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THE AMERICANJOURNAL OF CANCER

A Continuation of The Journal of Cancer Research

VOLUME XVI SEPTEMBER, 1932 NUMBER 5

ANALYSIS OF 104 CASES OF CARCINOMA OFTHE LARGE INTESTINE 1

HOWARD T. KARSNER, M.D., AND BURTON CLARK, JR., M.D.

(From the hl8titule of Pathology and the Department of Surgery, WC8tern Resene Uniuersiu}and Lakeside Hospital, Cleveland. Ohio)

The purpose of this paper is to report on an analysis of 104 casesof proved carcinoma of the large intestine admitted to LakesideHospital in the ten years ending in 1931. The material was obtained by resections, autopsies, and biopsies. In that period noinstances of sarcoma or melanoblastoma were observed.

AGE INCIDENCE

Age incidence covers a wide range, but there is no doubt thatthe greatest number of cancers of the colon occur between the agesof forty-one and sixty. In Kauffmann's series of 320 cases theincidence was slightly higher in the sixth than in the fifth decade,but in AnschUtz' series of 128 cases it was slightly higher in thefifth decade. In our much smaller series the fourth and fifthdecades showed about equal incidence, with a slight reduction inthe sixth. Hayden and Shedden found that in 303 cases of carcinoma of the rectum the greatest incidence was in the sixthdecade, with the seventh next and the fifth next. This is true,also, of Miles' 587 cases. In our series the incidence was about thesame in these three decades. It is noteworthy that carcinoma ofthe colon occurs at a somewhat earlier period than carcinoma of therectum, as can be seen by a comparison of Graphs 1 and 2.

The occurrence of cancer of the large intestine in the third andfourth and in the eighth and ninth decades is not inconsiderable.

1 Extension of an address delivered before the Ncw York Academy of Medicine,Feb. 4, 1932.

934 HOWARD T. KARSNER AND BURTON CLARK, JR.

At less than twenty years of age it is relatively uncommon, ourseries including but one case, in a male patient nineteen years old.Ewing refers to a cancer of the cecum at twelve years of age, :3 ofthe rectum at eleven to seventeen years, one of the sigmoid attwelve years, and one of the colon at three years. Phifer collected49 cases of cancer of the sigmoid and rectum in patients less thantwenty years old, including one in a newborn monster, one in amale nine years old, 22 in patients between eleven and fifteen years

Age Di.5tt"'ibutionCanc.er of Rectum

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GRAPH 1

liayden- Shedden gKaY'5ne.ro- Clarl<..~

GRAPH 2

and 25 in patients between sixteen and twenty. These casesshowed a definite predilection for the sigmoid flexure. Metastasiswas rare and principally to lymph nodes. Wainwright reportedone case, and collected 6 others from the literature, of carcinomaof the colon above the sigmoid, and Drinkwater added a case in it

girl of fifteen years. This would indicate that in early life carcinoma of the large intestine occurs with greatest frequency in thesigmoid, then in the rectum, and much less often in the rest of thecolon.

CARCINOMA OF LARGE INTESTINE 935

RACE AND SEX INCIDENCE

Comprehensive data on race incidence have not been found.Cleveland is a city with a large negro population, but only 2 of 100of our cases in which a note as to color was made occurred innegroes.

Considering cancer of the colon, exclusive of the rectum, Kauffmann reported 192 cases in males and 128 in females; AnschUtz 90in males and 38 in females. Anschutz quoted deBovis as finding

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the ratio 6 : 5. Rankin stated that at the Mayo Clinic the ratio isapproximately 2 : 1. Of our patients, 27 were males and 25 females.The data of Hayden and Shedden on rectal cancers showed 179males and 124 females. Miles reported 326 cases in males and 261in females. In our series there were 34 males and 19 females. Thecombination of these figures shows in the larger series, for the entirelarge intestine, 797 males and 551 females; in our series, 60 malesand 44 females. It cannot be said that sex ratio is significantly


different as between cancer of the rectum and of the colon. Inboth males are more often affected than females.

Cancers throughout the large intestine show their maximumincidence in females at a somewhat earlier age period than in

.sex DistributionCancers of Go10 nKarsner - Clark

..se.x DistributionCancers of RectumKarsner - ClarK

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males. As regards cancer of the colon and sigmoid before fortyyears of age, in Kauffmann's series it occurred in 15 per cent of themales and 22 per cent of the females. Before fifty years of age thelesion affected 43 per cent of the males and 48 per cent of thefemales; before sixty years of age, 77 per cent of the males and 73per cent of the females. Anschutz (1907) was impressed by this


difference, and an analysis of his 128 cases shows 15.5 per cent ofthe males and 36.8 per cent of the females affected before fortyyears of age, 42.2 per cent of the males and 64.7 per cent of thefemales before fifty, and 70.1 per cent of the males and 78.9 per

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cent of the females before sixty. In our smaller series the distribution before forty years of age is 26 per cent of males and 44per cent of females; before fifty years of age, 52 per cent of malesand 72 per cent of females; and before sixty years of age, 70 percent of males and 100 per cent of females.

An analysis of Hayden and Shedden's cases of rectal cancershows that, whereas 5.5 per cent of the male cases occurred beforeforty years of age, 8 per cent of the females were in the corresponding age period. Before fifty years of age the percentages are 26for males and 27 for females; before sixty years of age, 57 for malesand 60 for females. Little or no significance can be attached tothese two latter sets of figures. In our small series the differencesare more striking but even less significant. Our figures are asfollows: before forty years of age, 6 per cent of males and 21 percent of females; before fifty years of age, 30 per cent of males and

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GRAPH 9

938


58 per cent of females; before sixty years of age, 59 per cent ofmales and 79 per cent of females.

It is safe to conclude that the incidence of cancer of the colonfalls at a somewhat earlier period of life in females than in males.This probably applies, also, to cancers of the rectum, though theevidence is not so convincing as in cancers of the colon. Theinadequate data available on cancers occurring earlier than twentyyears of age show a great preponderance of males. The difference between males and females indicated above must be due

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principally to a relatively higher incidence in females in the thirdand fourth decades.

SITE OF CANCER

Carcinoma is far more frequent in the large intestine than inthe small intestine. Ewing quotes Nothnagel to the effect thatamong 343 cases of intestinal carcinoma coming to autopsy, 164were in the colon, 162 in the rectum, 7 in the duodenum, and 11 inthe ileum. Schlieps, also quoted by Ewing, is said to have foundamong 542 intestinal carcinomas 259 in the colon, 257 in the rectum,20 in the duodenum, and 16 in the ileum. Oberndorfer quotes

940 HOWARD T. KARSNER AND BUR'fON CLARK, JR.

Lubarsch as having reported on 1608 cases, of which GG4 were inthe colon, 846 in the rectum, (i!) in the duodenum, 22 in the ileum,and 7 in the appendix. In the ten-year period covered in thisreport 1693 autopsies were done. Among these were 13 cancers ofthe large intestine, or 0.08 per cent as compared with Oberndorfer's2.35-2.8 per cent, which included the entire intestine. For thesame period we had 19,490 surgical specimens, of which 91 were ofcancers of the large intestine. In this period autopsies showed onecase of cancer of the duodenum and one of the ileum, and thesurgical specimens one cancer of the ileum. No case of cancer ofthe appendix was observed, although many carcinoids were found.

TABLE I

Anatomical Distribution of Cancers of Colon

}(i)rte l Petermann, Kauffmann Karsner andand An.chuh * Clark

Cecum ..... " ....... ........... Vi.8 per cent 19.4 pel' cent 13.5 pel' centAscending colon .. .............. 7.4 7.5 17.3Hepatic flexure....... '" . ...... 6.4 7.5 .'5.8Transverse colon ............... 14.8 11.6 17.3Splenic flexure ................. 10.4 10.3 7.7Descending colon .. . . . . . . . . . . .. . 3.4 5.3 -

Sigmoid .... " .... " ........... 41.7 38.4 38.5

* Data compiled by Ewing.

Our cases of cancer of the large intestine include 52 cancers of thecolon and 52 of the rectum. This ratio differs from Lubarsch'sfigures-664 cancers of the colon and 846 of the rectum-and fromNothnagel's (quoted by Rankin)- 249 of the colon and 262 of therectum. As indicated by Oberndorfer, a certain factor of erroris introduced in the inability to determine whether extensivecancers at the junction are primary in the rectum or sigmoid. It isprobable, however, that about 15 per cent of all cancers are cancersof the large intestine and that these are divided almost equally between colon and rectum.

It has been thought that the flexures of the large intestine areespecially favorable sites for the development of cancer, and Hartwell asserted that the splenic flexure is the third most common sitefor the growth of colonic cancer. In material subjected to examination the exact situation is sometimes difficult to determine.

CAHCINOMA OF LAHGE INTESTINE 941

Table 1 represents a certain probability of error but in general maybe regarded as correct.

With this grouping it is apparent that except for the sigmoidthe flexures show no special predilection. The major incidence isin the cecum, transverse colon, and sigmoid. The splenic flexuremight be regarded as next in order, but our cases have beenclassified so as to include in this situation only those growthswhich actually affect the angle. OUf 7.7 per cent compares as wellwith deBovis' 4.9 per cent and Judd's 4.1 per cent as it does withthe other figures in Table 1. The data show no graded increaseof incidence from proximal to distal segments of the colon.

TABLE II

A natomical Distribution of Cancers of Colon

KarsnerFischer Ansohute Kauffmann and

Clark----Cecum }Ascending colon .... 36.1 per cent 33.6 per cent 34.1 per cent 36.5 per centHepatic flexureTransverse colon ..... 9.7 11.7 11.6 17.3Splenic flexure } 20.8 16.4 15.7 7.7Descending colon ...

Sigmoid ............. 33.4 38.3 38.6 38.5

Table II analyzes the situation in somewhat different fashion.It emphasizes the fact that there is no progression of incidence inthe colon. All the data indicate the preponderance of cancers ofthe colon in the proximal and distal parts of the gut. Except in thedata of Fischer, the sigmoid is found to be affected somewhat moreoften than the proximal part of the colon. In Judd's series thesigmoid was involved in 50.4 per cent of the cases as compared with27.5 per cent for proximal part of the colon. With a larger numberof observations, the divergence between the incidence of the diseasein transverse colon and in splenic flexure and descending colonmight be harmonized.

For the entire large intestine it may be said that cancer affectsthe rectum in about the same number of cases as the colon, and thatin the colon the proximal part, to and including the hepatic flexure,is affected with about the same frequency as the sigmoid. Eachof these situations represents about one third of cancers of thecolon i and the remaining third is made up of cancers of the transverse colon, splenic flexure, and descending colon.


CLASSIFICATION AND GROSS FEATURES

Except for multiple malignant changes in polyposis, multiplecancers of the large intestine are uncommon. Miller found 5 suchtumors which in general met the postulates of Billroth that (1) thetwo tumors should be different histologically, (2) each should growfrom its parent epithelium, and (3) each should have its separategroup of metastases. In the writers' series one case was observedin which there was a tumor in the sigmoid and another in thedescending colon. The latter was principally in the subserosa,was identical microscopically with the growth in the sigmoid, and

FIG.1. LONGITUDINAL SECTION OF PROJECTING-POLYPOUS FORM m' CANCER OF COLO~

Note muscle hypertrophy at proximal end.

was interpreted as metastatic from the sigmoid tumor, which wasplainly mucosal.

The variety in gross appearance of cancers of the large intestinehas led to a multitude of classifications, many of which are givenin outline by Oberndorfer. These may be simplified so that areasonably comprehensive scheme would include carcinomas whichare (1) projecting or polypoid, (2) infiltrating and ulcerative, and(3) stenosing. These forms may be combined, but since the termsare descriptive, joint terms are readily adapted to the conditionpresent. This classification is similar to that proposed by Fischer.

As will be indicated in the discussion of polyps, the cancerswhich project into the lumen of the gut may vary from polyps,adenomatous or villous, which show carcinomatous change, to


large cauliflower-like masses 8 or 10 em. in diameter or larger.They vary, also, from pedunculated to wide-based sessile forms.Usually soft, disposed to central and superficial necrosis withulceration, the intact surface is wrinkled, rough, and often villous.In the presence of extensive central ulceration it is often difficult todetermine whether the lesion was primarily projecting or whetherit represents an ulcerative form with the production of villous orpolypoid growth along the ulcer margins. The degree of deep infiltration into the surrounding tissues is variable. The microscopic picture is usually that of some form of adenocarcinoma, but

FIG. 2. TRANSVERSE SECTION OF ULCERATING CANCER OF SIGMOID

The intestine is open but not laid out flat. The lymph nodes in the mesosigmoidare hyperplastic but show no metastases.

it may be of the order of malignant adenoma or exhibit completeanaplasia. Mucin formation is variable, but the well differentiated mucinous carcinoma does not commonly occur in thisparticular gross form. Intestinal obstruction is due principally tothe size of the mass in the gut lumen, but occasionally the lesionis annular. If in the annular forms there be associated destructionof muscle, there may be adequate reason for ileus.

The ulcerating form may occur as a simple ulcerating surface,infiltrating the surrounding tissues to a variable degree. Thesimpler type of ulcerative lesion, without marginal polyposis israre. It occurs more often in the rectum than elsewhere, andwithout microscopic examination may be regarded as an inflammatory ulcer.

944 HOWARD T. KARSNER AND BURTON CLAHK, JR.

The infiltrating forms show varying degrees of ulceration, mayexhibit marginal papillary or polypoid projection, and in their deepextension lead to thickening of the gut wall. Most of the mucinouscarcinomas belong in this category. Rarely the extension of rectal

FIG. 3. LONGITUDINAL SECTION OF INVADING CANCER OF RECTUM

The large cystic areas originally contained protein material and mucin.

FIG. 4. LONGITUDINAL SECTION OF STENOSING CANCER OF COLON: CICATRICIAL TIRR1"E

IN SUBSEROSA; MARKED HYPERTROPHY OF MUSCULARIS AT PROXIMAL END OF LESION

cancers may be so great as to transform the gut into a rigid, woodlike tube, as exemplified in the cases reported by Bensaude, Cainand Orlean,

The stenosing cancers may be of a fibrous type or the stenosismay be due to cicatricial contraction of the connective tissues in


and outside the muscle layers. In either form ulceration is usuallypresent, and there may be marginal polyposis. The fibrocarcinomas are infiltrating but not extensively so. Occasionallycancers are found which show little disposition to penetration of

FIG. 5. LONGITUDINAL SECTION OF PROJECTING-INFILTRATING CANCER OF H,r,;CTlM

the muscle, but which, because of infection of the ulcer, may beaccompanied by inflammation in muscularis and subserosal connective tissue, which, proceeding through organization to cicatrization, leads to cicatricial contraction. Often what appear to bestenosing cancers are in reality papillary-polypous forms which,because of obstruction, lead to dilatation of the gut above, so thatthe involved area is relatively small in comparison. The distalpart of the tube is usually not dilated. A cast of the lumen illustrates this point better than observation of the opened intestine.

The so-called colloid cancers are often given a separate place inclassification, and not entirely without justification. Nevertheless, they can be placed in any of the groups enumerated above.They are usually of the infiltrating or projecting-infiltrating type,but the cells of the projecting-polypous and the stenosing formsmay in some instances produce considerable amounts of mucin.

MICROSCOPIC FEATURES

All morphological studies indicate that cancers of the largeintestine originate in crypt cells. These cells normally producemucin and are usually of goblet type. When the cells become the

91


components of cancers, they mayor may not secrete mucin.Those tumors which produce large quantities of mucin are oftenreferred to as "colloid" cancers, but the material is true epithelialmucin, and the name mucinous cancers is to be preferred. Ordinarily this term is applied to those forms in which the mucin,although in part intracellular, is principally extracellular. Thereare, however, cancers in which the mucin is practically all containedwithin goblet cells, but in which the cells show no disposition to

FIG. 6. GRADE I CARCINOMA OF SIGMOID. X 220

acinar arrangement. Between these completely anaplastic gobletcell cancers and the well differentiated mucinous cancers there arevarious intermediate forms. Parham's analysis of 203 mucinouscancers of the large intestine showed 22.2 per cent in the cecum,7.3 per cent in the transverse colon, 4.3 per cent in the sigmoid, and5.5 per cent in the rectum.

Rankin and Chumley found among 3202 instances of carcinomaof colon and rectum 158 "colloid" cancers, representing 4.9 percent. Our series showed a much higher proportion, namely 13of 104 (12.5 per cent), of which 2 were the signet-ring type. Mucinproduction was observed in 30 of the 104 tumors. The number ofgenuine mucinous cancers in our series, however, is too small tojustify analysis.

FIG. 7. GRADE II CAIICINOMA OF RECTUM. X 220

FIG. 8. GRADE III CARCINOMA OF RECTUM. X 220

947


By a special method of examination, Ochsenhirt graded 188cancers of rectum and colon as regards mucin production. Heconcluded that mucin production is an indication of differentiationand that the number of mucus-secreting cells is inversely proportional to the grade of malignancy. Rankin and Chumley compared grades of malignancy according to Broden,' method andmucus-cell content, with results which throw doubt on the fullvalidity of Ochsenhirt's conclusions. The majority of their cases

Fill. 9. GHAUE IV CARCINOMA m' SIGMOID. X 220

were of a low order of malignancy and a high grade of mucmproduction, thus conforming to Ochsenhirt's statement. Of the44.4 per cent which they graded as of highest order of malignancy,more than half (58.3 per cent) showed also the highest order ofmucin production. Our limited examination of the subject givesresults in agreement with those of Rankin and Chumley. Mostmucinous cancers, however, are low in characters of malignancy.Rankin and Chumley quoted Robertson to the effect that mucinsecretion represents a low order of functional differentiation, andthat the cells retain this character with exceeding tenacity. In ouropinion, mucin production is an incident in tumor development


and, although generally speaking the appearance of large quantitiesof mucin grossly can justify the assumption that the tumor is welldifferentiated, this is by no means always the case. The fact thatthe usual mucinous carcinomas do not metastasize extensively, if atall, and that they seem to offer a good immediate prognosis following surgical treatment, is probably due to the fact that they arewell differentiated tumors rather than that they produce mucin.In a personal communication Rankin has stated that the ultimate

FIG. 10. GRADE IV GOBLET-GELL CARCINOMA OF RECTUM. X 220

prognosis is bad in the outspoken mucinous cancers, but in thisrespect they differ little if at all from other cancers.

EXTENSION AND METASTASES

Although cancers may extend longitudinally in the gut, thereis often an obvious extension laterally. Hayden and Sheddenstated that 41 per cent of the cancers of the rectum which theystudied completely encircled the circumference and 34 per centextended around three quarters of the circumference. This leavesonly 25 per cent which were not in some degree annular. We havenot made a sharp distinction between those which are nearly com-


pletely and those which are completely annular. In not all ourcases was this feature recorded. Of 42 rectal cancers, 24, or 57per cent, were annular. Of 17 sigmoid cancers 14, or 82 per cent,were annular. Of 23 upper colon cancers 14, or 61 per cent, wereannular, as compared with 25 per cent of Hayes' cases. Of the 82cancers of the entire large intestine 52, or 63 per cent, were annular.Considering the smaller number of our cases, the figures are inreasonable harmony with those of Hayden and Shedden. Of especial interest is the fact that of 7 cancers of the cecum none wasannular. An examination of records as to symptoms and signs ofcomplete or partial obstruction shows that in all situations in thelarge intestine except the splenic flexure the percentage in whichobstruction occurred was much lower than the percentage of annular cancers. Obstruction is a feature of protruding or stenoticcancers and is not necessarily related directly to annular spread.

Cancers of the large intestine may extend locally, metastasizeto regional lymph nodes and to distant points. Local extension ofcancers of the colon is not frequent, although 2 of our cases of cecalcancer showed direct extension to mesocolon, mesoappendix andappendix. Local extension of rectal cancers is somewhat morefrequent. It. was found in 5 of our cases, in one of which therewas extension into the peritoneum, which, according to Oberndorfer, is rare. Extension along the tissues of the gut is also unusual.

In 13 of our rectal cases lymph nodes were examined. Theywere found to be involved in 9 cases. In the other 4 the nodes werelarge and hyperplastic, a finding which is common and to beexpected because of intestinal ulceration. Lymph nodes wereexamined in 5 of the sigmoid cases and were found to be involvedin 3 cases. The situation of these metastases was not adequatelynoted. Hahn spoke of the rare extension through lymphatics ofthe gut and referred to liver metastases as hematogenous, butSemba implies that they are lymphatic. Of 3 of our rectum casesin which autopsy was done, all showed metastases to liver and lungsand in one case there was really a generalized carcinomatosis.An exploratory operation in one additional case showed microscopically demonstrable liver metastasis. Of 4 autopsied sigmoidcases, only one showed distant metastasis, i.e., to the liver only.

Hahn described lymphatics extending to the groin, whichSemba noted as coming from zona columnis, zona intermedia, andzona cutanea of the anal part of the rectum. Thus cancers in thelower rectum may metastasize to the inguinal nodes. We have


had only 2 such cases, one a squamous epithelioma, the other anadenocarcinoma. Hahn also described lymphatics running fromthe upper part of the anal canal along the hemorrhoidal plexus tothe hypogastric chain of nodes. They penetrate the rectal wallabove and below the levator ani, the latter group passing throughthe fat of the ischiorectal fossa to nodes near the internal pudicartery. Lymphatics of the ampulla pass up to the nodes of thesigmoid mesocolon and ultimately drain to the preaortic nodesnear the origin of the inferior mesenteric artery. Since more widespread lymph node involvement than is thus indicated is observed,it is apparent that an extensive lymphatic transmission may occur.

Of 19 cases of cancer of the upper colon in which lymph nodeswere examined, 12 showed metastases. In 6 autopsies, metastasesbeyond the lymph nodes were observed in only 2 cases. Hayespointed out that colon cancers metastasize less frequently thanthose of any other part of the gastro-intestinal tract. He examined1406 lymph nodes from 100 cases and found that only 37 per centof these cases showed metastasis. The decreasing order of frequency is sigmoid, descending colon, transverse colon, hepaticflexure, splenic flexure, ascending colon. Our impression is thatcancers of rectum, sigmoid, and upper colon show metastases indecreasing order of frequency.

It is of interest to note that, whereas McVay found lymph nodemetastases in 47 per cent of 100 cases of rectal cancer, Craig andMacCarty found metastases in only 32 per cent of 100 cecal cancers.Clogg, in a study not adequately controlled by microscopic examinations, emphasized the local nature of colon cancers, and Millerfound only one of 128 cases with lymph node metastasis. Poirierand Cuneo stated that the colon other than the cecum and sigmoidis comparatively poor in lymphatics, and on this basis Schuldtexplained the rarity of metastasis from cancers in the transverseand descending segments of the colon. The cecum drains intoposterior and anterior groups of nodes in the immediate neighborhood, clustered about branches of the ileocecal artery. Craig andMacCarty observed that the posterior wall of the cecum is morefrequently cancerous than the anterior wall and that the posteriorileocolic nodes are more often the seat of metastasis than theanterior. In a general way the lymphatics follow the course ofthe ileocolic, right colic, and inferior mesenteric arteries to draininto mesenteric and retroperitoneal nodes, but those of the transverse colon communicate also with the lymphatics of the omentum.


Thus the further metastases of colonic cancer may follow the samecourse. Beyond the lymph nodes the liver is most often involved,as is true of rectal cancer, but Clogg also pointed out a relativelyfrequent invasion of ovaries. Hayes, McVay, and Craig andMacCarty all noted that cancers which protrude into the lumenof the gut metastasize less often than those which invade the wall.Aufses reported 8 cases of metastasis of cancer of the rectum tobones and confirmed the order of frequency established by vonRecklinghausen, namely vertebrae; femur. ribs; skull, sternum;humerus, pelvis, sacrum; radius, scapula, ulna. We have observedno instance of bone metastasis.

POLYPS

Polyps of the large intestine may be fibrous or fatty, but thesignificant varieties for this discussion, as well as the most frequent,are the adenomatous polyps. These are divided by Susman intotwo forms, polyposis coli universalis and polypi coli. The formercondition shows extremely numerous polypi of various formsthroughout the colon. It is a condition of early life and is includedin the adolescent variety of Erdmann and Morris. Leveuf andOdru regarded it as an uncommon condition and from the reportsin the literature found only 33 cases which they could includesatisfactorily in this category. One patient was five years old, 3in all were less than ten years old, 12 were between ten and twentyyears, 10 were between twenty and thirty years, 6 were betweenthirty and forty years, and 2 were over forty years of age. Thereis a preponderance of males over females. A familial tendency hasbeen noted by Doering, by Erdmann and Morris, by Hullsiek andothers. The data generally in the literature are unsatisfactorybecause of failure to identify the condition without question. Theage incidence of diffuse polyposis is somewhat earlier than for themore localized form.

The term polypi coli, as used by Susman, includes those instances where there is one polyp or several, but without diffusemultiple or universal disposition. In this category would beincluded Erdmann and Morris' acquired polyps. The termsadolescent and acquired cannot be entirely harmonized with theanatomical manifestations, since in adolescence there are instancesof polypi coli, and in adult life instances of polyposis coli universalis.

Hullsiek found in 106 cases in the literature, without clear distinction as to variety, that there is a rise in incidence from cecum


to rectum. Susman, in a series of 65 cases observed post mortem,counted 198 polypi, distributed as follows: 42 in the ascendingcolon, 43 in the transverse colon, 43 in the descending colon, 33 inthe sigmoid, and 37 in the rectum. Neither of these curves ofincidence can be superimposed on the curve of incidence of cancersof the large intestine with the demonstration of any degree ofsimilarity.

Fitzgibbon and Rankin studied the polypi of the large intestinein 13 cases and divided them into 3 groups. They included inGroup I small nodular or smooth masses varying from tiny knobs3 mm. in diameter to masses with a diameter of 2 em. or more,without papilla formation or branching of crypts. These constitute the only group entitled to the benign implication of the termpolyp. They are no more likely to become malignant than isnormal mucosa. In Group II are polyps which may attain greatsize, with failure of cell groups to differentiate into normal unitsproducing multilayered buds which project into lumens and intothe connective tissue, and tend inevitably to become malignant.In Group III are polyps which never exceed 1 em. in diameter.The cells attain only the most rudimentary character and proliferate so rapidly that the connective tissue cannot keep pace, theresulting polyp being a mass of epithelial complexes and tangledskeins of disorganized gland tubules, an immediate precancerouscondition. We find it difficult to identify such sharply separablegroups and observe that our material is in closer harmony with theclassification of Schmieden and Westhues. They believed that anypolyp may become transformed to a larger growth and that inany of the forms malignancy may supervene.

Schmieden and Westhues also divided the polyps into 3 forms.In Group I they placed polyps from the size of a cherry to that of awalnut, usually solitary, most often observed in children, pedunculated, rich in stroma and with gland formation, but exhibiting littleor no anaplasia. These can be distinguished from inflammatoryhyperplasia with great difficulty, are likely to remain benign butmay become malignant. In Group II are polyps, usually single,organoid in type, slowly growing, variable as to size but sometimesas large as an apple. They are often pedunculated and show awrinkled surface. The stroma is in papillary form. The glandsare elongated and irregularly dilated. The cells show activeproliferation, are often in multiple layers with disturbance ofpolarity, and the nuclei are long and hyperchromatic. Although


these polyps are generally blastomatous in character, dedifferentiation or anaplasia is progressive, beginning in the periphery or centerand extending throughout. Polyps of this group may apparentlyarise from Group I polyps, usually become malignant, but mayattain considerable size before this change occurs. In Group IIIare polyps varying in size from that of a lentil to that of a bean,usually multiple, sessile, highly anaplastic, and disposed to penetration into the gut wall. The cancers which arise from these areflat, ulcerated, plate-like tumors. Since 50 em. of the gut areremoved in the rectum cases in Schmieden's clinic, the materialavailable for this study is extraordinary.

Opinion varies as to the origin of polyps, but two views deservespecial mention. Ribbert believed that the polyp originates frommisplaced embryonal cells of the gut which may remain unaltereduntil an advanced age, but may be stimulated to activity at anytime by irritation. These groups of cells are small and isolated.Ribbert pointed out that a polyp does not become malignant as awhole, but only in part, and believed this change to be due toconditions which permit invasion rather than an alteration in theepithelial cells themselves. Verse did not agree with Ribbert thatthe polyps' are of embryonal origin but believed them to be theresult of catarrhal affections acting upon previously normal cells.He concluded that the cancer does not originate from a small groupof quasi-predestined cells but from moderately extensive areas ofthe mucosal surface and that between the original epithelial hyperplasia and the cancer there is always an intervening stage ofadenomatosis. Near the cancer new adenomata are observedwhich undergo malignant change and fuse with the main cancer.

Lockhart-Mummery and Dukes, in a discussion of precancerouschanges in the rectum and colon, expressed the view that theearliest recognizable lesion is a hyperplastic change scattered overan extensive area of the bowel, to be followed by visible tumorousadenomas, in what they call the precancerous stage, which areoften numerous. They state: "It would appear that carcinomaformation is an incident happening to a previously existingadenoma. With the development and dissemination of the malignant tumor, the neighboring epithelial proliferations tend to regressand disappear so that they are less evident in association with largemalignant ulcers." Ewing quoted Rotter as having observed thedisappearance of polyps, but an examination of Rotter's reportshows no evidence of a claim that polypi disappeared or that they


actually did so. Orth could find no malignancy in the specimens,and the idea that cancer regressed is based only on clinical assumption.

Doering noted that carcinoma occurred in 43 per cent of casesof polyposis and pointed out that this accounts for some of thecases of carcinoma in early life. Hullsiek quoted Soper as observing the same incidence, but in his own series observed malignancyin 34.6 per cent of the cases of polyposis. Yeomans in a study ofrectum cases estimated that malignancy occurs in about 40 to 50per cent of the cases of polyposis. Susman found malignancy in23 per cent of his colon cases and quoted Saint as having observedmalignant change in 29 per cent of similar cases.

As indicated above, Verse assumed that all cancers of thelarge intestine originate in polyps. Fitzgibbon and Rankin, onthe basis of their own studies and examination of the literature,stated that the evidence argues "persuasively for the extremelyplausible contention that the histogenesis of carcinoma of thecolon is mediated through precancerous polyp formations and nototherwise." Westhues stated that 40 per cent of the cancers of therectum observed in the Schmieden clinic still show polyps andclaimed that 100 per cent of rectal cancers originate in polyps.Susman found that in 34 cases of cancer of the colon, polypi coexisted in 15 or 44 per cent, a figure which approximates that ofWesthues.

In our series of 13 autopsies, polyps were noted in only 3 cases,1 in the rectum, 1 in the sigmoid, and 1 in the ascending colon.In 45 resections polypi were noted in 6 cases, 3 in the rectum, 2 inthe sigmoid, and 1 in the ascending colon. Large microscopicsections were made of 8 such tumors, in only 2 of which polyps werenoted grossly. In all of these there was some degree of polyposis ofthe tumor. We have insufficient material to reach a conclusionand it is easily possible that polypi were overlooked, but ourobservations indicate that polyposis is frequently present in somedegree. In one instance of resected cancer of the rectum withmultiple polyps, all the types described by Schmieden and Westhueswere present.

Acceptance of Verse's assumption as to histogenesis of cancerdoes not mean that all polyps become malignant, but does implythat all the large intestine cancers exhibit an adenomatous orpolypoid-adenomatous stage in their development. This conception of histogenesis is based entirely upon morphological interpreta-


tions. The fact that cancers may be of polypoid type does notpermit the unqualified assumption that they are derived frompolyps. Neither does the presence of polyps in the neighborhoodof a cancer justify the conclusion that the cancer is of polypoidorigin, for these polyps may be regarded as irritation hyperplasinsas suggested by Yeomans. The belief that as cancer develops inone polyp, others may disappear, as expressed by LockhartMummery and Dukes, seems to lack adequate proof, and iscertainly not supported by Rotter's report. Polyps must beregarded as potentially malignant, or precancerous, and it isprobably safe to believe that about 40 per cent of adult cases ofpolyposis become malignant. It is, however, not possible to statewith assurance that all cancers of the large intestine originate inpolyps, nor to state what percentage of cancers originate in thisfashion, though it must be accepted that polypi are the mostfrequent precancerous lesions.

GRADING

Rankin and Broders graded 598 rectal cancers according to themicroscopic criteria of degrees of malignancy. They found thatthe percentage of cases in which metastases were present was indirect proportion to the grade of malignancy and that the absenceof metastases increases in inverse ratio to the grade. They concluded that in a general way the dominant factor in prognosis is thegrade of malignancy rather than the presence of metastases.Even when both are considered together, the influence of grade isstill evident but not to such a marked degree. Almost as goodresults were obtained in Grade I cancers with metastases as inGrades III and IV without metastases. Largely on the basis ofbiopsy material, Stewart and Spies set up definite criteria forgrading. The substance of their specifications, according to ourinterpretation, is that adenomas with definite malignant characters,or malignant adenomas, are placed in Grade I, adenocarcinomaswith slight or moderate anaplasia are placed in Grade II, adenocarcinomas with considerable anaplasia are placed in Grade III,and the highly anaplastic tumors in Grade IV. The last includesthe signet-ring mucinous carcinomas. They found that theGrade IV tumors occurred at an earlier age period and werereported after a shorter duration of symptoms than was true ofGrade I, and that Grades II and III occupied an intermediateposition in these respects.


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In our series material was available for grading all the colonand sigmoid cancers and 48 of the 52 rectal cancers. The distribution of the rectal cancers in the 4 grades corresponds reasonably well with that reported by Stewart and Spies, thus givingassurance that their criteria were properly applied. The sigmoidcancers are grouped in essentially the same way. The cancersof the upper colon, somewhat more numerous than those of thesigmoid, show a much higher incidence of Grades III and IV thando those of the sigmoid and rectum. It will be seen from TableIII that this is due especially to the high incidence of those degrees

Perce.ntaqe 1) i5fr'lbutio n.of Grades ;71. Canc.eT'.5 ofUpper Golon ,Slgmoid,Rectum

60555045

~ 405 35tJ 30t. 2.5~ ZO

15~O5

Grad~ 1 If ill nLUpper Colcn-Slqmo'\(~ .----•.Rectum. .------.

GRAPH 11

of malignancy in cecum and ascending colon. The rectal cancersin our series show that the age incidence for the different gradesis about the same as in Stewart and Spies' series, except for GradeI, where the age in our series is much lower, the discrepancy beingdue probably to the small number of our cases. The sigmoidcancers show a more orderly arrangement, but the ages are considerably lower. The cancers of the upper colon show a definitelyhigher age incidence for Grade III than for the other grades.

The average age and average duration of symptoms in relationto grades are shown in Table IV. Our figures for age departfrom those of Stewart and Spies, probably because the latter had a


considerably larger series. The average duration of symptoms inour cases is much like that observed by Stewart and Spies, exceptthat in our groups the Grade III colon cases had an unusually longaverage duration as compared with the other grades. It is apparent that no satisfactory conclusions can be drawn as regards thecancers of sigmoid and upper colon until a much larger number isgraded than has yet been done.

TABLE III

A natomical Distribution According to Grades

GradeSituution

I II III IV---------

Cecum .... . . '" · . ·. · . .. . . · . ·. · . ·. · . · . · . ·. · . 1 1 2 3Ascending colon. .. · . · . ·. · . " .. .. · . ·. · . ·. · . · . - 2 5 2Hepatic flexure. ... · . · . · . · . ·. · . · . · . ·. " ·. .. - 2 1 -Transverse colon .... · . · . ·. · . " · . ·. · . · . · . · . · . - 2 6 1Splenic flexure .. . . · . · . · . · . · . ·. · . · . · . · . · . · . · . - 1 1 2

------------UPPER COLON TOTAl...... · . ·. · . · . · . ·. · . · . 1 8 15 8

---------

Sigmoid ..... .... . . . .. . ·. ., . ... . ., .. 2 11 6 1Rectum... .. .. . .. ·. · . · . · . · . · . · . · . · . · . .. · . .. · . 3 25 15 5

Percentage

Upper colon. .. " .. . . . . ... · . · . ·. .. " · . · . · . · . · . 3 25 47 25Sigmoid .... . . . . .. ·. .. · . ·. · . ·. · . · . .. · . ·. · . · . · . 10 ss 30 5Rectum.... . . . . . . · . · . · . · . · . · . · . · . · . · . · . · . · . 6.2 52 31.2 10.4

-------Rectum (Stewart and Spies) .... .. .. · . · . · . · . · . 11 56 24 Q

As noted above, Rankin and Broders found a direct proportionbetween the grade of malignancy and incidence of metastases. Theexamination of our material in this respect is limited. Of 2 casesin Grade I both showed metastasis. Of 12 in Grade II, 75 per centshowed metastasis, and of 17 in Grade III, 76 per cent showedmetastasis. Of 7 cases in Grade IV, all showed metastasis. Ifthe small number in Grade I be disregarded, it becomes apparentthat Grade IV cancers are definitely more disposed to metastasizethan are .those of Grades II and III.

That these inferences are applicable to cancers of the uppercolon is as yet open to question. The discussion of extension andmetastasis of colon cancers given earlier in this paper indicatesthat lymphatics are less numerous and that metastases are less


frequent in the upper colon than in the rectum. In general thereis no reason for assuming that practically the cancers of the colonare more disastrous by virtue of metastasis than are those of therectum. Thus microscopic grading in the cancers of the uppercolon may perhaps be of more use in making comparisons betweencancers as they occur in that part of the intestine than as a basis of

TABLE IV

Average Age (Years) in Rclation to Grades

Grade

I II III IV---~------

RectumStewart and Spies. ........................ 58 55 55 47Karsner and Clark......................... 44 54 54 49

Sigmoid...................................... 50 49 47 31'"Upper colon.. .............................. .. 40'" 45 54 40

Average Duration (Months) in Relation to Grades

RectumStewart and Spies ......................... 20 11 10 6Karsner and Clark ......................... 13.6 10.3 9.2 4

Sigmoid...................................... 13 10.4 5.7 8'"Colon ....................................... 48'" 8.8 10.9 8.1

'" 1 case only.

comparison between cancers of the upper colon and those ofsigmoid and rectum.

CLINICAL OBSERVATIONS

In a paper of this type, a complete discussion of the clinicalmanifestations cannot be furnished. Nevertheless, certain features deserve mention. The initial symptom was pain in 34 of the104 cases. In combination with other symptoms, such as constipation, bleeding, vomiting, it was observed in a total of 49 cases(47 per cent). It was the most frequent primary symptom in allsituations except the sigmoid and rectum. Among the sigmoidcases pain alone was reported by 5 patients as the initial symptom;by 2 others it was reported in association with constipation andvomiting. Constipation was the initial complaint of 9 patients.In the rectal csses constipation was reported as the initial symptomby 16 patients and bleeding by 15 patients, pain having beenreported by 12. Pain predominated as the initial symptom, with


constipation in second place, in patients with cancers of the righthalf of the colon, whereas the reverse was true of cancers of theleft half of the colon. Anschutz referred to general ill health,constipation, dyspepsia, diarrhea, and loss of weight as initialcomplaints, but stated that pain was a very early symptom infrom 80 to 90 per cent of cancers of the colon.

The duration of symptoms before examination ranged from tendays to forty-eight months. The shorter periods are found principally in cases initiated by ileus. The average duration for thewhole series is 10.2 months. Both averages and extremes areabout the same for all parts of the colon, except that the minimum

TABLE V

Symptollls and Signs

Pain Consti- Vomit- Diur- 111.,,1-No. pution jug rhea ing

cases ------No. % No. % No. % No. ~'o No. el

,0

- - - - - ~ - ~ - -Cecum........................... 7 6 86 4 .57 3 43 2 29 0 ()

Ascending colon ................... 9 8 89 6 67 3 33 3 33 3 33Hepatic flexure. ........... , ..... 3 3 100 2 67 2 67 0 0 1 33Transverse colon .................. 9 9 100 4 44 4 44 1 11 4 44Splenic flexure ................... 4 4 100 4 100 3 7.5 0 0 2 50Sigmoid......................... 20 20 100 Hi 80 8 40 5 2.5 10 .50

Entire colon ...................... 52 .50 96 36 69 25 48 11 21 20 38Right half ........................ 26 24 93 15 .58 13 50 6 23 7 27Left half ........................ 2() 26 100 21 81 12 46 5 19 13 50

Rectum .......................... 52 43 83 30 58 1 2 23 44 43 83- - - -- - - - - - -

ENTIRE St:RIES ................ 104 23 89 fiG 64 27 26 34 33 ()3 61

for splenic and hepatic flexures is two months and the average forthese situations is 12.9 months as compared with 9.8 months forthe rest of the colon. Examination of the figures presented byAnschutz shows that there is no clear ratio between duration andoperability, but it is suggested that recurrence is less likely in theearly operations. The duration in relation to the microscopicgrade of malignancy has been discussed above.

The symptoms and signs manifested either anamnestically orduring the period in the hospital, except weight loss, are shown inTable V. In one instance, a cancer of the rectum, visible andpalpable tumor was the only complaint. In another, an ascendingcolon cancer, a palpable mass and slight loss of weight were the


only manifestations. Noteworthy loss of weight was observed in83 per cent of the entire series of 104 cases, with a maximum lossof 75 pounds in a cancer of the transverse colon. All the patientswith cancer of the hepatic flexure, transverse colon, and splenicflexure lost weight. Of those with cancers of the cecum, 80 percent, with cancers of the ascending colon 88 per cent, cancers ofthe sigmoid 83 per cent, and cancers of the rectum 77 per cent, lostweight.

Pain was complained of by all the patients with cancer of thehepatic flexure, transverse colon, splenic flexure, and descendingcolon, by 86 per cent of those with cancer of the cecum, 89 per centof those with cancer of the ascending colon, and 83 per cent of thosewith cancer of the rectum. This represents 89 per cent of theentire series. This is contrary to the experience of Rankin and ofdeBovis, the latter reporting pain in less than 10 per cent of hiscases, but corresponds closely to the figures given by Anschutz.

Constipation was a common complaint, though somewhat difficult to evaluate in the age groups likely to be affected by cancer ofthe large intestine. It was observed in a slightly higher percentageof rectum than of colon cancers, and more often in cancer of theleft colon than of the right colon. It was present in a high percentage of cancers of the splenic, hepatic and sigmoid flexures, andof the ascending colon.

Vomiting was a complaint in only about one-fourth of all thecases. It seemed to be associated especially with cancers of thesplenic and hepatic flexures.

Diarrhea was a noteworthy symptom in about one-third of theentire series of cases. It was observed in nearly half the patientswith rectal carcinoma and in from about one-fourth to one-thirdof those with cancer of the cecum, the ascending colon, and thesigmoid, but in only one of the 9 transverse colon cases and in noneof the splenic or hepatic flexure cases. As regards the upper colon,there is no real difference in the incidence of diarrhea in cases ofcancer of the right half as against those of the left half. Whenpresent, diarrhea is usually much more disturbing than is the usualgrade of constipation.

Alternation of constipation and diarrhea was reported in 11 ofthe 52 rectum cases and 4 of the 20 sigmoid cases. I t was noted in5 of the 32 upper colon cases, namely one cancer of the cecum and4 of the ascending colon. This means a slightly higher percentagein the rectum (21) than in the sigmoid (20) and cecum (14) and a

92


distinctly higher percentage in the ascending colon (44) thanelsewhere, but these percentages may be of little or no significance.Rankin stated that this alternation occurs more often in cancersof the right half of the colon than does constipation or obstruction.In our series this is generally borne out by the observation that itwas reported in 58 per cent of the cases of cancer of the right half of

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Percentage of Gfl5e5 hevinq as a 5ympfomDie.r-r-he.a, I

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GRAPH 12

the colon as compared with 83 per cent of the left half cases, butdiarrhea was present about equally in both groups.

Blood in the stools was noted in 83 per cent of the rectal casesas compared with 50 .per cent of sigmoid and splenic flexure cases.One-third of the ascending colon and hepatic flexure cases, 44 percent of the transverse colon cases, and none of the sigmoid casesare reported as bleeding. As might be expected, bleeding was


observed in a greater percentage of cancers of the left colon thanthe right and more often in cancers of the rectum than in thoseof other situations. AnschUtz noted bleeding in only 2 of his casesin which the cancer was situated above the sigmoid.

Three of the sigmoid cases and one each of the splenic flexureand hepatic flexure cases were admitted with complete obstruction.

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Percentage. of GasesChronic,recurrent or acute ob1ruction° ..

Vomiting as a .5ymptom 0 0

GRAPH 13

One of the patients with cancer of the cecum entered the hospitalin obstruction, which was found to be due to a metastatic tumor inthe ileum rather than to the original growth. A history of minordegrees of obstruction was obtained in several cases, but itssignificance is doubtful. More definite partial obstruction wasnoted anamnestically and actually in 2 of the rectum cases (4 percent), 5 of the sigmoid cases (20 per cent), 2 of the splenic flexure


cases (50 per cent), 2 of the transverse colon cases (22 per cent),1 of the hepatic flexure cases (33 per cent), 3 of the ascending coloncases (33 per cent), and 1 of the cecum cases (14 per cent).

By combining the various manifestations of obstruction asrelated to vomiting as a special symptom it is seen that these areespecially prominent in relation to cancers of the splenic andhepatic flexures, and are observed more often in relation to cancersof any part of the colon than to those of the rectum. The featuresare shown in Graph 13.

TABLE VI

Blood Examination

Hemoglobin Erythrocytes% (in thousunds)

No. No.eases COMes

Maxi- Mini- Aver- Maxi- Mini- Aver-mum mum nge mum lIlum age--------------

Cecum............. " ............ 5 85 45 70 5 4,580 3,020 3,501Ascending colon .. , .... ..... , . .. 8 90 24 68 7 4,850 2,560 4,22fiHepatic flexure ... . . . . . . . . . . . . . . . . 2 86 70 78 2 4,700 3,850 4,275Transverse colon .................. 7 101 46 74 4 4,640 3,010 3,737Splenic flexure ............ ........ 3 80 75 77 2 5,464 4,280 4,872Sigmoid............ ..... ....... . 14 85 60 75 11 5,450 3,130 4,451Rectum .......................... 42 98 52 80 31 5,200 3,350 4,276

Right half of colon ...... ...... ... . 18 101 24 72 16 4,850 2,560 4,035Left half of colon ............ ..... , 19 85 60 74 14 5,464 3,010 4,408

Burgess reported that about 90 per cent of cases of acutecolonic obstruction are caused by malignant tumors, and that theleft side is much more frequently involved than the right side.Rankin quoted Carson to the effect that among 111 colon cancers,all the cancers of the splenic flexure were associated with obstruction. Anschutz observed ileus in 25 per cent of the cecum cases,44 per cent of the hepatic flexure cases, 7 per cent of the transversecolon cases, 52 per cent of the splenic flexure cases, and 63 per centof the sigmoid cases. Rankin stated the causes to be volvulus,intussusception, or actual growth of the tumor. In our cases therewere no instances of intussusception or volvulus. The obstructionwas due principally to growth of the tumor mass within the lumenof the gut and only infrequently to stenotic constriction of thewall.

The anemia incident to cancer of the large intestine has beenespecially studied by Alvarez and his associates, who reported


that patients with cancer of the right half of the large intestine showin general a more severe anemia than those with cancers of theleft half. The essential factor in inducing the severe degrees ofanemia appears to be the presence of a large ulcerated surfacefrom which blood can ooze and bacteria enter. The cecal cancershad an average surface area of 51.6 ± 2 sq. em., whereas those of

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GRAPH 14

the sigmoid had an average surface area of 31.2 ± 1.7 sq. em.The cecum has a usual diameter of 6 em., and the sigmoid 2.5 cm.,thus suggesting that patients with sigmoid tumors seek reliefearlier than those with tumors of the cecum. Conversely, patientswith cecal tumors harbor the disease for a long period of time beforetreatment, during which the large ulcerated cancer surface maybleed. The region in the gut itself is not significant, since, if it isshort circuited and allowed to remain so, the anemia disappears.

966 HOWARD T. KARSNER AND BURTON CLAHK, JR.

Furthermore tuberculosis of the cecum does not ordinarily producea severe anemia. Rankin emphasized toxic absorption from theeroded surface, but the subsequent work of Alvarez and his associates appears to attach greater significance to bleeding.

In our series the lowest erythrocyte count and hemoglobin percentage were observed in a case of cancer of the ascending colon.In general the averages for the right half of the colon are lower thanthose for the left half, including the sigmoid but not the rectum.For the purpose of comparing right and left halves, the cancers ofthe transverse colon were divided according to their situation.

::xl45 \'Jl

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GRAPH 15

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Graphs 14 and 15 illustrate the condition best in reference tominimum and average figures. As is true of Prickman's figures,the difference is especially apparent in the hemoglobin percentage.The duration of symptoms in the colon cancers varied betweenthree weeks and forty-eight months for those of the right half andone month and forty-nine months for the left half, the averagesbeing respectively 10.1 months and 10.3 months. These figurescan be regarded as representative but not necessarily significant.The duration of symptoms ill the 52 rectum cases was from ten daysto forty-eight months with an average of 10.3 months. The moresevere anemia in the case of cancers of the right half of colon cannot be based upon duration of anamnestieally noticeable symptoms


as compared with cases of cancer in other parts of the gut, but thisdoes not controvert Alvarez' assumption that the disease isgenerally of longer duration and of greater surface area in the rightthan in the left half. The generalization as regards anemia appearsto be valid, but individual variations are such that its value indiagnosis can be only indicative rather than pathognomonic.

SUMMARY

Carcinoma of the colon is a disease which occurs most often inthe fifth and sixth decades of life. The age incidence for cancerof the colon is slightly earlier than for that of the rectum. Thedisease is distinctly more common in males than females. If agecurves be set up for the sexes separately, it is found that in femalesthe highest incidence is at an earlier period than in males. I t isprobably much more common in whites than in negroes.

Anatomically, cancer is slightly more frequent in the rectumthan in the colon. Of cancers found in the colon, about one-thirdare in the sigmoid flexure, one third in the proximal colon up to andincluding the hepatic flexure, and the other third in the transversecolon, splenic flexure and descending colon. There is no specialpredilection for the hepatic and splenic flexures.

Carcinoma of the large intestine may assume (1) projecting orpolypoid, (2) infiltrating and ulcerative, and (3) stenosing forms.Excess production of mucus may occur in any of the forms, but ismost often observed in the infiltrating, well differentiated adenocarcinomas. The term mucinous carcinoma is more literallycorrect than is colloid carcinoma. The character of the tumor isdetermined by its cellular content and arrangement rather thanby its incidental production of mucin.

Extension and metastasis of rectal cancers are somewhat morefrequent than of colon cancers, probably due to differences inlymphatic drainage. Widespread metastasis is infrequent.Lymph nodes may be notably hyperplastic and not be the seat ofmetastasis.

Adenomatous polyps frequently become malignant. It is notestablished that all cancers of the large intestine originate inadenomatous polyps, but it may well be that this is true of about40 per cent of these cancers. The presence of marginal adenomatous polyps may be an irritation phenomenon and is not a proofof the origin of the cancer from polyps.

Grading on the basis of microscopic criteria makes it probable,


as regards rectal cancers, that as anaplasia increases, the age incidence, duration of symptoms, and length of life decrease. In theseries of cancers of the colon reported here, the higher degrees ofanaplasia in cancers of the cecum and ascending colon affect thefigures for the entire colon, so that the grades are definitely ofhigher order in the colon than in rectum. This has yet to beestablished satisfactorily on the basis of a sufficient number ofobservations. It may serve as a basis of comparison of malignancyin colon tumors but does not indicate practically that they are moremalignant than are rectal cancers.

Pain is a frequent initial symptom, more especially of cancersof the rectum and sigmoid. Pain is also common in the course ofthe disease in all parts of the colon. Constipation is more notablewith cancers of the left half of the colon than those of the right, butis particularly common with cancers of the three flexures and ascending colon. Vomiting is often recorded with cancers of the splenicand hepatic flexures. Diarrhea is most frequent with the rectal cancers, and the same is true of the alternation of diarrhea and constipation. Blood in the stools is common with the rectal cancers anddecreases in frequency as the cancer is situated higher in the colon.Obstruction is observed particularly with cancers of the splenic flexure and is next most common with those of the hepatic flexure.Anemia is likely to be more severe in cases of cancer of the righthalf of the large intestine than in those of the left half. Loss ofweight is frequent and is apparently most common in connectionwith cancers of the hepatic flexure, transverse colon, and splenicflexure.

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