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THE LANCET Vol33a Santrday 19 Ocroba 1991 No 8773 Cancer mortality among workers in chemical plant contaminatedwith dioxin A .\Lw% J. BERGER J. H.DU-YER D FLESCH-JAXY~ S S A G E L H W X Irscm-r Dioxin (2.3.7.8-tetrachlorodibenro-p-dioxin or TCDD) can arise as a contaminant in the production of herbicides. It causeschloracnein those exposed to it but its human carcinogenicity has been a matter of dispute Werepon here a mortalityfollow-upof 1583 workers (1 184 men. 399 women) employed in a Introduction nkthough a rehnon been of malignancyat s e v d s i t s and exposure to 23,7.8-tcoKhlorodibenro-pdioxin ,dioxin,TCDD:hasbeRlobscn.edinylimals,' 'thehuman arcmoeeniory of TCDD remains inntmvcwdl.'" The debate stems pnmvlly from moonsistent !indings in chemicalplant in Germany that produced herbicides. including processes contaminated with TCDD. Productionof TCDD was reducedfrom 1954aher an outbreak of chloracne. Vital status up to 1989was determlned for 97 1 % of worken hired between 1952and 1984.and 367 deaths (313 men, 54 women) were recorded. A case-referent rrudies rclatmq nsk of soh-tissue w c o m or non-Hulgh's ivrnphomy IO hcrbiude c x p u m . Several invesnprm have dermed a positive aswa3tinnb* but others have E p i d m o l o g ~ a lassmauons berwcm TCDD u p s u r e and other cancers have alu, been I'CFQKCd.'''' Follow-upof a US mhon of over 5ooo TCDD-exposed malignant neoplasm was the underlying cause of death in 93 men and 20 women. Standardised mortality ratios (SMR) were calculated with, as references, national mortality statistics for Wesr Germanyand deaths in a cohort of malegas workers: for total cancer mortal w :bey were 1 24 , OES: confidence in:erval 1 OC-1 5 2 ) and 1 39 ( 1 i G 1 75). respectively. among men. Cancer mortalirv was increased among men with 20 or more years of employment (SMR = 1 87 [Germany] and 1 82 [gas workers]) and among men who began 'r employment before 1955 ( S M R = l 61 and 1 87). The group with suspected highest exposure to t TCDD had SMRs of 1-42 and 1.78. Only 7% of cohort women worked in the high exposure locations in the plant compared with 39 6% of men and no increased risk of cancer mortality was ohservedarnnna womzr. hut breast ranter mortal~rv was :dised (S;iL1 - 2 i5 : . These results. togethec with a US occupational * Studv and J Gcrr::J:: ~r'.4jl:~J!lOn?f ~ c c I C C - ~ : ~ ~ exposure. suoprm rne nvpxnesis mar ii00 is a human carcinogen c LdnCCf 7 991. 338'95% 64 t I TABLE Ill-SOURCES OF DIAGNOSIS G MALIGNANT N E O P W M S AND OTHER CAUSES) VOL 338: OCT 19,1991 961 TABLE IV-STANOARDISED MORTALITY RATIOS (MEN ALL CAUSES) WITH WEST GERMAN NATIONAL DATA A N D GAS WORKERS AS REFERENCES Grouca Td Lw < I 9 5 4 Enm > I 9 5 4 Emplwnat m n LnphnTmnl :r)w Ij ! NO 0 W m Gaman rataancc E SMR 1 llQ ,313 3128 lCOlOBelIZ I 852 IPO ,1030 219 118 Y 181 2 2779 35- IO 091-1 21 101 0-1 I 3 OV50e+l33 Gas wortas r e h r m e ' 01E1 SMR I % , I 1.3-1 51) I47 I lob0 I T 1w9 3 21 3 l H t l 17-1 63) I Y I 1-+15r 103 0 6 5 I M *O-n*mn,o~-..n 3-*-.e f-..D.Cv.d s m - s r a m m - - m II .,o ..~*%%cI i Yi %2 THE LLUCET L O L 338 ocr 19,iwi TABLE VI- STANOARDISED MORTALITY RATIOS ( M E N M A L I G N A N T N L O P I A S U S I BY TCDD EXPOSURE GROUP A N D WITH WEST .. GERUAN YATIONA. DATA 4 N D GAS N ? R K E R S A 5 RiCEPENCES - _- - ,I "..,-e _ _ *.+---" c... __ - ..A" ~ "',,""-" c s m u i a YKWD \o 0 C bva 3 bvm __p_______i_i______-, I .il No d a h due IO Soft-IISUC SICOrlIa 1 0 171) *dS Observed 140% of deaths m men were due to unnatural causes (n = 43) There mere 22 suodes, yleldmg an S M R of 2 29 (1 3 8 , 3 5 7 wth West Germany as rhc rcfercna and 3 90 (2 42,5 97)wth rhe gas uorken Mortalily among women Smoking Data on smdring wcrc avadable for a non-repmentanve group of 361 men ul h e BcchnngCT cohort. 7396 were wlf-rcponed smckcrs. In the gas Harker mhon 76% of ?861) mcn wcrc smokers. Discussion Cancer incidence VOL 338: OCT 19,1991 7HE LANcEr 963 Outcome in patients with subarachnoid haemorrhageand negative angiography according to pattern of haemorrhage on computed tomography GABRIEL J. E. Rbr?EL EELCOF. M. WUDIatS DJOHAS.&!! GEORGE E. .M. KIEXSTRA CEES L. %.XE LOES M. HAGEMAE: .WARISW VERAELZEE~ JAY VAN Grm 15% of patients with spontaneous subarachnoid haemorrhagehave normalcerebralangiograms.they fare better than patients with demonstrated aneurysms though rebleeding and cerebral ischaemia can still occur In patients with a normal angiogramand accumulation of blood in the cisterns around the midbrain-"perimesencephalic nonaneurysmal haemorrhage"-outcome is excellent. To t e n the hyporbesis that rebleeding and disability in angiogram-negative subarachnoid haemorrhage mignt be limded to [hose with other parferns of haemonhage on initial computed tomography (CT), complications and long-term outcome were nudied in 113 patients with angiogram-negative subarachnoid haemorrhage. admitted between January, 1983. and July. 1990 All patients were investigated with third- generation CT scans within 72 h of the event. and with cerebral angiography The mean follow.up period was 45 (range 6-96) months None of 77 patients with a perimesencephalic panern of haemonhage on CT died or was letr disabled as a result of the haemorrhage (096 [95% confidence interval C-5%]) Among the other 36 patients, who had a blood distribution o n CT indistinguishable from that in proven aneurywnal bleeds. 4 had rebleedsand 9 died or were left disabled as result of the haemorrhage (25% [l4-d3%]) Thus, two distinct subsets of patients with angiogram-negative subarachnoid haemorrhage should be recognised. Patients with a permesencephalic panern of haemonhage have an excellent prognosis. Rebleeding, cerebral ischaemia. and residual disability occur exclusively in patients with aneurysmal panerns of haemonhage on initial CT. Repeated angiography in search of an occult aneurysm is lustified only in the patients with aneurysmal patterns. Lancer 1991,338: W E . Introduction More t hhalfof paucntsuith aneurysmalrupture&e or r m revcrcly dmbled.' Blood m h e b a d cmcms on computed tomography (Cr:suvngly suggcsts aneurysmal rupnrrc,'butrhcauuoflhcbleedranvlsuncun~it is confvmed by m + b d angiognphy. Despite subsmaal Impmanenu in imaging acquismon, anngiognphy fails IO rhow an .VKUTYYI] in 15% of paenn with spmraneous subarachnoid hacmorrhage.'*' I t is wdely believed hat ptirnts \nth angiogram-ncgauve subvacnnoid h 3 m o r h a p b v e a more favourabk p m p o s i s than thw HILI pUsiu\t- rn~Oio(p;LT&. S C I C C , i C i U . khc) TL, >utk: f a d rcblctds and long-term disab~~il'y.'~~'''. ADDRESSES Unwemriy 0epa.nm.nrr 01 Neurology. U t r w h i i G J E 9 m k U U O E F M Wildiclu U D Prof J ran Gqn W O I . and Roitwaam 1 0 H-n wo Pro1 U v e i m c w n uol. U ~ I Y ~ R I I Y D.w.nnwr1 of Nmtrowrgwv. Aud.m,c M m d i ~ ICanIra. Amsindam i L M H-n. WDI: and O*p.nm*nU of Nwrolagv. St E l i u b e t h Mo.p#Ial. Tiiburq i G E M Kmmtra. U O ) . and D. W8V.r H ~ p t l a iH. wrlm. th. N.ih.rlmd# t C L Frank.. u o ) CwmwnMnc*IO Dr Gibrml J E R m W Un8nnrrh Dewenmen! 01 NauroIr~~Hy.edeibmgim>100. 3584 CX UVech! :he Nethalands