Thrombosis-inducing activity found in plasma from two patients with advanced lung cancer

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52 Clinical assessment The value of mass radiographic screening fur the early detection of carcinoma of the lung Schildge J, Cegla M, Ortlieb H, Schultc-Monting J. Abt. Lungenchirur- gie, Chirug. Universirarsklinik Freiburg, Freiburg. Pneumologie 1989;43:500-6. On 30.6.1983, mass radiographic screening was abandoned despite objections to the effect that it offered the only chance of detecting carcinomaofthelungatanear1y stage. Inaretrospecdveanalysisofour patient malerial comprising 1.010 patients with bronclual carcinomas seen within thcpericdbetwccn 1 .l.l980m 31.12.1986,weinvcstigated lhe question as to whether these ObJeclions might not bc justified. Four hundred and thirty-seven patients seen prior to 30.6.1983 were com- pared with 537 palients examined after this date, on the basis of the following parameters: age-sex-symptomatology-cancer stage-histol- ogy-treatment. After stopping mass radiographic screening, an increase in age and symptomatic tumour findings was observed, and thus a shift towards more advanced stages of carcmoma. A relative decrease in the number of squamous cell carcinomas, and a relative increase in the number of adenocarcinomas were observed. All the parameters in the patients identified at mass radiographic screening were comparable wilh those seen in patients identified incidentally. In comparison with symptomatic patients, those identified by mass radiography screening more frequently presented with earlier turnour stages, and the lesions were more frequently rcsectablc. All in all, over a period of three and one-half years, mass radiographic screening revealed 23.8% of all cancers of the lung, and 36.8% of all rcscctable lesions. After the abandonment of mass radiographic screening, an mcrcasc in more advanced and symptomatic turnours was obscrvcd. Evalution of the extent of lung cancer Milleron B, Mayaud C, Akoun G. Cenrre de Pneurnologie el de ReanimaGon Respiraroire. Ilopiuzl Tenon, F-75970 Paris Cedex 20. Presse Med 1989;18:1387-9. The variety of individual opnnons cncountercd in the evaluation of lung cancer is due to the multiplicity of investigations. The inuathoracic extent is basically assessed by bronchial fibroscopy wnh tlcrcd biopsies and computerized tomography. The specificity of computeriLed Iomo- graphy in the evaluation of lymph node involvcmcnt ncvcr exceeds 75 per cent, and although this figure is higher as regards mediastinal or direct chest wall involvement, it ncvcr reaches 100 per cent. The information provided by magnetic resonance imaging is not better. Metastatic extension is evaluated by abdominal uluasonography and computerized tomography of Ihe brain and of Ihe upper abdomen. Sys- tematic radionuclide bone scanning is debatable and some other exami- nations must be reserved to certam histological types; this is the case with bone marrow biopsy (comphxed, if ncccssary, by monoclonal antibodies) or magnetic rcsonancc imaging of bones in small cell carcinomas. The levels of some markers arc well corrclatcd wnh tumoral dissemination. Cholecystokinin elevates cytosolic calcium in small cell lung cancer cells Slaley J, Fiskum G, Moody TW. Department of Biochemistry and Molecular Biology, George Washingron Unrversily SchoolofMedicine and Health Sciences, Washington, DC 20037. Biochem Biophys Res Commun 1989;163:605-10. The ability of cholecystokinin (CCK) to elevate intracellular Ca” levels in small cell lung cancer cells was mvestigated using the fluorescent Ca2+ indicator Fura 2. CCK-8 clcvated Ihe cytosolic Ca*+ levels in cell hne NCI-H345 in a dose dcpcndcnt manner. Nanomolar concenuation of CCK-8 elevated cytosolic Ca” levels m the absence or presence of cxuacellular Ca2’ . Potent CCK agonists such as gasuin-I and nonsulfated CCK-8 but not inacnve compounds such as CCK-27- 32-NH, elevated cytosolic Ca 2+levels. Thcsc dala suggest that CCK receptors may regulate the release of Ca2+from intracellular organelles in small cell lung cancer cells. Lack of relationship between in vitro tumor cell growth and prog- nosis in extensive-stage small-cell lung cancer Stevenson HC. Gazdar AF, Linnoila RI ct al. National Cancer Insritule- Navy Medical Oncology Branch, Naval Hospital, Bethesda. MD 20814. J Clin 0x01 1989;7:923-31. The ability to establish a conlinuously growing tumor ceil line from fresh tumor specimens has been associated with shortened survival in some human malignancies. Therefore. we assessed the relationship between survival and in vitro tumor cell growth from specimens obtained during routine staging procedures in 68 consecutive patients with untreated, extensive-stage small-cell lung cancer (SCLC) who received etoposide/cisplatin chemotherapy. Three groups of SCLC patientscouldbedistinguishcd: (1)23patientsm whomatumorcellline was established in vitro; (2) 28 patients in whom tumor-containing specimens were cultured but in vitro growth did not occur; and (3) 17 patients in whom no tumor-containing specimen could be procured. No significant difference in response rates to chemotherapy of the three groups was noted. Poor performance status (P, = X01), male gender (P2 =.0008),liverme~stases(P,=.0033),brainmetastases(P,=.0152),and the ability to obtain a tumor-conmining specimen from the patient for laboratory culture (P2 = X05) were all significant independent predic- tors of decreased survival in this patient population. While the ability to obtain a tumor cell specimen for cell culture using routine staging and diagnostic procedures identified patients with shortened survival, we found no significant survival differences between patients whose tumor cell specimens grew in cell culture v those that did not (median survival of 7 months v 11 months, P, = .72). Our study indicates that the clinical outcome ofextensive-stage SCLC patients from whom tumor cell lines can beestablished is not significantly dlffercnt than in thosecases from whom tumor-containing specimens could not be grown in vitro. Serum CK-BB as a tumor marker in patients with carcinoma confirmed histologically Arenas J, Diaz AE, Alcaide MJ, Santos I, Martinez A, Culebras JM. Servicio de Bioquimica. Hopital 12 de Octubre’ , 28041 Ma&id. Clin Chim Acta 1989;182:183-94. We determined serum CK-BB mass concentration using a specific RIA method, in 267 patients wilh carcmoma confirmed histologically distributed as follows: 46 pros&tic adenocarcinoma, 52 lung neoplasies, 70 colon carcinoma, 52 breast carcinoma and4 I gastric carcinoma; and also in 135 patients with histologically proved non-neoplastic diseases distributed as follows: 28 prostatic hyperplasy, 31 lung tuberculosis, 29 inflammatory bowel disease, 27 fibrocystic mastopathy and 20 gastro- duodenal ulcer. Reference values in healthy subjects (n = 360) were 5.46 f 2.68 (SD) &ml. We found that serum CK-BB mass concentration is not a specific tumor marker but it is a valuable indicator of responsing to therapy and metastatic widespread. Howcvcr, in prostatic carcinoma prevalence 0.25, prcdictivc positive value (PPV) 0.51 and predictive negative value (PNV) 0.88 and breast carcinoma prevalence 0.32, PPV 0.6Oand PNV 0.87 strum CK-BB can bc used as a tumor marker. Only 12 over 268 patients with different neoplasnc disease (4.47%) showed detectable serum CK-BB catalytic concentrations. Thrumhosis-inducing activity found in plasma from two patients with advanced lung cancer MaruyamaM, Yagawa K, Kinjo M etal. ResearchlnsritureforDiseases of rhe Chesr, Faculty of Medicine. Kyushu University, Fukuoka 812. Oncology 1989;46:25 1-4. In 2 patients with lung cancer, the coagulation system was supposed to be activated by the findings of elevation of plasma fibrinogen, fibrinogen degradation product (FDP) and/or peripheral platelet counts. The plasma thromboxane B, and 6.kern-prostaglandin F( 13 levels in 1

Transcript of Thrombosis-inducing activity found in plasma from two patients with advanced lung cancer

Page 1: Thrombosis-inducing activity found in plasma from two patients with advanced lung cancer

52

Clinical assessment

The value of mass radiographic screening fur the early detection of carcinoma of the lung Schildge J, Cegla M, Ortlieb H, Schultc-Monting J. Abt. Lungenchirur- gie, Chirug. Universirarsklinik Freiburg, Freiburg. Pneumologie 1989;43:500-6.

On 30.6.1983, mass radiographic screening was abandoned despite objections to the effect that it offered the only chance of detecting carcinomaofthelungatanear1y stage. Inaretrospecdveanalysisofour patient malerial comprising 1.010 patients with bronclual carcinomas seen within thcpericdbetwccn 1 .l.l980m 31.12.1986,weinvcstigated lhe question as to whether these ObJeclions might not bc justified. Four hundred and thirty-seven patients seen prior to 30.6.1983 were com- pared with 537 palients examined after this date, on the basis of the following parameters: age-sex-symptomatology-cancer stage-histol- ogy-treatment. After stopping mass radiographic screening, an increase in age and symptomatic tumour findings was observed, and thus a shift towards more advanced stages of carcmoma. A relative decrease in the number of squamous cell carcinomas, and a relative increase in the number of adenocarcinomas were observed. All the parameters in the patients identified at mass radiographic screening were comparable wilh those seen in patients identified incidentally. In comparison with symptomatic patients, those identified by mass radiography screening more frequently presented with earlier turnour stages, and the lesions were more frequently rcsectablc. All in all, over a period of three and one-half years, mass radiographic screening revealed 23.8% of all cancers of the lung, and 36.8% of all rcscctable lesions. After the abandonment of mass radiographic screening, an mcrcasc in more advanced and symptomatic turnours was obscrvcd.

Evalution of the extent of lung cancer Milleron B, Mayaud C, Akoun G. Cenrre de Pneurnologie el de ReanimaGon Respiraroire. Ilopiuzl Tenon, F-75970 Paris Cedex 20. Presse Med 1989;18:1387-9.

The variety of individual opnnons cncountercd in the evaluation of lung cancer is due to the multiplicity of investigations. The inuathoracic extent is basically assessed by bronchial fibroscopy wnh tlcrcd biopsies and computerized tomography. The specificity of computeriLed Iomo- graphy in the evaluation of lymph node involvcmcnt ncvcr exceeds 75 per cent, and although this figure is higher as regards mediastinal or direct chest wall involvement, it ncvcr reaches 100 per cent. The information provided by magnetic resonance imaging is not better. Metastatic extension is evaluated by abdominal uluasonography and computerized tomography of Ihe brain and of Ihe upper abdomen. Sys- tematic radionuclide bone scanning is debatable and some other exami- nations must be reserved to certam histological types; this is the case with bone marrow biopsy (comphxed, if ncccssary, by monoclonal antibodies) or magnetic rcsonancc imaging of bones in small cell carcinomas. The levels of some markers arc well corrclatcd wnh tumoral dissemination.

Cholecystokinin elevates cytosolic calcium in small cell lung cancer cells Slaley J, Fiskum G, Moody TW. Department of Biochemistry and Molecular Biology, George Washingron Unrversily SchoolofMedicine and Health Sciences, Washington, DC 20037. Biochem Biophys Res Commun 1989;163:605-10.

The ability of cholecystokinin (CCK) to elevate intracellular Ca” levels in small cell lung cancer cells was mvestigated using the fluorescent Ca2+ indicator Fura 2. CCK-8 clcvated Ihe cytosolic Ca*+ levels in cell hne NCI-H345 in a dose dcpcndcnt manner. Nanomolar concenuation of CCK-8 elevated cytosolic Ca” levels m the absence or presence of cxuacellular Ca2’. Potent CCK agonists such as gasuin-I and nonsulfated CCK-8 but not inacnve compounds such as CCK-27-

32-NH, elevated cytosolic Ca 2+ levels. Thcsc dala suggest that CCK receptors may regulate the release of Ca2+ from intracellular organelles in small cell lung cancer cells.

Lack of relationship between in vitro tumor cell growth and prog- nosis in extensive-stage small-cell lung cancer Stevenson HC. Gazdar AF, Linnoila RI ct al. National Cancer Insritule- Navy Medical Oncology Branch, Naval Hospital, Bethesda. MD 20814. J Clin 0x01 1989;7:923-31.

The ability to establish a conlinuously growing tumor ceil line from fresh tumor specimens has been associated with shortened survival in some human malignancies. Therefore. we assessed the relationship between survival and in vitro tumor cell growth from specimens obtained during routine staging procedures in 68 consecutive patients with untreated, extensive-stage small-cell lung cancer (SCLC) who received etoposide/cisplatin chemotherapy. Three groups of SCLC patientscouldbedistinguishcd: (1)23patientsm whomatumorcellline was established in vitro; (2) 28 patients in whom tumor-containing specimens were cultured but in vitro growth did not occur; and (3) 17 patients in whom no tumor-containing specimen could be procured. No significant difference in response rates to chemotherapy of the three groups was noted. Poor performance status (P, = X01), male gender (P2 =.0008),liverme~stases(P,=.0033),brainmetastases(P,=.0152),and the ability to obtain a tumor-conmining specimen from the patient for laboratory culture (P2 = X05) were all significant independent predic- tors of decreased survival in this patient population. While the ability to obtain a tumor cell specimen for cell culture using routine staging and diagnostic procedures identified patients with shortened survival, we found no significant survival differences between patients whose tumor cell specimens grew in cell culture v those that did not (median survival of 7 months v 11 months, P, = .72). Our study indicates that the clinical outcome ofextensive-stage SCLC patients from whom tumor cell lines can beestablished is not significantly dlffercnt than in thosecases from whom tumor-containing specimens could not be grown in vitro.

Serum CK-BB as a tumor marker in patients with carcinoma confirmed histologically Arenas J, Diaz AE, Alcaide MJ, Santos I, Martinez A, Culebras JM. Servicio de Bioquimica. Hopital ’ 12 de Octubre’, 28041 Ma&id. Clin Chim Acta 1989;182:183-94.

We determined serum CK-BB mass concentration using a specific RIA method, in 267 patients wilh carcmoma confirmed histologically distributed as follows: 46 pros&tic adenocarcinoma, 52 lung neoplasies, 70 colon carcinoma, 52 breast carcinoma and4 I gastric carcinoma; and also in 135 patients with histologically proved non-neoplastic diseases distributed as follows: 28 prostatic hyperplasy, 31 lung tuberculosis, 29 inflammatory bowel disease, 27 fibrocystic mastopathy and 20 gastro- duodenal ulcer. Reference values in healthy subjects (n = 360) were 5.46 f 2.68 (SD) &ml. We found that serum CK-BB mass concentration is not a specific tumor marker but it is a valuable indicator of responsing to therapy and metastatic widespread. Howcvcr, in prostatic carcinoma

prevalence 0.25, prcdictivc positive value (PPV) 0.51 and predictive negative value (PNV) 0.88 and breast carcinoma prevalence 0.32, PPV 0.6Oand PNV 0.87 strum CK-BB can bc used as a tumor marker. Only 12 over 268 patients with different neoplasnc disease (4.47%) showed detectable serum CK-BB catalytic concentrations.

Thrumhosis-inducing activity found in plasma from two patients with advanced lung cancer MaruyamaM, Yagawa K, Kinjo M etal. ResearchlnsritureforDiseases of rhe Chesr, Faculty of Medicine. Kyushu University, Fukuoka 812. Oncology 1989;46:25 1-4.

In 2 patients with lung cancer, the coagulation system was supposed to be activated by the findings of elevation of plasma fibrinogen, fibrinogen degradation product (FDP) and/or peripheral platelet counts. The plasma thromboxane B, and 6.kern-prostaglandin F( 13 levels in 1

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patient were measured and proved to be 160 and 20 times higher than the control level,respectively. When 0.5 ml ofplasma from each patient was given intravenously into Balb/c mice, the mice died within 5 min. The multiple thrombosis mainly composed of aggregated platelets and present in the lungs of these mice probably led to death of these animals. On the contrary, no such activity was found in plasma from healthy subjects or other patients with lung cancer who showed no manifesta- tions of cnhanccment in the coagulation system.

Thallium-201 accumulation in an unsuspected bronchogenic carci- noma Fakicr DR, Strauss EB. Deportmenr ofRadiology, Section ofNuclear Medicme. NonvalkIIo.~pital, Norwalk, CTO6856. Clin Nucl Med 1989; 14:460-l.

Lung tumors are frcqucntly thallium avid and, indeed, Thallium-201 maybemorespecificthanGallium-67inevaluationofmanyneoplasms. The authors present a case of unsuspected lung carcinoma detected on stress thallium Imaging performed for evaluation of coronary artery discasc

Acute phase reaction during chemotherapy in small cell lung cancer Mdroy R, Shapiro D, Shenkin A, Banham SW. Department ofRespira- tory Medicine, Royal Infirmary, Glasgow G31 2.5. Br J Cancer 1989:59:933-S.

We have measured the serum concentranon of the acute phase reactant, C-reactive protein (CRP), in 20 patients with histologically proven small cell lung cancer undergoing their fist pulse of induction cytotoxicchemotberapy. BaselineCRPconcentrationswereraisedin 16 of 20 patients (median baselme CRP 18.5 mg I ‘; normal range ~10 mg I ‘). CRP levels more than doubled in I 1 of 20 patients during inductIon chcmothcrapy. Ttns acute phase reaction was seen m seven of the 10 chemosensiuve patients, but was not observed in any of the five non- responding patients. Five patients were non-cvaluable for chemorc- sponse. These data indxate that there is a previously undescribed quantlfiablc acute phase response during chemotherapy for small cell lung cancer winch has potential for predicting chemoresponse.

Thallium-201 single photon emission computed tomography in the evaluation of suspected lung cancer Tonami N, Shukc N, Yokoyama K et al. Department qf Nuclear Medrcme. Kanazawa lintversity School of Medicine. Kanazawa 920. J Nucl Med 1989;30:997-1004.

Thallium-201 SPECT was performed in 30 patlcnrs with suspected lung cancer. Both early and delayed scans demonstrated abnormal accumulation inallof23 mal~gnantpulmonarylesionsincluding21 lung cancer and in two of seven benign conditions. There were significant dlffercnccs m delayed ratio (uptake ratio of the lesion to the normal lung on dclaycd scan) and rctcntion Index (degree of retention m the lesion) between lung cancer and benign conditions, respectively (p < 0.01, p < 0.05). The delayed ratio and rctcntion index revealed that adenocar- Cmoma showed higher “‘Taccumulationthan squamouscellcarcinoma and small ccl1 carcinoma (p < 0.05) and U’T clearance in squamous cell carcinoma was faster than in the other two (p < 0.05). Medlasdnal involvement wasdetected mfivcofsevenpadcntsondelayedscans.The smallcstlesiondepictcd was I .5 cm indiamctcr. Twofalscnegatives had small mciastaxs < 1 .O cm in diameter. This method seems to be useful todetectlungcancer.todiffcrcntiatcmal~gnantfromhen~gn lesions.and to c>aluatc mediastmal involvement from lung cancer.

Pre- and postoperative sequential study on the immunosuppressive activity of serum and cell-free skin bleb fluid of patients with lung cancer and esophageal cancer Zhou Q. Yang Z, Zhang H, Yang I. Xlao Y. Department of Thoractc Cardwvasrular Surgery. The First A@lrated IIosIxral. Wesl Chma (lnrwrztr~ oj Medrul S~~wnccs, Chengdu, Slchuan J Surg Oncol I989:ll:l?l-7

Serial changes of tmmunosupprcsslvc acuvlty of xxml and cell-fret skin bleb fluid that can suppress the actlvlty of aLId a naphthyl acetate csterasc (ANAE) of lymphocytes and phagocytoslc of macrophages were detected by immunoregulatory tests in vmo in SO lung cancer and 42 esophageal cancer patienls. In comparmg these tests with those of 53 cases of noncancerous thoracic lesion and 69 normal adults, the Immu- nosuppressive acuvity of serum and skm blcb fhnd from cancer patients IS sigmficantly higher than that of noncancerous thoraclc lesions and normal individuals (P < .Ol ). The acuvity is related to the stages of cancer, the sue of primary tumor, the prcscncc of lymph node mctasta- ~1% and tumor resectabihty, but not to histologIca classrflcation, sex, and age. The immunosuppressive acti\lty of serum and \km bleh flmd dccreascd gradually after the removal of the tumor and was climmarcd on the 30th postoperatlvc day. Thcsc rc\ultb suggest th.u serum and skin bleb flmd from cancerpatxntb may contam unmunosupprcsslve lactors thatcan suppress the Immune rcsponalrc functions ol lymphocytesand macrophages m vitro ma manner similar to that seen or. v~vo. Thereforc, complctc surgical removal of cancer IS likely the ~most cfl?ctlve Immu- nothcrapy.

Uptakeand kineticsofTc-YYm hexakis 2-methory isobutyl ionitrile in benign and malignant lesions in the lungs Hassan IM, Sahweil A, Constantimdc> C 1-t al. Dcp<xm~~nf ofNuclear Medicine, Faculty ofMedicine. Chcsr Ilospual. K,AHUI (‘:mrerControl Center. 13110 Safat Clin Nucl Med 1989:14:333J0

KineticsofTc-99m MlBI uptake was studlcd m I9 paucnu with lung lesions (6 benign, 13 mahgnant). Two dynamic studlcs were acquired after the I.V. injectionof IO-15 mCi (370-550 MB@: the firstwasevery second for 60 seconds. followed by a second on? every mmute for 30 minutes. Delayed images were acquired at two and three hours. By assigning regions of interest (ROI) over the lurlg Icl;lons (TRI. con- tralatcral normal lung (NL) and the heart (HI), Llrnc activity curves (TAC) were generated and time to peak actlvtty wa\ <alculated as well as the rauos of TR/NL. HllrR and HI/IIL.. The HI/NL rat10 w;t5 also assessed m five patrents rcfcrrcd wlrh dlagnosi\ 01 lxhacrnlr heart disease (IHD) for myocardlal nnagmg. There wa\ d Iocall/cd mcreasc of Tc-99m MlBl uptake in ten patlcnts with untreated maltgnant tumours of the lung. No Itxalt/rd uplahc wa\ found m one patient with untreated poorly differentlatcd squamous czll carcmoma. two treated lung cancer and four patlent? with non-mallgnant Irblon\ of the lungs. Two pahems with tibrosmg alvcohtl\ hhowcd ~dlffusc Incrcasc lung uptake In all posrtlvc \tudlc\ peak tumour was rcachc,d wltlun the first mmute. ThcreHaz,noslallsllcal dlffcrence lnthc ratloc,fHI/NL~twccn all groups cxccpt in patient\ with flbro\mg alvl:ohtl5. rhcre was no \Ignlficantdlffcrcnccb~t~‘~cn thcratlosTK/NL, HI/TRand HmLat S- IOminute~and75-.~Ominut~~.Thcrat~c~ofTR/N1.~t~5 .3Ominuteswas lSX*O.36m thcposmvccases verhus I +(I.?1 Inthenzg;ltlvcon~s.l’he mean H0R ratlo was I .7 + (1.35 m the poaitlbc one\ \ er\u\ 1.14 + 0.54 I” those with benign Ic~onsofthc lung,. Thl\ mltlal \tud! dcmonctrates the uptake of Tc-09m MIBI rn malignant tumourx alth prommcnt dlffcrcncc between hcnlgn and maltcnant lc’;mn\ ‘t I\ cvldcnt that radmthcrapy mhlhlt% this uptake.

Rronchogenic carcinoma in patients under age 10 Antkowiak JG, Regal A-M, Takita H. fleportm~r!t o/ I’h~racrc Sur@‘~ and Oncology, Rowe11 Park Memorial Inttltutr B&al/~ .SY I Q6.J. AnnThordcSurg 1989:47:391-3.

Eighty-nine patients aged I9 to 39 1 cx\ wcrc ueatcd Ior bnlncho- Sentc carcinoma at Roswell Park Mcmorlal Inatltutc hctwccn 1971 and 10X3. The malt to fcmalc ratlo was I .6: 1. T’hc vast maJorit) ofpaoenti wcrc habuual clgarcttc \mohcrs. Forty tour paurnt\ (4’J(; 1 had adrn- ocarcmoma or bronchoalveolar ccl1 ~arcmoma r&f. ntk-xeven (30% 1 had large ccl1 und~flcrcntlatcd carcmoma. hmc I IO”+) had sm.dl ccl1 carcmoma and 6 (7%). squamous ccl1 c:u~uxxna. At the taut ofdw~m~~~s, 7patients(2%) hadstage I disease, 3 (3%) hadstagc II &%asc,30(34%) had~la~clllAd1~~a~c,~~~3~~~ ~hads~;r~cllll~d~~c.~~c.an~llf~(lo“i~had