57

and IL-I produced a slgntficant mcrcasc in lung uptakeofradiolabeled

lymphocytes at 4 and 24 h, whcrcas IL-2 and IFN-gamma dccrcased

uptake at both time points. IL- I incrcascd uptake by liver al 4 and 24 h

while IL-2 mcrcascd uptake only at 4 h. WC conclude that the distribu- tlon or actlvatcd lymphocytes followmg adoptive tmnsfcr is altcred by

cylokincs. This findmg may have important rmplications for cell dclivcry dung adoptive immunotherapy.

Visualiration of bone pathologies and lung cancer with %Tc- glucose phosphate: A comparative study

Caner BE, Ercan MT, Bckdik CF, Varoglu E, Muczzinoglu S, Duman

Y ~1 al. Deparfmenl of Nuclear Medicine, Medical Faculty, llacerlepe

Universily. Ankara. Nuklcarmcduin 199 1;30: 132-6.

Glucose phosphate (GP) labcllcd with 99”‘Tc was used IO obtain

scintigraphic images of bone lesions in one group of patients (n = 28)

and of lung tumors in another (n = 35). All bone lesions detected by

P9”T~-MDP also demonsuatcd by P9”T~-GP; all lung tumors except 4

were dctcctcd by ‘vc-GP. the fatlure rate being about the same as that for6’Ga. The ~scof~~“Tc-GP isprcfcrablc t~thatof~~‘“Tc-MDP because

the fOrmcrdoesnotaccumulatc m normal bone; thcadvantag.~of~~“Tc-

GP over 67Ga hcs in its bcttcr physical charactcr&cs and the fact that the result or the study 1s available within a few hours rather than three days.

Small cell long cancer antigen expression difTers on ‘classic’ and

‘variant’ SCLC and carcinoid cells

Koros AMC. Atchison RW. Mitchell DL. Deparrmenl of lnfeclious D~seosesandMicrobiology, GraduateSchool offublic Health, Univer-

siry of Piusburgh, 130 DeSoro Sweel. fursburgh, PA 15261. Lung

Cancer 1991:7:225-34. The panel of 98 monoclonal anubodies (MOABS) (mouse or rat)

provided by the Second International Workshop on Small Cell Lung

Cancer Antigens was tested by Indirect immunolluorescence and flow

cytomeuy using prototype cell lines [NC]-H69 (SCLC ‘classic’), NCI-

N417 (SCLC ‘variam’), NCI-H727 (carcmoid) (A.F. Gazdar et al.,

Bethesda. MD)] as well as normal human peripheral blood lymphocytes

(PBL) and sea urchin coclomccytcs [Koros, A.M.C., Inl. J. Neurosci.

48: I61 (1989)J. Allcclls hadsomcrcactivitywthsomcofthcM0AB.S.

There ls, howcvcr. difCcrcnttaJ expression of anligens amongst the

prototype ccl1 hncs which may provide a us&l method forphenotypmg

human lung cancers.

Circulating heparin-like anticoagulant in a patient with small-cell lung carcinoma

Gamier G. Taillan B, Castancl J. Pcscc A. Dujardin P. Serwe de

Medecinelnrcmel, IlopiralDe Cuniez, BP 179.06003 Nice Cedex. Rev

Med lntcmc 1991;12:213-4.

Acqmrcd ctrculating heparin-like anticoagulants may have different

causes, the most frequent bcmg plasmocytc proltfcration. The authors

reporl an exceptional case of association between an heparin-like

Inhibitor and a small-cell anaplasttc lung carcinoma, and they revtew

the pathogcncsis, laboratory diagnostic methods and treatment of the

anticoagulant.

Initial staging of non-small cell lung cancer: Value of routine

radioisotope bone scanning Michel F, Solcr M. lmhof E, Pcrruchoud AP. Deparrmenl of Resprra-

lory Diseases. Universiry flospiral. C11403/ Bawl. Thorax 199 1;46:469- 73.

The excloslon of bone mctastascs IS important m the inmal staging of

non-small cell lung cancer, though there is dcbatc about whether bone

scans should be performed routmely or restricted to patients who

present with clintcal or laboratory indicators suggesting skeletal metas-

Lastx. In a prospcc~vc study ol’ I IO consecutive patients refcned for

inilial staging of non-small cell lung cancer, we assessed the sensitivity ofa group of clinical indicators (chest pain, skeletal pain, bone tender-

ness on physical cxammauon, swum alkaline phosphatase. and serum

calcmm) for the prcscncc of skclctal mctaslases as detcrmined by bone

scanning. The final staging rcstdt was validated with follow updataover at least three years. At the mitral staging 37 of 110 bone scans (34%)

showed arcas of incrcascd uptake, of which only nmc were confirmed

lo be mctastascs (by tomography, computed tomography, or biopsy).

Half the patlcnts (55) had at lcast one clinical indicator suggesting skclctal mctaslilscs, including all patients with proved skclctal mctasta-

scs. Thus the sensitivity of thcsc clmical mdicators was 100% and the

spcclficlty 54%. Within one year three of 27 patients with non-

confirmed posmvc bone scans had skclctal mctastascs, one of which

was m the arca that had shown incrcascd up&kc initially. All these

paticnls had clinrcal indicators [or skeletal mctastascs and all had

inoperable advanced turnours. Four al 69 patients wth an initially

negative bone scan dcvclopcd skclctal mctastascs within one year. It is

concluded that in non-small cell lung cancer bone scannmg can be

restrtctcd to paticnls with clinical indicators for skeletal metastases.

This approach rcduccs the number of bone scans and consccutivc

investigations without loss of scnsltivity in the dctcction of skeletal

mctastascs.

Immunochemical detection of a small cell lung cancer-associated

ganglioside (FucC(MI)) antigen in serum

VangstedAJ,Claoscn H,KjcldscnTB, WhiteT,Swecney B,Hakomori

S et al. Deparunenr of Tumor Cell Biology. The Fib&r Insrirule,

Dan&h Cancer Society. Ndr. Frlhavnsgade 70, DK-2100 Copenhagen.

Cancer Rcs 1991;51:2879-84.

Recently, the gangliostde FucG(Ml) Fuc_l-2Gal8l-3GalNAc8l 4[NeuAc_2-3]-Gal8l-4Glc8 I-1Cer)wasidcntificdasasmallcell lung

cancer (SCLC) marker both in chemical and histochemtcal studies. In order to further dctcrminc whcthcr the FucG(M1) gangliosidc IS shed

from the tumor site and conscqucntly is prcscnt in the serum of SCLC

patients, wc pmduccd a scrics of new monoclonal antibodies raised

against FucG(Ml) and rclatcd glycoliptds. Shedding of the FucG(Ml)

ganghosidc was stud& both in vitro and in vtvo using SCLC cell lmes

and nude mice xcnografts of SCLC cells as model systems, and finally

immunochemlcal analysts wcrc performed on scmm samples from

patients with SCLC. High-pcrformancc thin-layer chromatography

immunostaining dcmonsuatcd the prcscnce of FucG(Ml) in condi-

tioned culture media obtamcd from FucG(Ml)-posrtive SCLC cell

lines. Ftmhcrmorc, tumor extracts of SCLC cell line xenografts tn nude

mace were posttive for the FucG(M I ) marker, and more tmportantly the

marker was also prcscnt in swum samples from these mice. Twenty

serum samples wcrc obtained cram pattcnts with histologically vcnfied

SCLC. Eight patients had locali& discasc, and the remaining pattents had disscminatcd cancer involving mctastascs to other organ sites. Sera

from 4 of thcsc patients wcrc clearly positive, and 2 addittonal cases were found to be weakly positive. The positive patient sera were all

from patients with cxtcnsivc disease. Scra from I2 patients with non-

SCLC and 20 healthy mdivtduals wcrc all found to be negative. These

results clearly establish the FucG(M1) glycolipid as a potenual serum

marker of SCLC for which a sensttivc immunoassay should be devel-

oped and tested using a larger scrics of Serum samples.

Necrotizing bronchial aspergillosis in a patient receiving neoad-

juvant chemotherapy for non-small cell lung carcinoma

Niimi T, Kajita M, Saito H. Deparrmenr ojThoracic Surgery. Norio&

Chubu Hospital. 36-3 Gengo. Morioka-cho. Ohbu. Alchi 474. Chest 1991;100:277-9.

We describe a case of nccroti/.ing bronchlal aspergillosrs which

developed alter lobcctomy following ncoadjuvam chemotherapy in a 73-year-old woman with non-small cell lung cancer. The lesion was

visualized and biopsicd through FBS. which played a useful role for

early diagnosis of lhis disease. luacona/ole therapy was effective and safe.

Technetium-99m monoclonal antibody fragment (FAb) scintigra-

phy in the evaluation ofsmall cell lung cancer: A preliminary report

Morris IF, Krishnamurthy S, Antonovic R, Duncan C, Turner FE, Krishnamunhy GT. Nuclear Medicme Serwce (l/S). VA Medical

Cenrer, Ponland. OR 97207. Nucl Med Biol Int J Radtat Appl lnstmm

PartB 1991;18:613-20. Small cell lung cancer (SCC) has the most rapid growth rate of the

fourccll types and mcwtawcE early. Prcscnt imaging modalmcs for

58

sraging include chcs1 x-ray, CT, MRI and hone scans. In this prcliml- nary study. WC asscsscd the clinical role ofPO”Tc-monoclonal antibody

(MOAB) scinugraphy in f1vc paucn1s with histologically proven SCC. Each palicm was mfuscd vvnh 20-X) mC1 of9P”Tc labclcd Fab fragmcnl

of MOAB (NR-LU-IO, NcoRx, Scaulc, Wash.). Tolal body simulumc-

ous anccrior and pos1crw nnagcn wcrc obtained l4- I6 h posl mjcction.

SPECT images of 1hcchcs1 wcrc obuuncd through a 360°rola1ion ofthc

gamma camera and rccordcd on a 62 x 64 x I6 matrix. lmagcs (1.2 cm

thick) wcrcgcncratcd m 1ransaxnd. sagulal andcoronal VICWS. Fourteen

of fihccn chest lesions dclcclcd by CT wcrc confnmed by -“Tc MOAB

scinligraphy. Scinugraphy dc1cc1cd oncadditionalchcstlcsion not seen by CT. Scinugrephy failed 1odctccta brain lesion (2cm).achcalcsion, and two adrenal Icsions, all of which wcrc seen by CT. In one patienl

wi1h mulliplc (mom than IO) Icsions m the liver, both scinligraphy and

CTdctcctcdall Icsions. Three spine Icsn~nsaccn ~n~~“Tc MDPscanand

posirivc for mcn~slas~s on MRI conccntratcd 99”Tc MOAB, bu1 two rib

lesions seen on ““‘Tc MDP bone scan did notconccnua1c 99”‘Tc MOAB.

I1 is concluded from !hcsc preliminary rcsubs 1ha11hc poccnlial uscful-

ncss of99mTc MOAB scintigraphy as a complcmcntary imagmg modal-

ily in the siagmg of small cell lung cancer should bc invcsligatcd

rmhcr.

Preliminary reporl of gamma-enolase levels in patients with bron- chogenic carcinoma

Vcr;v.~nGT,ParvezZ,TakitaH, BhargavaA,Pclrclli N.Deparfmenrof Surgical Oncology. Rowell Park Cancer Ins~iture. Elm and Corlron

Sfreels. Buffalo, NY 14263. J Tumor Marker Oncol 1991;6:39-44.

Thu1y palicnls with bronchogcnic carcinoma had gamma-enolasc levels (w/ml) drawn a1 leas.1 a smglc poin1 during the course of their

discasc. The disuibuuon of cell 1ypcs is as follows: squamous cc11

carcinoma (13 palicnls); adcnocarcinoma (9 palicnts); small cell carci-

noma (6 paiicnls): and large ccl1 carcinoma (2 pa1icnts). Three patients

had lcvcls drawn a1 poin1s with discw as well as wi1h no evidence of

disease (NED). The mean serum level of gamma-enolase in the 10 Palicnls wi1h NED was 9.82 ng/ml (range 3.74 - > 24.9). The 23 patients

wi1h clinical dwxsc had a wan strum level of 34.6 ng/ml (range 3.87 > 2M)). Scvcn of the IO spccimcns with NED had levels < 12 ng/ml

(70%), whcrcas, I8 of23 spccimcns with discasc had lcvcls > 12 ng/ml (7%). The gamma-cnolasc lcvcls wcrc mcasurcd a1 1wo points during

1hccoursc oflhcdiscascin IOoflhc 30patients. Thcclimcal corrcla1ion

was c0ns1stcnl with a rise or fall in gamma-cnolasc in all 10 patients.

gamma-cnolasc shows pronusc as a 1umor marker in bronchogcnic carcmoma in the lung.

Soluble interleukin 2 receptor in lung cancer; An indirect marker

of tumor activity? Buccheri G, Marina P. Preatoni A, Ferrigno D. Moroni GA. Ospedole

A. Carle. 12100 Cuneo. Ches1 1991;99:1433-7.

Circulating levels of the soluble intcrleukin 2 receptor (sIL-2R) could provide an in viva measure of tic immunologic response lo human tumors. WC pcrformcd a lotal of326 slL-2R serum assays in 126

patients wi1h lung cancer (67 at diagnosis, 59 during and after trcal-

mcn1). I12 palicnts wuh pulmonary benign diseases, and 63 voluntary healthy subjccls. Paticnis with lung cancer had a median value of sIL-

2R of791 U/ml, which was supcr1or to that of both controls (398 U/ml,

p<O.OOl) and pa1icn1s with noninflammatory benign diseases (583 U/

ml,p<0.02). Howcvcr,infcc1iouspulmonarydisordcrs,suchas1ubcrcu-

losis and pncumoniu, wcrc aasociaicd with Ihc highest values of the

subsmncc (median, 1150 U/ml; p<O.OOl). A1 ihc dmgnosis of lung cancer, slL-2R corrclalcd ncilhcr wnh the stage ofdiscasc nor wuh ihe

cell 1ypc. on the contrary, postucatmcnt ICVCIS of the rcccplor were

significantly rclaicd todiscasc sunus (RO=.41 ,p<O.CQ2),parlicularly in the subgroup of nonsurgical paucnu (RO=.48, pcO.001). Palienls with

abnormal sIL-2R lcvcls had a nearly significam reduction in survival as compared with pa1icnts with normal values (p<O.l). Mcasurcmcnts of

slL-2R could bc uxful in moniloring palicnts under Uealmenl for bronchogcnic carcinoma, as well as in prognosiicaiion. In this selling. sIL-2R mtght open a new class of biologic markers, providing informa-

lion 1ha1 is complcmcnwy 10 1hosc of the more classic lumor-derived markers.

Quality of life assessment: An independent prognostic variable for

survival in lung cancer

Can/. PA, Lee JJ, Siau J. Deparlmenr of Medicine, Veterans Afairs Medical Cenrer. 16111 Plummer Srreer. Sepulveda. CA 91343. Cancer

1991;67:3131-5.

Improved quahiy of lift has long been ihc goal of cancer ucalmenl.

bu1 only rcccnlly have mvcstigators begun IO include a systematic

asscssmcm of qualily of lift in clinical trials. The major intcrcst for its inclusion in clinical trials has been to assess lreatmeni ou1come. An

evaluation of ihc rclauonsh1p bctwccn patient-r&cd quality of life and

survival is rcporlcd in a homogcncous samplcofpatients with advanced

metastatic lung cancer parucipadng m a clinical trial. Under the Cox

proportional-haLards model (wi1h quality of life, marital status, and

1heir intcracuon in the model), a statistically significant rcladonship

was obscrvcd bc1wccn ini1ial pa1icn1-ra1cd quality of life and subse-

qucm surwval. In addillon, being marocd led lo a significantly im-

proved surwval. Thcsc findings suggcs1 Thai nonmedical faciors, such

as quality of life asscssmcni and mariud sunus, play a role in survival

and 1ha11hcy should bc cvalualcd and dcscribcd as polcntial predictors

of survival in cancer paticnls 1n chnical trials.

Bilateral parotid secondaries from primary bronchial carcinoid tumour

Ddkcs MC, Birchall MA. EN’l’Deparrmenr. SI Mary’s llosp~lal. Pad-

dingron, London W2 INY. J Laryng 0101 1991;105:489-90.

Three years following a right lower lobcclomy for primary carcinoid

lumour of 1hc bronchus, a pa1icn1 prcscntcd wnh bilateral parotid

masses. On investigation, both these were shown to be carcinoid

lumours, consislcnl with mctastatic spread from the primary bronchial lumour. This unique cast 1s prcrcn1cd 1ogcthcr with a discussion of the diagnostic methods cmploycd.

DNA adducts in bronchial biopsies

Dunn BP, Vedal S, San RHC. Kwan W-F, Nclcms B, Enarson DA eial. British Columbia Cancer Research Cemre. 601 West 10th Avenue. Vancouver. BC V5% lL3. In1 J Cancer 1991:48:485-92.

To investigaic lhc feasibility of measuring DNA-carcinogen adducts

in Ihe lungs of non-surgical paucnis, cndobronchial biopsies were obtained from 78 paticnls undergoing rou1inc diagnostic bronchoscopy. Lung cancer was prcscnt m 37 (47%) of the patients. DNA was isolated from the tissues and analyzed by HPLC- or nuclcasc-PI-enriched 32P-

postlabelling, using proccdurcs selective for aromauc adducts. Chro- matograms from all 28 current smokers showed a distinctive diagonal adduct zone which was present in only 24 of 40 ex-smokers and 4 of 10 lifetime non-smokers. Adduct lcvcls and chromatographic patterns wre similar in bronchial tissue from different lobes of the lung, in bronchial and alveolar tissue. and in tumor and non-tumor bronchial lissuc taken from the same subject. Bronchial DNA adduci levels were

strongly associa1cd with cigarcttc smoking status and dropped rapidly aflcr smoking ccascd. Higher levels of DNA adducts seen in the lung- cancer patients wcrc mainly due to cigarette smoking. Frequenl alcohol intake was the only dietary factor associated with higher levels of bronchial DNA adducts. WC conclude that the lcvcl of bronchial DNA adducts is strongly associated with cigarcttc-smoking history and with alcohol intic, but is not associated wuh lung cancer independently from ils relation to smoking. The results indicate the feasibility of using “Ppostlabclling IO detect and quantitaie genetic damage in bronchial

biopsy specimens.

Could cell kinetics be a predictor of prognosis in non-small cell lung

CttnCer?

Silvcsuini R, Muscolino G, Costa A, Lcquaglic C, Vcncroni S, Mez-

zanollc G cl al. Oncologia Chirurgico Toracico, lstiruto Nazionole per lo Studio e la Cwa dei 7Lmor1. Milano. Lung Cancer 1991;7:165-70.

Ccl1 kinetics, cvaluatcd as ‘H-thymldinc labcbng mdex ([‘H]TdR LI). was asscsscd in 72 prcv~ously unucatcd non-small-cell lung can- ccrs (NSCLC) from paucnu opcratcd on during the period 1978 10 1982 a1 1hc Istiluto Nazionalc Tumori of Milan. Pathologic stage and histol-