299
Endoscopic Ultrasonography of the Mediastinum in the Diagnosis of Bronchial Carcinoma G. Schilder. H. lsrinqhaus, B. Kubale' , G. S eitz". and G. W Sybrecht:J
2
3
Dep artment of Thorac ic and Card iovascular Surgery Dep artme nt of Ra diology Dep a rtm e nt of Pathology Depa rtm e nt of Pneumology University lIospita l of Saarland. Hom bur g/Saa r , Germ any
Sum mary
Thoracic computed tomography (en is an essentia l component in the pre oper ative staging of bro nchial carcinomas as is medi astinoscopy (MSC) in cases of medi a stinal lymph oma . It is known that endoscopic ultrasonography (EUS). as a new diagnostic procedure, can pred ict lymph-node involvement in cases of tumors in the uppe r gastroi ntestinal tr a ct with an 80% probability. In a prospective stud y. we exam ined whet he r EUS could be use d to ascertain the pr esen ce of mediastinal lymph node s in cas es of bro nchial ca rcinoma . Since 1990, th er efor e, 32 patie nts with operable non -small-cell bro nchi al ca rcinoma have been exa mined with an Olympus-Aloka EU-M2 or EU-M3 (frequen cy 7.5 and 12 MHz) in addi tion to rou tin e dia gnosti cs. The gra ded cross-sectio ns of lym ph-n ode disse ctions obtained durin g subse que nt surgery se rved as evide nce as to the true or false prognos is of the lymph-node sta tus. Endoscopic ultrasonography ide ntifies the presence and estima tes the size of subca rina l, trac heo bronchial, pa ra ort al and parae sophageal lymph node s bette r than computed tomograp hy. Lymph node s lying behind org ans contai ning air (pr etracheal lymph nod es) ca n not be identifi ed by ultra sonography. Lymph -nod e involveme nt wa s correctly ident ified by EUS in 72 % of the case s, and th e specifi city was 86% . The poor se nsitivity, at 67 %. is explaine d by the high proport ion (37 %) of patients with an th racosilicosis, as the latter produces th e sa me echo pattern as malignant infiltration . In 47 % of all the cases, CT showe d enlarged medi ast inal lymph nod es whic h we re not actually infiltr ated in 6 7 %. Ofthes e lymph nod es, 33 % could be class ified a s definitely free of metas tases on the stren gth of their echo pattern , the rest were inflamed or really infiltrated by metast ases . The dia gno stic ad van tages of EUS, therefore, is tha t MSC is rendered unnecessa ry in cases of both unrem arkabl e and enla rged lymph-node stru ctures. This means a reduc tion of MSC of about 30 %. In cas es of suspected infiltra tion on EUS or silicosis, MSC is inevitable.
Key word s Non-s mall-cell lung ca nce r-Preo perative staging - Endoscopic ultr ason ography - Mediastinal lymphoma
Thorae . cardiovasc. Surge on 391 1991) 29 9-303 © Georg Th iem e Ver lag Stuttga rt . New York
Endoskopische Sonographie des Medi astinums in der lJiagn ostik des Bron chialkarzinoms Zum praoperativen Sta ging de s Bron chia lkarzinoms gehcrt ein thorakales Compute rtomogra mm (CT) un d im FaIle mediastinaler Lymphome die Medi astinoskopi e (MSK). Die Endoso nogra phie (EUS) als neues diagnostisches verfahren vermag bekanntlich bei Tumo re n des obe re n Gastrointest inaltr aktes mit eine r Wahrsch einlic hk eit von 80% eine rich tige Vorhersage des Lymphkno tenbefalls zu tr effen . In eine r pro spektiven Studie sollte untersucht werd en , ob d ie EUS auch beim Bronchialkarz inom zur Beurteilung mediast inaler Lymph knoten von Nutze n se in ka nn . Zusa tzlich zu r Routin ediagn ostik worde n des halb seit 19 90 mit eine m Olympus-Aloka EU-M2 bzw. EU-M3 (Freq uenz 7,5 und 12 MHz) 32 Patie nten mit oper abl em , nicht-kleinzelligem Bronchialkarzinom untersucht. Die Stufensch nitte der wahrend der an schliellenden Operati on entnomme nen Lym phk notendi ssektate dienten als Hefer enz filr die richtige oder falsche Vorhe rsage des Lymphknotensta tus . Besser als im CT geHngt der EUS die Darstellung und GroBenbeurteilung der subkari nalen, tr a cheobronchialen , pa ra a ort ale n und paraosophageal en Lymph knoten. Hinter lufthalugen Stru kturen liegende Lymphknoten [pr atracheale Lymphknoten) konn en nieht so nogra phiert werden . Insgesamt wird der Lymphknotenbefall du rch die EUS in 72% richtig vorherges agt , die Spezifltat betragt 86%. Die schlechte Sensitlvitat von 67 % wird durch eine n hohen Anteil (37 %) von Patien ten mit Anthrakosilikose erklarba r, da hierb ei da s gleiche Echomuster wie bei der malignen Infiltration vorliegt .
In 47 % aller Falle zeigt das CT vergroflerte Medi astinallymphknoten , die jedoc h zu 67 % nicht infiltriert waren . 33 % dieser Lymp hknoten kon nten aufgrund ihres Echomusters als siehe r me tast asenfr ei eingestuft werden. die iibrigen waren entziindli ch vera ndert ode r tatsac hllch me ta statisch infiltriert. Der diagno stische Gewinn dur ch die EUS liegt also darin, im Faile unauffalliger Lymphknotenstrukturen . a uch bei vergrbBert en Lymphknoten die MSK iiberfliissig zu machen . Die Einspa run g betragt ca. 30 %. Bei endoso nographischem Verdacht au f Infiltr ati on ode r bei Silikose wird na eh wie vor a uf die MSK nicht zu verzicht en sein.
Received for Publication: June 3, 1991
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I
Thome . eardiooase. Surgeon 39 (1991)
G. Schilder. 11. Isringhaus , B. Kubale, G. Seitz . and G. W. Sybrecht
a
Introdu ction Ultraso nics play a relatively unimp ort ant role in the pr eoper ative staging of bron chial carc ino mas , with the exception of ab dominal ultr asonography, despite the fact that reports on tr ansth oracic ultr asonograp hy showing the mediastin al structures have often appeared (14, 15). Bone an d air, however, still obst ruct reliable assessment, especially of the lymph nodes. The development of endosco pic ultraso nics (EUS) has mad e it possible for high freque ncy sonic probes to be intro duced into the body thus makin g ana tomic structures visible in high resolution . With EUS of the upp er gast rointest inal tract the wall of the stomach and intestines with its various anatomic layer s can be rende red visible, as can the immediate surro undings . In our prospective study on esophageal carcinoma patients we could prove that, in terms' of preoperative assessment of tumor infiltrati on and Iymphnode sta tus, EUS is more successful than either CT or nuclear magnetic resonance (13). Metastatic infiltration of the lymph nodes was prognosed correctly in 80% of the cases, whereas this was possible in only 50% when using computed tomography (CT) and magnetic resona nce imaging (NMR) . Stimulated by these facts, in the following study we wanted to ascertain whether high-frequency endoscopic ultra sonography can also be used profitably in the preoper ative staging of bron chial carcinomas .
b
Materials a nd Met hods Endoscopic ultrasonic exami nation was included in the routine diag nostics for all patients with a non-small-cell bronch ial carcinoma who were to be operated on. This was under taken either immediately preoperatively on the anesth etized patie nt, with ap prop riate consent. or as an isolated examination in our Endoscopic section. The Olympus-Aloka EU-M2 and . most recently. EUM3 were used for endos copic ultrasonography. This is a side -view endoscope of 13 mm diameter with a rotating transducer on its tip (Fig. 1). The frequency is 7.5 MHz. and the new model can be switched to 12 MH z if desired. A wat er-bag provides optimal sonographi c coupling. The instrument is passed through the mouth into the esophagus like a gastroscope . In conscious patients, the procedure is carried out in the left lateral position in order to limit the risk of aspiration. The gagging impulse is reduced by local anesthesia of the pharynx, a small premedication is occasion ally necessar y using O.4-0.6 mg Rohypno1. The transducer is then fed into the esophagus with slow movements as far as the stomac h. Here , routinely, the lymph nodes of the coeliac tr unk, the grea ter and lesser curvature, are viewed before the structures bordering on the esophagus are illustrated once more du ring the slow withdrawal of the instru ment. Sharply edged lymph nodes of an y size eliciting a poor echo are noteworthy. These wer e classified as metastatically infiltrated . Lymph nodes of unclearly edged structure giving ofT a strong echo are un remarkab le (Fig. 2). Computed tomograms were generated on a Siemens Somatom Plus or Somatom DR2. Mediastinoscopy was only carried out when media stinal or hilar lymph nodes of over a centimetre in size were detected . In thes e case s EUS was always undert aken before the mediastinoscopy, so tha t the examine r did not know the results of the latter. The type and extent of the operative interventio n was dictated by the location and the preoperatively, as well as intraoperatively, established sp read of the pulmonary tumor. An am ple lymph node dissectio n was untertaken in every case , as the minimum lymph node treatment recommended by the Ger man Society for Thoracic and cardiovascular Surgery (8). The graded cross-sections oflymph node dissections were pathologically evaluated according to their
Fi g. 1a Olympusect oenooscope (EU-M 3) witharotatingechoprobeonthe tip and with a switchablefrequency adapter b Magnifiedview of theechoprobeandtheside-view optic (withoutthe waterballoon)
location as given by the surgeon . All the documented results from CT, EUS and surgical findings were compared with the histopat hological results. By these mea ns it was possible to assess correct and incorre ct prognose s concerni ng the lymph node status.
Results Thirty-thr ee patients pr esent ed for exam ination, but in one case a narrow pharynx render ed endosco py impossible. There were no complications . Thus thirty-two patients with non-small-cell bron chial carcinoma could be evaluat ed. In all cases the subcarina l, par aesophageaI. an d hila r lymph nodes receptive to the tra nsduce r were reliably well prese nted. The paratr acheal , tra cheobron chial, and subaorta l lymph nodes could mostly be well detec ted. The pretrac hea l lymph nodes were not repr esent ed , nor were all those which, from the tr an sducer 's position, lay behind a bron chus containing air or other echoproof structur e. In seven cases (22 %) with a cent rally located tumor this, too, was pr esented. Infiltra tion as far as or into the pulmonar y artery and the pericardium, especially at the level of the left atrium, was clearly sh own (Fig. 3). Ofthe 32 patients, 15 (47%) had enlarged mediastin al lymph nodes, and therefo re suspected infiltr ation, according to CT, while the re maining 17 had lymp h nodes of less than one centimetre. Computed tomography gave the cor -
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Thomc. cardiovasc. Surgeon 39 (1991)
Endoscopic Ultrasonography cfthe Mediastinum
301
Fig.3 hypoechoictumor (T) with infiltrationof the pericardium atthelevelof the left atrium
b
Table 1 Prognosis of lymphnode staging. Comparison of CT and EUS withthe histopathological findings. Results are not specified in lymph-node regions Patient No.
CT
EUS
Histology
+
+ + +
+
+
+
+
1 2 3 4 5 6 7 8
+
+
9 10
11 12
+
+
+
+
13
+
14 15 16
+
17 Fig.2 a Echoendosccplc cross-section with theechoprobe (El insubcarinal position:sha rplyedgedlymph-node metastasis (Ll with apoorechopatte rn,left mainbronchus (LB), right mainbronchus(RB),aorta descendens (A) and vertebral column (V) b enlarged (13 lymph node (L) withastrong echopattern representing a ncnrnetastatic lymph node, left atrium (LA),aorta descendens(A)
rnnu
rect information concerning the lymph node stag e in 19 cases . Five of the se were in the group with enlarged lymph nodes and the remaining 14 had un affected lymph nodes . This gives a correct staging in 60 % of the cases. The most frequent mistak e lay in the incorr ect assumption of lymph node metastas es in 10 cases . The specificity was 65 %, and sensitivity 45 % (Table 1). Endos copic ultrasonography pr ovided accur ate information on lymph node staging in 23 cases, six were infiltrated by metastases and 17 were not. The reliability here is 72 %, whereby we counted the metastas es lying behind bronchi etc. which could not be picked up by EUS as incorrectly perceived. The specificity was 86% and sensitivity
18
+
+
19
+ +
+
20
+
21
22 23 24 25
26 27 28 29 30
+
+
+
+
+
+
+ + +
+
+
+
+ +
31
32 Total correct
(+ = LN-Metastasis, -
19
23
(5, +, 14, -)
(6, +, 17, - )
=
8x +, 14x -
no LN-Metastasis).
67 % with this method . The most frequent mistak e with this instrument was the false positive prediction, i. e. a not inconsid erable numb er oflymph nodes were wrongly assessed as infiltrated. When operating on these cases we found to our surprise that almost aUthese lymph nodes evidenced
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a
Thome. eardiovase. Surgeon 39 (1991)
G. Schilder. ll. lsrinqhuus . B. Kubale. G. Se itz, and G. W. Sybrechl
Table 2 Correctdiagnosis inpreoperative lymph-node stagingwhen CT shows enlargedlymph nodes (> 1em) (15cases)
metastasis oranth raco-silicosis onlyenlarged
CT correct
EUS
5110 0/5
5/10 5/5
anthracosilicotic changes. The per cent of miner s in the group was very high (37 %) and represents the high per cent of former miners in Saarl and. We only succeeded in working out certain criteria whi ch, in part, facilitate differentiation between anthracosilicotic and metasta ses-infiltrated lymph nodes after concluding this study. In cases of anthracosilicosis , for exampl e, minute diss eminated echoproof reflections app ear in the lymph nodes . Of the 47 % of cases which CT predicted as having enlarged lymph nodes, 67 % wer e not met astatically infiltrated. Thirt y-three per cent of the lymph oma s were assessed as free of meta stases by EUS, on the strength of th eir echo patterns. The correct pr ognosis in this group was 100 %. The remaining lymphomas were either inflamed or rea lly infiltrated by met astases. The reliability of endoscopic ultr asonograph y is therefore very high in the lymph node free of meta stases (Table 2).
Discussion
Staging is a cruci al part in the tr eatment of bron chial cancer, whereb y the lymph nod e status must be carefully considered (6). When the diagnosti c information pr ovided by conventional radiography turned out to be unsatisfactor y in terms of the involvement of the lymph nodes, mediastinoscopy pr oved to be an important diagnostic advance. However, this method is an operative procedure and carries the risk of possible - albeit seldom - complications. Greschu chn a and Maassen (3) give a morbidity rate of 1.5%-2 .5%. It is therefore not surprising tha t the introduction of computed tomography, as a non-in vasive procedure, was welcomed by all. This led to a reduction in the use of mediastino scopy and subsequent discussion as to the value of this procedure in comparison to computed tomography. Numerous reports (2, 10, 11, 12, 15, 17) pr esented comparative studies of media stinosc opy and computed tomography; the conclusion dr awn from these studies is that CT can only render mediastinoscopy partly unne cessary. Compari sons between CT and NMR have shown a slight advantage for NMR in the assessm ent of some groups of lymph nod es (7), however the higher costs and more limited availability spea k rather against its use. The rapid development of ultrasonic diagnostics with the introduction of the endoscopic ultrasonographic procedure leads to the expectat ion that this will also be used for jud ging meta stati cally infiltrat ed lymph nodes. This procedure fits with the everincre asing tendency to reach the diagnostic goal using as little invasive examination as possible. Difficulties in identifying metastatically infiltrated lymph nod es with CT 00, 12) were the reason for var ious studies on the possi ble use of ultr asoni cs. Wernecke and Za ng 09,20) report on the good represent ation of centrally located tum ors , especially in the ant erior mediastinum , using extracorporeal ultrasonics. However, reliable assess-
ment of medi astin al lymph nod es in term s of their metastatic infiltrati on is not possible. The necessary range is achieved with low frequen cy ultrasonics and so the high resolution is lost. In addition , bone and air present a sonographi c barrier. The developm ent of end oscopic ultrasono graphy (EUS) has mad e it possib le to introduce high-frequency transducers dir ectly into the gastr ointestinal tract so that this and its immediat e surroundings ca n be assess ed in high resolution. The majority opinion is that it is possible to differ entiate between norm al and meta stati cally infiltrat ed lymph nodes, as studies on cancer of the gastrointestin al tract have shown 0 , 13, 14, 16). By contrast , Ja cob et al. (5) report that ther e is no speci al echo patt ern for lymph node met astases, but this stud y was carried out using a 5 MHz B-scan probe whose poor resolution in close-up and limited presentation of detail probabl y led to this impression. Using a 7.5 or 12 MHz prob e, we achieved a correct prognosis of the lymph node stage in 72 %, where by it is necessary to str ess that metastatically infiltrated lymph nodes which lay in the sonic shadow or far away we re reckoned as not identified . By these mean s a weakness of the ultra sonic techniqu e is included in the sta tistics. If only the lymph nodes which could actually be rea ched by EUS are taken into account, the reliability was near by 80%. The high rat e of false positive prognoses, i. e. lymph nod es with a structure engendering poor echoes and sharp limits, could be explained, after the study was completed, by the lar ge numb er of miners with lymph nod es affected by anthracosilicosis in our pati ent population. Although it is known that metastatic infiltration virtually never occurs in such lymph nod es (9), it cannot be assum ed from the outset, of course, that a miner ha s hyaline callous transform ation of the lymph nodes. Endoscopic ultr asonograph y is not suitable for differentiating between a metastasis and silicosi s . Mediastinoscopy is always indicated wher e unusual lymph nodes are observe d. However , the high reliability of EUS in the identification of non- specifically enlarged, not metastatically infiltrated lymph nod es justifies forgoing a mediastinoscopy. Lymph-n ode meta stases in the interlobar cleft or of a br onchopulmonary ipsilateral nature, whether identified or not , would not hind er an oper ation, so that their not being picked up by EUS is of no consequence. If the patients with enlarged but , on EUS, unremarkable lymph nod es no longer had to undergo mediastinoscopy, this would mean a reduction of mediastinoscopy of about 30%, according to our figures , which is an advantage not only for the patient. Although EUS is an invasive procedure to some extent , we have had no complications in over 800 endoscopic ultrasonographi c examinati ons of the upper gastrointes tinal tract. The clinical importance ofEUS is emph asized by Vogel et al. in their study involving metastatically infiltrated lymph nodes ( 8); CT alone was not sufficient to establish the sta ging of bronchial carcinomas pr eoperatively. Ther e was not adequate correlation between the size of the lymph nodes and frequency of infiltration. Even in case s of lymph nodes of over two centimetres 36 % were free of tumorous tissue . Endobronchial sonography could pr ovide an inter esting complement to EUS of the mediastinum . By these mean s the br onchial wall and tumor itself could be better localized and represent ed (4). However , because of the limited range of only 1.75 cm, achieved with a 2 mm thick prob e, th is technique does not present the mediastinal lymph nodes
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302
sufficien tly well. For this. the comb ination of equipme nt mentioned in our study see ms the most reco mmendable . Accord ing to our current meth ods, lymph nodes of more than one centimetre on CT should then be exam ined using EUS. If they are jud ged to be unremarkab le her e. surgery can be carried out immediately. If, however, there is still some doubt or EUS shows a typical metastatic echo pattern , med ias tinosc opy must be the next step. Before EUS can be definitely included in routine diagnostics, how ever , further examination on a lar ger patient population is necessary.
Thom e. ca rdiova sc. S u rg eo n 3 9 (1991 ) 9
10
II
12
13
14
References 1
2
3
4
5
6 7
8
A ibe, T, T Ho. and T. Yoshida: Endosco pic ultr asonogra phy of lymp h-nodes su r rounding the upp er GI tra ct. Scan d. J. Gastroenterol. 21 (1986 ) t 64 Brian . J. P., C. Depauw. G. Kuh n. P. de Fran cquen. J. Friberg. P. Rocm ons. and 1. St ruuuen: Role of computed tomogra phy and med iastinoscopy in pre opera tive stagi ngorJung carcinoma . J . Comput. Assist. Tomogr. 9 (985) 480-484 Greschnchna. D. und ~v. Ma assen: Stad ienei nteilung und Ergebnisse der operat iven Behandlung des Bro nchialkarzinoms. Prax. Kli n. Pneumo!. 36 (982) 281 Hur te r. Th. und P. /l anra th: Endobron chiale Sonogr aphie zur Diagnosti k pulm onaler und mediastinaler Tumo ren. Dtsch. med . Wschr. 115 (1990 ) 1899 - 1905 Jakob. 11.. N. Born er, J. Lore nz . F. Schweden, R. Erbel. and II. Oelert. Mediastinal lymph-n ode staging with tra nsoeso phagea l Echography in cancer of the lung . The Europ. Ass. for Cardio -Thoraci c Surgery, 3rd Annua l Meeting. Abstract ( 989) Kon ietzk o. N.: Diagno stik un d prognostische Beurteilung des Bronchialkarz inoms . Chir urg 61 (1990) 55 1-557 Laurent. F.. 1. Drouilla rd, F. Dorcier. J. F. Veffy, 1. L. Barat , P. Grelet . C. Mar tigue. 1. Tavernier. and C. Couraud: Bronchogeni c carcinoma staging: CT versus MR imaging. Assess ment with su rge ry. Eur .-J.-ca rdiot horac ic Surg. 2 (988) 31-36 Maass en, w. . D. Gres chuch na. B. Kaiser. S. Liebig. R. Leddenk emp er. K. Stapenhorst. and JJ. Toomes: Recomm endati ons on Diagn osis, Staging and Surgical Therapy of Lung Canc er. Thora c. cardiovasc. Surgeon 36 (9 88) 295 -306
IS
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Menne. R.. K. Jun ker, and K. M. Milll er: Metastasen bosar tiger Lun gentumoren . Verh . Dtsch. Ges. Path . 68 (1984) 242 -245 Ratto, G. B., C. Frola. S . Cantoni, and G. Motta: Improving clinical efficacy of computed tomogr aphi c scan in the preoperative assessment or patients with non -small cell lun g canc er. J. Thora c. Cardiovase. Surg. 99(990) 41 6-425 Rea. JJ. H.. 1. E. Shell/and, and A. J. S. House: Accuracy of'computed tomogra phic scanning in assessment of the mediastinum in bron chial carcinoma. Thorac . ca rdiovasc. Surg . 81 (198 1) 825-8 29 S chm idt. M .. G. Schmidt, JI. G. Hickel. und W. M eiske: Zur Frage der N-Klassifikation beim prac perat lven Staging des Bronchialkarzinoms . Z. Klin. Med . 45 (1990 ) 625- 627 Schilder. G., B. Koch. G. Seitz. U. Hildebrand t, K. W. Ecke r. und G. FeifeJ: Endosonographisches Staging beim Oesophaguskarzinom : Ein pros pektiver Ver gleich mit herkbmmhchen bildgebend en Verfah ren. Fortsc hritte der gast roent. Endos kopie 20 ( 990) Takemoto . 7:. T. lto. and 7: Aibe: Endoscopic ultra sonogra phy in the diagnos is of oesop hagea l carcinoma. Endosco py 18 (1986 ) 22 Thermann. M. , JJ. Poser. K. II. M ulter-Hermelink; H. Troidl. S. Briefer. V. Amend. and D. Sch roder: Evaluation of tomogra phy and mediasti noscopy for the detection of mediastinal lymph -node metastases. Ann. Thorac. Surg. 37 (198 4) 443- 447 Tio. T. L., and G. N. 1. Tytgat: Endoscopic ultrason ography in analysing periintestina l Iymph-n ode ab nor mality. Scand. J. Gastroenter ol. 21 (1986) 158- 163 Ves tring. 711., R. A cha tzu . B. Wahlers. H N. Mo cha . und P. E. Peters: Mediastinales Stagi ng des nicht-kleinzelligen Bronchialkarzinoms. Hadiologie 30 (1990) 178-1 84 Vogel, P.. H. Deschner. 1. Lenz. und R. Sc hafe r: Uber den Zusam men hang von Lymph knotengrofle und metastati schem Befall der Lymphkn oten beim Bronchialkarzinom. Langen becks Arch. Chir. 375 (1990) 141- 144 ~Vern ecke. K.: Untersuchu ngstec hnik und lndikation der med iastina len Sonographie. ROFO 150 (1989) 501- 508 Zang. P.: Roentgenogra phy and real-time ultras onograp hy in the diagnosis of pulmonary and med iastina l les ions . Chun g-Ilua-Chieh1I0·1I0·lI si·Chih 12 11 989) 86 -88
Dr. Gerhard Schilder Chirurg ische Universitatsklinik Oskar-Ort h-Stral3e D-66 50 Homburg/ Saar Germ any
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En do s copic Ult ra so nograp hy cf the M edl a s tl nu m
Endoscopic Ultrasonography of the Mediastinum in the Diagnosis of Bronchial Carcinoma G. Schilder. H. lsrinqhaus, B. Kubale' , G. S eitz". and G. W Sybrecht:J
2
3
Dep artment of Thorac ic and Card iovascular Surgery Dep artme nt of Ra diology Dep a rtm e nt of Pathology Depa rtm e nt of Pneumology University lIospita l of Saarland. Hom bur g/Saa r , Germ any
Sum mary
Thoracic computed tomography (en is an essentia l component in the pre oper ative staging of bro nchial carcinomas as is medi astinoscopy (MSC) in cases of medi a stinal lymph oma . It is known that endoscopic ultrasonography (EUS). as a new diagnostic procedure, can pred ict lymph-node involvement in cases of tumors in the uppe r gastroi ntestinal tr a ct with an 80% probability. In a prospective stud y. we exam ined whet he r EUS could be use d to ascertain the pr esen ce of mediastinal lymph node s in cas es of bro nchial ca rcinoma . Since 1990, th er efor e, 32 patie nts with operable non -small-cell bro nchi al ca rcinoma have been exa mined with an Olympus-Aloka EU-M2 or EU-M3 (frequen cy 7.5 and 12 MHz) in addi tion to rou tin e dia gnosti cs. The gra ded cross-sectio ns of lym ph-n ode disse ctions obtained durin g subse que nt surgery se rved as evide nce as to the true or false prognos is of the lymph-node sta tus. Endoscopic ultrasonography ide ntifies the presence and estima tes the size of subca rina l, trac heo bronchial, pa ra ort al and parae sophageal lymph node s bette r than computed tomograp hy. Lymph node s lying behind org ans contai ning air (pr etracheal lymph nod es) ca n not be identifi ed by ultra sonography. Lymph -nod e involveme nt wa s correctly ident ified by EUS in 72 % of the case s, and th e specifi city was 86% . The poor se nsitivity, at 67 %. is explaine d by the high proport ion (37 %) of patients with an th racosilicosis, as the latter produces th e sa me echo pattern as malignant infiltration . In 47 % of all the cases, CT showe d enlarged medi ast inal lymph nod es whic h we re not actually infiltr ated in 6 7 %. Ofthes e lymph nod es, 33 % could be class ified a s definitely free of metas tases on the stren gth of their echo pattern , the rest were inflamed or really infiltrated by metast ases . The dia gno stic ad van tages of EUS, therefore, is tha t MSC is rendered unnecessa ry in cases of both unrem arkabl e and enla rged lymph-node stru ctures. This means a reduc tion of MSC of about 30 %. In cas es of suspected infiltra tion on EUS or silicosis, MSC is inevitable.
Key word s Non-s mall-cell lung ca nce r-Preo perative staging - Endoscopic ultr ason ography - Mediastinal lymphoma
Thorae . cardiovasc. Surge on 391 1991) 29 9-303 © Georg Th iem e Ver lag Stuttga rt . New York
Endoskopische Sonographie des Medi astinums in der lJiagn ostik des Bron chialkarzinoms Zum praoperativen Sta ging de s Bron chia lkarzinoms gehcrt ein thorakales Compute rtomogra mm (CT) un d im FaIle mediastinaler Lymphome die Medi astinoskopi e (MSK). Die Endoso nogra phie (EUS) als neues diagnostisches verfahren vermag bekanntlich bei Tumo re n des obe re n Gastrointest inaltr aktes mit eine r Wahrsch einlic hk eit von 80% eine rich tige Vorhersage des Lymphkno tenbefalls zu tr effen . In eine r pro spektiven Studie sollte untersucht werd en , ob d ie EUS auch beim Bronchialkarz inom zur Beurteilung mediast inaler Lymph knoten von Nutze n se in ka nn . Zusa tzlich zu r Routin ediagn ostik worde n des halb seit 19 90 mit eine m Olympus-Aloka EU-M2 bzw. EU-M3 (Freq uenz 7,5 und 12 MHz) 32 Patie nten mit oper abl em , nicht-kleinzelligem Bronchialkarzinom untersucht. Die Stufensch nitte der wahrend der an schliellenden Operati on entnomme nen Lym phk notendi ssektate dienten als Hefer enz filr die richtige oder falsche Vorhe rsage des Lymphknotensta tus . Besser als im CT geHngt der EUS die Darstellung und GroBenbeurteilung der subkari nalen, tr a cheobronchialen , pa ra a ort ale n und paraosophageal en Lymph knoten. Hinter lufthalugen Stru kturen liegende Lymphknoten [pr atracheale Lymphknoten) konn en nieht so nogra phiert werden . Insgesamt wird der Lymphknotenbefall du rch die EUS in 72% richtig vorherges agt , die Spezifltat betragt 86%. Die schlechte Sensitlvitat von 67 % wird durch eine n hohen Anteil (37 %) von Patien ten mit Anthrakosilikose erklarba r, da hierb ei da s gleiche Echomuster wie bei der malignen Infiltration vorliegt .
In 47 % aller Falle zeigt das CT vergroflerte Medi astinallymphknoten , die jedoc h zu 67 % nicht infiltriert waren . 33 % dieser Lymp hknoten kon nten aufgrund ihres Echomusters als siehe r me tast asenfr ei eingestuft werden. die iibrigen waren entziindli ch vera ndert ode r tatsac hllch me ta statisch infiltriert. Der diagno stische Gewinn dur ch die EUS liegt also darin, im Faile unauffalliger Lymphknotenstrukturen . a uch bei vergrbBert en Lymphknoten die MSK iiberfliissig zu machen . Die Einspa run g betragt ca. 30 %. Bei endoso nographischem Verdacht au f Infiltr ati on ode r bei Silikose wird na eh wie vor a uf die MSK nicht zu verzicht en sein.
Received for Publication: June 3, 1991
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I
Thome . eardiooase. Surgeon 39 (1991)
G. Schilder. 11. Isringhaus , B. Kubale, G. Seitz . and G. W. Sybrecht
a
Introdu ction Ultraso nics play a relatively unimp ort ant role in the pr eoper ative staging of bron chial carc ino mas , with the exception of ab dominal ultr asonography, despite the fact that reports on tr ansth oracic ultr asonograp hy showing the mediastin al structures have often appeared (14, 15). Bone an d air, however, still obst ruct reliable assessment, especially of the lymph nodes. The development of endosco pic ultraso nics (EUS) has mad e it possible for high freque ncy sonic probes to be intro duced into the body thus makin g ana tomic structures visible in high resolution . With EUS of the upp er gast rointest inal tract the wall of the stomach and intestines with its various anatomic layer s can be rende red visible, as can the immediate surro undings . In our prospective study on esophageal carcinoma patients we could prove that, in terms' of preoperative assessment of tumor infiltrati on and Iymphnode sta tus, EUS is more successful than either CT or nuclear magnetic resonance (13). Metastatic infiltration of the lymph nodes was prognosed correctly in 80% of the cases, whereas this was possible in only 50% when using computed tomography (CT) and magnetic resona nce imaging (NMR) . Stimulated by these facts, in the following study we wanted to ascertain whether high-frequency endoscopic ultra sonography can also be used profitably in the preoper ative staging of bron chial carcinomas .
b
Materials a nd Met hods Endoscopic ultrasonic exami nation was included in the routine diag nostics for all patients with a non-small-cell bronch ial carcinoma who were to be operated on. This was under taken either immediately preoperatively on the anesth etized patie nt, with ap prop riate consent. or as an isolated examination in our Endoscopic section. The Olympus-Aloka EU-M2 and . most recently. EUM3 were used for endos copic ultrasonography. This is a side -view endoscope of 13 mm diameter with a rotating transducer on its tip (Fig. 1). The frequency is 7.5 MHz. and the new model can be switched to 12 MH z if desired. A wat er-bag provides optimal sonographi c coupling. The instrument is passed through the mouth into the esophagus like a gastroscope . In conscious patients, the procedure is carried out in the left lateral position in order to limit the risk of aspiration. The gagging impulse is reduced by local anesthesia of the pharynx, a small premedication is occasion ally necessar y using O.4-0.6 mg Rohypno1. The transducer is then fed into the esophagus with slow movements as far as the stomac h. Here , routinely, the lymph nodes of the coeliac tr unk, the grea ter and lesser curvature, are viewed before the structures bordering on the esophagus are illustrated once more du ring the slow withdrawal of the instru ment. Sharply edged lymph nodes of an y size eliciting a poor echo are noteworthy. These wer e classified as metastatically infiltrated . Lymph nodes of unclearly edged structure giving ofT a strong echo are un remarkab le (Fig. 2). Computed tomograms were generated on a Siemens Somatom Plus or Somatom DR2. Mediastinoscopy was only carried out when media stinal or hilar lymph nodes of over a centimetre in size were detected . In thes e case s EUS was always undert aken before the mediastinoscopy, so tha t the examine r did not know the results of the latter. The type and extent of the operative interventio n was dictated by the location and the preoperatively, as well as intraoperatively, established sp read of the pulmonary tumor. An am ple lymph node dissectio n was untertaken in every case , as the minimum lymph node treatment recommended by the Ger man Society for Thoracic and cardiovascular Surgery (8). The graded cross-sections oflymph node dissections were pathologically evaluated according to their
Fi g. 1a Olympusect oenooscope (EU-M 3) witharotatingechoprobeonthe tip and with a switchablefrequency adapter b Magnifiedview of theechoprobeandtheside-view optic (withoutthe waterballoon)
location as given by the surgeon . All the documented results from CT, EUS and surgical findings were compared with the histopat hological results. By these mea ns it was possible to assess correct and incorre ct prognose s concerni ng the lymph node status.
Results Thirty-thr ee patients pr esent ed for exam ination, but in one case a narrow pharynx render ed endosco py impossible. There were no complications . Thus thirty-two patients with non-small-cell bron chial carcinoma could be evaluat ed. In all cases the subcarina l, par aesophageaI. an d hila r lymph nodes receptive to the tra nsduce r were reliably well prese nted. The paratr acheal , tra cheobron chial, and subaorta l lymph nodes could mostly be well detec ted. The pretrac hea l lymph nodes were not repr esent ed , nor were all those which, from the tr an sducer 's position, lay behind a bron chus containing air or other echoproof structur e. In seven cases (22 %) with a cent rally located tumor this, too, was pr esented. Infiltra tion as far as or into the pulmonar y artery and the pericardium, especially at the level of the left atrium, was clearly sh own (Fig. 3). Ofthe 32 patients, 15 (47%) had enlarged mediastin al lymph nodes, and therefo re suspected infiltr ation, according to CT, while the re maining 17 had lymp h nodes of less than one centimetre. Computed tomography gave the cor -
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Thomc. cardiovasc. Surgeon 39 (1991)
Endoscopic Ultrasonography cfthe Mediastinum
301
Fig.3 hypoechoictumor (T) with infiltrationof the pericardium atthelevelof the left atrium
b
Table 1 Prognosis of lymphnode staging. Comparison of CT and EUS withthe histopathological findings. Results are not specified in lymph-node regions Patient No.
CT
EUS
Histology
+
+ + +
+
+
+
+
1 2 3 4 5 6 7 8
+
+
9 10
11 12
+
+
+
+
13
+
14 15 16
+
17 Fig.2 a Echoendosccplc cross-section with theechoprobe (El insubcarinal position:sha rplyedgedlymph-node metastasis (Ll with apoorechopatte rn,left mainbronchus (LB), right mainbronchus(RB),aorta descendens (A) and vertebral column (V) b enlarged (13 lymph node (L) withastrong echopattern representing a ncnrnetastatic lymph node, left atrium (LA),aorta descendens(A)
rnnu
rect information concerning the lymph node stag e in 19 cases . Five of the se were in the group with enlarged lymph nodes and the remaining 14 had un affected lymph nodes . This gives a correct staging in 60 % of the cases. The most frequent mistak e lay in the incorr ect assumption of lymph node metastas es in 10 cases . The specificity was 65 %, and sensitivity 45 % (Table 1). Endos copic ultrasonography pr ovided accur ate information on lymph node staging in 23 cases, six were infiltrated by metastases and 17 were not. The reliability here is 72 %, whereby we counted the metastas es lying behind bronchi etc. which could not be picked up by EUS as incorrectly perceived. The specificity was 86% and sensitivity
18
+
+
19
+ +
+
20
+
21
22 23 24 25
26 27 28 29 30
+
+
+
+
+
+
+ + +
+
+
+
+ +
31
32 Total correct
(+ = LN-Metastasis, -
19
23
(5, +, 14, -)
(6, +, 17, - )
=
8x +, 14x -
no LN-Metastasis).
67 % with this method . The most frequent mistak e with this instrument was the false positive prediction, i. e. a not inconsid erable numb er oflymph nodes were wrongly assessed as infiltrated. When operating on these cases we found to our surprise that almost aUthese lymph nodes evidenced
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a
Thome. eardiovase. Surgeon 39 (1991)
G. Schilder. ll. lsrinqhuus . B. Kubale. G. Se itz, and G. W. Sybrechl
Table 2 Correctdiagnosis inpreoperative lymph-node stagingwhen CT shows enlargedlymph nodes (> 1em) (15cases)
metastasis oranth raco-silicosis onlyenlarged
CT correct
EUS
5110 0/5
5/10 5/5
anthracosilicotic changes. The per cent of miner s in the group was very high (37 %) and represents the high per cent of former miners in Saarl and. We only succeeded in working out certain criteria whi ch, in part, facilitate differentiation between anthracosilicotic and metasta ses-infiltrated lymph nodes after concluding this study. In cases of anthracosilicosis , for exampl e, minute diss eminated echoproof reflections app ear in the lymph nodes . Of the 47 % of cases which CT predicted as having enlarged lymph nodes, 67 % wer e not met astatically infiltrated. Thirt y-three per cent of the lymph oma s were assessed as free of meta stases by EUS, on the strength of th eir echo patterns. The correct pr ognosis in this group was 100 %. The remaining lymphomas were either inflamed or rea lly infiltrated by met astases. The reliability of endoscopic ultr asonograph y is therefore very high in the lymph node free of meta stases (Table 2).
Discussion
Staging is a cruci al part in the tr eatment of bron chial cancer, whereb y the lymph nod e status must be carefully considered (6). When the diagnosti c information pr ovided by conventional radiography turned out to be unsatisfactor y in terms of the involvement of the lymph nodes, mediastinoscopy pr oved to be an important diagnostic advance. However, this method is an operative procedure and carries the risk of possible - albeit seldom - complications. Greschu chn a and Maassen (3) give a morbidity rate of 1.5%-2 .5%. It is therefore not surprising tha t the introduction of computed tomography, as a non-in vasive procedure, was welcomed by all. This led to a reduction in the use of mediastino scopy and subsequent discussion as to the value of this procedure in comparison to computed tomography. Numerous reports (2, 10, 11, 12, 15, 17) pr esented comparative studies of media stinosc opy and computed tomography; the conclusion dr awn from these studies is that CT can only render mediastinoscopy partly unne cessary. Compari sons between CT and NMR have shown a slight advantage for NMR in the assessm ent of some groups of lymph nod es (7), however the higher costs and more limited availability spea k rather against its use. The rapid development of ultrasonic diagnostics with the introduction of the endoscopic ultrasonographic procedure leads to the expectat ion that this will also be used for jud ging meta stati cally infiltrat ed lymph nodes. This procedure fits with the everincre asing tendency to reach the diagnostic goal using as little invasive examination as possible. Difficulties in identifying metastatically infiltrated lymph nod es with CT 00, 12) were the reason for var ious studies on the possi ble use of ultr asoni cs. Wernecke and Za ng 09,20) report on the good represent ation of centrally located tum ors , especially in the ant erior mediastinum , using extracorporeal ultrasonics. However, reliable assess-
ment of medi astin al lymph nod es in term s of their metastatic infiltrati on is not possible. The necessary range is achieved with low frequen cy ultrasonics and so the high resolution is lost. In addition , bone and air present a sonographi c barrier. The developm ent of end oscopic ultrasono graphy (EUS) has mad e it possib le to introduce high-frequency transducers dir ectly into the gastr ointestinal tract so that this and its immediat e surroundings ca n be assess ed in high resolution. The majority opinion is that it is possible to differ entiate between norm al and meta stati cally infiltrat ed lymph nodes, as studies on cancer of the gastrointestin al tract have shown 0 , 13, 14, 16). By contrast , Ja cob et al. (5) report that ther e is no speci al echo patt ern for lymph node met astases, but this stud y was carried out using a 5 MHz B-scan probe whose poor resolution in close-up and limited presentation of detail probabl y led to this impression. Using a 7.5 or 12 MHz prob e, we achieved a correct prognosis of the lymph node stage in 72 %, where by it is necessary to str ess that metastatically infiltrated lymph nodes which lay in the sonic shadow or far away we re reckoned as not identified . By these mean s a weakness of the ultra sonic techniqu e is included in the sta tistics. If only the lymph nodes which could actually be rea ched by EUS are taken into account, the reliability was near by 80%. The high rat e of false positive prognoses, i. e. lymph nod es with a structure engendering poor echoes and sharp limits, could be explained, after the study was completed, by the lar ge numb er of miners with lymph nod es affected by anthracosilicosis in our pati ent population. Although it is known that metastatic infiltration virtually never occurs in such lymph nod es (9), it cannot be assum ed from the outset, of course, that a miner ha s hyaline callous transform ation of the lymph nodes. Endoscopic ultr asonograph y is not suitable for differentiating between a metastasis and silicosi s . Mediastinoscopy is always indicated wher e unusual lymph nodes are observe d. However , the high reliability of EUS in the identification of non- specifically enlarged, not metastatically infiltrated lymph nod es justifies forgoing a mediastinoscopy. Lymph-n ode meta stases in the interlobar cleft or of a br onchopulmonary ipsilateral nature, whether identified or not , would not hind er an oper ation, so that their not being picked up by EUS is of no consequence. If the patients with enlarged but , on EUS, unremarkable lymph nod es no longer had to undergo mediastinoscopy, this would mean a reduction of mediastinoscopy of about 30%, according to our figures , which is an advantage not only for the patient. Although EUS is an invasive procedure to some extent , we have had no complications in over 800 endoscopic ultrasonographi c examinati ons of the upper gastrointes tinal tract. The clinical importance ofEUS is emph asized by Vogel et al. in their study involving metastatically infiltrated lymph nodes ( 8); CT alone was not sufficient to establish the sta ging of bronchial carcinomas pr eoperatively. Ther e was not adequate correlation between the size of the lymph nodes and frequency of infiltration. Even in case s of lymph nodes of over two centimetres 36 % were free of tumorous tissue . Endobronchial sonography could pr ovide an inter esting complement to EUS of the mediastinum . By these mean s the br onchial wall and tumor itself could be better localized and represent ed (4). However , because of the limited range of only 1.75 cm, achieved with a 2 mm thick prob e, th is technique does not present the mediastinal lymph nodes
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sufficien tly well. For this. the comb ination of equipme nt mentioned in our study see ms the most reco mmendable . Accord ing to our current meth ods, lymph nodes of more than one centimetre on CT should then be exam ined using EUS. If they are jud ged to be unremarkab le her e. surgery can be carried out immediately. If, however, there is still some doubt or EUS shows a typical metastatic echo pattern , med ias tinosc opy must be the next step. Before EUS can be definitely included in routine diagnostics, how ever , further examination on a lar ger patient population is necessary.
Thom e. ca rdiova sc. S u rg eo n 3 9 (1991 ) 9
10
II
12
13
14
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4
5
6 7
8
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Dr. Gerhard Schilder Chirurg ische Universitatsklinik Oskar-Ort h-Stral3e D-66 50 Homburg/ Saar Germ any
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En do s copic Ult ra so nograp hy cf the M edl a s tl nu m
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