RADIOLOGY AND ONCOLOGY Radiology and O,icology 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 Tomaž Be,iulic Ljubljana, Slovenia Associate editors • Gregor Serša Ljubljana, Slovenia Viljem Kovac Ljubljana, Slovenia Editorial board Tullio Giraldi Branko Palcic Udine, ltaly Vancouver, Canada Marija Auersperg Andrija Hebrang Jurica Papa Ljubljana, Slovenia Zagreb, Croatia Zagreb, Croatia Haris Roko f>urtla Horvat Zagreb, Croatia Zagreb, Croatia Dušan Pavcnik Ljubljana, Slovenia Nataša V. Budihna Ltiszl6 Horvath Ljubljana, Slovenia Pecs, Hungary Stoja11 Ples,iicar Ljubljana, Slovenia Malte Clausen Berta Jereb Kiel, Germany Ljubljana, Slovenia Ervin B. Podgoršak Christoph Clemm Vladimir Jevtic Montreal, Canada Munchen, Germany Ljubljana, Slovenia Jan C. Roos Mario Corsi H. Dieter Kogelnik Amsterdam, The Netherlands Udine, ltaly Salzburg, Austria Horst Sack Christian Dittrich Ivan Lovasit Essen, Germany Vienna, Austria Rijeka, Croatia Slavko Šimunic Ivan Drinkovic Zagreb, Croatia Marijan Lovre,icit Zagreb, Croatia Zagreb, Croatia Gillia,i Duchesne Luka Milas Lojze Šmid Melbourne, Australia Houston, USA Ljubljana, Slovenia Bela Fornet Maja Osmak Andrea Veronesi Budapest, Hungary Zagreb, Croatia Gorizia, ltaly Publishers Slovenian Medica/ Society -Section of Radiology, Section of Radiotherapy Croatian Medica/ Association -Croatian Society of Radiology Affiliated with Sacietas Radialagarum Hungararum Friuli-Venezia Giulia regianal groups af S.LR.M. (Italian Saciety af Medica! Radialogy) Correspondence address Radiology and Oncology Institute af Oncalogy Vrazov trg 4 1000 Ljubljana Slovenia Phane: + 38661 1320 068 Fax: +386611314180 Readers far English Olga Shrestha Vida Kološa Design Monika Fink-Serša Key wards und UDC Eva Klemencic Secretaries Milica Harisch Betka Savski Printed by Tiskarna Tone Tomšic, Ljubljana, Slovenia Published quarterly Bank accaunt number 5010167848454 Fareign currency accaunt number 50100-620-133-27620-5130l6 LB -Ljubljanska banka d.d. Ljubljana Subscriptian fee far institutions 100 USD, individuals 50 USD. Single issue far institutians 30 USD, individuals 20 USD. The publication of the journal is subsidized by the Ministry af Science and Technalogy of the Republic of Slovenia According to the opinion of the Government of the Republic af Slovenia, Puhlic Relation and Media Office, the journal RADIOLOGY AND ONCOLOGY is a publicatian of informative value, and as such subject to taxation by 5 % sales tax. Indexed and abstracted by: BIOMEDICINA SLOVENICA CHEMICAL ABSTRACTS EXCERPTA MEDICAIELECTRONIC PUBLISHING DIVISION Radiology and Oncology is now available on the internet at: http :lwww. onko-i.silradiolag/rno 1. htm CONTENTS DIAGNOSTIC RADIOLOGY Congenital depression of the skull. A case report Giannakopoulou CC, Hassan EA, Hatzidaki EG, Koumantakis EE NUCLEAR MEDICINE Tl-201 SPECT for the detection of viable hybernating myocardium in chronic coronary occlusion Gltrcheva M, Piperkova E, Djorgova J, Petrov I 348 Long term follow-up after radiosynovectomy with yttrium-90 in patients with different rheumatic diseases Kos-Golja M, Budihna N V, Batagelj I 353 Influence of the radiation source on the quality of transmission bone phantom images Sera T, Mester J, Skretting A, Csernay L 358 EXPERIMENTAL ONCOLOGY Vinblastine increases antitumor effectiveness of bleomycin Cemažar M, Auersperg M, Serša G 364 Requirements for a clinical electrochemotherapy device -electroporator Puc M, Reberšek S, Miklavcic D 368 A role of a gender on the dimethylhydrazine induced colorectal tumors in Wistal rats Breskvar L, Cerar A 374 CLINICAL ONCOLOGY Cytology of mediastinal tumors Mermolja M, Kern /, Tercelj M, Jereb M 380 Early pyriform sinus cancer -results of treatment with partial vertical pharyngectomy Eto J, Balatoni Z, Tar T 384 REPORT 2nd international meeting on interventional cardiology Hadjiev J 388 SLOVENIAN ABSTRACTS NOTICES REVIEWERS IN 1997 399 AUTHOR INDEX 1997 400 SUBJECT INDEX 1997 403 Radio/ Oncol 1997; 31: 345-7. Congential depression of the skull. A case report Christina C. Giannakopoulou1 , Elsheikh A. Hassan2 , Eleftheria G. Hatzidaki1 , Eugene E. Koumantakis2 1Neonatal Unit, Department of Pediatrics University of Crete 2Department of Obstetrics and Gynecology University of Crete, Greece Congenital depressions oj the calvaria are rare. They are usually due to exaggerated or prolonged mechanical pressure applied to the head before or during birth. A Jemale newbom, 3200 grams, was delivered after 38 weeks oj gestation by cesarean section due to fetal distress. At birth, physical examination revealed a depression oj 5 cm in diameter and 2 cm in depth on the upper and back part oj the right parietal bone. The neurological examination was normal and the CT scan showed no associated fractures. Due to the absence oj abnormal neurological symptoms conservative management was followed. By the age oj 6 month, the neonate follow up revealed normal development mul tendency to spontaneous resolution. Key words: skull-abnormalities; craniofacial abnormalities; cephalometry; parietal bone-abnormalities Introduction Case report Congenital depressions of the skull are due to me­chanical factors that operate either before or during birth. Exaggerated or prolonged pressure applied to the head of the embryo in utero or during delivery may result in depression of a localized area of the skull. Theoretically, depressions of more than 5 cm may impinge on the cerebral cortex resulting in local­ized compression of the brain with resultant cerebral edema and decreased blood flow. Due to depression, simultaneous fracture of the skull may occur. Thus, a distinction must be made between congenital depres­sions with or without fractured skull.1 Treatment de­pends on intracranial complications. Traditionally, de­pressed skull fractures have been considered as an indication for neurosurgical elevation.2• 3 A case of congenital depression of the skull with fully spontane­ous resolution at the age of six months is reported. Correspondence to: Elsheikh Hassan, m.d., Pindarou la, 145 65 Ekali, Greece. Fax:+ 3081-392292 UDC: 616.715.4-007.2-053. I A female newborn, 3200 grams, was delivered after 38 weeks of gestation by cesarean section due to fetal distress. The mother, aged 24 years, gravida 1 para 1, was healthy and no pregnancy complica­tions were noticed. Immediately after birth the ne­onate needed resuscitation Tracheal intubation and mechanical support ventilation took place and the newborn was transferred to the intensive care unit. Physical examination revealed a depression 5 cm in diameter and 2 cm in depth on the upper and back of the right parietal bone. The overlying skin was normal without edema or hematoma. No other ab­normalities were noted and neurological examina­tion was normal. Skull X ray showed a deformed skull depression without fracture. Laboratory ex­aminations and chest x ray were within normal limits. The respiratory system was mechanically supported for 48 hours. Ultrasound examination showed no intracranial abnormality. Computerized tomography showed no obvious pathological find­ings in brain parenchyma (Figure 1). Giannakopoulou C C et al. Figure l. CT scan showing a congenital parietal depres­sion. The combination of ali findings is conclusive for a chronic pressure on the skull during intrauterine Iife. Due to newborn's good health and absence of abnormal neurological symptoms, a conservative non-surgical management was followed. During hospitalization, the neonate's reflexions were nor­mal with a good muscle tone, and no evidence of, neurological abnormality. At discharge, ten days after birth, the newborn was in good health. Follow up at 2 weeks, 2 and 3 months revealed normal development. The 3-month follow-up mag­netic tomography showed tendency to spontaneous resolution of the depression (Figure 2). Further­more, no picture of underlying brain damage is observed. Discussion Congenital depressions of the neonatal skull are rare and their incidence was found to be about 0,01 %.1 Usually, two types pathogenesis are distin­guished: deformation with or without skull fracture. The demorphity is usually due to mechanical fac­tors that operate either before or during birth. De­pressions present at birth and not associated with edema or hematoma of the underlying soft tissues are usually due to long-standing faulty fetal posi­tion rahter than to recent birth injury. Application of forceps to the fetal head and traction with exces­sive force is another although less common cause of congenital depressions that occur in labor. Se- Figure 2. 3-month follow-up magnetic tomography showing tendency to spontaneous resolution of the depres­sion. vere cranial deformities may also develop earlier during fetal life, long before labor sets in, owing to sustained abnormal fetal positions. Other rare caus­es are materna! pelvis and fibromas of the uterus. Diagnosis is simple as the depressions are visual­ized by direct inspections, but roentgenograms are often made in the search for associated fractures or bone fragments that might have injured the brain. Depressed skull fractures have been considered as an indication for neurosurgical elevation. Some authors have proposed non-surgical treatment by either digital or negative pressure after the exclu­sion of intracranial complications.1• 4• 5 Spontaneous elevation of the depression during the first year without adverse residual effects was reported.6 CT scan should be performed before the initiation of nonsurgical treatment in order to exclude intracra­nial complications. Spontaneous elevation as an ap­proach to congenital skull depression is less trau­matic to the infant. We believe that this treatment should be tried for selected cases where no neuro­logical intervention is needed. Reference l. Ben-Ari Y, Merlob P, Hirsch M, Ralsner H S. Congeni­tal depression of neonatal skull. Eur J Obstet Gynecol Reprod Biol 1986; 22: 249-55. Congenital depression 10% in the infarct area, and fina! (post-proce­dure) Tl-201 content :2:: 50%.9·w The aim of the study was to evaluate the viable hybernating myocardium in chronic occlusions with previous myocardial infarction accordif.lg to the SPECT criteria of Tl-201 myocardial perfusion scin­tigraphy. The influence of both: the duration of occlusion and of the presence of collateral circu!a­tion were also under estimation. The post-proce­dura! changes in the function and perfusion served as a reference method. Tl-201 Spect.fiJr the detection 1!f'viable hybernating myocardium in chmnic coronary occlusion Material and methods Twelve patients intended for PTCA with chronic occlusions and documented myocardial infarction during the last 1 to 14 months were included in the study. The left ventricular function was altered to a different degree (Table!). In 10 patients the revas­cularization (PTCA,CABG) was carried out and the changes in the function and the perfusion were eval­uated 2 months later. They were the base for the evaluation of the accuracy of previous viability de­termination. Table l. Pre-and post-procedura! characteristics of patients. being: 0-normokinetic, 1-hypokinetic, 2-akinetic and 3-dyskinetic. SPECT studies The myocardial perfusion abnormalities were as­sessed before and reassessed 2 months after revas­cularization. SPECT was performed using a rotat­ing large-field-of-view camera equiped with a low-energy all-purpose paral!el hole collimator. Thir-thy-two projections (40 sec/ projection) were Bcforc PTCA (CABG) Atcr PTCA (CABG) No Scx Agc MI-WMA Occlu Dura Coli. IAsgts Viablc LVEF Procedure Res 11.LVEF -sion -lion (mon) circul sgts % .steno.si.s 1 M 48 AntA/D LAD 6 o 7 o 31 2 M 65 Inf,PB H RCA 3 o 7 7 50 PTCA 0%,0% + 10% Rcx 1 3 M 38 ApicH LAD 6 1 1 1 69 PTCA 0% 0% 4 M 60 ALe,ApicH LAD 14 2 9 3 62 CABG CABG +3% 5 M 50 ALH LAD II 1 10 9 35 PTCA 50% +10% ApicD 1 Inf, PB A RCA 6 M 50 ABH RCA 2 o 7 4 31 PTCA 40%, +14% ALeA o 100% ApicD LAD PBA 7 F 47 InfH RCA 12 2 5 5 62 PTCA 100% +2% PBH Rcx 2 0% 8 M 58 AB,ALH LAD 6 o 6 5 50 PTCA+ 50%). In 2 of the patients a CABG was performed in the second stage because of the dis­section in one case and because of the developpe­ment of the LCA-stem stenosis in the other one. Functional improvement was detected in 8 patients. The mean left ventricular ejection fraction (L VEF) increase was 5.6%±4.6%. One patient demonstrnt­ed deteriorntion of left ventricular function (dissec­tion) and one remained without changes. The group with the left ventricular dysfunction (initial L VEF 39.5%±2.63%, n=6) had an increase of 7.6%±4.8%. The group without dysfunction (initial L VEF 64.5%±2.87%, n=4) had an increase of 1.75%±1.08%. Detection of viable hybernating myocardium. The quantitative analysis of the percentage of Tl­201 uptake in the segments with perfusion abnor­malities before and after revascularization. Of 79 segments included in the infarct area, 52 were with severe uptake reduction of Tl-201 uptake(<50%) and 27-with modernte or mild reduction (.50%). Forty-four segments (56%) were evaluated to be viable. Fifty-seven segments were reassessed after revascularization: 38 viable and 19 without viabili­ty according to the SPECT study. An improvement in Tl-201 uptake after PTCA was determined in 33 segments. Five segments remained without im­provement and showed Tl-uptake after procedure <50%. They were accepted to be false positive. Of the nonviable segments 16 showed no improvement Tl-201 Spectfin· the detection 1!f"iviable hybernating myocardium in chronic coro11a1y occlusion after revascularization and 3 increased their Tl­uptake to more than 50%. They were accepted to be false negative. The positive predictive value of the study was 87% (PPV= TP/fP+FP=33/38). The negative pre­dictive value of the study was 84% (NPV= TN/ TN+FN=l6/19). Perfusion, wall motion abnormalities and via­bility. Determination of WMA was done for 55 segments. 36 segments (66%) showed severe WMA (akinetic, dyskinetic) and 19 segments (34%) mild WMA (hypokinetic). According to this analysis, 31/36 (86%) of segments with severe WMA showed severe uptake reduction and 14 of them (39%) were viable. Sixteen out of 19 with mild WMA (84%) showed moderate uptake reduction (>50%) and 18 (95%) of them were viable (Figure 2). Relation between the viability and the duration of occlusion, as well as the collateral circulation. The patients with duration :::;3 months (n=3) had 52% viable segments (12 from 23 segments) . The patients with duration >3 months (n=9a) were with 57% viable segments (32 from 56). For the vascular territories with angiographically detected collateral circulation (n=l0) the percentage of viable seg­ments was higher 69% (34/49) than for the territo­ries without collateral circulation (n=7) 33% (10/30 segments). The extent of perfusion defects and the viability score (the number of viable segments) are shown in Table 1. Changes in the wall motion and perfusion after revascularization. WM improvement appeared in 45% (16/36) from akinetic (dyskinetic) segments and 84% (16/19) of hypokinetic segments. There was a good coincidence of the percentage of the segments with improved WM and the percentage of the previously detected viable segments for both: the severe and the mild WMA (Figure 2). Percentage of viablc and nonviablc scgmcnts (sgts) with difforent WMA bcforc PTCA (CABG) Dyskinctic , akinetic sgts n=36 Hypokinetic sgts n=l 9 ...;;i•blo CNcmvlablo n.1 . ¦Vlablo n•14 Jllll!IIIII¦ J IIIVlablo n-18 5% Changes in Tl-201 uptake after revasculariza­tion (Figure 3). Of ali segments included in the infarcted area (n=79), 27 (x=58.9%±7.3%) were with mild altered uptake and 52 segments showed severe altered uptake (x=33. l %±8.4%). Four hours later, there was an increase in the delayed uptake in both groups as a sign of viability. After revascu­larization, 37% (21/57) of of reassessed segments remained with severe reduced uptake, while 63% (36/57) of segments showed an uptake :2:50%. It seemed very important that while 66% of the seg­ments (52/79) were with severe uptake abnormali­ty, 58% (32/55) of the segments reassessed after procedure demonstrated functional improvement. Discussion There was a substantial number of viable segments in the vascular territory of the coronary arteries with chronic occlusions and previous myocardial infarction. The patients were with different altera­tions of left ventricular function: n=4 were with saved left ventricular ejection fraction and n=8 were with severe or moderate alterations. Segments with viable hybernating myocardium existed in both groups. The initial Thallium uptake was not predic­tive for the viability of myocardium. According to our findings, the group of segments with severe reduced early Thallium-uptake ( <50%) contained segments with uptake improvement on the delayed images and with uptake improvement after proce­dure to > 50% (Figure 3). The WMA were not E3 Sgts wllh Tl-201 uptako<50% 50 W Sgts wlth Tl-201 up tako >=50% 25 Ddort PTCA (CARG) Afler PTCA (CADG) Figure 3. Changes in Tl-201 segmenta! uptake after procedure Percentagc of scgmcnts with WM in the same groups after PTCA (CABG) predictive and improvement in the kinetic after .Wlthouf revascularization occured in both hypokinetic and IJWlthout rovemcmt lmprovcment lmp -l n•3 ¦lmproved n=16 akinetic (dyskinetic) segments (Figure 2). The my­ .r...ovod na16 .Iocardial perfusion criteria for viability seemed most important for the determination of hybemating my­Figure 2. Kinetic changes after PTCA (CABG) ocardium in the segments with severe WMA-aki­ Garcheva M et al. netic segments. The percentage of viable segments in this group was high enough according to our data (39%). The demonstration of viability in the hypo­kinetic segments was not so important because al­most all of them (95%) were viable. The positive and negative predictive value of the study were similar to those in the literature. w.n The influence of the duration of the occlusion was not proved in this study. The presence of col­lateral circulation was a predictor of high percent­age of viable segments, its absence-predicted 2­fold lower percentage of viable segments. A substantional functional improvement was detected in 8/10 patients post revascularization. The improvement was more pronounced in the pa­tients with left ventricular dysfunction. Conclusions Tl-201 perfusion scintigraphy has high positive pre­dictive value for the detection of hybernating myo­cardium in patients with chronic occlusions and previous infarction, and can predict the benefitial effect of revascularization. References l. Garot J, Scherrer-Crosbie M, Monin JL, Du Pouy P, Bourachot ML, Teiger E et al. Effect of delayed percu­taneous transluminal coronary angioplasty of occluded coronary arteries after acute myocardial infarction. Am J Cardiol 1996; 77: 915-21. 2. Anderson TJ, Knundtson ML, Roth DL, Hansen JL, Traboulsi M. Improvement in left ventricular function following PTCA of chronic totally occluded arteries (abstract). Circulation 1991; 84 Suppl II: 519. 3. Tillisch J, Brunken R, Marshall R, Schwaiger M, Man­delkern M, Phelps Metal. Reversibility of cardiac wall motion abnormalities predicted by PET. N Engl J Med 1986; 314: 884-8. 4. Marwick Th, Nemec J, Lafont A, Soldeco E, Macintyre WS. Prediction by postexercise fluoro-18 deoxyglu­cose positron emission tomography of improvement to exercise capacity after revascularization. Am J Cardiol l 992; 69: 854-9. 5. Dilsizian V, Bacharach SL, Perrone-Fillardi P, Arrighi JM, Maurea S, Bonow RO. Concordance and discord­ance between rest-redistribution thallium imaging and thallium-reinjection after stress-redistribution imaging for assessing viable myocardium: comparison with met­abolic activity by PET (abstract). Circulation 1991; 86: 84-9. 6. Rigo P, Benoit Th, Braat SH. The role ofTc-99111 sesta­mibi in the evaluation of myocardial viability. In: Dia­logues in Nucl Cardiol, N l. Dordrecht, Boston, Lon­don: Kluwer Ac. Pbs., 1994: 1-20. 7. Schroeder H, Friedrich M, Topp H. Myocardial viabili­ty what do we need? Eur J Nucl Med 1993; 20; 792­803. 8. Dondi M, Tartagni F, Fallardi F, Fanti S, Marengo M, Tommaso I, et al. A comparison of rest-sestamibi and rest-redistribution Thallium single photon emission to­mography: possible implications for myocardial viabil­ity detection in infarcted patients. Eur J Nucl Med 1993; 20: 26-3 1. 9. Ragosta M, Beller GA, Watson DD, Kaul S, Gimple LW. Quantitative planar rest redistribution TI 201 im­aging in detection of myocardial viability and predic­tion of improvement in left ventricular function after coronary bypass surgery in patients with severely de­pressed left ventricular function. Circulation 1993; 87: 1630-41. 10. Udelson J, Coleman PS, Metherall J, Pandian NG, Gomez A, Griffith JL, et al. Predicting recovery of severe regional ventricular dysfunction. Compaison of resting scintigraphy with Tl-201 and Tc-99m sesta­mibi. Circulation 1994; 89: 2552-61. 1 l. Rosetti C, Landoni C, Luciagnini G , Huang G, Bar­torelli AL, Guazzi MD, et al. Assessment of myocar­dial perfusion and viability with Tc-99m methox­yisobutylisonitrile and Thallium-201 rest-redistribntion in chronic coronary artery disease. Eur J Nucl Med 1995, 22: 1306-12. Radiol Oncol 1997; 31: 353-7. Long term follow-up after radiosynovectomy with yttrium 90 in patients with different rheumatic diseases Mojca Kos-Golja1 , Nataša V. Budihna2, Igor Batagelj3 1 University Medical Centre, Department of Rheumatology, 2/nstitute oj Oncology, 3 University Medica! Centre, Department of Nuclear Medicine, Ljubljana, Slovenia The aim of the retrospective study was to evaluate the efficacy of radiosynovectomy (with yttrium 90) mainly in patients with rheumatoid arthritis, less with some other rheumatic diseases. The evaluation period varied from half to nine years. The procedure was performed in 273 patients (225 females, 48 males) or in 463 joints (402 knees, 61 shoulders and ankles). The ejfect was evaluated by change in degree of morning stiffiiess, pain and swelling (score from O to 9). Very good results were obtained in 69 (15 %), good in 142 (30.5 %), moderate in 197 (42.5 %) and no effect in 55 ( 12 %) joints. Six months after the procedure 38 joints ( 8 % ), half to two years after 221 joints ( 48 %) were in good remission, after 3 to 4 years 95 joints (20 %), after 5 to 6 years 57 joints (12%) were well, 7 to 9 years later 52 joints (11 %) showed no signs oj arthritis. Joint pain and swelling were the most frequent procedure complications (5.6 %). In two patients with additional immunomodulating therapy chronic myeloid and lymphocytic leukaemia were diagnosed. Radiosynovectomy is considered to be an effective and saje treatment for synovitis in different rheumatic diseases. Key words: arthritis rheumatoid, synovial membrane-surgery; ytthrium radoisotopes Introduction Synovitis is a frequent cause of pain, swelling and functional joint impairment in different rheumatic diseases. For more than 100 years the removal of an inflamed synovial membrane (surgical synovec­tomy) has been a cornerstone in management of joint inflammation refractory to standard medica! treatment. However, the difficulty of removing all the diseased synovium often leads to regrowth, surgical reintervention is often contraindicated be­cause of fibrosis and scar tissue from the previous surgery. The interest for the non-invasivc methods of synovectomy was raised and stimulated by eas­ier procedure, Jack of complications and lower Correspondence to: Prim. Mojca Kos-Golja, M.D., Univer­sity Medica! Centre, Department of Rheumatology, Vodnikova 62, 1000 Ljubljana, Slovenia UDC: 616.72-002-77:616.72-018.36-089.87 costs. Many isotopes have been therefore suggest­ed and tested as the potential synovial ablati ve agents.1 The development of open arthroscopic, chemical and radiosynovectomy was the conse­quence of better knowledge of the pathophysiolo­gy of synovitis. Radiosynovectomy became an al­ternative to a surgica\ method. The interest in this procedure markedly increased in 1950, especially as a prevention method against recurrent and pro­gressive damage in rheumatoid arthritis (RA).2 It can in principle also be applied to joints in the variety of other inflammatory joint diseases, most frequently in haemophilic synovitis, osteoarthritis and pigmented villonodular synovitis. The first reported use of radiosynovectomy was in 1952 with gold-198. 3 Most often yttrium-90 with tissue penetration 3.6 mm is applied in large joints, rhe­nium-186 with 1.2 mm tissue penetration in medi­um sized joints, erbium-169 with tissue penetra­tion of 0.3 mm in small joints. Phosphorus-32, Kos-Golja Metial. radium-224 and dysprosium-165 are also used. Ali are high-energy B-emitting radio-pharmaceuti­cals.4.5 The average absorbed radiation 0.001). Mean pain score was 2.84±0.39 before and 1.47±0.7 after therapy (p>0.001). Mean joint swell­ing score was 2.59±0.56 and 1.43±0.7 before and after therapy respectively (p>0.001). The improvement was achieved in 88 % of treat­ed joints. No significant improvement was noticed in 12 % of joints. Excellent effect of the treatment was achieved in 15 % of joints (Table 1). The patients were followed-up in average for 4.03±2.6 years. The mean duration of observed ther­apeutic effect was 2.79±2.3 years. In 8 % of treated joints the effect lasted about 6 months and in 11 % the improvement lasted for 7 to 9 years. In majority of patients the effect was observed from six months to 7 years (Table 2). Table l. Patients according to degree of improvement. The complications of therapy were noted in 23 patients. Joint pain and swelling were the most frequent side effects (17 patients or 5.6 % ). In one transient fever and in two cases radiation necrosis at the injection site developed. In two patients chronic myelogenous and lymphatic leukaemia, respectively, was diagnosed, in one four years and in the other six months after radiosynovectomy. In a single patient hypernephroma and liposarcoma less than one year after radiotherapy were inciden­tall y found. Discussion Since the introduction radioisotope synovectomy remained one of the few possible radical treatments of severe joint pain due to chronic synovial inflam­mation in RA and some other chronic rheumatic diseases. According to the joint size yttrium-90 col­loid for large joints, rhenium-186 sulphide foreme- Follow-up Number Without Moderate Signifficant Excellent (years) of joints effect* effect effect effect 1 122 16 48 36 22 2 7 15 15 6 3 55 7 19 23 6 4 46 9 21 8 8 5 33 o 19 10 4 6 7 27 15 4 7 5 29 15 9 8 25 2 9 9 5 9 28 2 10 II 5 sum 463 55 197 142 69 (%) ____ (_10_()_.) (12 %) (42,5 %) (30,5 %) (15 %) Legend: *This group is considered as "no effect" according to score of improvement of less than 1.1. Table 2. Duration of improvement according to the years of follow-up. Follow-up Number Effect Effect Effect Effect Effect (years) of joints <0.5 o.s -2 3-4 5-6 7-9 year* years years years years 122 21 101 o o o o o o o o o 3 55 5 15 4 46 5 12 29 o o o 10 7 16 o 1 12 11 29 o 7 58 3 19 8 4 24 8 25 2 4 3 6 10 9 28 1 5 2 3 17 463 38 221 95 58 51 (%) (100%) (8%) (48%) (20%) (13%) (11%) sum Legend: *This group is considered as "no effect" according to too short duration of improvement. Kos-Golja Metal. dium sized joints, erbium-169 citrate for small joints are usually applied.5 Allergic reactions, fever and radiation necrosis at the injection canal are consid­ered the early complications.5 Radiation necrosis was reported after synovectomy with yttrium-90 in an ankle. The authors warn against injecting this radioisotope in small and medium sized joints.9 Yttrium-90 was used in our patients without serious side effects in spite of few medium sized joints included. In only two cases self-limited radiation necrosis was noticed in needle canal after yttrium injection in the ankle. Side effects were rare in our group as well as in the reports of others where flare up of synovitis is most often reported.t10• 11• 5 Myel­ogenous and lymphatic leukaemia after 4 years and after six months of radiotherapy occuring in our patients, could be considered as the late complica­tions, although according to the literature they have not been reported anywhere else with the exception of chromosomal aberrations in lymphocytes.5 On the other hand it is known that lymphatic leukaemia occurs with higher frequency in patients with RA.t12 Besides, the immunomodulatory treatment given to those patients in course of their disease could possi­bly play a role in development of leukemia. Hyper­nephroma and liposarcoma occurring in one of our patients less than one year after radiotherapy, can­not be considered as a consequence of radiation exposure after synovectomy. As already mentioned most of the radiation dose emanates from leaking of the radioactivity from the joint cavity. Leakage of radioactivity to the region­al lymph nodes is considered to cause chromosomal aberrations.t13 It is not possible to measure the leak­age when yttrium-90, pure B emitter, is used. There­fore the dose to lymph nodes was calculated for dysprosium-165. Doses of 13 Gy in the immobi­lised and over 80 Gy in mobilised patient were measured. The leakage is higher if the particles are very small.t1 To reduce the leakage our patients were immobilised for 2 to 3 days. Although 40 years of use of radiosynovectomy have already passed the reports on long term effects of this therapy are not numerous. w. 14 Although our study was large and long term it has a drawback of being retrospective. The natura! course of inflam­matory rheumatic disease is quite variable and es­pecially in retrospective studies it is sometimes not possible to teli the influence of different factors on rheumatic disease progress. 15 In spite of this the evaluation of therapeutic effects in patients with RA could be satisfactorily performed because they keep visiting rheumatologist regularly on long term basis when the mentioned criteria of efficacy of radiosynovectomy are evaluated, thus enabling con­scientious follow-up. Most of the authors report favourable results of the radiosynovectomy in 60 to 80%.t1• 16• 17 We were able to see the favourable effects of the radiosyn­ovectomy in significant number of our patients. The results of our study are satisfactory compared with the results of others.t14• 18• 19 Our experience is mostly limited to the patients with RA, since the number of patients with ankylosing spondylitis, os­teoarthritis and haemophilic arthropathies was quite small. The effect of treatment in a single patient, a young boy, with haemophilic arthropathy of the ankle was excellent and in accordance with the report of Van Kasteren et al.t10 In our patients the recommended age limit of 45 yearst20 was respected with the exception of the patient with haemophilic arthropathy. Hemophiliacs who need treatment are of. younger age since chronic arthropathy is the major complication of haemophilia.21 Fortunately the radiation dose for gonads is 1.05 µG/MBq which is not high. 22 In conclusion we can teli that the results of our study are in agreement with the reports in the litera­ture. We consider radiosynovectomy effective, safe and suitable non-invasive therapy for inflammed joints in rheumatoid arthritis and in some other rheumatic diseases that are not responding to con­ventional antirheumatic therapy. The long-term ef­fects are satisfactory, the side effects after synovec­tomy are not numerous and not severe. The method seems promising in haemophilic arthropathy as well. Less favourable results were achieved in oste­oarthritis. References 1. Deutsch E, Brodack JW, Deutsch KF. Radiation syn­ovectomy revisited. Eur J Nucl Med 1993; 11: II 13-27. 2. Newman AP. Synovectomy. In: Kelley WN, ED Har­ris, S Ruddy, CB Sledge, eds. Textbook 1!f'rheumatolo­gy. Philadelphia: WB Saunders, 1993: 649-70. 3. Fellinger K, Schmidt J. Die lokale behandlung der rheu­matischen erkrankungen. Wien Z Inn Med 1952; 32: 351-6. 4. Bahous I, Mueller W. Die lokale behandlung chro­nischer arthritiden mit radionukliden. Schweiz Med Wschr 1976; 106: 1065-73. 5. EANM task group radionuclide therapy. Hoefnagel CA, Clarke SEM, Fischer MF, Levington VJ, Chatal JF, Radiosynovectomy 1050Vcm·1 external 8 1.3 kVcm·1 external 8 1.5 kVcm·1 external 8 1.3 kVcm·1 external 6 1 kVcm·1 needle array 4+4 . 800 Vem·' needle arrat From Table I it is evident that the electrical parameters of ECT have been optimized since the first trials. According to the in vivo and clinical studies performed so far, a clinical electroporator should generate pulses with amplitude up to 3000V, but probably not much higher, since excessive strength of electric field strength diminishes the viability of cells,5 thus killing the cells around elec­trodes, causing necrosis. On the other hand, the electric field has to be strong enough to induce 370 Puc Metal. sufficient transmembrane voltage change A r a clinical electmchemotherapy device -electmporator 4. Mir LM, Devauchelle P, Quintin-Colonna F, Delisle F, Doliger S, Fradelizi S, et al. First clinical tria! of cat soft-tissne sarcomas treatment by electrochemothera­py. Br J Cancer; In press. 5. Neumann E, Sowers AE, Jordan CA. Electroporation and electr<)fitsion in celi biology. New York, Plenum Press: 1989. 6. Kotnik T, Bobanovic F, Miklavcic D. Sensitivity of transmembrane voltage induced by applied electric fields-a theoretical analysis. Bioelectrochem Bioenerg 1997; 43: 285-91. 7. Gilberd RA, Jaroszeski MJ, Heller R. Novel electrode designs for electrochemotherapy. Biochim Biophys Acta 1997; 1334: 9-14. 8. Okino M, Mohri H. Effects of high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res 1987; 78: 1319-21. 9. Mir LM, Orlowski S, Belehradek, Jr J, Paoletti C. Elec­trochemotherapy potentiation of antitumor effect ofble­omycin by Iocal electric pulses. Eur J Cancer 1991; 27: 68-72. 10. Serša G, Cemažar M, Miklavcic D. Antitumor effec­tiveness of electrochemotherapy with cis-Diammine­dichloroplatinum(II) in mice. Cancer Res 1995; 55: 3450-5. 11. Okino M, Esato K. The effects of a single high voltage electrical stimulation with an anticancer drug on in vivo growing malignant tumors. Jpn J Surg 1990; 20: 197-204. 12. Kanesada H. Anticancer effect of high voltage pulses combined with concentration dependent anticancer drugs on Lewis Lung Carcinoma in vivo. J Jpn Soc Cancer Ther 1990; 25: 2640-8. 13. Belehradek Jr J, Orlowski S, Poddevin B, Paoletti C, Mir LM. Electrochemotherapy of spontaneous Mam­mary tumours in mice. Eur J Cancer 1991; 27: 73-6. 14. Salford LG, Persson BRR, Brun A, Ceberg CP, Kongs­tad PC., Mir LM. A new brain tumor therapy combin­ing bleomycin with in vivo electropermeabilization. Biochem Biophys Res Commun 1993; 194: 938-43. 15. Belehradek Jr J, Orlowski S, Ramirez LH, Pron G., Poddevin B, Mir LM. Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin. Biochim Biophys Acta 1994; 1190: 155-63. 16. Heller R, Jaroszeski M, Leo-Messina J, Perrot R, Van Voorhis N, Reintgen D, Gilbert R. Treatment of Bl6 mouse melanoma with the combination of electroper­meabilization and chemotherapy. Bioelectrochem Bioenerg 1995; 36: 83-7. 17. Heller R, Jaroszeski M, Perrot R, Leo-Messina J, Gil­bert R. Effective treatment of B 16 melanoma by direct delivery of bleomycin electrochemotherapy. Melano­ma Res 1997; 7: 10-8. 18. Jaroszeski M, Gilbert R, Heller R. In vivo antitumor effects of electrochemotherapy in a hepatoma model. Biochim Biophys Acta 1997; 1334: 15-8. 19. Rudolf Z, Štabuc B, Cemažar M, Miklavcic D, Vo­dovnik L, Serša G. Electrochemotherapy with bleomy­cin. The first clinical experience in malignant melano­ma patients. Radio! Oncol 1995; 29: 229-35. Radio/ Oncol 1991; 31: 374-9. A role of gender in the occurrence of dimethylhydrazine induced colorectal tumors in Wistar rats Lj ubo Breskvar and Anton Cerar Medica[ Experimental Center, Institute oj Pathology, Medica[ School, University oj Ljubljana, Slovenia Human colorectal carcinoma appears more jrequently in males. The aim oj our study was to evaluate the influence oj gender on the induction oj colorectal carcinoma by 1,2-dimethylhydrazine (DMH) in Wistar rats. Sixty Wistar rats (30 males, 30 females) were subjected to weekly subcutaneous injections oj DMH (20 mg/kg) jor 15 weeks. Ajter 25 weeks jrom the beginning oj the experimem the animals were sacrificed and autopsied. All macroscopical lesions were evaluated histologically. Jnduction oj colorectal tumors succeeded in 37% oj males and 17% oj females. There were 21 tumors oj the large bowel jound, oj these 15 in males and 6 in jemales. Histologically, males had 1 I adenomas, 2 signet-cell carcinomas and 2 adenocarcinomas, while jemales had 4 signet-cell carcinomas and 2 adenomas. We also found extraco/onic tumors, mainly those oj the small intestine and oj the Zymbal glands. Wistar rats showed lower incidence oj DMH-iiuluced colorectal tumors in comparison with other strains oj rats. The gender-dependent difference in the incidence oj colorectal tumors was jound to be statistically marginally significant (p<0.08), whereas the difference in the incidence oj ali induced tumors between genders was significant (p<0.02). Males showed a greater incidence oj colorectal tumors and also a greater histological resemblance to human colorectal tumors than females. That is wh:y we recommend Wistar males rather than females far research on colorectal tumors. Key words: Colorectal neoplasms-chemically induced; dimethylhydralazines; rats Introduction Nowadays, colorectal cancer (CRC) represents one of the most frequent malignant neoplasms of man in the developed world. With respect to its inci­dence as well as mortality rates, in the United States of America it takes the third place1 while in Slove­nia it is on the second place.2 It is a well known fact that in humans, males will contract CRC more fre­quently than females. 1 A few studies that have been carried out on animal models yielded similar re­sults.3·4.5 The models in those studies differed from each other considerably, so with respect to the type Correspondence to: Assist. Prof. Anton Cerar, MD, PhD, Institute of Pathology, Korytkova 2, 1105 Ljubljana, Slovenia. Phone: +386 61 13 15 190; Fax: +386 61 301 816. UDC: 6l6.348-006.6:616.35-006.6-092.9 and strain of animals used as well as with respect to tumor induction methods. Nowadays, Wistar rats are the strain most commonly used for research purposes. As most authors give preference to male specimens while the published information on sex­related differences in the induction of CRC with DMH is very scarce, we have decided that this issue is worth of further studies. Materials and methods Animals Sixty Wistar rats (provider: Medica! Experimental Center, Ljubljana) 9 weeks of age were used. At the onset of the experiment the weight of males ranged between 220-280 g, and that of females between 140-180 g. The experiment was carried out at a A role 1fgender in the occurrence 1fdimenthylhydrazine induced tumor.1· room temperature of 20-23°C, humidity 40-70%, and at a natura! day/night cycle. The animals were fed on M-K-02 briquettes (supplier: Biotechnical Faculty, Ljubljana) and tap water. Carcinogenic agent CRC was induced by means of DMH (producer: Fluka Chemie, Switzerland) prepared according to the standard method 6•7: DMH-HCI was dissolved in 0.001 M EDTA and pH value adjusted to 6.5 using 0.1 M NaOH solution. Fresh solutions were pre­pared once weekly. Study design The animals were distributed into groups of 1 O per cage. Males and females were kept separately. Eve­ry three weeks the animals were weighted and the dose of DMH adjusted accordingly, so that it al­ways amounted to 20 mg/kg of body weight. The solution was injected subcutaneously (s.c.) into the skin fold on the hip once weekly throughout a peri­od of 15 weeks. The animals were left to live 10 weeks after completed DMH injection, and there­upon sacrificed by CO2 inhalation. Morphological investigation On autopsy, ali interna! organs except the central nervous system were examined. Particular attention was paid to possible presence of tumors in the outer auditory canal. The stomach was opened via the major curve while the intestine was approached longitudinally on the antemesenterial side; after opening, the organs were rinsed with water. The end part of the ileum, large intestine, anus and neoplasms in the small intestine were spread over a polystyrene board, with intestinal mucosa facing upwards. The tissue was fixed in 10% buffered formaldehyde. Three tissue samples of the large intestine were taken for histological examination from the follow­ing sites: the rectum, transversal colon and ascend­ing colon. Ali the macroscopically visible lesions were sampled as well. The tissue samples were paraffin embedded and cut into 4mm thick histo­logical sections. The sections were afterwards stained by thrichrome method according to Krey­berg. In the cases when histological picture or tu­mor stage could not be determined from a single section, a stepwise series of sections was made. Ali intestinal lesions were assessed by histological cri­teria used in human pathology.8 Carcinomas were distributed into three stages pC­cording to their phase of development:9 -Stage A: tumor tissue is limited to the intestinal wall; -Stage B: tumor tissue grows through the lamina muscularis propria; -Stage C: tumor tissue grows through the lamina muscularis propria and disseminates into the lymph nodes and distant organs. Histological criteria for diagnosis of adenoma were 1) cytological (multiplied mitoses, polymor­phism, and hyperchromatism of the nuclei, ba­sophilia of the cytoplasm, decreased mucine excre­tion), and 2) histological (stratification of the nu­clei, irregular proliferation of the glandular forma­tions). The criteria for diagnosis of carcinoma was the evidence of tumor growth through the muscula­ris mucosae. Statistical methods The significance of sex-related difference in the numeric results was tested by Pearson's Chi-square test. Results Ninety-five percent of animals survived throughout the duration of the experiment. One male was sacri­ficed 7 weeks before the end of experiment because of a large tumor of the Zymbal gland while another two males died spontaneously due to intestinal tu­mors (1 in the large and 1 in the small intestine) 10 and 1 days respectively before the end of experi­ment. During the experiment the animals.,were fed nor­mally, their body weight was increasin& by advanc­ing age. In the last two weeks, the boCly weight of five males was found to have decreased, and the presence of carcinomas of the Zymbal gland or intestine was confirmed in ali of them. Tumors oj the large intestine and rectum Twenty-one tumors were found in the large intes­tine, 15 of these in males and 6 in females (Table !). Tumors developed in 37% of males and 17% of females, i.e. in 27% of ali animals. Three males (10%) and one female (3%) had multiple primary tumors. Sex-related difference in the occurrence of ali colonic tumors was borderline significant (p<0.08). Breskvar L and Cerar A Table l. The number of tumors induced in the large intes­tine Histological type of tumor Sex Adenoca. Signet-cell ca. Adenoma Tota! Males 11 2 2 15 Females o 4 2 6 Tota! II 6 4 21 An analysis of sex-related differences in the number of colorectal carcinomas a!so showed a borderline significance (p<0.08). A majority of the induced tumors were found in the transverse colon (30%), followed by the as­cending col on (17% ), rectosigmoid (10%) and de­scending colon (7%) (Figure !). Most tumors in males were polypoid (Figure 2); a majority of them were situated in the transverse colon (73%), and none in the rectosigmoid. Intus­susception in the transverse and descending colon respectively was observed in two males. In females, the tumors induced in the large intes­tine were rare and relatively evenly distributed (Fig­ure 1). Three females presented with tumors in the rectum. There were neither tumors in the descend­ing colon nor intussusception observed. Macroscop­ically, most tumors in females were fiat. On a sub­sequent histological examination they were recog­nized as signet-cell carcinomas. In the review of histological samples 21 tumors were analysed (Table 1) as follows: there were 11 adenocarcinomas (Figure 3), 6 signet-cell carcino­mas and 4 adenomas. Ali the neoplasms were macroscopically visible. Further microscopic examination also revealed the C,ecum A mle r>( gender in the occurrence r>( dimenthylhydrazine induced tumo1:v mas. Poorly differentiated adenocarcinomas were rare. In contrast to that, signet-cell carcinomas were mostly flat lesions which infiltrated the wall. The sex-related differences in the number of tu­mors induced in the large intestine were not statisti­cally significant. In males 15 tumors were found in the colon and rectum as follows: there were 11 adenocarcinomas, 2 signet-cell carcinomas and 2 adenomas. In females 6 tumors were induced: 4 signet-cell carcinomas and 2 adenomas. When determining the stage of colorectal carci­nomas, the majority of tumors (7a1 % ) were found to be stage A (Figure 4). Many smaller, well-differ­entiated stage A tumors could be interpreted as adenomas, and therefore step-wise sections had to be made in a few cases in order to ascertain the invasion through the muscularis mucosae. The comparison of stage distribution by sex did not show statistically significant differences (p<0.14). In males the majority of carcinomas (77%) were stage A while the rest were stage B, the latter being invariably situated in the transverse colon. None of the males presented with a stage C tumor. Most tumors in females were stage A, ali of them were signet-cell carcinomas. One female had a stage C tumor. Histologically, this was a signet-cell car­cinoma with evidence of lymph node involvement and carcinosis of the !iver and peritoneum. Other tumors Apart from tumors of the large intestine, there were also 19 tumors of the small intestine and 5 tumors of the Zymbal gland found along with I hemangi­oma of the !iver and one hepatocellular carcinoma. 25% "' 20% E 20% ·2 o 15% (U lillll10% 10% 2 10% 3% 5% (U 0% O% o.. 0% A B C Tumor stage illl!Males IIFernales Figure 4. Comparison of grades of large intestine carcino­mas. The tumors of the small intestine were mostly large, polypoid and macroscopically similar to those found in the large intestine, although they were histologically different: a half of these tumors were signet-cell carcinomas, the majority (80%) of them being stage B. The rest were adenocarcinomas ex­hibiting focally increased mucine production. Tu­mors of the small intestine occurred in one third of males (33%); 80% of these presented with signet­cell carcinomas while the rest had moderately dif­ferentiated adenocarcinomas. Three males had mul­tiple primary tumors, and two showed evidence of intussusception. In females, tumors of the small intestine were found in 13%. A half of these were adenocarcinomas, while the other half were signet­cell carcinomas; 75% of ali tumors were in an ad­vanced stage B. The sex-related differences in the incidence of small-intestinal tumors were found borderline sig­nificant (p<0.07). The sex-related difference in the number of ali tumors induced was statistically sig­nificant (p<0.02). Discussion While CRC is a relatively frequent tumor in hu­mans, its spontaneous occurrence in rats is rare.10 DMH is one of the most effective CRC inducers in small rodents.11 This substance has been studied in large-scale experiments,12 and the tumors induced have been compared with those occurring naturally in humans10•, although any sex-related differenc­ 13•14 es were not clearly defined. Some authors claim to have established a lower incidence of DMH induced tumors in Wistar rats as compared to other strains of rats. 15 These findings have also been confirmed by our results showing that tumor induction was successful in 27% of the experimental animals only. The occurrence was con­siderably lower in females than in males, al­though the difference was only borderline signifi­cant. Histological examination revealed a few adeno­mas in the large intestine, which consisted of one or more glands. These lesions were not macroscopi­cally evident. Nevertheless, this finding is interest­ing as it confirms probable development of carcino­ma from adenoma 16•17, and points out the similarity with colorectal carcinogenesis in humans. Such ad­enomas were also reported by other authors18 al­though they were not evaluated quantitatively. Un­ Breskvar L and Cerar A doubtedly, there would have been even more ade­nomas found in our study, had we decided to exam­ine the entire intestine by systematic microscopy. This will be the subject of our further research. Our data on the sites of primary tumor induction in males are consistent with those of other authors, who report the greatest number of tumors in the transversal colon. 19 Comparable with our results, other authors also found rare tumors in the ascend­ing and descending col on but not in the caecum. 19 It is of interest to note that not a single tumor of the rectum could be found in males. Consistent with this observation, other authors also report rare tu­mor occurrence in this site (5%).7•20 In females as well tumors of the wide intestine were induced in the same sites as reported by other authors, 1 2 the only exception being the ascending colon where the numbers of induced tumors reported by other au­thors are somewhat higher. Likewise other authors, macroscopically we also found prevailingly polypoid tumors.a10-12 There was however, sex-related difference found with respect to the site of their occurrence. Thus males had a prevailing majority of polypoid tumors in the cen­tral part of the colon. Sessile tumors exhibiting endophytic growth were extremely rare. The latter were found prevailingly in the proximal part of the ascending colon. Intussusception, which was ob­served in a few animals, has also been reported by other authors. 6•10 The site of origin is just as usual in the transverse colon, which is consistent with the sites of origin of polypoid tumors.6 It is well known that large polypoid tumors are associated with more aggressive invasion of the intestinal wall.a19 This is responsible for hardening of the wall and conse­quential invagination into the distal part of the in­testine. In females, most tumors were situated in the rec­tum and proximal part of the ascending colon. Mac­roscopic differences were evident as well: a majori­ty (70%) of tumors were sessile and wall-invading. Intussusception was not noted. This could partly be attributable to the fact that those tumors were rela­tively small. Histologically, our number of adenocarcinomas was smaller than those reported by other authors who used other strains of rats and the same dose of DMH.6•7 The descriptions of histological pictures of tumors in males were consistent with our results, although the rate of signet-cell carcinomas in our series was greater (13% of ali tumors). According to some authors, the occurrence of the latter tumors is attributable to a higher dose of DMH.21 It has been found that ali those tumors were fiat and that they occurred in the proximal part of the ascending colon. This finding is consistent with the reports of other authors.13•22 The majority of polypoid tumors that were found in the transverse colon were adeno­carcinomas. Their histological picture depended on the tumor size. Thus, smaller tumors mostly showed a well differentiated adenocarcinomatous compo­nent with a minimal or no mucinous component, whereas larger polypoid tumors showed a greater rate of mucinous component, which has also been described by some other authors. 19 Our results of tumor stage analysis were compa­rable with those obtained by other authors, accord­ing to which a majority of tumors (71 %) were in stage A.9 Our comparison of carcinoma stage by sex has not shown statistically significant differ­ences, however it seems noteworthy that none of the females presented with a stage B tumor. The fact that most of those tumors were signet-cell car­cinomas renders this information ali the more inter­esting. A majority of authorslll·16 believe that this very type of tumors is the most aggressive. Stage was also associated with the degree of differentia­tion of colorectal tumors: the majority of stage B tumors were moderately or poorly differentiated carcinomas. Stages were rarely described in experi­mental studies with DMH, the only exception being individual cases of stage C with carcinosis and dis­tant metastases.6•16•23• Few authors studied the origin of sex-related dif­ferences in the occurrence of DMH induced tumors. The majority of investigations were centred on the study of the influence of sex hormones.24 A stimu­lating effect of male sex hormones on tumor induc­tion with DMH was established.5 Our results have shown that males developed significantly more colorectal tumors than females. Furthermore, the tumors in males were histologi­cally more similar to colorectal tumors in humans. Therefore, we recommend male rather than female Wistar rats to be used for experimental work with the mentioned tumor model. Acknowledgement: The authors wish to thank Mrs. Katja Skulj, DMV, for her valuable assistance with the experiments, Mrs. Lijana Kragelj-Zaletel, MD, Msc, for statisti­cal data processing, Mrs. Tadeja Klemenc and Maj­ A role 11f'gel!der ill tlze occurrence 1!fedime11thylhydrazille induced tumors da Prebil for histological sample preparation, Mr. Dane Velkavrh, BSc, for preparation of solutions, and Mr. Tomo Brezovar for photographs. References 1. Boring CC, Sqires TS, Tong T, Montgomery S. Cancer statistics. Cal!cer J Ciin 1994; 44: 9. 2. Register raka za Slovenijo. Incidenca raka v Sloveniji. Onkolo'ki in'titut v Ljubljani, 1994: 13. 3. Evans JT, Shows TB, Sproul EE, et al. Genetics of colon carcinogenesis in mice treated with 1,2-dimeth­ylhydrazine. Cancer Res 1977; 37: 134-6. 4. Balish A, Shih CN, Croft WA, et al. Effect of age, sex, and intestinal flora on the induction of colon tumors in rats. J Natl Cancer Inst 1977; 58: 1103-6. 5. Moon RC, Fricks CM, Schiff LJ. Effect of age and sex on colon carcinogenesis. Proc Am Assoc Cancer Res 1976; 17: 23-8. 6. Mmtin MS, Mmtin F, Michiels H, et al. An experimen­tal model for cancer of the col on and rectum. Digestioll 1973; 8: 22-34. 7. Maskens AP. Histogenesis and growth pattern of 1,2 dimethylhydrazine-induced rat colon adenocarcinoma. Cancer Res 1976; 36: 1585-1592. 8. Anon. General rules for clinical and pathological stud­ies on cancer of the col on, rectum and anus. Jpn J Surg 1983; 13: 574- 98. 9. Danzi M, Lewin MR, Cruse JP, Clark CG. Combina­tion chemotherapy with 5-fluorouracil (5FU) and l,3­bis(2-chloro-ethyl)-l-nitrosourea (BCNU) prolongs survival of rats with dimethylhydrazine-induced colon cancer. Gut 1983; 24: 1041-7. 1 O. Newberne PM, Rogers AE. Adenocarcinoma, Col on and Rectum, Rat. In: Jones TC, Popp JA, Mohr U, eds. Digestive system. Monographs on Pathology of Labo­ratory Animals. Springer, 1997: 432-7. 11. Druckrey H, Preussman R, Matzkies F, Ivankovic S. Selektive erzeugung von darmkrebs bei ratten durch 1,2-dimethylhydrazin. Natwwissenschaften 1967; 54: 285-6. 12. Roussel F, Laumonier R, Tayot J. Les etapes de la carcinogenese de tumeurs colique experimentales par la 1,2 D.M.H. Ann Anat Parol (Paris) 1978; 23: 5-22. 13. LaMont JT, O'Georman TA. Experimental colon can­cer. Gastreoentero/ogy 1978; 75: 1157-69. 14. Sjogren HO, Steele G. The immunology of the large bowel carcinoma in rat model. Cancer 1975; 36: 2469-7e1. 15. Turusov VS, Lanko NS, Krutovskikh VA, Parfenov YD. Strain differences in susceptability of female mice to 1,2-dimethyhydrazine. Carcil!ogenesis 1982; 3: 603-8. 16. Shinichi N, Isamu K, eds. Morphogenesis of experi­mental colonic neoplasms induced by dimethylhydra­zine. In: Pfeiffer CJ, ed. Animal mode/s for intestinal disease. CRC Press, 1985: 99-12e1. 17. Chang WW. Histogenesis of colon cancer in experi­mental animals. Scand J Gastroenterol Suppl; 104: 27-43. 18. Balansky R, Blagoeva P, Mircheva Z, Pozharisski K, De Flora S. Effects of metabolic inhibitors, methylxan­thines, antioxidants, alkali metals, and corn oil on 1,2 dimethylhydrazine carcinogenicity in rats. Anticancer Res 1992; 12: 933-40. 19. Davis AE, Patterson F, Crouch R. The efects of thera­peutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model. Br J Cal!cer 1992; 66: 777-80. 20. Deasy JM, Steele G, Ross DS, Lahey SJ, Wilson RE, Madara J. Gut-associated lymphoid tissue and dimeth­ylhydrazine-induced colorectal carcinoma in the Wis­tar/Furth rat. J Surg Oncol 1983; 24: 36-40. 21. Nauss KM, Locniskar M, Newberne PM. Effects of alterations in the quality and quantity of dietary fat on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats. Cancer Res 1983; 43: 4083-90. 22. Filipe IM. Mucinous secretion in rat colonic mucosa during carcinogenesis induced by dimethylhyedrazine. A moqihological and histochemical study. Br J Cancer 1975; 32: 60-77. 23. Rowlatt C, Cruse JP, Barton T, Sadrudin AA, Lewin MR. Comparison of the significance of three his­topathological thresholds of malignacy in experimen­tal colorectal tumours. Gut 1989; 30: 845-53. 24. Chao TC, Van Alten PJ, Greager JA, Walter RJ. Ster­oid sex hormones regulate the release of tumor necrosis factor by macrophages. Cel! Immunol 1995; 160: 43-9. Radio/ Oncol 1997; 31: 380-3. Cytology of mediastinal tumors Milivoj Mermolja, Izidor Kern, Marjeta Tercelj, Marjan Jereb Clinical Department for Respiratory Diseases and Allergy Golnik, University Clinic oj Interna! Diseases, Clinical Centre Ljubljana, Slovenia Our experience with cytological examinations oj tumorous mediastinal lesions is evaluated. A group oj 117 patients with mediastinal tumor have been included into the study. Among them carcinomas prevailed (60.7%),followed by lymphomas (18.8%), other tumors (15.4%) and thymic neoplasms (5.1%). Malignant or suspicious cells were jound in 77.4% oj patients with carcinoma. The cells indicating a possibility oj non­Hodgkin 's lymphoma were jound in 9 out oj 14 patients. In 5 out oj 6 thymic neoplasms the cytological pattern was consistent with the diagnosis oj thymic neoplasm. One case oj thymoma was cytologically jalsely diagnosed as malignant lymphoma. One case oj neurojibroma was jalsely diagnosed as adenocarcinoma. The sensitivity oj cytological examinations was 67.5%. lf 18 patients with diagnostically unsatisjactory material were excluded jrom the analysis, the sensitivity would increase to 80. 8%. Owing to the wide variety oj primary and metastatic tumors that can occur in the mediastinum, apart jrom the routine cytological techniques, additional staining methods should be used. Far fina[ cytological diagnosis the integration oj cytological jindings with clinical and radiological data is ojten required. Owing to the characteristics oj the obtained material and biological behaviour oj some mediastinal twnors, some tumors cannot be definitively diagnosed by cytological examinations alone. Key words: mediastinal neoplasms-pathology; biopsy, needle Introduction The mediastinal space is the site of many benign and primary or metastatic malignant tumors. The introduction of transthoracic fine needle aspiration biopsy (TFNAB) has facilitated the determination of the cytopathologic nature of the mediastinal le­sions. 1•2 It may provide information otherwise ob­tainable only by more invasive diagnostic tech­niques, such as mediastinoscopy, thoracoscopy or thoracotomy. It can also be performed at a relative­ly small discomfort to the patient; in experienced hands it provides a rapid and reliable guidance to 4 further treatment.3• Correspondence to: Scientific Counsellor Prof. Dr. Milivoj Mermolja, B. Se. Biol., Gorice 40, 4204 Golnik, Slovenia. UDC: 616.27-006e.6-076.5 This article reports our experience with cyto­logical examinations of tumorous mediastinal le­sions. The results and reliability of cytological ex­aminations are evaluated. A special attention is paid to the possibility of cytological determination of mediastinal tumors and diagnostic problems. Other factors that may influence the cytological examina­tion are also taken into account. Materials and methods In ten years' period (1986-1995), 204 TFNAB of the mediastinum from 182 patients were cytologically examined. In this study 117 patients with mediastinal tumors were included. Fina! diagnoses were estab­lished by means of histopathological examination, clin­ical documentation and follow-up. Ali TFNAB of the mediastinum were performed under radiologic guid­ Cytolo1;y 1d' mediastinal tunwrs Table 2. Frequency distribution of mediastinal tumors ance. In some cases a cytopathologist was present to evaluate the quality of the specimen. The smears were Carcinomas N % air dried, stained by May-Grlinwald-Giemsa method Squamous celi carcinoma 8 11,3 and fixed in Delaunay solution followed by Papanico­Small celi carcinoma 12 16,9 Adenocarcinoma 16 22,5 lau staining method. If material was suitable, immu­ 21,1 nocytochemistry was performed as well. Mediastinal Large celi carcinoma 15 Nonspecified carcinoma 7 tumors were classified into carcinomas, lymphomas, Nonverified 13 18,3 thymic neoplasms and other tumors. The carcinoma group includes squamous celi, small celi carcinoma, adenocarcinoma, large celi carcinoma and nonspeci­fied carcinoma. Lymphomas were divided into Hodg­kin' s and nonHodgkin's. Thymic neoplasms included thymomas and thymic carcinoids. Other tumors in­cluded germ-cell tumors, neurogenic tumors, benign soft tissue tumors and miscellaneous tumors. Cytolog­ical diagnoses were categorized as positive, suspi­cious and negative. By these terms, the presence or absence of tumorous cells was indicated regardless of their biological potential. In statistical analysis the samples with nondiagnostic material were included among negative ones. Results In 117 patients with proved mediastinal tumor, there were 76.5% males and 32.5% females (Table 1). Among tumors of the mediastinum, carcinomas pre­vailed (60.7%), followed by lymphomas (18.8%), other tumors (15.4%) and thymic neoplasms (5.1 %). Among carcinomas (Table 2) the adenocarcinomas prevailed (22.5%), followed by large celi carcino­mas (21.1%), small celi carcinomas (16.9%), squa­mous celi carcinomas (11.3%) and nonspecified car­cinomas (9.9%). In 18.3% of patients carcinoma was microscopically verified by examination of the extramediastinal lesions. Among lymphomas, 63.6% were nonHodgkin's and 36.4% Hodgkin's lymphomas. Among thymic neoplasms there were 5 cases of thymoma and one case of thymic carci­noid. Among other tumors there were 6 germ-cell tumors, 4 neurogenic tumors, 5 benign soft tissue tumors and 3 miscellaneous tumors (angiosarcoma, plasmocytoma, unclassified epithelial tumor). Table l. TFNAB of mediastinal tumors Tumors Men Women N Tota!e% Tumors Positive N % Suspicious N % Negative N % Carcinomas Lymphomas Thymic neoplasms Other tumors 56 II 3 9 15 II 3 9 71 22 6 18 60,7 18,8 5,1 15,4 Carcinomas Lymphomas Thymic neoplasms Other tumors 50 70,4 7 31,8 4 66,7 7 38,9 5 7,0 4 18,2 1 16,7 2 11,1 16 22,5 11 50,0 1 16,7 9 50,0 Tota! 79 38 117 100 Tota! 68 _58,1 12 10,3 37 31,6 Tota! 71 100 Thymic neoplasms N % Thymomas Thymic carcinoid 5 1 83,3 16,7 Tota! 6 100 Lymphomas N % Hodgkin's nonHodgkin's 8 14 36,4 63,6 Tota! 22 100 Other tumors N % Germ celi tumors 6 33,3 Neurogenic tumors Benign soft tissue tumors Miscellaneous tumors 4 5 3 22,2 27,8 16,7 Tota! 18 100 The results of cytological examination were most satisfactory in carcinomas, as malignant or suspicious cells were found in 77.4% of cases. Cells indicating the possibility of nonHodgkin's lymphoma were found in 9 out of 14 patients with nonHodgkin's lymphoma. In 8 cases with Hodg­kin's lymphoma suspicious cells were found in two patients. In thymic neoplams one case was cytolog­ically falsely diagnosed as malignant lymphoma. In four patients cytological pattern was consistent with the diagnosis of thymic neoplasm (three thymomas and one thymic carcinoid). In one patient with thym­ic neoplasm the obtained material was not diagnos­tically relevant. In the group of other tumors, in nearly half of the patients the tumorous cells were correctly identified so that cytological findings were consistent with fina! diagnoses. An exception was the case of neurofibroma which was cytologically diagnosed as adenocarcinoma. These data indicate that in patients with medi­astinal tumors the sensitivity of cytological exami- Tablc 3. Cytological examination of TFNAB of mediastinal tumors Mennolja Metal. nation was 67.5%. If 18 patients, with unsatisfac­tory material (Table 3), were excluded from the analysis, the sensitivity of cytological examination would rise up to 80.8%. Discussion TFNAB has proved to be a useful diagnostic proce­dure in the evaluation of patients with mediastinal lesions.2,5 By cytological examination of this type of material more than 80% of tumorous mediastinal lesions may be diagnosed. Owing to the wide variety of primary and met­astatic mediastinal tumors, interpretation of cyto­logic pattern requires large experience and precau­tions. Most metastatic carcinomas (Figure 1) and some non-malignant mediastinal tumors can be ac­curately diagnosed by cytological examination of only routinely stained smears. However, reliable determination of lymphomas, thymic neoplasms, neurogenic tumors and some other tumors often requires additional cytological teclmiques. Immu­nocytochemistry has mostly been used in the last years. In some cases even the electron microscopy is recommended.6 According to our experience, some mediastinal tumors cannot be definitively di­agnosed by cytology. The reasons are different. In our patients with lymphomas, the lymphatic cells were present in only about half of the samples. Apart from that, even if lymphatic cells were present, there were frequently only few of them, or they were destroyed (Figure 2), so that the ob­tained material was often not suitable for perform­ing the necessary immunocytochemistry, without which lymphoma can not be diagnosed and classi­fied reliably.7•8 Figure 2. Malignant lymphoma of the mediastinum. Poorly preserved abnormal lymphoid cells with enlarged nuclei and small amount of cytoplasm. In the thymic neoplasms one case of thymoma was cytologically falsely interpreted for malignant lymphoma. So, our experience is in accordance with the opinion that although thymomas have character­istic biphasic pattern,9•10 a few other differential di­agnostic possibilities should be considered as well. 11 In the group of other tumors ali three neurogenic tumors were diagnosed correctly. Namely, the cyto­logical features of benign schwannoma (Figure 3) Figure l. Small celi carcinoma of the lung. Malignant cells are in loose groupings. Mostly only stripped nuclei are Figure 3. Schwannoma of the mediastinum. Large group visible. of interlacing spindle cells with uniform elongated nuclei. Cytology 11/'emediastinal tumors reproduce characteristic and distinctive pattern of interlacing spindle cells12 thus allowing a reliable cytologic diagnosis. In one female patient the neu­rofibroma was cytologically falsely diagnosed as ad­enocarcinoma. By re-examination of the smears it was proved that severa! groups of interlacing spindle cells have been overlooked, while numerous atypical epithelial cells, being also in groups, were falsely identified as malignant. It could be concluded that our results of the cytological examination of mediastinal tumors are comparable with the results of other authors. 13•14 However, it should be considered that the mediasti­num is a host of numerous relatively unusual pri­mary neoplasms as well as a frequent site of meta­static tumors. Therefore, the performance of TF­NAB of mediastinal tumors is an exciting field of diagnostic cytology. For carcinomas, where the con­cordance between cytopathological and histopatho­logical examination is high, 15 cytopathological di­agnoses do not need to be additionally verified pri­or to therapy procedure. In most other tumors, apart from the routine cytological techniques, immuno­cytochemistry should be used frequently. In addi­tion to cytological examination, a cytopathologist always needs to integrate both clinical and radio­logical data to formulate the fina! diagnosis. For different reasons, some mediastinal tumors cannot be definitively diagnosed by cytological examina­tion alone. References l. Jereb M, Us-Krašovec M. Transthoracic needle biopsy of mediastinal and hilar lesions. Cancer 1977; 40: 1354-7. 2. Weisbrod GLe. Percutaneus fine-needle aspiration biop­sy ofethe mediastinum. Ciin Chest Med 1987; 8: 27-41. 3. Koss LG, Zajicek J. Aspiration biopsy. In: Koss LG, ed. Diagnostic cytology and its histopathological bas­es. Philadelphia: Lippincott Comp., 1992: 1336-402. 4. Liang-Che Tao. Lung, pleura and mediastinum. Guides to clinical aspiration biopsy. Igaku-Shoin, 1988: 2-9. 5. Powers CN, Silverman JF, Geisinger KR, Frable WJ. Fine-needle aspiration biopsy of the mediastinum: A multi-institutional analysis. Am J Ciin Pathol 1996; 105: 168-73. 6. Yazdi HM, Dardic l. What is the value of electron microscopy in fine needle aspiration biopsy. Diagn Cytopatol 1988; 4: 177-82. 7. Geisinger KR. Differential diagnostic considerations and potential pitfalls in fine-needle aspiration biopsies of the mediastinum. Diagn Cytopathol 1995; 13: 436­42. 8. Silverman JF, Raab SS, Kirn Park H. Fine-needle aspi­ration biopsy cytology of primary large cell lymphoma of the mediastinum. Cytomorphologic findings with potential pitfalls in diagnosis. Diagn Cytopathol 1993; 9: 209-15. 9. Pak HY, Yokota SB, Friedberg HAe. Thymoma diag­nosed by transthoracic fine needle aspiration. Acta Cy­tol 1982; 26: 210-6. 10. Tao LC, Pearson FG, Cooper JD, Sandse DE, Weis­brod GL, Donat EE. Cytopathology of thymoma. Acta Cytol 1984; 28: 165-70. 11. Herman SJ, Holub RV, Weisbrod GLe, Chamberlain DW. Anterior mediastinal masses: Utility of transtho­racic needle biopsy. Radiology 1991; 180: 167-70. 12. Hood IC, Quizilbash AH, Young JEM, Archibald SD. Needle aspiration biopsy of benign and malignant schwannoma. Acta Cytol 1984; 28: 157-64. 13. Sterrett G, Whitaker D, Shilkin K, Walters M. The fine needle aspiration biopsy of mediastinal lesions. Can­cer 1983; 51: 127-35. 14. Young G, Young I, Cowan D, Blei R. The reliability of fine-needle aspiration biopsy in the diagnosis of deep iesions of the Jung and medistinum: experience with 250 cases using a modified technique. Diagn Cy­topathol 1987; 3: 1-7. 15. Mermolja M. Possibilities and limitations of cytology in the diagnosis of Jung tumors. Radio! Oncol 1994; 28: 266-70. Radio/ Oncol 1997; 31: 384-7. Early piriform sinus cancer -results of treatment with partial vertical pharyngectomy Janos Elo, Zsuzsa Balatoni, Tibor Tar Uzsoki District Hospital, Budapest Dept. of Oto-Rhino-Laryngology -Head-and-Neck Surgery Dir: Prof Dr.Elo Jdnos Between 1986-1995, 179 patients with hypopha1yngeal carcinoma were surgically treated at our depart­ment. Among them, 35 had functional partial resection. Out of these, 13 patients had vertical partial pharyngolaryngectomy carried out ajier ipsilateral neck dissection. The access to the primary tumors was made via lateral pharyngectomy. Eight out oj thirteen patients are disease free two years after the treatment, with well functioning larynx. Some complications occurred, but there were no cases of surgery related death. The hypopharyngeal cancers are considered as supermalignant tumors. The achieved good functional results and survival rate prave that conservation surge1y -partial laryngopha,yngectomy -in selected cases of early hypopha,ynx carcinoma is a good altrnative to radical surge1y Key words: hypopharyngeal neoplasms-surgery; pharyngectomy; partial pharyngolaryngectomy Introduction Regardless the modem therapeutic approach used, the pyriform sinus cancer remains one of the most aggressi ve lethal human diseases. 1 Most of these tumors have high grade of malignancy and cause few symptoms at an early stage. In a great number of cases, clinically positive neck nodes call attention to hypopharyngeal tumors. This region is characterized by special anatomi­cal and functional conditions contributing to the rapid progression of cancer. The submucosal space is built up of loose connective tissue, rich in lym­phatics and blood vessels. Neither caudal nor crani­al direction have anatomical barrier against tumor dissemination. That is why the hypopharyngeaI can­cers can be regarded as a three-dimensional dis­ease.2 The irritation and permanently changing pres- Correspondence to: Elii Janos, Hungary, Budapest, Tei: 36-1-2517-333, FAeX: 36-1-251-4069 UDC: 616.327.4-006.6-089 sure caused by swallowing of foods and drinks are important factors in spreading of cancer cells.e3 The decision about indication for conservation surgery for hypopharyngeal cancers should be made with responsibility; it requires great experience, good surgical technique, as well as careful exami­nation and selection of patients, because an ade­quate resection of cancer is imperative.4·•5 Despite these facts, in 15-20 per cent of patients the hy­popharyngeal cancer can be removed with total or partial preservation of the larynx. A one-stage re­construction of pharyngeal defects is a very impor­tant part of surgery. In the presented paper, authors report on their surgical method for the treatment of early hypopharyngeal carcinoma, with which they preserve the larynx and swallowing function. Material and methods In the last ten years, 179 patients with hypopharyn­geal tumors were treated surgically in our depart­ Early pirifcmn sinus cancer -results r!f' treatment with partial vertical pharyngectomy 385 ment under the same conditions. After careful se­lection of patients with respect to their age, cardi­orespiratiory status, prognostic nutrition index (PNI),6 and after examination comprising directos­copy, histology, US,CT,MRI, among the evaluated 148 pyriform sinus cancer cases 35 were consid­ered suitable for organ preserving surgery. Table 1 shows the types of conservation surgery used. Table l. Distribution of 35 conservation procedures. No Procedure Access to the primary tumor 16 Horizontal PLP* Extended suprnglottic resection of the larynx Partial resection of posterior wall Laterni pharyngotomy 13 Vertical PLP* Laterni pharyngotomy * PLP: partial pharyngolaryngectomy In 13 patients vertical partial pharyngectomy was performed. These are subject of the present report. Ali of them had planocellular carcinoma: 4 patients had grade I, 6 grade II and 3 grade III of the dis­ease. Table 2 summarizes the distribution of these 13 patients according to the UICC TNM classifica­tion.7 In 8 of them TI primary tumors were local­ized on the upper part of the laterni wall of pyri­form fossa. Table 2. TN distribution -UICC classificatieon. TN No NI N2b N2c Ali TI T2 Ali St.l.:4, 4 1 5 St.ll.:eI, 3 1 4 1 2 3 St.III.: 4, o 8 1 5 1 13 St.IV.: 4 In five cases T2 tumors also involved a part of the oropharynx. In four cases ipsilateral radical neck dissection (RND), in 6 modified radical neck dis­section (MRND) and in one patient ipsilateral radi­cal and contralateral MRND were performed. The indication and type of functional conserva­tion surgery was tailored to the extent of the prima­ry disease. The access to the tumor was made via laterni pharyngotomy. The upper cornu and a part of thyroid cartilage were removed in T2 tumors together with the hyoid bone process. (Figure 1 ). The hypoglossal nerve was mobilized and elevat­ed. Before entering the pharynx, a videolaryngo­scope was introduced into the cancer infiltrated re­gion, so as to enable the surgeon to judge on a TV screen the right place and distance from the tumor for appropriate access during pharyngotomy. If the disease was not too extended -most of the early TI cancers -the mobilized surrounding soft tissue was suitable for covering the defect. (Figures 2­3). In cases of T2 cancers, a pectoralis maior (PM) myocutaneous tlap was used for reconstruction. (Figures 4-5)t. Seven patients with pathologically positive neck received postoperative radiotherapyt. Figure 2. A small tumor of the laterni wall of pyriform sinus. 386 EWJ etiat. Figure 3. The mobilized pharyngeal mucosa. Figure 4. Double tumor: l. on the pharyngeal wall, 2. on the laterni wall of pyriform fossa. Results All thirteen patients have been followed-up until death or for at least 2 years. Within the first two years, 4 patients died, 3 of them from recurrence above the clavicles, and one from an intercurrent disease. Nine patient (69.2%) were alive, 7 of them (53.8%) free of tumor. In one patient, radical sur­gery was carried out for local recurrence. In one case with no evidence of a primary tumor, occult neck metastases appeared, and RND was performed successfully. Eight of thirteen patients (61.5 %) survived the first two years tumor-free, with well functioning larynx, and one with total laryngecto­my. There were no surgery-related deaths among operated patients, however some complications oc­curred in the postoperative period. In 3 cases, par­tial skin and soft tissue necrosis with pharyngocuta­neous fistula developed. Fibrosis with pharyngeal stenosis caused delay in per os feeding in 2 cases. Figure 5. Reconstruction of a pharyngeal defect with a myocutaneous flap. Bronchopneumonia in 1 patient caused postopera­tive difficulties. Two of our patients received pre­operative radiotherapy (60 Gy) in some other insti­tute. The surgical salvage was done after radiother­apy failure. Both of them had postoperative compli­cations but have recovered within 4-5 weeks. Discussion and conclusions The hypopharyngeal tumors represent a specific en­tity of head and neck cancers. In this region there are no morphological barriers against the spread of disease. Because of the Jack of symptoms at early stages of the disease, most cases are recognized as an advanced disease. In view of these facts, the indications for conservation surgery in cases of py­riform sinus tumors should be a very responsible decision, requiring careful examination and selec­tion of patients, great experience and good surgical technique. During a ten-year period, 179 patients with hy­popharyngeal carcinoma were surgically treated at our department, but only 35 of them met the criteria for conservation surgery. Among them, in 13 cases vertical PLP was carried out. Eight patients sur­ Early pirif<>rm sinus cancer -results 1Jf' treatment with partial vertical pha,yngectomy vi ved the first two years free of disease. In one patient successful salvage surgery -total pharyngo­laryngectomy -was carried out for local recurrence. 3 patients died from locoregional recurrences with­in the first two years. In reviewing reliable reports -Fletcher, Jesse,8 Harrison,2 Kirchner,9 Ogura et al.4 -two year cut­off period was chosen for analyzing the results, since in hypopharyngeal cancers a two-year inter­val seems to be sufficient for the evaluation of treatment effect. The prerequisites for improving the survival rates and quality of life are as follows: early diagnosis, careful examination, -TNM stating, tailored and proper surgical procedures, reliable one-stage re­construction, planned combined treatment with post­operative irradiation. We prefer surgery as primary treatment, because it reduces the rate of complica­tions. Patients treated for hypopharyngeal cancer need a careful and long-term follow-up. In the first and second postoperative years, frequent endoscop­ic examinations are necessary for recognizing any residual or recurrent tumors. Preoperative radio­therapy does not represent a contraindication to later functional surgery. According to the results presented by Leroux­Roberts, 10 Marks et al.,11 Ogura et al.,4 and accord­ing to our own experience, the conservation surgery for selected hypopharyngeal tumor patients is an effective procedure which ensures voice preserva­tion and a better quality of life. References 1. Marks SC, Lolachi CM, Shamsa F, Robinson K, Aref A. Outcome of pyriformis sinus cancer. La,yngoscope 1996; 106: 27-31. 2. Harrison DFN. Pathology of hypopharyngeal cancer in relation to surgical management. J La,yngol Otol 1970; 84: 137-53. 3. El6 J, Balatoni Zs, Bartfai R. Prognostic features and therapy of hypopharyngeal carcinoma. Otola,yngol (Perague) 1995; 44: 224-7. 4. Ogura JH, Marks JE, Freeman RB. Results of conser­vation surgery for cancers of the supraglottis and pyri­form sinus La,yngoscope 1980; 90: 591-600. 5. Kleinsasser O. Tumoren des Larynx und der Hypophar­ynx. Georg Thieme Verlag 1988; Stuttgait-New-York. 6. Hooly R, Levine H, Flores TCe., Wheeler T, Steiger E. Complications and prognostic index (PNI) in patients with stage III or stage IV disease. Arch Otola,),ngol 1983;109: 83-5. 7. TNM classification