Carcinoma of the Colon and Rectum

CARCINOMA OF THE COLON AND RECTUM CAPTAIN

J.

EDW ARD BERK

l\h:mCAL CORPS, ARMY OF THE UNITED STATES

CARCINOMA of the large bowel is relatively uncommon in military personnel as compared with other disorders of the gastrointestinal tract. Lesions of this nature, however, are not altogether rare. In the large Army general hospitals in the Zone of the Interior, carcinoma of the colon and rectum is seen sufficiently often to constitute a distinct problem. Twenty-one patients with proved cancer of the large bowel have come under my observation in the course of four years of consecutive service in the gastrointestinal sections of two Army general hospitals in the Second Service Command. In many of these cases little or no suspicion of malignant disease was entertained during the early symptomatic stage. The comparative youth of the patients and the presumed unusual character of their manifestations were misleading features which often lulled the examining officer into a false sense of security. The important lesson drawn from this experience with military personnel is the need for a greater colon cancer awareness among physicians and laity alike. In the hope of contributing toward this end, a review of the subject of carcinoma of the colon and rectum is being presented utilizing our experience with military personnel for purposes of illustration.

INCIDENCE

Of all deaths from cancer about 11 per cent are caused by malignant neoplasms of the colon and 5 to 6 per cent by malignant neoplasms of the rectum and anus. Together these lesions are responsible for approximately 27,000 deaths in the United States yearly. The incidence of malignant tumors of the large bowel in military personnel is not to be estimated from the experience with these lesions in Army general hospitals in the Zone of the Interior. These hospitals would be expected to have the highest incidence in the Army since patients are sent to them from numerous installations which are more directly concerned with servicing troops in the field or in garrisons. Of lROl soldiers (enlisted men) discharged from the gastrointestinal sections of the Tilton and Rhoads General Hospitals with an established diagnosis between November 1, 1942, and August 31, 1945, seven, or 0.3H per cent, proved to have cancer of the colon or rectum. In addition to these cases, many others were encountered during the same period in officers and in enlisted men who were admitted directly to the Surgical Service. From the Tilton General Hospital, Fort Dix, New Jersey. 307

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ETlOLOGY

Previously existent benign colonic neoplasms, such as adenomatous polyps, may subsequently undergo malignant transformation. Although doubted by some, there is much to support the belief that this sequence . of events takes place fairly frequently. The malignancy index in cases of colonic polyposis varies widely. Reports of different observers range from 5 to 85 per cent7 with the incidence of malignant change greatest in those polyps found in carcinomatous colons. Very often both the gross and histologic appearance of a colonic neoplasm is such as to suggest that it developed on the basis of a previous polyp (Fig. 59). Patients with the heredofamilial type of disseminated polyposis almost invariably tend to develop colonic carcinoma sooner or later. This was the case in one of our patients, a white soldier, aged 26, who had proctosigmoidoscopic as well as roentgenologic evidence of a widely

Fig. 59.-An ulcerated adenocarcinoma of the rectum removed from a 27 year old white soldier. The polypoid character of the base of the lesion, especially at its periphery, suggests that the tumor originally may have been nodular in character and subsequently ulcerated. The appearance also suggests the possibility that the lesion may have had its origin in a preceding polyp . .

disseminated polyposis. Carcinomatous changes were shown to be present in several of the polypoid lesions. The tissues of the intestinal wall of those colons in which a carcinoma has developed have been shown by Dukes19 and by Bargen, Cromar and Dixon3 to show changes which they construe as potentially malignant. The possibility of a potentially malignant state in the colon acting as a precursor to the development of carcinoma is an attractive hypothesis, but it remains to be proved that the changes noted are precursors and not effects of the cancer. Inflammatory lesions Of the colon may predispose to the development of malignancy. Bargen, Jackman and Kerr4 reported an incidence of carcinoma of 3.2 per cent in 871 cases of chronic ulcerative colitis observed by them and Coffey and Bargen16 reported an incidence of carcinoma in polyposis associated with ulcerative colitis of 25 per cent. Most other investigators,

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however, have not encountered such a high percentage of carcinoma in cases of chronic ulcerative colitis. The consensus is that the polypoid lesions of ulcerative colitis may become malign:lnt but probably do so rarely. Diverticulitis has long been thought to predispose to cancer. Most physicians today consider the relationship between diverticulitis and cancer to be incidental rather than actual. l l The important thing to bear in mind is that an individual with diverticulitis may also have a carcinoma. We were misled in this regard in one of our cases, a 52 year old officer with a history of intermittent diarrhea and abdominal pain in whom a barium enema disclosed multiple diverticula with areas of spasm and irritability indicative of diverticulitis. One such area was present at the splenic flexure. A few months after discharge from the hospital the patient was readmitted with an advanced malignancy of the splenic flexure which had eroded through the stomach to form a gastrocolic fistula. Undoubtedly, the malignancy . had been present at the time the patient was first seen but waS mistakenly attributed to diverticulitis. Still another one of our patients with distinct roentgenologic evidence of diverticulosis of the colon showed areas of irregularity and narrowing in the sigmoid and,in the rectosigmoid. These proved to be separate carcinomatous tumors situated in a bowel which was also the seat of a widespread diverticulosis. Anal cancer may take origin in fistulas, fissures, inflamed anal tags and other inflarmllatory lesions of the anui"7 but is an exceedingly rare occurrence. Chronic irritation of the colon, as from constipation and parasitic infestation, appears to play little or no role in the production of cancer. A predisposition toward colonic cancer may be inherited5 but some exciting factor seems to be required, in addition to the inherited susceptibility, for the actual development of carcinoma. PATHOLOGY

About two-thirds of the malignant tumors of the large bowel involve the left colon and about one-:-third the right colon. 13 • 32 The rectum, sigmoid flexure, cecum and ascending colon, transverse colon, descending colon, hepatic flexure and splenic flexure tend to be involved in order of frequency. I. 28. 35 In this series of twenty-one cases in military personnel, the frequency of involvement was as follows: rectum, 3; rectosigmoid, 6; sigmoid flexure, 1; descending colon, 2; splenic flexure, 2;· transverse colon, 2; ascending colon, 3; and cecum, 2. In one case two separate lesions were present and in another, not included in the tabulation, several polyps in various locations in the bowel showed carcinomatous transformation. Adenocarcinomas of the large intestine may be divided for purposes of classification into four main types. (1 ) Nodular. This type projects into the lumen as a globular sort of mass which frequently ulcerates. Sometimes, especially in the cecum, the tumor adopts an en-

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cephaloid or fungoid appearance, grows to a large size, and oozes freely from its ulcerated surface (Fig. 60). The connective tissue content is variable but usually is plentiful enough to make the tumor mass hard. (2) Scirrhous. In this variety the fibrous tissue element is outstandingly prominent, pro.ducin~ an extremely hard, contracted mass. As a rule, tumors of thiS variety are small and give rise to the so-called "napkin-ring" type of growth. Intestinal obstruction is frequent. The scirrhous tumors are rare in the rectum and are found

Fig. 60.-Nodular fungoid adenocarcinoma of the cecum removed from a 39 year old Negro soldier. This illustrates the size to which lesions in this region may grow and demonstrates the ulcerative, necrotic character of the base from which sanguineous exudate characteristically oozes.

much oftener in the left than in the right colon (Fig. 61). (3) Colloid. This variety of growth is also ~nown as mucoid, mucinous or gelatinous, because of its shiny gelatmous appearance and rich content of mucinous material. Tumors of this nature are uncommon. They are found most commonly in the rectum and rectosigmoid and in the cecum and ascending colon. Ulceration occurs frequently. (4) Papillary. This type resembles a warty excrescence or papilloma. Usually shallow ulcerations take place. The tumors are not very common and tend to occur most often in the left colon.

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Microscopically, adenocarcinomas of the well-differentiated variety classically show well-formed glands. These are lined by large columnar cells with a darker than normal cytoplasm and a vesicular hyperchromatic nucleus many of which show mitotic figures. In the poorly differentiated tumors glandlike structures are much less in evidence and the tumor cells' tend to appear in masses or cords. In the colloid variety there is an excessive amount of mucinous material both inside the cells and outside in the intracellular spaces. Adenocarcinomas of the large intestine characteristically grow slowly and are of a relatively low grade of malignancy. Numerous

Fig. 61.-Scirrhous adenocarcinoma of the ascending colon. This was found at laparotomy in a 42 year old white soldier who described intermittent right lower quadrant abdominal pain and who showed signs of partial intestinal obstruction alld a palpable firm mass in the right lower quadrant of the abdomen. This type of lesion is comparatively uncommon in this portion of the bowel. The great tendency for these lesions to produce narrowing of the bowel and intestinal obstruction is well shown.

schemes have been advanced to classify carcinomas of the large intestine as to their grade of malignancy. The various criteria used include: (1) the boundaries reached (Dukes)20; (2) the pace of growth determined by the percentage content of differentiated as compared with undifferentiated cells observed microscopically (Broders)1°; (3) the degree of histologic differentiation 40 ; and (4) the amount of mucin demonstrable in the cancer cells, presuming that mucus formation is an expression of intestinal cell function. sI About 75 percent of carcinomas of the colon are Broders' Grade 1 or 2.26,32 Two-thirds of the carcinomas of the right colon and nearly three-fourths of those of left colon may be classified as Grade 1 or 2.36 The majority of rectal

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carcinomas are of Grade 2 malignancy and at least 75 per cent are either Grade 1 or 2. Stout40 found that only 22 per cent of rectal and 14 per cent of colonic cancers were undifferentiated or poorly differentiated. Widespread metastasis may occur with the regional lymph nodes, the liver and the lungs being the most common metastatic sites. Metastasis takes place usually in one of three ways: (1) by direct extension; (2) through the blood stream; (3) via the lymphatics. Of these, the lymphatic route is undoubtedly the most important. Careful dissection of all nodes, with or without special clearing of the bowel, has shown that metastasis to the nodes is present in from 65 to 70 per cent of the cases of carcinoma of the rectum17 • 22. 24 and in about 60 per cent of the cases of carcinoma of the colonP The tendency to metastasize is generally greatest in the rectum and sigmoid and least in the cecum. This is somewhat remarkable because the lymphatic structures in the cecum and appendix are more extensively developed than in any other segment of the large bowel. Regional lymphatic extension is extremely common and widespread in the colloid variety of adenocarcinoma despite the fact that this tumor is slow-growing and late in metastasizing. Some interesting features· regarding metastasis have been brought to light by the work of Gilchrist and David 24 and Coller, Kay and MacIntyre. 17 These investigators have shown among other things (1) that age apparently exerts no important influence; (2) that there is no correlation between the size of the lesion and the presence of metastasis, the incidence of metastasis even being higher in persons with smaller lesions than in those with larger ones; (3) that the higher the grade of malignancy the more likely the presence of nodal metastasis; and (4) that retrograde spread and interrupted spread may occur with normal nodes intervening between the primary site and the next nearest involved node. It has been estimated that approximately 5 per cent of colonic neoplasms are multiple and primary.29.38 This is an important but frequently forgotten feature of adenocarcinoma of the large intestine. In the flush' of discovery of a neoplasm of the colon or rectum one tends to neglect the remainder of the bowel which deserves also to be surveyed carefully for additional tumors. One of our patients showed two separate unrelated primary carcinomas, one in the rectum and the other in the sigmoid flexure. Another, previously noted, had multiple carcinomas engrafted on a preexistent diffuse polyposis. CLINICAL ASPECTS

The average age of, patients with cancer of the colon or rectum is about 55 years with from 85 to 90 per cent of the cases occurring in persons older than 40 years. This very preponderance of the older age group tends to make us forget that approximately 5 per cent of

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the cases are persons under the age of 30 years. In the group of twenty-one cases in military personnel the ages ranged from 20 to 59 with an avera~e of 36 years; seven, or 33.3 per cent were less than 30 years of age. The sex ratio in colonic carcinoma is approximately two males for each female. As might be expected, only one of the military personnel group was a female. The ratio of whites to Negroes is difficult to assess because of the variation in the population in the localities from which reports on the subject emanate. In the group of military personnel, two of the twenty-one were Negroes. A bare majority of patients with malignant disease of the colon and rectum, approximately 60 per cent, seek medical advice within a year after the onset of symptoms; only 20 per cent seek advice within the first three months. 26 The average interval from onset to hospitalization is about nine months in cancer of the rectum and one year in cancer of the colon. The duration of symptoms before diagnosis is longer on the average when the carcinoma is in the right colon than when if is in the left colon. Symptoms.-In the early stage of the disease the clinical pattern in colonic carcinoma, regardless of the portion of the large bowel involved, presents no pathognomonic symptoms. Any symptom sufficient to attract attention to the bowel may be a symptom of cancer. Completely asymptomatic cancer of the large intestine in the sense that a lesion may be discovered in a patient without symptoms of altered bowel function, abdominal cramps, pain or abnormal stools is rare. This was true of one of the patients in the group I observed, a 43 year old white soldier who complained of heartburn and rhythmical, postprandial, epigastric pain of an ulcer character. Roentgenologic examination disclosed a deformed duodenal cap consistent with duodenal ulcer. However, on physical examination a huge nodular, hard liver was felt and on barium enema examination an obstructing lesion was demonstrated in the descending colon just distal to the splenic flexure (Fig. 62). In patients with carcinoma of the right colon, constitutional symptoms are ,prominent and a tumor mass is often palpable while obstruction is not very common. There is some type of abdominal discomfort or distress in at least 75 per cent of the cases. When real pain is present it is usually mild and is commonly indefinitely localized to the right periumbilical area and the right lower quadrant. Almost half the patients describe dyspeptic phenomena such as anorexia, bloating, belching, epigastric fullness, nausea and vomiting. Weakness, fatigue arid weight loss are fairly common. Approximately one in four complains of constipation, but this is ordinarily not as marked as in carcinoma of the left colon; it is uncommon in patients with lesions of the cecum. Diarrhea occurs perhaps a little more frequently than constipation. Characteristically no blood is grossly discernible in the stools.

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The symptoms that characterize carcinoma of the left colon are predominantly those of intestinal obstruction. The obstructive phenomena usually appear fairly early so that evidence of constitutional deterioration develops late in the course of the disease. Ulceration with bleeding is more commonly apparent in the stools. Abdominal pain, which is described in from one-half to two-thirds of all cases, is of variable severity. In the initial stages it may amount to no more than a weighty feeling, an ache, a mild cramp, a dull pain or a feeling

Fig. 62.-A long malignant stricture of the descending colon just distal to the splenic flexure is clearly shown. This was discovered ina 43 yeal' old white soldier who had no symptoms referable to the large bowel, but who showed striking signs of widespread metastasis with a huge nodular liver.

of gaseousness associated with an increase in expulsion of flatus. The distress usually grows more pronounced as time passes and is succeeded in turn by griping and real colicky pain. Not uncommonly, intestinal obstruction with severe colic and abdominal distention develops rather abruptly and may even be the initial evidence of the disease. Constipation develops for the first time or becomes definitely more pronounced than had hitherto been true, in at least half the cases. The progressive character of the constipation is of the greatest importance. Diarrhea, which is encountered in from 10 to 20 per cent

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of all cases, is intermittent. Visible blood loosely attached to the outside of the stool is observed by approximately one-fourth of the patients. Weight loss is to be found in about a third or more of the cases but is a late developing change. Dyspeptic phenomena are uncommon. Carcinoma of the rectum is characterized in the main by a change in the character of the stool, alteration in bowel regularity and grossly visible bleeding. A gradually progressive alteration in the established bowel habit is one of the outstanding symptoms in patients with a rectal neoplasm. From 85 to 90 per cent of the patients observe blood or bloody mucus on defecation at some time in the course of the disease and the attention· of the patient not infrequently is first attracted by this. Pain ordinarily is not severe and is of a minimal character unless the anal sphincters are implicated or the tumor mass comes within the grasp of the sphincteric musculature. Extension of the growth into the perirectal structures or infiltration of the nerves also causes severe and pronounced pain. Characteristically, the pain is more of a distress, described as a weighty feeling in the pelvis or rectum, a sense of fullness about the outlet, soreness, irritation, itching or a mild cramping at the time of stool. Too much emphasis has been placed on the so-called "ribbon" or "pencil" stool as a prominent manifestation of cancer 'of the rectum. The fina-l form adopted by the stool is determined mainly by the caliber of the anal canal and a tumor mass is of . significance in this regard only when it involves the anus itself. Buie12 found deformed stools in only 14 per cent of 1937 patients of carcinoma of the rectum and sigmoid. Loss of weight and strength is present only in cases with advanced dise;lse and is usually antedated by other symptoms. Dyspepsia is rare unless metastasis has taken place to the liver or upper abdomen. Physical Findings.-The general appearance of a patient with a malignant tumor of the large bowel depends upon the duration of the ill- . ness, the stage of the groWth and the presence of complications such as abscess formation. In some patients with cancer of the cecum or ascending colon a pallor and sallowness may be seen even though nutrition is still good. If the abdomen is carefully palpated a mass may be found in about a third of all cases, irrespective of the location of the growth in the bowel. It is commonly believed that tumor masses are most often felt when the cancer is in the right colon, but this is open to question. If obstruction is present there may be audible and at times visible hyperperistalsis, abdominal distention and tympanites. Metastasis may be evidenced by distortion, hardening and thickening of the umbilicus; hardening, enlargement and nodularity of the liver; the presence of ascites; enlargement and firmness of the inguinal lymph nodes; the presence of an enlarged, palpable, left supraclavicular lymph node or enlarged, firm nodes in the axillae or at the outer border of the left pectoralis major muscle; or by physical abnormalities in the

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examination of the lung or demonstrable changes in the lung on roentgenologic examination. . Approximately 75 per cent of all rectal tumors are within the reach of the index finger provided a careful and adequate examination of the rectum is performed. Unfortunately, this simple yet important examination is still widely neglected. Not only will digital examination reveal the existence of a lesion, but in the presence of such a lesion it will also give important information as to its size, fixation, attachment to other structures and even the presence of enlarged lymph nodes. It has been estimated that six months is required for a lesion to traverse one-fourth of the circumference of the bowel. By this means a rough idea may be obtained as to the time the growth has been present. Occasionally, vaginal examination will disclose a mass in the rectosigmoid which was not felt on digital exploration of the rectum. LABORATORY FINDINGS

A variable degree of anemia will be found in about two-thirds of the patients with lesions of the right colon and about one-third of those with lesions in the pelvic colon. Anemia may be the only evidence of a cancer of the cecum or of the ascending colon. At times this may even mimic pernicious anemia. Leukocytosis is not especially common but occasionally remarkable elevations of the white blood cell count are seen, particularly when there is a great deal of necrosis, secondary infection or perforation with abscess formation. Occult blood will almost invariably be found in the stools. There is usually, but by no means always, an increase in the red blood cell sedimentation rate. PROCTOSIGMOIDOSCOPY

About 75 per cent of cancers of the large bowel develop in portions which may readily be visualized through the proctosigmoidoscope. Not only may the gross characteristics of a neoplastic lesion be observed through the instrument, but also its position, extent of local infiltration, mobility, and distance from the anal margin may be determined. An important adjunct of proctosigmoidoscopy in the presence of a suspicious lesion of the rectum or sigmoid colon is the taking of a biopsy. Too often, however, these specimens are reported by the pathologist as showing no evidence of cancer because no malignant tissue happened to be included in the biopsy. If there is some doubt about the malignancy of the lesion, another biopsy should be taken from near the base of the growth. If, however, the appearance of the lesion very strongly suggests malignancy, especially to a trained sigmoidoscopist, no delay should be countenanced in instituting therapy because of a negative report for carcinoma as determined from a biopsy sample. Adenocarcinomatous lesions appear through the proctosigmoido-

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scope as proliferative masses growing from one wall or encircling the bowel and blocking its lumen. In some cases an ulcerated lesion is seen with a necrotic base and heaped up nodular or polypoid edges. In still other cases the appearance is that of a necrotic tube lined by friable, easily traumatized, possibly polypoid, tissue. Characteristically, there is a fairly sharp line of demarcation between the cancer and the adjacent tissue. Rarely is there sufficient spasm or edema distal to the growth to obscure it. This is a feature of inestimable value in differentiating the lesion from more benign inflammatory states, such as diverticulitis. ROENTGENOLOGIC FEATURES

Roentgenologic examination in carcinoma of the large bowel is of the greatest usefulness as a means of demonstrating those lesions which are above the reach of the examining finger and beyond the view of the proctosigmoidoscope. If careful observation is made and roentgenograms taken in the oblique and lateral positions as well as the usual anteroposterior one, a diagnostic accuracy of over 90 per cent is to be expected. The use of the double contrast technic, wherein both air and barium are introduced to delineate the contour and mucosal pattern of the bowel, is an additional' aid in roentgenologic diagnosis. Occasionally, one encounters a patient who is unable to retain a barium enema in spite of the use of occluding rectal bags and other devices employed by the roentgenologist. In such cases a barium progress meal may reveal the tumor satisfactorily -especially if the lesion is in the right colon. If the barium meal is contraindicated in these cases because of intestinal Obstruction the introduction of a Miller-Abbott tube to the ileocecal valve and the injection then of a thin mixture of barium through the tube may succeed in delineating the lesion (Fig. 63). The lower portion of the bowel is notoriously difficult to examine by x-ray and diagnostic accuracy by this examination does not approach that for other portions of the bowel. Lesions in the flexures of the colon and those on the posterior wall of the cecum are also often difficult to demonstrate and are liable to be missed. Positive findings by x-ray are of the greatest value, but if one relies implicitly on a negative barium enema report one will often be misled. If there is any cause to doubt the findings, the barium enema should be repeated after a course of antispasmodics. The roentgenologic criteria of malignant infiltration in the large bowel are: (1) obstruction to the flow of the opaque medium which is persistent despite manipulation and change in position of the patient, especially if the head of the barium column is blunted and hooked; (2) a persistent filling defect whose outlines are jagged and irregular, particularly if the segment of colon involved is not very long; or (3) a stricture or annular narrowing of the bowel which is persistent and does not respond to antispasmodics.

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One should be very wary about forcing enema fluid beyond an area of narrowing and resistance in the large bowel. Small annular lesions of the sigmoid and descending colon may act in a ball-valve fashion, allowing the enema fluid to flow in easily but blocking its outflow. Or there may be some initial resistance to the passage of the opaque fluid followed by a sudden relaxation with a resultant rush of large quantities of fluid under considerable pressure into the bowel above

Fig. 63.-A roentgenogram of the terminal ileum, cecum and ascending colon obtained after introduction of a thin barium mixture through a Miller-Abbott tube in the patient whose specimen is shown in Figure 61. This demonstrates the value of such a procedure in the study of patients with suspected lesions of the right colon which cannot be shown by a barium enema and in whom a barium meal is contraindicated because of the presence of intestinal obstruction.

the lesion. In these cases the distending effect of the trapped enema fluid on bowel probably already weakened and thinned by preexisting obstruction may result in perforation. COMPLlCAnONS

The outstanding complication of adenocarcinomatous lesions of the large bowel is that of obstruction. Colic, constipation and abdominal

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distention are present in approximately 40 per cent of all patients with cancer of the large bowel. At least three-fourths of the tumors found in the left colon cause either partial or complete obstruction. Obstruction may develop acutely as a result of volvulus, intussusception, sudden clogging of a partially blocked lumen by accumulated fecal matter, or inflammatory changes with edema and swel1ing.,~One of the patients I observed, a 38 year old soldier, developed iI)t~titlal obstruction abruptly without any premonitory symptoms while in the hospital for the treatment of an unrelated orthopedic condition. At laparotomy a scirrhous adenocarcinoma of the transverse colon was found. Another soldier, 20 years of age, was admitted to a hospital because of the sudden onset of abdominal pain and abdominal distention. Retrograde barium enema study .disclosed an obstructing lesion just proximal to the hepatic flexure which had many of the characteristics of intussusception (Fig. 64, upper). Following evacuation of the enema the patient was completely relieved of his distress. Another barium enema examination performed at the Tilton General Hospital at a later date showed the intussusception no longer to be present and clearly demonstrated a large tumor mass in the ascending colon (Fig. 64, lower). Acute free perforation of an adenocarcinomatous tumor of the colon sometimes occurs with the development of peritonitis or a localized abscess. We observed this in a 33 year old soldier who suddenly developed severe abdominal pain with fever, leukocytosis and abdominal rigidity. Roentgenologic examination showed a dense fluid collection in the pleural space which was interpreted as an empyema. Injection ,of air after a diagnostic tap showed the air to be under the diaphragm and established the presence of a subphrenic abscess. This was surgically drained with distinct improvement. Abdominal pain developed during the period of convalescence together with evidence of distention and signs indicating progressing intestinal obstruction. At laparotomy a cecal carcinoma was found which had perforated and given rise to the subphrenic abscess and now had produced obstruction at the ileocecal junction. Invasion of adjoining viscera with the formation of a fistula is not too uncommon. Carcinomas of the transverse colon, for example, are especially prone to invade the stomach. Two of the patients in the group I have seen in military personnel had a gastrocolic fistula. In one, an officer 52 years of age, the jejunum was also involved. The remarkable feature of this case was the fact that the initial manifest~tion was a massive hematemesis without any symptoms referable to the large bowel. Urinary tract complications are fairly frequent because of the close anatomical relationship between this tract and the colon and rectum. Fistula formation, invasion of the bladder and obstruction of the ureter with resultant hydronephrosis are among the complications which may occur. At times the urinary symptoms dominate the clinical picture.

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Fig. 64.

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DIAGNOSIS

The diagnostic record in carcinoma of the iarge bowel leaves much to be desired. It is regrettable, but nonetheless true, that an average of nine months to a year elapses before the patient with cancer of the large bowel is admitted to a hospital or a correct diagnosis established. Despite all the advances which have been made in the field of medicine, the .diagnosis of carcinoma of the large bowel today is being made no earlier. Much of this is the fault of the laity. The average layman is not conversant with the potential importance of what may appear to be innocent symptoms referable to the colon. For one reason or another, a physician is not consulted until symptoms have been present for some time or until some dramatic symptom such as rectal bleeding occurs which arouses real concern. On the other hand, physicians are not. entirely blameless. Many practitioners delay more than seems warranted before arriving at a diagnosis or referring the patient to a responsible clinic. Very often this is due to circumstances beyond the practitioner'S control. There seems little excuse, however, for the findings of Braund and Binckley9 who reported that of one hundred patients with cancer of the rectum referred to the Memorial Hospital in New York City, 20 per cent had not received a rectal examination. Furthermore, a distressing number of patients are operated on for conditions alien to the major disorder. From 20 to 25 per cent of patients with cancer of the rectum and anus are subjected to hemorrhoidectomy within six months prior to recognition of the malignant' lesion. 2s • ss Approximately 15 per cent of patients with cancer of the right colon undergo appendectomy after the onset of symptoms.so In addition, about 25 per cent of patients with cancer of the left colon or rectum are given paregoric or bismuth for diarrhea for long periods, or receive vaccines for colitis or sulfonamide compounds for supposed bowel infection.27 It cannot be overemphasized that no patient should be subjected to an anal operation without thorough examination of the colon proximal to the anus. Nor must one treat diarrhea which lasts more than three days without attempting thoroughly to investigate the large bowel by all means available. Many more patients will be discovered to have carcinoma of the large bowel at a much earlier stage if malignant disease is held suspect Fig. 64.-Upper, Roentgenogram taken during retrograde barium enema study of a 20 year old white, soldier complaining of right upper quadrant abdominal pain. Obstruction to the passage of the barium at about the hepatic flexure is 'seen. There also is well demonstrated the oudine of an intussusceptum. Following evacuation of the barium clysma there was an abrupt relief of the abdominal pain. . Lower, Roentgenogram of a barium enema study made on the same patient six weeks later. During the intervening period he had been free of abdominal pain. This roentgenogram shows the intussusception. no longer to be present and demonstrates a marked filling defect of the ascending colon just proximal to the hepatic flexure.

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in all patients, especially those over thirty years of age, who manifest a change in bowel habit of more than brief duration, or recently acquired abdominal distress related to defecation, or gradual develop-" ment of increasing abdominal distention and peristaltic unrest. A malignant tumor ought still to be held suspect even if a thorough physical examination discloses some other defect sufficient in itself to produce the symptoms. This is well illustrated by one of our cases, a 44 year old nurse," who was seen because of constipation and abdominal cramping of short duration. Vaginal examination showed the uterus to be markedly enlarged and studded with multiple fibromyomas. A retrograde barium enema study of the colon was made before undertaking hysterectomy in order to make certain that no other cause for the symptoms was present. This disclosed an irregular filling defect in the upper descending colon which proved after resection to be an adenocarcinoma. TREATMENT

Operative Treatment.-The indications for radical surgery in patients with cancer of the colon and rectum have broadened considerably in recent years. This is reflected in the progressive increase in the operability rate so that at the present time about 60 to 70 per cent of all cases of cancer of the colon and rectum are considered worthy of surgical exploration when seen. 25 ,26 In approximately 70 per cent of the cases which are explored resection is done. This represents an average resectability rate at the present time of about 50 per cent. 1 , 15,32 Extension to adjacent organs is today no deterrent to radical surgery; all or part of some of the neighboring viscera or somatic structures may be sacrificed in order to accomplish the removal of a colonic cancer. Cattell and Sugarbaker14 estimate that from 15 to 20 per cent of successfully resected lesions require the removal in part or whole of some adjacent structure. Involvement of the lymph nodes and even distant metastasis to the liver are not necessarily contraindications to radical resection of the primary tumor. If the metastatic lesions in the liver are not numerous, death may be delayed some and the patient rendered much more comfortable during the time that remains to him. This was true of one of our patients who lived several months after resection of an adenocarcinoma of the sigmoid which was found at the time of laparotomy to have metastasized to the liver and to distant lymph nodes. Certain basic principles govern the surgical management of cancer of the large bowel. Foremost, it should be emphasized that operation is not an emergency except possibly in the case of obstruction. In the presence of obstruction the bowel must be" decompressed before any radical or major operative procedure is attempted. Whether or not a preliminary proximal drainage should be done routinely in all cases, regardless of the presence of obstruction, the age, or condition of the

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patient is still debated. Lastly, rigidly standardized surgical procedures are neither desirable nor possible. A maxim well worth observing is the one that advises fitting the operation to the patient rather than the patient to the operation. Preoperative Preparation.-If a patient with cancer of the colon or rectum is to be adequately prepared for operation at least three to seven days are required. During this preparatory period a low residue diet is fed which is rich in protein and carbohydrate. If required, vitamin concentrates and additional protein in the form of amino acid preparations or plasma may be given as supplements to the diet. During the forty-eight hours immediately prior to operation only concentrated liquids are given by mouth. If anemia is marked, bloodtransfusions, iron given orally, and liver injections may be administered. The bowel is cleansed and decompressed through the use of saline laxatives and enemas. As prevention against peritoneal infection a vaccine made up of a suspension of colon bacilli and green producing streP.tococci may be given in~raperitoneally over a period of from six to eIght days before operatlOn 1R or Coh-Bactragen39 can be introduced at operation. The employment of poorly absorbed sulfonamide compounds such as sulfasuxidine or sulfathalidine in doses of 3.0 gm. of the former or 1.5 gm. of the latter every four hours for seven days, has proved of real value in the hands of many investigators. 34 We have employed sulfasuxidine routinely in our patients with excellent results. Penicillin is an adjuvant drug ~hat ma~ ?e of some value but is without effect on the gram-negatIve bacIlh that frequent the intestinal tract. Streptomycin, the newest antibiotic, holds great promise but has yet to be completely evaluated. Finally, a Miller-Abbott tube may be introduced to prev~nt postoperative distention and pressure on suture lines and for purposes of feeding. In our hands this has proved a valuable procedure, especiallY in cases in which right colonic surgery is performed. Operative Procedure.-The technical procedures which are employed need not be detailed here. They vary depending on the portion of colon involved and the inclinations of the surgeon. Whenever ~ossible a one stage procedure is preferable to multiple-stage operatIons. However, situations are encountered in which the dictates of good judgment demand that too much not be attempted at one time. It would be foolish for example, to attempt time-consuming and extensive surgery in ;n elderly person in poor physical condition. Also, many lesions which appear to be inoperable because of abscess formation or inflammatory fixation not infrequently may be removed after a preliminary colostomy which puts the inflamed part at rest. Resection with primary anastomosis appears to be gaining in favor over the exteriorization type of procedures with delayed anastomosis. The expanding use of chemotherapy and the Miller-Abbott tube may further this trend.

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Postoperative Care.-Fluids ordinarily are not given by mouth until gas has been expelled. In most cases, however, the patient can tolerate small amounts of water of room temperature after the first twentyfour hours. If a Miller-Abbott tube is in place, some fluid may be introduced through this tube. The bulk of fluids and nutrients are given parenterally in the form of glucose, saline, distilled water and amino acid solutions. Plasma and blood are given as needed to maintain proper chemical balance. Vitamin supplements, especially vitamin C which plays a role in wound healing, may be given with the infusions or by injection. Continuous suction siphonage is maintained through the Miller-Abbott tube for the first twenty-four hour postoperative period at least. Readily absorbable sulfonamide compounds like sulfathiazole and sulfadiazine are given until the temperature is normal and has remained so for forty-eight hours in order further to combat peritonitis and wound infection. They may be given with the parenteral fluids until such time as the patient can tolerate material by mouth. Penicillin and streptomycin may supplant these drugs when they are available for wider use. If the operative procedure ended in a colostomy, as in the case of an abdominoperineal resection, there is little need for the poorly absorbed sulfonamides, sulfathalidine and sulfasuxidine. If, however, the operative procedure involved suture of the bowel with retention of the involved segment in the peritoneal cavity, Poth34 believes they should be given for twelve days postoperatively to control the intestinal bacterial flora. These, too, threaten to be replaced by streptomycin. Oxygen by mask or nasal catheter immediately after the operation will help avoid pulmonary complications, as will occasional whiffs of carbon dioxide, massage of the extremities, frequent change in position and the use of the anticoagulants, heparin and dicoumarol. A word might be said here about the care of a colostomy. The poor reputation which colostomies have is the result of experience with those done for purely palliative reasons. If the primary tumor is removed and certain principles of care are observed, life with a colostomy is not the dread existence it is popularly conceived to be. After healing has occurred the patient should be taught to irrigate the colostomy regularly each day. After irrigation the area is cleansed and covered with a protective film of petrolatum gauze or a dry dressing and an abdominal support is applied. A protective past~ of aluminum, zinc oxide ointment or a detergent such as alkyl sulfate in a bland base, may be coated over the skin should it become excoriated. With the use of a constipating type of diet and hydrophylic colloids, kaolin, and similar preparations, the irrigations may soon be stopped and a regular bowel habit developed. From four to six months is usually required before a colostomy functions most satisfactorily. Babcock2 favors placing the colostomy in the perineum rather than the ab-

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domen because in his experience less care is required, the situation is more like the natural one and better control is developed. Nonoperative Treatment.-Malignant growths which are accessible through the proctosigmoidoscope may be destroyed by means of surgical diathermy, employing either electrocoagulation or fulguration. Strauss41 and Ferguson21 report favorable results with the former, and Buie12 has been impressed with some results he has obtained with the latter method. However, the number of cases in which surgical diathermy may be employed is not great and the ultimate value of this form of treatment, especially as compared to other methods with which it must compete, is yet to be determined. Radiation therapy has a distinCt place in the management of cancer of the large bowel. Radium is especially useful in those technically inoperable or in recurrent lesions of the lower bowel so situated as to be accessible for local implantation of radium seeds. Radon seeds may also be applied preoperatively to reduce the size of a large growth and thereby permit a more conservative type of operation. Although the suitability of interstitial radiation is limited, external radiation may be more widely applied. 6 Roentgen radiation is most useful when combined with radium, particularly in inoperable lesions or in individuals who refuse surgery. Other forms of nonfJperative treatment have been employed in cases of malignancy of the large bowel, but none of them appear to have achieved any significant degree of success. These include the application of carbon dioxide snow, the intramuscular injection of colloidal metals, such as lead phosphate and selenide, copper and gold, the injection of a mixture of the toxins of Streptococcus erysipelatis and Bacillus prodigiosus, so-called Coley's fluid, and, more recently, the administration of avidin, a protein present in egg-white which is capable of reducing the amount of biotin available for storage in neoplastic tissue. The care of the patient witb advanced inoperable cancer of the colon or rectum is a taxing problem. Numerous methods of alleviating pain are available and may be employed as needed. These include the use of opiates, cobra venom, the introduction of alcohol or ammonium sulfate into the subarachnoid space, local sympathetic nerve block and, in desperate cases, chordotomy. Rectal irrigation with warm 1: 10,000 solution of potassium permanganate or physiological saline solution may help diminish rectal discharge. If bowel motions are frequent and troublesome, opiates may be given in sufficient ap10unts to paralyze the bowel. Liquid petrolatum or saline laxatives are of value to help overcome the threat of complete blockage in the presence of an obstructing lesion. Brandy or other alcoholic concoctions may stimulate a jaded appetite and food should be prepared and served in as attractive a manner as possible. An attempt should be made to keep the patient occupied writing, reading or otherwise en-

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gaged with the various productive endeavors offered by the occupational therapist. PROGNOSIS

The average operative mortality throughout the United States at the present time in cases of cancer of the large bowel is in the neighborhood of 10 per cent. The rate is steadily being reduced, however, and many competent surgeons have already achieved remarkably low rates, especially for combined abdominoperineal resection for cancer of the rectum and rectosigmoid. In the group of twenty-one military patients I have followed, twelve were operated on and a resection accomplished with one immediate postoperative death, a mortality of 8.3 per cent. With incomplete treatment, palliative treatment or no treatment whatsoever, patients with rectal cancer live an average of ten to eleven months after the diagnosis has been established. Under similar circumstances, patients with colonic cancer live an average of six months. 40 The bright note in prognosis is the fact that approximately half the patients with cancer of the colon or rectum who survive radical resection live for five years or more. 14 ,15 The unfortunate thing is that the lesion proves to be resectable in only half the cases when the patient is first seen. The results following radiation therapy are conflicting. Five year survival rates have been reported which range frolll 1.8 per centS to 50 per cent. 6 Electrocoagulation has still to be assessed; Strauss and his co-workers 42 have reported a survival rate of over five years in 25 per cent of the cases they treated. The outlook in malignant tumors of the large bowel seems much better than that for most other forms of internal cancer. As compared with cancer of the stomach, a disorder only slightly greater in frequency, the five year curability is at least three times as great. The progressive increase in operability rate and the concomitant decrease in mortality is resulting in a climbing survival rate and a greater total number of survivors. The problem remains largely that of early. diagnosis. If there could be established a rigidly observed program of periodic health examinations which would include a digital exploration of the rectum, and if all discovered precursor lesions, especially adenomatous polyps, were destroyed as by fulguration, the toll of death from malignant tumors of the colon and the rectum would be appreciably reduced. The laity must be induced to seek medical attention much earlier than has hitherto been the case. Physicians in turn must be exhorted to apply freely and without procr~stination those diagnostic procedures now at their command. Most important of all, a colon cancer awareness must be engendered in both the public and the members of the medical profession. ACKNOWLE\)(;MENT: I am greatly indebted to Dr. Henry L. Bockus for his kinJ permission to cite here some factual data contained in Volume II of Bockus' "Gastroenterology."

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REFERENCES I. Alien, A. W. and \Velch, C. E.: Malignant Diseases of the Colon. Factors

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Influencing the Operability, Morbidity and Mortality. Am. J. Surg., 46: 171 (Oct.) 1939. Babcock, W. W.: The Advantage of Perineal Over Abdominal Colostomy with Technic for Transferring the Abdominal Opening to the Perineum. J.A.MA.,113:1933 (Nov. 25) 1939. Bargen, J. A., Cromar, C. D. L. and Dixon, C. F.: Early Carcinoma of the Colon. n. Relation between Subclinical Inflammatory Processes and Carcinoma. Arch. Surg., ·,tj:I92 (Aug.) 1941. Bargen, J. A., Jackman, R. J. and Kerr, J. G.: Studies on the Life Histories of Patients with Chronic Ulcerative Colitis (Thrombo-Ulcerative Colitis), with Some Suggestions for Treatment. Ann. Int. Med., 12:339 (Sept.) 1938. Bargen, J. A., Mayo, C. \V. and Griffith, L. A.: Familial Trends in Human Cancer. J. Hered., 32:7 (Jan.) 1941. Binkley, G. E.: Results of Radiation Therapy in Primary Operable Rectal and Anal Cancer. Radiology, 31 :724 (Dec.) 1938. Bockus, H. L.: Gastroenterology. Philadelphia, W. B. Saunders Co., 1944, V 01. n, Chapter LXVI. Bowing, H. H. and Dixon, C. F.: Advances ill the Treatment of Carcinoma of the Rectum. M. C1,IK. NORTIJ AMERICA, 2>:915 (July) 1941. Braund, R. R. and Binldey, G. E.: A Plea for the Earlier Diagnosis of Rectal Cancer. New York State J. Med., 42:33 (Jan. 1) 1942. Broders, A. c.: Carcinoma: Grading and Pr2ctical Application. Arch. Path., 2:376 (Sept.) 1926. Brown, P. \V. and Marclcy, D. M.: Prognm;i, of Diverticulitis and Diverticulosis of the Colon. lA.M.A., 109:1328 (Oct. 23) 1937. Buie, L. A.: Practical Proctology. Philadelphia, \V. B. Saunders Company, 1937. Buirge, R. E.: Carcinoma of the Large Intestine. Review of 416 Autopsy Records. Arch. Surg., 42:801 (May) 1941. Cattell, R. B. and Sugarbaker, E. D.: Recent Advances in the Surgical Treatment of Carcinoma of the Colon and Rectum. Surgery, 11:644 (April) 1942. Coffey, R. c.: Cancer of the Rectum. A Study of Five-Year Cures. Surg., Gynec. & Obst., 58:465 (Feb.) 1934. Coffey, R. J. and Bargen, J. A.: Intestinal Polyps: Pathogenesis and Relation to }\;falignancy. Surg., Gynec. & Obst., 69:136 (Aug.) 1939. Coil er, F. A., Kay, E. B. and Maclntyre, R. 5.: (a) Regional Lymphatic Metastases of Carcinoma of the Rectum. Surgery, 8:294 (Aug.) 1940; (b) Regional Lymphatic Metastases of Carcinoma of the Colon. Ann. Surg., 114:56 (July) 1941. Dixon, C. F., Bargen, J. A. and Tennison, W. J.: Intraperitoneal Injection of Vaccine in Prevention of Postoperative Peritonitis. Arch. Sllrg., 4):507 (Oct.) 1942. Dukes, c.: Simple Tumors of the Large Intestine and Their Relation to . Cancer. Brit. J. Surg., 13:720 (April) 1926. Dukes, C. E.: The Classification of Cancer of the Rectum. J. Path. & Bact., 35:323 (May) 1932. . Fergllson, L. K.: Treatment of Carcinoma of the Rectum and Rectosigmoid by Electrocoagulation. Internat. Clin., 1:199 (March) 1940. Gabriel, W. B., Dukes, C. and Bussey, H. J. R.: Lymphatic Spread in Cancer of the Rectum. Brit. J. Surg., 23:395 (Oct.) 1935.

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23. Garlock, ]. H., Ginzburg, L. and Glass, A.: Complications and Causes of

Mortality of the Surgical Treatment of Carcinoma of the Colon and Rectum. Surg., Gynec. & Obst., 76:51 (Jan.) 1943. 24. Gilchrist, R. K. and David, V. c.: Lymphatic Spread of Carcinoma of the Rectum. Ann. Surg., 108.:621 (Oct.) 1938. 25. Goligher, ]. c.: The Operability of Carcinoma of the Rectum. Brit. M. ]., 2:393 (Sept. 20) 1941. 26. Gregg, R. O. and Dixon, C. F.: Malignant Lesions of the Colon and Rectum: Operability and Prognosis. Proc. Staff Meet., Mayo Clin., 16:657 (Oct. 15)

1941. 27. Jones, T. E.: Diagnosis and Surgical Aspects of Carcinoma of the Colon. Pennsylvania M. J., 46:208 (Dec.) 1942. 28. Judd, E. S.: A Consideration of the Lesions of the Colon Treated Surgically. South. M. ]., 17:75 (Feb.) 1924. 29. Mayo, C. W.: Multiple Primary Malignant Lesions of the Colon with Resection: Report of an Unusual Case. Proc. Staff Meet., Mayo Clin., 16: 479 (July 24) 1940. 30. Mayo, C. \V.: Malignant Lesions of the Right Portion of the Colon. Proc. Staff Meet., Mayo Clin., 16:67 (Jan. 29) 1941. 31. Ochsenhirt, N. Significance of Mucus-Forming Cells in Carcinoma of the Large Intestine and Rectum. Surg., Gynec. & Obst., 47:32 (July). 1928. 32. Ochsner, A. and DeBakey, M.: Operability, Morbidity and Mortality Factors in Carcinoma of the Colon. Am. ]. Surg., 46.:103 (Oct.) 1939.

c.:

33. Pemberton, J. de J. and Dixon, C. F.: Summary of the. End-Results of Treatment of Malignancy of the Thyroid Gland and the Colon, Including the Rectum and Anus. Surg., Gynec. & Obst., 58.:462 (Feb.) 1934. 34. Poth, E. ].: Succinylsulfathiazole and Phthalylsulfathiazole in Surgery of the Colon. Surgery, 17:773 (June) 1945. 35. Raiford, T. S.: Carcinoma of the Large Bowel. Part I. The Colon. Ann. Surg., 101:863 (March) 1935; Part 11. The Rectum. Ann. Surg., 101:1042 (April) 1935. 36. Rankin, F. W. and Johnston, C. C.: Cancer of the Colon (Chap. XL) (in Portis, S. A.: Diseases of the Digestive System). Philadelphia, Lea & Febiger, 1941. . 37. Rosser, c.: The Etiology of Anal Canct:r. Ann. J. Cancer, 11:328 (Feb.) 1931. 38. Schweiger, L. R. and Bargen, J. A.: Multiple Primary Malignant Lesions of the Large Bowel. Arch. Int. Med., 66:1331 (Dec.) 1940. 39. Steinberg, 8.: Experimental Background and Clinical Application of Escherichia Coli and Gum Tragacanth Mixture (Coli-Bactragen) in Prevention of Peritonitis. Am. J. Clin. Path., 6:253 (May) 1936. 40. Stout, A. P.: Human Cancer. Philadelphia, Lea & Febiger, 1932. 41. Strauss, A. A.: A New Method and End Results in the Treatment of Carcinoma of the Stomach and Rectum by Surgical Diathermy (Electrical Coagulation). ].A.M.A., 106:285 (Jan. 25) 1936. 42. Strauss, A. A., Strauss, S. F., Crawford, R. A. and Strauss, H. A.: Surgical Diathermy of Carcinoma of the Rectum. J.A.M.A., 104:1480 (April 27) 1935.