Protein turnover in advanced lung cancer patients

216

Abstracts/Lung

Significantlygreaterdifferencesindisruptionsofqurdityoflifeoccurred in women younger than 65 years (p = 0.04). women with recurrent disease @ = 0.003). and women with low income @ = 0.008). In stepwise regression. symptom distress predicted 53% of the variance followed by fonctional status (59 96)and recorrence (63 96) when QGL was the outcome variable.

Clinical manifestation3 of lung cancer Pate1 AM, Peters SG. Mayo Clin Prw 1993;68:273-7. Theiniti~cl~crlmpnif~tioasoflungcollcerarediverse~dmav lesions areproduced bb l&xl nrowth or invasion. &astaticdisea&

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syndrome or the superior vena cava syndrome are.relatively uncommoo but well recognized. M-tic bmg cancer can involve almost any anatomicareabybem&genowemstogeaous, lymphatic,or,occasionally, interalveolar dissemination. Complications related to malnutrition, infection, electrolyte distorbances, nod coexisting diseasea influence the initial manifestations. AlthoughiadividuPltumorcelltypesnresssocintedwith characteristic features, no constellation of tindiigs is pathognomonic for P specific histologic vtisnt. Becaose stwessfld treatroeat of pulmonary carcinoma depends on early detection, awareness of the typical clinical manifestations is importaot.

Partmeoplnstic syndromes pssoeiated with lung cancer Pate1 AM, DavilnDG, Peters SG. VniversiiyofAlabamn, Birmingham, AL Mayo Clii. Pmt. 1993:68:278-87. P~raneopl&ic pheaomerta associ&d with primary long caocerhave diverse initial manifestntions and epitomize the systemic nature of human malignant disease. The spectrum of clinical features in patients witb paraneoplastic syndromes ranges from mild systemic or cutaneous disease to bypercoagulability nod severe neoromyopatbic disorders. Although the diagnosis is often one of exclusion, a0 improved understandiig of the pstbogenesis involved io some of these syndromes has provided another means of recognizing the disorders and perhaps treating the affected patients. Proposed mechanisms of paraneoplastic processes include the aberraot release of bumoral mediators such as bonnones sod hormone-likepeptides, cytokinw, and antibodies. In this update, we review the potential mechanisms, diagnosis, and treatment of paraneoplastic syndromes associated with long cancer.

Diagnostic tests for lung cancer Karsell PR, McDougall JC. Mayo Clin Proc 1993;68:288-96. Tbegoalsofdiagnostic testing inpatients withsuspected long cancer are to establish the diagnosis and to determine the stage of the disease so that appropriate therapy can be initiated. Unless a patient has bemoptysls, fever, or a change in cough as an initial rnaoifestation, resectable lung cancer will seldom be diagnosed on the basis of the history. Screeoingtests-particularlycbestroatgwography-bavewully identified the abnormality. The managing pbysiciao should then select diagnostic procedures that are associated with low risk and that will provide further diagnostic and staging information. A biopsy will almost always be necessary before definitive therapy can be planned. In many cases, a single procedure-for example, a needle biopsy of a bepatic lesion or biopsy of P supraclavicolar lymph node- will provide a definitive diagnosis and establish the stage. of the disease.. The roles of cytology, histopatbologic examination, radiologic studies, and various types of biopsy in the diagnosis of lung cancer are reviewed in this report.

Serum tumor markers CEA, CA 50, TATI, and NSE in lung cancer screening Jsrvisalo J, Hakama M, Knekt P, Stenmao U-H, Leino A, Teppo Let al. Research and Dewlopmenr Vnir, Social Insurance Insrirurion, Pelmlantie 3, SF-2OMo

Turku. Cancer 1993:71: 1982-8.

Background. There are. no effective means for screening for long cancer, so the authors assessed the utility of four lung cancer honor markers for screening. Methods. A case-control study, nested in B cohort study based on the linkage of records of health survey exam&es

Cancer 10 (1993) 266-286

with Finnish Cancer Registry records, was used to test the validrty of honor markers carcinoembryonic antigen (CEA), tumor-associated trypsin inhibitor (TATI), neuron-specific eoolase (NSE), and CA 50 in lung cancer screening. Ten years after health examinations, record linkage indicated that 187 men bad lung caocer; 344 control subjects. matched for age, sex, and municipality were draw from the same records. Results. The data allowed assessment of the sensitivity of the marker assays at a 95 96 specificity level, which was highest for CEA (17% at a concentration level of 5.3 g/l). Logistic discrimination analysis indicated that of the other markers, only TATI, when used in combination. improved the discriminatory power of CEA. CEA and TAT1 levels correlated significantly with smoking. They also showed a significant gradient toward increasing risk of lung cancer from the lowest to the highest quintiles of marker levels (for CEA, crude relative risk between the highest and lowest quintiles, 8.6). The gradient also was evident in the subgroup whose cancer had been diagnosed more than 5 years after serum specimen collection. The trend persisted, although relative risk was balvedsfteradjustment for smoking. Conclusions. The markers do not seem to be useful tools for lung caocer screening. However, CEAaodTATl levelsseemtogiveinformationoncancerrisk long before the clinical cancer stage, as the quintile-based analyses of marker levels indicate. Lung cancer in patients with immunod&ciency syndrome Karp J, Profeta G. Marantz PR, Karpel JP. Monrefiore MedicoI Center, 111 Em 210th Srreet, Brom, NY 10467. Chest 1993;103:410-3. We report adenocarcinoma of the lung in seven patients with buman immunodeficiency virus (HIV) infection. We compared age, clinical findings sod survival data with B sex-matched control group of HIVnegative patients with adenocarcinoma of the lung. Median age of HIVinfected patients with hmgcancerwas lower than in control patients with lung cancer. The HIV- infected patients had more systemic symptoms and abnormal physical findings than control subjects. Both groups had smoking histories. Laboratory d&were similar but control subjects bad lower blood oxygen tensions than did HIV patients; HIV patients bad moreabnormalitiesoncbestroe.ntgenogramsaodcomputedtornograpby scans tbandidcontrol subjects. All HIV-infected patientswerestageIV. Median survival was 4 weeks. For control patients, 50percent bad stage IV disease; median survival was 25.5 weeks. Thus, patients with HIV infection develop lung cancer ntayoongerage than sex-matched control subjects and undergoa tnorefulminant course withshortened survivals.

Protein turnover in advanced lung cancer patients Richards EW, Long CL, Nelson KM, Tobver OK, Pinkston JA, Navari RM et al. Depanment of Research. Baprisr Medical Cenrers, 701 Princeron Ave. Birmingham, AL 35211. Metab Clin Exp 1993;42:2916 Understanding the extent to which changes in whole-body protein kinetics contribute to the commonly observed weight loss aod decrease in lean body mass (LBM) in patients with cancer is currently obscured by conflicting reports in the literature. While several studies have reported significant increases in whole-body protein tornover (WBPT), synthesis (WBPS), and catabolism (WL3PC) in patients with caocar, others have failed to confirm these observations. We have measured whole-body protein kinetics using II primed constant infusion of “Nglycine in a homogeneous group of 32 newly diagnosed advanced long cancer patients with cornparable staging nod before soy antineoplastic treatment, and in 19 normal healthy volunteer controls. Urinary urea and ammonia “N emicbment was determined io individully colle&d urine samples obtained during the 24-boor study period end averaged for the determination of protein kinetics. During the last 6 boors of urine collection, samples were obtained hourly for determination of “N plateau enrichment. Twenty-four-hour urinary nitrogen nod creatinine excretion was determined from 24-boor pooled urine samples. Resting metpbolic expenditore (RME) was determined by indirect calorimetry and LBM was estimated from deoterium oxide dilution. Age. body weight, LBM, RME, and 24-hour urinary nitrogen excretion did not differ between canceraod control subjects. WBPT, WBPC. and WBPS (g/kg/d) were significantly increased in long ceocer patients. However, when the same results were expressed either per kilogram LBM or per gram 24-hour urinary cnxtioine excretion, WBPT. WBPC, and WBPS rates were not statistically different from those of the controls. Net

Abstracts/Lung

Cancer

10 (1993)

266-286

protein synthesis (WBPS - WBPT) was not different from that of the controls, regardless of how data were expressed. These results reveal that protein kinetics in the lung cancer patients were not significantly different from those of the control group when normalized to active muscle OIPSS,sod suggest theI newly diagnosed ooncachectic advanced lung cancer patients do not exhibit a signiticanC increase in whole-body protan kinetic rates.

An ACTH-secreting bronchial carcinoid: Rgeneeofcorticotropinreleasing hormone, neumpeptide Y and endotbelin-1 in the tumor tissue

Murakami 0, T&h&i K, Sane M, Totsune K, Ohneda M, Itol K et al. SecondDeportment Infernal Medicine, Tohoku University, School of Medicine, I-I Seiryo-rho, Aoba-ku, Se&d, Miyagi980. ActaEndocriml 1993;128:192-6. The presence of three regulalory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-I, was studied by radioimmunoassay in the tumor tissue of no ACTH-secreting bronchial carcinoid. A 36.yearilld female was admitted to hospital because of moon face, central obesity end hypertension. High levels of plasma ACTH and cortisol and urinary I7-OHCS and 17.KS were found. One rug dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotroprin-releasing homrone (100 g, iv) strmulated plasma ACTH levels (0 mm: 34.8 pmolll; 30 min; 41.1 pmol/l). Thecomputerized tomography showed the preseoceofa tumor in the right lung. This lung tumor was removed surgically and has been shown by rmcroscopical examination to be a bronchial carcinoid with ACTh-positive cells. The tomor tissue concentrations of corticotropinreleasing homwne, neuropeptide Y and endothelin-1 were 3.34 pmol/ g wet waght, 8.07 pmollg wet weight end 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides werenotelevated. Reversephasehighperfonnanceliqurdchromatography showed that immunoreactive peptides in the tomor tissue were mainly eluted in the posltion of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of cortlcotropin-releasing hormone, neuropeptide Y and endothehn-I in Its tumor tissue and suggested that these peptides may act locally, III a paracrine or aulocnne manner, in the tumor.

Pancoast syndrome: An unusual presentation of adenoid cystic earriooma

J&ton MQF, Allen MB, Cooke NJ. Belvidere Hospiral, London Rd. Glasgow. Eur Respir J 1993;6:271-2. We report on a patient with primary pulmonary adenoid cystic carcinoma presenting with Pancoast syndrome. Pancoast syndrome has not previously been described with this hunour. Other unusual features of this case include the peripheral origin end mediastinal involvement, with lack of proximal endobronchial spread.

Patient progress modclling for small cell lung cancer

Pearce RM, Gallivao S. Jackson RRP. Clinical Operational Research Unit. Depuimenz of S?afistical Science. Universiry College. Cower Srreet,London WClE 6BT. EurJ CeruxPnri AGen. Top. 1993;29:7347 This paper describes the use of a mathematical technique called Patient Progress ModeRing to reassess the results of en MRC trial on small cell lung cancer. The trial eoncemed patients treated initially with chemotherapy and radiotherapy and achieving at Ieat e partial response. It cornpored the effects of giving maintenance chemotherapy with those of giving no maintenance therapy. ‘I& results of the MRC trial established that there was oo significant survival difference between the hvo groups overall. However, it was observed that amongst patients achievingammpleteresponse,thosereceiv~gmPin~cbemotherapy had P small survival time advantage. The analysis described here suggests the hypothesis tba1 this can be accour~tedfor by differences in the pattern of deaths n&r relapse. There appeared to be little difference in Ihe disease-free period. Spontaneous pneumothorax as initial symptom of bmncbial caminoma

Pohl D. Herse B, Criee C-P. Dali&au H. Klinikf: i’horar-. Her? und,

277

G$&rtirurgie,

Univ0sirarGorringen.W-34OOGntingen.

Pneumologie

1993;41:69-72. Spootaneous poeumothorax is cased by benign lung diseases in more than 95 percent. Mainly preeeoling in younger male patients between 20 and 40 years of age its prognosis is generally good. - On the otber~d,powmothonxasinitinlmPoifesrptionofbronchinlcnrcinoma is P rare complication with poor prognosis. We report such P case of a 70 year-old man, review the literature and describe charactenstical problems in diagnosis and therapy of very soul1 broocbogenic hunore. Estimating that only 2 percent of all spontaneous pneumothoraces are coexisted with melignenc long diseases - either primary or secondary this tumor-complicatioo especially most be considered in older patients. Their prognosis may be improved entirely by rapid diagnosis and therapy. Broncbogenic carcinoma in young patients at risk for acquired bnmunodefciency syndrome Chao

TK, Amode CP, Rom WN. Department of Medicine. Bellewe of Medicine. New York, NY. Chest 1993;103:862-4. Several case reports have suggested that broochogemc carcmoma occurs more frequently in youog patients who are human mrmunodeficiency virus (HIV) seropositive. We investigated the incidence of bronchogenic carcmoma and its clinical presentations in young patients aI risk for HIV infection. The tumor registry of Bellevue Hospital was reviewed, and 261 cases of bronchogenic carcinoma during the period from 1976 to 1979 @e-AIDS period) and 232 during the period from 1987 to 1990 (AIDS period) were identified. These cases were stratified into age groups: 45 or younger, 46 to 55,56 to 65, and 66 years or older. All patients aged 45 years or younger m the AIDS period were subdivided by HIV risk, and clinical characteristics were comparedamong thesubgroups. Results revealed no increased inadence of bronchogenic carcinoma from the pre-AIDS period compared with the AIDS period. These results suggest that HIV seroposltivlty 1s not a risk factor for bronchogenic carcinoma. Hospital, New York University Sch.

A random&d

study comparing cyclophospbamide, doxoruhicin,

vincristine (CAV) with cyclophospbamide, etoposide, vincristine, metbotrexate (CEVM)

in patients with small cell lung cancer

Erkasi M, Unsal M, Tunali C. Burgut R, Dorae F. Department of Oncology, University of Cukurova. Adana. J Chemother 1993;5:56-9. This tnal was carried out to assess the response rate and survwal benefit a&lewd. If any. by substitution of etoposlde for doxorubicm and addition of metholrexale in combmation with cyclophosphamide and vincristine m the treatment of 113 patients wth small cell lung carcinoma (SCLC). Cyclophosphamide, etoposide, vincristine, methotrexate (CEV-M) ylelded a response rate of 75% m localwed dwase(LD) aod63W inextensivedwease(ED), versus61 96 in LDaod 52% in ED m the cyclophosphamide, doxorubicin. vmcristme (CAV) arm. There was also a slgniticanl survival bznetit for the responders m favor of CEV-M (21.7 * 3.8 months of median survival compared lo 13.6 k 2.8 months in CAV arm) in p&ems wth LD.

Surgery Exercise testing, 6-min walk, and stair climb in the evaluation of patients at high risk for pulmonary resection Holden DA, Rice TW, StelmachK. Meeker DP. Cleveland Clinic Foundarion,

9500 Euclid Avenue, Cleveland, OH 44915-5038.

Chest

1992;102: 1774-9.

To evaluate thr= types of exercise testing in predlchon of death or prolonged mechanical ventilation afler lung resection in lugh-risk patients, 16 patients underwent evaluataon prior to resection. Eleven patients(group I)hadminorornocomplicatiotw(arrhythmia,atele&sis, pneumonu) sod five patients (group 2) died within 90 days of surgery. Exerase testing showed Ihat group 1 had a longer 6-min walk distance. and a higher stair climb than group 2. The maximum oxygen uptake on a cycle ergometer was not sigmficantly different between groups, althoughonly tenpatientscompleredthistest. Group I hadnslgnificaotly greater calculated oxygen uptake with stair climbing then group 2. A 6. mm walk distance of greater than I .OCOfeet and a stair climb of greater