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Medical Problems in the Management of Cancer
Medical Prohlems in the Management of Cancer DANIEL LASZLO, M.D. * HERTA SPENCER, M.D. **
THE management of the patient with cancer is one of the most serious medical problems of our time. Until recently it was in the hands of the surgeon and oi the radiotherapist. It attracted but few medical men, and many more are needed. 'rhe contribution of the general physician to the problem can be considerable in prevention, diagnosis, follow-up examinations and research. There is no other group better qualified to discover and treat the many medical problems which occur in a patient with cancer and which are entirely unrelated to the malignant disease. Why is this field less attractive than many other fields of medicine? Is it because of the apparent hopeless prognosis, or is it because cancer is assumed to be invariably associated with persistent suffering? Is it because of lack of effective therapeutic tools to treat or manage these patients? Is it because of the discouragingly slow progress in cancer research? The purpose of this presentation is to illustrate, by examples, that a more positive attitude and more active participation on our part may offer definite advantages to the patient and satisfaction to the physician. It is fully recognized that the internist ana the general practitioner are important members of a team engaged in research, in the diagnosis and in the treatment of patients with cancer. PREVENTION
Notable progress has been made in the preventive field of cancer. A larg;e number of carcinogenic substances have been isolated and obtained in chemically pure states. Their mode of action in inducing cancer From the Division of Neoplastic Diseases, Montefiore Hosp1·tal, New York City. * Chief of D1·vision of N eoplastic Diseases, M ontefiore Hospital. ** Adjunct Attending Physician, Division of N eoplastic Diseases, M ontefiore Hospital.
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has been carefully studied. "fhe recognition of the carcinogenic properties of such chemicals has led to the introduction of effective measures to minimize occupational and industrial hazards. The role of radiant energy (solar, x-ray, radium, radioactive isotopes) in carcinogenesis has been carefully studied and protective measures against its harmful effects have been suggested. The early treatment of chronic inflammatory lesions, of chronic irritations, and the removal of benign tumors which may represent precursors of malignancy, have been stressed. EARLY DETECTION
The importance of early diagnosis of cancer has been emphasized in numerous studies. The delay in the diagIlosis of cancer is still considerable. It is estimated that the five year survival rates of cancer patients could be doubled, even with our inadequate present-day methods of treatment, if cancer could be detected earlier.! The time Jag between the onset of symptoms and institution of treatment is in part due to the patient's delay in seeking medical advice and in part to the inability of the physician to recognize the symptoms promptly and thereby arrive at an early, correct diagnosis. Expansion of educational programs for the lay public and more active teaching programs of neoplastic diseases In medical schools in conjunction with postgraduate courses may help to remedy this serious delay. As long as no reliable screening tests are available for the early detection of cancer, such programs represent the only means to shorten the time lag in arriving at the diagnosis. PROBLEMS IN THE MANAGEMENT OF PATIENTS WITH CANCER
The Diagnosis of Cancer Has Been Established; Is the Patient Potentially Curable?
The boundaries of potential "cure" by surgery have been considerably widened during the past few decades. Better pre- and postoperative care, recognition of the importance of fluid and electrolyte balance, the use of antibiotics ~nd vitamins have helped to promote this advance. The improvement of surgical techniques and of anesthesia have enlarged the field of indications for major surgical procedures which are now being performed with relative safety even in old and debilitated patients. This is illustrated by two examples: CASE I. An 88 year old man (M.H. 51240) was well until 6 months prior to admission, when he began to have anorexia, weakness, weight loss, and alternating constipation and diarrhea. No melena or blood streaking of the stool was noted. On physical examination the patient was in good condition; blood pressure 155/70; the heart was normal. There was marked pulmonary emphysema; the
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liver was smooth and was palpable two finger breadths below the right costal Inargin. A large cauliflower mass was felt in the rectum, 2 cm. from the anus. A biopsy of this lesion revealed adenocarcinoma. At exploration under general anesthesia no local extension or metastases were found and an abdominoperineal resection was performed. Postoperatively, the patient did well except for a transient episode of auricular fibrillation and local wound infection. He was discharged to a nursing home. CASE II. An 82 year old woman (M.H. 54833) had noted progressive, painless swelling of the abdomen for 6 months. On admission a large, hard, freely movable mass was felt filling the entire abdomen; ascites and a left pleural effusion were present. The clinical impression was fibroma of the ovary, Meig's syndrome. X-rays of the osseous structures revealed partial collapse of D 11 and several poorly defined areas of decreased density of the skull. In spite of these findings, suggestive of bone metastases, but also consistent with senile osteoporosis, an exploratory laparotomy was performed. Under general anesthesia a large fibroma of the right ovary was removed; 1000 cc. of straw-colored fluid was present in the abdomen. The patient tolerated the operative procedure well. Postoperatively, the pleural effusion disappeared gradually. The patient was discharged in good condition.
Medical contraindications to major surgery are rare. One case description illustrates the problem: CASE Ill. A 28 year old woman (M.H. 50759) was admitted for the fourth time in congestive heart failure. The patient had rheumatic heart disease since the age of 7. For the past 5 years she had frequent bouts of congestive heart failure in spite of continuous treatment. Several pulmonary infarcts were diagnosed clinically in the past 2 years. Activity of rheumatic heart disease \vas suspected 2 years prior to this admission. A mass in the right breast was present for the past 2 years which had gradually increased rin ~size. Because of her cardiac status and because of her poor prognosis for life, curative surgery was deemed inadvisable. A shnple mastectomy, to be followed by radiotherapy was contemplated. Even this procedure could not be tolerated by the patient. On the operating table she developed pulmonary edema, and therefore only a local excision of the tUffior was feasible. This was followed by radiotherapy.
It is recognized that the operability cannot be defined in rigid terms. Tumors considered to be inoperable by one surgeon may be successfully removed by another even months or years later. This aspect has been previously discussed in another publication. 2 It was pointed out that inflammatory changes accompanying neoplastic growths can easily be mistaken for evidence of local tumor spread. Enlarged lymph nodes regional to the primary site may be due to chronic lymphadenitis. Only biopsy and histological confirmation should be considered as proof of the spread of malignancy. Metastases are usually diagnosed on the basis of indirect evidence which at times may be erroneous. Roentgenographic changes of the osseous structures such as compression fractures of vertebrae may be due to osteoporosis or to previous trauma. Central nervous system manifestations such as personality changes, epileptiform seizures,
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localizing neurological signs and involvement of cranial n~rves may not be proof of metastases,but may be manifestations of other diseases such as degenerative vascular disease so frequently encountered in the older age group. From these considerations it follows that radical surgery should be carried out unless metastases have been proved. A few more patients would thereby be salvaged. Should we fail to "cure" the patient, at least better palliation may be accomplished. This approach is also indicated because the removal of the primary tumor may prevent numerous complications which may occur later: bleeding, secondary infections, or obstruction of vital structures. Cases to illustrate the pitfalls leading to the assumption of local spread of the tumor or of metastases have been previously described. 2 Follow-up examinations of patients in whom radical surgery was performed is most important. These examinations should be closely spaced especially during the first postoperative year, the period of highest incidence of local recurrences and of distant metastases. The internist and general practitioner can contribute greatly to the early recognition of such spread. With their participation, local recurrences may be discovered early and the patient may be subjected to a second radical procedure. An occasional single metastatic focus may be discovered and removed and thereby a possible cure or at least palliation may be achieved. s Their aid in the differentiation of nonmalignant complications occurring in patients who had a neoplasm is important. It is a common error to attribute every sign and symptom to recurrent neoplasms in such patients. The omission of proper treatment for non-neoplastic conditions mistaken for recurrent neoplastic growths is indeed serious. An example of the difficulties encountered in the differential diagnosis is given: CASE IV. A 65 year old man (M.H. 42262) was admitted for chronic care. One year prior to admission an abdominoperineal resection was performed for carcinoma of the rectum. On admission, no clinical evidence of local spread or distant metastases was found. In the hospital the patient had an episode of fainting and melena. A diagnosis of a bleeding duodenal ulcer was made and a transthoracic vagotomy was performed. The patient did well postoperatively. Six months later there was no x-ray evidence of the duodenal ulcer. One year later the patient suddenly developed severe generalized abdominal pain, muscular spasm and rebound tenderness. There was no elevation of temperature, the white blood count was 16,200. No free air was seen under the diaphragm by x-rays. However, the small intestines were dilated and fluid levels were present. The impression was that this patient had intestinal obstruction with peritonitis, possibly secondary to intussusception. On exploration, the abdomen was filled with foul smelling, sanguineous fluid. Strangulation and gangrene of the small intestine was found in the sac of a ventral incisional hernia at the site of the colostomy. Ten inches of gangrenous bowel was resected. However, the patient expired 2 days later. The postmortem examination re-
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vealed acute hemorrhagic infarction of the upper jejunum and necrosis of the greater part of the ileum secondary to torsion of the mesentery. The duodenal ulcer was healed. A single mesenteric lymph node was involved by tumor metastases.
This patient was referred to this hospital for recurrent rectal neoplasm. The abdominal pain, bloody stools and extreme weakness could have been ascribed to this cause. However; the source of the bleeding was found to be a duodenal ulcer. A second noncancerous complication of an acute surgical abdomen occurred: a strangulated hernia and massive gangrene of the small intestine. Errors in Diagnosing Incurable Cancer When No Cancer Was Present Within the large group of "incurables" is hidden a small, yet by no means insignificant, group of potentially salvageable patients, in whom the diagnosis of incurability was made in error. Such cases are encountered even in large medical centers and probably many more could be found in areas poorly provided with medical facilities. A number of such instances have been previously described. 2 The errors are usually attributable to the omission of important diagnostic procedures, e.g., to misinterpret gross findings on exploratory operation rather than to correctly interpret surgical specimens by microscopic examinations: to omit endoscopies or to fail to remove tissues through endoscopic instruments, or to rely on roentgenograms rather than to explore. It is evident that an untreated lung abscess mistaken for bronchogenic neoplasm, diverticulosis for cancer of the colon, or pernicious anemia for gastric neoplasm can be as fatal as cancer. On the other hand, rehabilitation of such patients, once the corrected diagnosis has been established, is most gratifying. The following example further illustrates the chain of errors which can lead to the assumption of advanced metastatic cancer when a potentially curable noncancerous disease is present: CASE V. A 57 year old man (M.H. 53295) was admitted with a diagnosis of cancer of the lung with cerebral metastases. Changes of personality were noted 1 ~'2 years prior to admission; the patient also had several convulsive seizures. A right hemiplegia, clubbing of the fingernails and toenails, pain in the left chest and intermittent nonproductive cough were present for 6 months. The patient had a weight loss of 20 pounds in the past year. There was no previous history of hypertension. Several courses of antibiotics were given in the past for upper respiratory and for urinary tract infections. The patient was previously hospitalized at another institution for urinary retention caused by an enlarged middle lobe of the prostate. On admission, the patient had a right hemiparesis, was aphasic, had crying and laughing spells; blood pressure 130/40; the temperature was normal. The heart was enlarged to the left, a double aortic murmur was audible. The liver was tender, extended three finger breadths below the right costal margin. There
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was an indwelling catheter in the urinary bladder. X-ray of the chest showed a questionable left hilar mass. Because of recurrent episodes of urinary retention and infection the urinary obstruction was relieved by suprapubic cystotomy. Postoperatively, the patient did well fo'r 5 days when he suddenly developed restlessness and cyanosis and expired. Postmortem examination revealed enlargement of the heart, healed mitral and aortic rheumatic valvulitis, and severe involvement of the aorta by ulcerative and vegetative lesions of subacute bacterial endocarditis. There was no cancer of the lung. Only dilatation of the pulmonary arteries was present. The erroneous diagnosis of cancer of the lung with cerebral metastases was apparently based on the presence 9f a questioI).able mass in the lung on x-ray, on personality changes, the right hemiplegia, chest pain, cough, clubbing and weight loss. A more careful examination of the heart might have pointed toward the diagnosis of rheumatic heart disease and superimposed bacterial endocarditis earlier. Elevation of temperature which so frequently accompanies this disease may have been masked by previous courses of antibiotics. ADVANCED CANCER
Duration of Illness
Data on the average duration of metastatic disease secondary to a specific primary site and those secondary to all sites are available.' The average duration of the metastatic phase of cancer is estimated to be 1.6 years. However, wide fluctuations around this average should deter one from making statements as to the duration of life for anyone patient. It seems that the malignant growth is not a continuous geometrical progression of cell mult.iplication without any defense reaction on the part of the host. Although no authenticated cases of complete, spontaneous regression of cancer are reported in the recent literature, numerous wellsubstantiated observations on the fluctuant and prolonged course of cancer are on record. A feeling of well-being and the ability to perform daily activities may be preserved for months or years of such remissions. Examples of remissions in patients with advanced cancer who received no, or minimal treatment are mentioned. CASE VI. A 61 year old man (MH 41486) was admitted in October~ 1946 for pain in the buttocks with radiation down the posterior aspects of both legs, urinary frequency and constipation. On admission, the only abnormalities were tenderness of the lumbosacral spine and absence of the left ankle jerk.. Laboratory data and roentgenograms were normal. A lumbar puncture was performed which revealed a normal pressure and normal manometries; the fluid was bloody, prot~ins 141 mg. per 100 cc. The fluid obtained on cysternal puncture was clear, protein content 68 mg. per 100 cc. A cysternal myelogram showed obstruction of the pantopaque column between L5 and 81. A laminectomy was perforlued and a large encapsulated intradural tumor was removed. The histological diagnosis was metastatic carcinoma, primary site unknown, possibly of gastrointestinal or prostatic origin. An exhaustive search failed to reveal the location of the primary tumor. Postoperatively, the urinary and bowel symptoms harl subsided.
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Follow-up examinations were essentially negative up to the present day, 6 years after a metastatic site had been proved. Because of urinary incontinence and cystitis a myelogram was done in 1951. It revealed no block. A transurethral prostatectomy was performed in June 1952; tissue examination revealed only benign hypertrophy of the prostate. ' CASE VI. A 46 year old man (M.H. 42488) had intermittent upper abdominal pain since 1943. An exploratory laparotomy in 1944 revealed a pancreatic tumor with involvement of the regional lymph nodes and of the omentum. Postoperatively, the patient was well for the next 3 years. Because of an episode of hematemesis, fever, anemia, a 32 pound weight loss, and x-ray evidence of extrinsic pressure upon the stomach, he was explored for the second time in 1947. An enlarged nodular liver was found. One of the nodules revealed on histologic examination a malignant tumor of either pancreatic or hepatic origin. On a high caloric, high protein and high vitamin diet the patient showed a surprisiJ;lg recovery for the second time, with a weight gain of 19 pounds in 4 weeks. He was then well for 17'2 years during which time a course of radiation therapy was given to the epigastrium without change in the size of this mass. Two years after the second exploration, weakness, weight loss and spiking fever recurred. With supportive therapy alone, remarkable improvement again occurred. The final phase of his illness began 6 months later and he died 7 years after the onset of the first symptoms. On postmortem examination, hepatoma with metastases to the body and tail of the pancreas was diagnosed.
This case history illustrates 'well the long duration of illness and the fluctuant course with three "spontaneous" remissions, one of which lasted for three years. In each of these, a desperately ill patient changed into a seemingly well person. Pain and Its Treatment
The opinion appears to prevail in the medical profession that severe pain requiring potent analgesics and narcotics frequently occurs in advanced cancer. !-i"ortunately, this does not appear to be the case. Fear and anxiety, the patient's need for more attention from the family or from the physician are frequently mistaken for expressions of pain. Reassurance and an unhesitating approach in presenting a plan of management to the patient are well known potent "remedies," and probably the clue to success of many medical quackeries. Since superficial psychotherapy as practiced by physicians without psychiatric training is often helpful, actual psychiatric treatment is expected to be of more value. Unfortunately, the potential therapeutic usefulness of this tool has barely been explored. A survey conducted in this institution on approximately 300 patients with advanced cancer disclosed that over 50 per cent of patients who had received analgesics for long periods of time could be adequately controlled by plaeebo medication.;) rI'his survey implies that analgesics should be prescribed only after an adequate trial of placebos (tablets at first, to be follo,ved by injectiol:S, if tablets are ineffective). If placebos
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fail, the weakest analgesic should be tried first. Nerve block and topically applied anesthetics are helpful at times. Neurosurgical procedures such as chordotomy or lobotomy are helpful but are only rarely necessary for the alleviation of pain. By careful evaluation of the patient's need for analgesics, untoward side reactions may be minimized. Drowsiness, anorexia, nausea, pernicious vomiting, decreased fluid and food intake often initiate a vicious cycle leading to prerenal azotemia. Many instances of unexpected improvement of a moribund patient are attributable to the discontinuation of narcotics, while their continuation would only further aggravate the already existing electrolyte imbalance and dehydration. CA!'E VIII. A 58 year old woman (M.H. 45173) with carcinoma of the breast and widespread osteolytic metastases was admitted for "severe" pain in the left hip. She had received the following pain medication in sequence over a period of 26 months: morphine sulfate 8 mg. (~~ grain) for 10 months; codeine 32 mg. (~'2 grain) and aspirin 0.65 gr. (10 grains) for 3 months; codeine 65 mg. (1 grain) and 2 APe tablets, for 2 months; Demerol 100 mg. for 8 months; methadone 10 mg. for 3 months. These drugs were given every 4 hours. On admission her last medication, i.e. injections of methadone, 10 mg. every 4 hours, were continued for 5 days. She then received placebo injections with equally good pain relief for the next 106 days.
Nutrition and Hydration
Anorexia, weight loss, cachexia, hypoproteinemia and multiple vitamin deficiencies are frequently seen in patients with advanced cancer. Therefore, a diet adequate in calories and in essential nutrients should be provided. With the lack of appetite as the limiting factor, this is a difficult task. It can be only partially solved. by frequent servings of concentrated, easily digestible and attractively prepared food. Occasionally supplementation with oral or parenteral protein or vitamin concentrates is necessary. A metabolic equilibrium and even partial repletion can thus be accomplished, since the absorption and utilization of nutrients are not majorly impaired. Restriction of caloric intake and elimination of certain essential amino acids or of vitamins from the diet was shown to decrease the incidence of the development of tumors in susceptible animals. 6 , 7 However, once the tumor was already established, its growth was not majorly influenced by dietary restrictions. Similarly, no evidence is available that certain food components accelerate malignant growths in man. Therefore, the advice of certain physicians to restrict the. quantity of food or certain food components in the treatment of cancer seems to lack experimental evidence. Dehydration due to limitations of fluid intake or due to excessive losses by vomiting or diarrhea occurs frequently. Measurements of fluid intake and urinary output may help to prevent such complications.
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Determination of serum electrolytes (sodium, potassium, chlorides) and of blood urea nitrogen are helpful guides in the prevention and treatment of electrolyte imbalance and of prerenal azotemia. Gastrointestinal irritation secondary to analgesic medication is not infrequently the etiologic factor causing these disturbances. Ambulation
The deleterious effect of prolonged immobilization upon circulation and metabolism are well documented in the recent literature. They can be produced experimentally even in healthy normal persons who are immobilized for some weeks. s They develop much more rapidly in patients who are already debilitated by chronic disease. Circulatory asthenia, tendency to thrombosis and embolism, negative nitrogen balance, osteoporosis, increased tendency to fracture, formation of renal stones and hypercalcemic crises can be caused by immobilization and, indeed, are complications which occur quite frequently in immobilized patients with advanced cancer. Therefore, it seems that the risks of mobilization are in many instances less than those of continued immobilization. It is not surprising then that pathologic fractures occur less often in carefully ambulated patients with extensive bone disease than in those who were immobilized. If ambulation can be accomplished only by palliative surgical procedures it seems that such methods are well worthwhile. For example, the treatment of pathologic fractures by intramedullary nailing may be preferable to the conservative treatment of plaster cast or Buck's extension. 9 Home Care
Should a patient with advanced terminal cancer be hospitalized or can he be cared for at home? Although it is recognized that these patients require a great deal of medical attention, they may not require the highly specialized facilities of a hospital. The advantages of keeping a patient in his home surroundings need not be emphasized. In order to test whether adequate care could be given to these patients in their home, a home care service was instituted at this hospital in 1947. 10 It has proved its value in providing continuous medical care. With the aid of a visiting nurse numerous therapeutic procedures, such as blood transfusions, infusions and removal of fluid from body cavities, have been performed in the patient's home. Members of the family are taught to aid in the nursing care, to administer certain medications and to prepare adequate diets. Physiotherapy and occupational therapy are given to these patients. These and many other measures can be applied under the supervision of the family physician. They aid in making life comfortable for the patient, psychologically and physically.
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To illustrate the rehabilitation of a bedridden patient in her home, a case is described: . CASE IX. A 22 year old wonlan (M.H. 42089) had a laminectomy in 1941; an extradural giant cell tunlor was removed. One year later a bone graft was applied for collapse of the third lumbar vertebra. Three years postoperatively, a large right upper quadrant mass was diagnosed as giant cell turnor by needle biopsy. On admission (March 1947) the patient was bedridden; there was weakness and atrophy of the right leg and absence of the knee and ankle jerks. An attempt was made to ambulate the patient again. A Knight-Taylor brace was supplied and the patient was discharged to the Home Care Departlnent. While at home, leg braces were supplied. A visiting nurse supervised her daily in getting in and out of bed. She received physiotherapy, e.g. massage, walking exercises and treatments to increase the range of motion of her legs. Within 4 lnonths she had learned to walk with crutches. She was then taught to walk stairs and within another 5 months she was able to go downstaris. She was discharged from the Home Care Program after 1 year (1948). Since that time she has been attending the Outpatient Clinic of this hospital. She has been employed for the past 2 years and is able to travel back and forth to work. Recently (July 1952) she received deep x-ray therapy to a destructive lesion of the right femur. This patient, now 33 years of age, has had a proven giant cell tumor for the past 11 years. Metastases are present in bones and soft tissue. She was completely incapacitated and bedridden 5 years ago. Conservative Ineasures such as orthopedic appliances, occupational therapy and physiotherapy, given to her while at home, have restored her to a fairly normal, comforable life. She has been rehabilitated to a degree that she is able to work and travel daily.
Palliative Treatment
Three rp.ethods of palliative treatment are available: medical (e.g. chemotherapy and hormonal therapy); radiation (e.g. deep x-rays, radium and radioisotopes), and surgical palliation. a. M edical Treatment. The remarkable beneficial effects of castration and/or estrogenic therapy for advanced prostatic carcinoma stimulated the therapeutic trial of a great variety of hormonal and chemotherapeutic agents. The results so obtained will be discussed in a separate clinic in this issue. Subjective improvement was induced by female or male sex hormones in the majority of cases of metastatic breast carcinoma. However, objective evidence of improvement was noted only in 20 to 30 per cent of the cases. ll Whether the life span of these patients is significantly prolonged by such agents is as yet uncertain. Careful selection and supervision of cases under hormonal treatment are essential. Serious complications such as congestive heart failure due to sodium retention and hypercalcemic crisis due to an increased rate of demineralization have occasionally occurred. 12 Estrogens are being used in postmenopausal patients only, as occasionally rapid progression of the neoplastic process was noted in
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Mar~agemer~t of
Cancer
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premenopausal patients who received this treatment. Orchidectomy and/or estrogenic treatment appear to have a definite place in the treatment of advanced carcinoma of the breast in males. l3 Folic acid antagonists, urethane, nitrogen mustard and related compounds, ACTH and cortisone appear to have limited value in the treatment of patients with advanced carcinoma. Their value in the treatment of Hodgkin's disease, lymphosarcoma, leukemia and multiple myeloma will be discussed elsewhere. b. Deep X-ray Therapy, Radium and Radioisotopes. The palliative value of these agents is well recognized. R,elief of pain, regression of large radiosensitive tumors, relief of pressure symptoms, and recalcification of osteolytic bone lesions have been observed in many instances. Radiation castration in patients with metastatic carcinoma of the breast has resulted in temporary improvement in about 20 per cent of the cases. Radiation to metastatic brain tumors has occasionally resulted in relief of subjective and objective pressure symptoms. Radioiodine is useful in the diagnosis and treatment of thyroid carcinoma. Occasionally the thyroid origin of metastases can be discovered by the specific uptake of 1131 • Decrease of bone pain and apparent slowing down of the growth rate of these tumors have been occasionally accomplished by the administration of therapeutic doses of radioiodine. The surgical removal or the radioiodinedestruction of the thyroid gland occasionally induces or increases the uptake of radioiodine in metastases. 14 The use of p32 in the treatment of malignant lymphoma and leukemia will be discussed in a separate chapter. The intracavitary use of radio-gold Hi and of other radioisotopes 16 for the treatment of effusions caused by cancer appears to promise results which may be superior to those obtained by deep x-ray therapy. c. Surgical Treatment. Surgical palliative procedures require discussion because of the reluctance of the physician to consider these methods as too drastic in patients who cannot be cured. It is of course desirable to perform palliative surgical procedures at the time of primary surgery or exploration if curative surgery is not feasible. These procedures have been brought into disrepute to some extent because they were performed at a late and frequently the last stage of the disease. This delay accounts for the high mortality and low rate of palliation, e.g. gastrostomies performed on a highly debilitated patient can be of only little avail. On the other hand, the value of procedures such as enterostomies, urological procedures to relieve obstruction, laminectomies to relieve spinal cord compression and paraplegia is unquestionable when performed early in the course of such complications. They can afford prolongation of life and comfort to the patient. Numerous such instances have been reported. An example to
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illustrate the value of early surgical palliation is described: CASE X. A 58 year old woman (M.H. 45173) had a radical mastectomy followed by radiotherapy for a carcinolna of the breast. Three years later \videspread bone lnetastases were first noted. A year and a half later she was admitted because of inability to move her legs and urinary and fecal incontinence of 4 weeks' duration. On admission paraplegia, secondary to spinal cord compression at the level of D7 was diagnosed. X-rays showed destruction of the ninth dorsal vertebra. A decompression laminectomy was performed. A thick plaque of brownish tumor was removed from the dura underlying D7. Postoperatively radiotherapy was given to this area. Sixteen days after the laminectomy she was able to move both legs and urinary and bowel control became normal. The motion of the legs improved steadily and 5 months postoperatively she was able to use a walker and she was discharged to the Home Care Department, with almost perfect motion of both legs.
This example illustrates the value of a neurosurgical procedure performed in a patient with widespread osteolytic bone involvement. A five year palliation of a serious complication-paraplegia with loss of sphincter control-was achieved although the operative procedure was carried out as late as four weeks after the onset of symptoms. The Management of Nonmalignant Diseases in Cancer Patients
It is all too often that complications arising in patients who at one time had or still have a neoplasm are misinterpreted as progression of the malignant disease. The difficulties in differentiating two unrelated diseases are at times great indeed-yet it has to be attempted. Innumerable are the cases of errors; they are regrettable because they preclude treatment. They do not appear in morbidity or mortality statistics because they are masked by the assumed diagnosis of cancer. Congestive heart failure, pneumonitis, meningitis, jaundice due to hepatitis or to gallstone obstruction, peritonitis due to appendicitis or to perforation of a viscus, and intestinal obstruction secondary to adhesions or incarcerated hernias are but a few examples which have been labelled cancer. CASE XI. A 36 year old woman (M.H. 41914) with an inoperable carcinoma of the breast and extensive local, osseous and visceral spread developed signs and symptoms of obstructive jaundice with noncolicky epigastric pain. The differential diagnosis was intra- or extrahepatic obstructive jaundice due to tumor versus obstruction of the common duct by a gallstone. Past history revealed a cholecystectomy for gallstones, 10 years previously. On exploration stones were removed from the common duct. The patient was discharged 2 \veeks postoperatively relieved of jaundice. She died 16 months later. CASE XII. A 53 year old man (M.H. 50847) had an exploratory thoracotomy for a "pleural effusion" which was discovered on routine exalnination. The diagnosis of mesothelioma was made on thoracotomy. Ten days postoperatively abdominal pain and distention occurred which improved and recurred over a
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period of 4 weeks. At one time fecal vomiting was noted. The impression was that the patient had intestinal obstruction secondary to cancer implants. The patient died 6 weeks after the onset of abdominal symptoms. On postmortem examination a constricting fibrous band was found near the umbilicus causing kinking and distention of the jejunum and ileum. Multiple small intestinal ulcerations and a perforation of the ileum with fecal peritonitis were present. Past history revealed that the patient had an appendectomy 5 years previously. A few small tumor nodules were present on the parietal peritoneum, in no apparent relation to the constricting band.
Complications of cancer therapy are all too often mistaken for·progression of the disease. In all probability the majority of such errors remain unnoticed since the fatality is attributed to cancer. Many such cases have been observed. Two examples are briefly mentioned. CASE XIII. A 68 year old woman (M.H. 52230) was admitted to the hospital with a diagnosis of papillary adenocarcinoma of the uterine body. On examination an asymptomatic adhesive pericarditis with calcification was discovered and treatment with intrauterine radium implantation and deep x-ray therapy was instituted. Five months after the completion of this treatment, fever, pain in the left lower quadrant, pyuria and a mass in the left parametrium developed. The diagnosis was: extension of the tumor with secondary infection and block of the left ureter with pyelonephritis. Because of weakness in the left lower extremity the diagnosis of an epidural abscess was also considered. However, there were no sensory changes and the spinal fluid examination was negative. Ten days later the spinal fluid was cloudy and a block was demonstrated. The patient expired. At autopsy no cancer was found. However, severe radiation fibrosis of bladder, uterus and sigmoid colon, an abscess between L5 and 81 with liquefaction of the intervertebral disk and an epidural abscess with purulent meningitis were found.
This case well illustrates the difficulties in differentiating progression of cancer from sequelae of treatment-in this case postirradiation injury with secondary infection. CASE XIV. A 76 year old man (M.H. 52607) was admitted to the hospital for rectal bleeding, with a diagnosis of advanced neoplasm. Five months previously a carcinoma of the sigmoid colon was removed, an end-ta-end anastomosis and a palliative cecostomy were performed. Postoperatively a fecal fistula developed. When admitted here he was extremely cachectic, had a cecostomy and a fecal fistula. However, there was no evidence of tumor recurrence. Therefore, a transverse colostomy was performed and the fecal fistula and the cecostomy were closed. In a subsequent operation the bowel continuity was re-established by a colostomy closure. Th~ patient showed a remarkably rapid recovery, gained weight and is well 1;'2 years postoperatively.
CONCLUSIONS
Early diagnosis and improved management of cancer patients need not await tomorrow's discoveries. These can be accomplished with the present-day methods, by more and better trained general physicians,
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and by a change in the attitude toward the management of this disease. Some of the deficiencies encountered in the care of these patients have been described and suggested methods for improvement are briefly emphasized. In the prevention of cancer, environmental factors should be carefully evaluated as possible carcinogenic agents; precancerous lesions should be promptly treated. The causes for the delay in diagnosis have been dealt with extensively in numerous publications. Full and early use of the dia.gnostic tools in periodic examinations of asymptomatic persons and especially of those with symptoms could remedy this serious delay. Radical surgery is occasionally refused because of advanced age; or because of medical complications; or because of the assumption of local spread of the tumor or distant metastases. With the advances in surgery a.nd anesthesia, age alone is rarely a contraindication to surgery; with proper treatment of medical complications and modern preoperative care, patients previously considered unsuitable for surgery can now be operated on with safety. Errors have been made by assuming local spread of the tumor or distant metastases when none was present. These errors could be minimized by careful and critical evaluation of the evidence upon which this assumption has been based. Should the tumor not be resectable, palliative surgical procedures should be carried out at the time of exploration: better palliation with less operative risks results therefrom. Patients with advanced cancer require considerable medical attention as is true in any chronic disease. Problems of ambulation, nutrition, hydration, the evaluation of the patient's pain pattern and the selection of suitable analgesics require careful consideration. Palliative measures (radiotherapeutic, medical or surgical) when applied early and fully add to the comfort and prolong life of the patient. The differentiation of medical and surgical conditions entirely unrelated to the malignancy which the patient once had or still has is of major concern. There is no one better qualified to avoid these dangerous pitfalls than the general physician. It is safer to assume that complications are of nonmalignant nature unless proven otherwise. Such an attitude promotes a more active diagnostic and therapeutic regimen. Continuity of medical care of the cancer patient is of paramount importance. A closely knit single team of the family physician and specialist is the best guarantee of this continuity'. All too often a patient is transferred from an acute to a chronic hospital, then to a home for incurables. His morale is thereby lowered~ his confidence destroyed and the efficiency of his treatment greatly impaired. Whether to disclose or to withhold the true diagnosis and prognosis
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from the patient has been widely discussed. No general rule seems applicable to all patients. However, for the majority, no benefit seems to be derived from such disclosures: a grave and at times unbearable burden is put on the patient when he is least able to carry it and needs the most psychological and physical support. The fear associated with this diagnosis in the minds of the public is so great that its disclosure often induces an acute depression and, not infrequently, suicidal attempts have been made. Man lives by hope. Truly rare are the reasons which justify its deprivation. Sharing the responsibility ,vith the family, and presenting the patient with a concise, unhesitating plan of management, usually avoids difficulties. lVIembers of the family often request information on the probable duration of the illness. It is safer to assume that the patient will be one of the exceptions who will be able to carry on his daily activities longer than expected. ~ While an inotensive and relentless search for the "great discovery" must go on) optimal use of all methods now available should help to alleviate today's pressing problem. REFERENCES 1. Steiner, P. E.: An Evaluation of the Cancer Problelu. Cancer Research 12: 455, 1952. 2. Laszlo, D., Calmer, M. L., Silver, G. B. and Standard, S.: Errors in Diagnosis and Management of Cancer. Ann. lnt. Med. 33: 670, 1950. 3. Flavell, G.: Solitary Cerebral Metastases from Bronchial Carcinoma. Brit. Med. J. S: 736, 1949. 4. Terminal Care for Cancer Patients. Survey of the Central Service for the Chronically III of the Institute of Medicine of Chicago. Chicago, Illinois, 1950. 5. Spencer, H. and others: Relief of Pain and Suffering Due to Cancer by Means of Placebo Therapy. In preparation. 6. Tannenbaum, A.: Genesis and Growth of Tumors; Effects of Caloric R,estrictions per se. Cancer Research 2: 460 and 468, 1942. 7. White, J., Mider, B. G. and Heston, W. E.: Effect of Amino Acids on the Induction of Leukemia in Mice. J. N at. Cancer Inst. 4: 409, 1944. 8. Deitrick, J. E., Whedon, G. D. and Shorr, E. E.: Effects of Immobilization upon Various Metabolic and Physiologic Functions of Normal Men. Am. J. Med. 4.: 3, 1948. 9. Altman, H.: Intramedullary Nailing of Pathological Impending and Actual Fractures of Long Bones. Bull. Hospital of Bone and Joint Diseases 13 (2): 239 (Oct.) 1952. 10. llome Care. Origin, Organizatinn and Present Status of the I~xtramural Program of Montefiore IIospital. }{eport of M ontefiore Hospital, New York City, 1949. 11. Proceedings of the First Conference on Steroid Hormones and 1\Iammary Cancer: The Therapeutic Trials Committee of the Council on Pharmacy and Chemistry of The American Medical Association, Chicago, 1949. 12. Laszlo, D. and others: Effect of Testosterone on Patients with Bone lVletastases. J.A.M.A. 148: 1502) 1952. 13. Treves, N.: Castration as a Therapeutic Measure in Cancer of the Male Breast. Cancer 2: 191, 1949.
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14. Seidlin, S. M., Rossrnan, T., Oshry, E. and Siegel, E.: Radio-iodine Therapy '. ~ of Metastases from Carcinoma of the Thyroid. Six Years Progress lleport. J. Clin. Endocrinol. 9: 1122, 1949. 15. Goldie, H. and Hahn, P. H.: Distribution and Effect of Colloidal Radio-active Gold in Peritoneal Fluid Containing Free Sarcoma 37 -Cells. Proc. Soc. Exp. BioI. Med. 74: 638, 1950. 16. Lewin, R. and others: Effect of La 139 _ and La 14 °-chloride on Mice Bearing Ehrlich Ascites Turnors. Cancer Research 12: 278, 1951.
THE management of the patient with cancer is one of the most serious medical problems of our time. Until recently it was in the hands of the surgeon and oi the radiotherapist. It attracted but few medical men, and many more are needed. 'rhe contribution of the general physician to the problem can be considerable in prevention, diagnosis, follow-up examinations and research. There is no other group better qualified to discover and treat the many medical problems which occur in a patient with cancer and which are entirely unrelated to the malignant disease. Why is this field less attractive than many other fields of medicine? Is it because of the apparent hopeless prognosis, or is it because cancer is assumed to be invariably associated with persistent suffering? Is it because of lack of effective therapeutic tools to treat or manage these patients? Is it because of the discouragingly slow progress in cancer research? The purpose of this presentation is to illustrate, by examples, that a more positive attitude and more active participation on our part may offer definite advantages to the patient and satisfaction to the physician. It is fully recognized that the internist ana the general practitioner are important members of a team engaged in research, in the diagnosis and in the treatment of patients with cancer. PREVENTION
Notable progress has been made in the preventive field of cancer. A larg;e number of carcinogenic substances have been isolated and obtained in chemically pure states. Their mode of action in inducing cancer From the Division of Neoplastic Diseases, Montefiore Hosp1·tal, New York City. * Chief of D1·vision of N eoplastic Diseases, M ontefiore Hospital. ** Adjunct Attending Physician, Division of N eoplastic Diseases, M ontefiore Hospital.
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has been carefully studied. "fhe recognition of the carcinogenic properties of such chemicals has led to the introduction of effective measures to minimize occupational and industrial hazards. The role of radiant energy (solar, x-ray, radium, radioactive isotopes) in carcinogenesis has been carefully studied and protective measures against its harmful effects have been suggested. The early treatment of chronic inflammatory lesions, of chronic irritations, and the removal of benign tumors which may represent precursors of malignancy, have been stressed. EARLY DETECTION
The importance of early diagnosis of cancer has been emphasized in numerous studies. The delay in the diagIlosis of cancer is still considerable. It is estimated that the five year survival rates of cancer patients could be doubled, even with our inadequate present-day methods of treatment, if cancer could be detected earlier.! The time Jag between the onset of symptoms and institution of treatment is in part due to the patient's delay in seeking medical advice and in part to the inability of the physician to recognize the symptoms promptly and thereby arrive at an early, correct diagnosis. Expansion of educational programs for the lay public and more active teaching programs of neoplastic diseases In medical schools in conjunction with postgraduate courses may help to remedy this serious delay. As long as no reliable screening tests are available for the early detection of cancer, such programs represent the only means to shorten the time lag in arriving at the diagnosis. PROBLEMS IN THE MANAGEMENT OF PATIENTS WITH CANCER
The Diagnosis of Cancer Has Been Established; Is the Patient Potentially Curable?
The boundaries of potential "cure" by surgery have been considerably widened during the past few decades. Better pre- and postoperative care, recognition of the importance of fluid and electrolyte balance, the use of antibiotics ~nd vitamins have helped to promote this advance. The improvement of surgical techniques and of anesthesia have enlarged the field of indications for major surgical procedures which are now being performed with relative safety even in old and debilitated patients. This is illustrated by two examples: CASE I. An 88 year old man (M.H. 51240) was well until 6 months prior to admission, when he began to have anorexia, weakness, weight loss, and alternating constipation and diarrhea. No melena or blood streaking of the stool was noted. On physical examination the patient was in good condition; blood pressure 155/70; the heart was normal. There was marked pulmonary emphysema; the
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liver was smooth and was palpable two finger breadths below the right costal Inargin. A large cauliflower mass was felt in the rectum, 2 cm. from the anus. A biopsy of this lesion revealed adenocarcinoma. At exploration under general anesthesia no local extension or metastases were found and an abdominoperineal resection was performed. Postoperatively, the patient did well except for a transient episode of auricular fibrillation and local wound infection. He was discharged to a nursing home. CASE II. An 82 year old woman (M.H. 54833) had noted progressive, painless swelling of the abdomen for 6 months. On admission a large, hard, freely movable mass was felt filling the entire abdomen; ascites and a left pleural effusion were present. The clinical impression was fibroma of the ovary, Meig's syndrome. X-rays of the osseous structures revealed partial collapse of D 11 and several poorly defined areas of decreased density of the skull. In spite of these findings, suggestive of bone metastases, but also consistent with senile osteoporosis, an exploratory laparotomy was performed. Under general anesthesia a large fibroma of the right ovary was removed; 1000 cc. of straw-colored fluid was present in the abdomen. The patient tolerated the operative procedure well. Postoperatively, the pleural effusion disappeared gradually. The patient was discharged in good condition.
Medical contraindications to major surgery are rare. One case description illustrates the problem: CASE Ill. A 28 year old woman (M.H. 50759) was admitted for the fourth time in congestive heart failure. The patient had rheumatic heart disease since the age of 7. For the past 5 years she had frequent bouts of congestive heart failure in spite of continuous treatment. Several pulmonary infarcts were diagnosed clinically in the past 2 years. Activity of rheumatic heart disease \vas suspected 2 years prior to this admission. A mass in the right breast was present for the past 2 years which had gradually increased rin ~size. Because of her cardiac status and because of her poor prognosis for life, curative surgery was deemed inadvisable. A shnple mastectomy, to be followed by radiotherapy was contemplated. Even this procedure could not be tolerated by the patient. On the operating table she developed pulmonary edema, and therefore only a local excision of the tUffior was feasible. This was followed by radiotherapy.
It is recognized that the operability cannot be defined in rigid terms. Tumors considered to be inoperable by one surgeon may be successfully removed by another even months or years later. This aspect has been previously discussed in another publication. 2 It was pointed out that inflammatory changes accompanying neoplastic growths can easily be mistaken for evidence of local tumor spread. Enlarged lymph nodes regional to the primary site may be due to chronic lymphadenitis. Only biopsy and histological confirmation should be considered as proof of the spread of malignancy. Metastases are usually diagnosed on the basis of indirect evidence which at times may be erroneous. Roentgenographic changes of the osseous structures such as compression fractures of vertebrae may be due to osteoporosis or to previous trauma. Central nervous system manifestations such as personality changes, epileptiform seizures,
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localizing neurological signs and involvement of cranial n~rves may not be proof of metastases,but may be manifestations of other diseases such as degenerative vascular disease so frequently encountered in the older age group. From these considerations it follows that radical surgery should be carried out unless metastases have been proved. A few more patients would thereby be salvaged. Should we fail to "cure" the patient, at least better palliation may be accomplished. This approach is also indicated because the removal of the primary tumor may prevent numerous complications which may occur later: bleeding, secondary infections, or obstruction of vital structures. Cases to illustrate the pitfalls leading to the assumption of local spread of the tumor or of metastases have been previously described. 2 Follow-up examinations of patients in whom radical surgery was performed is most important. These examinations should be closely spaced especially during the first postoperative year, the period of highest incidence of local recurrences and of distant metastases. The internist and general practitioner can contribute greatly to the early recognition of such spread. With their participation, local recurrences may be discovered early and the patient may be subjected to a second radical procedure. An occasional single metastatic focus may be discovered and removed and thereby a possible cure or at least palliation may be achieved. s Their aid in the differentiation of nonmalignant complications occurring in patients who had a neoplasm is important. It is a common error to attribute every sign and symptom to recurrent neoplasms in such patients. The omission of proper treatment for non-neoplastic conditions mistaken for recurrent neoplastic growths is indeed serious. An example of the difficulties encountered in the differential diagnosis is given: CASE IV. A 65 year old man (M.H. 42262) was admitted for chronic care. One year prior to admission an abdominoperineal resection was performed for carcinoma of the rectum. On admission, no clinical evidence of local spread or distant metastases was found. In the hospital the patient had an episode of fainting and melena. A diagnosis of a bleeding duodenal ulcer was made and a transthoracic vagotomy was performed. The patient did well postoperatively. Six months later there was no x-ray evidence of the duodenal ulcer. One year later the patient suddenly developed severe generalized abdominal pain, muscular spasm and rebound tenderness. There was no elevation of temperature, the white blood count was 16,200. No free air was seen under the diaphragm by x-rays. However, the small intestines were dilated and fluid levels were present. The impression was that this patient had intestinal obstruction with peritonitis, possibly secondary to intussusception. On exploration, the abdomen was filled with foul smelling, sanguineous fluid. Strangulation and gangrene of the small intestine was found in the sac of a ventral incisional hernia at the site of the colostomy. Ten inches of gangrenous bowel was resected. However, the patient expired 2 days later. The postmortem examination re-
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vealed acute hemorrhagic infarction of the upper jejunum and necrosis of the greater part of the ileum secondary to torsion of the mesentery. The duodenal ulcer was healed. A single mesenteric lymph node was involved by tumor metastases.
This patient was referred to this hospital for recurrent rectal neoplasm. The abdominal pain, bloody stools and extreme weakness could have been ascribed to this cause. However; the source of the bleeding was found to be a duodenal ulcer. A second noncancerous complication of an acute surgical abdomen occurred: a strangulated hernia and massive gangrene of the small intestine. Errors in Diagnosing Incurable Cancer When No Cancer Was Present Within the large group of "incurables" is hidden a small, yet by no means insignificant, group of potentially salvageable patients, in whom the diagnosis of incurability was made in error. Such cases are encountered even in large medical centers and probably many more could be found in areas poorly provided with medical facilities. A number of such instances have been previously described. 2 The errors are usually attributable to the omission of important diagnostic procedures, e.g., to misinterpret gross findings on exploratory operation rather than to correctly interpret surgical specimens by microscopic examinations: to omit endoscopies or to fail to remove tissues through endoscopic instruments, or to rely on roentgenograms rather than to explore. It is evident that an untreated lung abscess mistaken for bronchogenic neoplasm, diverticulosis for cancer of the colon, or pernicious anemia for gastric neoplasm can be as fatal as cancer. On the other hand, rehabilitation of such patients, once the corrected diagnosis has been established, is most gratifying. The following example further illustrates the chain of errors which can lead to the assumption of advanced metastatic cancer when a potentially curable noncancerous disease is present: CASE V. A 57 year old man (M.H. 53295) was admitted with a diagnosis of cancer of the lung with cerebral metastases. Changes of personality were noted 1 ~'2 years prior to admission; the patient also had several convulsive seizures. A right hemiplegia, clubbing of the fingernails and toenails, pain in the left chest and intermittent nonproductive cough were present for 6 months. The patient had a weight loss of 20 pounds in the past year. There was no previous history of hypertension. Several courses of antibiotics were given in the past for upper respiratory and for urinary tract infections. The patient was previously hospitalized at another institution for urinary retention caused by an enlarged middle lobe of the prostate. On admission, the patient had a right hemiparesis, was aphasic, had crying and laughing spells; blood pressure 130/40; the temperature was normal. The heart was enlarged to the left, a double aortic murmur was audible. The liver was tender, extended three finger breadths below the right costal margin. There
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was an indwelling catheter in the urinary bladder. X-ray of the chest showed a questionable left hilar mass. Because of recurrent episodes of urinary retention and infection the urinary obstruction was relieved by suprapubic cystotomy. Postoperatively, the patient did well fo'r 5 days when he suddenly developed restlessness and cyanosis and expired. Postmortem examination revealed enlargement of the heart, healed mitral and aortic rheumatic valvulitis, and severe involvement of the aorta by ulcerative and vegetative lesions of subacute bacterial endocarditis. There was no cancer of the lung. Only dilatation of the pulmonary arteries was present. The erroneous diagnosis of cancer of the lung with cerebral metastases was apparently based on the presence 9f a questioI).able mass in the lung on x-ray, on personality changes, the right hemiplegia, chest pain, cough, clubbing and weight loss. A more careful examination of the heart might have pointed toward the diagnosis of rheumatic heart disease and superimposed bacterial endocarditis earlier. Elevation of temperature which so frequently accompanies this disease may have been masked by previous courses of antibiotics. ADVANCED CANCER
Duration of Illness
Data on the average duration of metastatic disease secondary to a specific primary site and those secondary to all sites are available.' The average duration of the metastatic phase of cancer is estimated to be 1.6 years. However, wide fluctuations around this average should deter one from making statements as to the duration of life for anyone patient. It seems that the malignant growth is not a continuous geometrical progression of cell mult.iplication without any defense reaction on the part of the host. Although no authenticated cases of complete, spontaneous regression of cancer are reported in the recent literature, numerous wellsubstantiated observations on the fluctuant and prolonged course of cancer are on record. A feeling of well-being and the ability to perform daily activities may be preserved for months or years of such remissions. Examples of remissions in patients with advanced cancer who received no, or minimal treatment are mentioned. CASE VI. A 61 year old man (MH 41486) was admitted in October~ 1946 for pain in the buttocks with radiation down the posterior aspects of both legs, urinary frequency and constipation. On admission, the only abnormalities were tenderness of the lumbosacral spine and absence of the left ankle jerk.. Laboratory data and roentgenograms were normal. A lumbar puncture was performed which revealed a normal pressure and normal manometries; the fluid was bloody, prot~ins 141 mg. per 100 cc. The fluid obtained on cysternal puncture was clear, protein content 68 mg. per 100 cc. A cysternal myelogram showed obstruction of the pantopaque column between L5 and 81. A laminectomy was perforlued and a large encapsulated intradural tumor was removed. The histological diagnosis was metastatic carcinoma, primary site unknown, possibly of gastrointestinal or prostatic origin. An exhaustive search failed to reveal the location of the primary tumor. Postoperatively, the urinary and bowel symptoms harl subsided.
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Follow-up examinations were essentially negative up to the present day, 6 years after a metastatic site had been proved. Because of urinary incontinence and cystitis a myelogram was done in 1951. It revealed no block. A transurethral prostatectomy was performed in June 1952; tissue examination revealed only benign hypertrophy of the prostate. ' CASE VI. A 46 year old man (M.H. 42488) had intermittent upper abdominal pain since 1943. An exploratory laparotomy in 1944 revealed a pancreatic tumor with involvement of the regional lymph nodes and of the omentum. Postoperatively, the patient was well for the next 3 years. Because of an episode of hematemesis, fever, anemia, a 32 pound weight loss, and x-ray evidence of extrinsic pressure upon the stomach, he was explored for the second time in 1947. An enlarged nodular liver was found. One of the nodules revealed on histologic examination a malignant tumor of either pancreatic or hepatic origin. On a high caloric, high protein and high vitamin diet the patient showed a surprisiJ;lg recovery for the second time, with a weight gain of 19 pounds in 4 weeks. He was then well for 17'2 years during which time a course of radiation therapy was given to the epigastrium without change in the size of this mass. Two years after the second exploration, weakness, weight loss and spiking fever recurred. With supportive therapy alone, remarkable improvement again occurred. The final phase of his illness began 6 months later and he died 7 years after the onset of the first symptoms. On postmortem examination, hepatoma with metastases to the body and tail of the pancreas was diagnosed.
This case history illustrates 'well the long duration of illness and the fluctuant course with three "spontaneous" remissions, one of which lasted for three years. In each of these, a desperately ill patient changed into a seemingly well person. Pain and Its Treatment
The opinion appears to prevail in the medical profession that severe pain requiring potent analgesics and narcotics frequently occurs in advanced cancer. !-i"ortunately, this does not appear to be the case. Fear and anxiety, the patient's need for more attention from the family or from the physician are frequently mistaken for expressions of pain. Reassurance and an unhesitating approach in presenting a plan of management to the patient are well known potent "remedies," and probably the clue to success of many medical quackeries. Since superficial psychotherapy as practiced by physicians without psychiatric training is often helpful, actual psychiatric treatment is expected to be of more value. Unfortunately, the potential therapeutic usefulness of this tool has barely been explored. A survey conducted in this institution on approximately 300 patients with advanced cancer disclosed that over 50 per cent of patients who had received analgesics for long periods of time could be adequately controlled by plaeebo medication.;) rI'his survey implies that analgesics should be prescribed only after an adequate trial of placebos (tablets at first, to be follo,ved by injectiol:S, if tablets are ineffective). If placebos
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fail, the weakest analgesic should be tried first. Nerve block and topically applied anesthetics are helpful at times. Neurosurgical procedures such as chordotomy or lobotomy are helpful but are only rarely necessary for the alleviation of pain. By careful evaluation of the patient's need for analgesics, untoward side reactions may be minimized. Drowsiness, anorexia, nausea, pernicious vomiting, decreased fluid and food intake often initiate a vicious cycle leading to prerenal azotemia. Many instances of unexpected improvement of a moribund patient are attributable to the discontinuation of narcotics, while their continuation would only further aggravate the already existing electrolyte imbalance and dehydration. CA!'E VIII. A 58 year old woman (M.H. 45173) with carcinoma of the breast and widespread osteolytic metastases was admitted for "severe" pain in the left hip. She had received the following pain medication in sequence over a period of 26 months: morphine sulfate 8 mg. (~~ grain) for 10 months; codeine 32 mg. (~'2 grain) and aspirin 0.65 gr. (10 grains) for 3 months; codeine 65 mg. (1 grain) and 2 APe tablets, for 2 months; Demerol 100 mg. for 8 months; methadone 10 mg. for 3 months. These drugs were given every 4 hours. On admission her last medication, i.e. injections of methadone, 10 mg. every 4 hours, were continued for 5 days. She then received placebo injections with equally good pain relief for the next 106 days.
Nutrition and Hydration
Anorexia, weight loss, cachexia, hypoproteinemia and multiple vitamin deficiencies are frequently seen in patients with advanced cancer. Therefore, a diet adequate in calories and in essential nutrients should be provided. With the lack of appetite as the limiting factor, this is a difficult task. It can be only partially solved. by frequent servings of concentrated, easily digestible and attractively prepared food. Occasionally supplementation with oral or parenteral protein or vitamin concentrates is necessary. A metabolic equilibrium and even partial repletion can thus be accomplished, since the absorption and utilization of nutrients are not majorly impaired. Restriction of caloric intake and elimination of certain essential amino acids or of vitamins from the diet was shown to decrease the incidence of the development of tumors in susceptible animals. 6 , 7 However, once the tumor was already established, its growth was not majorly influenced by dietary restrictions. Similarly, no evidence is available that certain food components accelerate malignant growths in man. Therefore, the advice of certain physicians to restrict the. quantity of food or certain food components in the treatment of cancer seems to lack experimental evidence. Dehydration due to limitations of fluid intake or due to excessive losses by vomiting or diarrhea occurs frequently. Measurements of fluid intake and urinary output may help to prevent such complications.
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Determination of serum electrolytes (sodium, potassium, chlorides) and of blood urea nitrogen are helpful guides in the prevention and treatment of electrolyte imbalance and of prerenal azotemia. Gastrointestinal irritation secondary to analgesic medication is not infrequently the etiologic factor causing these disturbances. Ambulation
The deleterious effect of prolonged immobilization upon circulation and metabolism are well documented in the recent literature. They can be produced experimentally even in healthy normal persons who are immobilized for some weeks. s They develop much more rapidly in patients who are already debilitated by chronic disease. Circulatory asthenia, tendency to thrombosis and embolism, negative nitrogen balance, osteoporosis, increased tendency to fracture, formation of renal stones and hypercalcemic crises can be caused by immobilization and, indeed, are complications which occur quite frequently in immobilized patients with advanced cancer. Therefore, it seems that the risks of mobilization are in many instances less than those of continued immobilization. It is not surprising then that pathologic fractures occur less often in carefully ambulated patients with extensive bone disease than in those who were immobilized. If ambulation can be accomplished only by palliative surgical procedures it seems that such methods are well worthwhile. For example, the treatment of pathologic fractures by intramedullary nailing may be preferable to the conservative treatment of plaster cast or Buck's extension. 9 Home Care
Should a patient with advanced terminal cancer be hospitalized or can he be cared for at home? Although it is recognized that these patients require a great deal of medical attention, they may not require the highly specialized facilities of a hospital. The advantages of keeping a patient in his home surroundings need not be emphasized. In order to test whether adequate care could be given to these patients in their home, a home care service was instituted at this hospital in 1947. 10 It has proved its value in providing continuous medical care. With the aid of a visiting nurse numerous therapeutic procedures, such as blood transfusions, infusions and removal of fluid from body cavities, have been performed in the patient's home. Members of the family are taught to aid in the nursing care, to administer certain medications and to prepare adequate diets. Physiotherapy and occupational therapy are given to these patients. These and many other measures can be applied under the supervision of the family physician. They aid in making life comfortable for the patient, psychologically and physically.
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To illustrate the rehabilitation of a bedridden patient in her home, a case is described: . CASE IX. A 22 year old wonlan (M.H. 42089) had a laminectomy in 1941; an extradural giant cell tunlor was removed. One year later a bone graft was applied for collapse of the third lumbar vertebra. Three years postoperatively, a large right upper quadrant mass was diagnosed as giant cell turnor by needle biopsy. On admission (March 1947) the patient was bedridden; there was weakness and atrophy of the right leg and absence of the knee and ankle jerks. An attempt was made to ambulate the patient again. A Knight-Taylor brace was supplied and the patient was discharged to the Home Care Departlnent. While at home, leg braces were supplied. A visiting nurse supervised her daily in getting in and out of bed. She received physiotherapy, e.g. massage, walking exercises and treatments to increase the range of motion of her legs. Within 4 lnonths she had learned to walk with crutches. She was then taught to walk stairs and within another 5 months she was able to go downstaris. She was discharged from the Home Care Program after 1 year (1948). Since that time she has been attending the Outpatient Clinic of this hospital. She has been employed for the past 2 years and is able to travel back and forth to work. Recently (July 1952) she received deep x-ray therapy to a destructive lesion of the right femur. This patient, now 33 years of age, has had a proven giant cell tumor for the past 11 years. Metastases are present in bones and soft tissue. She was completely incapacitated and bedridden 5 years ago. Conservative Ineasures such as orthopedic appliances, occupational therapy and physiotherapy, given to her while at home, have restored her to a fairly normal, comforable life. She has been rehabilitated to a degree that she is able to work and travel daily.
Palliative Treatment
Three rp.ethods of palliative treatment are available: medical (e.g. chemotherapy and hormonal therapy); radiation (e.g. deep x-rays, radium and radioisotopes), and surgical palliation. a. M edical Treatment. The remarkable beneficial effects of castration and/or estrogenic therapy for advanced prostatic carcinoma stimulated the therapeutic trial of a great variety of hormonal and chemotherapeutic agents. The results so obtained will be discussed in a separate clinic in this issue. Subjective improvement was induced by female or male sex hormones in the majority of cases of metastatic breast carcinoma. However, objective evidence of improvement was noted only in 20 to 30 per cent of the cases. ll Whether the life span of these patients is significantly prolonged by such agents is as yet uncertain. Careful selection and supervision of cases under hormonal treatment are essential. Serious complications such as congestive heart failure due to sodium retention and hypercalcemic crisis due to an increased rate of demineralization have occasionally occurred. 12 Estrogens are being used in postmenopausal patients only, as occasionally rapid progression of the neoplastic process was noted in
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premenopausal patients who received this treatment. Orchidectomy and/or estrogenic treatment appear to have a definite place in the treatment of advanced carcinoma of the breast in males. l3 Folic acid antagonists, urethane, nitrogen mustard and related compounds, ACTH and cortisone appear to have limited value in the treatment of patients with advanced carcinoma. Their value in the treatment of Hodgkin's disease, lymphosarcoma, leukemia and multiple myeloma will be discussed elsewhere. b. Deep X-ray Therapy, Radium and Radioisotopes. The palliative value of these agents is well recognized. R,elief of pain, regression of large radiosensitive tumors, relief of pressure symptoms, and recalcification of osteolytic bone lesions have been observed in many instances. Radiation castration in patients with metastatic carcinoma of the breast has resulted in temporary improvement in about 20 per cent of the cases. Radiation to metastatic brain tumors has occasionally resulted in relief of subjective and objective pressure symptoms. Radioiodine is useful in the diagnosis and treatment of thyroid carcinoma. Occasionally the thyroid origin of metastases can be discovered by the specific uptake of 1131 • Decrease of bone pain and apparent slowing down of the growth rate of these tumors have been occasionally accomplished by the administration of therapeutic doses of radioiodine. The surgical removal or the radioiodinedestruction of the thyroid gland occasionally induces or increases the uptake of radioiodine in metastases. 14 The use of p32 in the treatment of malignant lymphoma and leukemia will be discussed in a separate chapter. The intracavitary use of radio-gold Hi and of other radioisotopes 16 for the treatment of effusions caused by cancer appears to promise results which may be superior to those obtained by deep x-ray therapy. c. Surgical Treatment. Surgical palliative procedures require discussion because of the reluctance of the physician to consider these methods as too drastic in patients who cannot be cured. It is of course desirable to perform palliative surgical procedures at the time of primary surgery or exploration if curative surgery is not feasible. These procedures have been brought into disrepute to some extent because they were performed at a late and frequently the last stage of the disease. This delay accounts for the high mortality and low rate of palliation, e.g. gastrostomies performed on a highly debilitated patient can be of only little avail. On the other hand, the value of procedures such as enterostomies, urological procedures to relieve obstruction, laminectomies to relieve spinal cord compression and paraplegia is unquestionable when performed early in the course of such complications. They can afford prolongation of life and comfort to the patient. Numerous such instances have been reported. An example to
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illustrate the value of early surgical palliation is described: CASE X. A 58 year old woman (M.H. 45173) had a radical mastectomy followed by radiotherapy for a carcinolna of the breast. Three years later \videspread bone lnetastases were first noted. A year and a half later she was admitted because of inability to move her legs and urinary and fecal incontinence of 4 weeks' duration. On admission paraplegia, secondary to spinal cord compression at the level of D7 was diagnosed. X-rays showed destruction of the ninth dorsal vertebra. A decompression laminectomy was performed. A thick plaque of brownish tumor was removed from the dura underlying D7. Postoperatively radiotherapy was given to this area. Sixteen days after the laminectomy she was able to move both legs and urinary and bowel control became normal. The motion of the legs improved steadily and 5 months postoperatively she was able to use a walker and she was discharged to the Home Care Department, with almost perfect motion of both legs.
This example illustrates the value of a neurosurgical procedure performed in a patient with widespread osteolytic bone involvement. A five year palliation of a serious complication-paraplegia with loss of sphincter control-was achieved although the operative procedure was carried out as late as four weeks after the onset of symptoms. The Management of Nonmalignant Diseases in Cancer Patients
It is all too often that complications arising in patients who at one time had or still have a neoplasm are misinterpreted as progression of the malignant disease. The difficulties in differentiating two unrelated diseases are at times great indeed-yet it has to be attempted. Innumerable are the cases of errors; they are regrettable because they preclude treatment. They do not appear in morbidity or mortality statistics because they are masked by the assumed diagnosis of cancer. Congestive heart failure, pneumonitis, meningitis, jaundice due to hepatitis or to gallstone obstruction, peritonitis due to appendicitis or to perforation of a viscus, and intestinal obstruction secondary to adhesions or incarcerated hernias are but a few examples which have been labelled cancer. CASE XI. A 36 year old woman (M.H. 41914) with an inoperable carcinoma of the breast and extensive local, osseous and visceral spread developed signs and symptoms of obstructive jaundice with noncolicky epigastric pain. The differential diagnosis was intra- or extrahepatic obstructive jaundice due to tumor versus obstruction of the common duct by a gallstone. Past history revealed a cholecystectomy for gallstones, 10 years previously. On exploration stones were removed from the common duct. The patient was discharged 2 \veeks postoperatively relieved of jaundice. She died 16 months later. CASE XII. A 53 year old man (M.H. 50847) had an exploratory thoracotomy for a "pleural effusion" which was discovered on routine exalnination. The diagnosis of mesothelioma was made on thoracotomy. Ten days postoperatively abdominal pain and distention occurred which improved and recurred over a
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period of 4 weeks. At one time fecal vomiting was noted. The impression was that the patient had intestinal obstruction secondary to cancer implants. The patient died 6 weeks after the onset of abdominal symptoms. On postmortem examination a constricting fibrous band was found near the umbilicus causing kinking and distention of the jejunum and ileum. Multiple small intestinal ulcerations and a perforation of the ileum with fecal peritonitis were present. Past history revealed that the patient had an appendectomy 5 years previously. A few small tumor nodules were present on the parietal peritoneum, in no apparent relation to the constricting band.
Complications of cancer therapy are all too often mistaken for·progression of the disease. In all probability the majority of such errors remain unnoticed since the fatality is attributed to cancer. Many such cases have been observed. Two examples are briefly mentioned. CASE XIII. A 68 year old woman (M.H. 52230) was admitted to the hospital with a diagnosis of papillary adenocarcinoma of the uterine body. On examination an asymptomatic adhesive pericarditis with calcification was discovered and treatment with intrauterine radium implantation and deep x-ray therapy was instituted. Five months after the completion of this treatment, fever, pain in the left lower quadrant, pyuria and a mass in the left parametrium developed. The diagnosis was: extension of the tumor with secondary infection and block of the left ureter with pyelonephritis. Because of weakness in the left lower extremity the diagnosis of an epidural abscess was also considered. However, there were no sensory changes and the spinal fluid examination was negative. Ten days later the spinal fluid was cloudy and a block was demonstrated. The patient expired. At autopsy no cancer was found. However, severe radiation fibrosis of bladder, uterus and sigmoid colon, an abscess between L5 and 81 with liquefaction of the intervertebral disk and an epidural abscess with purulent meningitis were found.
This case well illustrates the difficulties in differentiating progression of cancer from sequelae of treatment-in this case postirradiation injury with secondary infection. CASE XIV. A 76 year old man (M.H. 52607) was admitted to the hospital for rectal bleeding, with a diagnosis of advanced neoplasm. Five months previously a carcinoma of the sigmoid colon was removed, an end-ta-end anastomosis and a palliative cecostomy were performed. Postoperatively a fecal fistula developed. When admitted here he was extremely cachectic, had a cecostomy and a fecal fistula. However, there was no evidence of tumor recurrence. Therefore, a transverse colostomy was performed and the fecal fistula and the cecostomy were closed. In a subsequent operation the bowel continuity was re-established by a colostomy closure. Th~ patient showed a remarkably rapid recovery, gained weight and is well 1;'2 years postoperatively.
CONCLUSIONS
Early diagnosis and improved management of cancer patients need not await tomorrow's discoveries. These can be accomplished with the present-day methods, by more and better trained general physicians,
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and by a change in the attitude toward the management of this disease. Some of the deficiencies encountered in the care of these patients have been described and suggested methods for improvement are briefly emphasized. In the prevention of cancer, environmental factors should be carefully evaluated as possible carcinogenic agents; precancerous lesions should be promptly treated. The causes for the delay in diagnosis have been dealt with extensively in numerous publications. Full and early use of the dia.gnostic tools in periodic examinations of asymptomatic persons and especially of those with symptoms could remedy this serious delay. Radical surgery is occasionally refused because of advanced age; or because of medical complications; or because of the assumption of local spread of the tumor or distant metastases. With the advances in surgery a.nd anesthesia, age alone is rarely a contraindication to surgery; with proper treatment of medical complications and modern preoperative care, patients previously considered unsuitable for surgery can now be operated on with safety. Errors have been made by assuming local spread of the tumor or distant metastases when none was present. These errors could be minimized by careful and critical evaluation of the evidence upon which this assumption has been based. Should the tumor not be resectable, palliative surgical procedures should be carried out at the time of exploration: better palliation with less operative risks results therefrom. Patients with advanced cancer require considerable medical attention as is true in any chronic disease. Problems of ambulation, nutrition, hydration, the evaluation of the patient's pain pattern and the selection of suitable analgesics require careful consideration. Palliative measures (radiotherapeutic, medical or surgical) when applied early and fully add to the comfort and prolong life of the patient. The differentiation of medical and surgical conditions entirely unrelated to the malignancy which the patient once had or still has is of major concern. There is no one better qualified to avoid these dangerous pitfalls than the general physician. It is safer to assume that complications are of nonmalignant nature unless proven otherwise. Such an attitude promotes a more active diagnostic and therapeutic regimen. Continuity of medical care of the cancer patient is of paramount importance. A closely knit single team of the family physician and specialist is the best guarantee of this continuity'. All too often a patient is transferred from an acute to a chronic hospital, then to a home for incurables. His morale is thereby lowered~ his confidence destroyed and the efficiency of his treatment greatly impaired. Whether to disclose or to withhold the true diagnosis and prognosis
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from the patient has been widely discussed. No general rule seems applicable to all patients. However, for the majority, no benefit seems to be derived from such disclosures: a grave and at times unbearable burden is put on the patient when he is least able to carry it and needs the most psychological and physical support. The fear associated with this diagnosis in the minds of the public is so great that its disclosure often induces an acute depression and, not infrequently, suicidal attempts have been made. Man lives by hope. Truly rare are the reasons which justify its deprivation. Sharing the responsibility ,vith the family, and presenting the patient with a concise, unhesitating plan of management, usually avoids difficulties. lVIembers of the family often request information on the probable duration of the illness. It is safer to assume that the patient will be one of the exceptions who will be able to carry on his daily activities longer than expected. ~ While an inotensive and relentless search for the "great discovery" must go on) optimal use of all methods now available should help to alleviate today's pressing problem. REFERENCES 1. Steiner, P. E.: An Evaluation of the Cancer Problelu. Cancer Research 12: 455, 1952. 2. Laszlo, D., Calmer, M. L., Silver, G. B. and Standard, S.: Errors in Diagnosis and Management of Cancer. Ann. lnt. Med. 33: 670, 1950. 3. Flavell, G.: Solitary Cerebral Metastases from Bronchial Carcinoma. Brit. Med. J. S: 736, 1949. 4. Terminal Care for Cancer Patients. Survey of the Central Service for the Chronically III of the Institute of Medicine of Chicago. Chicago, Illinois, 1950. 5. Spencer, H. and others: Relief of Pain and Suffering Due to Cancer by Means of Placebo Therapy. In preparation. 6. Tannenbaum, A.: Genesis and Growth of Tumors; Effects of Caloric R,estrictions per se. Cancer Research 2: 460 and 468, 1942. 7. White, J., Mider, B. G. and Heston, W. E.: Effect of Amino Acids on the Induction of Leukemia in Mice. J. N at. Cancer Inst. 4: 409, 1944. 8. Deitrick, J. E., Whedon, G. D. and Shorr, E. E.: Effects of Immobilization upon Various Metabolic and Physiologic Functions of Normal Men. Am. J. Med. 4.: 3, 1948. 9. Altman, H.: Intramedullary Nailing of Pathological Impending and Actual Fractures of Long Bones. Bull. Hospital of Bone and Joint Diseases 13 (2): 239 (Oct.) 1952. 10. llome Care. Origin, Organizatinn and Present Status of the I~xtramural Program of Montefiore IIospital. }{eport of M ontefiore Hospital, New York City, 1949. 11. Proceedings of the First Conference on Steroid Hormones and 1\Iammary Cancer: The Therapeutic Trials Committee of the Council on Pharmacy and Chemistry of The American Medical Association, Chicago, 1949. 12. Laszlo, D. and others: Effect of Testosterone on Patients with Bone lVletastases. J.A.M.A. 148: 1502) 1952. 13. Treves, N.: Castration as a Therapeutic Measure in Cancer of the Male Breast. Cancer 2: 191, 1949.
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14. Seidlin, S. M., Rossrnan, T., Oshry, E. and Siegel, E.: Radio-iodine Therapy '. ~ of Metastases from Carcinoma of the Thyroid. Six Years Progress lleport. J. Clin. Endocrinol. 9: 1122, 1949. 15. Goldie, H. and Hahn, P. H.: Distribution and Effect of Colloidal Radio-active Gold in Peritoneal Fluid Containing Free Sarcoma 37 -Cells. Proc. Soc. Exp. BioI. Med. 74: 638, 1950. 16. Lewin, R. and others: Effect of La 139 _ and La 14 °-chloride on Mice Bearing Ehrlich Ascites Turnors. Cancer Research 12: 278, 1951.