tion of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients. Am J Med 1979;. 66: 248-256. Malignant pleural mesothelioma.
ter septicemia develops spontaneously is at risk of a relapsing infection and must be watched closely. A prolonged course of appropriate antibiotic therapy should be given parenterally but may not be curative. If relapse follows, long-term prophylaxis should be attempted, but the optimal agent is not known. In our experience erythromycin failed, whereas trimethoprim-sulfamethoxazole was successful. Tetracycline, to the best of our knowledge, has not been tried. We do feel that trimethoprim-sulfamethoxazole merits further trial. we thank Dr. Mohamed A. Karmali for advice and for the laboratory studies.
References I. VERON M, CHATELAIN R: Taxonomic study of the genus Campylobacter Sebald and V.ron and designation of the neosype strain for the type species, Campylobacter fetus (Smith and Taylor) Sebald and Vtron. mt J Syst Bacteriol 1973; 23: 122-134 2. RETTIG PJ: Campylobacter infections in human beings.
J Pedjair 1979; 94: 855-864 3. HOLT JG (ed): The Shorter Bergey's Manual of Determinative Bacteriology, 8th ed, Williams & Wilkins, Baltimore, 1977: 74 4. SKERMAN VBD, MCGOWAN V, SNEATH PHA: Approved lists of bacterial names. mt . Syst Bacteriol 1980; 30: 225-420 5. KARMALI MA, FLEMING PC: Campylobacter enteritis. Can Med AssocJ 1979; 120: 1525-1532
6. Campylobacter infections in Britain 1977. Br Med J 1978; 1:1357 7. BOKKENHEUSER VD, RICHARDSON NJ, BRYNER JH, Roux DJ, SCHUTTE AB, KOORNHOF HJ, FREIMAN I,
8.
9.
10.
11.
HARTMAN E: Detection of enteric campylobacteriosis in children. J Clin Microbiol 1979; 9: 227-232 GUERRANT RL, LAHITA RG, WINN WC JR, ROBERTS RB: Campylobacteriosis in man: pathogenic mechanisms and review of 91 bloodatream infections. Am J Med 1978: 65: 584-592 SCHMIDT U, CHMEL H, KAMINSKI Z, SEN P: The clinical spectrum of Campylobacter fetus infections: report of five cases and review of the literature. Q J Med 1980; 49: 43 1-442 KAPLAN RL: Campylobacter. In LENNETrE EH, BA. LOWS A, HAUSLER WJ JR, TRUANT JP (edt): Manual of Clinical Microbiology, 3rd ed, Am Soc Microbiol, Washington, 1980: 235-241 KARMALI MA, DE GRANDIS 5, FLEMING PC: Antimicrobial susceptibility of Campylobacterjejuni and Cam. pylobacter fetus subap. fet us to eight cephalosporint with special reference to species differentiation. Antimi-
crob Agents Chemother 1980; 18: 948-951 12. VINzENT R, DUMAS J, PICARD N: Septic6mie grave au court de Ia grostesse, due S un vibrion. Avortement cons&usif. Bull Acad NatI Med (Paris) 1947; 131: 9092 13. CURTIS AH: A motile curved anaerobic bacillus in uterine discharges. J Infect Dis 1913; 12: 165-169 14. COLLINS HS, BLEVINS A, BENTER E: Protracted bacteremia and meningitis due to Vibrio fetut. Arch Intern Med 1964; 113: 361-364 15. WILLIS MD, AUSTIN Wi: Human Vibrio fetus infec-
tion. Am J Dis Child 1966; 112: 459-462 16. CHUNG Y, LEE SY: Vibrio fetut human infection isolation from a subacute bacterial endocarditis case. YonseiMedi 1970; 11: 126-130 17. LEE MY, LUDWIG J, GERACI JE, WASHINGTON JA II: Fatal Vibrio fetus endocardisis: report of one case and review of the literature. Virchows Arch IPathol Anati 1970; 350: 87-94 18. DOLEV E, ALTMANN G, PADEH B: Vibrio fetus septicemia.Acasereport.IsrJMedScil97l;7: 1188-1191 19. FILE TM JR, BARNISHAN J, FASS Ri: Campylobacter fetus sepsis with mycotic aortic aneurysm. Arch Pathol Lab Med 1979; 103: 143-145 20. KILO C, HAGEMANN P0, MARZI J: Septic arthritis
and bacteremia due to Vibrio fetus: report of an unusual case and review of the literature. Am J Med 1965; 38: 962-971
21. BROWN Wi, SAUTTER R: Campylobacter fetus septicemis with concurrent salpingitis. J Clin Microbiol 1977; 6: 72-75 22. TARGAN SR, CHOW AW, GuzE LB: Spontaneous peritonitis of cirrhosis due to Campylobacter fetus. Gassroenterology 1976; 71: 311-313 23. LAWRENCE GD, BIOGS RD JR. WOODWARD TE:
Infection caused by Vibrio fetus. Report of two cases. Arch Intern Med 1967; 120: 459-464 24. LAWRENCE R, NIBBE AF, LEVIN S: Lung abscess secondary so Vibrio fetus, malabsorplion syndrome and acquired agammaglobulinemiaChest 1971; 60: 191-194 25. BLASIUS C, ULLMANN U, ACHINGER R: Vibrio-fetusSepsis bei Thrombophlebitis. Zentralbi Bakieriol [Orig Al l970; 214: 17-22 26. SOONATTRAKUL W, ANDERSEN BR, BRYNER JH:
Raw liver as a possible source of Vibrio fetus septicemia in man. Am J Med Sd 1971; 261: 245-249 27. BOKKENHEUSER V: Vibrio fetus infection in man. 1.
Ten new cases and some epidemiologic observations. Am J Epidemiol 1970; 91: 400-409 28. McCOY EC, DOYLE D, BURDA K, CORBEIL LB, WINTER AJ: Superficial antigens of Campylobacter (Vibrio) fetus: characterization of ansiphagocysic component. Infect Immun 1975; 11: 5 17-525 29. BUTZLER Jr. DEREUME JP, BARBIER P. SMEKENS L, DEKEYSER J: L'origine digestive des septictmies h Campylobacter. Nouv Press Med 1977; 6:1033-1035 30. CHOW AW, PATTEN V, BEDNORz D: Susceptibility of
Campylobacter fetus to twenty-two antimicrobial agents.
Antimicrob Agents Chemother 1978; 13: 416-418 31. TAYLOR DE, KEYSTONE JS, DEvLIN HR: Resistance to trimeshoprim and other antibiotics in Ontario Shigel-
Ise (C). Lancet 1980; 1: 426 32. VANHOOF R, GORDTS B, D1ERIcKx R, COIGNAU H,
BuTZLER JP: Bacteriossasic and bactericidal activities of 24 antimicrobial agents against Campylobacter fetus
subsp. jejuni. Antimicrob Agents Chemother 1980; 18: 118-121 33. GURWITH MJ, BRUNTON JL, LANK BA, HARDING
GKM, RONALD AR: A prospective controlled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients. Am J Med 1979;
66: 248-256
Malignant pleural mesothelioma presenting as superior vena cava syndrome GLENN F. RAGALIE,* MD BASIL VARKEY, MD,* FRCP[C] HONGYUNG CHoI,t MD
Superior vena cava syndrome SVCS; it is the first such case, to (SVCS) is usually caused by malig- our knowledge, to have been reportnant neoplasms, the most common ed. being bronchogenic carcinoma, which accounts for 50% to 70% of Case report cases;'-' it is followed in frequency by lymphoreticular, mediastinal and A 61-year-old man was admitted metastatic neoplasms. We describe a to our hospital in July 1978 with a case in which malignant pleural 5-month history of progressively inmesothelioma initially presented as creasing pain in the anterior and lateral aspects of the right side of From the pulmonary disease section, medical and the chest. The pain was sharp and tpathology services, Veterans Administration Medical constant. In the month preceding his Center, Wood, Wisconsin, and *the departments of medicine and pathology, Medical College of Wisconsin, Milwaukee admission he had noted facial flushReprint requests to: Dr. Basil Varkey, Veterana ing, mainly in the morning, promiAdministration Medical Center, 5000 W National Ave., Wood (Milwaukee), WI 53193, USA nent veins on his chest, shortness of
breath on exertion and episodes of near syncope. He had smoked about 20 cigarettes a day for 40 years. Although he had worked as an industrial welder and assembler for 30 years he denied any exposure to asbestos. At the time of admission the patient appeared to be in no distress, and his vital signs were normal. He had a ruddy complexion, supraclavicular fullness without palpable lymph nodes, and marked venous prominence over the anterior chest and neck. There was no clubbing. Percussion and auscultation of the
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chest, as well as the rest of the physical examination, gave results within normal limits. The laboratory findings were normal, as was an electrocardiogram. A chest roentgenogram showed a paratracheal density and a lateral opacity, both on the right side, suggesting a disease process in the pleura. (Fig. 1). Tomograms revealed that the paratracheal density was in the superior mediastinum, extending far anteriorly and posteriorly; it could not be separated from the brachiocephalic vessels. Venography showed almost total occlusion of the superior vena cava (Fig. 2). Cytologic studies of the sputum were nondiagnostic. Because of the fear of impending complete obstruction of the superior vena cava and the potential hazards of invasive diagnostic procedures, radiation therapy to the mediastinum was begun. After 1000 rad the patient noted less facial flushing, but his chest pain was unabated. A week later fibreoptic bronchoscopy was performed. However, no endobronchial lesions were seen, and no malignant cells were found in the bronchial aspirates. Members of the thoracic surgical service were consulted but declined to do a mediastinoscopy. Bone and liver scans and a bone marrow aspiration biopsy did not reveal any evidence of neoplastic metastasis. The patient was discharged from the hospital a month after admission, when the facial flushing and venous prominence had markedly decreased. Radiation therapy was con-
tinued to a total dose of 6000 rad, even though no definitive diagnosis had been made. In December, 3 months after completion of the radiation therapy, a right-sided pleural effusion developed. A serous exudate was found by thoracentesis. Since a percutaneous needle biopsy of the parietal pleura had revealed no diagnostic abnormality an open pleural biopsy through a right anterolateral thoracotomy was done. The drained serosanguineous pleural fluid contained atypical epithelial cells suggestive of malignant mesothelioma. A few small, circumscribed, raised lesions were noted in the mediastinal pleura, and two greyish fibrous pleural masses measuring 3 X 3 cm were found adhering to the right side of the diaphragm. These masses and a thickened area in the pleura over the 10th rib were excised. Microscopic examination of the specimens revealed neoplastic cells with pleomorphism, hyperchromatic nuclei and scanty cytoplasm arranged in tubules, clefts and solid irregular nests in a dense fibrous stroma (Fig. 3). The tissue did not take up mucicarmine, a stain specific for mucin. Malignant pleural mesothelioma was diagnosed. Specimens of the masses and the thickened area of pleura were also sent to a reference laboratory for electron microscopy. The microscopist noted the following features of the tumour cells, which were in small groups within the fibrous tissue: long intercellular junctions; long microvilli (occasionally over 1 .tm in length) projecting from the apical surface of the cells; intracellular lumina; frequent lipid
droplets and tonofilaments in the cytoplasm, as well as phagocytic vacuoles, pinocytotic vesicles and polysomes; large, irregularly shaped nuclei; and large nucleoli with a prominent nucleolemma. These features were judged to be most consistent with those reported for mesotheliomas. The patient was followed up in the chest clinic and treated with analgesics. Over the next 10 months, because of the possibility of concurrent bronchogenic carcinoma, multiple cytologic examinations of the sputum as well as repeat bronchoscopy with bronchial brushings were done, but they did not reveal any neoplastic cells or endobronchial lesions. Because of persistent chest pain and weight loss the patient was given three courses of chemotherapy with cyclophosphamide, vincristine, doxorubicin and dacarbazine. However, chest pain, progressive weight loss and shortness of breath continued, and he died in December 1979. Permission for an autopsy was denied. Discussion
Malignant pleural mesothelioma is an uncommon neoplasm that rarely metastasizes to distant sites and then only late in its course.5'6 However, Roberts7 found metastases to hilar and mediastinal nodes in 53% of cases in a necropsy study, and Elmes and Simpson8 reported that malignant mesothelioma was fre*quently found to be compressing mediastinal structures and that "some degree of venous obstruction on the side of the pleural lesion was sometimes noted" at autopsy. It would thus be logical to assume that SVCS would be a frequent manifestation of malignant mesothelioma. However, this is not borne out by a review of the literature. In their review of 193 cases of malignant pleural mesothelioma Legha and Muggia6 noted chest pain and dyspnea as the most frequent symptoms, occurring in 69% and 68% of the patients respectively; pleural effusion was present in 78%. The only reference to SVCS was made in an earlier article, by Ratzer and associFIG. 1-Right-sided paratracheal densiates,9 who found congestion and ty. Opacity along lateral aspect of chest (arrows) and costophrenic angle suggest FIG. 2-Near-total occlusion of superior edema in the upper limbs, head and vena cava, demonstrated by venography. neck "late in the course of the disease process in pleura.
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Rubino and coworkers" found a history of asbestos exposure in 11% to 91% of the patients with mesothelioma. Thus, although a history of asbestos exposure is helpful in diagnosis, its absence does not rule out mesothelioma because the exposure may have been remote and incidental, and other factors may have been involved.'2 Although the combination of persistent chest pain and dyspnea in a patient with undiagnosed pleural effusion suggests mesothelioma, these problems present in other diseases. Chest roentgenograms are usually nonspecific,'3 and examination of
disease in a few patients". In a recent paper on SVCS Schraufnagel and colleagues3 listed without description 1 case of mesothelioma among 107 cases of SVCS. To our knowledge there has been no report of malignant mesothelioma initially presenting as SVCS. The association of asbestos exposure and mesothelioma has been documented by Selikoff and collaborators,'0 who found in a postmortem study that 3% of the patients with asbestos exposure had mesothelioma, although the expected frequency in the general population was 0.01%. In their review of 16 studies
'7 f
I
A: 1.y.
4
pleural fluid and of pleura obtained by percutaneous needle biopsy is often nondiagnostic. It is generally agreed that the diagnosis of mesothelioma requires thoracotomy and an adequate biopsy of the pleura. The gross appearance of malignant mesothelioma is characteristic, and the diagnosis can be confirmed by detailed histologic and histochemical studies. The histologic features are closely similar to those of other neoplasms, particularly adenocarcinoma and bronchoalveolar carcinoma; however, histochemical studies (with periodic acid, Schiffs reagent and mucicarmine) are helpful in differentiating mesothelioma from adenocarcinoma, although the results should be interpreted with care. Electron microscopy also aids in differentiating malignant mesothelioma from other neoplasms.'4 In addition to these studies, computed tomography of the chest, cytologic studies of the sputum, bronchoscopy, bronchial brushings and transbronchial lung biopsy (in the presence of a lung lesion) should be done to rule out bronchogenic carcinoma. The conventional approach to SVCS was to treat it as an emergency with radiation therapy even when there was no histopathologic diagnosis. Lokich and Goodman4 warned against overzealous efforts to establish the site of obstruction and make a histopathologic diagnosis. In our case there was reluctance to perform mediastinoscopy or thoracotomy early in the course of the disease. Since repeated cytologic examinations of the sputum and bronchoscopy failed to reveal a diagnosis, however, an open pleural biopsy was done 6 months after the patient's admission to hospital. More recently the conventional approach has been challenged,"3'5 and the safety of invasive procedures has been demonstrated. Now most clinicians favour establishing a specific diagnosis with the use of invasive procedures (i.e., mediastinoscopy and thoracotomy), if necessary, to tailor the treatment. References 1. TEIRSTEIN AS: Diagnostic procedures in patients with superior vena cava syndrome. JAMA 1981; 245: 956
FIG. 3-Section of excised pleural mass, showing neoplastic cells with pleomorphism, hyperchromatic nuclei and scanty cytoplasm arranged in tubules (top) and solid irregular nests in dense fibrous stroma (bottom) (hematoxyhn eosin, X 160).
2. PARISH IM, MARSCHKE RF JR, DINES DE, LEE RE:
Etiology considerations in superior vena cava syndrome. Mayo Clin Proc 1981; 56: 407-413
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first, by Ming T. Tsuang, has eloquent patient histories and a great deal of historical data with technical references to explain where the current body of knowledge on schizophrenia came from. Dr. Tsuang writes clearly, in a good scientific style, and his book contains selected references, mainly to classic texts on this group of diseases. Although Dr. Tsuang explains the disease phenomena well, he gives little information on how to cope with day-to-day issues confronting a patient or the family members. I see his book as being pitched toward the scientifiMAJ. S.E. AITKEN, MD, FRCP[CJ Department of medicine cally oriented relatives of patients National Defence Medical Centre with schizophrenia and toward nursOttawa, Ont. ing students, medical students in the early clinical years and social workers. Two books on schizophrenia The second book certainly lives up Schizophrenia. The Facts. Ming T. to its title. As well as describing the Tsuang. 95 pp. Oxford University disease and covering some of the Press, Don Mills, Ont., 1982. etiologic hypotheses and theories, $19.50. ISBN 0-19-261336-7 the authors address a number of Living and Working with Schizo- extremely important and practical phrenia. M.V. Seeman, S.K. Litt- issues about daily living, always mann, E. Plummer, J.F. Thornton bearing in mind that someone with and J.J. Jeffries. 146 pp. University of schizophrenia has considerable conToronto Press, Toronto, 1982. $6.95, tact with psychiatric hospitals and paperbound. ISBN 0-8020-6474-4 therapists. Questions on the sex life It is a fortunate coincidence that of schizophrenics and what approtwo high-quality books for the lay priate expectations might be are person on schizophrenia have ap- addressed, as are practical compeared at about the same time. The ments on financial affairs, the price of drugs, whether schizophrenics MALIGNANT should take drug holidays and continued from page 691 what key factors are involved in 3. SCHRAUFNAGEL DE, HILL R, LEACH JA, PARE IA: maintaining remission. The authors Superior vena caval obstruction. Is it a medical emertake the reader on a guided tour gency? AmiMed 1981; 70: 1169-1174 4. Loscic. J, GOODMAN R: Superior vena cava syndrome. from prodromal symptoms through Clinical management. JAMA 1975; 231: 58-61 admission to hospital to after-care 5. BoRow M, CoNSToN A, LIVoRNESE' L, SCHALET N: Mesothelioms following exposure to ssbestos: a review with the goal of social rehabilitation. of 72 cases. Chest 1973; 64: 641-646 Particularly useful is the chapter on 6. LEGHA SS, MUGGIA FM: Pleural mesothelioma: clinical featurea and therapeutic implications. Ann Intern Med how relatives can help and what 1977; 87: 613-621 support is available for them. The 7. ROBERTS GH: Distant visceral metastases in pleural mesothelioma. Br J Dis Chest 1976; 70: 246-250 final part contains the personal acof 8. ELMEs PC, SIMPSON JMC: The clinical aspects counts of a mother, a father, a mesothelioma. Q J Med 1976; 179: 427-449 9. RATZER ER, POOL JL, MELAMED MR: Pleural mesopatient and a doctor involved in theliomas. Clinical experiences with thirty seven papainful dilemmas concerning schizotients. Am J Roentgenol 1967; 99: 863-880 10. SELIKOFF Ii, CHURO I, HAMMOND EC: Relation bephrenia. These real-life, compassiontween exposure so asbestos and mesothelioma. N Engi J ate and personal contributions bring Med 1965; 272: 560-565 11. RsBINO GF, ScANSErrl G, DONNA A, PALESTRO G: the facts alive, and without in Epidemiology of pleural mesothelioma in northwestern any way underestimating the morItaly. Br J md Med 1972; 29: 436-442 12. CHABOT IF, BEARD D, LANoLoss Al, BEARD JW bidity of the condition they make it Mesotheliomas of peritoneum, epicardium and pericardiclear that a person can live and urn induced by strain MC29 avian leukosis virus. Cancer Res 1970; 30: 1287-1308 work with schizophrenia and expect 13. TARYLE DA, LAKSHMINARAYAN 5, SAHN SA: Pleural much benefit from life. This book, mesotheliomas - an analysis of 18 cases and review of the literature. Medicine (Baltimore) 1976; 55: 153-162 then, appears pitched more toward 14. WANG N: Electron microscopy in the diagnosis of the lay population who want reliapleural mesotheliomas. Cancer 1973; 31: 1046-1054 15. SHIMM DS, LOGUE GL, Rioanv LC: Evaluating the ble, clear information on this disease superior vena cava syndrome. JAMA 1981; 245: 951and who have questions about why 953
options available to physicians and indicates not only that changes in attitude are taking place but also that the role of the patient in the decision-making process is important. I think that a patient with newly diagnosed breast cancer would find the wealth of information available in this book somewhat overwhelming. None the less, there is no doubt whatsoever that this book has earned an important place on bookshelves and should be made readily available to the general public.
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certain forms of therapy are used and why hospitals have certain bureaucratic procedures for psychiatric units. The authors have obviously addressed themselves carefully to the questions patients and their relatives struggle with. A particularly helpful appendix is a list of self-help groups for schizophrenics and for their friends and relatives. The list of suggested reading material is directed more toward the lay population than to the scientific aspects of the condition, which are addressed more thoroughly in Dr. Tsuang's book. These two books are a welcome addition to the tiny library of explanatory books on schizophrenia. Each has a slightly different focus and considerable merit. DAVID S. PALFRAMAN, MD
Director, adult psychiatric outpatient department clinics Ottawa General Hospital Ottawa, Ont.
Diagnosing pulmonary disease Office Diagnosis and Management of Chronic Obstructive Pulmonary Disease. Geoffrey M. Davies. 135 pp. Illust. Lea & Febiger, Philadelphia, 1981. $10.75. ISBN 0-81210823-X This small monograph is intended to simplify and clarify the recognition and treatment of obstructive lung diseases in office practice. Its stated intent is to lead to a clear diagnosis by history-taking, physical examination, chest roentgenography and simple laboratory tests, including pulmonary function tests. The chapters follow in an orderly fashion. However, the chapter "Problems in diagnosis" places too much emphasis on differentiating the various obstructive pulmonary disease syndromes; for example, an attempt is made to distinguish bronchiectasis and cystic fibrosis from the obstructive pulmonary disease syndrome. As this text is directed toward office management there is little value in being so specific. The chapter on pulmonary function testing in the office is concise and contains reasonable amounts of information. It is interesting that the chapter on treatment begins with physical