 1996; 3: 94-9. Radiol Oncol 2008; 42(4): 225-31. research article A phantom to assess the accuracy of tumor delineation using MRSI Amr A. Heikal, Keith Wachowicz, Steven D. Thomas, Biagio Gino Fallone Department of Medical Physics, Cross Cancer Institute; Departments of Oncology and Physics, University of Alberta, Edmonton, Alberta, Canada Background. Studies have demonstrated that magnetic resonance spectroscopic imaging (MRSI) can detect regions of abnormal activity (tumor) that would not have been covered using conventional imaging and contouring methods. With increased interest in MRSI it is important that its accuracy in tumor delineation be investigated. While some effort has been made to design phantoms to examine the performance of MRSI sequences, most phantoms rely on using traditional glass or acrylic as the phantom building material. Material and methods. In this work, a gel-based detail phantom has been developed to assess the ability of the spectroscopic imaging sequences to accurately represent the geometry of tumors. The gel-based phantom is used as an alternative to conventional acrylic or glass based phantoms for use with MRSI. Results. Gel-based phantoms have the advantage of having a magnetic susceptibility close to that of water. In addition, we demonstrate the benefits of having no finite wall thickness separating phantom compart­ments. The utility of the phantom was illustrated in comparisons between different MRSI sequences of the same nominal resolution as well as different filtering parameters. Conclusions. Due to their ease of construction and the reduced artifacts, gel phantoms are a reliable tool for assessing the performance of MRSI sequences. Key words: MR spectroscopic imaging; tumor; phantoms; brain; 3 T Introduction The advantages that spectroscopic imaging can offer cancer therapy are significant. By measuring different metabolite levels - effectively a means of non-invasive biopsy Received 23 September 2008 Accepted 1 October 2008 Correspondence to: Amr A. Heikal, Department of Medical Physics, Cross Cancer Institute; Departments of Oncology and Physics, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada; Phone: +1 780 989 4342; Fax: +1-780 432 8615; E-mail: aheikal@phys.ualberta.ca - magnetic resonance spectroscopic imag­ing (MRSI) can detect tissue abnormalities that may not yet be visible in conven­tional MRI. Pirzkall et al. and Pallud et al. have shown that tumor extent as shown by MRSI may differ greatly from the ex­tent shown on conventional MRI scans.1;2 Moreover, Walecki et al. have shown that MRSI may help in identifying patients who have a high risk of recurrence.3 This has led to an increase in interest in incorporating MRSI into treatment planning by adding a biological target volume in the contouring process. More recently, several methods of tumor identification and registration tech­niques have been used to integrate MRSI results into the radiotherapy process.4;5 Such studies have demonstrated that MRSI can detect regions of abnormal activity (tumor) that would not have been covered using conventional imaging and contour­ing methods.5 As such, the delineation of the tumor volume in treatment plans for radiotherapy has changed when MRSI me­tabolite information was considered. In the midst of the move to improve the spatial resolution of MRSI, it is important to remember that the ability to properly visualize detailed tumor boundaries is in­fluenced by many imaging and processing parameters, not just the nominal resolution of the scan. Also, with the increased impor­tance of spatial definition of the tumor site for radiotherapy, it is of great importance to have a method of evaluating the accuracy of the boundaries derived from an MRSI sequence under development for use in ra­diotherapy planning. While some effort has been made to de­sign phantoms to examine the performance of MRSI sequences; most phantoms have relied on using traditional glass or acrylic as the phantom building material.6,7 Detail phantoms utilizing acrylic or glass contain­ers are vulnerable to susceptibility artifacts arising from the interface of the compart­ment wall material and the solution used to fill the phantom.8 Those artifacts are more pronounced in high-detail and irregularly shaped phantoms. Moreover, detail phantoms rely on a sharply defined boundary between two regions of the phantom. The amount of detail an imaging sequence can reproduce is measured by how accurately it can re­produce that boundary. Having a finite wall containing no metabolites causes a pronounced partial volume artifact in the spectral data. Those artifacts enhance that boundary in a way that is not representa­tive of a human brain. This is demonstrated in the results and discussion section. In this work, a gel-based detail phantom has been developed to assess the ability of the spectroscopic imaging sequences to ac­curately represent the detailed geometry of tumors. The gel-based phantom is used as an alternative to conventional acrylic or glass based phantoms for use with MRSI be­cause it avoids susceptibility and compart­ment wall-related partial volume artifacts. The use of the phantom is demonstrated by comparing the performance of three MRSI sequences. Material and methods Gelatin detail phantom design A phantom designed to simulate tumors was constructed using 5% by weight porcine gel containing clinically relevant concentra­tions of choline chloride (3 mM) and creat­ine hydrate (10 mM).9 A cast acrylic wedge (base: 3.8 cm, height: 9 cm, width: 3.8 cm) was inserted in the liquid gel and later removed when the gel hardened. The void left by the wedge was filled with a solution containing elevated levels of choline chlo­ride (10 mM), and the same concentration of creatine as in the background (Figure 1). The higher concentration of choline inside Radiol Oncol 2008; 42(4): 232-9. Figure 2. The spectroscopic imaging pixel locations overlaid on the T2 weighted image of the phantom. The spectra on the right correspond to the highlighted pixels. The peaks shown are Choline (left) and Creatine (right). The change in the Choline concentration inside the wedge-shaped compartment is clearly noticeable on the spectra. the wedge-shaped void was used to simu­late the presence of a malignancy. Comparison of MRSI sequences The phantom is designed to assess the abil­ity of the spectroscopic imaging sequences to accurately represent the detailed geom­etry of tumors. The utility of this phantom was demonstrated by comparing the output of different MRSI sequences with the same nominal resolution. The phantom was scanned with 3 MRSI sequences: 2-D Point Resolved Spectroscopy (PRESS), 2-echo Spin Echo Spectroscopic Imagine (SESI), and 4-echo SESI, all of nominal voxel size 5×5×10 mm3. A 10 mm thick single-slice T2-weighted image of the phantom was acquired at a position coinciding with the spectroscopic scans (Figure 2). This allowed a proper comparison of the spectroscopic results to the phantom geometry. Cho/Cr ratio maps were calculated for each of the spectroscopic scans. Comparison of k-space filters The phantom can also be used to optimize filter parameters. Such use is demonstrated by comparing the Cho/Cr maps resulting from the same 2-D PRESS sequence using different k-space filters. Since 2-D cosine k-space filters are routinely used on our system to reduce ringing, it was the type of filter chosen for this demonstration. The phantom was scanned with 2-D PRESS of nominal voxel size 5×5×10 mm3. The data was reconstructed twice; once using no k-space filter and once using a 2-D cosine k-space filter shown in Figure 3. Similar to the previous comparison, a 10 mm thick single-slice T2-weighted image of the phan­tom was acquired at a position coinciding with the spectroscopic scans to allow for a proper comparison of the spectroscopic results to the phantom geometry. Spectroscopic imaging scan parameters All scans were performed on a Philips Intera 3 T MRI (Philips Medical Systems, Bothell, WA) unit together with a transmit/ receive birdcage head coil. In this work two types of sequences were used: 2-D PRESS and SESI. The PRESS sequence is a stand­ard sequence used for many in-vivo MRSI studies, especially those interested in high signal-to-noise.10,11 SESI offers the choice of acquiring more than one echo per repetition, hence de­creasing the overall scan time.11 The SESI sequence consists of 2 RF pulses applied on the same plane. The first 90° pulse excites the slice of interest and then a 180° refo­cusing pulse generates an echo at TE1. More echoes can be generated by applying subse­quent 180° refocusing pulses on the same plane each with a different phase encoding (Figure 4). This is analogous to a fast spin echo sequence in imaging. In the multi-echo SESI sequences the centre of k-space is filled with the first echoes while the edges are filled with data from the later echoes. This produces a T2 weighting artifact in the form of decreased contrast at high spatial resolution compared to 2-D PRESS or single-echo SESI. For all sequences the TR was set to 1500 ms, and the TE to 144 ms. The number of phase encodes and FOV was set to 24×24 and 120 mm, respectively, yielding a nomi­nal voxel size of 5×5×10 mm3 for all se­quences. For the SESI sequences the inter-echo spacing was set to 288 ms. Prior to running the MRSI scans, second order shimming was established over the volume-of-interest (VOI).12 Water suppres­sion was achieved by a mix of chemical shift selective (CHESS) suppression and in­version recovery.13; 14 First, a CHESS excita­tion pulse for water is applied followed by crusher gradients. This yielded a dephased negative water signal that tends to return to equilibrium through T1 relaxation. The measurement is then acquired at the zero crossing of the water signal in a fashion similar to inversion recovery. Processing The raw data acquired from the MRSI scans were processed on the scanner console using MR Systems Intera (release 1.5.4.3) (Philips Medical Systems, Bothell, WA). First, a cosine filter was applied to the raw k-space data to reduce ringing. The data was then reconstructed to xy-space and adopized by a Lorentzian – Gaussian filter to reduce noise. Zero-order phase, inhomo­geneities, and eddy currents were corrected using unsuppressed water measurements collected during the scans. Finally, the frequency domain data was exported to Matlab (The MathWorks, Inc., Natick, MA) where it was further analyzed using in-house developed software that calculates the area under different metabolite peaks. Peak fitting The in-house developed peak fitting algo­rithm fitted a sum of Lorentzians to the complex spectra based on seeding values for the chemical shift, estimated peak heights, and full width half maxima (FWHM).15 A Levenberg-Marquardt algorithm was used to minimize the sum of squares of the dif­ference between the raw spectrum and the Radiol Oncol 2008; 42(4): 232-9. Figure 5. Percentage difference images between simulated 5×5 mm2 pixel images and the phantom geometry using: (a) no compartment wall, (b) 1 mm wall, (c) 2 mm wall. Lorentzians to achieve the best fit.16 The Lorentzian parameters (peak heights, chemical shift, and FWHM) re­sulting from the peak fitting algorithm were used in the software to analytically calculate the area under the peaks from each spectrum. Since phase was corrected in the processing stage, the real spectrum is assumed to be equal to the absorption spectrum. Hence the area under the peak is calculated as (p/2×FWHM×peak height). Finally, the software produced metabolite area maps, as well as a choline-to-creatine ratio map. In-plane interpolation of the metabolite maps has been routinely used in the liter­ature to correlate MRSI with CT and MRI images for treatment planning.17 The inter­polation smoothes the appearance of the metabolite maps and allows for better com­parison with CT and MRI images. In this work, the metabolite maps were linearly interpolated to 0.5 mm pixels in-plane. Results and discussion Effects of the phantom wall material The rationale behind the choice of the phantom material was to minimize mag­netic susceptibility artifacts and partial volume artifacts caused by the presence of compartment walls of finite thickness. While it has been suggested in the litera­ture that the use of water equivalent glass can solve problems of magnetic suscepti­bility, the problem of wall-related partial volume artifacts would still persist.8 The use of porcine gel as the phantom’s building material can remedy both these is­sues. The magnetic susceptibility of the por­cine gel is very close to that of water mak­ing susceptibility differences negligible. Furthermore, the lack of a physical compart­ment wall in this design eliminates the issue of its related partial volume artifacts. In a simple demonstration conducted in Matlab (The MathWorks, Inc., Natick, MA), the two-dimensional geometry of the phan­tom was modeled using pixel dimensions of 0.5 mm. Derived from a 2-D PRESS scan of a choline filled phantom, the wedge shaped compartment was assigned arbitrary pixel values of 4000 while the pixels outside the wedge were assigned a value of 1500. A compartment wall was included in the geometric simulation whose thickness was varied between 0 mm and 2 mm and was assigned a pixel value of 0. The pixel values of the 0.5 mm model were then averaged to 5 mm pixels, a resolution achievable by MRSI. Figures 5(a), 5(b), and 5(c) show that with a thickness as small as 1 mm, com­partment walls can produce visible artifacts Figure 6. Comparison of the Cho/Cr ratio map and the phantom geometry. The scale represents the Cho/Cr value. The dashed line represents the phantom geometry and the solid line represents the contour at Cho/Cr = 2.5. The sequences left to right are 2-D PRESS sequence, 2-echo SESI sequence and 4-echo SESI sequence. that degrade the accuracy and performance of the phantom. Comparison of MRSI sequences Three MRSI sequences of the same nominal resolution were used to illustrate the utility of the gel detail phantom. Figure 6 shows the Cho/Cr ratio maps of a 2-D PRESS, a 2-echo SESI, and a 4-echo SESI sequence compared to phantom geometry. The tip of the wedge forming the high-detail region of the phantom is intended to show differences in high-detail accuracy be­tween the three sequences. From Figure 6, it is apparent that the 2-D PRESS and the 2­echo SESI ratio maps reveal a higher choline-to-creatine ratio extending further into the high detail region of the phantom than in the case of 4-echo SESI. Overall, 2-D PRESS and 2-echo SESI show better conformance to the phantom geometry than 4-echo SESI. One can quantitatively compare the dif­ferent sequences by analyzing the deviation between of area of the wedge as shown by the T2 weighted image and the metabolite map. For this purpose the user can choose the suitable tumor contouring criterion for the metabolite maps whether it is a specific metabolite ratio (e.g. Cho/Cr, or Cho/NAA) or z-score (e.g choline-to-NAA index).5;18;19 In this demonstration an arbitrary Cho/Cr = 2.5 was chosen as the tumor contouring criterion. The metabolite maps of the three sequences were automatically contoured at that value and the percentage difference of the areas was found to be 13.7%, 24.4%, and 38.3% for 2-D PRESS, 2-echo SESI, and 4­echo SESI, respectively. Due to the lack of T2 weighting, 2-D PRESS exhibits the smallest deviation from the phantom geometry. The larger deviations shown by multi-echo SESI can be attributed to T2 losses accumulated in acquiring more than one echo per excita­tion. Such losses are progressively more ev­ident with the increasing number of echoes per excitation. Comparison of k-space filters The ability of MRSI to accurately detect tu­mor boundaries is sensitive to factors such as k-space sampling and filtering. Like the T2 weighting artifacts discussed earlier, the k-space filter parameters can greatly dete­riorate tumor boundary accuracy in MRSI. The phantom was used to reveal differences in tumor delineation resulting from chang­ing k-space filtering. Figure 7 shows the Cho/Cr ratio maps of a 2-D PRESS scan of the phantom reconstructed using unfiltered and 2-D cosine filtered k-space respectively. While the filtered dataset produces fewer noise fluctuations in the ratio map, there Radiol Oncol 2008; 42(4): 232-9. is a much more prominent transition zone visible along the wedge margin. The differ­ence in tumor delineation between the two reconstructions is clear in the lower high-detail region of the wedge shape. The phantom can be used to evaluate how the detected tumor volume is influenced by different combinations of k-space sampling and filtering during the development phase of a new MRSI sequence. Furthermore, it is useful as a quality assurance tool to en­sure the preservation or improvement of the quality of tumor delineation when develop­ing an MRSI sequence or signal processing methods. Conclusions Studies have shown that MRSI has the po­tential of detecting areas of tumors growth that were otherwise undetectable using con­ventional imaging. However the ability of MRSI to accurately represent tumor ge­ometry is not always clearly defined by its nominal voxel size, which is influenced by many imaging and processing parameters. It is therefore important to understand and quantify such ability if MRSI is to be used with radiotherapy planning. In this work a detail phantom has been introduced to as­sist in the process of improving the ability of the spectroscopic imaging sequences to ac­curately represent the geometry of tumors. Figure 7. Comparison of the effects of k-space filtering on tumor delineation. The scale represents the Cho/Cr value. The dashed line represents the phantom geometry and the solid line represents the contour at Cho/Cr = 2.5. The phantom was developed for assess­ing the performance of MRSI sequences. Traditionally, MRSI phantoms are suscepti­ble to magnetic susceptibility artifacts and wall-related partial volume artifacts arising from their building material. The use of a porcine gel phantom minimizes the suscep­tibility artifacts, and the lack of a physical compartmental wall eliminates the associ­ated partial volume artifacts. The phantom was shown to be successful in demonstrating the differences in tumor boundary definition shown by three MRSI sequences of the same nominal resolution. It was also used to show the differences resulting from applying different k-space filters to the same sequence. There are a number of imaging and filtering parameters that can influence high-resolution contrast of an MRSI sequence. For example, harsh k-space filtering parameters tend to minimize the signal at the edges of k-space. Similarly, increasing the number of echoes acquired per excitation will produce a T2 weighted k-space, resulting in decreased contrast at high spatial-resolution in the metabolite maps. While a sequence may be designed to achieve a desired nominal resolution, the above mentioned factors can influence the spatial accuracy of tumor boundary deline­ation to an extent which may not be intui­tive to the user. The phantom introduced in this work can be used as a development tool to investigate the effects of those im-aging and filtering parameters on the accu­racy of tumor delineation before applying the developed sequences clinically. Finally, the reduced artifacts associated with using porcine gel coupled with its relative ease of construction make this kind of phantom a viable option for evaluating the perform­ance of MRSI sequences in both clinical and scientific settings. Acknowledgements Discussion with Dr. Burkhard Maedler from Philips Medical Systems, are appreciated. We acknowledge the financial support of the Canadian Institutes of Health Research, Translational Research Training in Cancer, Canada Foundation for Innovation, and the Alberta Science and Research Investments Program. References 1. Pallud J, Devaux B, Nataf F, Roux FX, Daumas-Duport C. Spatial delimitation of low grade oli­godendrogliomas. Neurochirurgie 2005; 51: 253-9. 2. Pirzkall A, Li X, Oh J, Chang S, Berger MS, Larson DA, et al. 3D MRSI for resected high-grade gliomas before RT: tumor extent according to metabolic activity in relation to MRI. Int J Radiat Oncol Biol Phys 2004; 59: 126-37. 3. Walecki J, Tarasow E, Kubas B, Czemicki Z, Lewko J, Podgorski J, et al. Hydrogen-1 MR spectroscopy of the peritumoral zone in patients with cerebral glioma: assessment of the value of the method. Acad Radiol 2003; 10: 145-53. 4. Chang J, Thakur S, Perera G, Kowalski A, Huang W, Karimi S, et al. Image-fusion of MR spectro­scopic images for treatment planning of gliomas. Med Phys 2006; 33: 32-40. 5. McKnight TR, Noworolski SM, Vigneron DB, Nelson SJ. An automated technique for the quan­titative assessment of 3D-MRSI data from patients with glioma. J Magn Reson Imaging 2001; 13: 167-77. 6. Hunjan S, Adalsteinsson E, Kim DH, Harsh GR, Boyer AL, Spielman D, et al. Quality assurance of magnetic resonance spectroscopic imaging-de­rived metabolic data. Int J Radiat Oncol Biol Phys 2003; 57: 1159-73. 7. Woo DC, Kim BS, Jung SL, Park HJ, Rhim HS, Jahng GH, et al. Develpment of a cone-shaped phantom for multi-voxel MR scpectroscopy. J Neurosci Methods 2007; 162: 101-7. 8. Rice JR, Milbrandt RH, Madsen EL, Frank GR, Boote EJ, Blenchinger JC. Anthromorphic 1H MRS head phantom. Med Phys 1998; 25: 1145-56. 9. Barker PB, Hearshen DO, Boska MD. Single-voxel proton MRS of the human brain at 1.5T and 3.0T. Magn Reson Med 2001; 45: 765-9. 10. Drost DJ, Riddle WR, Clarke GD. Proton magnetic resonance spectroscopy in the brain: Report of AAPM Task Group #9. Med Phys 2002; 29: 2177-97. 11. Nishimura DG. Principles of magnetic resonance imaging: Stanford: Stanford University; 1996. 12. Haacke EM. Magnetic resonance imaging, physics principles and sequence design. New York: John Wiley & Sons; 1999. 13. Doddrell DM, Galloway G, Brooks W, Filed J, Bulsing J, Irving M, et al. Water signal elimination in vivo, using suppression by mistimed echo and repetitive gradient episodes. J Magn Reson 1986; 70: 176-80. 14. Hasse A, Frahm J, Hanicke W, Mattaei W. 1H NMR chemical shift selective (CHESS) imaging. Phys Med Biol 1985; 30: 341-4. 15. Mierisova S, Ala-Korpela M. MR spectroscopy quantitation: a review of frequency domain meth­ods. NMR Biomed 2001; 14: 247-59. 16. Moré JJ. The Levenberg-Marquardt algorithm: im­plementation and theory. In: GA Watson, edi­tor. Lecture notes in mathematics. Heidelberg: Springer Verlag; 1977. p. 105-16. 17. Nelson SJ, Graves E, Pirzkall A, Li X, Chan AA, Vigneron DB, et al. In vivo molecular imaging for planning radiation therapy of gliomas: an applica­tion of 1H MRSI. J Magn Reson Imaging 2002; 16: 464-76. 18. Narayana A, Chang J, Thakur S, Huang W, Karimi S, Hou B, et al. Use of MR spectroscopy and functional imaging in the treatment planning of gliomas. Br J Radiol 2007; 80: 347- 54. 19. Jeun SS, Kim MC, Kim BS, Lee JM, Chung ST, Oh CH, et al. Assessment of malignancy in gliomas by 3T 1H MR spectroscopy. J Clin Imaging 2005; 29: 10-5. Radiol Oncol 2008; 42(4): 232-9. Radiol Oncol 2008; 42(4): 173-80. Kakšen je najpogostejši mamografski videz T1a in T1b invazivnih rakov dojk? Podkrajšek M, Žgajnar J, Hocevar M zhodišce. Podatki o mamografskem videzu pod 1 cm velikih invazivnih rakov dojk (RD) so skopi. Avtorji uporabljajo razlicna merila. Namen naše raziskave je bil ugotoviti najpogostej­ši mamografski videz majhnih invazivnih RD (T1a in T1b). Bolniki in metode. V raziskavo je bilo vkljucenih 100 žensk s 102 invazivnim RD, manjše velikosti (1-10 mm), ki smo jih našli pri mamografiji na Onkološkem inštitutu v 16 mesecih. Mamografski videz smo opisali kot: tumor, tumor s mikrokalcinacijami, samo mikrokalci­nacije in drugo (asimetricna zgostitev, arhitekturni nemir). Rezultati. Najpogosteje smo našli tumor brez kalcinacij (60/102; 59%). Pri 12/102 (11%) je bil viden tumor s kalcinacijami. Samo mikrokalcinacije so bile ugotovljene pri 12/102 (11%) ter asimetricna zgostitev in arhitekturni nemir pri 18 invazivnih RD (18%). Najvec invazivnih RD (44/60) je imelo videz zvezdastega tumorja. Odstotek tipa razvejanih mikrokalcinacij je bil višji pri ženskah pod 50. letom starosti. Zakljucek. Najpogostejše mamografski videz majhnih invazivnih RD je ne glede na starost bolnic zvezdast tumor. Kalcinacije z/brez tumorja so pogostejše pri ženskah pod 50. letom starosti. Radiol Oncol 2008; 42(4): I-VIII. Radiol Oncol 2008; 42(4): 181-6. Obliterativna hepatokavopatija – ultrazvocna in kavografska diagnostika – prikaz primera Kutlu R zhodišca. Obliterativna hepatokavopatija je relativno nov pojem, ki definira primarno trombozo spodnje votle vene in membranozno obstrukcijo spodnje votle vene pri Budd-Chiari sindromu. Prikaz primera. Prikazan je primer kavografskih in ultrazvocnih sprememb pri popolni zapori spodnje votle vene pri 36 letni bolnici, ki je bila pregledovana zaradi diagnostike posledic B hepatitisa. Zakljucki. Ta bolezen je bila dosedaj prvenstveno zdravljena s kiriurškimi posegi, npr. z portalno-mezentericnim sistemskim odvodom (shuntom) ali s presaditvijo jeter. V zadnjem casu pa se v takih primerih enako uspešni tudi interventni radiološki posegi, kot sta trans-jugularni intrahepaticni portosistemski odvod in perkutana angioplastika jetrnih ven s postavitvijo žilnih opornic. Radiol Oncol 2008; 42(4): 187-95. Gastrointestinalni stromalni tumor želodca Žokalj , Culinovic-Caic R, Magaš Z, Pavcec Z, Saghir H, grec J, Marotti M zhodišca. Gastrointestinalni stromalni tumorji (GIST-i) so najbolj pogosti mezenhimalni tumorji prebavnega trakta. Ne moremo jih preprosto deliti na benigne in maligne, ker je veliko vmesnih oblik. Na potek bolezni znatno vpliva njihova velikost in mitotska aktivnost, prav tako mesto, kjer se pojavijo. Najdemo jih kjerkoli vzdolž prebavnega trakta, v mezente­riju ali omentumu. GIST-i so najveckrat benigni tumorji, v 70-80% pa se pojavijo v želodcni steni. V clanku predstavljamo primer 70-letne bolnice z želodcno obliko GIST-a. Prikaz primera. Pri bolnici smo naredili ultrazvocno preiskavo trebuha zaradi tipljive zatr­dline v epigastriju. Videli smo vecinoma hiperehogeno okroglo maso z majhnimi hipoeho­genimi areali v centralnem delu. Preiskava z racunalniško tomografijo pa je pokazala veliko ekspanzivno maso, heterogene strukture v želodcni steni. Tumor je kazal vecji atenuacijski koeficient na periferiji in nižji v centralnem delu. Med operativnim zdravljenjem smo od­stranili velik ekzofiticen tumor želodcne stene. Diagnozo GIST želodca smo postavili po patohistološkem in imunohistokemicnem pregledu tumorja. Zakljucki. GIST-i so statisticno redki tumorji (0,1%-0,3% vseh gastrointestinalnih tumor-jev), a ko najdemo bolnika z okroglo, vecinoma ekzofiticno tumorsko maso na steni ga­strointestinalnega trakta ali peritoneja, moramo pomisliti tudi na GIST. Z ultrazvokom in racunalniško tomografijo lahko postavimo klinicno predoperativno diagnozo in opredelimo razširjenost bolezni. Radiol Oncol 2008; 42(4): I-VIII. Radiol Oncol 2008; 42(4): 196-206. Casovna odvisnost ucinkov elektricnih polj na celicno membrano. Kriticni pregled pomena trajanja elektricnih pulzov in njihova terapevtska uporabnost Teissié J, Escoffre JM, Rols MP, Golzio M zhodišca. Elektroporacija je ena od nevirusnih metod vnosa molekul v celice tkiva in tumorje. Uspešno se uporablja za dostavljanje kemoterapevtikov in tudi genov. Metoda je uporabna pri zdravljenju tumorjev kot tudi pri genski terapiji. Prispevek obravnava casovno komponento elektroporacije pri vnosu malih molekul (< 4 kDa) in procese, ki vplivajo na vnos DNA v celice in vivo. Opisani so procesi, ki se dogajajo pred elektroporacijo, med njo (ms) in po njej (ms in h), pri prenosu DNA v celico. Ta proces je sestavljen iz vec dogodkov, ki imajo dobro definirano kinetiko. Ne moremo ga opisati kot dogodek, ki tvori luknje v celicni membrani, ne kot samo dvostopenjski proces. Zakljucki. Hitri dogodki so v casu ns, in so pod vplivom zunanjega elektricnega polja, medtem ko so pocasnejši dogodki povezani z metabolizmom membrane. Zato je nadaljne raziskovanje dogodkov na membrani pod vplivom elektricnih polj pomembno za varno uporabo elektroporacije v kliniki. Radiol Oncol 2008; 42(4): 207-14. Prospektivna raziskava kakovosti življenja bolnikov po kombiniranem zdravljenju raka danke Velenik V, Oblak , Anderluh F zhodišca. Iz porocil v literaturi ni razvidno, da bi trajna stoma poslabšala kakovost življenja bolnikov z lokalno napredovalim rakom danke (T3-4 in/ali N+). Naš namen je bil primerjati kakovost življenja bolnikov z abdominoperinealno amputacijo danke in bolnikov z ohra­njeno kontinuiteto crevesa, zdravljenjih s predoperativno radiokemoterapijo v prospektivni raziskavi faze II. Bolniki in metode. 57 bolnikov je bilo obsevanih 5-krat tedensko in z dnevnim odmerkom 1,8 Gy do skupne doze 45 Gy. Socasno z obsevanjem so prejemali peroralno kemoterapijo s kapecitabinom v odmerku 825 mg/m2/12 ur. Operacijo smo nacrtovali 4-6 tednov po zaklju-ceni predoperativni radiokemoterapiji. Po operaciji so bolniki prejeli 4 kroge kemoterapije. Pri ocenjevanju kakovosti življenja so bolniki, ki so bili po = 2 letih sledenja brez znakov ponovitve bolezni, izpolnili vprašalnika, ki ju je razvila European Organisation for Research and Treatment of Cancer (EORTC): prvi je bil specificen za bolnike z rakom (EORTC QLQ­C30) in drugi za bolnike z rakom debelega crevesa in danke (EORTC QLQ-C38). Rezultati. Vprašalnik je izpolnilo 28 od 37 primernih bolnikov (87,5 %). Srednji cas od ope-racije do izpolnjevanja vprašalnikov je bil 35 mesecev. Pri nobenem vprašanju iz vprašalni­kov EORTC QLQ-C30 in EORTC QLQ-C38 med skupinama ni bilo statisticno pomembnih razlik v srednjem številu zbranih tock. Zakljucki. Razlike v kakovosti življenja med bolniki s trajno stomo in bolniki z ohranjenim analnim sfinktrom nismo zasledili. Radiol Oncol 2008; 42(4): I-VIII. Radiol Oncol 2009; 43(1): 215-24. Obvladovanje neželenih ucinkov na kožo s kremo z vitaminom K1 pri bolnikih zdravljenih s cetuksimabom Ocvirk J, Rebersek M zhodišca. Cetuksimab je cloveško-mišje monoklonalno protitelo proti receptorju za epi­dermalni rastni dejavnik (EGFR). V klinicnih raziskavah se je izkazal za ucinkovitega pri številnih malignih obolenjih. Ob uporabi inhibitorjev EGFR so pogosti neželeni ucinki na koži, med katerimi je najpogostejši akniformni izpušcaj. Pri nekaterih bolnikih opazimo tudi kserozo, ekcem, fisure, teleangiektazije, spremembe nohtov in paranihijo, hiperpi­gmentacija pa je bolj redka. Z dobrim obvladovanjem neželenih ucinkov na kožo pomaga-mo bolnikom in izboljšamo kakovost življenja. V vecini primerov je ucinkovita standardna uporaba topicnih ali sistemskih antibiotikov ter protivnetnih zdravil. Kljucnega pomena pri obvladovanju kožne toksicnosti sta edukacija bolnikov pred pricetkom zdravljenja ter hitro in ucinkovito ukrepanje ob prvih znakih neželenih ucinkov na kožo. Namen pricujoce raziskave je bil ocenjevanje neželenih ucinkov na kožo med zdravljenjem s cetuksimabom in ugotavljanje ucinkovitosti kreme z vitaminom K1. Metode. Od septembra 2006 do avgusta 2007 smo zdravili 30 bolnikov z razsejanim rakom debelega crevesa in danke s cetuksimabom in kemoterapijo, ki so imeli tudi akniformni iz­pušcaj zaradi zdravljenja. Sledili smo jih vsaj tri mesece, enkrat tedensko. Za obvladovanje akniformnega izpušcaja smo uporabljali kremo z vitaminom K1 in ureo (Reconval K1®). Bolniki so jo priceli uporabljati neposredno po ugotovljenem pojavu kožne toksicnosti. Kožne neželene ucinke smo ocenjevali glede na NCI CTCAE, ver. 3. Rezultati. Šest od 30 bolnikov je imelo akniformni izpušcaj tretje stopnje, 18 druge in 6 prve stopnje. Reconval K1® smo uporabljali dvakrat dnevno. Pri vseh bolnikih smo opazili izboljšanje neželenih ucinkov na koži. Srednji cas do izboljšanja je bil 8 dni in 18 dni do znižanja stadija neželenih ucinkov vsaj za eno stopnjo. V nasprotju s podatki o do sedaj zdravljenih bolnikih s cetuksimabom, pri katerih je na­stopila 3. stopnja kožne toksicnosti ter je bilo pri vseh priporoceno in tudi nujno znižanje odmerka cetuksimaba, pa pri nekaterih naših bolnikih to ni bilo potrebno. Pri samo 3 od 6 bolnikov s 3. stopnjo kožne toksicnosti smo morali znižati odmerek cetuksimaba. Pri bolnikih s 1. in 2. stopnjo kožne toksicnosti ni bilo potrebno znižati odmerka ali odložiti zdravljenja. Ob topicni uporabi kreme Reconval K1® nismo opazili nobenih lokalnih ali sistemskih neželenih ucinkov. Zakljucki. Po naših podatkih je to prva objavljena raziskava o ucinkovitosti kreme z vita-minom K1 pri zmanjševanju neželenih ucinkov na kožo ob zdravljenju s cetuksimabom pri bolnikih z razsejanim rakom debelega crevesa in danke. Reconval K1® je ucinkovit v obvladovanju kožne toksicnosti pri bolnikih zdravljenih s cetuksimabom. Potrebne bodo nadaljne raziskave za ugotavljanje vpliva na kvaliteto življenja in odgovore na zdravljenje. Radiol Oncol 2008; 42(4): 225-31. Metastaza ledvicnega raka v hipofizi: prikaz primera Bišof V, Juretic A, Šaric N, Melada A, Perkovic Z, Radoš M, Padovan Štern R zhodišca. Solitarna metastaza ledvicnega raka v hipofizije je zelo redka in le v 7% povzroca simptome bolezni. Prikaz primera. Opisujemo 52-letnega bolnika, ki je imel motnje vida in glavobole 3 leta po zdravljenju metastatskega ledvicnega raka. Preiskava z magnetno resonanco je pokazala tumor v supraselarnem podrocju, ki je pritiskal na opticno hiasmo. Drugih metastatskih sprememb pa nismo videli. Bolniku smo naredili transsfenoidalno redukcijsko operacijo. Patohistološki pregled, ki je obsegal tudi imunohistološko priskavo, je pokazal, da smo odstranili metastazo svetlocelicnega ledvicnega raka. Zakljucki. Naš primer je petindvajseti, ki je opisan v literaturi kot bolnik s simptomatsko metastazo ledvicnega raka v hipofizi. Radiol Oncol 2008; 42(4): I-VIII. Radiol Oncol 2008; 42(4): 232-9. Fantom za ocenjevanje natancnosti obrisovanja tumorjev z magnetno resonancno spektroskopijo (MRS) Heikal AA, Wachowicz K, Thomas SD, Fallone BG zhodišca. Raziskave so pokazale, da lahko z magnetnoresonancne spektroskopije (MRS) zaznamo podrocja nenormalne aktivnosti (kot so v tumorju), ki bi jih z obicajnimi metoda-mi spregledali. Zaradi vse vecjega zanimanja za MRS je pomembno raziskati njeno natan-cnost pri obrisovanju tumorjev. Kljub temu, da je bilo v izdelavo fantomov za preucevanje ucinkovitosti MRS zaporedij vloženega že precej truda, so jih vecino izdelali iz obicajnega ali akrilnega stekla. Material in metode. V clanku predstavljamo fantom iz nehomogene želatine, ki smo ga razvili za ocenjevanje zmogljivosti spektroskopskih slikovnih zaporedij pri dolocanju geo­metrijskih oblik tumorjev. Fantom uporabljamo kot alternativo konvencionalnim fantomom iz obicajnega in akrilnega stekla namenjenim MRS. Rezultati. Fantomi iz želatine imajo prednost, ker je njihova magnetna susceptibilnost blizu magnetni susceptibilnosti vode. Poleg tega v clanku dokažemo prednosti fantoma brez predelnih sten med deli z razlicno homogenostjo. Uporabnost fantoma prikažemo s primerjavami med razlicnimi MRS zaporedji pri isti nazivni locljivosti ter s primerjavami med razlicnimi parametri filtriranja. Zakljucki. Zaradi enostavne izdelave in zmanjšanih artefaktov, so fantomi iz želatine zane­sljivo orodje za ocenjevanje uspešnosti MRS zaporedij. 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. Radiation oncology January 22-24, 2009 The symposium “Advances in Technology: Practical Aspects on IMRT and Proton Therapy” will be offered in Chandler, Arizona, USA. 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Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Molecular oncology April 26-30, 2009 The ESTRO teaching course ‘’Molecular Oncology for the Radiation Oncologist’’ will take be offered in Santorini, Greece. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiation oncology April 27-29, 2009 The international IAEA’s conference “Advances in Radiation Oncology (ICARO)” will be held in Vienna, Austria. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; see http://www/astro.org Thoracic oncology May 1-3, 2009 The European Multidisciplinary Conference in Thoracic Oncology (EMCTO) will take place from in Lugano, Switzerland. Contact EMCTO Conference Secretariat, c/0 ESMO Congress Department, Via Luigi Taddei 4, CH-6962 Viganello-Lugano, Switzerland; or fax +41 (0)91 973 19 18, or see www.emcto.org Rectal cancer May 10-12, 2009 The ESTRO multidisciplinary teaching course on evi­dence and research in rectal cancer will take place in Rome, Italy. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiotherapy May 10-14, 2009 The ESTRO teaching course on radiotherapy wi­th protons and ions will be offered in Villingen, Switzerland. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiotherapy May 17-21, 2009 The ESTRO teaching course on IMRT and other con­formal techniques in practice will be held in Milan, Italy. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Thyroid cancer May 27-31, 2009 The “World Congress on Thyroid Cancer’’ will be held in Toronto, Canada. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; see http://www/astro.org Clinical oncology May 29 – June 2, 2009 The American Society of Clinical Oncology Conference (ASCO 2009) will be offered in Orlando, USA. E mail enews@asco.org; or see http://www/asco.org Clinical trial statistics June 9-12, 2009 The EORTC course “Clinical Trial Statistics for Non Statisticians” will be held in Brussels, Belgium. See http://www.eortc.be/Seminar/Educationpgm/ Stats2009/Default.htm Oncology June 20-26, 2009 The ECCO-AACR-ASCO workshop “Methods in Clinical Cancer Research” will be offered in Flims, Switzerland. Contact the Workshop Coordinator Mrs. Kaat Cumps at kaat.cumps@ecco-org.eu; or see http://www.ecco­org.eu (go to the section Eduction/Flims/Flims11) Radiotherapy June 21-25, 2009 The ESTRO teaching course ‘’Imaging for Target Volume Determination in Radiotherapy’’ will be held in Tours, France. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiation oncology June 25-27, 2009 The “MASCC/ISOO 2009 International Symposium of Supportive Care in Cancer: Multinational Association of Supportive Care of Cancer/International Society of Oral Oncology” will be held in Rome, Italy. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; see http://www/astro.org Paediatric oncology June 28-30, 2009 The ESTRO teaching course on paediatric oncology will be offered in Brussels, Belgium. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Prostate cancer June 28-30, 2009 The ESTRO teaching course on brachytherapy for pro­state cancer will take place in Istanbul, Turkey. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiol Oncol 2008; 42(4): IX-XI. Radiotherapy June 28 — July 2, 2009 The ESTRO teaching course on 2D-3D planning and imaging will be offered in St Petersburg, Russia. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Oncology July 2-5, 2009 The Educational Cancer Convention (ECCLU) will be held in collaboration with European Society for Medical Oncology in Lugano, Switzerland. E-mail www.cmelcher@eso.net; or see www.eso.net Lung cancer July 31 - August 4, 2009 The “13th World Conference on Lung Cancer” will be offered in San Francisco, USA. Contact Conference Secretariat International Conference Services Ltd., Suite 2101 - 1177 West Hastings Street, Vancouver, BC Canada V6E 2K3; or call +1 604 681 2153; or e-mail wclc2009@meet-ics. com; or see http://www.2009worldlungcancer.org/ Radiotherapy August 30 - September 3, 2009 The 19th Biennial ESTRO Conference” will be held in Maastricht, the Netherlands. Phone +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Oncology September 4-8, 2009 The “34th ESMO Congress” will take place in Vienna, Austria. Contact ESMO Head Office, Congress Department, Via La Santa 7, CH-6962 Viganello-Lugano, Switzerland; or +41 (0)91 973 19 19; or fax +41 (0)91 973 19 18; or e­mail congress@esmo.org; or see http://www.esmo.org Medical physics September 7-12, 2009 The “World Congress 2009 - Medical Physics and Biomedical Engineering” will take place in Munich, Germany. See http://www. wc2009.org/world-congress-2009 Brachytherapy September 10-12, 2009 The ESTRO teaching course ‘’3D Image-Based Brachytherapy for Gynaecological Malignancies’’ will be offered in Amsterdam, The Netherlands. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiation oncology September 13-16, 2009 The “8th International Conference on Dose, Time and Fractionation in Radiation Oncology” will be held in Madison, Wisconsin, USA. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; see http://www/astro.org Oncology September 20-24, 2009 The “15th ECCO and 34th ESMO Multidisciplinary Congress” will be offered in Berlin, Germany. See http://www.ecco-org.eu Nuclear medicine October 10-14, 2009 The “EANM’09 Annual Congress of the European Association of Nuclear Medicine” will take place in Barcelona, Spain. Contact EANM Executive Secretariat and call +43 1 212 80 30; or fax +43 1 212 80 309; or e-mail office@ eanm.org; or see http://www. eanm.org Radiation oncology October 11-16, 2009 The ESTRO teaching course Evidence Based Radiation Oncology: Methodological Basis and Clinical Application ‘’ will be offered in Vienna, Austria. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Lung Cancer October 15-17, 2009 The ESTRO multidisciplinary teaching course on lung cancer will be held in Prague, Czech Republic. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Radiobiology October 18-23, 2009 The ESTRO teaching course on basic clinical radiobio-logy will be offered in Toledo, Spain. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Therapeutic radiology and oncology November 1-5, 2009 The “American Society for Therapeutic Radiology and Oncology Annual Meeting ASTRO” will take place in Chicago, USA. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; or see http://www.astro.org Radiotherapy November 15-19, 2009 The ESTRO teaching course on IMRT and other conformal techniques in practice will take place in Gliwice, Poland. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org PET in radiation oncology November 21-22, 2009 The ESTRO / EANM educational seminar on PET in radiation oncology will take place in Vienna, Austria. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org PET in radiation oncology December 13-17, 2009 The ESTRO teaching course on image-guided radi­otherapy in clinical practice will take place in Brussels, Belgium. Contact ESTRO office, Avenue E. Mounierlaan, 83/12, B-1200 Brussels, Belgium; or call +32 2775 93 40; or fax 32 2779 5494; or e-mail events@estro.org; or see http://www/estro-events.org Head and neck cancer February 25-27, 2010 The multidisciplinary symposium on head and neck cancer will be offered in Chandler, Arizona, USA. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; see http://www/astro.org Clinical oncology June 4-8, 2010 The American Society of Clinical Oncology Conference (ASCO 2010) will be offered in Chicago, USA. E mail enews@asco.org; or see http://www/asco.org Oncology October 8-12, 2010 The “35th ESMO Congress” will take place in Milan, Italy. Contact ESMO Head Office, Congress Department, Via La Santa 7, CH-6962 Viganello-Lugano, Switzerland; or call +41 (0)91 973 19 19; or fax +41 (0)91 973 19 18; or e-mail congress@esmo.org; or see http://www. esmo.org Radiol Oncol 2008; 42(4): IX-XIV. Nuclear medicine October 9-13, 2010 The “EANM’10 Annual Congress of the European Association of Nuclear Medicine” will take place in Vienna, Austria. Contact EANM Executive Secretariat and call +43 1 212 80 30; or fax +43 1 212 80 309; or e-mail office@ eanm.org; or see http://www. eanm.org Therapeutic radiology and oncology October 31 - November 4, 2010 The “American Society for Therapeutic Radiology and Oncology Annual Meeting ASTRO” will take place in San Diego, California, USA. Contact ASTRO, 8280 Willow Oaks Corporate Dr., Suite 500, Fairfax, VA 22031; or call +1 703 502-1550; or see http://www.astro.org Clinical oncology June 3-7, 2011 The American Society of Clinical Oncology Conference (ASCO 2010) will be offered in Chicago, USA. E mail enews@asco.org; or see http://www/asco.org Lung cancer July 3-7, 2011 The “14th World Conference on Lung Cancer” will be offered in Amsterdam, The Netherlands. See http://www.iaslc.org Oncology September 23-27, 2011 The “16th ECCO and 36th ESMO Multidisciplinary Congress” will be offered in Stockholm, Sweden. See http://www.ecco-org.eu Nuclear medicine October 15-19, 2011 The “EANM’11 Annual Congress of the European Association of Nuclear Medicine” will take place in Birmingham, United Kingdom. Contact EANM Executive Secretariat and call +43 1 212 80 30; or fax +43 1 212 80 309; or e-mail office@ eanm.org; or see http://www. eanm.org Oncology September 27 – October 1, 2013 The “17th ECCO and 38th ESMO Multidisciplinary Congress” will be offered in Amsterdam, The Netherlands. See http://www.ecco-org.eu Lung cancer 2013 The “15th World Conference on Lung Cancer” will be offered in Sydney, Australia. See http://www.iaslc.org As a service to our readers, notices of meetings or courses will be inserted free of charge. Please send information to the Editorial office, Radiology and Oncology, Zaloška 2, SI-1000 Ljubljana, Slovenia. Authors ndex 2008 Abdullaev R: 1/39-44 Aleinikova O: 1/45-49 Anderluh F: 4/207-214 Besic N: 3/143-150 Bešlic Š: 1/1-12; 3/136-142 Bilalovic N: 3/136-142 Bišof V: 4/225-231 Carmeli S: 2/102-113 Caluk J: 3/136-142 Cemažar M: 2/82-92 Corovic S: 2/93-101 Culinovic-Caic R: 4/187-195 Dilic M: 1/1-12 Dobrenkov K: 1/39-44 Eleršek T: 2/102-113 Escoffre J: 4/196-206 Fallone B: 4/232-239 Franko A: 2/66-68 Gao Q: 1/32-8 Gjikolli B: 1/1-12 Golzio M: 4/196-206 Grach-Pogrebinsky O: 2/102-113 Hadžihasanovic B: 1/1-12 Hadžimehmedagic A: 1/1-12 Heikal A: 4/232-239 Herceglija E: 1/1-12 Hocevar M: 3/143-150; 4/173-180 Holjar-Erlic I: 2/66-68 Ilievska Poposka B: 3/151-158 Inushkina E: 1/39-44 Jaganjac S: 1/1-12 Jancar B: 1/13-14; 3/169-169 Jing X: 1/32-8 Jovanovska Crvenkovska S: 3/151-158 Jurdana M: 1/15-22 Juretic A: 4/225-231 Kachanov D: 1/39-44 Kamenšek U: 2/82-92; 3/115-135 Keller F: 2/59-65 Kovac V: 1/23-31 Kutlu R: 4/181-186 Lah Turnšek T: 2/102-113 Li W: 1/32-8 Lincender L: 1/1-12 Lu W: 2/59-65 Magaš Z: 4/187-195 Marotti M: 4/187-195 Melada A: 4/225-231 Merhemic Z: 1/1-12 Mesojednik S: 2/82-92 Miklavcic D: 2/93-101; 3/159-168 Miletic D: 2/66-68 Nikšic M: 1/1-12 Oblak I: 4/207-214 Ocvirk J: 4/215-224 Padovan Štern R: 4/225-231 Park W: 2/59-65 Pavcec Z: 4/187-195 Pavcnik D: 2/59-65 Pavšelj N: 3/159-168 Peric B: 3/143-150 Perkovic Z: 4/225-231 Petrusevska G: 3/151-158 Pilko G: 3/143-150 Podkrajšek M: 4/173-180 Prnjavorac B: 3/136-142 Radoš M: 4/225-231 Rajer M: 1/23-31 Reberšek M: 4/215-224 Rols MP: 4/196-206 Rosch J: 2/59-65 Rumyantsev A: 1/39-44 Saghir H: 4/187-195 Savva N: 1/45-49 Sedmak B: 2/102-113 Serša G: 3/115-135 Sever N: 2/102-113 Shamanskaya T: 1/39-44 Smickova S: 3/151-158 Sofic A: 3/136-142 Softic D: 3/136-142 Solakovic E: 1/1-12 Staebler A: 2/51-58 Stefanovski T: 3/151-158 Strojan P: 2/69-81 Strojnik A: 3/170-172 Szeimies U: 2/51-58 Šaric N: 4/225-231 Šehovic N: 3/136-142 Teissié J: 4/196-206 Thomas S: 4/232-239 Timmermans H: 2/59-65 Uchida B: 2/59-65 Varfolomeeva S: 1/39-44 Vasilevska V: 2/51-58 Velenik V: 4/207-214 Wachowicz K: 4/232-239 Wang Z: 1/32-8 Yang J: 1/32-8 Zafirova Ivanovska B: 3/151-158 Zagar S: 3/143-150 Zborovskaya A: 1/45-49 Žgajnar J: 4/173-180 Žokalj I: 4/187-195 Županic A: 2/93-101 Radiol Oncol 2008; 42(4): XVI-XIX. Subject ndex 2008 3 T: 4/232-239 aging: 1/15-22 anabaenopeptin: 2/102-113 arteriovenous malformation (AVM): 2/66-68 asymmetric density: 4/173-180 Baker cyst: 2/51-58 balloon dilation: 1/1-12 brain: 4/232-239 breast cancer: 4/173-180 cancer registry: 1/45-49 casting: 4/173-180 cathepsins: 2/69-81 cavography: 4/181-186 cells: 1/32-8 cetuximab: 4/215-224 children: 1/39-44; 1/45-49 chromosome breaks: 1/32-8 cutaneous side-effects: 4/215-224 colorectal cancer: 4/215-224; 3/136-142 colorectal polyps: 3/136-142 compression: 1/23-31 computed tomography: 4/187-195 electrochemotherapy: 2/93-101; 3/159-168 electropermeabilization: 4/196-206; 3/159-168 electroporation: 3/159-168; 4/196-206; 2/82-92; 2/93-101 electropulsation: 4/196-206 electrotransfection: 4/196-206 environmental health: 2/102-113 epidemiology: 1/39-44 epidermoid: 2/66-68 experimental model, ovine: 2/59-65 fibrosarcoma: 2/82-92 finite element method: 2/93-101; 3/159-168 fractionation: 3/170-172 gastrointestinal stromal tumours: 4/187-195 gene electrotransfer: 3/159-168 gene therapy: 3/115-135 head and neck cancer: 2/69-81 heavy ions: 1/32-8 HER-2/neu, lung cancer: 3/151-158 immunohistochemistry: 3/151-158 inferior vena cava: 4/181-186 intentional subintimal recanalisation: 1/1-12 interventional radiology: 2/59-65 intraventricular: 2/66-68 jugular vein: 2/59-65 LQ model: 3/170-172 magnesium sulphate: 3/143-150 mammographic appearance: 4/173-180 medial compartment knee osteoarthritis: 2/51-58 metastasis: 4/225-231 microcalcifications, stellate: 4/173-180 microcystin: 2/102-113 MR spectroscopic imaging: 4/232-239 MRI: 2/51-58 muscle satellite cells: 1/15-22 neuromuscular junction: 1/15-22 numerical modeling: 3/159-168; 2/93-101 obliterative hepatocavopathy: 4/181-186 optimization: 2/93-101 phantoms: 4/232-239 pituitary gland: 4/225-231 plasmid DNA: 2/82-92 polypectomy: 3/136-142 preoperative radiochemotherapy: 4/207-214 prognosis: 2/69-81 quality of life: 4/207-214 radiation effects: 1/15-22 radiotherapy: 1/23-31; 3/115-135; 3/170-172 randomised study: 3/143-150 rectal cancer: 4/207-214 rectum MRI: 3/136-142 renal cell carcinoma: 4/225-231  restenosis: 1/1-12 shRNA: 2/82-92 skin: 3/159-168 solid tumors: 1/39-44 spinal cord: 1/23-31 stefins: 2/69-81 subclavia steal syndrome: 1/1-12 subcutaneous tumor: 2/93-101; 3/159-168 surgery: 1/23-31 survival: 3/151-158 theoretical simulation: 1/32-8 total thyroidectomy: 3/143-150 toxic cyanobacterial blooms: 2/102-113 transcriptional targeting: 3/115-135 transient hypocalcemia: 3/143-150 tubulovillous adenoma: 3/136-142 tumor: 4/232-239 tumour promoters: 2/102-113 ultrasound: 4/181-186 vitamin K1 creme: 4/215-224 Radiol Oncol 2008; 42(4): XVI-XIX. Fundacija "Docent dr. J. Cholewa" je neprofitno, neinstitucionalno in nestrankarsko zdrućenje posameznikov, ustanov in organizacij, ki ćelijo materialno spodbujati in poglabljati raziskovalno dejavnost v onkologiji. Dunajska 106 1000 Ljubljana ĆR: 02033-0017879431 Activity of "Dr. J. Cholewa" Foundation for Cancer Research and Education – a report for the final quarter of 2008 Docent Dr. J. Cholewa Foundation for Cancer Research and Education continues to support the activities and advancement of oncology related sciences and is of opinion that excellent and unorthodox ideas must not be prevented to succeed for the simple lack of funding. It primarily supports cancer research and education ac­tivities in Slovenia, it continues to assess carefully the requests for research grants and scholarships submitted by Slovenian experts in oncology and other associated scientific activities, and helps putting resulting advances in cancer therapy in practice. The “Docent Dr. L. Cholewa Foundation for Cancer Research and Education« continues to support the regular publication of "Radiology and Oncology” interna­tional medical scientific journal, that is edited, published and printed in Ljubljana, Slovenia. This support emphasizes the need for the spread of information advances in experimental and clinical cancer research to professionals and interested indi­viduals in public in Slovenia and elsewhere. “Radiology and Oncology” is an open access journal, available free of charge on its own website, thus allowing its users and readers to access without hindrance. The Foundation considers the support of the publication of the results from cancer research in Slovenia and from Slovenian authors in international scientific journals and other means of communication worldwide as one of its main activities. Its careful assessment of requests and proposals for research grants and scholarships submitted by experts in oncology and other associated scientific activities serves this goal in accordance with the spread of advanced knowledge of therapy and education in cancer. Borut Štabuc, MD, PhD Andrej Plesnicar, MD, MSc Tomaž Benulic, MD Vse za rentgen dobite pri nas! • rentgenski filmi in kemikalije • rentgenska kontrastna sredstva • rentgenska zašcitna sredstva • aparati za rentgen, aparati za ultrazvocno diagnostiko in vsa ostala oprema za rentgen Sanolabor, d.d., Leskoškova 4, 1000 Ljubljana tel: 01 585 42 11, fax: 01 524 90 30 www. sanolabor.si Radiology and Oncology Editorial policy Editorial policy of the journal Radiology and Oncology is to publish original scientific pa­pers, professional papers, review articles, case reports and varia (editorials, reviews, short communications, professional infor­mation, book reviews, letters, etc.) perti­nent to diagnostic and interventional radi­ology, computerized tomography, magnetic resonance, ultrasound, nuclear medicine, radiotherapy, clinical and experimental on­cology, radiobiology, radiophysics and radi­ation protection. The Editorial Board requi­res that the paper has not been published or submitted for publication elsewhere: the authors are responsible for all statements in their papers. Accepted articles become the property of the journal and therefore can­not be published elsewhere without written permission from the editorial board. Papers concerning the work on humans, must comply with the principles of the declarati­on of Helsinki (1964). The approval of the ethical committee must then be stated on the manuscript. Papers with questionable justification will be rejected. Manuscript written in English should be submitted to the Editorial Office in triplica­te (the original and two copies), including the illustrations: Radiology and Oncology, Institute of Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia; (Phone: +386 (0)1 5879 369, Tel./Fax: +386 (0)1 5879 434, E-mail: gsersa@onko-i.si). Authors are also asked to submit their manuscripts electronically, either by E-mail or on CD rom. The type of computer and word-processing package should be specified (Word for Windows is preferred). All articles are subjected to editorial re­view and review by independent referee selected by the editorial board. Manuscripts which do not comply with the technical re­quirements stated herein will be returned to the authors for correction before peer-review. Rejected manuscripts are generally returned to authors, however, the journal cannot be held responsible for 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 for 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, BMJ 1991; 302: 6772; JAMA 1997; 277: 927­34.). 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. The technical data should conform to the SI system. The manuscript, including the references may not exceed 20 typewritten pages, and the number of figures and tables is limited to 8. If appropriate, organize the text so that it includes: Introduction, Material and meth­ods, Results and Discussion. Exceptionally, the results and discussion can be combined in a single section. Start each section on a new page, and number each page consecu­tively with Arabic numerals. Title page should include a concise and informative title, followed by the full name(s) of the author(s); the institutional affiliation of each author; the name and ad­dress of the corresponding author (includ­ Radiology and Oncology ing telephone, fax and e-mail), and an ab­breviated title. This should be followed by the abstract page, summarising in less than 200 words the reasons for the study, experi­mental approach, the major findings (with specific data if possible), and the principal conclusions, and providing 3-6 key words for indexing purposes. The text of the re­port should then proceed as follows: Introduction should state the purpose of the article and summarize the rationale for the study or observation, citing only the es­sential references and stating the aim of the study. Material and methods should provide enough information to enable experiments to be repeated. New methods should be described in detail. Reports on human and animal subjects should include a statement that ethical approval of the study was ob­tained. Results should be presented clearly and concisely without repeating the data in the tables and figures. Emphasis should be on clear and precise presentation of results and their significance in relation to the aim of the investigation. Discussion should explain the results rather than simply repeating them and in­terpret their significance and draw conclu­sions. It should review the results of the study in the light of previously published work. llustrations and tables must be num­bered and referred to in the text, with ap­propriate location indicated in the text margin. Illustrations must be labelled on the back with the author’s name, figure number and orientation, and should be accompanied by a descriptive legend on a separate page. Line drawings should be supplied in a form suitable for high-qual­ity reproduction. Photographs should be glossy prints of high quality with as much contrast as the subject allows. They should be cropped as close as possible to the area of interest. In photographs mask the identi­ties of the patients. Tables should be typed double spaced, with descriptive title and, if appropriate, units of numerical measure­ments included in column heading. References· must be numbered in the order in which they appear in the text and their corresponding numbers quoted in the text. Authors are responsible for the accu­racy of their references. References to the Abstracts and Letters to the Editor must be identified as such. Citation of papers in preparation, or submitted for publication, unpublished observations, and personal communications should not be included in the reference list. If essential, such mate­rial may be incorporated in the appropriate place in the text. References follow the style of Index Medicus. All authors should be list­ed when their number does not exceed six; when there are seven or more authors, the first six listed are followed by “et al”. The following are some examples of references from articles, books and book chapters: Dent RAG, Cole P. 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 or sent by E­mail to the corresponding author. 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.