How We Die (35 page)
Authors: Sherwin B Nuland
Though chaotic in appearance and inconsistent in size, the community of malignant cells is not necessarily always anarchic. In a few forms of cancer, in fact, all individuals are found to choose a specific uniform shape that suits a shared element in their willfulness. Such malignancies exist as though to demonstrate an obstinate refusal to conform to the accustomed disharmony expected of them; their cells reproduce myriads of virtually identical selves, like so many millions upon millions of little poisonous apples, boringly similar to one another but quite different from their tissue of origin. Even the predictability of malignancy’s unpredictability is unpredictable.
The central structure of the cancer cell, its nucleus, is larger and more prominent than that of mature relatives and is often as misshapen as the cell itself. Its dominance over the protoplasm surrounding it is intensified by the enhanced avidity with which it takes up standard laboratory stains, a characteristic that gives it a darkened, ominous look. The evil-eye nucleus reveals its disordered independence in yet another way: Instead of dividing neatly into two symmetrical halves during the process of reproduction known as mitosis, the chromosomes (the components of the nucleus that carry the DNA) align themselves in bizarre patterns, attempting with varying degrees of success to multiply, figuratively head over heels, without any element of precision or accountability. The rate of mitosis of some cancers is so rapid that a quick look through the microscope will catch many times the number of cells in the act of trying to reproduce as are found in mature normal tissue, and every one of them seems to be doing it in its own haphazard way. Small wonder that the surviving offspring are ill-suited to their surroundings in the ordered, consistent tissue of the organs of which they were originally meant to be a part. So pugnaciously “other” are the new masses of cells, in fact, that they not only invade but also push their law-abiding grown-up neighbors out of the way as they infiltrate and preempt surrounding territory.
In a word, cancer is asocial. Having escaped the constraints that govern nonmalignant cells, the newly formed tissues pursue uncontrolled and domineering relationships with their host organs and cannot be made to restrict their encroaching margins to the foci that gave them birth. Unrestrained and patternless growth enables a cancer to force its way into nearby vital structures to engulf them, prevent their functioning, and choke off their vitality. By this means, and by destroying the organs from whose stem cells they are made, the masses of cancer cells kill the gradually sickening person after feasting on the nutrients that were to have sustained him.
Although it begins as a microscopic phenomenon, the process of malignant growth, once properly established, inevitably continues until it can be seen with the naked eye or felt with the exploring hand. For a while, the growing mass may remain too small or confined to produce symptoms, but in time, the cancer’s victim will sense that something untoward is happening to him. By that point, the malignancy may have grown so large that it is beyond cure. Particularly in certain solid organs, a cancer may reach considerable size before it makes its host aware of its presence. It was for this reason, of course, that the disease achieved its legendary reputation as a noiseless killer.
A kidney, for example, may be found to harbor a perfectly huge growth when it first reveals its advanced state of disease by spilling visible blood into the urine or causing a dull ache in the flank. If an operation is done at that point, the surgeon’s efforts will be defeated by the wide extent of involvement of surrounding tissues. The otherwise-symmetrical brown smoothness of the organ will be found to have been eaten away in one large area by an ugly, lobulated protrusion of coarse gray hardness that has forced its way through to the surface, invaded the adjacent fat, and drawn all nearby tissues into it, the misbegotten whole forming one great puckered grotesquerie of bunched-up aggression. Of all the diseases they treat, cancer is the one that surgeons have given the specific designation of “The Enemy.”
The visible structure and invasiveness of a cancer are only two of its many forms of unruliness. One of the most duplicitous of malignancy’s misbehaviors is the way in which it seems to elude the defenses ordinarily mounted by the body against tissue it perceives as not belonging to it. Theoretically at least, cells that have become cancerous should be detectable as foreign or “other” by an intact immune system and then killed, much as is a virus. This actually does happen to an extent; some researchers believe that our tissues are continually making cancers, which are just as continually being destroyed by this kind of mechanism. Clinical malignancies would then develop in those rare instances when the surveillance system fails. An example of support for such a thesis is to be found in the prevalence in people with AIDS of tumors such as lymphoma and Kaposi’s sarcoma. Overall, the incidence of malignancies in immunocompromised individuals is some two hundred times that found in the general population, and for Kaposi’s the figure is more than twice what it is for the average tumor. One of the most promising fields of today’s biomedical research is the study of tumor immunity with a view toward strengthening the body’s responses to the antigens that cancers may produce. Although there have been some promising results, the target cells continue, for the most part, to outwit the scientists.
Normal cells require a complex mixture of nutrients and growth factors in order to continue functioning and retain viability. Throughout all tissues of the body, they are bathed in a life-giving nutrient soup called extracellular fluid, which is constantly being restored and cleansed by exchanging substances with circulating blood. The blood’s plasma, in fact, amounts to one-fifth of the body’s extracellular fluid; most of the other four-fifths lies between the cells, and is called interstitial. The interstitial fluid accounts for approximately 15 percent of body weight; if you weigh 150 pounds, your tissues are soaking in 22 pints of the salty stuff. The nineteenth-century French physiologist Claude Bernard introduced the term
milieu intérieur
to name and describe the function of this internal environment in which cells live within us. It is as though the earliest groups of prehistoric cells, when they first began to form complex organisms in the marine depths from which they drew sustenance, brought some of the sea into and around themselves so that they might continue to be nourished by it. Among the unique features of malignant tissues is their reduced dependence on the nutritional and growth factors in the extracellular fluid. Their lessened need for sustenance from the surroundings enables them to grow and invade even those areas beyond optimal supply lines.
milieu intérieur
to name and describe the function of this internal environment in which cells live within us. It is as though the earliest groups of prehistoric cells, when they first began to form complex organisms in the marine depths from which they drew sustenance, brought some of the sea into and around themselves so that they might continue to be nourished by it. Among the unique features of malignant tissues is their reduced dependence on the nutritional and growth factors in the extracellular fluid. Their lessened need for sustenance from the surroundings enables them to grow and invade even those areas beyond optimal supply lines.
No matter that each cellular unit can get along with less, the helter-skelter increase in population soon accumulates so many malignant cells that the requirements of the aggregate tend to outstrip whatever supplies are available. As a result, a total tumor mass will often develop an increased demand for nutrition, even though each individual within it may require less than a normal amount of it. If growth is rapid enough, blood supply after a time will be insufficient to restore used-up nutrients, especially because new vessels usually do not appear rapidly enough to keep pace with the needs of the whole expanding tumor.
The result is that a portion of an enlarging tumor may die, literally of malnutrition and oxygen lack. It is for this reason that cancers tend to ulcerate and bleed, sometimes producing thick, slimy deposits of necrotic tissue (from the Greek
nekrosis
, meaning “becoming dead”) within their centers or at the periphery. Until mastectomy became a common operation less than a hundred years ago, the most dreaded complication of breast malignancy was not death but the fetid running sores it produced as a hapless woman’s chest wall was digested away. This is precisely why the ancients referred to
karkinoma
as the “stinking death.”
nekrosis
, meaning “becoming dead”) within their centers or at the periphery. Until mastectomy became a common operation less than a hundred years ago, the most dreaded complication of breast malignancy was not death but the fetid running sores it produced as a hapless woman’s chest wall was digested away. This is precisely why the ancients referred to
karkinoma
as the “stinking death.”
In the late eighteenth century, Giovanni Morgagni, the author of a landmark text of pathological anatomy, said of the cancer he saw in his patients and at their autopsies that it was “a very filthy disease.” Even in relatively recent times, when much more was known, malignant tumors continued to be viewed as repugnant sources of self-loathing and decay, a humiliating abomination to be concealed behind euphemisms and lies. Many are the stories of women with breast cancer who withdrew from friends, secluded themselves at home, and lived their final months as recluses, sometimes even from their own families. As recently as the period of my training, just over thirty years ago, I saw a few such women who had finally been prevailed upon to come to the clinic because their situations had become intolerable. Of the several reasons we still hesitate to utter the word
cancer
in the presence of a patient or family assaulted by it, the residual heritage of its odious connections is the one most difficult for our generation to expunge.
cancer
in the presence of a patient or family assaulted by it, the residual heritage of its odious connections is the one most difficult for our generation to expunge.
Not enough that a rapidly growing cancer may so infiltrate a solid organ like the liver or kidney that insufficient tissue remains to perform the organ’s functions effectively; not enough that it may obstruct a hollow structure like the intestinal tract and make adequate nourishment impossible; not enough that even a small mass of it can destroy a vital center without which life functions cannot go on, as some brain tumors do; not enough that it erodes small blood vessels or ulcerates sufficiently to result gradually in severe anemia, as it often does in the stomach or colon; not enough that its very bulk sometimes interferes with the drainage of bacteria-laden effluents and induces pneumonia and respiratory insufficiency, which are common causes of death in lung cancer; not enough that a malignancy has several ways by which it can starve its host into malnutrition—a cancer has still other ways to kill. Those just mentioned refer, after all, only to potentially lethal consequences of encroachment by the primary tumor itself, without its ever having left the organ where it first arose. These are the kinds of damage cancer does in its own neighborhood. But it has an additional way of killing that takes it out of the category of localized disease and permits it to attack a wide assortment of tissues far from its origin. That mechanism has been given the name
metastasis
.
metastasis
.
Meta
is a Greek preposition meaning “beyond” or “away from,” and
stasis
connotes “position” or “placing.” Introduced as early as the Hippocratic writings to indicate a change away from one form of fever to another,
metastasis
later came to be applied specifically to migration of bits of tumor. In modern times, this one word,
metastasis
, has come to articulate the defining feature of malignancy—cancer is a neoplasm that has the potential to go beyond its home and travel to some other place. A metastasis is, in effect, a transplant of a sample of the primary tumor to another structure or even a distant part of the body.
is a Greek preposition meaning “beyond” or “away from,” and
stasis
connotes “position” or “placing.” Introduced as early as the Hippocratic writings to indicate a change away from one form of fever to another,
metastasis
later came to be applied specifically to migration of bits of tumor. In modern times, this one word,
metastasis
, has come to articulate the defining feature of malignancy—cancer is a neoplasm that has the potential to go beyond its home and travel to some other place. A metastasis is, in effect, a transplant of a sample of the primary tumor to another structure or even a distant part of the body.
Cancer’s ability to metastasize is both its hallmark and its most menacing characteristic. If a malignant tumor did not have the ability to travel, surgeons would be able to cure all but those that involve vital structures, which cannot be removed without compromising life. In order to travel, the tumor must erode through the wall of a blood vessel or lymph channel, and then some of its cells must become detached and pass into the flowing stream. Either individually or clumped into an embolus, the cells are then carried to some other tissue, where they implant and grow. Determined by the route of blood or lymph flow as well as other still-unclear factors, various cancers have a predilection to be deposited in certain specific organs. For example, a breast cancer is most likely to metastasize to bone marrow, lungs, liver, and, of course, the lymph nodes in the armpit, or axilla. A cancer of the prostate commonly travels to bone. Bones, in fact, along with the liver and kidney, are the most common sites for metastatic deposits, regardless of the malignancy’s organ of origin.
In order to take root in a distant location, tumor cells need to be hardy enough to resist destruction while on their journey. The simple mechanical dangers of traveling through the jolting circulation complicate the possibility of being killed by the host’s immune system during the course of the passage. If they survive the voyage, the cells must then establish a new home and be provided a reliable source of nutrition. This means
a priori
that the transplanted bit of cancer cannot create a viable colony on the newly reached distant shore unless it is capable of stimulating the growth of tiny new blood vessels to supply its needs.
a priori
that the transplanted bit of cancer cannot create a viable colony on the newly reached distant shore unless it is capable of stimulating the growth of tiny new blood vessels to supply its needs.
So difficult is it to satisfy all of these requirements that very few of the migrating cells ever do manage to colonize some far-flung site. When tumor cells are experimentally injected into mice, only one-tenth of 1 percent survive beyond twenty-four hours; it is estimated that only one of each 100,000 cells entering the bloodstream lives to reach another organ, and a far smaller proportion successfully implant themselves. Were it not for obstacles such as these, massive numbers of metastases would appear as soon as a cancer becomes sufficiently large to shed many cells into the circulation.
By the twin forces of local invasion and distant metastasis, a cancer gradually interferes with the functioning of the various tissues of the body. Tubular organs are obstructed, metabolic processes are inhibited, blood vessels are eroded sufficiently to cause minor and sometimes major bleeding, vital centers are destroyed, and delicate biochemical balances are deranged. In time, a point is reached at which life can no longer be sustained.
In addition, there are less direct ways for cancer to take its toll on those in whom its growth is unchecked, and they are usually the result of the debilitation, poor nutrition, and susceptibility to infection that come with the malignant process. Nutritional depletion is so common that a term has been devised to designate its effects:
cancer cachexia
. Cachexia is derived from two Greek words meaning “bad condition,” which is exactly the situation in which advanced cancer patients find themselves. It is characterized by weakness, poor appetite, alterations in metabolism, and wasting of muscle and other tissues.
cancer cachexia
. Cachexia is derived from two Greek words meaning “bad condition,” which is exactly the situation in which advanced cancer patients find themselves. It is characterized by weakness, poor appetite, alterations in metabolism, and wasting of muscle and other tissues.
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