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The Early Diagnosis of Cancer
The Early Diagnosis of Cancer EMERSON DAY, M.D.*
t:EARLY diagnosis and early treatment of cancer is the basis of the major ~J;clinical attack on this disease today. The exact extent to which early
~:aiagnosis can increase cancer cures and reduce cancer deaths is not yet ~/established. The releases of the American Cancer Society state that ,one-third of the cancers which now result in death, or approximately 75,000 per annum, could be cured by the application of currently avail;: able methods of early diagnosis, with no improvement in methods of treatment. While the statistics of this statement are still unproved, the ,concept that the cancer death rate can be significantly reduced by 'early diagnosis is supported by certain facts and reasoning: 1. Surgery and its ancillary services has now progressed to the point 'where organs such as the lung, the stomach, segments of the bowel, or jC,the pelvic viscera can be removed with consistent operative success. " 2. The natural course of many cancers includes a stage during which 'the tumor is localized within a single organ. In the earliest phase the ,tumor consists of a microscopic lesion confined to the tissue of origin. (This in situ stage of cancer may persist for a long period of time before '~ither local invasion or distant metastasis takes place. In the case of the cervix uteri, where intraepithelial carcinoma has been most intensively studied, it has been demonstrated that the preinvasive stage may persist for many years.! Similar in situ lesions have been identified in the breast, and the respiratory, gastrointestinal and genitourinary tracts. It is probable that all cancers originating in a single tissue or ;ergan pass through such a primary focal stage. " 3. It follows that cancer confined to a single organ which can be re'IPloved by surgery, or to a tissue which can be destroyed by radiother/apy or other means, is curable cancer if detected at that stage, and the jJroblem of cancer cure does, in fact, resolve itself into one of increasing ~he practice of early diagnosis. t ',e
* Director, Strang
Cancer Prevention Clinic, Memorial Center; Associate Profes-
IO .•~ T, Clinical Public Health and Preventive Medicine, Cornell University Medical lj()llege, New York.
t
In reply to those who claim that biological tumor type rather than time of 639
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The achievement of maximum early cancer diagnosis depends upon the widespread practice of certain simple principles and procedures. These have been developed and demonstrated in cancer diagnostic clinics for symptomatic patients and in cancer detection centers for presumably well adults without symptoms. 3 In the private office, where most patients are first seen and where the success of the cancer program is ultimately determined, maximum effective early diagnosis depends upon a combination of diagnostic and detection techniques. The symptomatic patient presents an opportunity for early diagnosis and cure to every phyEician ,vho thinks of cancer by habit and initiates certain standard diagnostic procedures when indicated. And asymptomatic adults who are presenting themselves in doctors' offices in increasing numbers in response to the campaign for periodic examinations by health and cancer agencies, represent candidates for presymptomatic cancer detec,tion and the ideal opportunity for diagnosis of cancer at a curable stage. It is the purpose of this paper to review the established diagnostic and detection techniques and discuss their practical application in the private office and general clinic. GENERAL PRINCIPLES
There are no specific symptoms or signs of early cancer and there is no reliable general·screening test for the disease. The early diagnosis of cancer depends upon careful examination by a physician. The first requirement for success is conviction on the part of the examining physician that early cancer diagnosis is both possible and important. There is no requirement of specialist training, only of adequate interest and time for the performance of a thorough examination. Success is achieved in direct proportion to the frequency of thinking cancer; every diagnostic lead which could mean cancer must be considered cancer until proved otherwise. The stage of the disease at diagnosis and thereby its curability are importantly determined by this "state of mind" of the original examining physician. The methods of examination for early cancer are basically (1) a careful history, (2) direct inspection and palpation wherever possible, (3) selected diagnostic tests when indicated by 1 and 2, and (4) biopsy for final diagnosis. These apply equally to the patient being examined for localized or for general systemic complaints, and to the asymptomatic, presumably well individual receiving a cancer detection examination. diagnosis is the determining factor in cancer end results, Hammond has recently published a brief review of the role of early diagnosis in cancer curability.2 Histologic type, invasiveness, and potential for metastasizing are obviously important factors in cancer, but for all tumors arising in a primary site there will always be a localized stage. Lack of improvement in end results is attributable to current inability or failure to diagnose and treat the disease at that stage.
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'fhe detection examination includes certain screening procedures for accessible organs but the methods of cancer diagnosis are the same, whatever the source of the patient. These will be considered by site after a brief review of biopsy and related microscopic techniques and an outline of a general detection examination. BIOPSY
Biopsy, the obtaining of a tissue specimen for pathologic examination, is the crux of cancer diagnosis. It should be employed promptly for all accessible suspicious lesions. There are a number of methods of biopsy and the proper choice is important in determining results. The appropriate method will vary with the site and with the competence and experience of the pathology laboratory to which the specimen is to be submitted. The essential requirement is that the tissue be representative of the lesion and that it not be crushed, coagulated, or otherwise rendered unreadable. As a rule, biopsy should be obtained by cutting with a scalpel or sharp punch instrument rather than by pulling, tearing or electrocautery. The ideal biopsy takes an entire lesion or mass for pathological examination. l'his is often possible with small skin lesions or polyps. In such cases the specimen should include a margin of normal-appearing tissue and the pathology report should note whether or not this is free of disease. Adequate sampling of a lesion may require the taking of several specimens from different areas, vvhich should then be separately identified both for the pathologist's reading and for the clinician's interpretation of the report. In surfacE( biopsies at least one specimen should include a junction with normal tissue at the periphery of the lesion. Aspiration or needle biopsy may be used to obtain histological, and cytological, specimens from a mass belovv a surface. It requires a laboratory experienced with the method for satisfactory interpretation, and is always limited by the uncertainty that the specimen is representative of the tumor. A positive reading by a competent pathologist is helpful in planning treatment, but a negative report never rules out cancer. CYTOLOGICAL TEST FOR CANCER
A method of obtaining material for microscopic study closely related to tissue biopsy is the Papanicolaou smear technique or the cytological test for cancer (CTC).4 This utilizes single cells or clusters of cells exfoliated from the surface of tissues and can provide reliable information in regard to the nature of a lesion when read by a competent cytologist or cytopathologist. The cytological smear technique has its widest use in screening for
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uterine cancer, but is also applicable as a diagnostic adjunct for any site from which exfoliated cells are shed. This includes the respiratory, gastrointestinal and urinary tracts, the serous cavities, and such organs as the breast and prostate when secretions are obtainable. In many cases the cytological smear may reveal the presence of cancer before a lesion can be seen or reached for tissue biopsy. It has the advantage over biopsy of providing a total surface sample and therefore is of increasing importance as attempts progress to identify cancer at the earliest preclinical or in situ stage. The specific applications of the smear technique will be referred to in the discussion of cancer diagnosis by site. In using the cytological test for cancer the following principles should be adhered to: 1. Cytological smears for cancer should be read by a cytologically trained person. Positive reports must be given only by a cancer cytologist or by a pathologist experienced in reading cytological preparations. 2. A positive smear must be confirmed by biopsy before planning treatment. The only exception is in cases of tumors inaccessible to bronchoscope, gastroscope, proctoscope or cystoscope where surgery may have to serve as a diagnoE;tic approach. Even at operation the nature of the exposed lesion should be confirmed by frozen section biopsy if possible before proceeding with definitive treatment. The requirement of histological confirmation of a cytological diagnosis before proceeding with treatment is sound and must be complied with in whatever way possible at this stage in the development of cytology. CANCER DETECTION
Cancer detection, the diagnosis of presymptoItiatic cancer, is a logical extension of the concept of early diagnosis as a means of cancer control. During the past fifteen years the experience of cancer detection centers and associated cJinic and office programs throughout the country has demonstrated practical detection methods for a number of accessible sites. The type and extent of examination varies but always incorporates the routine performance of established screening procedures. Many of these procedures can be effectively applied in general practice. At the Strang Clinic, Memorial Center, where experience is based on over 100,000 general cancer detection examinations, the routine consists of the following: History Fanlily history of cancer Significant past illnesses, operations, and environrnental exposures Review of systems Physical Examination Skin and superficial lymph nodes
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Nose, mouth, throat and vocal cords Neck and thyroid gland Breasts Thorax and lungs Abdomen Genitalia Digital exarnination of rectum and prostate Pelvic examination and vaginal-cervical smears Musculoskeletal and neurologic survey
Laboratory
Hemoglobin White blood cell count and differential Peripheral blood smear Urinalysis with microscopic examination of centrifuged sediment Stool guaiac test for occult blood Papanicolaou vaginal-cervical smears
X-Ray
Photoroentgen film of the lungs Proctosigmoidoscopy is performed on a return visit for all persons 45 and older; stomach survey photofluorographic films are advised for the same group. Biopsy is an integral part of the examination when suspicious lesions of accessible areas are encountered. Suggestive leads from the routine history, physical examination, laboratory or x-ray are follo,ved by referral for further diagnostic tests or examinations as indicated.
The routine history and physical examination
The methods which have proved effective in cancer detection and early diagnosis are reviewed for each site, starting with the pel~ic examination ,which historically provides the first example of screening techniques , applied to an accessible organ.
Female Genitalia Examination for early cancer of the female genitalia requires both careful pelvic examination and the taking of cytological smears. Neither
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alone is adequate. Together they form a simple and effective standard office procedure. At Strang Clinic the routine is as follows: 1. External Examination. Note introitus and any abnormalities of skin, glands and urethra. 2. Vaginal Smear. Aspirate posterolateral fornices with vaginal pipette (Fig. 56). Spread secretion thinly on clipped glass slide and place immediately in bottle of ether-alcohol solution. 3. Internal Inspection. Insert speculum without lubricant; inspect vagina and cervix carefully'. Note character of vaginal discharge if present. 4. Cervical Smear. Swab entire cervical surface with cotton applicator, then insert and rotate applicator inside cervical os. Roll applicator on unclipped slide making a thin, even smear. Place slide immediately in ether-alcohol solution. 5. Iodine Test. Do not perform if patient gives history of iodine sensitivity. ,<:With cotton applicator apply 3.5 per cent iodine sparingly to cervix only. INote position and size of nonstaining areas. 6. Bimanual Examination. Include palpation of fornices and adnexa as well as cervix and fundus, and rectovaginal examination using finger cot over glove. 7. Endocervical Smear. To be done in addition to above if there is: (a) history of abnormal bleeding, (b) enlargement of uterus, (c) blood on cotton swab when rotated in external os for routine cervical smear. Wipe cervix clean if lubricant has been used. Insert cannula well into endocervical canal and exert gentle suction by drawing back on syringe (Fig. 56). Spread secretion thinly on slide and place in ether-alcohol solution. 8. Biopsy. (a) Biopsy any suspicious granular or eroded areas, including those which do not take iodine stain and areas of leukoplakia. (b) Record biopsied areas for pathologist and on clinical chart. Figure 56 shows the equipment used in taking vaginal and cervical smears by the Papanicolaou method. Other means of obtaining material from the cervix, such as the cervical scrape, may be substituted for the s\vab technique if the laboratory receiving the material is acquainted with the method. In all cases the cytologist should be given clinical data in regard to menses, hormone or other gynecological therapy, pregnancy and infection ~ince these. factors may be associated with cytological changes. 8 Cervical Cancer Detection. Vaginal-cervical smears properly taken and interpreted, combined with biopsy of all suspicious areas, will detect essential.ly every case of carcinoma of the cervix. In a series of 36 cases at Strang Clinic approximately 90 per cent were in situ or preinvasive cancer; 42 per cent were detected as a result of the routine smear before there were clinical findings by history or pelvic examip.a,~ipn. 9 In cases
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with a suspicious or positive cytology report and a normal appearing cervix, four-point biopsies are taken as recommended by Foote and Stewart. 10 Cases with repeated abnormal smears and no focus of cancer demonstrable by biopsy are followed at frequent intervals by a specialist. It is important that no cauterization or other treatment be undertaken at the first examination, or until cytological and pathological reports
Fig. 56. Set-up for routine vaginal-cervical cytological smears and endoc·ervical aspiration.
are received, in order not to obscure a lesion and confuse subsequent care. Corpus Uteri and Adnexa. While the smear-and-hiopsy program is highly successful in detecting asymptomatic cancer of the cervix, cytological techniques are not as effective for cancer of the fundus and adnexa. Cells from these sites may appear in routine smears, but as a rule clinical suspicion based on abnormal bleeding or findings on bimanual pelvic examination, followed by appropriate diagnostic measures such as endometrial biopsy and dilatation and curettage for the fundus or laparotomy for the adnexa, will be necessary for diagnosis of cancer of the upper
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genital tract. Recently Hecht has demonstrated that more frequent use of endometrial aspiration smears as an office procedure can aid in the early diagnosis of cancer of the fundus. ll Breast
Recent reports indicate that the female breast is the commonest site of human cancer. 12 Yet in spite of its accessibility, it presents a major problem in early cancer diagnosis. Adequate examination is based primarily on inspection and palpation. It demands care, attention to detail and a minimum of three to five minutes of a practiced doctor's time. Casual and rapid examination can discover only relatively large and late cancer. Routine Breast Examination. Inspection is made with the patient sitting facing the examiner in good light. The contour and symmetry of the breasts are noted with arms relaxed at the side, with arms raised, with pectoral muscles tensed, and with the patient leaning forward. The pectoral areas and axillae are best examined during this part of the procedure. Thorough palpation of the breast tissue is performed while the patient is supine with the arm raised and shoulder elevated or body turned slightly so that the breast tissue is distributed evenly over the chest wall. In this position all quadrants are palpated methodically using firm but gentle pressure of the finger pads. Special attention should be paid to the subareolar tissue and to the nipple. Cytology. If there is a history of nipple secretion a gentle attempt should be made to obtain fluid from each duct. When nipple secretion is obtained as above, or appears spontaneously, it should be smeared for cytological study, with notation of the position of the duct from which it came. Smears, when obtained, may lead to a diagnosis of carcinoma before the development of a palpable mass. 'rhey also may be helpful in distinguishing benign from early malignant tumors of the breast in the occasional case when exfoliated secretions are encountered. Clinical Aids to Differential Diagnosis of Breast Masses. When an abnormal mass is found in the breast, certain aids are available which may help to determine its nature clinically. 1. AGE. The probability that a mass in the breast is cancer increases with age. After the menopause any mass must be considered cancer until proved otherwise. 2. FEEL AND BEHAVIOR OF THE LESION. The significant breast lesion is usually firm and well demarcated from the surrounding breast tissue. Fixation is a relativeJy late change in cancer and should not be waited for. Benign fibrocystic changes are frequently palpable in the functioning breast but tend to be irregular in size and consistence and more prominent premenstrually. Regression on re-examination after menses is a , clinical finding which favors the benign nature of a lesion.
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3. TRANSILLUMINATION. Transillumination requires a darkened room for accuracy and is not used as part of the routine examination. It is a }useful diagnostic adjunct, however, in differentiating a fluid-filled cyst from a solid tumor. , 4. ASPIRATION. Needle aspiration can be helpful in collapsing a cyst and establishing its benign nature. rrhe aspiration of solid tumors is used to obtain histologic and cytologic preparations for microscopic study, but this technique has the important limitations outlined in the section 'on biopsy and is not appropriate for general use. Final Diagnosis. l-'he nature of any lesion which remains clinically suspicious must be determined by excisional biopsy. l'1his is a surgical procedure usually best performed in a hospital by a surgeon with a pathologist in attendance and facilities for frozen section readings. The promptness with which the patient with a suspicious lesion is referred for excisional biopsy is one of the primary factors in determining end results in breast cancer. Rectum and Colon
The rectum and distal colon become accessible' and highly productive sites for cancer detection by the routine practice of two procedures, digital examination of the rectum and proctosigmoidoscopy. Digital Examination of the rectum should be routine in every physical examination. When thoroughly performed it can reach most large lesions of the lower rectum. Even good digital examination, however, will miss early mucosal and soft polypoid lesions. It cannot be depended upon to rule out disease of the rectum and is not an adequate detection procedure alone. Proctosigmoidoscopy permits visualization of the mucosa of the rectum and sigmoid colon and biopsy of any lesion seen. It thus meets the b-asic requirements for successful cancer detection, namely direct access, with opportunity for pathological examination of tissue specimens when indicated. The effectiveness of such a detection device is emphasized in the experience at Strang Clinic where cancer of the rectum and colon is the second most frequent cancer diagnosed in men and the third most frequent in women. 6 Figure 57 shows the equipment necessary for office proctosigmoidoscopy. Any type of lighted sigmoidoscope is adequate. The tube to the left of the scope is a suction tip for attachment to vacuum pump or line. This may not be necessary in a well cleansed patient. The most common lesion encountered on routine proctosigmoidoscopy is the rectal or colon polyp. All such lesions should be routinely biopsied or removed for microscopic diagnosis. This can be easily accomplished by using a long biopsy forceps through the sigmoidoscope at the time of routine examination. Even though appearing benign clinically, a signifi-
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cant number of polyps will prove to be early cancer or will show premalignant changes. In one series of 479 polyps found on routine examination, 5 per cent revealed adenocarcinoma, and 3 per cent showed atypias. 13 For the detection of lesions of the colon beyond the reach of the sigmoidoscope, all patients with mucosal lesions at proctosigmoidoscopy and patients with symptoms or laboratory evidence of bleeding are regularly referred for barium enema ,vith air contrast studies. The
Fig. 57. Equipment for routine proctosigmoidoscopy.
determination of the nature of tumors or lesions proximal to the sigmoid may be aided by special studies such as colonic washing for cytology,13a but will often require the direct approach of laparotomy. Prostate
Digital palpation through the rectum is the standard means of detecting early cancer of the prostate. This should be routine in every male examination. The significant finding is a very firm to stony hard area or nodule. While such a finding may be due to calculus, chronic infection or adenoma, the possibility that it IS cancer must always be entertained, especially after the fifth decade.
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In the differential diagnosis of a clinically suspicious gland, Papanicolaou smears of prostatic fluid obtained by careful massage may be helpful if positive. They have been disappointing, however, in routine screening of men over 50 for preclinical carcinoma of the prostate. 14 There is also no established biochemical test for cancer of the prostate before it has extended beyond the capsule of the gland. At present, routine digital examination is the' one practical and reliable means of detecting early prostatic cancer. Skin and Lip
The early diagnosis of cancer of the skin is achieved by a habit of careful inspection of all body surfaces and the judicious use of biopsy. Early diagnosis may be of relatively little vital importance in the slo\v growing and rarely metastasizing basal cell carcinomas, and of only moderate importance in many squamous cell carcinomas of the skin and lip. But the malignant melanoma demands the earliest possible diagnosis and treatment. Since the histological nature of a skin lesion is often difficult, if not impossible, to predict clinicaliy, it is essential that determination of the histopathology of all potentially malignant lesions be accomplished by biopsy as promptly as possible. The proper management of skin lesions requires judgment on the part of the examining physician. Since most individuals have multiple pigmented moles or nevi, it is totally impractical to remove them all. The decision in regard to management of a specific lesion should be~based on the following current understanding of skin cancer: ~ 1. The classic signs of malignancy in a skin lesion, namely increase in size, alteration in color, or ulceration, are often evidence of late cancer in the case of melanoma. 2. There are no reliable distinguishing features of the premalignant or early malignant skin lesion. It may be pigmented or nonpigm.ented, papillary or smooth surfaced. As a general rule, the blue nevus, the hairy mole, and the wen or steatoma are rarely the site of cancer. 3. The junction cell nevus is the precursor of most melanocarcinoma. 15 Unfortunately, the junction cell nevus has no specific clinical characteristics and diagnosis depends upon biopsy of appropriate lesions. Since there is a higher relative incidence of primary melanoma of the skin of the feet, the genitalia, and the head and neck, removal and microscopic study of all nevi of these sites is recommended as, a routine procedure. Head and Neck
The head and neck examination should include direct inspection of the nasal and pharyngeal passages, inspection and palpation of the oral ~avity, tongue and floor of the mouth, and mirror visualization of the
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hypopharynx, larynx, and vocal cords. Where this is done routinely early lesions have been detected before the onset of complaints of "fullness" or "lump" or hoarseness. Usually the early lesion is accessible for direct biopsy but cytologic smears obtained by swab or washings may be useful in special instances. Careful palpation of the neck for masses and of the thyroid gland is an essential part of the detection examination. Adenomas of the thyroid are the site of cancer in from 5 to 10 per cent of cases. 16 Although the solitary adenoma is more apt to be malignant, there are no absolutely reliable clinical means of differentiating the benign from the early malignant lesion of the thyroid. Therefore, the objective of early cancer diagnosis requires a policy of surgical removal and microscopic study of all thyroid adenomas. The finding of a cervical node in an adult must be considered evidence of possible malignant disease either locally or elsewhere. If it cannot be attributed to infection, and if persistent for more than two weeks, biopsy is indicated. In experienced hands, aspiration of cervical nodes or masses can be a useful diagnostic procedure, but as a general rule the approach should be by surgical excision. The head and neek area completes the list of sites which are accessible for direct examination and practical screening procedures in the general office. For other sites the early diagnosis of cancer will depend on proper selection and timing of diagnostic studies following symptoms elicited on history, or leads obtained from routine laboratory tests such as blood count, stool guaiac, urinalysis and chest x-ray. '"fwo sites, lung and stomach, though not accessible for routine direct examination, merit special attention because of their importance as sources of cancer and the fact that specific aids to diagnosis can be outlined for each. Lung
Detection. Chest x-ray for asymptomatic lung cancer have yielded poor results in general population surveys but are practical for persons with increased risk of pulmonary cancer. These include men over 45, particularly with a history of long-term heavy smoking or exposure to kno\vn lung irritants. 17 Periodic chest x-rays should be provided for these groups either as part of the office examination or through community programs. Fluoroscopy should be done if it is the only facility available, but it does not take the place of an x-ray film in screening for an early lesion. Any abnormality on fluoroscopy or on survey minifilm should be followed by full diagnostic x-rays. Early Diagnosis. Early diagnosis of lung cancer requires alertness for all possible clinical leads and the prompt utilization of special diagnostic procedures. The following clinical findings must be considered evidence
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of cancer until proved otherwise, particularly in men in the fifth decade and older: 1. 1'umor, or any undiagnosed abnormality, detected on x-ray examination. 2. Chronic cough, \vhether or not associated with sputum or recent change in charaeter. 3. Vague pulmonary complaints such as "discomfort" or "uneasiness" in the chest. Pain, dyspnea, hemoptysis are usually symptoms of late cancer. 4. Recent history of pneumonitis or atypical or recurrent pneumonia, even if followed by complete resolution. In the presence of the above or related findings, the following studies are required: 1. Diagnostic x-ray studies, type to be determined by location and characteristics of lesion if present. Whether radiographic studies are positive or negative, workup should proceed to 2. Cytological studies on: (a) Sputum if produced. Three satisfactory specimens should be obtained before accepting negative reports as ruling out cancer. (b) Tracheal or bronchial washings. Tracheal washings can be used for obtaining smears as a relatively simple office procedure. I8 Bronchial washings are performed at bronchoscopy. 3. Bronchoscopy, with biopsy of any suspicious area, and selective bronchial washings. As diagnostic studies are initiated earlier in the course of disease, lesions tend to be smaller or more peripheral and less accessible for biopsy. In such cases directed bronchoscopic washings for cytology are a reliable means of determining the nature and location of a peripherallesion. I9 4. rrhoracotomy with direct exploration of tumor or suspicious area. Surgical approach may be the only means of establishing the presence of early cancer. 20 Thoracotomy should be employed with increasing frequency for diagnostic purposes when other methods fail. Delay for evidence of cancer by tumor growth, progressive symptoms or biopsy proof is frequently the reason for inoperability when the chest is finally explored. Stomach
Detection. There is no practical method of screening all examinees for cancer of the stomach. In contrast to the rectum and sigmoid colon, the upper gastrointestinal tract is not accessible to simple office techniques. Visualization by gastroscope is a major procedure; the taking of cytological specimens entails time and inconvenience for the patient; and the use of standard gastrointestinal series x-ray studies is limited by cost and the requirement of a roentgenologist. Methods must be employed for improving the yield of positive findings
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and making diagnostic procedures in asymptomatic patients productive. These are based on the use of clinical selection factors as follows: 1. Age over 45. 2. Evidence of bleeding either by unexplained occult blood in the stool or unexplained anemia. 3. Achlorhydria. A method of gastric analysis has recently been developed which avoids intubation and makes this prescreening procedure acceptable to well patients. 21 The presence of normal acidity does not rule out the possibility of cancer. 4. Pernicious anemia. 5. History of gastric ulcer. 6. Family history of gastrointestinal cancer. In a few medical centers stomach x-ray surveys by rapid fluoroscopy or photofluorography have been demonstrated as a means of determining which individuals in older age groups should have full diagnostic x-rays.22 Photofluorographic films are reliable and economical for screening purposes but are now, and probably always will be, of limited availability because of the requirement of special equipment. Early Diagnosis. The major hope for earlier diagnosis and higher cure rates in gastric cancer rests in the office and general clinic where symptomatic patients are seen. The decision in regard to which patients should have diagnostic studies is notoriously difficult. It can be aided by applying the clinical factors listed under the prescreening devices above. The standard diagnostic procedure is gastrointestinal x-ray series. When this reveals abnormal mucosal patterns, filling defects or ulceration, further diagnostic tests to establish the nature of the lesion should be undertaken promptly without waiting to "observe the course." The one exception may be gastric ulcer where a trial on medical treatment is acceptable if carefully supervised and checked at short, i.e., two week, intervals. Both the benign ulcer and the ulcer associated with cancer may show signs of healing but the benign ulcer should be completely healed, with normal gastric wall and mucosa, in a maximum of four weeks. Any other course is strong presumptive evidence of cancer. There are three direct ways of establishing the nature of a lesion demonstrated on gastrointestinal series. Generally they should be employed in order as follows: 1. Cytological studies. Smears of cells obtained from the gastric mucosa are an established diagnostic adjunct. Freshness of cells must be assured by use of such techniques as the abrasive balloon. 23 2. Gastroscopy. Biopsy through the gastroscope is a means of proving the presence of cancer when the lesion can be reached, but gastroscopy has the limitation that it cannot reach all areas of the stomach. 3. Exploratory laparotomy. In the presence of persisting clinical suspicion, whatever the evidence by cytology or gastroscopy, laparotomy
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should be performed for direct exploration of the stomach. In the stomach, as in other viscera such as lung, large bowel and ovary, competent surgical exploration must be used with increasing frequency as a diagnostic measure if cancer is to be treated at the stage when surgery can be curative. AIDS TO PRACTICE OF CANCER DETECTION AND EARLY DIAGNOSIS
In the practice of cancer detection and early diagnosis the efficiency and thereby the effectiveness of procedures can be improved by use of certain aids. The importance of a systematized method of examination has already been stressed. Preprinted history and physical examination forms for the routine detection examination can save time in recording findings and expedite accuracy and usefulness of charts. 7 Self-administered family history and screening personal history questionnaires can also be used to spare physician time. If such forms are used, however, it is important that the examining physician personally explore all positive leads with the patient, particularly in the review of systems. In addition to methods of conserving professional time by systematized forms and office procedures, there are means of increasing the effectiveIl,ess of examinations for cancer by concentrating efforts on those patients and groups with higher cancer risk. A minimum age of 35 for women and 45 for men is based on the over-all age-specific trends of cancer incidence by sex and is a practical measure in the face of limited facilities. Other selection factors which should give patients priority for examination are strong family history of cancer, previous cancer, and history of exposure to known environmental or industrial carcinogens. The effectiveness of cancer detection and diagnostic procedures in an office or clinic will be determined to a considerable extent by the support :'available in the community. Lay education programs are important in 'acquainting the public with the symptoms which may mean cancer and in promoting periodic health examinations and such special programs as breast self-examination. In some communities professional groups and health agencies have 1~rganized educational and diagnostic services to aid examinations in the ~private office and cancer clinic. Efforts are also being made to increase !~~he number and quality of pathological and cytological facilities available ~J;o the profession. In all of these efforts the attitude of the practitioner is the key to sucilress or failure of the cancer program.
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REFERE~CES
Younge, P. A., Hertig, A. T. and Armstrong, D.: A Study of 135 Cases of Carcinoma in Situ of the Cervix at the Free Hospital for Women. Am. J. Obst. Gynec. 58: 867-895, 1949.
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2. Hammond, E. C.: Early Diagnosis and Cancer Cure Rates. CA Bull. Cancer Prog. 3: 175-176, 1953. 3. Crowell, B. C. and Branch, C. F.: Cancer Clinics-Cancer Diagnostic ClinicsCancer Detection Centers. Bull. Am. ColI. Surge 32: 131-143, 1947. 4. Papanicolaou, G. N.: The Cell Smear Method of Diagnosing Cancer. Am. J. Pub. Health 38: 202-205, 1948. 5. Cameron, C.: Recent Trends in Early Diagnosis of Cancer. New York State J. M. 52: 2099-2102, 1952. 6. Day, E.: The Strang Cancer Prevention Clinic Memorial Center-A "Second Look." J.A.M.A. 8: 169-171, 1953. 7. Day, E., Rigney, T. G. and Beck, D. F.: Cancer :Detection. An Analysis and Evaluation of 2111 Examinations. Am. J. Hyg. 57: 344-365, 1953. 8. Scapier, J., Day, E. and Durfee, G. R.: Intraepithelial Carcinoma of the Cervix. Cancer 5: 315-323, 1952. 9. Day, E.: Cytological Techniques in Screening Uterine and Lung Cancer. CA Bull. Cancer Prog. 2: 57-62, 1952. 10. Foote, F. W. and Stewart, F. W.: The Anatomical Distribution of Intraepithelial Epidermoid Carcinomas of the Cervix. Cancer 1: 431-439, 1948. 11. Hecht, E. L.: The Value of the Endometrial Smear in the Detection of Malignancy. New York State J. M. 52: 2745-2752,1952. 12. Gerhardt, P. R. and Handy, V. H.: Cancer Diagnosis. Morbidity and Mortality Statistics. New York State J. M. 52: 2235-2236,1952. 13. Miller, C. J., Day, E. and L'Esperance, E. S.: The Value of Proctoscopy as a Routine Examination in Preventing Deaths from Cancer of the Large Bowel. New York State J. M. 50: 2023-2027,1950. 13a. Bader, G. M. and Papanicolaou: The Application of Cytology in the Diagnosis of Cancer of the Rectum and Descending Colon. Cancer 5: 307-314, 1952. 14. Strang Clinic, Memorial Center: Unpublished data. 15. Allen, A. C. and Spitz, S.: Malignant Melanoma. Cancer 6: 1-45, 1953. 16. Cope, 0.: Diseases of the Thyroid Gland (Part II). New England J. Med. 246: 451-457, 1952. 17. Wynder, E. L. and Graham, E. A.: Etiologic Factors in Bronchiogenic Carcinoma with Special Reference to Industrial Exposures. A. M. A. Arch. Indus. Hyg. & Occup. Med. 4: 221-235, 1951. 18. Cahan, W. G. and Parr, H. W.: Tracheal Aspiration-An Additional Method for the Early Diagnosis of Carcinolna of the Lung. Cancer 3: 475-480, 1950. 19. Watson, W. L. and others: Recent Advances in the Diagnosis of Early Lung Cancer. New York Med. 7: 16-20, 1951. 20. Bernatz, P. E. and Clagett, O. T.: Exploratory Thoracotomy in Diagnosis and Management of Certain Pulmonary Lesions. J.A.M.A. 152: 379-381, 1953. 21. Segal, H. L., Miller, L. L. and Morton, J. J.: Detection of Achlorhydria by Tubeless Gastric Analysis. J. Nat. Cancer Inst.13: 1079-1086, 1953. 22. Wigh, R. and Swenson, P. C.: Photofluorography for the Detection of Unsuspected Gastric Neoplasms. Am. J. Roentgenol. 69: 242-267,1953. 23. Cooper, W. A. and Papanicolaou, G. N.: Balloon Technique in the Cytological Diagnosis of Gastric Cancer. J.A.M.A. 151: 10-14, 1953. 444 East 68th Street New York 21
t:EARLY diagnosis and early treatment of cancer is the basis of the major ~J;clinical attack on this disease today. The exact extent to which early
~:aiagnosis can increase cancer cures and reduce cancer deaths is not yet ~/established. The releases of the American Cancer Society state that ,one-third of the cancers which now result in death, or approximately 75,000 per annum, could be cured by the application of currently avail;: able methods of early diagnosis, with no improvement in methods of treatment. While the statistics of this statement are still unproved, the ,concept that the cancer death rate can be significantly reduced by 'early diagnosis is supported by certain facts and reasoning: 1. Surgery and its ancillary services has now progressed to the point 'where organs such as the lung, the stomach, segments of the bowel, or jC,the pelvic viscera can be removed with consistent operative success. " 2. The natural course of many cancers includes a stage during which 'the tumor is localized within a single organ. In the earliest phase the ,tumor consists of a microscopic lesion confined to the tissue of origin. (This in situ stage of cancer may persist for a long period of time before '~ither local invasion or distant metastasis takes place. In the case of the cervix uteri, where intraepithelial carcinoma has been most intensively studied, it has been demonstrated that the preinvasive stage may persist for many years.! Similar in situ lesions have been identified in the breast, and the respiratory, gastrointestinal and genitourinary tracts. It is probable that all cancers originating in a single tissue or ;ergan pass through such a primary focal stage. " 3. It follows that cancer confined to a single organ which can be re'IPloved by surgery, or to a tissue which can be destroyed by radiother/apy or other means, is curable cancer if detected at that stage, and the jJroblem of cancer cure does, in fact, resolve itself into one of increasing ~he practice of early diagnosis. t ',e
* Director, Strang
Cancer Prevention Clinic, Memorial Center; Associate Profes-
IO .•~ T, Clinical Public Health and Preventive Medicine, Cornell University Medical lj()llege, New York.
t
In reply to those who claim that biological tumor type rather than time of 639
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The achievement of maximum early cancer diagnosis depends upon the widespread practice of certain simple principles and procedures. These have been developed and demonstrated in cancer diagnostic clinics for symptomatic patients and in cancer detection centers for presumably well adults without symptoms. 3 In the private office, where most patients are first seen and where the success of the cancer program is ultimately determined, maximum effective early diagnosis depends upon a combination of diagnostic and detection techniques. The symptomatic patient presents an opportunity for early diagnosis and cure to every phyEician ,vho thinks of cancer by habit and initiates certain standard diagnostic procedures when indicated. And asymptomatic adults who are presenting themselves in doctors' offices in increasing numbers in response to the campaign for periodic examinations by health and cancer agencies, represent candidates for presymptomatic cancer detec,tion and the ideal opportunity for diagnosis of cancer at a curable stage. It is the purpose of this paper to review the established diagnostic and detection techniques and discuss their practical application in the private office and general clinic. GENERAL PRINCIPLES
There are no specific symptoms or signs of early cancer and there is no reliable general·screening test for the disease. The early diagnosis of cancer depends upon careful examination by a physician. The first requirement for success is conviction on the part of the examining physician that early cancer diagnosis is both possible and important. There is no requirement of specialist training, only of adequate interest and time for the performance of a thorough examination. Success is achieved in direct proportion to the frequency of thinking cancer; every diagnostic lead which could mean cancer must be considered cancer until proved otherwise. The stage of the disease at diagnosis and thereby its curability are importantly determined by this "state of mind" of the original examining physician. The methods of examination for early cancer are basically (1) a careful history, (2) direct inspection and palpation wherever possible, (3) selected diagnostic tests when indicated by 1 and 2, and (4) biopsy for final diagnosis. These apply equally to the patient being examined for localized or for general systemic complaints, and to the asymptomatic, presumably well individual receiving a cancer detection examination. diagnosis is the determining factor in cancer end results, Hammond has recently published a brief review of the role of early diagnosis in cancer curability.2 Histologic type, invasiveness, and potential for metastasizing are obviously important factors in cancer, but for all tumors arising in a primary site there will always be a localized stage. Lack of improvement in end results is attributable to current inability or failure to diagnose and treat the disease at that stage.
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'fhe detection examination includes certain screening procedures for accessible organs but the methods of cancer diagnosis are the same, whatever the source of the patient. These will be considered by site after a brief review of biopsy and related microscopic techniques and an outline of a general detection examination. BIOPSY
Biopsy, the obtaining of a tissue specimen for pathologic examination, is the crux of cancer diagnosis. It should be employed promptly for all accessible suspicious lesions. There are a number of methods of biopsy and the proper choice is important in determining results. The appropriate method will vary with the site and with the competence and experience of the pathology laboratory to which the specimen is to be submitted. The essential requirement is that the tissue be representative of the lesion and that it not be crushed, coagulated, or otherwise rendered unreadable. As a rule, biopsy should be obtained by cutting with a scalpel or sharp punch instrument rather than by pulling, tearing or electrocautery. The ideal biopsy takes an entire lesion or mass for pathological examination. l'his is often possible with small skin lesions or polyps. In such cases the specimen should include a margin of normal-appearing tissue and the pathology report should note whether or not this is free of disease. Adequate sampling of a lesion may require the taking of several specimens from different areas, vvhich should then be separately identified both for the pathologist's reading and for the clinician's interpretation of the report. In surfacE( biopsies at least one specimen should include a junction with normal tissue at the periphery of the lesion. Aspiration or needle biopsy may be used to obtain histological, and cytological, specimens from a mass belovv a surface. It requires a laboratory experienced with the method for satisfactory interpretation, and is always limited by the uncertainty that the specimen is representative of the tumor. A positive reading by a competent pathologist is helpful in planning treatment, but a negative report never rules out cancer. CYTOLOGICAL TEST FOR CANCER
A method of obtaining material for microscopic study closely related to tissue biopsy is the Papanicolaou smear technique or the cytological test for cancer (CTC).4 This utilizes single cells or clusters of cells exfoliated from the surface of tissues and can provide reliable information in regard to the nature of a lesion when read by a competent cytologist or cytopathologist. The cytological smear technique has its widest use in screening for
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uterine cancer, but is also applicable as a diagnostic adjunct for any site from which exfoliated cells are shed. This includes the respiratory, gastrointestinal and urinary tracts, the serous cavities, and such organs as the breast and prostate when secretions are obtainable. In many cases the cytological smear may reveal the presence of cancer before a lesion can be seen or reached for tissue biopsy. It has the advantage over biopsy of providing a total surface sample and therefore is of increasing importance as attempts progress to identify cancer at the earliest preclinical or in situ stage. The specific applications of the smear technique will be referred to in the discussion of cancer diagnosis by site. In using the cytological test for cancer the following principles should be adhered to: 1. Cytological smears for cancer should be read by a cytologically trained person. Positive reports must be given only by a cancer cytologist or by a pathologist experienced in reading cytological preparations. 2. A positive smear must be confirmed by biopsy before planning treatment. The only exception is in cases of tumors inaccessible to bronchoscope, gastroscope, proctoscope or cystoscope where surgery may have to serve as a diagnoE;tic approach. Even at operation the nature of the exposed lesion should be confirmed by frozen section biopsy if possible before proceeding with definitive treatment. The requirement of histological confirmation of a cytological diagnosis before proceeding with treatment is sound and must be complied with in whatever way possible at this stage in the development of cytology. CANCER DETECTION
Cancer detection, the diagnosis of presymptoItiatic cancer, is a logical extension of the concept of early diagnosis as a means of cancer control. During the past fifteen years the experience of cancer detection centers and associated cJinic and office programs throughout the country has demonstrated practical detection methods for a number of accessible sites. The type and extent of examination varies but always incorporates the routine performance of established screening procedures. Many of these procedures can be effectively applied in general practice. At the Strang Clinic, Memorial Center, where experience is based on over 100,000 general cancer detection examinations, the routine consists of the following: History Fanlily history of cancer Significant past illnesses, operations, and environrnental exposures Review of systems Physical Examination Skin and superficial lymph nodes
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Nose, mouth, throat and vocal cords Neck and thyroid gland Breasts Thorax and lungs Abdomen Genitalia Digital exarnination of rectum and prostate Pelvic examination and vaginal-cervical smears Musculoskeletal and neurologic survey
Laboratory
Hemoglobin White blood cell count and differential Peripheral blood smear Urinalysis with microscopic examination of centrifuged sediment Stool guaiac test for occult blood Papanicolaou vaginal-cervical smears
X-Ray
Photoroentgen film of the lungs Proctosigmoidoscopy is performed on a return visit for all persons 45 and older; stomach survey photofluorographic films are advised for the same group. Biopsy is an integral part of the examination when suspicious lesions of accessible areas are encountered. Suggestive leads from the routine history, physical examination, laboratory or x-ray are follo,ved by referral for further diagnostic tests or examinations as indicated.
The routine history and physical examination
The methods which have proved effective in cancer detection and early diagnosis are reviewed for each site, starting with the pel~ic examination ,which historically provides the first example of screening techniques , applied to an accessible organ.
Female Genitalia Examination for early cancer of the female genitalia requires both careful pelvic examination and the taking of cytological smears. Neither
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alone is adequate. Together they form a simple and effective standard office procedure. At Strang Clinic the routine is as follows: 1. External Examination. Note introitus and any abnormalities of skin, glands and urethra. 2. Vaginal Smear. Aspirate posterolateral fornices with vaginal pipette (Fig. 56). Spread secretion thinly on clipped glass slide and place immediately in bottle of ether-alcohol solution. 3. Internal Inspection. Insert speculum without lubricant; inspect vagina and cervix carefully'. Note character of vaginal discharge if present. 4. Cervical Smear. Swab entire cervical surface with cotton applicator, then insert and rotate applicator inside cervical os. Roll applicator on unclipped slide making a thin, even smear. Place slide immediately in ether-alcohol solution. 5. Iodine Test. Do not perform if patient gives history of iodine sensitivity. ,<:With cotton applicator apply 3.5 per cent iodine sparingly to cervix only. INote position and size of nonstaining areas. 6. Bimanual Examination. Include palpation of fornices and adnexa as well as cervix and fundus, and rectovaginal examination using finger cot over glove. 7. Endocervical Smear. To be done in addition to above if there is: (a) history of abnormal bleeding, (b) enlargement of uterus, (c) blood on cotton swab when rotated in external os for routine cervical smear. Wipe cervix clean if lubricant has been used. Insert cannula well into endocervical canal and exert gentle suction by drawing back on syringe (Fig. 56). Spread secretion thinly on slide and place in ether-alcohol solution. 8. Biopsy. (a) Biopsy any suspicious granular or eroded areas, including those which do not take iodine stain and areas of leukoplakia. (b) Record biopsied areas for pathologist and on clinical chart. Figure 56 shows the equipment used in taking vaginal and cervical smears by the Papanicolaou method. Other means of obtaining material from the cervix, such as the cervical scrape, may be substituted for the s\vab technique if the laboratory receiving the material is acquainted with the method. In all cases the cytologist should be given clinical data in regard to menses, hormone or other gynecological therapy, pregnancy and infection ~ince these. factors may be associated with cytological changes. 8 Cervical Cancer Detection. Vaginal-cervical smears properly taken and interpreted, combined with biopsy of all suspicious areas, will detect essential.ly every case of carcinoma of the cervix. In a series of 36 cases at Strang Clinic approximately 90 per cent were in situ or preinvasive cancer; 42 per cent were detected as a result of the routine smear before there were clinical findings by history or pelvic examip.a,~ipn. 9 In cases
Early Diagnosis of Cancer
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with a suspicious or positive cytology report and a normal appearing cervix, four-point biopsies are taken as recommended by Foote and Stewart. 10 Cases with repeated abnormal smears and no focus of cancer demonstrable by biopsy are followed at frequent intervals by a specialist. It is important that no cauterization or other treatment be undertaken at the first examination, or until cytological and pathological reports
Fig. 56. Set-up for routine vaginal-cervical cytological smears and endoc·ervical aspiration.
are received, in order not to obscure a lesion and confuse subsequent care. Corpus Uteri and Adnexa. While the smear-and-hiopsy program is highly successful in detecting asymptomatic cancer of the cervix, cytological techniques are not as effective for cancer of the fundus and adnexa. Cells from these sites may appear in routine smears, but as a rule clinical suspicion based on abnormal bleeding or findings on bimanual pelvic examination, followed by appropriate diagnostic measures such as endometrial biopsy and dilatation and curettage for the fundus or laparotomy for the adnexa, will be necessary for diagnosis of cancer of the upper
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genital tract. Recently Hecht has demonstrated that more frequent use of endometrial aspiration smears as an office procedure can aid in the early diagnosis of cancer of the fundus. ll Breast
Recent reports indicate that the female breast is the commonest site of human cancer. 12 Yet in spite of its accessibility, it presents a major problem in early cancer diagnosis. Adequate examination is based primarily on inspection and palpation. It demands care, attention to detail and a minimum of three to five minutes of a practiced doctor's time. Casual and rapid examination can discover only relatively large and late cancer. Routine Breast Examination. Inspection is made with the patient sitting facing the examiner in good light. The contour and symmetry of the breasts are noted with arms relaxed at the side, with arms raised, with pectoral muscles tensed, and with the patient leaning forward. The pectoral areas and axillae are best examined during this part of the procedure. Thorough palpation of the breast tissue is performed while the patient is supine with the arm raised and shoulder elevated or body turned slightly so that the breast tissue is distributed evenly over the chest wall. In this position all quadrants are palpated methodically using firm but gentle pressure of the finger pads. Special attention should be paid to the subareolar tissue and to the nipple. Cytology. If there is a history of nipple secretion a gentle attempt should be made to obtain fluid from each duct. When nipple secretion is obtained as above, or appears spontaneously, it should be smeared for cytological study, with notation of the position of the duct from which it came. Smears, when obtained, may lead to a diagnosis of carcinoma before the development of a palpable mass. 'rhey also may be helpful in distinguishing benign from early malignant tumors of the breast in the occasional case when exfoliated secretions are encountered. Clinical Aids to Differential Diagnosis of Breast Masses. When an abnormal mass is found in the breast, certain aids are available which may help to determine its nature clinically. 1. AGE. The probability that a mass in the breast is cancer increases with age. After the menopause any mass must be considered cancer until proved otherwise. 2. FEEL AND BEHAVIOR OF THE LESION. The significant breast lesion is usually firm and well demarcated from the surrounding breast tissue. Fixation is a relativeJy late change in cancer and should not be waited for. Benign fibrocystic changes are frequently palpable in the functioning breast but tend to be irregular in size and consistence and more prominent premenstrually. Regression on re-examination after menses is a , clinical finding which favors the benign nature of a lesion.
'Early Diagnosis of Cancer
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3. TRANSILLUMINATION. Transillumination requires a darkened room for accuracy and is not used as part of the routine examination. It is a }useful diagnostic adjunct, however, in differentiating a fluid-filled cyst from a solid tumor. , 4. ASPIRATION. Needle aspiration can be helpful in collapsing a cyst and establishing its benign nature. rrhe aspiration of solid tumors is used to obtain histologic and cytologic preparations for microscopic study, but this technique has the important limitations outlined in the section 'on biopsy and is not appropriate for general use. Final Diagnosis. l-'he nature of any lesion which remains clinically suspicious must be determined by excisional biopsy. l'1his is a surgical procedure usually best performed in a hospital by a surgeon with a pathologist in attendance and facilities for frozen section readings. The promptness with which the patient with a suspicious lesion is referred for excisional biopsy is one of the primary factors in determining end results in breast cancer. Rectum and Colon
The rectum and distal colon become accessible' and highly productive sites for cancer detection by the routine practice of two procedures, digital examination of the rectum and proctosigmoidoscopy. Digital Examination of the rectum should be routine in every physical examination. When thoroughly performed it can reach most large lesions of the lower rectum. Even good digital examination, however, will miss early mucosal and soft polypoid lesions. It cannot be depended upon to rule out disease of the rectum and is not an adequate detection procedure alone. Proctosigmoidoscopy permits visualization of the mucosa of the rectum and sigmoid colon and biopsy of any lesion seen. It thus meets the b-asic requirements for successful cancer detection, namely direct access, with opportunity for pathological examination of tissue specimens when indicated. The effectiveness of such a detection device is emphasized in the experience at Strang Clinic where cancer of the rectum and colon is the second most frequent cancer diagnosed in men and the third most frequent in women. 6 Figure 57 shows the equipment necessary for office proctosigmoidoscopy. Any type of lighted sigmoidoscope is adequate. The tube to the left of the scope is a suction tip for attachment to vacuum pump or line. This may not be necessary in a well cleansed patient. The most common lesion encountered on routine proctosigmoidoscopy is the rectal or colon polyp. All such lesions should be routinely biopsied or removed for microscopic diagnosis. This can be easily accomplished by using a long biopsy forceps through the sigmoidoscope at the time of routine examination. Even though appearing benign clinically, a signifi-
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cant number of polyps will prove to be early cancer or will show premalignant changes. In one series of 479 polyps found on routine examination, 5 per cent revealed adenocarcinoma, and 3 per cent showed atypias. 13 For the detection of lesions of the colon beyond the reach of the sigmoidoscope, all patients with mucosal lesions at proctosigmoidoscopy and patients with symptoms or laboratory evidence of bleeding are regularly referred for barium enema ,vith air contrast studies. The
Fig. 57. Equipment for routine proctosigmoidoscopy.
determination of the nature of tumors or lesions proximal to the sigmoid may be aided by special studies such as colonic washing for cytology,13a but will often require the direct approach of laparotomy. Prostate
Digital palpation through the rectum is the standard means of detecting early cancer of the prostate. This should be routine in every male examination. The significant finding is a very firm to stony hard area or nodule. While such a finding may be due to calculus, chronic infection or adenoma, the possibility that it IS cancer must always be entertained, especially after the fifth decade.
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In the differential diagnosis of a clinically suspicious gland, Papanicolaou smears of prostatic fluid obtained by careful massage may be helpful if positive. They have been disappointing, however, in routine screening of men over 50 for preclinical carcinoma of the prostate. 14 There is also no established biochemical test for cancer of the prostate before it has extended beyond the capsule of the gland. At present, routine digital examination is the' one practical and reliable means of detecting early prostatic cancer. Skin and Lip
The early diagnosis of cancer of the skin is achieved by a habit of careful inspection of all body surfaces and the judicious use of biopsy. Early diagnosis may be of relatively little vital importance in the slo\v growing and rarely metastasizing basal cell carcinomas, and of only moderate importance in many squamous cell carcinomas of the skin and lip. But the malignant melanoma demands the earliest possible diagnosis and treatment. Since the histological nature of a skin lesion is often difficult, if not impossible, to predict clinicaliy, it is essential that determination of the histopathology of all potentially malignant lesions be accomplished by biopsy as promptly as possible. The proper management of skin lesions requires judgment on the part of the examining physician. Since most individuals have multiple pigmented moles or nevi, it is totally impractical to remove them all. The decision in regard to management of a specific lesion should be~based on the following current understanding of skin cancer: ~ 1. The classic signs of malignancy in a skin lesion, namely increase in size, alteration in color, or ulceration, are often evidence of late cancer in the case of melanoma. 2. There are no reliable distinguishing features of the premalignant or early malignant skin lesion. It may be pigmented or nonpigm.ented, papillary or smooth surfaced. As a general rule, the blue nevus, the hairy mole, and the wen or steatoma are rarely the site of cancer. 3. The junction cell nevus is the precursor of most melanocarcinoma. 15 Unfortunately, the junction cell nevus has no specific clinical characteristics and diagnosis depends upon biopsy of appropriate lesions. Since there is a higher relative incidence of primary melanoma of the skin of the feet, the genitalia, and the head and neck, removal and microscopic study of all nevi of these sites is recommended as, a routine procedure. Head and Neck
The head and neck examination should include direct inspection of the nasal and pharyngeal passages, inspection and palpation of the oral ~avity, tongue and floor of the mouth, and mirror visualization of the
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hypopharynx, larynx, and vocal cords. Where this is done routinely early lesions have been detected before the onset of complaints of "fullness" or "lump" or hoarseness. Usually the early lesion is accessible for direct biopsy but cytologic smears obtained by swab or washings may be useful in special instances. Careful palpation of the neck for masses and of the thyroid gland is an essential part of the detection examination. Adenomas of the thyroid are the site of cancer in from 5 to 10 per cent of cases. 16 Although the solitary adenoma is more apt to be malignant, there are no absolutely reliable clinical means of differentiating the benign from the early malignant lesion of the thyroid. Therefore, the objective of early cancer diagnosis requires a policy of surgical removal and microscopic study of all thyroid adenomas. The finding of a cervical node in an adult must be considered evidence of possible malignant disease either locally or elsewhere. If it cannot be attributed to infection, and if persistent for more than two weeks, biopsy is indicated. In experienced hands, aspiration of cervical nodes or masses can be a useful diagnostic procedure, but as a general rule the approach should be by surgical excision. The head and neek area completes the list of sites which are accessible for direct examination and practical screening procedures in the general office. For other sites the early diagnosis of cancer will depend on proper selection and timing of diagnostic studies following symptoms elicited on history, or leads obtained from routine laboratory tests such as blood count, stool guaiac, urinalysis and chest x-ray. '"fwo sites, lung and stomach, though not accessible for routine direct examination, merit special attention because of their importance as sources of cancer and the fact that specific aids to diagnosis can be outlined for each. Lung
Detection. Chest x-ray for asymptomatic lung cancer have yielded poor results in general population surveys but are practical for persons with increased risk of pulmonary cancer. These include men over 45, particularly with a history of long-term heavy smoking or exposure to kno\vn lung irritants. 17 Periodic chest x-rays should be provided for these groups either as part of the office examination or through community programs. Fluoroscopy should be done if it is the only facility available, but it does not take the place of an x-ray film in screening for an early lesion. Any abnormality on fluoroscopy or on survey minifilm should be followed by full diagnostic x-rays. Early Diagnosis. Early diagnosis of lung cancer requires alertness for all possible clinical leads and the prompt utilization of special diagnostic procedures. The following clinical findings must be considered evidence
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of cancer until proved otherwise, particularly in men in the fifth decade and older: 1. 1'umor, or any undiagnosed abnormality, detected on x-ray examination. 2. Chronic cough, \vhether or not associated with sputum or recent change in charaeter. 3. Vague pulmonary complaints such as "discomfort" or "uneasiness" in the chest. Pain, dyspnea, hemoptysis are usually symptoms of late cancer. 4. Recent history of pneumonitis or atypical or recurrent pneumonia, even if followed by complete resolution. In the presence of the above or related findings, the following studies are required: 1. Diagnostic x-ray studies, type to be determined by location and characteristics of lesion if present. Whether radiographic studies are positive or negative, workup should proceed to 2. Cytological studies on: (a) Sputum if produced. Three satisfactory specimens should be obtained before accepting negative reports as ruling out cancer. (b) Tracheal or bronchial washings. Tracheal washings can be used for obtaining smears as a relatively simple office procedure. I8 Bronchial washings are performed at bronchoscopy. 3. Bronchoscopy, with biopsy of any suspicious area, and selective bronchial washings. As diagnostic studies are initiated earlier in the course of disease, lesions tend to be smaller or more peripheral and less accessible for biopsy. In such cases directed bronchoscopic washings for cytology are a reliable means of determining the nature and location of a peripherallesion. I9 4. rrhoracotomy with direct exploration of tumor or suspicious area. Surgical approach may be the only means of establishing the presence of early cancer. 20 Thoracotomy should be employed with increasing frequency for diagnostic purposes when other methods fail. Delay for evidence of cancer by tumor growth, progressive symptoms or biopsy proof is frequently the reason for inoperability when the chest is finally explored. Stomach
Detection. There is no practical method of screening all examinees for cancer of the stomach. In contrast to the rectum and sigmoid colon, the upper gastrointestinal tract is not accessible to simple office techniques. Visualization by gastroscope is a major procedure; the taking of cytological specimens entails time and inconvenience for the patient; and the use of standard gastrointestinal series x-ray studies is limited by cost and the requirement of a roentgenologist. Methods must be employed for improving the yield of positive findings
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and making diagnostic procedures in asymptomatic patients productive. These are based on the use of clinical selection factors as follows: 1. Age over 45. 2. Evidence of bleeding either by unexplained occult blood in the stool or unexplained anemia. 3. Achlorhydria. A method of gastric analysis has recently been developed which avoids intubation and makes this prescreening procedure acceptable to well patients. 21 The presence of normal acidity does not rule out the possibility of cancer. 4. Pernicious anemia. 5. History of gastric ulcer. 6. Family history of gastrointestinal cancer. In a few medical centers stomach x-ray surveys by rapid fluoroscopy or photofluorography have been demonstrated as a means of determining which individuals in older age groups should have full diagnostic x-rays.22 Photofluorographic films are reliable and economical for screening purposes but are now, and probably always will be, of limited availability because of the requirement of special equipment. Early Diagnosis. The major hope for earlier diagnosis and higher cure rates in gastric cancer rests in the office and general clinic where symptomatic patients are seen. The decision in regard to which patients should have diagnostic studies is notoriously difficult. It can be aided by applying the clinical factors listed under the prescreening devices above. The standard diagnostic procedure is gastrointestinal x-ray series. When this reveals abnormal mucosal patterns, filling defects or ulceration, further diagnostic tests to establish the nature of the lesion should be undertaken promptly without waiting to "observe the course." The one exception may be gastric ulcer where a trial on medical treatment is acceptable if carefully supervised and checked at short, i.e., two week, intervals. Both the benign ulcer and the ulcer associated with cancer may show signs of healing but the benign ulcer should be completely healed, with normal gastric wall and mucosa, in a maximum of four weeks. Any other course is strong presumptive evidence of cancer. There are three direct ways of establishing the nature of a lesion demonstrated on gastrointestinal series. Generally they should be employed in order as follows: 1. Cytological studies. Smears of cells obtained from the gastric mucosa are an established diagnostic adjunct. Freshness of cells must be assured by use of such techniques as the abrasive balloon. 23 2. Gastroscopy. Biopsy through the gastroscope is a means of proving the presence of cancer when the lesion can be reached, but gastroscopy has the limitation that it cannot reach all areas of the stomach. 3. Exploratory laparotomy. In the presence of persisting clinical suspicion, whatever the evidence by cytology or gastroscopy, laparotomy
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should be performed for direct exploration of the stomach. In the stomach, as in other viscera such as lung, large bowel and ovary, competent surgical exploration must be used with increasing frequency as a diagnostic measure if cancer is to be treated at the stage when surgery can be curative. AIDS TO PRACTICE OF CANCER DETECTION AND EARLY DIAGNOSIS
In the practice of cancer detection and early diagnosis the efficiency and thereby the effectiveness of procedures can be improved by use of certain aids. The importance of a systematized method of examination has already been stressed. Preprinted history and physical examination forms for the routine detection examination can save time in recording findings and expedite accuracy and usefulness of charts. 7 Self-administered family history and screening personal history questionnaires can also be used to spare physician time. If such forms are used, however, it is important that the examining physician personally explore all positive leads with the patient, particularly in the review of systems. In addition to methods of conserving professional time by systematized forms and office procedures, there are means of increasing the effectiveIl,ess of examinations for cancer by concentrating efforts on those patients and groups with higher cancer risk. A minimum age of 35 for women and 45 for men is based on the over-all age-specific trends of cancer incidence by sex and is a practical measure in the face of limited facilities. Other selection factors which should give patients priority for examination are strong family history of cancer, previous cancer, and history of exposure to known environmental or industrial carcinogens. The effectiveness of cancer detection and diagnostic procedures in an office or clinic will be determined to a considerable extent by the support :'available in the community. Lay education programs are important in 'acquainting the public with the symptoms which may mean cancer and in promoting periodic health examinations and such special programs as breast self-examination. In some communities professional groups and health agencies have 1~rganized educational and diagnostic services to aid examinations in the ~private office and cancer clinic. Efforts are also being made to increase !~~he number and quality of pathological and cytological facilities available ~J;o the profession. In all of these efforts the attitude of the practitioner is the key to sucilress or failure of the cancer program.
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~j'
REFERE~CES
Younge, P. A., Hertig, A. T. and Armstrong, D.: A Study of 135 Cases of Carcinoma in Situ of the Cervix at the Free Hospital for Women. Am. J. Obst. Gynec. 58: 867-895, 1949.
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Emerson Day
2. Hammond, E. C.: Early Diagnosis and Cancer Cure Rates. CA Bull. Cancer Prog. 3: 175-176, 1953. 3. Crowell, B. C. and Branch, C. F.: Cancer Clinics-Cancer Diagnostic ClinicsCancer Detection Centers. Bull. Am. ColI. Surge 32: 131-143, 1947. 4. Papanicolaou, G. N.: The Cell Smear Method of Diagnosing Cancer. Am. J. Pub. Health 38: 202-205, 1948. 5. Cameron, C.: Recent Trends in Early Diagnosis of Cancer. New York State J. M. 52: 2099-2102, 1952. 6. Day, E.: The Strang Cancer Prevention Clinic Memorial Center-A "Second Look." J.A.M.A. 8: 169-171, 1953. 7. Day, E., Rigney, T. G. and Beck, D. F.: Cancer :Detection. An Analysis and Evaluation of 2111 Examinations. Am. J. Hyg. 57: 344-365, 1953. 8. Scapier, J., Day, E. and Durfee, G. R.: Intraepithelial Carcinoma of the Cervix. Cancer 5: 315-323, 1952. 9. Day, E.: Cytological Techniques in Screening Uterine and Lung Cancer. CA Bull. Cancer Prog. 2: 57-62, 1952. 10. Foote, F. W. and Stewart, F. W.: The Anatomical Distribution of Intraepithelial Epidermoid Carcinomas of the Cervix. Cancer 1: 431-439, 1948. 11. Hecht, E. L.: The Value of the Endometrial Smear in the Detection of Malignancy. New York State J. M. 52: 2745-2752,1952. 12. Gerhardt, P. R. and Handy, V. H.: Cancer Diagnosis. Morbidity and Mortality Statistics. New York State J. M. 52: 2235-2236,1952. 13. Miller, C. J., Day, E. and L'Esperance, E. S.: The Value of Proctoscopy as a Routine Examination in Preventing Deaths from Cancer of the Large Bowel. New York State J. M. 50: 2023-2027,1950. 13a. Bader, G. M. and Papanicolaou: The Application of Cytology in the Diagnosis of Cancer of the Rectum and Descending Colon. Cancer 5: 307-314, 1952. 14. Strang Clinic, Memorial Center: Unpublished data. 15. Allen, A. C. and Spitz, S.: Malignant Melanoma. Cancer 6: 1-45, 1953. 16. Cope, 0.: Diseases of the Thyroid Gland (Part II). New England J. Med. 246: 451-457, 1952. 17. Wynder, E. L. and Graham, E. A.: Etiologic Factors in Bronchiogenic Carcinoma with Special Reference to Industrial Exposures. A. M. A. Arch. Indus. Hyg. & Occup. Med. 4: 221-235, 1951. 18. Cahan, W. G. and Parr, H. W.: Tracheal Aspiration-An Additional Method for the Early Diagnosis of Carcinolna of the Lung. Cancer 3: 475-480, 1950. 19. Watson, W. L. and others: Recent Advances in the Diagnosis of Early Lung Cancer. New York Med. 7: 16-20, 1951. 20. Bernatz, P. E. and Clagett, O. T.: Exploratory Thoracotomy in Diagnosis and Management of Certain Pulmonary Lesions. J.A.M.A. 152: 379-381, 1953. 21. Segal, H. L., Miller, L. L. and Morton, J. J.: Detection of Achlorhydria by Tubeless Gastric Analysis. J. Nat. Cancer Inst.13: 1079-1086, 1953. 22. Wigh, R. and Swenson, P. C.: Photofluorography for the Detection of Unsuspected Gastric Neoplasms. Am. J. Roentgenol. 69: 242-267,1953. 23. Cooper, W. A. and Papanicolaou, G. N.: Balloon Technique in the Cytological Diagnosis of Gastric Cancer. J.A.M.A. 151: 10-14, 1953. 444 East 68th Street New York 21