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Pneumococcal serotype 3 accounted for about 25% of all

pneumococcal infections but for over 50% of deaths. Thefrequency of other types is similar to that in previous reportsfrom Britain.9,lo 80% of the types implicated in this study areincluded in the effective and available pneumococcal vaccine(’Pneumovax’: Thomas Morson Pharm.). Since antibioticsalone have not solved the problem of this common infection,the older patient with chronic illness, who is at special risk,may benefit from pneumococcal vaccination.

Legionnaires’ disease (LD) was the second commonestcause of pneumonia (15%). This is the highest incidencefound in a prospective study. In Bristol,3 only 3 cases werediagnosed from 210 consecutive patients seen with

pneumonia. Half of our LD patients were not seriously ill andthe diagnosis would have been missed if convalescent

serological tests had not been performed. This suggests thatthe reported incidence of LD depends on completeserological follow-up. Serological screening of populationssuggests that the incidence of LD is no higher in Nottinghamthan elsewhere." 3 of our patients appeared to haveinfections with other legionella species and such infectionsare now also being recognised in non-immunocompromisedpatients in North America. 12,13 Although no patients died ofLD, 9 had a complicated course and 3 required assistedventilation, emphasising the potential severity of thisinfection. The seasonal variation in incidence suggests that itshould be suspected particularly in the summer, when itaccounted for nearly half of all our cases of pneumoniaadmitted to hospital.Mycoplasmal pneumonia was uncommon in this series

which reflects its variable incidence.14 Peaks occur every 3-5years, the last being in 1979 during the period of the Bristolsurvey3 in which mycoplasmal pneumonia was diagnosed in14% of patients. M. pneumoniae was not recovered from sputaor throat swabs in our series, an indication that the normalcarrier rate is low. The presence of cold agglutinins was not areliable indicator of sporadic mycoplasmal pneumonia sincethere were several false positives.Other causes of pneumonia were less common, although

the mortality from haemophilus and staphylococcalpneumonia was high.Although ampicillin is probably the commonest antibiotic

prescribed in and out of hospital to treat pneumonia, aquarter of the organisms from our study were resistant to thepenicillins. It is therefore now our policy that all patients

_

admitted with severe pneumonia receive high-dose ampicillinand erythromycin intravenously at least until laboratoryevidence of the cause becomes available. Such a regimen iscombined with oxygen therapy, frequent monitoring of-arterial blood gases, and early assisted ventilation whenrequired. We hope that this approach, together with a betterunderstanding of the causes of pneumonia, will reduce itsmorbidity and mortality.We thank Dr D. Davies, Dr W. H. Roderick Smith, our medical, nursing,

and laboratory staff colleagues, Dr D. Taylor Robinson, and Dr B. E.’Andrews. The study was supported by a N.H.S. locally organised researchgrant.

Correspondence should be addressed to J. T. M., Department of ThoracicMedicine, City Hospital, Hucknall Road, Nottingham NG5 1PD.

REFERENCES

1. Cecil RL, Baldwin HS, Larsen NP. Lobar pneumonia. A clinical and bacteriologicstudy of two thousand typed cases. Arch Intern Med 1927; 40: 253-80.

2. Bath JCJL, Boissard CPB, Calder MA, Moffat MAJ. Pneumonia in hospital practice inEdinburgh 1960-62. Br J Dis Chest 1964; 58: 1-16.

3. White RJ, Blainey AD, Harrison KJ, Clarke SKR. Causes of pneumonia presenting to adistrict general hospital. Thorax 1981; 36: 566-70.

4. Davies D. Legionnaires’ disease. Advanced Medicine 1980; 16: 51-58.5. El-Refaie M, Dulake C, Tait R, Dische FE. Pneumococcal antigen in pneumonia A

post mortem study with the histological and bacteriological findings Postgrad Med J1976; 52: 497-500.

6. El-Refaie M, Dulake C. Counter-current immunoelectrophoresis for the diagnosis ofpneumococcal chest infection. J Clin Pathol 1975; 28: 801-06.

7. Macfarlane JT, Finch RG, Laverick A, Macrae AD. Pittsburgh pneumonia agent andlegionellosis in Nottingham. Br Med J 1981, 283: 1222.

8. Barrett-Connor E. The non value of sputum culture in the diagnosis of pneumococcalpneumonia. Ann Rev Resp Dis 1971; 103: 845-48.

9. Turk DC. Pneumococcal types causing serious disease in Britain. Royal Society ofMedicine international congress and symposium series No. 27. 1980; 23-27.

10. Parker MT. Serotype distribution of pneumococci. Royal Society of Medicineinternational congress and symposium series No. 27. 1980; 11-21.

11. Macrae AD, Appleton PN, Laverick A. Legionnaires’ disease in Nottingham, England.Ann Intern Med 1979; 90: 580-83.

12. Ackley AM. Community acquired Legionella micdadei pneumonia. Lancet 1981; i 221.13. Aronson MD, Komaroff AL, Pasculle W, Myerowitz RL. Legionella micdadei

(Pittsburgh pneumonia agent) infection in nonimmunosuppressed patients withpneumonia. Ann Intern Med 1981; 94: 485-86.

14. Noah ND, Urquhart AM. Epidemiology of Mycoplasma pneumoniae infection in theBritish Isles 1974-9. J Infection 1980; 2: 191-94.

Treatment of Malignant Disease

QUALITY OF BREAST-CANCER CAREIN ITALIAN GENERAL HOSPITALS

A. LIBERATIF. COLOMBO

S. FRANCESCHI

A. ANDREANIC. CONFALONIERIC. LA VECCHIA

G. TOGNONI

Istituto di Ricerche Farmacologiche "Mario Negri", Milan, and 2ndMedical Division, Ospedale di Rho, Milan, Italy

Summary The diagnostic and therapeutic care

and degree of follow-up delivered to 2406breast-cancer patients over two years (1978 - 79) in 31 Italianhospitals are reviewed. Although there was broad agreementabout recommended treatment protocols, staging bystandard methods was recorded in only 44% of patients,assessment and reporting of side-effects was considered inonly 49% of all treated patients, follow-up data at two yearswere available for only 54% of living patients, and thedropout rate from chemotherapy protocols was 35%.

Improvement of these unsatisfactory aspects of care wouldallow a better appreciation of the real benefit that could beachieved with recommended protocols and would result in amore effective use of health resources.

INTRODUCTION

BREAST cancer is the commonest malignant tumour inWestern countries besides non-melanotic skin cancers. 1

Positive reports on the success of treatment by surgery,radiotherapy, and chemotherapy2-’ 1 contrast with thecontroversies about primary prevention,’2 earlydiagnosis, 13-15 and adjuvant chemotherapy and the

management of advanced stages in relation to survival and

quality of life.16-23This study investigates how such problems are reflected in

routine clinical practice in Italy.

PATIENTS AND METHODS

Medical records of all breast-cancer patients seen in two years(1978-79) in 31 general and community hospitals in Italy werescreened by medically qualified investigators, with the agreement of

259

the medical staff in charge. The hospital sample included 3 hospitalswith full oncology departments, 10 hospitals with oncology wardsand outpatient facilities, and 18 hospitals with no specific oncologydepartments. 1934 women previously diagnosed as having breastcancer and 472 newly diagnosed patients were included in the study.Data were analysed for: (i) clinical history preceding and leading tothe index hospital admission; (ii) staging and hospital treatment; and(iii) variables selected as indicators of quality of care (accuracy offollow-up, documentation of side-effects).Data were checked and coded by the principal investigators. 18

patients were excluded because of benign neoplasia, secondaryneoplasia, and diagnostic inconsistencies between hospitalregistries and patients’ charts. The Statistical Package for the SocialSciences (SPSS) was used for data analysis.

RESULTS

The stage of disease was recorded for only 44% of allpatients and there was both histological confirmation andknowledge of lymph-node status for only 31% (see table).Lymph-node status was not recorded for 887 patients (37%):for 319 of these patients histology only was reported, and forthe remaining 568 data were not available. Standardclassification was adopted for histological findings in 1267cases (53%), other classifications were adopted for 344

patients (14%), and no information was available for 795patients (33%). 2210 patients (92%) underwent surgery and1781 (80%) had radical mastectomies (Halsted or Patey). 67%had supplementary treatment with chemotherapy (44%),radiotherapy (34%), and hormonal therapy (32%). Only 84received monochemotherapy. The remainder had poly-chemotherapy, the proportion of patients increasing fromstage 1 (30%) to stage IV (74%). Most of the 927 patients whoreceived first-line combination chemotherapy had

cyclophosphamide, methotrexate, and 5-fluorouracil (CMF).Hormonal treatment was given to 865 patients, and 79% ofthem had drugs rather than ablative treatment. Side-effectswere reported for only 588 (49%) of the patients whounderwent chemotherapy. These included nausea and

vomiting (32%), leucopenia (20%), hair loss and alopecia

DISTRIBUTION OF 2406 CASES OF BREAST CANCER ACCORDING TO

STAGE, HISTOLOGY, AND CLINICAL DIAGNOSTIC PROFILE

(16%), thrombocytopenia, amenorrhoea, and paraesthesiae(4%), stomatitis (3%), and cystitis (2%).

1517 patients (63%) had been diagnosed within the

previous two years, and stage notification appeared to be onlyslightly more frequent in recently diagnosed patients. Only1148 (54%) patients were regularly followed up according tostandard protocols.

DISCUSSION

We had two working hypotheses for this study. The firstwas to assume that a picture of what really happens inuncontrolled cancer care is needed to interpret researchfindings, and that such a picture can be obtained fromavailable data. The second assumption was that reliable datafrom a survey such as this are the best guide for planning acoherent and comprehensive approach to cancer care. Wetherefore compared our data with those obtained from muchlarger samples in the U.S.A. 24,25 and found that they were inbroad agreement. The larger proportion of our patientstreated with surgery plus chemotherapy (27% versus 17%and 18% respectively) may be due to the influence of thestrong promotion in Italy of this strategy of treatment by anationwide programme.26 The consistency of our findings isconfirmed by a comparison with other data from the U.K.and U.S.A. (discussed in detail elsewhere27).Delay in diagnosis was a most striking finding, the interval

between presentation of symptoms and diagnosis beinglonger than six months in 25% of cases. The clinical impli-cations of these data cannot be evaluated, since there is atpresent no firm evidence that earlier diagnosis of breastcancer is associated with improved survival.15 However,since another study has documented a similar phenomenonfor endometrial cancer, for which a delayed diagnosis isassociated with a worse prognosis,28 this finding suggests aproblem peculiar to Italy, possibly attributable to physicians’non-caring attitudes and to lack of health education amongthe women. The most successful treatments have been largelyaccepted (78% of all patients were treated according to ItalianNational Breast Task Force recommendations26), but otheraspects of the management of breast-cancer patients present agloomy picture: standard stage classification was reported inonly 44% of patients; the pathological status of ipsilateralaxillary nodes was unknown in 37% of cases; chemothera-peutic protocols were inadequately documented in 39% ofcases (e.g., cycles or dosages not reported); and no reason isgiven why 416 (35%) of 1189 patients did not complete theirplanned chemotherapy schedules. For 56% of patients noinformation is given on the radiation dosage. Side-effects arenot mentioned in the medical records of 5107o of patients: ofthe 1148 patients in follow-up only 429 (37%) appear to havebeen regularly followed for more than two years. Thus aserious gap between recommended standards and actual prac-tice emerges from the above findings, and these cannot beattributed simply to unsatisfactory reporting in medicalrecords. The picture should not, however, be viewed as anexample of malpractice typical only for Italy. Similar resultshave been reported in a large survey of breast-cancer manage-ment in 170 radiological departments in the U.S.A., wheresites and sizes of primary lesion were not documented in 20%and 40% of patients, respectively, and clinical stage wasstated in the charts of fewer than one-third of the patients.29The quality of life of cancer patients undergoing various

forms of aggressive treatment is likely to attract increasingattention and to become an integral part of the evaluation ofthe overall outcome.30,31 Assessment of the benefit/risk ratio

260

will become reliable and consequent attempts to obtain

patients’ understanding and compliance will become success-ful only when the quality of delivered care can claim to becomparable with the best achievable results. Careless

organisation and documentation of clinical activity are

inevitably seen as reflecting the quality of care and willdiminish the effectiveness of diagnostic and therapeuticmeasures. Comparative data from other countries stronglysuggest that the overall picture documented here could be ofrelevance outside Italy and point to the need for a systematicfollow-up of recommended diagnostic and therapeutic prac-tices, to allow a more accurate estimate of their benefits.

We thank the following for their help with regional coordination and localdata collection: Dr Marino Cecere, Dr Domenico Ferrari, Dr Gianni Fran-chin, Dr Saverio Giomi, Dr Ulrico Martinelli, Dr Ilde Piccioli, Dr FaustoRoila, Dr Renato Talamini, Dr Maurizio Tonato. Clinicians from thefollowing hospitals made this study possible through their help in dataretrieval: Arezzo, Avellino, Carrara, Chiavenna, Citta di Castello, Como,Cuggiono, Foligno, Gorizia, Grosseto, Gualdo Tadino, Lecco, Legnano,Lucca, Magenta, Morbegno, Monfalcone, Palmanova, Perugia, Pistoia,Pontedera, Pordenone, Rho, Sacile, S. Vito al Tagliamento, Salerno, Sondalo,Sondrio, Tirano, Todi, Val di Chiana. We thank Anna Mancini for her help inpreparing and editing the manuscript, Judy Baggott for revising the Englishtext, and Anna Maria Chimienti for preparing the reference.

This study was supported by a contract of the Italian National ResearchCouncil, Progetto Finalizzato "Controllo della Crescita Neoplastica"contratto no. 80.01660.96, and by the Italian Association for Cancer Research,Milan, Italy.

Correspondence should be addressed to A. L., Istituto di Ricerche

Farmacologiche "Mario Negri", Via Eritrea 62, 20157 Milan, Italy.

REFERENCES

1. Saracci R, Repetto F. Epidemiology of breast cancer. Semin Oncol 1978; 5: 342-49.2. Bonadonna G, Valagussa P, Rossi A, et al. Are surgical adjuvant trials altering the

course of breast cancer? Semin Oncol 1978; 5: 450-64.3. DeVita VT, Jr. The evolution of therapeutic research in cancer. N Engl J Med 1978;

298: 907-10.4. Fisher B. Breast-cancer management. Alternatives to radical mastectomy. N Engl J Med

1979; 301: 326-28.5. Golinger RC. Breast cancer controversies: Surgical decisions. Semin Oncol 1980; 7:

444-59.6. Henderson IC, Canellos GP. Cancer ofthe breast. The past decade. N Engl J Med 1980;

302: 17-30; 78-90.7. Lipsett MB. Postoperative radiation for women with cancer of the breast and positive

axillary lymph nodes. Should it continue? N Engl J Med 1981; 304: 112-14.8. Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mastectomy with

quadrantectomy, axillary dissection, and radiotherapy in patients with small cancersof the breast. N Engl J Med 1981; 305: 6-11.

9. Martin DS. The scientific basis for adjuvant chemotherapy. Cancer Treat Rev 1981; 8:169-89.

10. Henney JE, De Vita VT. Future perspectives in the treatment of breast cancer. SeminOncol 1978; 5: 465-68.

11. Moxley JH III, Allegra JC, Henney J, Muggia F. Treatment of primary breast cancer.Summary of the National Institutes of Health consensus development conference.JAMA 1980; 244: 797-800.

12. Kelsey JL A review of the epidemiology of human breast cancer. Epidemiol Rev 1979;1: 74-109.

13. Editorial. Early diagnosis and survival in breast cancer. Lancet 1981; ii: 785-86.14. Elwood JM, Moorehead WP. Delay in diagnosis and long-term survival in breast

cancer. Br Med J 1980; 280: 1291-94.15. Enstrom JE, Austin DF. Interpreting cancer survival rates The available data on

survival are not a sensitive measure of progress in cancer control. Science 1977; 195:847-51.

16. Rossi A, Bonadonna G, Valagussa P, Veronesi U. Multimodal treatment in operablebreast cancer: Five-year results of the CMF programme. Br Med J 1981; 282:1427-31

17. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breastcancer. N Engl J Med 1981; 304: 10-15.

18. Carter SK. Adjuvant chemotherapy of breast cancer. N Engl J Med 1981; 304: 45-47.19. Levitt SH, Polish RA. The case for adjuvant CMF chemotherapy in breast cancer. Has

it been made? Cancer Clin Trials 1981; 4: 363-69.20. Palmer BV, Walsh GA, McKinna JA, Greening WP. Adjuvant chemotherapy for

breast cancer: Side effects and quality of life. Br Med J 1980; 281: 1594-97.21. Powles TJ, Coombes RC, Smith IE, Jones JM, Ford HT, Gazet J-C. Failure of

chemotherapy to prolong survival in a group of patients with metastatic breastcancer Lancet 1980; i: 580-82.

22. Carter SK, Rubens RD Management of locally advanced and disseminated breastcancer. Lancet 1981; ii: 795-97.

23. Paterson AHG, Lees AW, Hanson J, Szafran O, Cornish F. Impact of chemotherapy onsurvival in metastatic breast cancer. Lancet 1980; i: 312.

24. Vana J, Bedwani R, Mettlin C, Murphy GP. Trends in diagnosis and management ofbreast cancer in the U.S.: From the surveys of the American College of SurgeonsCancer 1981; 48: 1043-52.

25. Albert S, Belle S, Swanson GM Recent trends in the treatment of primary breastcancer. Cancer 1978; 41: 2399-404.

26. Forza Operativa Nazionale sul Carcinoma Mammario. I tumori della mammella.Protocollo di trattamento. Milan: Istituto Nazionale per lo Studio e la Cura dei

Tumori, 1979.27. Liberati A, Andreani A, Colombo F, Confalonieri C, Tognoni G. Care of cancer

patients in thirty-one Italian general and community hospitals. Methodologicalaspects and general findings. Eur J Cancer Clin Oncol (in press).

28. Franceschi S, La Vecchia C, Gallus G, et al. Delayed diagnosis of endometrial cancer inItaly. Cancer (in press).

29. Brickner TJ. Carcinoma of the breast. Radiation Oncology Study Center, Philadelphia.Patterns of care study newsletter, July 1978.

30. McNeil BJ, Weichselbaum R, Pauker SG. Fallacy of the five-year survival in lungcancer. N Engl J Med 1978; 299: 1397-401.

31. McNeil BJ, Weichselbaum R, Pauker SG. Speech and survival. Tradeoffs betweenquality and quantity of life in laryngeal cancer. N Engl J Med 1981, 305: 982-87.

Occasional Survey

ON DETERMINING TRACE ELEMENT LEVELSIN MAN:

THE USES OF BLOOD AND HAIR

MARTIN LAKER

Department of Child Health, Royal Hospital for Sick Children,St Michael’s Hill, Bristol B52 8BJ

Trace elements are those elements which occur in the bodyat very low concentrations, that is, at less than 0-01% of thebody’s weight. It is now realised that despite their low

concentrations, many such elements have important effectson the functioning of living organisms, and 9 are known to beessential to man: iron, zinc, copper, manganese, iodine,molybdenum, chromium, and selenium. At least 3 more(fluorine, vanadium, and silicon) are probably also essential.Certain other elements in trace concentrations are harmful,including lead, mercury, cadmium, and arsenic. A surfeit ordeficiency of any trace element can be wholly or partlyresponsible for a number of disorders, and so it is importantto be able to determine accurately the levels of trace elementsin the human body. Modern techniques of analyticalchemistry, such as flameless atomic absorption spectro-photometry, neutron activation analysis, and electron

microprobe analysis allow for accurate determination ofmany trace elements at concentrations down to 0 - 1 parts permillion and sometimes less. To obtain a representativepicture of the element status, however, it must be decidedwhich part of the body to take as a specimen.Many relevant specimens are not available from living

patients: lead, for example, is stored in bones and cadmium inthe liver and kidneys. Information on the body’saccumulation of these elements cannot be obtained easily,and so, in general, a sample must be chosen which, while notso straightforward to interpret, is readily available. Possiblespecimen sources include blood, urine, hair, teeth, and nails.Three of these can be discounted for general use, althoughcircumstances arise where they may be useful: urine givesinformation only on what the body has lost, not on what it hasretained; teeth are rarely used because they are not readilyavailable (the study by Needleman et all on lead in children’smilk teeth is a notable exception); and little is known aboutnails-neither the normal range of elements present, norwhether nails are likely to be contaminated by externalcontact. Two possibilities are left: blood and hair. Before therelative merits of either are considered, it must be emphasised