SURGICAL REMOVAL

of BRAIN TUMOURS

In 1884, a patient, who had developed twitching and weakness of the left arm and leg was brought to Alexander Bennett, physician at the National Hospital for the Paralysed and Epileptic. Bennett consulted Hughlings Jackson, who diagnosed a tumour ina specific region of the brain cortex. As Bennett was not a surgeon, he instructed J R Godlee as to where the tumour would be so that he could operate. Godlee opened the patient`s skull, and found in the cortex, as Jackson had diagnosed, a tumour which he removed by blunt dissection. The patient recovered and his convulsions, headaches, and paralysis of the left leg all cleared up, but his left arm, which had been partially paralysed had become completely paralysed - indicating that during the operation functional remnants of the particular motor centre had been damaged. Although the patient died a month after the operation, this was not due to the surgical procedure but to infection due to incomplete asepsis. This surgery - the first of its kind - proved that it was possible to cut into the brain without immediate disaster, and that care was need in not only avoiding damge to other motor centre but also that asepsis was essential(1).

In the same year that Godlee performed the first removal of a tumour from a human brain, Victor Horsley began a series of experiments on the brains of animals which was to span seven years(2). It was not until May 1886 that Horsley performed his first operation on a human brain and removed the scar tissue. Later that year, Horsely diagnosed a brain growth, specified its location in the patient and removed a tumour growth. The patient recovered, the fits stopped, and paralysis "improved". But the tumour returned and the patient died(3). Horsley had not only been preceded in diagnosis and surgery by clinicians but his patient faired no better in respect of the paralysis, and his patent died from recurrence of the tumour he supposedly removed, whereas Godlee`s died of infection - unconnected with the tumour. By the end of 1886, Horsley had performed 10 brain operations with one operative death - i.e. 10% mortality. From 1884 to 1891, he and his colleagues performed numerous animal experiments and read eight papers to the Royal Society(4) but for all this, his "success-rate" in brain operations on humans worsened. By 1899, he had performed 44 brain operations, with 10 deaths(5) - i.e. mortality of 25%.

At the benining of the 20th century, mortality from brain surgery was high, with many patients dying without the tumour being located(6).

In 1909, Harvey Cushing reported on his first 30 cases of operating on brain tumours in humans and in that year was invited to the International Medical Congress in Budapest(6). Four years later, Cushing went to Harvard, where he improved his method. He trained surgeons who took his teachings abroad - spreading his reputation(7). It has been said that Cushing`s diagnosis of, localisation of, and surgical removal of tumours came from his experiments on the effects of raised intra-cranial pressure in animals(8). But, diagnosis of a brain tumour in a human patient was made by Hughlings Jackson in 1884, for Godlee`s first surgical removal of a brain tumour in a human patient the same year, the priciples of localisation had been shown by Broca`s autopsy studies in 1871(9), Bartholow`s clincial studies in 1874(10), and Gower`s clincial observations, also in 1874(11) - all before Cushing went to Switzerland in 1899 where he experimented on intra-cranial pressure in animals(12). From his return from Switzerland and up to 1904, Cushing had performed brain surgery on human patients but had not successfully removed a tumour. It was only "with each [clinical] attempt... his results became more encouraging"(13).

refs

1. Thorwald,J. The Triumph of Surgery. Thames & Hudson. 1980.

2. Merrington,WR. University College Hospital & Its Medical School. Heinemann. 1976.

3. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

4. Merrington,WR. University College Hospital... Heinemann. 1976.

5. Lloyd,WEB. A Hundred Years of Medicne. Paperduck. 1971.

6. Reidman,SR. Masters of the Scalpel. Bailey Bros & Swinfen Ltd. 1973.

7. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971. 

8. Millar,D et al. Cambridge Dictionary of Scientists. Cambridge Uni Press. 1996.

9. Thorwald,J. The Triumph of Surgery. Thames & Hudson. 1980.

10. Bartholow,R. Am J Med Sci. Apr 1874.

11. Jackson,JH. Medical Times & Gazette. 21 Jul 1874.

12. Merrington,WR. University College Hospital... Heinemann. 1976.

13. Reidman,SR. Masters of the Scalpel. Bailey Bros & Swinfen Ltd. 1973.

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SURGERY of the BREAST

and REMOVAL of CANCER TUMOURS

Descriptions of surgical amputation of the breast appeared within the books of Paul of Aegina (625-690), which was first printed in Venice, Italy in 1528(1).

It was not until the late 16th/early 17th century that attempts were made at surgical treatment of cancer of the breast. The first dissection of the armpit to treat the disease was performed by Fabricius Hildanus (1560-1634)(1). In 1672, Barbette taught that to prevent a reoccurence of breast cancer, nothing should be left behind. Some surgeons disapproved of excising muscle in surgery of the breast, and debate ensued over whether or not the lymph nodes should be surgically removed during the operation. Sharpe in 1743 said he had removed the lymph nodes without injurying the great vessels, James in 1745 and Le Dran in 1749, warned against that leaving the lymph nodes behind left the patient "uncured"(2) - all preceded Bernard Peyhrihle - who in 1775 injected cancerous material into a dog(3) but killed the animal without recording the result(4) - recommended removal and dissection of the nodes in the armpit(5).

Gooch wrote, in 1773, of the necessity to remove healthy tissue from around the breast cancer tumour - before animal experimenter John Hunter, in 1786-77, lectured his students on extending the incision to the surrounding area(6).

Other animal experimenters followed. Sir Astley Cooper, in 1824, wrote of surgical removal of the breast and has been credited with advocating radical mastectomy. When Charles Moore, in 1867, attempted Cooper`s operation on a human patient, he was unsuccessful(7). Theodor Billroth operated on cadavers, served as an assistant in a surgical department and experimented on animals(8). In 1879, he reported that only 35 of 141 women who had breast surgery survived for any length of time(9).

William Halsted experimented on animals and also spent time in the clinic(10). He put together a diverse group of findings by others from around 1880 - which has been called the "Halstedian hypothesis"(11). In 1889, Halsted planned treating breast cancer by removing all the tissue of the breat and in the region of the armpit, subcutaneous connective tissue, the entire breast, both of the pectoral muscles, and all of the lymphatic glands and connective tissue in the armpit, and to cover the chest-wall defect with a skin graft. Out of the first 50 cases, three had a tumour recurrence(12). Halsted`s hypothesis was accepted as a pattern for managing breast cancer(13). His operation was introduced in 1890 and for over a century was "the treatment of choice for breast cancer"(14).

Despite the wide-spread use of Halsted`s operation, the `British Medical Journal` reported in 1937 that an equal percentage of patients had survived less severe surgery.Geoffrey Keynes of St Bartholomew`s Hospital recorded good results with a simple removal of the breast tumour(15). In 1948, R McWhirter reported on successes with simple mastectomy and went on to adopt a new regime because of concerns that radical surgery failed to get rid of all of the tissue from the area operated on. McWhirter opened the floodgates. Surgeons, world-wide, argued for and against radical surgery(16).

It was not until 1971 that a clinical trial was initiated to confirm or deny Halstedian principles. Results of the trial, to 1985, with a mean follow-up of nearly 10 years, indicated that in patients withou clinical evidence of node involvement, three different surgical methods - radical mastectomy, simple mastectomy with radiation, or simple mastectomy and removal of nodes that later became clinically positive - produced no significant difference in overall treatment failure, distant metastases, or survival. Employment of Halsted`s "radical" operation waned and, instead, use of less extensive operations increased. By the late 1970s, Halsted`s method waslaready a minority opertion(16).

refs

1. Garrison.FH. History of Medicine. WB Saunders Co. 1929.

2. Omingho,WIB. Medical History. vol VI. 1962.

3. Nery,R. Cancer: An Enigma... Croom Helm. 1986.

4. MacGregor,AB. Medical History. vol X. 1966.

5. Porter,R. The Greatest Benefit to Mankind. Fontana Press. 1999.

6. Omingho,WIB. Medical History. vol VI. 1962.

7. Porter,R. The Greatest Benefit to Mankind. Fontana Press. 1999.

8. Rutkow,JM. Surgery - An Illustrated History. Mosby Year Book Inc. 1993

9. Porter,R. The Greatest Benefit to Mankind. Fontana Books. 1999.

10. Reidman,R. Masters of the Scalpel. Bailey Bros & Swinfen. 1973. 

11. Veronessi,IJ. Bonnadonna,G[eds]. Clinical Trials in Cancer Medicine. Academic Press. 1985. 

12. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

13. Veronessi,IJ. Bonnadonna,G [eds[. Clinical Trials in Cancer Medicine. Academic Press. 1985.

14. Lett,H. Lancet. i. 1902. 

15. Keynes,G. British Medical Journal. 1937.

16. Veronessi,IJ. Bonnadonna,G [eds]. Clinical Trials in Cancer Medicine. Academic Press. 1985.

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OPERATION for ECTOPIC GESTATION

In 1892, the gynaecologist, Dr Robert Lawson Tait gave his account of the delay in the introduction of the operation for ectopic gestation -

"The rationale of the proposed operation was fully explained about 50 years ago, but the whole physiology of the normal rocess, and the pathology of the perverted one, were obscured and mispresented by a French physiologist`s experiments on rabbits and dogs. I went outside the experimenter`s conclusions, went back to the true science of the old pathologist and of the surgeons, and performed the operation in scores of cases with almost uniform success. My example was immediately followed throughout the world, and during the last five or six years, hundreds if not thousands of women`s lives have been saved, whilst for nearly forty years the simple road to this gigantic success was closed by the folly of vivisection"(1).

refs

1. Tait,RL. Birmingham Daily Post. 4 Oct 1892

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                 HIP REPLACEMENT SURGERY

John Charnley developed an arthoplasty of the hip in 1946, but a preliminary trial led him to believe that it was unsatisfactory(1).

In 1949, Charnley received a Home Office licence to experiment on animals, and it is said that he grafted bones in goats but did not record the results. Likewise, he did not publish ANY papers on any animal experiments he may have conducted(1). Charnley wrote "A few observations on the human are often of more value than a large series of experiments on animals..."The `crucial` experiment was an isolated observation"(2). The `crucial` experiment had been performed on a human patient(3).

Later, Charnley measured co-efficiency of the fracture of articular cartilage. This could be done quite simply in an engineering laboratory but it was not so easy in animal joints, since the cartilage could not be fashioned into a plane surface. Charnley checked the published papers and found two written in 1934 and 1936 by E S Jones, who had described his experiments on the knees of horses but Charnley believed that such experiments were open to various objections and decided to make measurements on a freshly amputated knee joint of a human patient(3).

Thus, Charnley may have had a vivisector`s license and, possibly, did conduct some animal experiments - but he realized that the progress had to come from clinical work - which he did.

refs

1. Waugh,W. John Charnley - the man and the hip. Springer-Verlag.

2. Charnley,J. 1956. quoted in ibid.

3. Waugh,W. John Charnley - the man and the hip. Springer-Verlag. 

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OPERATION on, and REMOVAL of,

the PROSTATE GLAND

Surgical excision of prostate cancer was attempted as early as 1867 but, except for cancers in the very early stages, had little chance of success. In the 1880s, surgeons operated to relieve obstructions of the prostate but, at first, these were incidental to removal of bladder stones(1).

In 1887, Arthur McGill, of Leeds Royal Infirmary, showed that prostectomy could be of use in its own right, when he successfully performed the operation on three patients(1). By 1890, McGill had performed 37 prostectomies with good results(2). Around this time, the operation was taken up in America(3), where William Belfield of Chicago, in 1890, reported on 80 cases with 14% mortality - considered excellent at that time(4). With studies of kidney function prior to operation, and clearing of infection before surgery, the technique improved and mortality was reduced(5).

In July 1893, J W White reported that castration had resulted in clinical improvement in men with benign,enlarged, prostate glands and that the glands had reduced in size(6). Three years later, A T Cabot reported similar findings, clinically(7).

Although it had been known for years that in humans, castration before puberty usually prevents the developemnt of the prostate gland and that in adults, castration causes regression of the accessory sex glands(8), in the 1930s, experimenters conducted castraction experiments in animals and reached different conclusions. D Price, in 1936, found that castration of rats before puberty did not greatly interfere with development of the prostate gland in puberty until the animal reached an age of 35 days or more(9). In July 1939, E D Sayles reported that castration of guinea pigs does not cause complete regression of accessory sex glands(10) - both in contrast to what happens in humans.

Charles Huggins, at Chicago University, had castrated some dogs prior to measuring effects of testosterone injections, when he made a chance observation that castration had caused regression of tumours which had arisen spontaneously in elderly dogs(11). In 1939, Huggins, R E Stevens and C V Hodges started a series of clinical castrations for advanced or metastatic carcinoma of the prostate(12) - over a year before Huggins and Clark published a paper reporting that castration caused rapid shrinkage of prostatic tumours in dogs(13). Although Huggins claimed "experiments on canine neuplasia proved relevant to human prostate cancer"(14), he also said, in the same speech, that "Most of the canine prostatic tumours are benign growths with much hyperplasia of epithelium and many cysts; carcinoma is usually detected only by histological examination... At first, it was vexatious to encounter a dog with prostatic tumour"(14). In May 1940, Huggins and R E Stevens showed that wasting away of the tissue covering the external surface was present three months after castration(15) - as White and Cabot had found, clinically, in the 1890s. By December 1940, Huggins, Stevens and Hodges had performed 21 clinical castrations for advanced or metastatic carcinomas of the prostate. Four of the patients died with eight months of the operation, 15 showed some improvement, and the other two had only recently been operated on and it was considered too early to deduce if there was any benefit(16). Later, Alexander Haddow reported that, for the years 1946-47, of 45 consecutive cases, in 5 patients castration caused no improvement, in 9 there was only slight, temporary improvement, and 31 showed inhibition for up to 30 months(17).

Years later, the Veterans Administration Cooperative Urologic Research Group (VACURG) launched a prospective randomnized clinical trial regarding treatment of prostatic carcinoma. All of the patients were randomnly assigned to prostatectomy plus placebo, or just to placebo. The findings showed that progression and survival rates of the patients were similar whether subjected to prostectomy plus placebo, or just to placebo(18). W F Whitmore Jnr of the Memorial Sloan-Kettering Cancer Center, New York, informed the Sixth Annual Bristol-Meyers Symposium on Cancer Research - held in Oct 1983 "the data do not suggest any advantage to radical prostatectomy over placebo in up to 9 years of follow-up"(19).

refs

1. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

2. Porter,R. The Greatest Benefit to Mankind. Fontana Press. 1999.

3. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

4. Porter,R. The Greatest Benefit to Mankind. Fontana Press. 1999. 

5. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

6. White,JW. Annals of Surgery. vol 18. 1893.

7. Cabot,AT. Annals of Surgery. vol 24. 1896.

8. Young,HH. in Cabot,H. Modern Urology. Lea & Febiger. 1936.

9. Price,D. Am J Anat. vol 60. 1936.

10. Sayles,ED. Physiol Zool. vol 12. 1939.

11. Sneader,W. Drug Discoveries. John Wiley & Sons. 1989.

12. Huggins,C et al. Archives of Surgery. vol 43. 1941.

13. Huggins,C. Clark,PJ. J Exp Med. vol 72. 1941.

14. Huggins,C. Nobel Lecture. 13 Dec 1966.

15. Huggins,C. Stevens,RE. J Urol. vol 43. 1940.

16. Huggins,C et al. Archives of Surgery. vol 43. 1941.

17. Haddow,A. British Medical Bulletin. vol 4. 1946/7.

18. Byar,DP. Corle,DK. Suppl Urol. vol 17. 1981.

19. Whitmore,WF Jnr. in Veronessi,U. Bonnadonna,G [eds]. Clinical Trials in Cancer Medicine. Academic Press. 1985. 

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OPERATION on, and REMOVAL of,

the THYROID GLANDS

Early in the 19th century, Raynard of Lyons, France said that removal of the thyroid glands in dogs was fatal, whereas Astley Cooper of London reported, in 1827, that puppies who had their thyroid glands cut out "remained well" after being allowed to recover(1).

In the 1850s, clinical and autopsy studies showed a connection between lack of the thyroid gland and mental deficiency. Thomas Curling, in 1850, described two mentally-deficient children with pads of fat above their collar-bones but neither showed any signs of swelling of the thyroid gland. After both had died, post-mortem examinations revealed an absence of the thyroid glands. Curling suggsted that the presence of the abnormal fat might have been due to "absence of those changes which result from the thyroid"(2) and described the condition of absence of the thyroid glands with defective brain development(3).

After Curling`s clinical findings, experimenters, during the 1870s, removed the thyroid glands of animals - with different results in different species. Moritz Schiff, Prof of Comparative Anatomy, in Berne, performed  thyroidectomes on dogs and guinea pigs in 1856 and 1857 - with fatal results(4) and that whilst removal of the thyroid glands of cats was also fatal, this was not so in rabbits and rats(5). Jacque Reverdin, professor of pathology at the University of Geneva, partly removed the thyroid glands of animals - experimentally-inducing a condition resembling myxoedema(6) and thought that there was some interference with the blood-forming function of the thyroid glands(7).

But the animal experiments did not instill confidence in clinicians. Paul August Sick, in 1869, carried out his first total thyroidectomy on a human patient, but was cautious in his choice of patients and in 1877 he warned against trying the operation for "cosmetic" reasons(8). Two years later, Edward Crisp told the Royal Commission on Vivisection "I have been a vivisector for some time. For several years I cut into animals, removing their spleens and thyroid glands and performed many other experiments; and as I advanced with age,and I hope in wisdom, I saw fit to alter many opinions that I had formed at an earlier period; and I have come to the conclusion that vivisection as practised,especially on the Continent, has not led to the good that its advocates believe"(9).

Surgeons were reluctant to perform thyroidectomies on human patients due to risks of haemorrhaging. Although about 190 such operations were carried out between 1850 and 1877, mortality was 20%(10). Albert Billroth performed thyroidectomies on 20 patients - 8 of which died(11). Theodor Kocher, a pupil of Billroth, warned, at that time, that removal of the thyroid glands was "one of the most dangerous operations"(12).

In 1882, the Reverdins published a short report on "bizarre" changes seen in some patients following an operation on the thyroid. Swiss surgeons already knew, clinically, of similar cases of myxoedema after degeneration or absence of the thyrid gland(13).

Kocher informed the German Surgical Congress, in the Spring of 1883, that in follow-up studies of 30 out of the first 100 thyroidectomies performed by him and his colleagues, presented "a definite, characteristic disease picture" - which they called cahexia strumipriva(14). In that year, Felix Simon addressed a meeting of the Clinical Society in London, where he refered to Kocher`s work and stated that cahexia strumipriva, myxoedema, and dwarfism were all due to loss of function of the thyroid. As more cases of these conditions appeared, the Clinical Society appointed a committee in December 1883 to investigate(15). One of the members of the committee was Sir Victor Horsley, who later recounted "I was appointed to make the crucial experiment of removing the thyroid gland in a monkey, in order to see whether that was the cause or whether it was due to damage of the nerves of the neck; and my experiments proved that it was due to the loss of the thyroid gland"(16). Horsley started his experiments in 1884 and described that removal of the thyroid glands of four monkeys resulted in one developing nervous tremours(17). Schiff, who had performed thyridectomies on animals in the 1850s - with differing results - repeated his animal experiments and then he and Horsley tried to treat experimentally-induced myxoedemia by grafting the thyroid glands of the animal back into parts of the body of the same animal, but these attempts were only "temporarily successful", as the thyroid gland was soon absorbed(18).

By 1895, Kocher had conducted more than 1000 thyroidectomies, and almost 20 years later the number had exceeded 2000 - and the mortality rate had dropped to 4.5%(19).

In 1906, Prof Swale Vincent and a Mr W A Jolly removed the thyroid glands of various species of animals - including monkeys, cats, dogs, prairie wolves, badgers, foxes and rats - and reported that such operations resulted in death in dogs, cats, foxes and wolves(20). A year later, at the Second Royal Commission on Vivisection, Horsley was questioned about these experiments by Dr Wilson, who suggested to Horsley that monkeys, with their thyroid gland removed, did not show the slight symptoms of myxoedema. Horsley admitted, in his reply "many of the animals did not show anything at all"(21) - in contrast to the findings in his own experiments, and in agreement with Schiff`s initial findings of "species differences".

The clinicians had preceded and succeeded where the animal experimenters failed. Cushing`s clinical work of 1850 was before Schiff`s experiments with their contradictory findings, Kocher`s clinical studies were ahead of Horsley`s monkey experiments, Sciff`s repeat of his own experiments, and the contradictory results of experiments by Vincent and Jolly.

refs

1. Lancet. 2 Dec 1933.

2. Singer,C. Underwood,EA. A Short History of Medicine. Oxford Uni Press. 1962.

3. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

4. Singer,C. Underwood,EA. A Short History of Medicine. Oxford Uni Press. 1962.

5. Lancet. 2 Dec 1933.

6. Lloyd,WEB. A Short History of Medicine. Paperduck. 1971.

7. Merrington,WR. University College Hospital and its Medical School. Heinemann. 1976.

8. Singer,C. Underwood,EA. A Short History of Medicine. Oxford Uni Press. 1962.

9. Crisp,E. evidence before first Royal Commission on Vivisection. 1875.

10. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

11. Singer,C. Underwood,EA. A Short History of Medicine. Oxford Uni Press. 1962.

12. Kocher,T. Les Prix Nobel. 1909.

13. Lloyd,WEB. A Hundred Years of Medicine. Paperduck. 1971.

14. Singer,C. Underwood,EA. A Short History of Medicine. Oxford Uni Press. 1962.

15. Merrington,WR. University College Hospital... Heinemann. 1976.

16. Horsley, Sir V. evidence before Second Royal Commission on Vivisection. 13 Nov 1907.

17. Merrington,WR. University College Hospital... Heinemann. 1976.

18. Singer,C. Underwood,EA. A Short History of Medicine. Oxford Uni Press. 1962.

19. ibid.

20. Vincent,S. Jolly,WA. J of Physiology. Aug 1906.

21. Horsley, Sir V. evidence before Second Royal Commission on Vivisection. 13 Nov 1907

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