158 Abstracts/Lung Cancer 14 (19%) 149-179

between ~53 expression and other pretreatment variables. Response to radiotherapy was found in II p53-negative cases (65%) versus 10 p53- positive cases (42%). Freedom from local progression was significantly better in the p53-negative cases as compared with the p53-positive cases. The p53-negative cases who responded to radiotherapy showed an excellent freedom from local progression rate after 2 years of IOO%, whereas all p53-positive cases without response to radiotherapy showed local progression within 24 months. Overall survival between p53- negative and-positive cases didnot differ, howeverthe disease-specific survival was found to be worse in the p53-positive cases as compared to the negative cases (median survival 8.4 vs. 14.4 months (P < 0.05)). No correlation was found between p53 expression and the frequency of distant metastases. In conclusion, the results of this study suggest that ~53 protein expression may be of prognostic value on freedom from local progression in non-small cell lung carcinoma.

Microvessel count predicts metastatic disease and survival in non-small cell lung cancer Fontanini G, Bigini D, Vignati S, Basolo F, Mussi A, Lucchi M et al. Institute of Pathology. University ofPisa. 57, Via Roma. I-56126 Pisa. J Path01 1995;177: 57-63.

The growth ofnewly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents ameasure of tumour angio- genesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, headandneck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small cell lung cancer (NSCLC) patients. Microvessels were counted by highlignting endothelial cells with snti- Factor VIII monoclonal antibody (MAb) in methacam-fixed hunour samples. In univariat analysis, MC (P~O.OOOOOl), sex (P=O.O036), histotype (P<O.O14), tumour status (p<O.O07), and vessel invasion (P<O.O19) were significantly related to hilar an&or media&al nodal involvement. However, in the stepwise logistic regressionanalysis, MC (P~0.000003)retainedthemostimportantinfluenceonnodalmetastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC (225 vessels/held) were signifi- cantly associated with increased death risk (log-rank test P=O.O0067; Cox’s test P=O.O0046; Gehan’s Wilcoxon test P=O.OOlOS). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis duringfollow-upshowedahigherMC,eitherasadichotomous(P=O.Ol) or as a continuous (P=O.O03) variable, than patients who bad developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence ondistantmetastases.Microvesselcount,asamethodforthequantitation of twnour angiogenesis, has an important prognostic role in non-small cell lung carcinomas.

Osteolytic bone lesions in a patient with idiopathic myelo- tibrosis and bronchial carcinoma ClutterbuckDJ,Monison AE,LudlamCA. DepanmentoJHaematologv, Royal Infnnary of Edinburgh, Lou&on Place, Edinburgh EH3 9W. J Clin Path01 1995;48:867-8.

A 59 year old man with longstanding myelotibrosis and previous splenectomy was incidently found to have a large lytic lesion in his left femur which required operative fixation. He had undergone right upper lobectomy for squamous carcinoma of the bronchus five years earlier. Histologicalanalysisofbonereamingsshowednoevidenceofmetastatic carcinoma. Osteosclerosis is frequently noted in patients with myelofibrosisbutosteolyticlesionsareuncommonandmaybeconfused with metastatic malignancy.

Imaging and staging of small-cell lung cancer: Is there a future role for octreottde scintigraphy? StokkelMPM, KwaBH,PauwelsEKJ.&ptDiagnosticRadiolNuclear Med. Universiry Hospital Leiden. Rijnsburgerweg IO, 2333 AA Leiden. Br J Clin Pratt 1995;49:235-8.

Insmall-cellhmg~ancer(SCLC),CTscanremainsthemostacc~te imaging modality for evaluating local extension and specific sites of metastaticdisease.Theroleofnuclearmedicineinthework-upofSCLC is still limited to the detection of bone metastases. Recently, a new potential diagnostic tool has been introduced based on the presence of somatostatin receptors in SCLC. With the use of radiolabelled somate statin analogues it is hoped that an equally effective but simpler staging system has been found that gives a better separation of prognostic subgroups. Tbis article reviews the role of nuclear medicine in general and somatostatin receptor scintigraphy in particular in the imaging and staging of SCLC. Clinical value in terms of sensitivity and specificity is discussed in relation with other imaging and staging modalities,

A case of postoperative hyponatremia caused by Sheehan syn- drome associated with lung carcinoma Ozaki S, Nakanishi R, Sskata K, Mitsudomi T, Yasumoto K. Second Department of Surgery. School oj Medicine, Univ. of Occupational/ Envtl. Health. Yahatanishi-ku, Kitakyushu 807. J Uoeh 1995;17:199- 205.

A 54-year-old woman underwent a letI upper lobectomy for lung carcinoma after which hyponatremia developed within 5 days. Her serum concentration of ADH was within normal range disapproving the presence of SIADH frequently associated with lung carcinoma. An endocrinological examination showed panhypopituitarism. From her anamnesis it was seen that there was much perinatal bleeding and amenorrhea. She was diagnosed as suffering from Sheehan syndrome. Shewastreatedwithglucocorticoidandbeneficialresultswereobtained. Herserumconcentrationofnatriumreturnedtonormalandshedischarged on the 74th postoperative day. We present this paper because we had difficulty in determining that she had Sheehan syndrome, and think that a careful search for a diagnosis before operation is important for the management of the patient during the perioperative aud postoperative period.

ClinicalutilItyofhyaluronicacidvaluesinserumand broncho- alveolar lavage fluid as tumor marker for bronchogenic carcinoma Hemandez Hemandez JR, Garcia Garcia JM, Martinez Muniz MA, Allende Monclus MT, Ruibal Morel1 A. Section de Neurologia, 7 Planra. Hospital NS Sonsoles, Carrerera de Madrid Km 109, 05004 Avila. Int J Biol Markers 1995; 10: 149-55)

Various authors have proposed the use of hyaluronic acid (HA) as a tumor marker. In order to analyze its usefulness as a marker in bronchogenic carcinoma, the most common carcinoma in men, we determined the HA values in serum and bronchoalveolar lavage fluid (BAL). We performed prospective studies on two groups of patients: 8 1 diagnosedashavingbronchialcarcinomaand34withbcnignrespiratory diseases. HA values were higher in patients with cancer than in those with benign diseases (serum: 79.8 @ml vs 63.7 rig/ml; BAL: 927 ng/ mlvs522ng/mg). Also,thepercentageofpatientstithlevelsexceeding the established cutoff was greater in the group with cancer than in the group with benign diseases (SERUM: 24.6 vs 17.6; BAL: 25.3 vs 3). Statistically significant differences in these percentages were found in BAL @<O.O 1). Patients with extended small cell carcinoma bad higher HA values (p=O.O4) than those with limited disease, and the percentage of patients with abnormal HA values was larger in the group with extended disease than in the group with extended disease than in the

Abstracts/Lung Cancer I4 (19%) 149-179 159

group with limited disease (p=O.O04). The serial determinations of HA values in serum reflected the clinical evolution after treatment in 73% of the small cell carcinomas. Most of the patients with benign diseases whose HA values exceeded the cutofflevel s&&cd from acute infectious diseases. Once these cases were excluded, the specificity of HA value determination in the diagnosis ofcarcinoma was very l&h (serum 96%. BAL 100%). The determination of HA levels in serum or BAL did not have any prognostic value in this study. We conclude that the HA levels in serum and BAL could be of interest as a tumor marker, especially in patients with small cell carcinoma

Evaluation ofthe serum markers CEA, NSE, TPS aad CYFRA 21.1 in lung cancer Giovanella L, Ceriani L, Bandera M, Beghe B, Roncar G. Diportimenro di Medicino Nucleare. Ospedale RegionoIe di Varese, V Ie Born’. 2 7, Varese. Int J Biol Markers 1995; IO: 156-60.

We investigated the role of tumor markers CEA, NSE, TPS and CYFRA 2 I. I in lung cancer diagnosis and staging in I69 patients with histologically confirmed lung cancer (43 SCLC and 126 NSCLC). In SCLC patients NSE and CYFRA 21. I showed the highest senstitivity and their combination improve significantly the diagnostic sensitivity and accuracy. In NSCLC patients CYFRA 21. I showed the highest sensitivity and global accuracy and no markers association was as effective as CYFRA 2 I. I alone. Based on data from our study it can be concludedthatinpatientswithsuspectedlungcancertheserumNSEand CYFRA 21. I assay is a suitable association to confirm the clinical

hesis. NSE in SCLC and CYFRA 21.1 in NSCLC are useful in the ation of disease extent and successive treatment planning.

The early detection of pleural dissemination of lung cancer by thin-slice computed tomography YamadaK,OshitaF,YoshiokaT,NomuraI, NodaK,YamagataTet al. Jpn J Lung Cancer 1995;35:43743.

To facilitate the accurate diagnosis of pleural dissemination oflung cancer, we evaluated the use of thin slice computed tomography (CT). Conventional CT and thin slice CT images of 100 patients with lung cancer who underwent thoracotomy were retrospectively reviewed. The conventional CT and thin slice CT images were examined by an extended scale (window level: -600, window width: 1900) using high resolution images. Ninety one of these patients were recognized postoperativelyashavingnotumordisseminationon thepleuralsurface. Of the remainder, nine patients had tumor dissemination on the pleural surface of the chest wall or in the interlobar fissures. For the 9 1 patients without pleural dissemination, preoperative thin slice CTimages clearly showed asemicircularhigh attenuation line in the interlobar fissures. As for the nine patients with pleural dissemination, preoperative thin slice CT images of five patients (56%) clearly showed the presence of multiple small nodular lesions, while no surface irregularity in the mterlobar fissures was visible on the conventional CT images. Our results may suggest that thin slice CT images could play a significant clinical role in the early detection of pleural dissemination by demonstrating multiple small nodular lesions ofthe interlobar fissures.

Prognostic analysis of lung cancer patients with brain metastasis and evaluation of long term survivors Sakai H. Yoneda S, Sakura M, Kimura K, Hibino S, Goto 1 et al. Department ofDiagnostic Radiology, Saitamo Cancer Center, Saitama. Jpn J Lung Cancer 1995;35:407-15.

Toevaluatc therapeutic strategiesagainst brainmetastasis from lung cancer, 327 cases clinically diagnosed tohave metastasis to the brain out

of a total of 1586 lung cancer cases treated since 1977 were examined, andsingle factoranalysisofthesurvivalratefromtheonsetofmetastasis to the brain was conducted by prognostic factor and by therapeutic factor. Multivariate analysis was then performed to find the extent of contribution of the items demonstrating statistic significance to the survival rate by each factor,usingCox’spropottionalhaxardmodel. The single factor analysisindicated significant difference in the performance status (PS) upon discovery of metastasis to the brain, control status of the primary lesion, metastasis to organs other than the brain, resection of the me&&tic lesion, cerebral irradiation and dose, and the time metastasis appeared. The factors demonstrated to be significant by multivariate analysis were PS upon discovery ofmetastasis to the brain, cerebral irradiation, resection of the me&static lesion, control status of the primary lesion and metastasis to organs other than the brain, in order of greater contribution to the survival rate. In non small cell carcinoma cases, longer survival of patients was observed when cerebral surgery and radiological treatment were combined, but the surgery did not achieve better result in small cell carcinoma cases. If the conditions of PSandprimarylesioncontrolandextracerebmlmetastasisare favorable, aggressive multidisciplinary treatment is recommended for longer survival with emphasis on radiotherapy and cerebral surgety if possible in patients with non small cell carcinoma and emphasis on radiotherapy in patients with small cell carcinoma.

Detection of circulating cancer cells by RT-PCR in patients with resectable lung cancer Yokouchi H, Doi 0, Higashiyama M, Kodama K. Deporfmenr of Surgery, Center for Adult Diseases, Osokn. Jpn J Lung Cancer 1995;35:401-6.

We established an assay system to detect very small amounts of cancer cells among a large amount of peripheral blood mononuclear cells (PBMNC) through expression of keratin 19 gene specific for epithelial cells by RT- PCR. Expressions of keratin 19 gene were not detected in normal PBMNC but were detected in a lung cancer cell line, CADGLC4dilutedwith 1060fnonnalPBMNC. Weappliedthissystem for 21 resected cases of primary lung cancer (1 I stage I cases, 2 stage II, 8 stage III) and detected keratin 19 expressions in PBMNC of 3 cases ofstage 1. There was no correlation between the keratin l9-positive rate and vascular invasion. The keratin 19positive rate of squamous cell carcinoma was higher than that of adenocarcinoma (2/7 vs l/14). Whether circulating cancer cells reflect occult distant metastases or not should be determined based on the outcome after appropriate follow up.

Insulin like growth factor (IGF) and IGF binding proteins in growth hormonedysregulation and abnormal glucose tolerance in small cell lung cancer patients Reeve JG, Morgan J, Clark PMS, Bleehen NM. Medical Research Council. Clin. Oncol./Rodiotheropeutics Unit, MRCCenne, HillsRoad. Combridge CB2 2QH. Eur J Cancer Part A Gen Top 1995;3 1: 1455-60.

Growth hormone (GH) regulation, glucose tolerance and serum concentrations of insulin-like growth factor (IGF) and IGF binding proteins (IGFBP) have been investigated in small cell lung cancer (SCLC) patients. Elevated serum GH was observed in the patient and smoking control groups but not in non-smoking control subjects. Glucose suppression of GH was observed in the few SCLC patients with raised basal GH but most SCLC patients exhibited a paradoxical increase in GH following oral glucose. Abnormal glucose tolerance and iusulin resistance with respect to plasma glucose. was observed in most patients Patients showing GH dysregulation exhibited higher serum concentrations of IGFBP-2 than those showing no increase in GH. Abnormal glucose tolerance was associated with decreased serum