251

THE HIDDEN BLEEDING-POINT

1. Quattlebaum, J. K. Ann. Surg. 1954, 139, 743.2. Sheldon, W. C., Lazar, H. P., Richards, J. W., Henegar, G. C. Amer.

J. dig. Dis. 1959, 4, 817.3. Langrall, H. M., Baggenstoss, A. H., Wollaeger, E. E. Proc. Mayo Clin.

1960, 35, 195.4. Bingham, J. R. Canad. med. Ass. J. 1959, 80, 704.5. Marchand, P. Brit. J. Surg. 1960, 47, 515.6. Wangensteen, O. H., Root, H. D., Jenson, C. B., Imamoglu, K., Salmon,

P. A. Surgery, 1958, 44, 265.7. Khalil, H. H. Lancet, 1958, i, 1092. Khalil, H. H., Mac Keith, R. Brit.

med. J. 1954, ii, 734.8. Ulin, A. W., Sokolic, I. H., Thompson, C. Ann. intern. Med. 1959, 50,

1395.

MAsSIVE gastrointestinal bleeding may arise fromobscure causes-aneurysm of the hepatic artery 1 for one,duodenal divertiCUIUM 2 for another-but the source of

bleeding from even the commoner causes may baffle thesurgeon. This difficulty led Langrall et al.3 to undertake apathological evaluation of patients who had died of

massive hxmorrhage at the Mayo Clinic between 1944and 1955. These accounted for 135 out of 7312 necropsies,and almost 75% (93) of the haemorrhages were due topeptic ulceration (50) or oesophageal varices (43). 15%(20 cases) were due to cancer in stomach, oesophagus,pancreas, or duodenum; in a further 11 cases haemorrhagewas due to a blood dyscrasia, while in 4 even the patho-logist was unable to detect a lesion at a complete examina-tion. It is comforting to know that by far the most likelysites of bleeding are the stomach, lower oesophagus, orduodenum; but necropsy figures give a false picture of theincidence in clinical practice, since some conditions areless amenable to treatment than others-bleeding fromoesophageal-varices, for example-and thus more suchcases come to necropsy. In a similar period (1945-54)784 patients were admitted to the Toronto Western

Hospital for treatment of upper-gastrointestinal hxmor-rhage 4; almost 80% of these cases were due to peptic ulcerand only 9% to oesophageal varices.Why, then, is it difficult for the exploring hand and eye

always to locate the lesion responsible for bleeding ? Some-times folds of mucosa hide an acute or superficial lesionwith little induration to attract attention; sometimes amanifest lesion distracts attention from the site of bleed-ing, as when duodenal ulcer is associated with a bleedingulcer in a hiatus hernia: Marchand 5 has reported bleedingin 37 of 138 cases of hiatus hernia, and in 19 this reachedmassive proportions. Surgery suffers from the limitationthat the site of the lesion must be found if bleeding isassuredly to be stopped by excision or ligation. Wangen-steen’s method of hypothermia using a refrigeratingcirculation within a balloon placed in the stomach-anapparatus similar to Khalil’s 7-has much to recommendit if further trials substantiate his original findings in 5patients. The lesions included gastric and duodenal ulcerand oesophageal varices; in all 5, haemorrhage ceased.Gastric hypothermia is therefore more widely effectivein the anatomical sense than the surgeon, for it does notdemand precise localisation of the lesion.

Langrall et al.3 found no deaths due to hxmorrhagefrom the lower intestine and ascribe this to the fact thatdiverticulitis, ulcerative colitis, regional enteritis, polyps,and carcinoma (though they may cause bleeding) seldomcause exsanguination. Nevertheless they sometimes do,and Ulin et al.8 describe 5 cases of " major " bleedingdue to diverticulitis, in 1 of which emergency resectionhad to be undertaken because the patient seemed likelyto die. The absence of bowel lesions from the MayoClinic necropsy series may reflect the relative efficacy oftreatment. Nevertheless anyone who has been forced toopen the abdomen on account of bleeding from the bowel

9. Monroe, L., Steelquist, J. Gastroenterology, 1960, 38, 650.10. Sandegard, E. Acta chir. scand. 1959, 117, 465.11. Bennette, J. G. British Empire Cancer Campaign annual report, 1957;

p. 19.12. Bennette, J. G. ibtd. 1958, p. 139.13. Bennette, J. G. tbid. 1959, p. 13.14. Bennette, J. G. "Vature, Lond. 1960, 187, 72.

will be aware that here, too, the exact site of bleeding,whether from diverticulitis or colonic telangiectasia, 9is sometimes difficult to locate-though this difficulty cansometimes be overcome in blunderbuss fashion by theradical approach of transverse colostomy to locate large-bowel bleeding in the proximal or distal half, followed bythe appropriate hemicolectomy.10

ASCITES TUMOURS DESTROYED BY

NON-PATHOGENIC FILTRATE

DURING serial grafting of an ascites tumour Bennette 11found an unusual appearance in some of the grafted mice.This consisted in clumping of inoculated cells, absenceof ascitic fluid, fibrinous exudates, and gelatinousdegenerate tumour growths. These changes led to intes-tinal adhesions and death. Serial transplantation of theabnormal intraperitoneal tumours ended in their loss.From the same original source, however, the usual typeof ascites-’tumour cells had been maintained in other mice.All the host mice, which were of mixed stock, had beentreated with vaccinia lymph as a prophylactic measureagainst ectromelia.12 At this stage it became advisable touse line-bred mice as hosts for the grafts and C3H werechosen. Bennette then found that, by adding vaccinelymph to Krebs-2 ascites samples before inoculation, orby injecting it intraperitoneally after implantation, theinoculated cells were destroyed, resulting in

" no-takes ".Addition of vaccine to tumour inocula induced theabnormalities that were seen originally. A less closeassociation of abnormal growths with vaccinia, which haslong been known to destroy certain mouse ascites tumours,was found in a subline which had shown no unusualfeatures for many transfer generations. Typical ascites-tumour cells from this source were then grafted into C3Hmice which had not been vaccinated. In the tenth serialtransfer in unvaccinated mice the characteristic abnor-malities developed.

These and other observations led to testing of sterilefiltrates of extracts of abnormal growths 13 14 for tumour-destroying capacity. Samples from one abnormal tumoursubline which had been stored at -50°C provided abacterially sterile filtrate that had a potent destructiveeffect on five different kinds of ascites tumours.14 A small

group of normal mice which were given 106 times thetumour-destroying dose of filtrate were observed for twomonths without showing signs of illness The implica-tion is that filtrates from degenerating ascites-tumourgrafts can cause these same degenerative changes and evencomplete failure to

" take " when injected with inocula ofthe usual typical ascites cells. As there was also evidenceof increase with passage, the destructive factor is believed

by Bennette to be a virus. Some attempts to demonstratevaccinia itself have failed. 12 Control filtrates from typicalforms of Krebs and Ehrlich ascites tumours prepared inthe same way never gave rise to destruction of tumoursor even modified the final yield, compared with untreatedand saline controls.

The morphological degeneration in the affected ascitestumours is distinctive and is clearly unusual. Ascites

growths have now been observed for over half a century,and if these changes were seen earlier they did not attract