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secondary implantation establishing themselves.

There is nothing strange in this reasoning, for we know that treatments which would induce resistance in normal animals have, as a rule, no influence on a tumour that has already established itself, and started growing; the protection is directed against the establishment of newly introduced grafts only, not against their continued growth once they have established themselves. In some series of experiments it seemed, too, as if the secondary inoculation yielded worse results when the primary tumour had arisen from the introduction of big doses of tumour tissue; but experiments especially directed to elucidating this point have yielded no conclusive proof, because the series of experiments were unsatisfactory. Eight tumours arose from 18 inoculations with 03 ccm., and in the eight mice three secondary inoculations were positive. On the other hand, out of 31 inoculations with 0·05 ccm. only nine tumours were obtained, and in these mice the secondary inoculations yielded only two positive results. These experiments must be repeated at a future date on a larger scale t. The theory of atrepsia seems to have received great support through the notable experiments of Schöne. He showed that the resistance to secondary inoculation disappeared after removal of the primary tumour by operation; the tumours had been obtained by inoculation according to the Frankfort technique. Still I maintain that it is not necessarily proved that the mere disappearance of the influence exerted by the tumour effected this revolution in the mouse organism. If the explanation I have given in accordance with my results is right, viz. that the negative result of the secondary inoculation is not referable to atrepsia but to acquired resistance induced by the primary introduction of larger doses, then it is possible to explain Schöne's facts by assuming that resistance can be destroyed by drastic operation; and this is moreover, as a matter of fact, a possibility which Schöne himself entertains.

The fact ascertained with material in London and by the methods. there applied, that tumour-subjects offer the best chances for tumour implantation, suggested utilising such mice for practical purposes. It seemed conceivable that they might offer a specially suitable fostering soil for transplanting primary tumours also, which might be of great

* Cf. p. 36.

† Dr. Bashford has recently told me that after experiments by Dr. Russell on other tumours, a distinct effect following the inoculation of big doses was not forthcoming Perhaps a difference exists here too between primary tumours and those which have been propagated for a long time.

advantage in view of the low transplantability often exhibited at the inception of propagation. Experiments made by me for this purpose with two spontaneous tumours did not yield exactly encouraging results. But, in both instances they were tumours such as are generally transplanted with difficulty or not at all. One of them was a sarcoma with spindle-cells (No. 92) of the axillary region, which was analogous to that recently described by Ehrlich and Apolant, in its periphery remains of mammary tissue being enclosed. No tumours developed in the control mice. The implanted tumour tissue was obviously living in one of the six tumour mice employed, 39 days after inoculation. The other primary tumour (No. 91) was hæmorrhagic, and was successfully transferred in two out of eleven control mice and in one out of eight tumourmice. Hertwig and Poll report some unsuccessful attempts to transplant a primary tumour into mice already bearing inoculated tumours. Further experiments will show whether primary tumours behave differently in this respect from the inoculated tumours, or whether better results can be obtained.

It is also conceivable that in yet another respect the receptivity of tumour-mice may be used, viz., to overcome the difficulties that so often attend transplantation into strange races. But as I have made no experiments in this direction, I only mention the idea by the way.

It is incumbent on me at the conclusion of these observations to express my most respectful thanks to the Committee of the Imperial Cancer Research Fund in London for permission to work in their admirably appointed laboratory. Above all I am indebted to the Director of the Laboratory, Dr. Bashford, for placing the material and the facilities for experiment at my disposal, and for his aid and support and ever ready advice, for which I return my warmest thanks. The Assistants of the Institute, Dr. Murray and Dr. Haaland, have also most courteously helped me in my researches.

LITERATURE.

APOLANT.-Die epithelialen Geschwülste der Maus. Arb. a. d. Kgl. Institut für exper. Therapie zu Frankfurt a/M. Jena, 1906.

APOLANT.-Die experimentelle Erforschung der Geschwülste. Handb. d. pathogenen Mikro-organismen I. Erg.-Bd., 1906.

APOLANT.-Uber experimentell erzeugten Rückschlag von Mäusekarcinom in den histologischen Typus des Adenoms. Münch. med. Woch., 1907.

BASHFORD, MURRAY, & BOWEN.-Die experimentelle Analyse des Karcinomwachstums. Zeitschr. f. Krebsforschung, Bd. v., 1907; and Proceedings of the Royal Society, vol. 78, 1906,

BASHFORD, MURRAY, & CRAMER.-The Natural and Induced Resistance of Mice to the Growth of Cancer. Ibid., vol. 79, 1907.

BASHFORD, MURRAY, & HAALAND.-Ergebnisse der experimentellen Krebsforschung. Berl. klin. Woch., 1907.

BORREL & HAALAND.-Tumeurs de la souris. Soc. de Biol., 1905; and Annales de l'Inst. Pasteur, 1905.

BORREL.-Le problème du Cancer. Bull. de l'Inst. Pasteur, Nos. 12-15, 1907.
BRIDRE.-Recherches sur le Cancer expérimental des souris. Annales de l'Inst.
Pasteur, xxi. 1907.

EHRLICH.-Experimentelle Karcinomstudien an Mäusen. Arb. a. d. Kgl. Institut
für experimentelle Therapie zu Frankfurt a/M., Jena, 1906.
HERTWIG & POLL.-Zur Biologie der Mäusetumoren.
Abhandl. d. Kgl. preuss.

Akad. d. Wissensch., Berlin, 1907.

LEWIN. Experimentelle Beiträge zur Morphologie und Biologie bösartiger Geschwülste bei Ratten und Mäusen. Zeitschr. f. Krebsforschung, Bd. 6, 1907. LUBARSCH.-Über destruierendes Wachstum und Bösartigkeit der Geschwülste, Zeitschrift f. Krebsforschung, Bd. v. 1907.

MICHAELIS.-Versuche zur Erzielung einer Krebsimmunität bei Mäusen. Zeitschrift. f. Krebsforschung, Bd. v. 1907.

MICHAELIS.-Weitere experimentelle Untersuchungen über den Tierkrebs. Verein für innere Medizin zu Berlin, April 8th, 1907. Deutsche med. Woch, p. 826, 1907.

SCHÖNE.-Untersuchungen über Karcinomimmunität bei Mäusen. Münchener med. Woch., 1906.

SCHÖNE.-Untersuchungen über Geschwulstimmunisät bei Mäusen.

deutschen Gesellschaft für Chirurgie, 1907.

Verhandl. d.

L

THE EFFECTS OF SURGICAL INTERFERENCE WITH THE BLOOD SUPPLY ON THE GROWTH OF TRANSPLANTED CARCINOMATA AND SARCO

MATA.

By W. H. BOWEN, M.S., F.R.C.S.

THIS Paper deals with an investigation undertaken to elucidate the result of obliterating the blood supply of a tumour. The tumours were of three kinds-first, those resulting from the transplantation of strains of an alveolar carcinoma; secondly, of similar transplantations of two adeno-carcinomata of special interest because of the tendency to hæmorrhage and formation of cysts containing blood; and thirdly, of a transplantable squamous-celled carcinoma. The observations are being extended to a transplantable spindle-cell sarcoma. These tumours were taken as being comparable to different varieties of malignant growth, characterised by distinctive relations to the blood supply.

For the object of this investigation, the anatomical conditions provided by tumours resulting from artificial propagation seem ideal. From a surgical standpoint the tumours are easily separated from their surroundings at the time of operation and their blood supply can be entirely cut off. I mention particularly that these ideal conditions exist at the time of operation since there comes a time when such complete separation is impossible, or attended with such great difficulty as to prevent the attainment of the object of the experiment. transplanted carcinomata in the mouse infiltration of surrounding tissues, muscle and skin, is usually a late manifestation. In a few cases where we have attempted operation with such conditions present, we have been compelled to kill the mouse during the operation owing to the attendant difficulties. Our aim has always been to completely

*Jensen's tumour.

In

destroy the continuity of the vessels passing to the growths and to watch the result in a set of uniform experiments.

Some anatomical considerations are necessary to the proper com

[graphic][merged small][merged small][subsumed][merged small][merged small]

FIG. 1.-Dissection to show blood supply to tumour.

The skin over the front of the abdomen is reflected with the tumour attached. In separating the tumour from the abdominal wall some adhesions of its capsule to the muscular parietes have been torn through. Small blood-vessels are divided in effecting this separation. a. Main axillary supply to tumour: this comes off from the vessel of the arm. a1. Anterior branch of main axillary supply. a2. Posterior branch of main axillary supply. abd. Small twigs which ran in the fine fibrous adhesions uniting the capsule of the tumour to the abdominal wall. Car. Main vessel of neck. fem. Main vessel of thigh. 7. Main vascular supply to posterior part of tumour coming from a lumbar vessel. ziph. Xiphoid cartilage.

prehension of the technique of the operations. The tumours were obtained as the result of inoculation of tumour tissue by a hypodermic needle introduced at the groin pushed forward to the axillary region, the tumour cells thus introduced being deposited in the lax tissues

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