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i i^etu York State Journal of Medicine(ISSN 002S-762BJ -Y T. PuMithil matuMy utth iht Minim of Ih* Houm of D*l*f*IN *M*d in March by the Madtca) Sosoy of tht Suu of Ne* York. Copyright 1*81 by tin Mmjc*) Soon* of thr Suu of No* York. All tnaimtl tevtrttl in thth'tw York Suu* Journal efMttUom may be phMOccpi*e lor nontemmtraol rrirnii/ir or rdurotiiwo/ oar nUy. Spruel oironfrmmK one prrmuuon or# nqmrtd from tot outnoth) of tV porimior oruti* and from tin 4uo* lot nv other puroott. Eduonml. Circulation, and Atfurnuinf Offittt *!0 LakrviU* W.. Lakr Sucewt, N.Y". 11M! Choipt a/Ahknu' NoUe* tpouid nrir --b*tW or not ohaan u ptnoaorm ajid thould intluor Iht old addraa. Su oioaka noucx ia npuirod to aftao a chant* of addraaa. TVcv ctnu per oopy--S3-S0 par yoai. yorripn lutormpLiom I3.&0 audacnptton piui tlJO for maiiiaf S*eonh*tio** pociofr paid ai No* Wyd* Per*. N r., end*`ui-.ilmmJMriiiof // POSTMASTER SrnSPODIorm3S79iuhtw York Suit Joumolof UtOiunt. 420LoaouMihd.. Uokt Suttm. N Y. 11042. Contents MARCH 1981 VOLUME 81 NUMBER 3 The Editor* of tht Journal assume do reaponaibility for opinion* and claim* expressed is the arti cle* contributed by individual author*. Contribution! accepted for oritiaa) publication only. . 1, V 321 324 e 327 illv 331 336 l; -it1 353- 339 343 347 349 '31 - 57 360 * 362 365 368 ?72 7^ C 376 Scientific Articles Campylobacter Fetus Jejuni Enteritis; in New York City Anne C. Mostnthal.B.A,, Richard L. Monet, MD.,end VictorX.Xokkenheuser, MX. Extrahepatic Bile Duct Cancer Edith D. Grttnwald, Edward S. Grtenwold, MX)., and Stephan M. Brenner, MX. Percutaneous Endoscopic Extraction Retained Stone*; endoecopic extracuon from common bile duct and gallbladder Jerome H. Siegel, M.D.. G Thomas Harding, MX., Frank Chateau, P.A.-C., Howard 1. Sherman, MX., Carier Davis, Jr.,M.D., and William A. Webb, MX. Cervical Cancer Screening, need among hospital inpatients John Bovcc, M.D..F.A C.O.G., Rachel Fruchter, Ph,D.,Mary Thompson, R.H., Claudia Con/y, R.A'., Mendis Jones, R.S., Joan Moloney, R.N., and Randall Bloomfield, MX., F.A.C.O.G. Metastatic Carcinoma; insensitivity of buffy coat preparations Jonathan Rubins, MX., Virginia Adams, M.S.,M.T., (A.S.C.P.)S.H., Judith Winchester, HAA.S.C.P.), and Judith E. Wall, MX. Lung Cancer preoperative radiation therapy and surgery Paul A. Kirschner, MX., F.A.C.S., F.C.C.P. Blood Grouping Tests for Psternitv and Nonpaternity Leon is. Sussman,M.D.,eniBal K. Gilja,MX. . Electrocardiograms of the Month Questions 311 and 312 Ira L. Rubin, MX., and Julian Frieden.MX., Editors Radiologic Problem of the Month Acute Abdomen Kakarle Subbarao, MX. Case Reports Volume Receptor Control of ADH Release in Essentia) Hypernatremia Steven Jay Rosansky, MX., and Bernard D. Nidus, MX. Splenorrhaphv; tuccetsfu) application in prematurity Neil D. Hu tin, MX., Rolando Sanchez, MX., and Modhu Bhogol, MX. Pehnc Cecum; cause of signs and symptoms Andreas Boutros, M.D..F.A.A.P., and John P. Curran, MX. Bernard-Homer Syndrome; associated with Swan-Gam catheter Richard B. Birrer, MX., end Charles M. Plots, MX., MsdScX. Pseudoeneurysm of Aortic Stump; rupture in pregnancy Stephen Matseoane ,MX.,F.A.CB.,F.A.C.O.G., Harold Freeman, MX., F.A.C.S., Johnny Williams, M.D.,Gonepola Ganepoia, MX..F-A.CX., and Samuel Brisbane, MX. Tuberculosis of Myocardium Michael K. Jason, MX., Samuel Zoneraich, MX.,F^.C.C,,and Gertrude Silverman, MX. Metastasizing Fibroleiomvoma Horry Steinberg, MX.,Robert ChaU.MX., Jamas Sciubba, DMX-. PhX,, Belinde Aftalion, MX., and George PUlari,MX. Enragonada) Germ-Cell Cancer Syndrome Patrick R. Bergturn, MX., Sandra Harrit-Comda, MX,, Yvonne Lamy, MX., and Raul Alessondri, MX. 1111/Men York State Journal of Medicine 305 OLI Extrahepatic Bile Duct Cancer EDITH D. GREENWALD,* New York, New York EDWARD S. GREENWALD, M.D.b The Bronx, New York STEPHEN M. BRENNER, M.D.* The Bronx, New York * GrMuete Assistant. (nstnuf* et Environmanial Meotcmc. New York University MaOiCSl Center. 6 Acting Cruet, Department of Oneotogy. Montefiore Hospital and Medical Center. ' Adjunct Division of Gastroenterology. Department of Medicine. Montefiore Hotpital and Medical Center This review was undertaken after one of the authors (SJvi.B.) noted an increased incidence of ex trahepatic bileiuet cancer at Montefiore Hospital and Medical Center. Although the etiology of this uncommon tumor is not known, one hypothesis is that extrahepatic bile duct cancer may be caused by a carcinogen in the bile, either ingested or inhaled, or a transformation product of an ingested or inhaled substance. At Montefiore Hospital and Medical Center the number of cases of extrahepatic bile duct cancer re ported was: Before 1960 1960-65 ... . 1965-70 1970-75 '- Jam-1,1976, to Dec 31,1979 . 7 10 12 20 19 Possible explanations for this increase are: (1) in creased diagnostic skills resulting in more diagnoses; (2) referral of cases to a large center; and (3) a true increase in incidence. It is unlikely that the second hypothesis is true because almost all patients were self referred to Montefiore Hospital and Medical Center or to its affiliated physicians. Incidence All authors agree that tumors of the biliary tract are comparatively rare, although there is a possibility of significant underreporting because of difficulties in both macroscopic and microscopic diagnosis. There is a 2:3 female-to-male ratio, with the age- adjusted incidence rate generally higher in whites. The age range is wide, with peak incidence in the sixth decade in several series.1 Incidence is signifi. cantly higher in American Indians,2-3 in the Mexican population in the southwestern pan of the United States,4 and in Japanese migrants to the United States.5 The incidence of cancer of the extrahepatic bile ducts may be expressed in several ways. In a review of 12 autopsy series published in 195',6 there was a variation in incidence from 0.012 percent to 0,458 percent, while carcinomas were found in 0.3 percent and 1.8 percent of all biliary tract operations per formed in 2 series. As a percentage of all hospital admissions, cancer of the extrahepatic biliary tract accounted for 0.007 to 0.041 percent of the total figure. The National Cancer Institute's Third Natior i! Cancer Survey7 estimated 11.800 new cases of c; *cinoma of the liver and biliary passages in 1976, wh t the U.S. government vital statistics report for 195 j* listed 4,276 deaths due to malignant lesions of the biliary passages. If 40 percent of the anticipated new cases of liver and bile passage malignant neoplasms during 1976 are bile duct carcinomas, approximately 4.500 new cases can be expected in this countrv in 1980. The average annual crude incidence rate from 1969 through 1971 for biliary tract cancer in the United States is 1.2 per 100,000, while the average annual age-adjusted incidence rate (1970 standard) is 1.3 per 100,000.7 It is difficult to ascertain a trend because, while the Third National Cancer Survey7 classifies gallbladder cancer separately from other biliary tract neoplasms, which are primarily extrahepatic biie duct carcinomas, in previous cancer surveys data for gallbladder cancer and other biliary tract neoplasms were lumped together. Another handicap is the failure of the International Classification of Diseases to distinguish between cancers of the liver and the biliary system until the seventh revision in 1958.' Many authorities believe that gallstones are ei iologically related to bile duct cancer. Data published by Stewart, Lieber, and Morgan,9 Neibling, Dock* erty, and Waugh,10 Sako, Seitxinger, and Garside,* and Ross, Braasch, and Warren11 have shown that gallstones are associated with 20 to 57 percent of such cancers. Although, on the average, gallstones art found in about one third of patients with bile duct cancer, this fact is of unknown significance. Biliary tract carcinoma is possibly 10 times more frequent in patients with ulcerative colitis than in the general population.12 A series of 13 patients with bile duct cancer (excluding gallbladder cancer) and associated chronic ulcerative colitis seen at the Mayo Clinic from 1935 to 197313 and a review of the liter ature suggest that the relationship between cbr n*c ulcerative colitis and bile duct cancer is not just chance occurrence. The carcinoma has an onset approximately three decades earlier than cancer of the bile duett without chronic ulcerative colitis, end nfitl of m exte. relat of tl esus j bilia .trim with ; dent Tl kith This infix in tb duct rnuc St C1UC that of tl trahsepa In sugg bile bon ciati . ``-.nati < ..-'Mad I -.stito cast ! -siro ' Che L itrai rino cent cheL biliar -`jluct. 324 New York State Journal of Medicine/March 1081 OLX 6671 -hn. I inti* i" Uni. uc bile review s v*a 3 0.456 >eroea >$ perl of.piu3 y trade total atioa^;. of cer?v i, wharf 19MSof the' ednev' olasm; tnaiek j itry in n 1965 Jnited mnuai 1.3 per ic bile'-: staibfT ilasmsis ibe' etitti id tbe 58.' eetiolished Dockside* n That f such es are r duel more in the ; with -) and Mayo liuer-t ironitV just a'-l onse`'1 cert 1 p-:ther surgical removal of the diseased colon, mode oj medical management of the unresected colon, nor extent or severity of the colonic disease heve any relationship to tbe subsequent development of cancer 0f the bile ducts.13 However, no mechanism of causation is apparent, and "it would appear that biliary tract cancer is another member of the spec trum of hepatic disorders that may occur in patients with ulcerative colitis, but which progress indepen dently of the colonic disease."13 There is a strong association of bile duct carcinoma with congenital biliary tract cysts (choledochal cysts). This may result from interaction between chronic inflammation and carcinogenic substances excreted in the bile. Tbe presence of a cyst could lead to bile duct stasis with resultant prolonged exposure of the mucosa to bile.14 Studies of vinyl chloride workers have shown a much higher rata of liver and biliary tract cancer than that expected, but, unfortunately, the significance of these data could not be ascertained because extrahepatic biliary tract cancer was not classified separately.15'16 In 1970, an epidemiologic survey of rubber workers suggested an excess of cancer of the gallbladder and bile ducts.17 There was also a shift in age distribu* lion to younger gTOUps, which would support association with employment. Occupational mortality statistics from California demonstrate that gall bladder and bile duct cancers are prominent among automotive and rubber plant workers, while bile duet cancers show increased incidence in workers in the ai' craft, chemical, and wood finishing industries.1* Chemical factors Laboratory.animals have been used to demon strate the excretion in the bile of experimental car cinogens or their metabolites, with associated con centration in the bile and gallbladder. A number of chemicals tested by animal bioassay have produced biliary- tract changes, proliferation of bile ducts, bile duct hypertrophy, cholangiomas, cholangiocarcinorr.as, and carcinomas in the bile ducts. A number of complex chemicals used in the rubber it ustry, including nitrosamine compounds, benzid. t, Flectol H, and M-toluylene diamine were shown b> investigators to be injurious to the hepatobiliary system. Rats fed Flectol H, a polymer of 1 -2 dihy dro-22,4-trimethyl quindine, developed biliary tract hyperplasia, atypical proliferation of the biliary ducts and of fibrous tissue, and cholangioflbrosis, consid ered a precursor to biliary duct carcinoma. Oral administration of M-toluylene diamine induced proliferation of tbe bile ducts, followed by carcinoma. Cyclohexylamine, a carcinogenic metabolic product of eydamates, is also used in the rubber industry. Therefore, many investigators conclude that certain chemicals are an etiologic factor in the development of carcinoma of the bile ducts among rubber workers.11 An increased number of sell-referred patients with extrahepatic bile duct cancer hove been seen at Montefiare Hospital and Medical Center in the last ten years. Although improved diagnostic methods may partially explain this phenomenon, oetual in creased incidence is suggested. The literature is reviewed for known causative factors in cxtrohepatic bile duet cancer. Transhepolic cholangiography, routinely carried out in extrahepatic bile duct cancer patients, would be a good source of bile for study of carcinogenic and mutagenic activity. Daily oral doses of the pesticide aramite led to the production of gallbladder and bile duct carcinoma in dogs in at least one experiment.1* Two dogs who were fed 8-aminoazotoluene, one for 30 months and tbe second for 62 months, developed adenocarcino mas involving the entire biliary tract which resem bled the diffuse involvement of the biliary tract by canqer in human beings.19 Mice fed cholesterin, cholic acid, and the carcinogen 2-acetamidofluorene or its N-hydroxy derivative developed proliferation of mucosa in the extrahepatic bile duct, atypical cells in the mucosal epithelium of the bile duct, and, oc casionally, adenocarcinoma of the common bile duct Metabolites of the carcinogen and its derivative were found in the bile of these mice.20 Some investigators believe that the typical American diet of 45 percent fat results in the excre- * tion of large quantities of bile acids which may act as cocarcinogens.21 People who eat large quantities of smoked food or work in meat-smoking factories have a particularly high incidence of digestive cancers, possibly caused by polycyclic aromatic hydrocarbons and/or N-nitrosamines. Nitrites and secondary amines present in food and nitrates and nitrites added as preservatives react to form N-nitrosamines under mild conditions of temperature and pH. Nnitroeamines have been implicated in cancer causa tion in a wide variety of animals and in virtually every organ in the rat, and it is therefore postulated that man is also sensitive to these compounds.22 The carcinogenic action of aflatoxins, metabolites of some strains of Aspergillus flaws, has been studied in fish, birds, and mammals. Although the liver was the organ most affected in all species, marked intrahepatic bile duct proliferation, possibly reprasenting a premalignanl lesion, was noted in the rat, duckling, chicken, cattle, monkey, guinea pig, dog, and trout. Cholangiocarcinoma in the intrahepatic bile duct was seen in one rat, while bile duct hyperplasia occurred in the rabbit and in the cat. It is assumed that aflatoxin in the bile may be a factor in the production of bile duct proliferation and oc casional areas of fibrosis. Although there is now no direct evidence that man is susceptible to aflatoxins, their demonstrated carcinogenicity in a broad spec trum of animals make them suspect as a hazard to Mare* iMi/Mew York State Journal of Medicine 325 OLI 6672 man. Furthermore, there is a high incidence of hepatocellular carcinoma but not extrahepatic bile duct cancer in many areas where climatic conditions favor the growth of such molds.23 Liver-fluke infections of the orient, CLonorchis sinensis and Opisthorchis felintus in the most populous countries of Asia, and Opisthorchis uiverrini in parts of Thailand and Malaysia, are highly associated with bile duct carcinoma. The simplest explanation is that these flukes are responsible for an inflammatory reaction in the bile ducts, poten tiating the action of carcinogenic agents excreted in the bile. Cancer did not develop in any Syrian golden hamsters given the carcinogen dimethylnitrosamme in their drinking water in an experiment, but cholangiocarcinomas and cholangioflbrosis appeared in all when intragastric roetacercariae of 0. uioerrini were administered first. The diet of northeastern Thais is rich in a fermented fish product containing substances transformable to nitrosamines.14 The etiology of extrahepatic biliary tract cancer is unknown, but there is certainly evidence from the literature to suggest that environmental factors cause biliary tract cancer, and that further epidemiologic investigation is warranted. Case-control studies are unlikely to provide clues as to the cause of bile duct cancer. Study of carcinogenic and mutagenic ac tivity in bile of cancer patients compared to controls without malignant illness might be more productive. At present the best way to diagnose bile duct cancer is to perform a transhepatic cholangiogram. This technique allows the physician to collect bile for study without added risk to the patient. Bile could also safely be collected from patients who have ab dominal surgery for benign conditions. Comparative studies could then be carried out for carcinogenic and mutagenic activity. Specific carcinogens could be isolated, and bile could be studied for distribution patterns of bile acids and their conjugates. c J - -- Montafiot* Hospital and Medical Center Ill East 210th Street , Bronx New York 10467 <DR E. S. GREENWaLD) References 1. Longmirt. W.P.. Jr.: Tumor* of the extrahepatic hiliarv radicals, Curr. Probl. Cancer 1: 5 (1976), 2. Rudolph. R, Cohen, J. J,, and Gascoigne. R. H.: Biiiarv cancer amonf Southwestern American Indiana, Arizona Med. 27; 1 0970). 3. Dunham, L. J., Bailer, J. C,, HI. and Laqueur. C. L : Histologically diagnosed cancers in 693 Indiana of the United States. 1&50-65, J. Nad Cancer Inst- 50; 1119 (1973). 4. Bornstein, F. P.: Gallbladder carcinoma m tht Mexican population of the Southwestern United States, Path. Microbiol 35:189(1970). 5. Kraus. L. S.: Gallbladder and extrahepatic bile duel carcinoma Analvsis of 1,808 cases. Geriatrics 27: 111 (1972). 6. Seko. K,, Seitzinger, G. L.. and Garaide. E.: Carcinoma of the extrahepatic bile duett, review uf the literature and report of six cases. Surgery 41: 416 (1957). 7. Third National Cancer Survev Incidence Data. Monograph 41. Biometry Branch. Nat') Cancer Institute. 1975. 8. Vita) Statistics of the United States. 1959. Monograph. Department of Health. Education, and Welfare. Washington. D C . U.S. Government Printing Office. 1961, to). 2, table 74. p. 114 9. Stewart, H. L., Lieber. M. M., and Morgan. D. R.; Ca cinoma of the extrahepatic bite ducts. Arch. Surf. 41; ft- ' (1940). 10. Niebling, H. A., Dockerty, M B.. and Waugh, J. N Carcinoma of the extrahepatic bile ducts. Sura. Gvnec. L Ob- 85: 429 (1949). 11. Roes, A. P.. Brsasch, J. W.. and Warren, K. W.: Carci noma of the proximal bile ducts, ibid. 136:923 (1973). 12. Ritchie, 3. K,, et al.: Biliary tract carcinoma associated with ulcerative colitis. Quart. J. Mad. 43: 263 (1974). 13. Akwari, 0. E., Van Heerden. J, A.. Foulk. W. T.. and Bagenstoss, A.: Cancer of the bile ducts associated with ulcerative colitis, Ann. Surf. 181: 303 (1975). 14. Bismuth. H,, and Malt. R Au Current concepts in cancer carcinoma of the biliarytract. New England J. Med. 301:704 (Sept. 27) 1979. 15. Monaon, R R Peters, J. M., and Johnson, M. N.: Pro portional mortality among vinyl-chloride workers. Lancet 2:397 (1974). 16. Waxweiler, R J., Stringer, W., Wagoner, J. K., and Jonei, J- Neoplastic risk among workers exposeo to vinvl chloride, Ann. New York Acad. Sc. 271:40 (1976). 17. Mancuao, T. F., and Brennan. M. J.: Epidemiological considerations of cancer of the gallbladder, bile ducts and salivary glands in the rubber industry, J. Occup. Med. 12: 333 (1970). 16. Gallagher, P. J., Millis, R R.. and Mitchinson, M. J.; Congenital dilatation of the intrahepetit bile ducts with eholan- giocarctnoma. J. Clin. Path. 25: 804 (1972). 19. Fraumeni, F. J., Jr.: Cancers of pancreas and biliary tract: epidemiological considerations, Cancer Ret. 35; 3437 119751- 20. Enomoto, M., et al.: Carcinogenesis in extrahepatic bile duct and gallbladder--carcinogenic effect of N-bvdroxv.2-ace- tamidofluorene in mica fed a `'gallstone-inducing1' diet' Jap. ). Exp. Med. 44; 34 (1974). 21. Vital*. J. J4 Possible role of nutrients in neoplasia, Cancer Rea. 35:3320 (1975). 22- Sinhuber, Ru Food contaminants and cartanoeeneait, in Clark. R_ Ed_- OnoJogy, Chicago, Year Book Medical Publishers. 1971, voL 5, p. 257.* " 23. Newbumt, P. M., and Butler. W. H.: Acute and chronic effects of aflatexin on the liver of doroeeot and laboratory animals: a review. Cancer Raa. 29; 236 (1969). En bil JEf G. FR) N HO' Ti CA! A Wll Free Uni* J. Crw* j ' vOpa I " tAM i 4'- . Thi gur; con gall othThii 326 Naw York State Journal Of Mefllcine/March 1981 OLI 6673 '