Medical Thoracoscopy vs CT Scan-Guided Abrams Pleural Needle Biopsy for Diagnosis of Patients With Pleural Effusions

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1 CHEST Originl Reserch PLEURAL DISEASE Medicl Thorcoscopy vs CT Scn-Guided Abrms Pleurl Needle Biopsy for Dignosis of Ptients With Pleurl Effusions A Rndomized, Controlled Tril Muzffer Metints, MD; Guntulu Ak, MD; Emine Dundr, MD; Huseyin Yildirim, MD; Rgip Ozkn, MD; Emel Kurt, MD; Sinn Erginel, MD; Fusun Alts, MD; nd Selm Metints, MD, PhD Bckground: In cses of pleurl effusion, tissue smples cn be obtined through Abrms needle pleurl biopsy (ANPB), thorcoscopy, or cutting-needle pleurl biopsy under the guidnce of CT scn (CT-CNPB) for histopthologic nlysis. This study imed to compre the dignostic efficiency nd relibility of ANPB under CT scn guidnce (CT-ANPB) with tht of medicl thorcoscopy in ptients with pleurl effusion. Methods: Between Jnury 2006 nd Jnury 2008, 124 ptients with exudtive pleurl effusion tht could not be dignosed by cytologic nlysis were included in the study. All ptients were rndomized fter the CT scn ws performed. Ptients either underwent CT-ANPB or thorcoscopy. The two groups were compred in terms of dignostic sensitivity nd complictions ssocited with the methods used. Results: Of the 124 ptients, mlignnt mesotheliom ws dignosed in 33, metsttic pleurl disese in 47, benign pleurl disese in 42, nd two were of indeterminte origin. In the CT-ANPB group, the dignostic sensitivity ws 87.5%, s compred with 94.1% in the thorcoscopy group; the difference ws not sttisticlly significnt ( P 5.252). No difference ws identified between the sensitivities of the two methods bsed on the cuse, the CT scn findings, nd the degree of pleurl thickening. Compliction rtes were low nd cceptble. Conclusion: We recommend the use of CT-ANPB s the primry method of dignosis in ptients with pleurl thickening or lesions observed by CT scn. In ptients with only pleurl fluid ppernce on CT scn nd in those who my hve benign pleurl pthologies other thn TB, the primry method of dignosis should be medicl thorcoscopy. Tril registrtion: clinicltrils.gov; Identifier: NCT CHEST 2010; 137(6): Abbrevitions: CT-ANPB 5 CT scn-guided Abrms needle pleurl biopsy; CT-CNPB 5 CT scn-guided cuttingneedle pleurl biopsy; df 5 degrees of freedom Pleurl effusions re often the presenting feture of pleurl disese. If clinicl suspicion of mlignncy is high in ptients with such finding, cytologic exmintion of pleurl fluid smples is recommended. 1 When cytology is nondignostic, closed percutneous needle biopsy hs trditionlly been performed blindly using reverse-beveled needle, such s n Abrms or Rmel needle. 2-4 However, needle biopsy for pleurl tissue ws dignostic in only 50% of ptients presenting with mlignnt effusions. 5 For this reson, the role of closed pleurl needle biopsy in dignosing mlignnt effusions hs been questioned Medicl thorcoscopy for cses of exudtive pleurl effusion not hving ny dignosis by either clinicl, rdiologic, lbortory, or cytologic investigtion 7,8 is the method tht hs been performed routinely in mny clinics. In recent yers, some uthors suggest tht rel time CT scn-guided cutting-needle pleurl biopsy (CT-CNPB), performed by rdiologist, is promising technique for smpling the pleur, becuse it cn improve dignostic sensitivity to bout 80% for pleurl mlignncy. 6,9-11 On the other hnd, some uthors hve suggested tht further detiled studies to determine the reltionship Originl Reserch

2 between the mount of pleurl thickening nd the dignostic sensitivity of the Abrms needle biopsy re needed. 5,12 Abrms needle biopsy is esy to use, sfe, inexpensive, nd rpid, nd cn be performed s bedside procedure in the deprtment. 5 Actully, the only dvntge of imge-guided cutting needle biopsy is the CT scn guidnce. Therefore, if we cn use CT scn guidnce for biopsies performed with n Abrms needle, we cn increse the sensitivity of this trditionl method. Additionlly, it hs been pointed out tht prospective studies re needed to compre the sensitivity nd the costeffectiveness of closed pleurl biopsy with Abrms needle with thorcoscopy in the setting of pleurl mlignncy nd TB. 5,10,12 In this study, we compred the dignostic sensitivity nd sfety of medicl thorcoscopy with Abrms needle pleurl biopsy under CT scn guidnce (CT-ANPB) in ptients with pleurl effusion who require pleurl tissue smpling. Mterils nd Methods This prospective, rndomized, prllel study ws conducted in the Chest Diseses Deprtment of the Medicl Fculty of Eskisehir Osmngzi University from Jnury 2006 to Jnury The study ws pproved by the Ethicl Committee of Eskisehir Osmngzi University Medicl Fculty ( nd 2006/387). Ptients Ptients with the following criteri were dmitted to prticipte in the study: evidence of exudtive pleurl effusion for which specific dignosis could not be determined by cytologic exmintion nd willingness to prticipte in the study nd undergo n invsive procedure. Exclusion criteri were s follows: ptients, 18 or. 85 yers old, pleurl thickening or pleurl-bsed mss without pleurl effusion in rdiologic investigtion, presence of prpneumonic effusion, ny contrindiction for pleurl biopsy or medicl thorcoscopy, or ny other systemic disese tht could ffect CT scn. Ptients were thoroughly informed before rndomiztion into the study, nd their written consent ws requested. Mnuscript received April 10, 2009; revision ccepted Jnury 6, Affilitions: From the Deprtment of Chest Diseses (Drs M. Metints, Ak, Yildirim, Kurt, Erginel, nd Alts), the Deprtment of Pthology (Dr Dundr), the Deprtment of Rdiology (Dr Ozkn), nd the Deprtment of Public Helth (Dr S. Metints), Eskisehir Osmngzi University Medicl Fculty, Eskisehir Osmngzi University, Eskisehir, Turkey. Funding/Support: This study hs been supported by the Reserch Fund of Eskisehir Osmngzi University (Project Number: ). Correspondence to: Muzffer Metints, MD, Deprtment of Chest Diseses, Eskisehir Osmngzi University Medicl Fculty, Eskisehir, Turkey 26040; e-mil: muzffermetints@gmil.com. Reproduction of this rticle is prohibited without written permission from the Americn College of Chest Physicins ( site/misc/reprints.xhtml ). DOI: /chest Ptients were rndomized fter being hospitlized, nd contrst enhncement CT scn of ll ptients ws tken first with the Toshib Aquill 64 MDBT device (Tokyo, Jpn). The thorx ws scnned t thickness of 5 mm from the pex of the lungs to the costophrenic recess. Before the nlysis, 80 ml of nonionic contrst substnce ws dministered through n rm vein, nd the scn ws initited 30 s fter the infusion of contrst medium. Findings were clssified s in previous relevnt publictions. 13,14 Rndomiztion ws crried out in complince with the Consolidted Stndrds of Reporting Trils sttement recommendtions. A totl of 31 envelopes were prepred t once for rndomiztion. In ech sequence four crds were prepred, two mrked s A nd two mrked s B, which were then inserted into ech envelope. Ptients who picked the A crd underwent CT- ANPB, nd those who picked B underwent thorcoscopy. After completion of the preceding rndomiztion sequence for four ptients, new envelope ws initited. Ptients in rm A who hd filed dignosis by CT-ANPB underwent medicl thorcoscopy. Ptients for whom precise dignosis could not be determined fter medicl thorcoscopy underwent second thorcoscopy or dignostic thorcotomy on their consent. Ptients who rejected these options nd those with sbestos-relted benign pleurl disese, TB, or nontuberculous benign cuses were followed with minimum follow-up period of 12 months. CT-ANPB nd Medicl Thorcoscopy Abrms biopsy procedures were performed in rm A just fter determintion of the entry site with the id of CT scn, which ws obtined before the procedure. The entry site ws selected s the most suitble nd ccessible prt of the lesion by looking t the hrd copy of the CT scns while ptients were in the bronchoscopy room. The distnce between the entry site nd the trget point ws mesured two-dimensionlly by thorcic CT scns. For instnce, Figure 1A shows tht the entry site ws 13 cm wy from the bottom edge of the scpul nd 7 cm wy from the spinl process of the vertebre. In nother exmple, the entry site ws 0.5 cm bove the crin horizontlly nd 9 cm wy from the midsternl line lterlly ( Fig 1 B ). Mesurements were mde ccording to the scle locted on CT scns. After tking the mesurements described bove, the entry site for Abrms needle ws mrked on the skin of the ptient s the corresponding point for the lesion on the CT scn. Four to six biopsy specimens were tken from the prietl pleur using Abrms needle through the sme entry point by n experienced pulmonologist (G. A.) in bronchoscopy/thorcoscopy room. 15 Medicl thorcoscopy ws done with rigid thorcoscope (Krl Storz; Tuttlingen, Germny) under mild sedtion nd locl nesthesi by tem tht consisted of M. M. plus G. A. or M. M. plus H. Y. At lest six biopsy specimens were tken from bnorml sites of prietl pleur t thorcoscopy. After ech procedure, the biopsy specimens were immeditely fixed in formlin nd sent to the pthology deprtment for histopthology nlysis. If suspicion of tuberculous pleurisy ws high, then one further biopsy specimen ws sent to the lbortory in n isotonic sline solution for bcteriologic investigtion, including serch for Mycobcterium tuberculosis. Biopsy smples were evluted by the sme pthologist in the Eskisehir Osmngzi University Medicl Fculty Pthology Deprtment. The cses were ctegorized primrily s benign nd mlignnt, nd those tht were mlignnt were lso ctegorized ccording to the cell properties. Immunohistochemicl stins were used to differentite tumors of mesothelil origin from those of epithelil origin. Among these, there were ntibodies, such s crcinoembryonic ntigen, Ber Ep4, B 72.3, nd CD 15 (Leu M1), s well s mesothelil cell determinnts, such CHEST / 137 / 6 / JUNE,

3 Figure 1. Choosing the entry site for CT scn-guided Abrms needle pleurl biopsy. Exmples of n entry site wy from the bottom edge of the scpul nd from the spinl process of the vertebre (A) nd bove the crin horizontlly nd wy from the midsternl line lterlly (B). s clretinin, Wilms tumor 1, thrombomodulin, nd cytokertin 5/6. Additionlly, epithelil membrne ntigen, vimentin, p53, nd wide-spectrum kertin were used when required. The pthologist lso stined the specimens with Ziehl-Neelsen to investigte for cid-resistnt bcilli ( M tuberculosis ). Sttisticl Anlysis Considering tht the dignostic sensitivity ws 90% for thorcoscopy16 nd 80% for CT-ANPB, 17 smple size needed for this study ws estimted t minimum of 48 ptients in ech rm, with power of 80% nd significnce of 5%. However, we extended the number of ptients up to 62 for both rms in cse some ptients were excluded in the course of the study. The primry end point of this study ws the determintion of sensitivity nd compliction rte of both invsive methods in the dignosis of pleurl diseses. SPSS version 12.0 softwre (SPSS Inc.; Chicgo, IL) ws used for sttisticl nlysis. Sensitivities were compred using the x 2 test. Results The totl number of ptients included in the study ws 124, with 72 men nd 52 women; the men ge ws yers. The distribution of dignoses for ptients included in the study is shown in Tble 1. The rndomiztion digrm-tril profile of ptients in the study is shown in Figure 2. Thorcoscopy ws performed on 62 ptients, 33 (53%) men nd 29 (47%) women. The men ge ws yers ( r, 27-85). CT-ANPB ws performed on 62 ptients, 39 (63%) men nd 23 (37%) women. The men ge ws yers ( r, 22-84). There were no differences in terms of sex ( x ; degrees of freedom [ df ] 5 1; P 5.27), ge (t ; df 5 122; P 5.90), the distribution of dignoses between the two groups ( x ; df 5 2; P 5.921), or the distribution of mlignnt cses inside the groups ( x ; df 5 2; P 5.848). Two cses were of indeterminte origin. Becuse these two ptients died fter, but unrelted to, thorcoscopy, finl dignosis could not be reched. As seen in Figure 2, 48 of 62 ptients who underwent CT-ANPB were evluted fter dignosis. Dignostic sensitivity of CT-ANPB for 48 ptients with mlignnt or tuberculous pleurl effusion ws 87.5% (42/48). For the thorcoscopy group, 51 ptients of the 62 ptients who underwent thorcoscopy were evluted fter dignosis. Dignostic sensitivity of thorcoscopy for 51 ptients with mlignnt or tuberculous pleurl effusion ws 94.1% (48/51). There ws no significnt difference between the two methods regrding dignostic sensitivity ( x ; df 5 1; P 5.252). Dignosis ws chieved with the use of thorcoscopy in four of six ptients in whom specific dignosis ws not reched with CT-ANPB. The finl dignoses for these four ptients were s follows: mesotheliom in two, lung cncer metstsis in one, nd other orgn metstsis in one. We could not chieve dignosis in two ptients with thorcoscopy. Tuberculous pleurisy ws dignosed in one of these ptients cliniclly becuse of n elevted denosine deminse level (68 units/dl); this ptient improved with nti-tb tretment. In the other ptient, fter Tble 1 Distribution of Dignoses of 124 Ptients Included in the Study Dignosis No. % Mlignnt mesotheliom Mlignnt pleurl effusion due to lung cncer Mlignnt pleurl effusion due to other orgn crcinoms Tuberculous pleurisy Benign sbestos pleurisy Rheumtoid pleurisy Uremic pleurl effusion Chronic crdic filure Rdiotherpy-relted pleurl effusion Virl pleurl effusion Prmlignnt pleurl effusion Indeterminte cses Originl Reserch

4 Figure 2. Rndomiztion tril profile of the ptients. CT-ANPB 5 CT scn-guided Abrms needle pleurl biopsy. 6 months of follow-up the pleurl fluid nd clinicl signs of mlignnt disese becme bundnt gin, nd with second thorcoscopy mesotheliom hs been dignosed in the ptient. Rtes of sensitivities for both methods regrding the dignosis re shown in Tble 2. Dignostic sensitivity of CT-CNPB for 38 mlignnt cses ws 86.8% (33/38; 95% CI, 76.1%-97.5%); the sme rte for thorcoscopy ws 95.2% (40/42; 95% CI, 88.7%-100%). There ws no sttisticl difference between the two methods for ll mlignnt cses ( x ; df 5 1; P 5.184). Tble 3 shows the sensitivity of the two methods regrding rdiologic chrcteristics for CT scn of the thorx. Three of 11 ptients with smooth pleurl thickening showed no positive result with CT-ANPB. Of these three ptients, two hd mlignnt mesotheliom nd one hd tuberculous pleurisy. One of two cses of mlignnt mesotheliom ws ble to be dignosed using thorcoscopy, wheres disese in the other two ptients ws not ble to be dignosed using thorcoscopy. On exmintion of Tble 3, we cn see tht only four of 99 (4%) ptients hd pleurl effusion without thickened pleur. Any kind of pleurl chnge could be observed in other ptients. We evluted whether pleurl thickness ffects dignostic sensitivity of both methods. The findings re shown in Tble 4. Of the 27 cses, 22 (82%) with pleurl thickening, 1 cm were dignosed with CT-ANPB nd 25 of 27 (93%) by thorcoscopy; no sttisticl difference ws seen. For both methods there ws lso no sttisticl difference in cses with pleurl thickening. 1 cm. The type nd frequency of complictions for both methods is shown in Tble 5. In one ptient from the Abrms needle group who hd pleurl fluid on CT scn but no pleurl thickening, hemorrhge occurred fter the procedure, which required tube thorcostomy nd blood trnsfusion. No further tretment ws required for this cse. Pneumothorx occurred in one cse in the Abrms group. Tube thorcostomy for 3 dys ws required to tret the pneumothorx. Percutneous emphysem round the entry site, which occurred frequently in the thorcoscopy group, ws not observed in ny cse in the Abrms group. Discussion Although CT-CNPB nd medicl thorcoscopy hve higher dignostic yield thn closed pleurl biopsy in mlignnt disese, both re more expensive nd time consuming. 16,18-20 Imge-guided pleurl biopsy, on the other hnd, cn be performed in outptient conditions 9,10,19 nd cn be used in ptients without pleurl effusion. It requires n experienced rdiologist, disposble cutting biopsy needle, nd extr use of CT scnning, nd it must be performed in the rdiology deprtment. As n lterntive, CNPB cn be performed under ultrsound guidnce. 6-11,19,21 Tble 2 Sensitivity Rtes of CT Scn-Guided Abrms Needle Pleurl Biopsy nd Thorcoscopy CT-ANPB Thorcoscopy Dignosis No. Performed Sensitivity (%) No. Performed Sensitivity (%) P Vlue Mlignnt mesotheliom (80) (94).308 Mlignnt pleurl effusion (93) (100) cused by lung cncer Pleurl metstsis due to other 8 7 (88) 10 9 (90) orgn crcinoms Tuberculous pleurisy 10 9 (90) 9 8 (89) CT-ANPB 5 CT scn-guided Abrms needle pleurl biopsy. Two-sided Fisher exct test. CHEST / 137 / 6 / JUNE,

5 Tble 3 Sensitivity of the Two Methods According to the Distribution of Pleurl Pthologies Observed in CT Scns CT-ANPB Thorcoscopy CT Scn Findings No. Performed Sensitivity (%) No. Performed Sensitivity (%) P Vlue Only pleurl effusion Circumferentil nodulr pleurl involvement Seprte nodulr involvement 9 8 (89) (92) Irregulr pleurl thickening (92) (95) Smooth pleurl thickening 11 8 (73) (100).214 Pleurl bsed mss with effusion 1 1 See Tble 2 for expnsion of bbrevition. Two-sided Fisher exct test. Some uthors suggest tht the technique of Abrms needle pleurl biopsy still hs plce in the dignosis of exudtive pleurl effusions nd should not be bndoned becuse of its lower cost nd its reltively high sfety, simplicity, nd dignostic sensitivity for metsttic pleurl diseses nd tuberculous pleurisy. 5,12,22 The limittion of Abrms biopsy is the blindness of the procedure. In the thorcoscopic procedure, smple is tken on visul observtion, which overcomes this problem, nd the dignostic sensitivity is notbly incresed. Use of cutting needle biopsy under CT scn guidnce overcomes this problem. 6 When the thick or seemingly problemtic pleurl zone is locted using CT scn, dignostic sensitivity is incresed to. 80%. 11,19 Could this not be performed in bronchoscopy suite s for Abrms needle? If it could, it would bring bout two dvntges: First, simple nd inexpensive method such s Abrms pleurl biopsy could be pplied; second, CT scn guidnce would be ensured in the bronchoscopy room. The ide for the present study rose in light of the bove discussion. We performed Abrms needle biopsy using stndrd procedures. The only difference ws to mrk the most probble lesion re on the ptient s skin, s determined by CT scn of the thorx before the biopsy procedure ( Fig 1 ). Becuse CT scn ws lredy obtined for these ptients, our ppliction did not ber ny dditionl cost to the stndrd ppliction of Abrms needle. In conclusion, we did not find ny significnt difference between the sensitivity of the procedures (87.5% vs 94.1%; P 5.252). Regrding the dignosis of mlignnt pleurl diseses or tuberculous pleurisy, there ws no sttisticl difference between the sensitivities of the two methods (86.8%-95.2%, P for mlignnt diseses nd 89%-90%, P for tuberculous pleurisy). The sensitivity of both methods ws similr in ptients with mlignnt pleurl effusion due to either lung or other cncer nd tuberculous pleurisy. There ws smll but nonsignificnt difference between the two methods (80% vs 94%) in mlignnt mesotheliom. We previously reported tht the success rte of CT-ANPB ws 83% in mesotheliom, finding which is similr to the present study. 17 In our study, no difference ws found between the two methods in terms of the CT scn ppernce of pleurl pthology ( Tble 3 ). When n nlysis ws mde regrding the pleurl thickness, no difference could be found between the two methods in our series. In the study by Mskell nd collegues, 6 for ptients with pleurl thickness, 5 mm the sensitivity of CT scn-guided needle biopsy ws 75%. Therefore, if CT scn-guided biopsy is performed in cses with minor pleurl thickness, there my be lower probbility tht sufficient mount of tissue will be obtined. However, Abrms needle is cpble of obtining lrger smples; thus, the difficult smpling problem ssocited with tht group of ptients my not be encountered with Abrms needle. CT-CNPB cn be performed in ptients with pleurl thickness without pleurl fluid, which is not convenient when using Abrms needle. However, the rte of ptients without fluid is, 10%, nd most of them re benign sbestos pleurisy or fibrothorx. 13,14 Tble 4 Sensitivity of the Two Methods Regrding the Presence of Pleurl Thickness in CT Scn of the Thorx CT-ANPB Thorcoscopy Pleurl Thickening No. Performed Sensitivity (%) No. Performed Sensitivity (%) P Vlue 1 cm (95) (96) 1.000, 1 cm (82) (93).420 P vlue See Tble 2 for expnsion of bbrevition. Two-sided Fisher exct test Originl Reserch

6 Tble 5 Complictions of Dignostic Methods Complictions CT-ANPB (n 5 62) Thorcoscopy (n 5 62) Minor bleeding 2 2 Mjor bleeding 1 0 Hypotension 4 3 Syncope 1 0 Pin b 3 4 Fever 0 2 Percutneous 0 10 emphysem Extended ir lekge c 0 2 Pneumothorx 1 0 Percutneous edem 2 0 Wound infection d 0 1 Nuse 0 1 See Tble 2 for expnsion of bbrevition. Bleeding t level requiring tube thorcostomy nd blood trnsfusion. b Pin requiring dditionl nlgesic. cair lekge. 3 d. d Infection limited to the wounded re, which recovers fully with ntibiotics. In both cses, biopsy would not be sufficient for the finl dignosis, which requires further clinicl nd rdiologic investigtions s well s follow-up. In this study, the results of the ptients in whom benign sbestos pleurisy, rheumtoid pleurisy, prmlignnt pleurl effusion, virl infection-relted pleurl effusion, or rdiotherpy-relted pleurl effusion ws dignosed were not considered for evlution, becuse direct observtion of pleur nd considerble time period of follow-up of ptients were required for the exct dignosis. The dvntge of medicl thorcoscopy is certinly tht the biopsies cn be tken from severl res of the thorcic cvity, including the diphrgm nd viscerl pleur of the lung, under direct observtion. When the two methods were compred in terms of complictions, both were observed to be sfe. In one ptient, with presence of fluid only, to whom Abrms needle ws pplied, hemorrhge developed tht required tube thorcostomy nd blood trnsfusion. In conclusion, we suggest tht the present method of CT-ANPB be used s first dignostic evlution fter cytologic investigtion of the fluid in those cses with pleurl thickness or pleurl lesion observed in the thorx CT scn. This group comprises significnt mjority of the ptients with pleurl pthology. 13,14 However, in ptients with only fluid ppernce on CT scn, thorcoscopy should be the first method used in order to improve the chnces for finl dignosis. Also, if benign sbestos pleurisy or ny other benign disese other thn TB is suspected, the first method for dignosis should preferentilly be thorcoscopy for the exclusion of mlignncy. For exmple, in cses in which there is no pleurl thickening, procedures other thn thorcoscopy, which re performed without seeing the pleurl spce, my increse the risk of vsculr injury, especilly in ptients with high hydrosttic vsculr pressure in prietl pleur. CT-CNPB should be used preferentilly in cses in which there is only pleurl thickening but no pleurl fluid. Furthermore, in very rre occsions in which smll single lesions re locted in spots tht my be difficult to rech with n Abrms needle, such s posterior to the scpul or djcent to the vertebrl column or the sternum, CT-CNPB or thorcoscopy is preferred. On the other hnd, for some cses n dditionl dvntge of thorcoscopy is tht dignostic nd therpeutic ims, such s dringe nd pleurodesis, cn be chieved in single session. Acknowledgments Author contributions: Dr M. Metints: contributed to the ide for nd design of the study, performing thorcoscopy, nd drfting nd editing of the mnuscript. Dr Ak: contributed to the ide for nd design of the study nd performing thorcoscopy. Dr Dundr: contributed to performing histopthologic studies on biopsy smples of the ptients. Dr Yildirim: contributed to performing thorcoscopy. Dr Ozkn: contributed to investigting CT scns of the ptients. Dr Kurt: contributed to mnging the ptients in the clinic nd editing the mnuscript. Dr Erginel: contributed to mnging the ptients in the clinic. Dr Alts: contributed to mnging the ptients in the clinic. Dr S. Metints: contributed to the ide for nd design of the study nd drfting the mnuscript. Finncil/nonfinncil disclosures: The uthors hve reported to CHEST tht no potentil conflicts of interest exist with ny compnies/orgniztions whose products or services my be discussed in this rticle. References 1. Mskell NA, Butlnd RJ ; Pleurl Diseses Group, Stndrds of Cre Committee, British Thorcic Society. BTS guidelines for the investigtion of unilterl pleurl effusion in dults. Thorx ;58(suppl 2 ):ii8-ii Renshw AA, Den BR, Antmn KH, Sugrbker DJ, Cibs ES. The role of cytologic evlution of pleurl fluid in the dignosis of mlignnt mesotheliom. Chest ; 111 ( 1 ): Prksh UB, Reimn HM. Comprison of needle biopsy with cytologic nlysis for the evlution of pleurl effusion: nlysis of 414 cses. Myo Clin Proc ;60(3): Abrms LD. A pleurl-biopsy punch. Lncet ;271(7010): Chkrbrti B, Rylnd I, Sherd J, Wrburton CJ, Eris JE. The role of Abrms percutneous pleurl biopsy in the investigtion of exudtive pleurl effusions. Chest ;129(6): Mskell NA, Gleeson FV, Dvies RJ. Stndrd pleurl biopsy versus CT-guided cutting-needle biopsy for dignosis of mlignnt disese in pleurl effusions: rndomised controlled tril. Lncet ;361(9366): Loddenkemper R, Grosser H, Gbler A, Mi J, Preussler H, Brndt HJ. Prospective evlution of biopsy methods in the dignosis of mlignnt pleurl effusions. Am Rev Respir Dis ;127(4)(suppl 4 ): CHEST / 137 / 6 / JUNE,

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