In accordance with the fair use exception to copyright for teaching purposes, I am engaging with it here to bring out points that are directly relevant educationally to stakeholders in the massage community, and to provide links to clarify specialized knowledge as needed.
That way, when we're trying to navigate among terms, concepts, and referents in discussing this article to get at what it all means, we have the advantage of a shared vocabulary and approach to help us work together with each other.
ANNALS of SURGERY VOL. LXXV FEBRUARY, 1922 No. 2
THE RELATIONSHIP OF MASSAGE TO METASTASIS IN MALIGNANT TUMORS*
* From Columbia University, Institute of Cancer Research, F. C. Wood, M.D., Director, New York.
BY LEILA CHARLTON KNOX, M.D. OF NEW YORK, N. Y.
One of the most important aspects of the practical study of tumors is the determination of the anatomical and biological conditions which facilitate or prevent metastases. These phenomena have long been studied in man without much definite information having been collected. About all we know is that, in general, carcinomata are prone to metastasize through the lymph-channels and sarcomata through the blood-vessels, and that metastases do not always follow in the direction of flow of the current, but in a certain proportion of instances the emboli travel by a retrograde course or the tumors progress by direct extension, the so-called permeation of the lymphatics.
What are the important points that Knox is making here?
Structually, what part of the research article that you would expect to see here is missing? What might be a reason that this research review article does not have the structure that you would normally expect?
It has been generally assumed, without direct experimental proof, that a number of the factors favoring the production of metastasis are purely physical, for instance, the size and connective-tissue relations of the tumor cells, the pulsating or contractile movements of the organs in which they are implanted, the number of the blood-vessels and the thickness of their walls, with consequent susceptibility to trauma by pressure or massage. On the other hand, accurate clinical study and experimental work as well have caused the occult and convenient theories of tissue predispositions and specific "immunity" of organs to assume a less creditable position than they formerly held, and quite properly, for until it is shown that simple mechanical and biological facts do not account for the peculiarities in the occurrence and distribution of metastases vague theories should not be substituted.
What exactly is she saying here about material mechanical and biological facts?
Is she arguing from a realist position or not? How do you know?
At this point, unless we have some specific knowledge of particular claims about metastasis made at this time in history, it's unclear exactly what she means by "occult and convenient theories of tissue predispositions and specific "immunity" of organs". At a very general level, however, what does she appear to be talking about? Remember this point--she'll clarify it later in her discussion.
Where does she use Occam's Razor in her argument here, and why?
The importance of vascular embolism in the spread of tumors has long held an unchallenged position in instances in which the pulmonary veins were known to be grossly involved and the arterial circulation in that way obviously open to a supply of tumor cells. A valuable contribution on this phase of the subject was made when M. B. Schmidt showed that not infrequently the tumor cells readily pass the pulmonary capillaries and are deposited elsewhere before macroscopic growth appears in the lung. In a study of forty-one cases of primary abdominal carcinomata without extensive gross metastases, the lungs of fifteen were found to contain microscopic arterial emboli of tumor cells, showing that once the cells gain entrance to the blood stream they may reach any portion of the body and are not necessarily always retained or destroyed within the lungs. This may, however, be their fate, for Schmidt found many small thrombosed vessels with degenerating tumor cells entangled in the clot. These phenomena have been duplicated experimentally by Takahashi and by Iwasaki, both of whom injected tumor cells into the blood stream of animals. Both these authors have well shown that although embolic cells are frequently treated as foreign bodies and phagocyted, many, on the contrary, survive the adverse conditions, and invade and replace the vascular endothelium or undergo mitosis even before they become implanted on the vessel wall.
What does she mean by "the pulmonary veins were known to be grossly involved and the arterial circulation in that way obviously open to a supply of tumor cells"? Describe the relationship between pulmonary veins and arterial circulation that she is referring to.
What is M.B. Schmidt's valuable contribution on the subject, and why is it so valuable?
What did Takahashi and Iwasaki show, and what does it mean?
Notice the unusual term "phagocyted"; it means the same thing as "phagocytosed", which is the term you see more often nowadays, as in this example from Wikipedia:
Phagocytosis (from Ancient Greek φαγεῖν (phagein) , meaning "to devour", κύτος, (kytos) , meaning "cell", and -osis, meaning "process") is the cellular process of engulfing solid particles by the cell membrane to form an internal phagosome by phagocytes and protists...Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed.
For purely physical reasons, however, we must suppose that cells of small size accomplish this more readily than do larger ones, and experience shows that the large spindle and giant cells, or those distended with mucus as many from the gastro-intestinal tumors are, do not find their way through the pulmonary capillaries except in small numbers. Whether or not the ameboid motion of the cells is a factor in facilitating this is not known. That such motion exists was shown by Carmalt in 1872 and later by Lambert and Haynes.
What are two possible physical explanations that could account for smaller cells establishing metastases beyond the lungs more successfully than larger cells do?
The localization and growth of embolic tumor cells within the dilated capillaries of the bone-marrow have been explained as due to the physiological hyperaemia which is practically constant in that situation. Slowing of the blood current and adhesion of the tumor cells to the endothelium seems to produce circumstances favorable to the growth of such emboli.
Is she saying that bone marrow is particularly susceptible to metastasis from tumors that originated elsewhere in the body? Why or why not?
Lymphatic embolism, either direct or retrograde, has also been unquestionably a frequent and important means of tumor dissemination; but the status of lymphatic permeation, although very convincingly demonstrated by Handley in certain cases, is perhaps a less constant phenomenon than he at first believed.
Notice the British spelling of "tumour", and beware the typo in "pulmonary"--this image was probably created by a non-native English speaker, but is factually correct with regard to the referent, although they misspelled the term.
Tell me what we're looking at here--what structures and processes do you see?
The process, as Handley described it, consists in the proliferation of tumor cells which, having gained access to the superficial lymphatics in the proximity of the tumor, continue to grow within them and to extend through their branches, often appearing in the skin, where they form cutaneous nodules. Secondarily, there often occurs an inflammatory fibrosis and obliteration of portions of the lymph-channel, a process analogous to the thrombosis which is common in invaded vascular channels. Handley studied especially breast carcinomata and melanomata--two of the tumors which most frequently exhibit regional cutaneous recurrences and extensions; and it is on the basis of his evidence that one may perhaps regard some of the recurrences in surgical scars as accidental occurrences due to the proliferation of tumor cells present in the lymphatics prior to the incision, though possibly accelerated in growth by the increased vascularity of the wound area. Probably, however, a majority of the local recurrences are due to a mechanical transplantation from an infected to a non-infected field.
What metastases do breast cancer and melanoma frequently exhibit?
What is the connection between metastasis and surgical scars?
What are 2 possible mechanisms for their occurrence?
Notice the use of "infected" to refer to cancer cells here.
FIG. 1.-Metastasis of breast carcinoma in pectoralis muscle following massage in man.
What different kinds of cells and other material physical things do you see there?
What indicates that you are looking at muscle cells?
What, particularly, indicates the pectoralis muscle?
In the case of the melanomata this mechanical transfer by operation is not a completely adequate explanation, for the nodules are often found far from the region of the incision, and, indeed, are frequently seen in unoperated cases, giving a striking illustration of the fact that tumor cells, especially those of moderate size, have the capacity to invade the cutaneous lymphatics for long distances and to spread against the direction of flow of the lymph. When the vessel is large, as in the abdominal trunks, permeation would not be expected to occur, and it is probable that extensive backward spread of tumor cells is due to a combination of several processes. Vogel has described two such cases, one a carcinoma of the gall-bladder, which extended into the left kidney hilus [RST: This is an old name; it means the same thing as "hilum"] and there perfectly outlined the perivascular lymphatics of that region; the other a pancreatic carcinoma which extended directly along the mesenteric and aortic trunks into these nodes.
What are two explanations that Knox provides for why surgery is not the only thing that accounts for metastasis?
Vogel described two cases where the spread was far away, and it travelled retrograde to the direction of lymphatic flow.
In what direction did the gall bladder tumor have to travel to reach the hilum of the kidney?
How far did it have to travel?
What did it have to pass through to get there?
Where have we seen a hilum of an organ before in this discussion? What do they have in common with each other?
It is well known also that oesophageal carcinomata are prone to spread longitudinally along the lymphatics of the submucosa and that small secondary nodules often appear considerably below and separated from the oldest portion of the tumor by uninvolved mucosa. It used to be the fashion to describe these as implantation growths, but this view is now generally abandoned. Zahn has even described one situated as high as the tracheal bifurcation, but associated with three small carcinomatous nodules beneath the mucosa on the gastric side of the cardia. This occurred also in an oesophageal carcinoma with tracheal fistula (St. Luke's Hospital, No. 1309), the secondary nodule being 4 cm. from the main mass of the neoplasm. The mechanism of the formation of these multiple nodules, as well as of multiple papillary gastric carcinomata, has not been shown to be necessarily a process of permeation, although theoretically this would readily explain their occurrence.
"Oesophageal" is an older, Latin/Greek-based, spelling for "esophageal".
Why does the esophagus have carcinomata?
If you're a tumor cell, how far away is 4 cm in proportion to your size?
At the time Knox wrote this, did they know the mechanism by which these secondary metatastic tumors got away from the primary tumors?
On the other hand, emboli are, no doubt, prevented from growing by the mechanical activity of muscles and muscular organs. Metastases are singularly rare in the cardiac muscle, being practically never seen except in the case of extremely vascular tumors with scanty stroma from which the loosened cells spread and overwhelm the whole arterial circulation with countless emboli. The aortic valves must also act to deflect emboli from the mouths of the coronary arteries. Benecke, studying the invasion of the walls of vessels from carcinomatous thrombi, believed that the infrequency of metastasis in the muscular coat was due to the physiological tonus of the muscle. This is a reasonable conclusion, and the principle holds good for striated muscle as well. Metastases into the latter are extremely rare, due in part to the contractility of the fibres, a condition which offers considerable resistance. The fact that lymphatics are lacking within striated muscle bundles is certainly not the reason for the rarity of metastases, for if the emboli were lymphatic, not vascular, and if the motion did not play so large a part in preventing their growth, they should be present in tendons where lymphatics are very numerous. Direct permeation of both striated and unstriated muscle is, however, frequently seen, showing that the soil is not unsuitable provided the cells once gain access to the tissue.
What protects muscles, and muscular organs like the heart, against metastasis?
Does this protection always work perfectly?
How do we know that it's not just the lack of lymphatic vessels in skeletal muscle that protects them?
Normal peritoneum has been shown by Jones and Rous to possess a high resistance to the implantation of tumor cells, but when it was injured by a mechanical irritant, tumor growth was at once made possible. This offers an explanation for the frequently observed fact that carcinoma of the stomach often metastasizes into the ovary, producing the so-called Krukenberg tumor of the latter organ, without any intermediary deposits on the peritoneal surface. That such deposits will eventually occur in late stages of carcinomatosis is, of course, well known, but it is probable that the constant motion of the opposed serous surfaces is an important factor in destroying whatever cells may find their way to it. It has long been recognized that it is the gelatinous carcinomata of the ovary, stomach, and intestine that are most widely distributed in the abdominal cavity. This is, of course, as would be expected, for the bulk and consistency of the mucus make it in a sense a foreign body and must keep the cells in contact with the peritoneum and also irritate it, and so indirectly facilitate adhesion and ultimate vascularization, whereas a few free cells would be more likely to be destroyed.
Is peritoneal tissue normally relatively vulnerable or relatively resistant to metastasis?
What is a proposed mechanism that could account for that tendency?
What can change that tendency?
Post-operative human results have occasionally shown the remarkable persistence which cells from malignant tumors may exhibit. During the quiescent period the cells are probably most frequently inactive in the lymph-nodes, occasionally for as long as ten to twenty years. Late recurrences usually appear first in the nodes to which drainage was directed, and if the morphology of the tumor is that of the primary growth there can be no question that these are really late recurrences from previous metastatically deposited cells. For example, small groups of living cells from a gastric carcinoma have been observed by Rohdenburg in the liver and omentum ten years after the operation on the primary tumor, with a clinical cure. Such a case may be the result, like many of the very late cutaneous recurrences from breast tumors, of slow permeation along the efferents of a node or even from a small group of cells for years quiescent in the tissue spaces.
How long after a tumor is removed can a recurrence or metastasis happen?
How can it do that, since the tumor was removed?
How can they tell it was a recurrence of the old cancer, rather than the development of a brand-new different cancer?
A spindle-cell sarcoma has occasionally recurred after a very long period. A tumor of this type, originating in the cervical fascia, has been seen by the writer recurring as a mass the size of a walnut twelve years after the first operation, the patient being free from symptoms during the greater part of the period. Such a phenomenon is difficult to explain, since only rarely does this type of sarcoma metastasize into the lymphnodes, and there form a focus for new growth. As this recurrence was in the centre of a large skin graft made at the first operation, it seems more probable that it was a recurrence in situ of very slowly growing cells situated in the deep fascia below the graft.
What happened in this case?
Was it what you would usually expect?
How does Knox explain it?
Other rare and late metastases which give no hint as to the mechanism of their localization and long course are cited by Schmidt and Goldmann, who observed a cerebral metastasis four years after a rectal carcinoma with no local or lymphatic return. Schmidt believes that such tumors are derived from latent intravascular cell groups in the pulmonary vessels. Another still more remarkable observation is that of Crouzon, who described a cerebral metastasis eighteen to twenty years after operation on a bilateral breast carcinoma. Gathmann and Schmidt have each observed cases in which four years after operation on similar tumors, with apparent cure, widespread skeletal metastases appeared. In such a case a general emboli distribution of cells by the blood into the capillaries of the myeloid canals must have occurred fairly early, and the growth processes have been very slow.
What happened in these cases?
Why are they so surprising?
How does Knox explain these events?
The frequency of skeletal metastases is so much greater than can possibly be demonstrated by clinical or röntgenological means until a very advanced stage that the high percentage of such growths is not often appreciated. Although the vascularity of the marrow is great, the stroma reaction may be here as marked as elsewhere and the metastasis of a scirrhous breast carcinoma be only a sclerotic nodule of the same appearance as the primary growth. When the bones are noticeably eroded or spontaneous fractures occur the process is far advanced and statistics drawn from such cases only give misleading data as to the frequency of the process.
"Röntgenological" is an old-fashioned word for "x-ray", because in 1895 the German physicist Wilhem Röntgen was the first person to discover x-rays in nature.
Is the skeleton particularly resistant to metastasis?
What does that translate to in clinical observations?
This view of the localization of metastases has not, however, been universally accepted, and many convenient hypotheses have had to give way to the increasing weight of pathological and experimental evidence. The theory of the specific adaptation of some tissues, as the liver, for neoplastic cells, and the relative immunity of others, as the brain, has been prevalent in the literature for many years. Virchow stated that organs in which carcinoma is never primary do not serve as a site for metastases. Recent observation has shown these conclusions to be wholly incorrect, as the brain is the site of secondary metastatic carcinomatous deposits in at least 0.3 per cent. of all autopsies (Krasting). Adherents to this theory point out, however, that some types of tumors have distinctly greater capacity to metastasize into certain organs than others, since not all tumor cells readily grow within the bones, but others very commonly do so, as those of the breast, thyroid, adrenal and ovary. Von Recklinghausen even advanced the idea that breast and prostatic carcinomata were apt to form metastases in similar regions because they were in a sense analogous organs, each being a part of the genital system. Bamberger and Paltauf believed that there was some specific organ susceptibility, and offer as evidence the fact that not only the small-cell carcinomata of the prostate metastasized to the bones, but the large-cell medullary carcinomata of the gland behaved in the same way.
Remember earlier, when she mentioned "occult and convenient theories of tissue predispositions and specific "immunity" of organs"?
What are some of those theories?
Rudolph Carl Virchow is called the "father of modern pathology", because of all the discoveries and knowledge contributions he made. Was he correct about metastasis sites? Why or why not?
When it comes to the concepts and terms of a big name, versus material physical referents, which do we believe, and why?
What is the other choice of belief called? Is it a logical fallacy?
The spleen also has been called "immune" to metastases by various writers because gross tumors in it are not especially frequent and microscopic ones often escape detection; but late stages of breast carcinoma are not infrequently accompanied by palpable enlargement of that organ due to a diffuse carcinomatosis, while E. E. Goldmann demonstrated that animal tumors inoculated into the spleen grow as readily there as elsewhere. While the vascularity of the organ exposes it to numerous emboli, yet as it possesses no efferent lymphatics and is in practically constant motion, embolic cells can not proliferate within it with as much facility as in some other organs. The great vascularity of the adrenals, as well as their protected position and absence of intrinsic motion, provides a suitable location for the secondary growths so often found in them. It is possible that the wide vascular sinuses of the pituitary, which resemble those in the adrenal, facilitate the location of metastatic tumors in this organ as well.
Again, this is an example of the "occult and convenient theories of tissue predispositions and specific "immunity" of organs" she referred to earlier.
Is the spleen immune to metastases? What does the evidence say?
How about the immunity or vulnerability of the adrenal glands and the pituitary? What might explain their situations?
External mechanical influences have for some years been recognized as an important factor in dealing with any malignant tumor. Gerster, in 1885, discussed the apparent breakdown of the forces which keep a malignant tumor for a time localized, and believed them to be largely mechanical. He pointed out the need, for example, of high amputation, not alone for the purpose of obtaining an uninfected field, but in order that the neoplasm itself should be free from manipulations, and so facilitate cellular dissemination. This writer further compared the results of malignant tumor massage to that which is sometimes effected by massaging a sprained joint--a process which certainly disseminates inflammatory exudate rapidly and widely. The effect of pressure, rubbing, or active massage on the tumor has been frequently observed in human beings as the result of osteopathic or massage treatment of malignant tumors, and many examples have been seen in recent years of wide dissemination of a primary growth very effectively accomplished by this procedure.
What were the two reasons Gerster advocated amputation in the case of cancer?
What is the analogy he drew with massage?
Does the evidence back up that analogy?
Such an instance has recently occurred at St. Luke's Hospital, and furnishes one of the rare instances in which extensive gross metastatic invasion of muscle could be observed. The patient stated that massage treatment had been regularly employed for some time previous to admission. When the breast tumor was examined there was found a fairly extensive area of eczema overlying a large very hard tumor which was fixed to the pectoralis fascia. Small white tumor nodules were scattered widely throughout the muscles, even invading the individual fibres. (See Fig. 1.)
What was unusual about this patient's case?
Does the evidence back up Knox's claim that massage accomplished this metastasis?
While, therefore, much interesting and important information has thus been obtained by clinical, operative, and post-mortem studies, the number of cases is too small to enable final conclusions to be drawn.
Is this consistent with everything that Knox said earlier?
The determination of the weight of a factor in producing metastases can not be judged from single experiences on man, as it is impossible to eliminate conflicting conditions. Only by the use of a homogeneous material in which the size of the cells, their histological and biological qualities, and the vascularity of the surrounding tissue, etc., are practically constant can valid conclusions be drawn, and this elimination of variables is possible to obtain only by the use of animal tumors of a long transplanted strain, so that the morphological and biological characters are well known. The possibility of obtaining by inoculation in a single day more tumors than any one surgeon observes in a lifetime of active practice also eliminates the occurrence of errors due to random sampling affecting the result--a condition never possible in human material. For example, following the discussion produced by the publication from the Crocker Fund of a paper on the results of the incision of tumors, many surgeons brought forward individual instances which they thought were of value in proving the danger of diagnostic incision, not realizing that from a statistical aspect a single instance is of no value. Even from a basis of reasoning, so remote from the complexities of mathematics as what is ordinarily termed common sense, many of those who cited these single instances were unable to deny on cross examination that pre-operative manipulation by the patient, or that dragging or pressure on the tumor during the operation might have equally well caused the evident dispersal of tumor particles, as evinced by the subsequent course of events.
What is she saying here about individual observations? About confounds?
It was not until Tyzzer, in 1913, demonstrated that gentle massage of a transplanted carcinoma in a mouse greatly increased the number of metastases observed in the lung that definite evidence was brought forward to substantiate these occasional clinical observations. The number of Tyzzer's experiments was small, and he obtained results with only one tumor, a highly malignant neoplasm of the Japanese waltzing mouse. With the Ehrlich mouse tumor No. 11 and the Jensen rat sarcoma he was unable to obtain metastases artificially by massage of the implanted tumors. Rous states that his experiments in massaging rats with adenocarcinoma resulted in the death of all the animals, but did not cause more than the ordinary number of metastases.
What did Tyzzer's and Rous' studies demonstrate? Were they definitive?
Several recent clinical experiences of the writer in which after the removal of a very small primary tumor of the breast by perfect surgical technic (no involvement of the axillary nodes being present), the patient died of generalized carcinoma in a short period thereafter, pointed to the desirability of further extension of Tyzzer's experimental results. We will say, in passing, that in one of these human tumors which had been somewhat vigorously palpated by a number of physicians, a small hemorrhagic area was found in the middle of the growth, and in the vessels surrounding the tumor numerous emboli of cancer cells were present.
What is the clinical relevance of Tyzzer's and Rous' studies?
What did the physical evidence show in one case?
What does this table tell us?
A considerable variety of transplantable carcinomata or sarcomata of the mouse and rat were used for the experiment. Some of these tumors under normal conditions, especially the spindle-cell sarcomata, do not produce spontaneous metastases in the animals in any number. Others, especially the carcinomata, are apt to metastasize early.
What were they comparing in this experiment? What is the internal validity likely to be?
The following tumor strains were employed: Crocker Fund mouse carcinomata, Nos. 5, 11, and 48, the Borrel mouse carcinoma, the Ehrlich mouse carcinoma and the Flexner rat carcinoma; Crocker Fund mouse sarcomata Nos. 7 and 180, and the Ehrlich mouse sarcoma.
The method employed was as follows, with the exception of the two series described separately below: The animals were inoculated subcutaneously in the inguinal or axillary region with a tumor particle weighing about 0.003 gm. When the tumor reached a diameter of approximately 5 mm. it was gently massaged for half a minute every other day for about two weeks. The tumor was then removed by operation to prevent further metastasis, in order to obviate the difficulty of having to decide whether embolic masses in the vessels of the lung were really growing tumor particles, or only recently deposited emboli which might ultimately die without giving rise to a tumor nodule. In the final results only those masses are considered as true metastases in which the vessel wall was invaded, a separate column giving the number of instances in which emboli were found in the lumen of the pulmonary vessels.
What were they studying in this experiment? What did the method provide?
In one series, mouse carcinoma No. 11, the experiment was repeated, and the technic was varied as follows: The tumor was massaged vigorously for one minute on each of two consecutive days. After the second massage treatment all tumors, both controls and those which had been manipulated, were excised and the animals all killed twenty-seven days later. (No. 11, Series II.)
In order to check the results a third series of mice were inoculated two years after the first lot with the Crocker Fund mouse sarcoma No. 180. The mice were all of the same breed, and the conditions were kept as nearly as possible the same as in the preceding experiments. This time the mice were inoculated in the right axillary region, and as soon as the tumors were easily palpable the massage was begun on one-half of the mice, the others being reserved for controls. As before, the massage was carried out for thirty seconds on alternate days for about two weeks. The tumors were then very large, and many of the mice died at this time. In those surviving the tumors involved the thoracic wall too extensively to make removal feasible, so the aninmals were, therefore, allowed to die and then were autopsied. The results of this experiment are recorded as No. 180, Series II.
What does the variation in the method mean for the validity of the study?
In all the series the lungs were carefully removed, distended through the trachea with 4 per cent. formaldehyde, and hardened, and six sections from each animal were examined. Much difficulty was experienced in determining microscopically whether a mass of cells in a vessel should be considered as a true metastasis or merely an embolus. When emboli cease to be capable of forming a tumor we do not know. Careful morphological studies have been made by Takihashi and others to determine the early degenerative and proliferative changes which occur in emboli of tumor cells, but the two processes are frequently coincident, and, as many groups showed no evidence of either process even after being in the vessels many days, we cannot be too cautious in deciding whether a death point has been reached. Such emboli were found, for example, in specimens 9515, 6363, 6359, thirty-two, twenty-seven, and twenty-six days after removal of the primary tumor and no local recurrence at the site of inoculation had taken place from which such emboli could have been derived. Presumably such cells are dead; hence these groups have been called emboli, not metastases. In one sense, however, they are just as important as a growing lung tumor in showing that emboli of cancer cells can be set free in the blood stream by massaging a tumor, and any embolus in its early stage carries the potentiality of metastasis formation.
What is the meaning of the different kinds of things they found in the animal's lungs?
What do they tell us about massaging a tumor?
How meaningful is that for the kind of massage that we would do for someone living with cancer?
Only six sections of the lungs were studied, for it was found after a few complete sets of serial sections had been examined that the gain in number of emboli or small tumors discovered was unimportant.
This means that the distribution of emboli and small tumors was relatively uniform throughout the lungs they studied, and they were able to work with a smaller data set than they had originally thought they would need.
The tabulated records of the experiments are self-explanatory and need no further elucidation.
No, I disagree. Remember, a lot of the statistical tests that we presently use to interpret studies were being developed at about the same time as Knox wrote this article.
While I don't fault her for not using something that she didn't have access to in her time, it remains true that without those tools to interpret her results with, we necessarily have to consider them weaker than we would similar results that had stood up to robust statistical testing.
The point of these tests is to make sure that we are, in reality, seeing what we think we see. Without the assurance provided by those tests, such as tests of statistical significance, confidence level, and the like, we just cannot consider these results as explanatory and self-evident as she considers them.
Examination of the chart (Fig. 2) shows that, in general, with nine tumor strains, there was a more or less distinct increase after massage in the number of embolic particles in the lungs, the increase varying from 1 to 37 per cent.
FIG. 2.-Chart showing percentage of emboli (hatched areas) and of metastases (solid areas), and their relative numbers in controls and massaged animals. In each case the column at the right represents the massaged animals, that at the left, the controls.
Tell me, what does this bar mean?
What does this one mean?
What does this one mean?
What does this one mean?
What does this one mean?
Can you find any cases where the control animals had more emboli or metastases than the study animals did? How does Knox explain these unexpected results?
The actual percentages can be considered of little importance, and it is even surprising to find that the tendency is so general. With the carcinomata the results are in many cases unequivocal; for example, the Ehrlich carcinoma, at the time showing no regression and 75 per cent. of takes, in other words, in its positive phase, formed more than twice as many metastases after massage as without it. A similar condition obtained with the Borrel carcinoma, at that time spontaneously regressing in 50 per cent. of inoculations, but still showing numerous metastases after massage. The ratio is probably artificially high as the number of control animals which survived was very small.
"The actual percentages can be considered of little importance"? Well, no; they are vitally important to the question we are trying to answer.
You can see here a cultural shift in how science used to be interpreted from how it now is.
The emboli are found in both lymph-and blood-vessels, frequently in both locations in the same lung. The perivascular space can frequently be seen filled with cells from which the parenchyma is invaded, but the primary process is evidently in the vessels, as it is seen in all stages within them. The lymphatic system of the mouse being developed to a much less extent than in man, it may also be expected to show relatively less tumor involvement. One reason for this may very probably be, as is pointed out by Murray, that the lymphatics are so delicate and quickly obscured by an inflammatory reaction that metastatic particles apparently freely growing in the tissues may have originated from an embolus either in a lymph-vessel or the nodal capsule. In these studies, however, there is seldom room for doubt that the emboli are vascular in the great majority of cases. Multiple emboli nearly filling both large and small vessels of a lobe are occasionally found, in the controls as well as in the massaged animals, but cell groups are much more frequent in the treated ones.
The illustration (Fig. 3) is from a massaged animal which died twenty-four days after inoculation. Both proliferation and degeneration are seen, and most of the stages described by Takahashi may be found in some area.
FIG. 3.-Multiple emboli of tumor cells in pulmonary vessels of a massaged mouse tumor.
Which things in this slide are the vessels? Which are the emboli?
How can you tell the difference?
Fig. 4 (No. 18363) and Fig. 5. (No. 18319) each show a small embolus which is certainly undergoing dissolution, as the surrounding lung is well preserved, but the tumor cells stain poorly. The outlines of cell walls and the nuclear membrane are indistinct, and the cytoplasm granular.
FIG. 4.-Degenerative changes in cells of a tumor embolus in pulmonary vessels.
Can you see the embolus clearly?
What is different about the pulmonary vessel the tumor embolus is in, compared to the other blood vessels in this slide?
FIG. 5.-Embolus of tumor cells in pulmonary vessel. Embolic cells are undergoing early degenerative changes. The lung tissue is well preserved.
What is the meaning of her explanation here?
On the other hand, occasionally even small emboli may be seen in which the actively invasive tendency of the tumor cells is plainly demonstrated.
Fig. 6 (No. 18322) shows a small embolus which has apparently lifted up the endothelium from the vessel wall and so given itself a fibrous surface upon which to obtain a footing.
FIG. 6.--Endothelium of vessel containing embolic tumor cells stripped from wall. Early stage of attempt to localize.
Tell me, what do you see here?
What do you see here?
What looks to you like an "attempt to localize"?
Another phase of apparently successful implantation is shown in Fig. 7 (No. 18343), where a number of well preserved tumor cells are growing in direct continuity with the endothelium.
FIG. 7.--Later stage in implantation of embolic tumor cells. A few have replaced the endothelium.
What do you see here? Where do you think the emboli have replaced the endothelium?
Figs. 8 and 9 show two small pulmonary emboli from a case of carcinoma of the stomach in a human being. In Fig. 8 there is no adhesion of the embolus to the endothelium, although nearly a third of the mass is made up of mucus produced by the epithelial cells;
FIG. 8.--Small embolus from case of carcinoma of stomach in man, showing invasion of pulmonary vessels. Nuclei surround a central mass of mucus.
Where do you see the vessel here? The nuclei? The mucus?
in Fig. 9 one cell only appears to have invaded the endothelium.
FIG. 9.--Beginning adhesion of tumor cells to endothelium in pulmonary capillary from case of carcinoma of stomach in man.
What structures and processes do you see here?
Another lung furnishes a picture of a more advanced stage of invasion, Fig. 10 (No. 18384). The endothelium can no longer be distinguished, as practically the whole circumference of the muscularis is lined with the tumor cells, and the lumen is almost filled with a carcinomatous embolus in which early degenerative or thrombotic changes have occurred [sic]. Similiar parietal thrombi were examined by Schiedat throughout their length and were found to extend for some distance along the surface of the wall and eventually to break through it.
FIG. 10.-Embolic tumor cells replacing endothelium of pulmonary vessel.
What do you see happening here?
The same process is illustrated in Fig. 11(a) where a large vascular sinus is shown containing many embolic cells from a bone sarcoma in man. The nuclei already show pycnosis, swelling, agglutination by fibrin, and are being surrounded by polymorphonuclear and lymphocytic cells. In (b) is another large blood-vessel from the same tumor with a giant cell among the red blood-cells. This, although of the "endothelial" type and not itself likely to invade other tissues, is of interest in showing that all types of cells may gain access to the blood stream.
FIG. 11.--(a) Embolus from bone sarcoma in man. Cells are of several types and illustrate early degenerative changes and phagocytosis. (b) Giant cell in blood-vessel in bone sarcoma.
That most of the small vascular emboli are derived from larger ones in the main vessel, and not from primary lymphatic involvement, is seen from such an extensive embolus as appears in Fig. 12 (No. 18343), a fairly frequent picture. A very large mass is found in one of the main pulmonary veins and many of its cells are degenerating, the nuclei are pycnotic, and some of the cells have been phagocyted.
FIG. 12--Larger tumor embolus in pulmonary artery.
Figure 13 shows a smaller group of cells surrounded by a thrombotic mass containing many polymorphonuclears, as would be expected in such a situation.
FIG. 13.-Polymorphonuclear cells surrounding a few embolic tumor cells; probably an early stage of thrombus formation.
It may only occasionally be seen that the cells break into the lymphatics and there grow freely, but it is shown in Fig. 14(No. 18307).
FIG. 14--Large embolus of tumor cells in perivascular lymph space; probably an extension from a vascular thrombus.
Not infrequently, as in tissues from human beings with tumors, multiple emboli are found in the vessels which may be densely crowded with cells, most of them small, and though hyperchromatic only with difficulty to be distinguished from lymphocytes--in fact, to make a differential diagnosis is very hazardous in spite of the absence of inflammation elsewhere in the section (Fig. 15).
FIG. 15.--Multiple emboli of small cells in pulmonary vessels, possibly tumor cells, but resembling lymphocytes.
Inspection of Table III shows that among the controls metastases and emboli were coincident only four times in twenty-one animals, or in 19 per cent., while among the massaged this occurred nine times in twenty-five animals, or in 36 per cent. of the cases. The average duration of life was the same in each case. There seems little doubt but that the massage has effected a wider distribution of the tumor even though it is impossible to decide in all the cases just what the ultimate fate of the scattered cells may be, whether they will die or succeed in establishing themselves in the vessel wall.
Crocker Fund No. 180
Total number metastases in controls = 23
Total number emboli in controls = 24
Total number metastases in massaged = 41
Total number emboli in massaged = 38
On the whole, the polyhedral-cell sarcomata (Crocker Fund No. 180 and Ehrlich mouse sarcoma) seemed just as apt to produce metastases as the carcinomata. In the spindle-cell tumors, metastases are apt to be scanty. This may be explained upon mechanical grounds, from the fact that the cells of most fibro-or spindle-cell sarcomata are more definitely intermingled with and attached to the surrounding connective tissue than in the case of the free-lying cells of the carcinomata. This sustains the view that anatomical relationships of the cells are important in determining metastases.
It would be incorrect, however, to assume that the mechanical factor is of so great importance in determining the ultimate production of a growing tumor as distinct from an embolus as the biological characteristics of the tumor itself. Examination of the chart shows that the correlation between the percentages of total metastases in controls and massaged animals is negative, that is, that those tumors which metastasize spontaneously in a high percentage do not show as great an increase after massage as do those in which spontaneous metastasis is low. For example, the Crocker Fund carcinoma No. 5 shows a smaller increase in its percentage of metastases than does the Flexner rat carcinoma. The same is true of the Ehrlich sarcoma, a strain in which Haaland also found a high percentage of spontaneous metastases; in fact, this writer reports approximately the same percentage of metastases in the twenty-three mice which he observed (60 per cent.) as were seen in the twenty-six animals used in this experiment (58 per cent.).
What is she claiming in her discussion here?
In these freely metastasizing highly vascular tumors the organism is evidently flooded with emboli before manipulation, and hence many tumor cells may be found in the pulmonary capillaries at all times. Less difference, therefore, can be detected following the massage.
What is the effect of massage in these cases, and why?
There can be no question under these circumstances that concomitant immunity has any influence on the prevention of appearance or growth of the metastases.
Is it clear what she means here?
1. Study of human material in many ways suggests, but does not finally prove, the importance of massage as a means of inducing metastasis of tumor cells. In animals, on the contrary, very gentle massage for a total period of from two to five minutes, distributed over a number of days, has been shown to set free numerous particles of tumor which form emboli in the lungs.
Is this the correct approach to take in studying the question?
Does the study show what she states that it shows?
2. Such emboli produce metastatic tumors in a variable proportion of instances, depending upon the growth activities of the tumor. Tumors which take in low percentages when implanted in the subcutaneous connective tissues give much fewer metastases than those of high virulence.
Is this consistent with what you would expect to see?
3. Carcinomata and also sarcomata of the loose polyhedral-cell type are easily generalized, but sarcomata of the compact spindle-cell variety are not influenced.
How do we know this from the information in her article?
4. The importance of avoiding diagnostic or operative manipulation of a tumor in man is obvious.
I agree it's a good idea in general. Does the evidence show that it's as obvious as Knox says it is?
No, it cannot. Massage of a solid tumor site should be avoided, but there is more to a person than a tumor site.
An old myth warned that massage could, by raising general circulation, promote metastasis since tumor cells travel through blood and lymph channels. We now recognize that movement and exercise raise circulation much more than a brief massage can, and that routine increases in circulation occur many times daily in response to metabolic demands of our tissues. In fact, physical activity usually is encouraged in people with cancer; there is no reason to discourage massage or some form of skilled touch. Massage is practiced widely at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering, and growing numbers of hospitals around the country. Metastasis is not a concern; instead, patients and researchers report countless benefits.
Bamberger and Paltauf: Wein klin. Wchnschr., 1899, vol. xii, p. 1100.
Benecke: Beitr. z. path. Anat. u. z. allg Path., 1890, vol. vii, p. 95.
Carmalt: Virchow's Arch. f. path. Anat., 1872, vol. lv, p. 481.
Crouzon: Bull. et mém. Soc. méd. d. hôp. de Par., 1920, vol. xlvi, p. 500.
Ernst: Beitr. z. Path. Anat., 1905, Supp., vol. vii, p. 29.
Ewing: Neoplastic Diseases, Philadelphia, 1920.
Gathmann: Ein Fall von allgeimeinen Karzinome des Knochensystems, Leipzig, 1902.
Gerster: New York M. J., 1885, vol. xli, p. 233.
Goldmann: Bruns Beitr. z. klin. Chir, 1897, vol. xviii, p 595.
Goldmann: Bruns Beitr. z. klin. Chir., 1911, vol. cxxii, p. 1.
Haaland: Berl. klin. Wchnschr., 1906, vol. xxxiv, p. 1126.
Handley: Arch. Radiol. and Electroth., 1919, vol. xxiv, p. 137.
Handley: Cancer of the Breast and Its Operative Treatment. London, 1906.
Handley: Lancet, 1907, vol. i, p. 927.
Iwasaki: J. Path. and Bacteriol., 1915-16, vol. xx, p. 85.
Jones and Rous: J. Exper. M., 1914, vol xx, p. 404.
Krasting: Ztschr. f. Krebsforsch., 1906, vol. iv, p. 315.
Lambert and Haynes: J. A. M. A., 1911, vol. vi, p. 791.
Murray: Seventh Scientific Report, Imperial Cancer Research Fund, London, 1921, p. 63.
Poirier et Charpy: Traite D'Anatomie Humaine, Paris, 1909, Tome II.
Rohdenburg: Proc. New York Path. Soc., 1920, n. s., vol. xx, p. 141.
Rous: J. A. M. A., 1913, vol. lx, p. 2021.
Sabin: The Harvey Lectures, 1915-16, Series xi, p. 124.
Schiedat: Ueber den Untergang maligner Geschwulstmetastasen in der Lung, Leber, und Lymphdrusen, Inaug.-Diss., Königsberg, 1908.
Schmidt: Die Verbreitungswege der Karzinome und die Beziehung generalisirter Sarkome zu den leukämischen Neubildungen, Jena, 1903.
Takahashi: J. Path. and Bacteriol., 1915-16, vol. xx, p. 1.
Tyzzer: J. M. Res., 1913, vol. xxiii, p. 309.
Van Raamsdonk: Nederlandsch Tijdschrift v. Geneeskunde, 1921, vol. i, p. 3355.
Virchow: Die Krankhaften Geschwulste, Band 2. Berlin, 1864-5.
Vogel: Virchow's Arch. f. path. Anat., 1891, vol. cxxv, p. 495.
Von Recklinghausen: Virchow's Arch. f. path. Anat., 1885, vol. c, p. 503.
Wood: J. A. M. A., 1919, vol. lxxiii, p. 764.
Zahn: Virchow's Arch. f. path. Anat., 1899, vol. cxvii, p. 30.
What have we learned from this discussion?
At the beginning of this post, I asked you the following questions:
Where did the idea that massage promotes metastasis, and therefore, we shouldn't offer massage to patients living with cancer, come from?
What is the current best practices recommendation for massaging someone with a history of cancer, and on what basis is that best practices recommendation formed?
Why is the idea that we shouldn't massage someone with a history of cancer, because it might promote metastasis, so persistent in the face of what we actually know?
Have your answers to them changed over the course of this discussion? If they have changed, then in what way have they done so?
What else did you learn during this discussion? Can you explain it to someone else now?
How relevant is this discussion to what we practice as MTs?
In medicine, a fistula (/ˈfɪstjʊlə/; pl. fistulas (/ˈfɪstjʊləz/), or fistulae (/ˈfɪstjʊli/ or /ˈfɪstjʊlaɪ/)) is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect.
A highly malignant epithelial tumour with a fulminant [quick, intense, and severe] clinical course, bizarre histologic appearance and poor prognosis [predicted outcome]; it is most common in the lung and thyroid, but is well-described in the endometrium, breast and elsewhere.
From Ancient Greek ὑπέρ (huper, “over”) + αἷμα (haima, “blood”).
excess of blood in a body part.
Wiktionary "lymphocyte", accessed 29 December 2012
A lymphocyte is a type of white blood cell in the vertebrate immune system.
Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells (NK cells). Small lymphocytes consist of T cells and B cells.
A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature...
There has been debate over the exact mechanism of metastasis of the tumor cells from the stomach, appendix or colon to the ovaries. Classically it was thought that direct seeding across the abdominal cavity accounted for the spread of this tumor, but spread by way of the lymphatic is considered more likely.
Latin, from Ancient Greek μέλας (melas, “black, dark”) and -oma (“disease, morbidity”).
melanoma (plural melanomas or melanomata)
(oncology, pathology) A dark-pigmented, usually malignant tumor arising from a melanocyte and occurring most commonly in the skin.
Wiktionary "metastasis", accessed 27 December 2012
From Late Latin, from Ancient Greek μετάστασις (metastasis, “removal, change”), from μεθίστημι (methistemi, “to remove, to change”)
metastasis (plural metastases)
(medicine) The transference of a bodily function or disease to another part of the body, specifically the development of a secondary area of disease remote from the original site, as with some cancers.
Latin permeātus, participle of permeāre, meaning to pass through.
permeate (third-person singular simple present permeates, present participle permeating, simple past and past participle permeated)
To pass through the pores or interstices of; to penetrate and pass through without causing rupture or displacement; -- applied especially to fluids which pass through substances of loose texture; as, water permeates sand.
Phagocytosis (from Ancient Greek φαγεῖν (phagein) , meaning "to devour", κύτος, (kytos) , meaning "cell", and -osis, meaning "process") is the cellular process of engulfing solid particles by the cell membrane to form an internal phagosome by phagocytes and protists...Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed.
Pyknosis (from Greek pyknono meaning "to thicken up, to close or to condense"), or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis. It is followed by karyorrhexis, or fragmentation of the nucleus.
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes (PMN or PML) because of the varying shapes of the nucleus, which is usually lobed into three segments. In common parlance, the term polymorphonuclear leukocyte often refers specifically to neutrophil granulocytes, the most abundant of the granulocytes. Granulocytes or PMN are released from the bone marrow by the regulatory complement proteins.
serous (comparative more serous, superlative most serous)
(medicine) Containing, secreting, or resembling serum; watery; a fluid or discharge that is pale yellow and transparent, usually representing something of a benign nature. (This contrasts with the term sanguine, which means blood-tinged and usually harmful.)
Spindle cell sarcoma is a type of connective tissue cancer in which the cells are spindle-shaped when examined under a microscope. The tumors generally begin in layers of connective tissue such as that under the skin, between muscles, and surrounding organs, and will generally start as a small lump with inflammation that grows...Spindle cell sarcoma can develop for a variety of reasons, including genetic predisposition but it also may be caused by a combination of other factors including injury and inflammation in patients that are already thought to be predisposed to such tumors. Spindle cells are a naturally occurring part of the body's response to injury. In response to an injury, infection, or other immune response the connective tissues will begin dividing to heal the affected area, and if the tissue is predisposed to spindle cell cancer the high cellular turnover may result in a few becoming cancerous and forming a tumor.
What anatomical system (or systems, depending on how you count them) do we and other complex animals (like dogs, cats, bears, elephants, and tigers) use for movement?
Easy question straight out of Anatomy 101, right? But did you ever think about how organisms or organism parts that don't have muscles and bones are still able to solve the challenge of moving from one place to another?
Amoeboid movement is a crawling-like type of movement accomplished by protrusion of cytoplasm of the cell involving the formation of pseudopodia. The cytoplasm slides and forms a pseudopodium in front to move the cell forward. This type of movement has been linked to changes in action potential; the exact mechanism is still unknown. This type of movement is observed in amoeboids, slime molds and some protozoans, as well as some cells in humans such as leukocytes. Sarcomas, or cancers arising from connective tissue cells, are particularly adept at amoeboid movement, thus leading to their high rate of metastasis.
While several hypotheses have been proposed to explain the mechanism of amoeboid movement, the exact mechanism is still unknown.
What it comes down to, then, is that sarcomas and other cells use a method of movement very similar to the amoeba (or ameba: a one-celled animal-like microscopic organism) you see in this video:
As the definitions mentioned, in the video, you saw the cytoplasm slide to stick out (protrude) in the direction the amoeba moved.
Like the amoebas, individual cells in multi-cellular organisms (like us) can also move in a very similar way. Watch how nimbly responsive the human neutrophils (white blood cells) in this video are to the presence of a chemical attractant (this response is called chemotaxis):
As the Wikipedia definition mentioned, the ability of sarcomas to move in this way--although not yet fully explained--is thought to be a factor in their ability to metastasize aggressively.
The esophagus (oesophagus, commonly known as the gullet) is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach. The word esophagus is derived from the Latin œsophagus, which derives from the Greek word oisophagos, lit. "entrance for eating."...
The layers of the oesophagus are as follows:
nonkeratinized stratified squamous epithelium: is rapidly turned over, and serves a protective effect due to the high volume transit of food, saliva and mucus.
lamina propria: sparse.
muscularis mucosae: smooth muscle
submucosa: Contains the mucous secreting glands (esophageal glands), and connective structures termed papillae.
muscularis externa (or "muscularis propria"): composition varies in different parts of the esophagus, to correspond with the conscious control over swallowing in the upper portions and the autonomic control in the lower portions:
Occam's razor (also written as Ockham's razor, Latin lex parsimoniae) is the law of parsimony, economy, or succinctness. It is a principle stating that among competing hypotheses, the one that makes the fewest assumptions should be selected.
Parenchyma is the bulk of a substance. In animals, a parenchyma comprises the functional parts of an organ and in plants parenchyma is the ground tissue of nonwoody structures.
The term parenchyma is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour".
The parenchyma are the functional parts of an organ in the body. This is in contrast to the stroma, which refers to the structural tissue of organs, namely, the connective tissues.
In cancer, the parenchyma refers to the actual mutant cells of the single lineage, whereas the stroma is the surrounding connective tissue and associated cells that support it.
Early in development the mammalian embryo has three distinct layers: ectoderm (external layer), endoderm (internal layer) and in between those two layers the middle layer or mesoderm. The parenchyma of most organs is of ectodermal (brain, skin) or endodermal origin (lungs, gastrointestinal tract, liver, pancreas). The parenchyma of a few organs (spleen, kidneys, heart) is of mesodermal origin. The stroma of all organs is of mesodermal origin.
The peritoneum (pron.: /ˌpɛrɨtənˈiəm/) is the serous membrane that forms the lining of the abdominal cavity or the coelom—it covers most of the intra-abdominal (or coelomic) organs—in amniotes and some invertebrates (annelids, for instance). It is composed of a layer of mesothelium supported by a thin layer of connective tissue. The peritoneum both supports the abdominal organs and serves as a conduit for their blood and lymph vessels and nerves.
The abdominal cavity (the space bounded by the vertebrae, abdominal muscles, diaphragm and pelvic floor) should not be confused with the intraperitoneal space (located within the abdominal cavity, but wrapped in peritoneum). The structures within the intraperitoneal space are called "intraperitoneal" (e.g. the stomach), the structures in the abdominal cavity that are located behind the intraperitoneal space are called "retroperitoneal" (e.g. the kidneys), and those structures below the intraperitoneal space are called "subperitoneal" or "infraperitoneal" (e.g. the bladder).
When we look at it from the outside, the brain appears to be composed of two major regions: the larger cerebrum and the smaller cerebellum.
In this brain photograph--which, if it were still connected to its eyes, you would see that you are viewing it from the left side--the cerebrum is the larger region, superior to (above) the smaller cerebellum, which has been stained a light purple color.
The cerebrum controls the processing of sensory input, complex cognitive processes such as using language and decision-making (such as consciously deciding to move skeletal muscles), and memory, among many other things. We'll talk about it later in its own dedicated post.
The cerebellum, on the other hand, tends to operate with different aspects of movement than the cerebrum does, at an involuntary or unconscious level. Its most well-understood function is in controlling aspect of movement that we don't think about consciously, such as coordination, balance, and motor control.
Loca, the pug who couldn't run, shows what happens when the cerebellum is damaged or otherwise impaired--what you see in this video appears to be some kind of damage to the cerebellum that permits her to walk relatively normally, but severely disrupts her running.
You can use Loca as a mnemonic (a memory aid) to remember the functions of the cerebrum compared to those of the cerebellum--watch her movement, coordination, balance, and motor control as she tries to run, and you'll see what happens to those functions when the cerebellum doesn't work quite right.
Yet, as far as we can see from the video, there is no indication of any disorder of the cerebrum--she decides to run at appropriate times, when other dogs are running and playing.
The decision to run--made in Loca's cerebrum--seems perfectly normal, at least, as far as we can tell from a short movie.
It's the non-voluntary parts of the running, such as her balance and her coordination, where the difficulty lies. And those non-voluntary aspects of movement go back to her cerebellum.
Scope of practice note
I cannot diagnose, but as a anatomy/physiology teacher, Loca's movement disorder looks to me like cerebellar damage or impairment of some kind.
I checked with my cats' veterinarian, Dr. Davis, to make sure that I wasn't overlooking something that a clinician would see right away.
As an ethical practitioner, she would never definitively diagnose any animal only at a distance through a video alone, without an examination and a thorough history, but she agrees that--as far as we can see from the small sample contained in this video--the way that Loca runs is certainly consistent with some type of condition in which the cerebellum is damaged.
There is a word used for emphasis in the video which is a very strong and emphatic curse or swear word in American English.
In Irish English, on the other hand, the word "feckin" is used much more easily and casually by many people, and is not nearly so shocking as the American English equivalent is in context.
You should know that before you listen to the video, or show it to someone else, so that if strong language is something you want to avoid, you're not taken by surprise.
cheers, to Anne Davis, and to Loca and her family!
(This is a reworking of a post I originally wrote in 2007.)
So here's a wonderful example of modeling physiological processes across species: Schutte  details the reproductive cycle of the dog, Durrant adapts that information and applies it to the panda, and then Durrant's group and ours uses that panda information to study other species of bear--specifically, sun bears.
Anyway, this is a presentation slide that I adapted (animated, colored) from Schutte's 1967 original drawing [2,3,4] for a talk on using informatics to aid in the reproduction of endangered species at the 2004 American Veterinary Medical Association conference:
What you are seeing, as you read left to right, is the change over time in the shape and color of the vaginal epithelial cells, collected by swabbing the animal (like taking a Pap smear).
Shape changes (from more round to more irregular and from a high nucleus-to-cell size ratio to a much lower one, approaching or reaching zero in some cases), and color changes between pink/red (acidophilic) and blue (basophilic) can be seen as the cycle progresses. Although the hormone level peaks and the white and red blood cells (leukocytes and erythrocytes) are shown as well, we'll ignore those for the moment to concentrate on the changes in the colored cells in the middle of the diagram.
With a break in between, the cycle resumes at the left, and the whole process is repeated over and over again through the animal's reproductive life.
The important take-away points from this slide are the irregular borders and small nuclei of the aging cell, and the colors blue and pink (depicted above), and golden (which is also significant in pandas, but which Schutte did not address in dogs in his work).
So keeping those factors in mind, you can see why I was practically dumbstruck when I walked into a glass art studio in Fremont (a Seattle neighborhood) and noticed the piece by James Curtis titled "Little Bang":
I mean, it's all there! Large, irregular cell borders, tiny nuclei, and pink (cranberry), blue (teal), and golden color. Even the rack on which it is mounted looks like a graph over time of a cycle.
I swear, if I had commissioned the artist to render mature vaginal epithelial cells in glass, he could not have carried it out more faithfully.
A huge shout-out to James and his assistant Tara for patiently working with me while I arranged financing and donation of the work to our sun bear reproductive project for auction at a later date. If you're looking for glass art, I would recommend The Edge of Glass in Seattle unconditionally for their quality, their vision, and their customer service. On several subsequent occasions, they have donated pieces to support my research, and I am deeply grateful.
James told me he probably will not use the teal again, or if he does, it won't be very often--it is simply so hard to work with that it's not practical. So the bears and I did indeed get very lucky to get in there before someone else bought the piece, and we would never had known about it.
I also thank my husband, Iain, for deciding to surprise me with a drop-in visit there; it worked out so much more beautifully than I could ever have imagined.
The poem on the surface explores violation of nature and its resulting psychological effects on the Mariner, who interprets the fates of his crew to be a direct result of his having shot down an albatross.----Wikipedia, "The Rime of the Ancient Mariner: Interpretations", Samuel Taylor Coleridge, 1798 accessed 18 August 2012
Spoiler alert! (although there's a decent chance you already had to read this poem in elementary school, so in that case, you already know what happens to the Ancient Mariner and his crew).
The Ancient Mariner is a sailor who commits an unnecessary act of cruelty, even a crime in Coleridge's estimation--with his bow and arrow, he shoots the albatross (a water bird, like a seagull) who had led his lost ship out of dangerous waters.
With his cruel bow he laid full low
The harmless Albatross.
After the killing of the bird, more bad things continue to happen to the ship and crew. All the other crew members are eventually killed, but his punishment is to remain alive, tormented, and to wander the earth telling his story as a warning to others.
He partially redeems himself when--seeing the sea creatures that he had earlier despised, he recognizes how beautiful they really are. He wanders the earth eternally, trying to reach others with his lesson before it's too late for them to learn from it.
There is a metric boatload of things we could discuss about this poem, anywhere from conservation biology, history, psychology, and literature aspects, just to scratch the surface--but I want to talk about my trip to Padilla Bay estuary today, and what living in a littoral environment means for kidney function in animals--and Coleridge's observation about water is the perfect jumping-off point for that discussion.
An estuary is a body of water where fresh water from rivers and oceanic saltwater come together and mingle. So it's a complex transition zone, and organism functions that work one way in fresh water and another way in saltwater have to be covered in both cases there.
The littoral zone is the area of a body of water closest to the shoreline. So in an estuary, the littoral zone is where the fresh water and the saltwater mix--it's saltier than the fresh water is, but it's also less salty than the ocean water.
You probably know that, if you're ever lost on a boat on the ocean, you shouldn't drink seawater--not even a little bit, not even if you're very, very thirsty.
Globetrooper's diagram shows what it looks like when things are balanced inside the cell and outside of it: a situation called "isotonic": the "same pressure" by water on the cell membrane from both sides.
The large gray circles represent salt ions (to be more specific, sodium ions and chloride ions), and the small blue circles represent water. The proportion of salt dissolved in the water--the concentration--inside the cell is about the same as the proportion of salt dissolved in the water outside the cells. The inside and the outside of the cell are in equilibrium (isotonic), and there is no pressure from the water either to leave or to enter the cell.
Globetrooper's next illustration shows a situation that is no longer isotonic. Salt ions (the gray circles) are dissolved in the water (the blue circles) inside the cell, but outside the cell, there are no salt ions--the water outside the cell is pure water, with no salt in it. This situation is called a hypotonic solution.
Since the inside and the outside of the cell are no longer in balance, a process called osmosis occurs--the movement of fluid (in this case, water) across a semipermeable membrane (a membrane that substances can move through) from an area of lower concentration (in this case, of salt) to a area of higher concentration.
The effect is to bring the concentrations more into balance (isotonic).
The green arrow in this figure shows the movement of water (its osmotic pressure) from the area of low salt concentration outside of the cell to the area of higher salt concentration inside the cell. That movement of water into the cell dilutes the salt concentration, making it lower inside the cell.
This is what happens when we drink fresh water.
The opposite situation occurs when the water outside the cell is more salty (has a higher salt concentration: lots of gray circles, very few little blue circles) than the water inside the cell. This situation is called a hypertonic solution.
In a hypertonic solution, water flows out of the cells--the osmotic pressure of the water is toward the higher concentration of salt.
So you see what would happen? If you drank even a little salt water, it would draw water out of your cells. Instead of quenching your thirst, salt water would leave you more dehydrated than you were when you started.
At the cellular level, this is what it would look like:
In the hypertonic solution, the osmotic pressure comes from the water leaving the cells, leaving behind shriveled, badly dehydrated, cells (left side of image).
In the isotonic solution, the osmotic pressure balances out to zero, as equal amounts of water enter and leave the cells. The red blood cells in an isotonic state look normal and healthy with the indentation in the center that is typical of them.
In the hypotonic solution, the osmotic pressure pushes water into the cells, stuffing and waterlogging them--the normal indentation starts to disappear as the cell is too full of water.
These microphotographs of real red blood cells show how they really look, as they react to the different solutions we just described.
So now that we've discussed how cells behave in different kinds of solutions (hypertonic, isotonic, and hypotonic), does Coleridge's verse
And all the boards did shrink;
make even more sense now?
Why is that?
What is he describing, and why did the boards shrink as a result?
Osmoregulation (the control of osmotic pressure in body fluids, such as blood) is controlled in humans and other vertebrates by the kidneys--that's an important function they have in addition to production and excretion of urine.
Hormones produced by the pituitary gland and the adrenal glands, among others, signal to the kidneys what state the solutions in the blood are--hypertonic, isotonic, or hypotonic--and the kidney responds accordingly by reserving water or by releasing it to restore the balance.
As we are land animals, our kidneys have to respond to fluids we drink or take in in other ways (like an IV solution in the hospital, for example), but that's basically it. Fish, on the other hand, are surrounded by fluid, and their kidneys have to respond to that fluid and balance the water that their cells take in.
Too much water, and the cells swell up and get waterlogged--the hypotonic solution in the previous pictures.
Too little water, and the cells shrink and dehydrate and rupture--the hypertonic solution in the previous pictures.
The fish kidneys have to get the solution just right, and in a situation where the fish is surrounded by fluid of a different concentration.
So freshwater fish and ocean fish have adapted to this problem in pretty much opposite ways--that would seem to make a lot of sense.
But salmon live part of their lives in fresh water, and part of the time in salt water--so how can they have adapted to both, when the adaptations are the opposite of each other?
Salmon have adapted to both lifestyles--they can barely drink and urinate a lot when they live in fresh water, and then change to drinking a lot and barely urinating when they're out in the ocean.
Specialized cells in their body can work in opposite ways, depending on what they need at which stage they are in their lives.
But they can't turn it on a dime--they need days or weeks to make the transition between fresh water and ocean water.
And that's where the importance of the estuarine environment, like Padilla Bay, comes in--as an intermediate zone between the two other environments, it provides a place where salmon can make the transition.
In a region where the salmon can move around in the littoral zone to find the right amount of salt concentration they need, estuaries ensure the survival of those salmon leaving the fresh water where they were born, to go out and spend a large part of their lives in the ocean.
And they also ensure a place where--when it's time to go back up the freshwater river and breed--salmon have a place to adjust back from the ocean to the river environment, so that they can give birth to the next generation, and continue the cycle.
So often, in massage school, we don't have time to teach anatomy this deeply, and that's a real shame. If you just have time to memorize the fact that the kidneys control osmoregulation, so that you can recognize it when the MBLEX or the NCBTMB/NCBTM asks you about it, then that doesn't give you any particular preparation for clinical practice.
But if, at a deeper level, you understand what is going on, and you can draw a line from how the kidneys are involved in salt balance to what happens when that balance gets out of control one way or another, then you can understand what is going on with people living with renal failure or other kidney disease, and you are better equipped to know whether or not it's safe for you to provide massage under the circumstances.
The meaning that is important to us here and now is "abstract" as a property, or quality, or aspect of things after they have gone through a process of abstraction. "Concrete" is the opposite of "abstract" in this sense.
The process of abstraction means concentrating on what things have in common with each other, and classifying them on that basis.
Wikipedia has a good example, proceeding from more abstract to less abstract (and, in that way, proceeding from less concrete to more concrete):
Thus something as simple as a newspaper might be specified to six levels, as in Douglas Hofstadter's illustration of that ambiguity, with a progression from abstract to concrete in Gödel, Escher, Bach (1979):
(1) a publication
(2) a newspaper
(3) The San Francisco Chronicle
(4) the May 18 edition of the The San Francisco Chronicle
(5) my copy of the May 18 edition of the The San Francisco Chronicle
(6) my copy of the May 18 edition of the The San Francisco Chronicle as it was when I first picked it up (as contrasted with my copy as it was a few days later: in my fireplace, burning)
In a healthcare context, you could abstract from "Miguel's kidney"--a concrete, tangible object that you can actually hold in your hand--to the class (like a set) of human kidneys, of which Miguel's kidney is one of many.
All of those human kidneys have a lot of structural and functional things in common with Miguel's kidney, which makes them all members of the abstract class "human kidney".
Although they have lots of differences too, it's the similarities we focus on in the process of abstraction--they are "kidney-bean" shaped; they are composed of a medulla and a cortex, they are located retroperitoneally in the abdominal cavity, and they are part of the human urinary system, among many other qualities they share.
So while you can hold Miguel's concrete kidney in your hand, and it may have unique qualities of its own--larger or smaller than usual, perhaps suffering from some kind of condition or disease--it also shares common or universal qualities with other member of the class of "human kidney".
We can continue to perform abstraction: if we take away the description requirement that it has to be in a human, we can abstract from Miguel's kidney to the abstract class "Mammalian kidney", whose members have many of the same qualities as each other.
If we take away the requirement that it has to be located retroperitoneally in the abdominal cavity, and that it has to be kidney-bean-shaped, then we can bring in the fishes whose kidneys migrate during develoment to a position near their heads. Then we can abstract even further, all the way from Miguel's kidney to the abstract class "Vertebrate kidney".
The members of this class also have many of the same qualities, although they have fewer of those, and are more different from each other, than the members of the class "Mammalian kidney". In turn, members of the class "Mammalian kidney" are more diverse than are the members of the class "Human kidney".
The more abstract a class is, the less all the members have in common with each other, and the more they vary from one another. Still, they all have a certain foundational similarity that is the basis for their membership in the class.
What is the purpose of this kind of classification and abstraction? Based on their similarity, we can talk about things that are universal ("kidneys in animals filter urine"), rather than being constrained to only the concrete ("Miguel's kidney filters urine") and nothing more.
So, since research studies are carried out on individuals, rather than being able to say only "massage reduces anxiety in 25 selected elderly residents of a long-term care facility", we can--if the research is carried out in a methodologicallysound fashion--use those similarities that connect members of a class ("elderly residents of a long-term care facility") to use that abstraction to reason about the validity of applying those results to other members of that class.
That abstraction is at the heart of how we can carry out a study on a sampling of a population, and--if the study's methods are sound--use the outcomes from that sample population to reason that, because the sample has things in common with the larger abstract class, that we would expect to see those results in the larger class, or population.
It makes possible the change from "this treatment worked on this one small group of people and that's all we can say" to "because this treatment worked on this one small group of people, we expect it will work in a similar fashion on the larger population that this small group has characteristics in common with".
Cancer is different from other diseases, because cancers are not natural to the Universe. The man-made chemicals that cause cancers are foreign to the Universe. Man created the cancer; Man must treat the cancer, by killing or excising the cancer. Because Man created the cancer: Man must kill it.
--variations on this idea have been seen around the net on different MT forums
This article is an older one, but since we're talking about brains this month, it is still timely. It contains interesting information both about cancer, and about the scientific method--how scientists know about things that happened millions of years before any of us were ever born.
On October 23, [2003,] a team of paleontologists and pathologists announced that they had discovered a massive, possibly lethal brain tumor in the fossilized skull of a Gorgosaurus,
Source: http://upload.wikimedia.org/wikipedia/commons/8/80/Gorgosaurus_BW.jpg accessed 7 December 2011
You can read this as a clock that starts just past noon at 4.6 billion years ago (4.6 Ga). Continuing clockwise, the formation of the earth takes place 4550 million years ago (= 4550 Ma). At 3 billion years ago (3 Ga), 2 Ga, and 1 Ga, things are happening, but life on Earth doesn't really explode into prominence until about 530 Ma with the Cambrian explosion.
The dinosaurs lived alongside early mammals from about 230 Ma to 65 Ma, and humans arrived just before midnight on this clock: around 2 Ma.
The Cretaceous period, where this case report happened, follows the Jurassic period of Hollywood fame, and both are part of the green band representing the Mesozoic ("middle-life" or "middle-animal") era. Gorgosaurus roamed what would eventually become North America about 75 Ma or so.
Fossils of dinosaur bones are no surprise, but soft tissue doesn't fossilize the same way bones do, which is why we have so little information on dinosaur viscera. How, then, do we have a fossil sample of brain tumor?
A matrix of bone within this dinosaur's brain tumor allowed it to fossilize along with the rest of the animal's skeleton.
The tumor, possibly an unusual type of bone-forming cancer called an extraskeletal osteosarcoma, filled nearly the entire area formerly occupied by the cerebellum and brainstem and probably impaired the cerebrum, the part of the brain that controls thought and memory.
How do we know that dinosaur brains work like ours do--that the cerebellum and brainstem control movement and autonomic functions, and that the cerebrum controls thought and memory?
Like us, dinosaurs are vertebrates, and moreover--just like us--they are tetrapods.
Understandably, this vocabulary might be confusing: τετρά/tetra is Greek for 4, and quadr- is Latin for 4. πόδ/pod is Greek for foot, and ped is Latin for foot. And we know that quadrupeds are animals who walk on all fours, like dogs, cats, and horses, right?
So since tetrapod means the same thing in Greek as quadruped means in Latin, and since we're not quadrupeds (we're bipeds), how can we possibly be tetrapods?
It's because--although the meanings of the word roots are the same in their respective languages--they've come to mean different things in biology. Tetrapod refers roughly to structure, while quadruped refers roughly to function. So all animals that descended from the paired-limbed fish who evolved into land vertebrates are tetrapods, either because we all have two pairs of limbs (our arms and our legs), or because we used to have them before they changed a great deal (birds' and bats' wings are modified arms), or because we used to have them before they diminished greatly in size (whales, dolphins) or disappeared altogether (snakes).
Quadruped, on the other hand, refers to the action of walking on all fours, whether flat-footed like a bear, or on the toes like dogs and cats, or on the toenail, like horses. All of the animals listed in this paragraph are quadrupeds and tetrapods, because they walk on their pairs of limbs. The animals in the previous paragraph, on the other hand, do not walk on all fours--so although they are tetrapods, they are not quadrupeds.
So as different as we look on the outside, you see that there is a deep structural similarity we share.
And that structural similarity about vertebrate brains is the basis for how we reason about what effects the tumor must have had on this dinosaur when it began compressing structures in her brain.
We know how such a tumor affects other vertebrates, and we reason from that similarity about how it must have affected her vertebrate brain.
“As the tumor grew, the dinosaur—a female perhaps three years old— would have forgotten where she left her last kill, and then she would have forgotten to go to the bathroom,” says paleontologist Peter Larson of the Black Hills Institute in Hill City, South Dakota.
Sadly, you can see the same progression in loss of function in people living with the effects of brain tumors or other brain conditions. First, it can affect higher-order cerebral functions like thought and memory, but it can progress to a point where the autonomic functions directed by the cerebellum and the brainstem--the ones we don't consciously think about, like breathing or urinating--can be compromised.
The tumor would also have put pressure on the dinosaur’s cerebellum and brain stem, which regulate motor function and other autonomic functions such as heart rate. “The tumor would have impaired mobility and affected the animal’s balance. She would have fallen down a lot,” says veterinary pathologist Rachel Reams of Eli Lilly & Company, who studied the fossil.
Usually, as MTs, we don't see clients in this condition, because they are so compromised that other health issues are of much higher priority at that point.
Unfortunately for what the poor dinosaur went through, there is physical evidence to back up Reams' inferences about what happened to her.
Larson and his colleagues found ample evidence confirming that conclusion. Throughout the Gorgosaurus’s skeleton, the researchers saw signs of debilitating injuries: a smashed shoulder blade, a bad infection in the lower jaw, broken ribs, and a torn tendon in the left leg. “The leg eventually healed and became useful again, but for a while she would have been dragging that leg around,” Larson says. The creature never recovered from a badly broken right fibula, the small bone of the lower leg. The fracture had healed for barely two weeks at the time of the animal’s death. That was probably the last injury the she suffered, although scientists do not know exactly what killed her. “She was a very sad dinosaur,” says Larson.
Nobody likes to think of an animal in distress, even as long ago as this happened, and even as scary a predatory beast as she was. The poor sad dinosaur lived and died alone with her disease, experiencing all the problems it created for her quality of life.
The only possible silver lining to suffering is if we can learn something from it that we can, in turn, use to prevent further suffering.
From what the poor Gorgosaurus has taught us through her brief life and awful death in the Cretaceous, how could you change the quotation at the very top so that MTs could share correct information about cancer with other MTs in public forums?
What do we now know about cancer from this 75-million-year-old "case report"?
terrestrial nests: nests dug in holes in the ground
68C = 154.4 degrees Fahrenheit
(b) Egg collection
funnel traps: this is the basic idea of a trap where the turtle enters through a funnel, and then can't get out, but don't take this too literally as being the actual trap they used, as I couldn't find a picture of that
oxytocin: a hormone that has many effects, from inducing labor in humans and other mammals to promoting bonding. There's way too much knowledge about oxytocin to go into here, but it's interesting that it has analogous effects (inducing labor, stimulating egg-laying) in animals that appear so different as humans and turtles
oviposition: laying eggs
clutch: all the eggs laid at the same time by one animal
developmental asynchrony = developmental "not-same-time" = development at different times from each other
Experimental treatments were designed to test whether less advanced embryos were either hatching prematurely or potentially adjusting developmental rates throughout the incubation period.
They were investigating whether the less advanced embryos sped up development to match the stage where the more advanced ones already were, or whether they kept going at their normal rate and just ran out of time at the end before finishing development.
26C: 78.8 degrees Fahrenheit
30C: 86 degrees Fahrenheit
31C: 87.8 degrees Fahrenheit
two-tailed t-tests: a statistical test to determine whether to reject the null hypothesis and consider the study's alternative hypothesis to be confirmed
VCO2: volume of carbon dioxide
(d) Metabolic and heart rates
closed system respirometry: respirometry is the measurement of metabolic rates, and here, they used carbon dioxide breathed out over time as a marker of metabolic rate. Because the system was closed, they knew no carbon dioxide was coming in from outside, so any increase in CO2 had to come from the turtles' breathing it out. Measuring that increase in CO2 over time gave them the rate at which the turtles were producing it, thus, their metabolism.
A Qubit (S500) respirometer (Kingston, ON, Canada) was used to measure carbon dioxide production
Incubation period was measured as the number of days from initial egg collection until pipping. Pipping (when the eggshell is first slit) is better than hatching as an index of the end of the incubation period, because it shows less variability than hatching .
Another example of trying to cut down on confounds--since pipping is less variable than hatching, there is less opportunity for those variations to create confounds.
Righting trials--I think this means they flipped them, and timed how long it took the turtles to right themselves to a standing position, but don't take my word for this. I will look it up when I get to the university and can get behind the paywall to read the Colbert article, and will update at that point.
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