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Relief of Pain in Cancer Patients
Relief of Pain in Cancer Patients DANELY P. SLAUGHTER, M.D., F.A.C.S.* HARRY W. SOUTHWICK, M.D., F.A.C.S.** HAROLD L. HARRIS, M.D.t
IF
were an early symptom in developing cancer, a great many more patients would be cured of this disease than at present. Unfortunately, by the time pain becomes a clinical feature in the course of the disease, the patient usually is in an incurable condition and only palliative measures are possible. Two aspects of this situation deserve emphasis, namely the statistical enormity of the problem and the numerous variations in therapy that are today available to the thoughtful physician. With the exception of cancer of the skin and lip, considerably less than half of the other malignant tumors are eliminated by present day treatment methods. There are many reasons why modern surgery and irradiation are not utilized more effectively to their full potential, but the fact remains that probably three-fourths of patients with internal cancer succumb to their disease. There is, therefore, a vast number of such patients who need help from the time a stage of incurability becomes apparent until their demise. Too often physicians apply the fact of the eventual hopelessneHs of the situation to all aspects of the patient's care and the result is neglect of the patient and dereliction of their duty as physicians. Why we will give meticulous attention to the incurable cardiac or hypertensive patient with congestive failure, and consign the equally affiicted cancer patient to his own devices, remains a mystery, but this is too frequently the case. PAIN
RELIEF OF PAIN BY TUMOR CONTROL
Control of pain due to cancer may be achieved in two ways. These are, first, treatment which eliminates the tumor or causes temporary regres-
* Associate Professor of Surgery and Director of the Tumor Clinic, University of Illinois College of Medicine, Chicago; Director of the Tumor Clinic, St. Francis Hospital, Evanston, Illinois.
** Assistant Professor of Surgery, University of Illinois College of Medicine; Director of the Tumor Clinic, Presbyterian Hospital, Chicago. t Chief of Anesthesiology, St. Francis Hospital, Evanston, Illinois. 51
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Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
sion, and second, treatment which obtunds sensory perception of pain or eliminates specific pain pathways. Direct attack on the tumor is the most logical and usually results in the greatest good to the patient, but is applicable to fewer patients, and those only in the earlier phase of incurability. Palliation by tumor control is based on a fundamental concept which frequently is either poorly understood or not appreciated at all. This concept is the fact that almost all malignant tumors have fairly definite behavior patterns of growth and spread, and that the uncontrolled natural history of a given tumor is predictable within reasonably broad limits. Too many physicians tend to attribute all possibilities of spread to all cancers, whereas this is simply not true of the great majority of malignant tumors. As an example, the squamous cell carcinomas, whether of the lip, tongue, or cervix of the uterus, confine their metastatic activities almost entirely to the lymphatic pathways, and metastases from such tumors are usually found, even at autopsy, to be confined to the regional lymph nodes draining the anatomic site of origin. The most frequent cause of death in women with cancer of the cervix is about an ounce of cancer surrounding each lower ureter, with consequent renal failure. In patients with oral cancer, the usual causes of death are hemorrhage, inanition, and airway obstruction. In contrast, adenocarcinomas of the stomach or colon metastasize by invasion of veins in addition to lymphatics, so that not only the local regional nodes but also the liver, via the portal venous system, will become involved. The principal conditions of unpredictability occur with malignant melanomas, or with carcinomas in the lung, primary or secondary, where they may invade pulmonary veins and thus be spread by way of the systemic arterial circulation. Aside from these situations and a few other rare neoplastic entities, it is practically possible in many instances to channel the inevitable progression of an incurable cancer in a manner that minimizes or, rarely, eliminates pain. The ultimate goal in partial or palliative tumor control is to arrange the patient's demise as a chemical death from hepatic, renal or pulmonary failure. This ponderoussounding remark is more realistic than it may appear if one stops to think of the thousands of palliative gastric or colon resections that are performed each year in the face of liver metastases, in order to avoid death from obstruction. The only curative treatment of cancer today is by destructive methods, either surgery or irradiation. These are crude approaches to a phenomenon which is essentially a chemical aberration of the fundamental biological processes within the cell. For the time being these two modalities are our only effective therapy, but most of these therapeutic attempts are palliative in effect, even though curative in intent. Therefore the majority of cancer patients become problems in palliation eventually. When the chips are down, and incurability is clinically apparent, con-
Relief of Pain in Cancer Patients
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siderable assistance still may be given the patient in the way of maintaining an active and productive life, let alone a relatively supportable existence. It is our function as physicians to see that these patients receive all of the available "breaks." PALLIATIVE SURGERY
Surgical relief of the patient with incurable cancer fits into two categories, namely, relief of obstruction, and amputation or adequate excision of painful or ulcerated tumor masses. Relief of Obstruction
Obstruction due to cancer is usually amenable to surgical relief, even if only palliative, in the following areas: (1) airway, (2) swallowing, (3) gastric, (4) small bowel, (5) colon, (6) biliary tract and (7) urinary tract. The only painful obstructions are those involving the small bowel, colon and urinary tract, especially the latter when there is infection above the point of obstruction. It is not the purpose of this discussion to detail the surgical procedures available. Suffice it to say that the indications for operation are usually clear. It should be emphasized that excisional surgery is almost always preferable to by-passing procedures. For example, palliative resection of the esophagus with restoration of continuity is better than gastrostomy, and certainly resection of the colon with end-to-end anastomosis is far better than leaving a patient with a loop colostomy because of the finding of liver metastases, if the primary lesion is at all resectable. This is not to compare the pleasures of deglutition with those of defecation, as the point should be obvious. In the case of cancer obstructing the extrahepatic biliary tract, every effort should be made to shunt bile flow internally if the tumor is inoperable. If the patient's life expectancy is a year or more, a Roux-Y choledochojejunostomy is the procedure of choice, otherwise an end-toside anastomosis using the gallbladder may be done. The urinary tract may be rearranged in many ways to give relief from obstruction or fistulas. Palliative surgery is definitely worthwhile, as the authors have repeatedly seen patients live two and three years with liver metastases, leading a comfortable and productive life for most of that time, if the primary cancer has been removed. CASE 1. Mrs. M.F., aged 41 years, had an excision of a large right ovarian tumor at another hospital at the age of 32. This was reported as benign. Five years later, at the age of 37, a carcinoma of the left ovary was excised. This recurred and heavy doses of 200 kv. radiation were utilized through the lower abdomen. She was re-explored 2 years later and an inoperable tumor mass was found in the pelvis obstructing the sigmoid colon. A loop colostomy was performed. Urinary tract infection followed and the left kidney ceased to function. One year later a spontaneous urinary fistula occurred through the colostomy. This added to her misery but was a life-saving accident. The patient was having constant back and pelvic pain and became bedridden.
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Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
She was admitted on the senior authors' service in Apl'iI1954, 9 years after her first operation. A large fixed tumor mass filled the pelvis and was palpable through the abdomen. The abdominal wall was fibrosed and telangiectatic flOm irradiation. A constantly draining wet colostomy macerated the already damaged and infected skin. After preparation with transfusions and the administration of needed electrolytes and fluids, exploratory laparotomy was performed. It was possible to remove the tumor mass by resecting the sigmoid colon, left ureter, upper vagina, a loop of incorporated small bowel, pelvic peritoneum, and a part of the abdominal wall. There was no cancer apparent elsewhere in the abdomen. The left ureter was simply ligated. The right ureter was found to be double, and its lower portion was destroyed by the tumor mass, which also had destroyed a portion of the sigmoid colon, thus creating the urinary fistula back through the colostomy. It was possible to exteriorize the intact rectosigmoid, and the double right ureter was implanted into the descending colon which was brought out in apposition to the exteriorized lower colon, thus creating a second double-barreled wet colostomy, in the same spot as the original one, which had to be excised in removing the tumor mass. The patient recovered without undue difficulty. Eight weeks later the patient was again hospitalized and the colostomy closed by utilizing as an artificial bladder the loop of the descending colon which ended as the upper barrel of the colostomy. This was done by sectioning the colon proximal to the ureteral implant and closing this end, dropping this closed end free into the abdomen, carrying the ureteral implantation with it. The open distal end of this isolated loop was left in position through the abdominal wall as the external opening of the artificial bladder. The rectosigmoid was then freed and anastomosed to the proximal descending colon, thus restoring intestinal continuity. The patient has normal bowel function, has gained 50 pounds in weight, controls the artificial bladder easily with a Rutzen bag, and is apparently well more than 14 months later.
This case history illustrates an extreme but worthwhile attempt at surgical palliation of a patient with cancer causing pain, and obstructing both the large bowel and upper urinary tracts. Permanent cure is exceedingly unlikely. From the patient's standpoint, she is happy with the result. Effective palliation in cancer patients is very much the same problem as that of the prisoner condemned to capital punishment. Will he be content to hang tomorrow, or will he make all appeals possible, to postpone the inevitable until a year from tomorrow? Alllputations or Radical Excision of Large TUlllor Masses
Sarcomas and melanomas of the extremities, and occasionally metastatic cancer, may become huge ulcerating tumor masses which not only produce a useless extremity but cause severe pain, which may become intolerable. The consequent paralysis, infection and hemorrhage make amputation reasonable in such situations even in the presence of distant metastatic disease precluding cure. This is equally true of tumors involving the abdominal or chest walls, particularly if they are low grade or well differentiated and radioresistant lesions. Deliberate palliative breast amputation, when disseminated disease is present, is not as frequent a decision as the high incidence of breast cancer might lead one
Relief of Pain
~in
Cancer Patients
to expect. The highly anaplastic breast cancers with local lymphat.ie permeation, "infiammatory" carcinoma, are often worsened by surgical intervention, whereas the low grade, well differentiated breast cancer" are susceptible to considerable control by irradiation or endocrine management. When this latter lesion is first seen in an advanced and incurable condition, the patient is usually an unintelligent individual whose disease is one of long standing and active neglect. Such a clinical setting may occasionally be benefited by local wide excisional surgery, usually undertaken after maximum irradiation has failed of local control, but where systemic disease may otherwise allow further longevity. PALLIATIVE IRRADIATION
For practical purposes, the curative use of radiotherapy is confined to treatment of surface lesions or intracavitary irradiation of cancer of the upper respiratory tract and uterus. Present day and future developments in supervoltage ranges may replace surgical measures for lesions of the esophagus and lung, but for the time being the most frequent use of radiotherapy is in the palliation of incurable cancer. Irradiation, in its various modalities, is an extremely useful tool for this purpose. Radiation is most effective when used to treat the more radiosensitive tumors such as the lymphomas, including Hodgkin's disease, and the amenable carcinomas such as metastatic mammary or papillary thyroid cancer, and some ovarian cancers. Almost all malignant tumors are radiosensitive to some degree, as compared to their normal tissue derivation. However, as an extreme example, irradiation of a low grade chondrosarcoma or a chordoma is so ineffective that more damage will be done to soft tissues than will be sustained by the tumor. In such a case the law of diminishing returns will be on the negative side, past the decimal point. Localized painful metastatic deposits of relatively radioHensitive cancer are very effectively treated by irradiation. Breast cancer metm;tatic to the spine may often be controlled for years in this manner. Pathological fractures often may be forestalled or prevented for years by irradiation, and it is stupid and inhumane to allow a patient to develop a pathological fracture of the femoral neck by withholding radiation because of hepatic or pulmonary metastases. When disseminated carcinoma becomes too widespread for efficient radiotherapy, then its use should be confined to the most critical or painful areas, or chemotherapy substituted. Both chemotherapy and irradiation of too great a surface area have a common hazard, namely aplastic anemia from bone marrow destruction. CASE H. ;\1rs. P.C. was first seen in Sept8mber 1953 at the age of 72, with a history of having had a right mdieal mastec:tomy in 1940 for breast c:anc:er. In 1949 she developed left pleural effusion whieh revealed c:ancer cells on aspiration and pulmonary metastases on x-ray. She was treated with androgens and mul-
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Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
tiple thoracenteses with some slight effect for 10 months. She was then placed on stilbestrol by mouth and all clinical symptoms and findin:~s promptly dis'lppeared. When first seen by us in September 1953 there were several painful subcutaneous nodules of cancer; in particular, one large one over the left parotid gland. Biopsy revealed adenocarcinoma consistent with mammary cancer. Because of imminent facial nerve paralysis, this parotid lesion was treated with xradiation and it has apparently been obliterated. The patient was again given stilbestrol, 6 mg. per day by mouth, since she had had no medication for 15 months previously. The other skin lesions ceased to grow but did not regress. The patient remained well until October 1954, when she developed severe dysphagia and lost 20 pounds in weight. X-ray examination disclosed obstruction of the midmediastinal thoracic esophagus, and planograms showed mediastinal node enlargement in this area. Esophagoscopy and bronchoscopy both produced biopsy evidence of carcinoma consistent with a mammary origin. X-radiation to the site of obstruction produced complete relief of symptoms and clearing of xray signs, and avoided a tracheoesophageal fistula. In March 1955 the skin lesions began to grow and 2 or 3 ulcerated. These lesions, widely separated and located singly in the upper thighs, buttocks, abdominal and chest walls, and neck, were probably a result of spread from pulmonary foci through the systemic arterial system. These skin deposits, being released from endocrine control, were treated individually with single massive doses of 120 kv. x-radiation, and have since healed, leaving only radiation scars in their place. Recent studies by fluoroscopy and esophagoscopy reveal no cancer at the site of obstruction, and the patient is clinically well for the time being. She has been living with incurable breast cancer for 15 years, and apparently will continue to do so for some time. At the moment there is no evidence of clinical activity of her disease. CHEMOTHERAPY
Control of cancer by systemic drug therapy is, without question, the hope and trend for the future of cancer therapy. In the last few years a glimmer of light has been brought to this field so that at least a start has been made. No curative chemotherapy has yet been achieved, but effeetive palliation is now possible in several clinical situations. The nitrogen mustards used intravenously in doses of 0.1 mg.jkg. of body weight will temporarily control systemic and disseminated Hodgkin's disease, lymphosarcoma to a lesser extent, and leukemias still less. Use of this drug should be confined to advanced cases, radiation-fast, and untreatable otherwise. The most practical program of administration is a five day course, giving the dose by rapid intravenous drip in saline, at night, to a patient so narcotized that he sleeps through the transient acute reaction and nausea, and thus can maintain his nutrition during the day. The bone marrow must be watched daily, and for some time after a course of therapy, by peripheral blood studies, particularly white cell and platelet counts. While the very radiosensitive neoplasms mentioned are the most sensitive to the radiomimetic action of the nitrogen mustards, bronchogenic carcinoma is also susceptible to appreciable palliation by intravenous use of the drug. No other epithelial cancers seemed to respond, but when the explanation of this paradox became clear, namely that the lung
Relief of Pain in Cancer Patients
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first receives the full concentration of the drug before systemic dilution, it led to the intra-arterial use of nitrogen mustard. This method, used selectively, is another effective means of causing major tumor regression. It is utilized by cannulating the arterial supply of a tumor area with a polythene cannula for long-continued multiple injections over a period of days or weeks, or for single massive injections, which may be made through the hepatic artery for treatment of liver metastases. Apparently all tumors will respond to a sufficient concentration of the drug in about the same scale of sensitivity as they respond to radiation. If liver metastases are to be treated, two points are pertinent: first a single massive dose, by catheterization or needle injection, is relatively safe because the drug is detoxified by the hepatic parenchyma; second, the injection must be intra-arterial because metastatic cancer in liver develops its blood supply from the arterial side, and because of the danger of portal vein thrombosis. Other drugs are being used, such as aminopterin, methopterin (useful in acute leukemias), TEM (triethylene melamine) and TEPA (triethylene phosphor amide). These can be given by mouth, and TEM has been referred to as the "oral mustard." They are effective to a slight degree in disseminated cancer, more so in the lymphomas, but are so toxic that it is fortunate that they were not available to the Borgias. Consideration of p32 and 1'31 is not within the scope of this discussion except to say that painful metastatic thyroid cancer, and even pathological fractures, may be relieved and even made to heal in occasional instances by the use of radioactive iodine. The most thought-provoking aspect is that, rarely, metastatic thyroid cancer which does not take up radioiodine may be led to re-differentiate towards the normal, as judged histopathologically, to a functional state where the tumor cells may pick up radioiodine in quantities sufficient to destroy themselves. This is effected by removing all normal thyroid tissue, preferably surgically, so that a state of physiologic need is created. We have had two patients with pathological fractures of the femur due to thyroid cancer whose lesions were made to heal by such a program. ENDOCRINE MODIFICATION
Since Huggins first demonstrated that the course of human prostatic cancer could be modified by changing its endocrine milieu, great advances have been made in the palliative control of two of the most common malignant neoplasms that affect the human race, namely carcinoma of the breast and of the prostate gland. The treatment of prostatic cancer by castration and/or estrogenic hormone is so well known and standardized that it needs no elaboration here, except to note that the disease is usually painful because of metastases to the spine and pelvis. Endocrine relief is by far the most effective treatment available. In the case of breast cancer, it should be emphasized that endocrine
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Danely P. Slaughter, Harry W. SouthwZ:ck, Harold L. Harris
management in no way replaces the standard curative methods of radical mastectomy, with or without supplemental x-radiation. Neither does it replace palliative irradiation of localized l"(~current disease occurring in the 50 per cent or more of pati(~ntH in whom the original treatment failed to cure. Endocrine modification should be utilized, therefore, only in the patient with advanced, disseminated and otherwise untreatable breast cancer. For such a patient the following outline probably exemplifies most current thought on the subject. Patients Under 55 Years of Age
Castration. About 30 per cent of breast cancers in premenopausal women show some regression after castration. This regression may occasionally be dramatic, and the effect may last from ten months to, rarely, two or three years. Logically, oophorectomy is the most effective means of castration, but it is likely that roentgen dosage, in the order of two or three times that required to stop the menses, may be just aH effective. The question of routine prophylactic castration of the premenopausal patient with breast cancer is a philosophical one, because if all cancer cells have been destroyed by the definitive curative attempt, there is no need to add an artificial menopause to the patient's problemH. If the tumor recurs, castration will probably be just as effective, and no more so, than it would have been originally. Androgens. Male sex hormone is effective in about 50 per cent of premenopausal women and is particularly useful in the treatment of painful bone metastases. Objective x-ray evidence of recalcification of osteolytic metastases occurs in 40 per cent or more, and the effect lasts from ten months to two years or more. Dosage is usually 100 mg. of testoHterone propionate three times weekly, and usually masculinization to some degree must be apparent for tumor effect. Small or temporizing doses have little or no effect. If cancer regression is to occur it will usually be apparent within three to six weekH. Prophylactic use of androgens is either a waste of time or harmful. The Hide effects of steroids of this character are not only annoying but can be dangerous because of their salt and water retention effect. Borderline cardiac and hypertensive patients can be placed in acute congeHtive failure by the latent edema, evident from the sudden weight gain all patients undergo when androgens are given. Androgenie therapy Hhould generally be used with or following castration. If tumor regression occurs, after three or four months the patient may be given methyltestosterone, 25 mg./day by mouth, for maintenance. Adrenalectomy. Adrenalectomy is the last chance to afford an incurable breast cancer patient another year or more of life. This operation is still under clinical investigation, and is not to be considered routine. We as physicians confront certain moral hazards in placing patients in
Relief of Pain in Cancer Patients
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the daily jeopardy of possible Addisonian crisis, for problematical temporary relief. About 40 per cent of our patients have had objective regression of metastatic breast cancer, with considerably more pain relief than this would indicate. The effect is sometimes dramatic, with bedridden addicts out mowing their lawns in a few weeks, but the tumor control averages only 10 to 18 months. Some patients are still doing well after three years, however. Tlw opera1jon is a major procedure, but so far we have had no surgical fatality in over 75 cases. No patient over 61 years of age has shown any benefit, and the pattern is beginning to emerge that we have objective regression in over 60 per cent of the group whose breast cancer started at the time of or before the menopause, whose disease is of long standing and therefore relatively low grade, and who have improved temporarily by castration and androgenic management. The finding of metastatic mammary cancer in almost three-fourths of the excised ovaries and adrenals in our series explains in part why it takes so long for many terminal breast cancer patients to die. Patients 55 to 65 Years of Age
This is the equivocal group whose breast cancer is least likely to respond to endocrine management. The patients are best handled like those in the younger age groups, but respond less frequently and to a lesser degree. Estrogenic hormone is dangerous in this group and in all younger patients, since female sex hormones often stimulate the tumor to more rapid growth. Patients Over 65 Years of Age
Painful metastatic and recurrent breast cancer at this age, when other treatment has failed, is most likely to regress on estrogenic therapy. The usual treatment is from 6 to 15 mg. of stilbestrol in divided doses daily by mouth. This is more than physiological dosage and, of course, will activate the endometrium in the female with an intact uterus, a condition more common in rural than urban populations. The older the patient, the more likely it is that her breast cancer will respond to estrogens. ·When regression does occur it is frequently more rapid and profound than occurs with androgens in the younger age groups, and it is our impression that soft tissue lesion,; are somewhat more affected. CONTROL Of' PAIN BY SENSORY
BI~OCK
Neurosurgical Potentialities
It must be emphasized that, though our material has been categorized for simplicity of presentation, the various modalities offered for the relief of pain are not mutually exclusive. As a matter of fact, it is often highly advantageous to combine the various pharmacologic and surgical approaches to the problem. This is particularly important where neuro-
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Danely P. Slaughter, Harry W. Southwiclc, Harold L. Harris
surgical procedures are under consideration. There is often the tendency to avoid "another operation" when the narcotic limits have not been extended to the point of negligible return. The effectiveness of the neurosurgical operation is often greatest, however, and the magnitude less, when relief is obtained before the pain pattern has become fixed. Peripheral Nerve Section. If the pain is sufficiently localized, it is occasionally possible to find isolated specific nerves which may be divided by a relatively minor procedure. Of course, if the tumor mass producing the pain is solitary and relatively easily resected, its surgical removal is indicated as mentioned earlier. However, in the face of widespread disease, a simpler attack may be in order. This is particularly true where intercostal nerves are involved. Section of these often gives complete relief; the number of nerves involved is predetermined by procaine infiltration about the specific segments. Care should be exercised to reach above and below the specific lesion, not only for the immediate relief but to allow for the inevitable local extension of the existing disease. Dorsal Rhizotomy. Dorsal rhizotomy is also limited in its application to those patients who have only a few dermatomes involved, either unilaterally or bilaterally. When it is reasonable to believe that the disease process is not a rapidly progressive one, the intradural division of the sensory nerve roots is quite effective. The advantage of this procedure over section of a peripheral nerve with motor components is obvious. Pain from tumors of the head and neck area can often be controlled by trigeminal rhizotomy; this is particularly advantageous when it is the result of certain slowly growing tumors such as some parotid carcinomas. Frequently, the extent of the lesion in the head and neck is such that section of the glossopharyngeal nerve as well as the sensory roots of the upper cervical plexus is necessary to obtain complete pain relief. Chordotomy. In the anterolateral quadrant of the spinal cord, between the dentate ligament and the anterior root, lie the nerve fibers which carry the sensation of pain centrally. Concern is often expressed over the possibility of limitation of motor function following chordotomy, but this complication is seldom encountered. The large crossed pyramidal tract lies posteriorly, and if the plane of division is kept anterior to the landmark of the dentate ligament, the chance of such damage is negligible. Much more extensive areas can be rendered anesthetic by this procedure than by dorsal rhizotomy. A patient with unilateral pain below the level of the arm is an ideal candidate, and relief is obtained in a high percentage of the cases without modification of use of the leg or sphincter power. When pain is bilateral, the results are not as satisfactory. The pain itself can be controlled, but the complications previously mentioned are all too frequent. Of course, if the tumor itself has already rendered the patient incontinent and bedridden, it is a "free go" as far as pain relief is concerned, and the side effects would be no cause for concern.
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Lobotomy. Frontal lobotomy, as described by Freeman and Watts, has its primary therapeutic effect focused on certain psychiatric disorders. However, as an incidental finding, it was found that the occasional patient who had both a psychiatric as well as a painful disease was relieved of both in successful cases. Since then, the procedure has been adopted as one other specific measure for the relief of pain. The neurophysiology responsible for the effectiveness of the operation is dependent on the fact that, though the pain perception pathways are still intact, elimination of the function of the frontal lobes results in only brief recognition and insignificant recollection of the unpleasant stimuli. In the successful case in which lobotomy is performed for relief of pain, the now secondary effects of elimination of worry and apprehension have distinct advantages to our way of thinking. The procedure is often carried out unilaterally, but the favorable results under these circumstances are much less frequent. Though the risk of personality change and incontinence is greater in the bilateral operation, the vastly improved results justify this in the minds of most neurosurgeons who have had significant experience with this work. Of course, again, if the tumor has already eliminated sphincter control, this latter concern is of no consequence. Under normal conditions the operative mortality associated with any of the neurosurgical procedures outlined is not great. A sound understanding between the physician or surgeon and the patient's family and the patient himself is essential prior to the undertaking of any of these procedures. With the outcome of the disease inevitable, even rather major risks are justified if the prospect of relief of pain is reasonably good. Pharlllacologic Control of Pain
Control of cancer pain by the use of analgesics and narcotics requires several considerations in the mind of the prescribing physician. First, drugs are not an efficient substitute for the other effective methods of therapy when these are applicable. Nerve block by alcohol injection or surgical interruption is incomparably superior when localized somatic or visceral pain is amenable to such an attack. Secondly, the minimal pharmacologic weapon should be used that will afford pain relief and still leave the patient in a functional condition. He should be maintained as a self-sustaining and productive unit for as long as possible. He should not be narcotized into a stupor when coal tar derivatives suffice for pain relief. This is meant in the metaphorical sense of the "tack and sledgehammer" connotation. Codeine may be added when the salicylates fail to maintain comfort. When the time comes for the more potent narcotics, there is a wide range of choice. Dilaudid in graded doses of 1.6 to 6 mg. 0/40 to 1/10 grain) every three to four hours, orally or by hypodermic, is an effective narcotic
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Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
with potent analgesic abilit.y and less sedative effect and fewer side reactions than morphine or Demerol. Finally one come" to the use of morphine or Demerol in gradually increa8ing d08e8, without limit, until relief is obt.ained. If t.he pain intensifie8, or if tolerance to t.he narcotic8 develop8, one must 8teadily increa8e the dosage level. There i" no rea:mn to withhold t.he drug because of fear of addiction. The disease is progressive and withdrawal will not become a problem. As tolerance to the analgesic effects of morphine develops there is also tolerance to the other depressing effects. One need not fear undue respiratory depression from doses even larger than G5 to 120 mg. Cl to 2 grains). Doses of morphine or Demerol that just achieve pain relief do not unduly depress respiration. The likelihood of addiction is minimized if the dose of narcotic drugs i" adjusted to that which will give pain relief but will be short of inducing narcotic "leep or euphoria. This is of importance if removal of the painful tumor masses or surgical interruption of pain pathways is to be done to remove the source of pain. Numerous other synthetic narcotic drugs are available as substitutes for morphine. We have not been able to establish their superiority. They may be tried if one feels that the side effects are leSt-; disturbing in the individual case. The nausea and vomiting that is sometimes seen with narcotics, especially morphine, is usually a rcsult of overdosage. One usually finds that if the dose is decreased to the level that just gives pain relief the nausea disappears and the patient still has the benefit of the analgesia. Thorazine, ] 0 to 15 mg. three times a day, is a useful adjunct to narcotic therapy. There is substantial potentiation of the narcotic effect by the Thorazine so that the dose of morphine or Demerol need be only one-third to one-half that previously employed. There is also the additional factor of the ereation of a mild euphoric state and altered reaction pattern to pain that is useful. 30 N. Michigan Avenue Chicago 2, Illinois
IF
were an early symptom in developing cancer, a great many more patients would be cured of this disease than at present. Unfortunately, by the time pain becomes a clinical feature in the course of the disease, the patient usually is in an incurable condition and only palliative measures are possible. Two aspects of this situation deserve emphasis, namely the statistical enormity of the problem and the numerous variations in therapy that are today available to the thoughtful physician. With the exception of cancer of the skin and lip, considerably less than half of the other malignant tumors are eliminated by present day treatment methods. There are many reasons why modern surgery and irradiation are not utilized more effectively to their full potential, but the fact remains that probably three-fourths of patients with internal cancer succumb to their disease. There is, therefore, a vast number of such patients who need help from the time a stage of incurability becomes apparent until their demise. Too often physicians apply the fact of the eventual hopelessneHs of the situation to all aspects of the patient's care and the result is neglect of the patient and dereliction of their duty as physicians. Why we will give meticulous attention to the incurable cardiac or hypertensive patient with congestive failure, and consign the equally affiicted cancer patient to his own devices, remains a mystery, but this is too frequently the case. PAIN
RELIEF OF PAIN BY TUMOR CONTROL
Control of pain due to cancer may be achieved in two ways. These are, first, treatment which eliminates the tumor or causes temporary regres-
* Associate Professor of Surgery and Director of the Tumor Clinic, University of Illinois College of Medicine, Chicago; Director of the Tumor Clinic, St. Francis Hospital, Evanston, Illinois.
** Assistant Professor of Surgery, University of Illinois College of Medicine; Director of the Tumor Clinic, Presbyterian Hospital, Chicago. t Chief of Anesthesiology, St. Francis Hospital, Evanston, Illinois. 51
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Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
sion, and second, treatment which obtunds sensory perception of pain or eliminates specific pain pathways. Direct attack on the tumor is the most logical and usually results in the greatest good to the patient, but is applicable to fewer patients, and those only in the earlier phase of incurability. Palliation by tumor control is based on a fundamental concept which frequently is either poorly understood or not appreciated at all. This concept is the fact that almost all malignant tumors have fairly definite behavior patterns of growth and spread, and that the uncontrolled natural history of a given tumor is predictable within reasonably broad limits. Too many physicians tend to attribute all possibilities of spread to all cancers, whereas this is simply not true of the great majority of malignant tumors. As an example, the squamous cell carcinomas, whether of the lip, tongue, or cervix of the uterus, confine their metastatic activities almost entirely to the lymphatic pathways, and metastases from such tumors are usually found, even at autopsy, to be confined to the regional lymph nodes draining the anatomic site of origin. The most frequent cause of death in women with cancer of the cervix is about an ounce of cancer surrounding each lower ureter, with consequent renal failure. In patients with oral cancer, the usual causes of death are hemorrhage, inanition, and airway obstruction. In contrast, adenocarcinomas of the stomach or colon metastasize by invasion of veins in addition to lymphatics, so that not only the local regional nodes but also the liver, via the portal venous system, will become involved. The principal conditions of unpredictability occur with malignant melanomas, or with carcinomas in the lung, primary or secondary, where they may invade pulmonary veins and thus be spread by way of the systemic arterial circulation. Aside from these situations and a few other rare neoplastic entities, it is practically possible in many instances to channel the inevitable progression of an incurable cancer in a manner that minimizes or, rarely, eliminates pain. The ultimate goal in partial or palliative tumor control is to arrange the patient's demise as a chemical death from hepatic, renal or pulmonary failure. This ponderoussounding remark is more realistic than it may appear if one stops to think of the thousands of palliative gastric or colon resections that are performed each year in the face of liver metastases, in order to avoid death from obstruction. The only curative treatment of cancer today is by destructive methods, either surgery or irradiation. These are crude approaches to a phenomenon which is essentially a chemical aberration of the fundamental biological processes within the cell. For the time being these two modalities are our only effective therapy, but most of these therapeutic attempts are palliative in effect, even though curative in intent. Therefore the majority of cancer patients become problems in palliation eventually. When the chips are down, and incurability is clinically apparent, con-
Relief of Pain in Cancer Patients
53
siderable assistance still may be given the patient in the way of maintaining an active and productive life, let alone a relatively supportable existence. It is our function as physicians to see that these patients receive all of the available "breaks." PALLIATIVE SURGERY
Surgical relief of the patient with incurable cancer fits into two categories, namely, relief of obstruction, and amputation or adequate excision of painful or ulcerated tumor masses. Relief of Obstruction
Obstruction due to cancer is usually amenable to surgical relief, even if only palliative, in the following areas: (1) airway, (2) swallowing, (3) gastric, (4) small bowel, (5) colon, (6) biliary tract and (7) urinary tract. The only painful obstructions are those involving the small bowel, colon and urinary tract, especially the latter when there is infection above the point of obstruction. It is not the purpose of this discussion to detail the surgical procedures available. Suffice it to say that the indications for operation are usually clear. It should be emphasized that excisional surgery is almost always preferable to by-passing procedures. For example, palliative resection of the esophagus with restoration of continuity is better than gastrostomy, and certainly resection of the colon with end-to-end anastomosis is far better than leaving a patient with a loop colostomy because of the finding of liver metastases, if the primary lesion is at all resectable. This is not to compare the pleasures of deglutition with those of defecation, as the point should be obvious. In the case of cancer obstructing the extrahepatic biliary tract, every effort should be made to shunt bile flow internally if the tumor is inoperable. If the patient's life expectancy is a year or more, a Roux-Y choledochojejunostomy is the procedure of choice, otherwise an end-toside anastomosis using the gallbladder may be done. The urinary tract may be rearranged in many ways to give relief from obstruction or fistulas. Palliative surgery is definitely worthwhile, as the authors have repeatedly seen patients live two and three years with liver metastases, leading a comfortable and productive life for most of that time, if the primary cancer has been removed. CASE 1. Mrs. M.F., aged 41 years, had an excision of a large right ovarian tumor at another hospital at the age of 32. This was reported as benign. Five years later, at the age of 37, a carcinoma of the left ovary was excised. This recurred and heavy doses of 200 kv. radiation were utilized through the lower abdomen. She was re-explored 2 years later and an inoperable tumor mass was found in the pelvis obstructing the sigmoid colon. A loop colostomy was performed. Urinary tract infection followed and the left kidney ceased to function. One year later a spontaneous urinary fistula occurred through the colostomy. This added to her misery but was a life-saving accident. The patient was having constant back and pelvic pain and became bedridden.
54
Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
She was admitted on the senior authors' service in Apl'iI1954, 9 years after her first operation. A large fixed tumor mass filled the pelvis and was palpable through the abdomen. The abdominal wall was fibrosed and telangiectatic flOm irradiation. A constantly draining wet colostomy macerated the already damaged and infected skin. After preparation with transfusions and the administration of needed electrolytes and fluids, exploratory laparotomy was performed. It was possible to remove the tumor mass by resecting the sigmoid colon, left ureter, upper vagina, a loop of incorporated small bowel, pelvic peritoneum, and a part of the abdominal wall. There was no cancer apparent elsewhere in the abdomen. The left ureter was simply ligated. The right ureter was found to be double, and its lower portion was destroyed by the tumor mass, which also had destroyed a portion of the sigmoid colon, thus creating the urinary fistula back through the colostomy. It was possible to exteriorize the intact rectosigmoid, and the double right ureter was implanted into the descending colon which was brought out in apposition to the exteriorized lower colon, thus creating a second double-barreled wet colostomy, in the same spot as the original one, which had to be excised in removing the tumor mass. The patient recovered without undue difficulty. Eight weeks later the patient was again hospitalized and the colostomy closed by utilizing as an artificial bladder the loop of the descending colon which ended as the upper barrel of the colostomy. This was done by sectioning the colon proximal to the ureteral implant and closing this end, dropping this closed end free into the abdomen, carrying the ureteral implantation with it. The open distal end of this isolated loop was left in position through the abdominal wall as the external opening of the artificial bladder. The rectosigmoid was then freed and anastomosed to the proximal descending colon, thus restoring intestinal continuity. The patient has normal bowel function, has gained 50 pounds in weight, controls the artificial bladder easily with a Rutzen bag, and is apparently well more than 14 months later.
This case history illustrates an extreme but worthwhile attempt at surgical palliation of a patient with cancer causing pain, and obstructing both the large bowel and upper urinary tracts. Permanent cure is exceedingly unlikely. From the patient's standpoint, she is happy with the result. Effective palliation in cancer patients is very much the same problem as that of the prisoner condemned to capital punishment. Will he be content to hang tomorrow, or will he make all appeals possible, to postpone the inevitable until a year from tomorrow? Alllputations or Radical Excision of Large TUlllor Masses
Sarcomas and melanomas of the extremities, and occasionally metastatic cancer, may become huge ulcerating tumor masses which not only produce a useless extremity but cause severe pain, which may become intolerable. The consequent paralysis, infection and hemorrhage make amputation reasonable in such situations even in the presence of distant metastatic disease precluding cure. This is equally true of tumors involving the abdominal or chest walls, particularly if they are low grade or well differentiated and radioresistant lesions. Deliberate palliative breast amputation, when disseminated disease is present, is not as frequent a decision as the high incidence of breast cancer might lead one
Relief of Pain
~in
Cancer Patients
to expect. The highly anaplastic breast cancers with local lymphat.ie permeation, "infiammatory" carcinoma, are often worsened by surgical intervention, whereas the low grade, well differentiated breast cancer" are susceptible to considerable control by irradiation or endocrine management. When this latter lesion is first seen in an advanced and incurable condition, the patient is usually an unintelligent individual whose disease is one of long standing and active neglect. Such a clinical setting may occasionally be benefited by local wide excisional surgery, usually undertaken after maximum irradiation has failed of local control, but where systemic disease may otherwise allow further longevity. PALLIATIVE IRRADIATION
For practical purposes, the curative use of radiotherapy is confined to treatment of surface lesions or intracavitary irradiation of cancer of the upper respiratory tract and uterus. Present day and future developments in supervoltage ranges may replace surgical measures for lesions of the esophagus and lung, but for the time being the most frequent use of radiotherapy is in the palliation of incurable cancer. Irradiation, in its various modalities, is an extremely useful tool for this purpose. Radiation is most effective when used to treat the more radiosensitive tumors such as the lymphomas, including Hodgkin's disease, and the amenable carcinomas such as metastatic mammary or papillary thyroid cancer, and some ovarian cancers. Almost all malignant tumors are radiosensitive to some degree, as compared to their normal tissue derivation. However, as an extreme example, irradiation of a low grade chondrosarcoma or a chordoma is so ineffective that more damage will be done to soft tissues than will be sustained by the tumor. In such a case the law of diminishing returns will be on the negative side, past the decimal point. Localized painful metastatic deposits of relatively radioHensitive cancer are very effectively treated by irradiation. Breast cancer metm;tatic to the spine may often be controlled for years in this manner. Pathological fractures often may be forestalled or prevented for years by irradiation, and it is stupid and inhumane to allow a patient to develop a pathological fracture of the femoral neck by withholding radiation because of hepatic or pulmonary metastases. When disseminated carcinoma becomes too widespread for efficient radiotherapy, then its use should be confined to the most critical or painful areas, or chemotherapy substituted. Both chemotherapy and irradiation of too great a surface area have a common hazard, namely aplastic anemia from bone marrow destruction. CASE H. ;\1rs. P.C. was first seen in Sept8mber 1953 at the age of 72, with a history of having had a right mdieal mastec:tomy in 1940 for breast c:anc:er. In 1949 she developed left pleural effusion whieh revealed c:ancer cells on aspiration and pulmonary metastases on x-ray. She was treated with androgens and mul-
.56
Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
tiple thoracenteses with some slight effect for 10 months. She was then placed on stilbestrol by mouth and all clinical symptoms and findin:~s promptly dis'lppeared. When first seen by us in September 1953 there were several painful subcutaneous nodules of cancer; in particular, one large one over the left parotid gland. Biopsy revealed adenocarcinoma consistent with mammary cancer. Because of imminent facial nerve paralysis, this parotid lesion was treated with xradiation and it has apparently been obliterated. The patient was again given stilbestrol, 6 mg. per day by mouth, since she had had no medication for 15 months previously. The other skin lesions ceased to grow but did not regress. The patient remained well until October 1954, when she developed severe dysphagia and lost 20 pounds in weight. X-ray examination disclosed obstruction of the midmediastinal thoracic esophagus, and planograms showed mediastinal node enlargement in this area. Esophagoscopy and bronchoscopy both produced biopsy evidence of carcinoma consistent with a mammary origin. X-radiation to the site of obstruction produced complete relief of symptoms and clearing of xray signs, and avoided a tracheoesophageal fistula. In March 1955 the skin lesions began to grow and 2 or 3 ulcerated. These lesions, widely separated and located singly in the upper thighs, buttocks, abdominal and chest walls, and neck, were probably a result of spread from pulmonary foci through the systemic arterial system. These skin deposits, being released from endocrine control, were treated individually with single massive doses of 120 kv. x-radiation, and have since healed, leaving only radiation scars in their place. Recent studies by fluoroscopy and esophagoscopy reveal no cancer at the site of obstruction, and the patient is clinically well for the time being. She has been living with incurable breast cancer for 15 years, and apparently will continue to do so for some time. At the moment there is no evidence of clinical activity of her disease. CHEMOTHERAPY
Control of cancer by systemic drug therapy is, without question, the hope and trend for the future of cancer therapy. In the last few years a glimmer of light has been brought to this field so that at least a start has been made. No curative chemotherapy has yet been achieved, but effeetive palliation is now possible in several clinical situations. The nitrogen mustards used intravenously in doses of 0.1 mg.jkg. of body weight will temporarily control systemic and disseminated Hodgkin's disease, lymphosarcoma to a lesser extent, and leukemias still less. Use of this drug should be confined to advanced cases, radiation-fast, and untreatable otherwise. The most practical program of administration is a five day course, giving the dose by rapid intravenous drip in saline, at night, to a patient so narcotized that he sleeps through the transient acute reaction and nausea, and thus can maintain his nutrition during the day. The bone marrow must be watched daily, and for some time after a course of therapy, by peripheral blood studies, particularly white cell and platelet counts. While the very radiosensitive neoplasms mentioned are the most sensitive to the radiomimetic action of the nitrogen mustards, bronchogenic carcinoma is also susceptible to appreciable palliation by intravenous use of the drug. No other epithelial cancers seemed to respond, but when the explanation of this paradox became clear, namely that the lung
Relief of Pain in Cancer Patients
57
first receives the full concentration of the drug before systemic dilution, it led to the intra-arterial use of nitrogen mustard. This method, used selectively, is another effective means of causing major tumor regression. It is utilized by cannulating the arterial supply of a tumor area with a polythene cannula for long-continued multiple injections over a period of days or weeks, or for single massive injections, which may be made through the hepatic artery for treatment of liver metastases. Apparently all tumors will respond to a sufficient concentration of the drug in about the same scale of sensitivity as they respond to radiation. If liver metastases are to be treated, two points are pertinent: first a single massive dose, by catheterization or needle injection, is relatively safe because the drug is detoxified by the hepatic parenchyma; second, the injection must be intra-arterial because metastatic cancer in liver develops its blood supply from the arterial side, and because of the danger of portal vein thrombosis. Other drugs are being used, such as aminopterin, methopterin (useful in acute leukemias), TEM (triethylene melamine) and TEPA (triethylene phosphor amide). These can be given by mouth, and TEM has been referred to as the "oral mustard." They are effective to a slight degree in disseminated cancer, more so in the lymphomas, but are so toxic that it is fortunate that they were not available to the Borgias. Consideration of p32 and 1'31 is not within the scope of this discussion except to say that painful metastatic thyroid cancer, and even pathological fractures, may be relieved and even made to heal in occasional instances by the use of radioactive iodine. The most thought-provoking aspect is that, rarely, metastatic thyroid cancer which does not take up radioiodine may be led to re-differentiate towards the normal, as judged histopathologically, to a functional state where the tumor cells may pick up radioiodine in quantities sufficient to destroy themselves. This is effected by removing all normal thyroid tissue, preferably surgically, so that a state of physiologic need is created. We have had two patients with pathological fractures of the femur due to thyroid cancer whose lesions were made to heal by such a program. ENDOCRINE MODIFICATION
Since Huggins first demonstrated that the course of human prostatic cancer could be modified by changing its endocrine milieu, great advances have been made in the palliative control of two of the most common malignant neoplasms that affect the human race, namely carcinoma of the breast and of the prostate gland. The treatment of prostatic cancer by castration and/or estrogenic hormone is so well known and standardized that it needs no elaboration here, except to note that the disease is usually painful because of metastases to the spine and pelvis. Endocrine relief is by far the most effective treatment available. In the case of breast cancer, it should be emphasized that endocrine
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Danely P. Slaughter, Harry W. SouthwZ:ck, Harold L. Harris
management in no way replaces the standard curative methods of radical mastectomy, with or without supplemental x-radiation. Neither does it replace palliative irradiation of localized l"(~current disease occurring in the 50 per cent or more of pati(~ntH in whom the original treatment failed to cure. Endocrine modification should be utilized, therefore, only in the patient with advanced, disseminated and otherwise untreatable breast cancer. For such a patient the following outline probably exemplifies most current thought on the subject. Patients Under 55 Years of Age
Castration. About 30 per cent of breast cancers in premenopausal women show some regression after castration. This regression may occasionally be dramatic, and the effect may last from ten months to, rarely, two or three years. Logically, oophorectomy is the most effective means of castration, but it is likely that roentgen dosage, in the order of two or three times that required to stop the menses, may be just aH effective. The question of routine prophylactic castration of the premenopausal patient with breast cancer is a philosophical one, because if all cancer cells have been destroyed by the definitive curative attempt, there is no need to add an artificial menopause to the patient's problemH. If the tumor recurs, castration will probably be just as effective, and no more so, than it would have been originally. Androgens. Male sex hormone is effective in about 50 per cent of premenopausal women and is particularly useful in the treatment of painful bone metastases. Objective x-ray evidence of recalcification of osteolytic metastases occurs in 40 per cent or more, and the effect lasts from ten months to two years or more. Dosage is usually 100 mg. of testoHterone propionate three times weekly, and usually masculinization to some degree must be apparent for tumor effect. Small or temporizing doses have little or no effect. If cancer regression is to occur it will usually be apparent within three to six weekH. Prophylactic use of androgens is either a waste of time or harmful. The Hide effects of steroids of this character are not only annoying but can be dangerous because of their salt and water retention effect. Borderline cardiac and hypertensive patients can be placed in acute congeHtive failure by the latent edema, evident from the sudden weight gain all patients undergo when androgens are given. Androgenie therapy Hhould generally be used with or following castration. If tumor regression occurs, after three or four months the patient may be given methyltestosterone, 25 mg./day by mouth, for maintenance. Adrenalectomy. Adrenalectomy is the last chance to afford an incurable breast cancer patient another year or more of life. This operation is still under clinical investigation, and is not to be considered routine. We as physicians confront certain moral hazards in placing patients in
Relief of Pain in Cancer Patients
59
the daily jeopardy of possible Addisonian crisis, for problematical temporary relief. About 40 per cent of our patients have had objective regression of metastatic breast cancer, with considerably more pain relief than this would indicate. The effect is sometimes dramatic, with bedridden addicts out mowing their lawns in a few weeks, but the tumor control averages only 10 to 18 months. Some patients are still doing well after three years, however. Tlw opera1jon is a major procedure, but so far we have had no surgical fatality in over 75 cases. No patient over 61 years of age has shown any benefit, and the pattern is beginning to emerge that we have objective regression in over 60 per cent of the group whose breast cancer started at the time of or before the menopause, whose disease is of long standing and therefore relatively low grade, and who have improved temporarily by castration and androgenic management. The finding of metastatic mammary cancer in almost three-fourths of the excised ovaries and adrenals in our series explains in part why it takes so long for many terminal breast cancer patients to die. Patients 55 to 65 Years of Age
This is the equivocal group whose breast cancer is least likely to respond to endocrine management. The patients are best handled like those in the younger age groups, but respond less frequently and to a lesser degree. Estrogenic hormone is dangerous in this group and in all younger patients, since female sex hormones often stimulate the tumor to more rapid growth. Patients Over 65 Years of Age
Painful metastatic and recurrent breast cancer at this age, when other treatment has failed, is most likely to regress on estrogenic therapy. The usual treatment is from 6 to 15 mg. of stilbestrol in divided doses daily by mouth. This is more than physiological dosage and, of course, will activate the endometrium in the female with an intact uterus, a condition more common in rural than urban populations. The older the patient, the more likely it is that her breast cancer will respond to estrogens. ·When regression does occur it is frequently more rapid and profound than occurs with androgens in the younger age groups, and it is our impression that soft tissue lesion,; are somewhat more affected. CONTROL Of' PAIN BY SENSORY
BI~OCK
Neurosurgical Potentialities
It must be emphasized that, though our material has been categorized for simplicity of presentation, the various modalities offered for the relief of pain are not mutually exclusive. As a matter of fact, it is often highly advantageous to combine the various pharmacologic and surgical approaches to the problem. This is particularly important where neuro-
60
Danely P. Slaughter, Harry W. Southwiclc, Harold L. Harris
surgical procedures are under consideration. There is often the tendency to avoid "another operation" when the narcotic limits have not been extended to the point of negligible return. The effectiveness of the neurosurgical operation is often greatest, however, and the magnitude less, when relief is obtained before the pain pattern has become fixed. Peripheral Nerve Section. If the pain is sufficiently localized, it is occasionally possible to find isolated specific nerves which may be divided by a relatively minor procedure. Of course, if the tumor mass producing the pain is solitary and relatively easily resected, its surgical removal is indicated as mentioned earlier. However, in the face of widespread disease, a simpler attack may be in order. This is particularly true where intercostal nerves are involved. Section of these often gives complete relief; the number of nerves involved is predetermined by procaine infiltration about the specific segments. Care should be exercised to reach above and below the specific lesion, not only for the immediate relief but to allow for the inevitable local extension of the existing disease. Dorsal Rhizotomy. Dorsal rhizotomy is also limited in its application to those patients who have only a few dermatomes involved, either unilaterally or bilaterally. When it is reasonable to believe that the disease process is not a rapidly progressive one, the intradural division of the sensory nerve roots is quite effective. The advantage of this procedure over section of a peripheral nerve with motor components is obvious. Pain from tumors of the head and neck area can often be controlled by trigeminal rhizotomy; this is particularly advantageous when it is the result of certain slowly growing tumors such as some parotid carcinomas. Frequently, the extent of the lesion in the head and neck is such that section of the glossopharyngeal nerve as well as the sensory roots of the upper cervical plexus is necessary to obtain complete pain relief. Chordotomy. In the anterolateral quadrant of the spinal cord, between the dentate ligament and the anterior root, lie the nerve fibers which carry the sensation of pain centrally. Concern is often expressed over the possibility of limitation of motor function following chordotomy, but this complication is seldom encountered. The large crossed pyramidal tract lies posteriorly, and if the plane of division is kept anterior to the landmark of the dentate ligament, the chance of such damage is negligible. Much more extensive areas can be rendered anesthetic by this procedure than by dorsal rhizotomy. A patient with unilateral pain below the level of the arm is an ideal candidate, and relief is obtained in a high percentage of the cases without modification of use of the leg or sphincter power. When pain is bilateral, the results are not as satisfactory. The pain itself can be controlled, but the complications previously mentioned are all too frequent. Of course, if the tumor itself has already rendered the patient incontinent and bedridden, it is a "free go" as far as pain relief is concerned, and the side effects would be no cause for concern.
Relief of Pain in Cancer Patients
61
Lobotomy. Frontal lobotomy, as described by Freeman and Watts, has its primary therapeutic effect focused on certain psychiatric disorders. However, as an incidental finding, it was found that the occasional patient who had both a psychiatric as well as a painful disease was relieved of both in successful cases. Since then, the procedure has been adopted as one other specific measure for the relief of pain. The neurophysiology responsible for the effectiveness of the operation is dependent on the fact that, though the pain perception pathways are still intact, elimination of the function of the frontal lobes results in only brief recognition and insignificant recollection of the unpleasant stimuli. In the successful case in which lobotomy is performed for relief of pain, the now secondary effects of elimination of worry and apprehension have distinct advantages to our way of thinking. The procedure is often carried out unilaterally, but the favorable results under these circumstances are much less frequent. Though the risk of personality change and incontinence is greater in the bilateral operation, the vastly improved results justify this in the minds of most neurosurgeons who have had significant experience with this work. Of course, again, if the tumor has already eliminated sphincter control, this latter concern is of no consequence. Under normal conditions the operative mortality associated with any of the neurosurgical procedures outlined is not great. A sound understanding between the physician or surgeon and the patient's family and the patient himself is essential prior to the undertaking of any of these procedures. With the outcome of the disease inevitable, even rather major risks are justified if the prospect of relief of pain is reasonably good. Pharlllacologic Control of Pain
Control of cancer pain by the use of analgesics and narcotics requires several considerations in the mind of the prescribing physician. First, drugs are not an efficient substitute for the other effective methods of therapy when these are applicable. Nerve block by alcohol injection or surgical interruption is incomparably superior when localized somatic or visceral pain is amenable to such an attack. Secondly, the minimal pharmacologic weapon should be used that will afford pain relief and still leave the patient in a functional condition. He should be maintained as a self-sustaining and productive unit for as long as possible. He should not be narcotized into a stupor when coal tar derivatives suffice for pain relief. This is meant in the metaphorical sense of the "tack and sledgehammer" connotation. Codeine may be added when the salicylates fail to maintain comfort. When the time comes for the more potent narcotics, there is a wide range of choice. Dilaudid in graded doses of 1.6 to 6 mg. 0/40 to 1/10 grain) every three to four hours, orally or by hypodermic, is an effective narcotic
62
Danely P. Slaughter, Harry W. Southwick, Harold L. Harris
with potent analgesic abilit.y and less sedative effect and fewer side reactions than morphine or Demerol. Finally one come" to the use of morphine or Demerol in gradually increa8ing d08e8, without limit, until relief is obt.ained. If t.he pain intensifie8, or if tolerance to t.he narcotic8 develop8, one must 8teadily increa8e the dosage level. There i" no rea:mn to withhold t.he drug because of fear of addiction. The disease is progressive and withdrawal will not become a problem. As tolerance to the analgesic effects of morphine develops there is also tolerance to the other depressing effects. One need not fear undue respiratory depression from doses even larger than G5 to 120 mg. Cl to 2 grains). Doses of morphine or Demerol that just achieve pain relief do not unduly depress respiration. The likelihood of addiction is minimized if the dose of narcotic drugs i" adjusted to that which will give pain relief but will be short of inducing narcotic "leep or euphoria. This is of importance if removal of the painful tumor masses or surgical interruption of pain pathways is to be done to remove the source of pain. Numerous other synthetic narcotic drugs are available as substitutes for morphine. We have not been able to establish their superiority. They may be tried if one feels that the side effects are leSt-; disturbing in the individual case. The nausea and vomiting that is sometimes seen with narcotics, especially morphine, is usually a rcsult of overdosage. One usually finds that if the dose is decreased to the level that just gives pain relief the nausea disappears and the patient still has the benefit of the analgesia. Thorazine, ] 0 to 15 mg. three times a day, is a useful adjunct to narcotic therapy. There is substantial potentiation of the narcotic effect by the Thorazine so that the dose of morphine or Demerol need be only one-third to one-half that previously employed. There is also the additional factor of the ereation of a mild euphoric state and altered reaction pattern to pain that is useful. 30 N. Michigan Avenue Chicago 2, Illinois