Etiologic Factors in Polyposis and Carcinoma of the Colon

J. ENGLEBERT DUNPHY, M.D., W. BRADFORD PATTERSON, M.D.,MERLE A. LEGG, M.D.

From the Department of Surgery, Harvard Medical School; the Fifth Surgical Service and Sears SurgicalLaboratory, Boston City Hospital; and the Laboratories of Pathology,

New England Deaconess Hospital

SPONTANEOUS REGRESSION of cancer is arare but fully documented phenomenon.3 5The therapeutic significance of such varia-tions and regressions in the growth of tu-mors is small and lies only in the hopewhich can be held out to the patient whohas what appears to be an incurable cancer.However, the leads which this phenomenonof spontaneous regression may furnish withreference to the etiology of cancer requireincreasing consideration. This paper specu-latively explores this problem with refer-ence to carcinoma and polyps of the colonon the basis of personal observations andsome collected reports from the literature.

The Effect of Diversion of the FecalStream on Carcinoma of the Colon

In the days when two-stage operationswere commonly performed for carcinomaof the colon every surgeon of experiencecan recall instances in which a marked re-gression in the size of a tumor took placefollowing a preliminary colostomy. This re-duction in size of the tumor was attributedto the subsidence of "inflammation" follow-ing diversion of the fecal stream. While thisundoubtedly was true in certain instances,there is some justification for consideringthis change in tumor size as a temporaryregression in growth. The details of thefollowing case to which we have referredelsewhere 4 are pertinent.

* Presented before the American Surgical Asso-ciation, San Francisco, Calif., April 15-17, 1959.

Supported in part by a grant from the Amer-ican Cancer Society and by a gift from the lateGlenwood J. Sherrard.

Case 1: A 46-year-old male was first seen inDecember 1948, because of acute and chronicalcoholism, peripheral neuritis, advanced cirrhosisof the liver and a severe psychosis. In the course ofhis examination he was found to have a huge, fixed,polypoid tumor involving the anterior and lateralwalls of the rectum just above the prostate. Onproctoscopic examination the mass appeared to bepolypoid with central ulceration. A biopsy revealedadenocarcinoma (Fig. 1). The patient's psychoticstate, hepatic insufficiency and avitaminosis re-quired prolonged therapy before operation couldbe performed.

At operation on January 15, 1949, a huge tu-mor was found extending from the peritoneal re-flexion of the rectum deep into the hollow of thesacrum. An umbilicated, hard nodule was palpablein the left lobe of the liver. It was consistent witha metastasis but could not be visualized or biopsied.In view of the generally poor condition of the pa-tient and the extent and fixation of the tumor, thefirst stage of a Lahey abdominoperineal resectionwas done.

Because of continued poor hepatic function,peripheral edema and neuritis, the secod stage waspostponed for ten weeks, during which time thedistal segment of bowel was irrigated daily withwarm water. For seven days prior to the secondoperation it was washed with a solution of sulfa-suxidine. The second stage was performed March28, 1949. The nodule in the liver seemed to beunchanged but, as so often happens, there wasmarked regression in the size of the tumor of therectum. Operation was completed without difficulty.

Pathologic examination of the specimen re-vealed a fibrotic ulcer with polypoid margins andno evidence of neoplasm. The gross appearancewas utterly different from that originally noted onproctoscopic examination. There was no fungatingmass, the lumen of the bowel was narrowed bya lesion which had produced considerable fibrosisand thickening of the lumen. Numerous micro-scopic sections showed only a chronic inflamma-tory lesion with extensive fibrosis and a tendencyfor the mucosa to be thrown into papillary folds at

488

Volume 150Number 3 POLYPOSIS AND CARCINOMA OF THE COLON 489

E'~~~~~~~'FIG. 1. Photomicrograph showing biopsy specimen of carcinoma of the rectum in Case 1.

The lesion appeared on sigmoidoscopic examination as a large fungating tumor with a centralcore of ulceration. The gross appearance was characteristic of carcinoma. Prior to diversion ofthe fecal stream, tumor was regarded to be of boarder line operability.

the periphery (Fig. 2). There were several benignpolyps elsewhere in the rectum. A review of theoriginal biopsy left no doubt about it being adeno-carcinoma.

The patient did well following abdominoper-ineal resection. Eighteen months later, because ofcontinued good health, a "second-look" procedurewas performed with the intention of resecting theleft lobe of the liver for what had been thought,on the basis of palpation, to be a solitary metasta-sis. At the time of this exploration, no tumor nodulecould be palpated within the liver. Biopsy at thesite of the previous mass showed only scar tissue.Unfortunately, the original hepatic lesion was notbiopsied.

The patient remained fairly well until October1954, when he was hospitalized for pulmonarytuberculosis and progressively severe alcoholism.

Two similar cases have been reported inthe literature. In 1954, Ferguson and Black 6reported the disappearance of what wasthought to be an inoperable carcinoma ofthe descending colon following a righttransverse colostomy. The patient received

300 roentgen units for intractable pain. Twoyears later the patient was well and re-operation disclosed complete disappear-ance of the tumor. The entire descendingcolon had been reduced to a fibrotic stringof tissue. Biopsies taken at the time of thecolostomy from two small sinus tracts asso-ciated with the tumor mass had shownhistologic adenocarcinoma. Dr. Ernest Da-land 2 has reported a similar experience.In this instance, however, the patient wasgiven a total of 5,500 r to the tumor. Fiveweeks after completion of the x-ray treat-ments an exploratory laparotomy was per-formed, the mass had shrunk markedly insize and following resection no evidence ofcarcinoma could be found. A previous bi-opsy had shown adenocarcinoma, Grade II,of the sigmoid. The colostomy had beenperformed about ten weeks prior to thefinal resection.

490 DUNPHY, PATTERSON AND LEGG

Here, then, are three cases of clear-cutregression of carcinoma of the distal colonfollowing diversion of the fecal stream. Theexact role of the x-ray treatment is difficultto evaluate. In one instance it was not usedand in a second the dosage was so small asto be unlikely to have had a significant ef-fect. In the third instance one must assumethat the heavy irradiation contributed tothe regression and disappearance of thetumor.

Effect of Irradiation on Cancer of theColon and Rectum

We have had one other instance in whichwhat was thought to be a technically in-operable carcinoma of the rectum regressedfollowing colostomy and irradiation in theamount of 1,600 r. At the initial explorationthe tumor appeared to be associated with acompletely frozen pelvis. The regression fol-lowing diversion of the stream and irradia-tion was so striking that six weeks later anextirpation by abdominoperineal resectionwas possible. Pathologic examination dis-closed a large undifferentiated carcinomawith massive lymph node metastases. Therewas marked necrosis of the tumor withinthe nodes. It is not possible in this case tosay categorically that the regression repre-sented subsidence of tumor or "inflamma-tion." It is significant, however, that therewas no evidence of systemic reaction to theinflammatory lesion. Moreover, following anabdominoperineal resection, which was re-garded as palliative, the patient remainedwell and free of disease for 16 years. Seven-teen years after this operation a second pri-mary carcinoma with metastases appearedin the right colon.Such isolated instances of good response

to irradiation and diversion of the fecalstream are difficult to evaluate and mighteasily be dismissed as mere straws in thewind were it not for what appears to bea signal contribution in the recently re-ported experience of the Memorial Hos-pital.7 Over a 12-year period from 1939 to

Annals of SurgerySeptember 1959

FIG. 2. Photomicrograph of ulcerated area inrectum following second stage abdominoperinealresection. All evidence of carcinoma has disap-peared.

1951, preoperative irradiation was used in971 cases of cancer of the rectum. The five-year survival rate in 195 cases with lymphnode metastases was 37 per cent. In a com-parable series treated without irradiationthe five-year survival rate was 23 per cent.A 37 per cent five-year arrest in category

C (Dukes' Classification) is so striking thatit merits the most careful evaluation. Onthe basis of the available evidence, pre-liminary colostomy, and preoperative ir-radiation would appear to be more impor-tant adjuncts to the surgery of cancer of therectum than current efforts with chemo-therapeutic agents.

Regression of Congenital Polyposis of theColon Following Subtotal Colectomy

and IleocolostomyFor some years a number of surgeons

have noticed regression or disappearance ofpolyps in the rectum of patients with con-genital polyposis following subtotal colec-tomy and ileocolostomy. Usually this hasoccurred in conjunction with fulguration ofthe polyps and the idea of a spontaneousregression has not been given due con-sideration. In 1957, Hubbard9 reported

Volume 150Number 3

POLYPOSIS AND CARCIN

":_;i '..L: :; :....I....,.:.: -.-j:-M -I....................::...... ...

FIG. 3. Photomicrograph showing polyposis ofcolon in Case 2. This appearance was typical ofthe entire mucosal surface of the colon from cecumto upper rectum. Note the polypoid changes, thehyperchromatism, and the scattered areas of hyper-plasia.

complete regression of polyps in the rectumfollowing ileorectal anastomosis in a nine-year-old boy with diffuse polyposis. In thisinstance because of the patient's age, ful-guration of the polyps had been deferredfor several months following the operation.On re-examination five months followingileorectal anastomosis there was a markeddecrease in the number of polyps. No ful-guration was performed. Over the course ofthe next six months complete regression ofthe polyps occurred. In a recent communi-cation Hubbard reports that a few isolatedpolyps have reappeared in the rectum inthe last year.'10The following case is another example of

this phenomenon.

Case 2: A 26-year-old male was first seen inTMarch 1957. He was well with no complaints buthad been informed that his brother, a physician,had been found to have diffuse polyposis of therectum. The patient's mother died of cancer ofthe colon and his father of cancer of the stomach.The patient was referred for examination for this

OMA OF THE COLON 491

reason. Sigmoidoscopic examination disclosed dif-fuse polyposis of the rectum. This was confirmedradiographically by barium and double contrastenemas which showed multiple small defects char-acteristic of multiple polyposis throughout the rec-tum and colon.

In July 1957, subtotal colectomy and ileorectalanastomosis was performed. Pathologic examina-tion of the specimen disclosed diffuse polyposisthroughout the colon. This was confirmed bymicroscopic section. Between August 1957 andMarch 1958, repeated fulguration of the polypsin the lower rectum were performed. It was notedthat there was marked improvement in the appear-ance of the distal rectum. The upper rectum, how-ever, looked very polypoid and it was not feasibleto fulgurate this segment. A decision was, there-fore, made to excise 50 per cent of the remainingrectum. Just prior to this procedure, sigmoidoscopicexamination showed such striking improvement inthe appearance of the distal rectum that the pos-sibility of spontaneous regression was considered.

In June 1958, the upper half of the rectum wasexcised with anastomosis of the ileum to a smallrectal stump. Pathologic examination of the re-moved segment of rectum showed no evidence ofpolyposis on gross or microscopic examination. Thissegment had not been fulgurated at any time.

Since operation all polyps have disappearedfrom the small retained rectal segment withoutfurther fulguration. Examination of the patient inMIarch 1959 shows no recurrence of the polyps tothis date. A biopsy of the rectal mucosa was de-scribed as showing slight chronic inflammation.

The histologic sequences in the colon initiallyand in the rectum following regression merit amore detailed description (Fig. 3, 4 5). The prin-cipal microscopic findings are limited to the mucosaof the large bowel. Focally cells of the surfaceepithelium and in the glands of Lieberkuhn aredensely crowded columnar cells with few gobletcells, in contrast to the normal mucosa with itsabundant goblet cells. The general outline of theinvolved glands is maintained although they areoften larger and slightly more folded. The nucleiare hyperchromatic, more variable in shape andsize than normal cells, and are much less uniformlyplaced at the bases of the cells. Mitoses are nu-merous, the number ranging up to four mitoses ina cross section of a single gland. Abnormal mitosesare not present and the basement membrane isintact. The transition from normal epithelium isabrupt at the surface but less so in the glands.

The areas of involvement vary from a singlegland of Lieberkuhn to true adenomatous polypsup to 0.4 cm. in diameter. The small areas tend toinvolve the mucosa in a triangular fashion with the

DUNPHY, PATTERSON AND LEGG Annals of SurgerySeptember 1959

FIG. 4. Photomicrograph of typical area of intestinal mucosa 11 months after subtotalcolectomy and ileorectal anastomosis. All polyps have disappeared but there are numerousareas of hyperplasia and hyperchromatism remaining.

base of the triangle at the surface and the apexnear the muscularis mucosa, the changes thus be-ing mainly in the surface and the superficial halvesof the glands. The larger projecting polypoidmasses are generally sessile but an occasional onehas a short stalk. The intervening segment of nor-mal mucosa between areas of involvement is inmany cases less than 0.1 cm.

The difference both grossly and microscopicallybetween the initial specimen, i.e., the cecum,ascending, transverse, and descending colon, andthe last two specimens representing rectosigmoidand rectum is quantitative rather than qualitative.Grossly a fine nodular appearance of the mucosawith distinguishable small polyps was seen in thefirst two specimens throughout the large bowel. Inthe rectosigmoid and rectum the nodular charac-ter was not as prominent and distinct polyps werenot seen.

Histologically, the areas of mucosal changeare larger with more obvious polyp formation andmore numerous foci in the colon. The mucosalchanges of the rectum and sigmoid are identicalin character but with smaller and less abundantfoci.

These mucosal changes are similar in characterto those seen in single adenomatous polyps and

distinct from inflammatory pseudopolyps as seenin ulcerative colitis.

The significance of the regression ofpolyps following ileorectal anastomosis isnot easy to appraise. It seems likely, how-ever, that this is not a rare or isolated phe-nomenon. Hubbard 9 reviewed 17 caseswhich he collected from the literature. Inall instances fulguration or excision of therectal polyps were performed, but in 11no new polyps or only very occasionalpolyps recurred. Ian Todd 11 of St. Mark'sHospital, London, commented on thistendency of polyps to re-form less vigor-ously after subtotal colectomy before thisSociety * in 1956. Spontaneous regressionof the polypoid lesions was not recognizedbut the possibility of some agent whichcauses polyps but which is removed or al-tered on proximal colectomy was empha-sized.

tAmerican Surgical Association.

492

POLYPOSIS AND CARCINOMA OF THE COLON

FIG. 5. Photomicrograph of a rectal biopsytaken 20 months after ileorectal anastomosis inCase 1. The mucosa appears essentially normal.There is evidence of slight inflammatory change.Multiple microscopic sections showed a few areasof hyperchromatism and local hyperplasia similarto those so characteristically found in the originalresected specimen of the colon.

Sir Stanford CadeI also, in a personaldiscussion with one of the authors some

years ago, suggested the possibility of a

carcinogenic substance which required ac-

tivation by the colonic mucosa before beingeffective, hence the greater tendency forcarcinoma to form in the distal colon andrectum.

Turnbull,12 of the Cleveland Clinic, hasobserved spontaneous regression of polypsin several instances following ileorectalanastomosis. He has kindly permitted us toreport a particularly significant observation.In one case, ileosigmoidal anastomosis hadbeen performed 12 years earlier for multi-ple polyposis. When Dr. Turnbull first sawthe patient, there were countless polyps inthe rectum which could not be controlledeven by vigorous fulguration, and it was

not possible to reach the polyps in theupper sigmoid. Accordingly, a second re-

section of the sigmoid and pelvic colon was

performed with a low ileorectal anastomo-sis. Following this procedure the polypshave disappeared from the rectal segment.This suggests that even a small amount ofcolon may be sufficient to provide the hypo-thetical stimulating factor and makes it un-likely that mere reduction of the bulk ofthe fecal stream is the cause for disappear-ance of the polyps.One other observation of Turnbull is of

interest. He has noted in two siblings uponwhom ileorectal anastomosis and subtotalcolectomy were performed for multiplepolyposis that in the sister complete regres-sion of the polyps occurred, but in thebrother no regression was observed. Thisisolated observation complicates the prob-lem further by suggesting that the hypo-thetical stimulating factor might in some

way be sex linked.

Epithelial Hyperplasia in the CheekPouch of the Hamster FollowingHeterotransplantation of a Car-

cinoma of the Colon

The regression of carcinoma and polypsafter colostomy and subtotal colectomy re-spectively could be explained if one as-sumed that a mucosal stimulating factor isproduced or activated by the colonic mu-

cosa as suggested by Todd and Sir StanfordCade. This substance might act on the in-testinal mucosa in a quantitative fashion.If its production by colectomy or diversionof the fecal stream was sufficiently lowered,the cycle of hyperplasia, polyp formationand carcinogenesis might be broken or

lengthened.There is little doubt that some polyps at

least develop in areas of focal hyperplasiaas a result of peristaltic forces acting on

the mucosa. Hoelzel and Da Costa,8 forexample, have shown that polyps can beproduced in the colon of rats by the feed-ing of inert material such as Kaolin or tal-cum powder. That peristaltic factors aloneare not the responsible agent is suggestedby the observation of Turnbull noted above.

Volume 150Number 3 493

,a# . . . - . - -,k.;.io-w ; .:

494 DUNPHY, PATTERS

FIG. 6A. Photomicrograph of normal cheek pouchof hamster over a transplanted melanosarcoma.

O0N AND LEGG Annals of SurgerySeptember 1959

cells is approximately doubled and there isan obvious increase in mitosis with loss ofcell polarity. There is little question thatthe hyperplasia is directly related to thepresence of the tumor, since there is anabrupt change to normal mucosa immedi-ately adjacent to the area of the tumorfragment (Fig. 6).

It is of interest, however, that this par-ticular patient does not have evidence ofmultiple polyposis. We have also had anopportunity to examine two other trans-plantable carcinomas of the colon andneither of these have demonstrated the ef-fect of mucosal hyperplasia. Nevertheless,we think the observation is of sufficient im-portance so that it should be mentioned inreference to the problem currently underdiscussion. There may be many different

.......i

He found that even a small difference inthe amount of retained colon affected thetendency to regression.One more "straw in the wind" in relation

to a hypothetical factor which may stimu-late epithelial hyperplasia has been pro-vided by the following observation relativeto the growth of a transplantable carcinomaof the colon. This tumor originated in thetransverse colon of a 29-year-old man, andwas transplanted to hamsters in March1958. Since then it has been passed throughmany generations of animals. It has a lim-ited growth period of about five weeks inthe hamster cheek-pouch before it is re-jected by the host. The unique character-istic of this particular tumor is the devel-opment of epithelial hyperplasia in thehamster cheek-pouch overlying the tumor.This has occurred in every transplant ofthis particular tumor. Such hyperplasia hasnever been seen with transplants fromother strains of human tumors which nownumber about two dozen. The hyperplasiais characterized by increased thickness inthe mucous membrane. The number of

FIG. 6B. Cheek pouch of hamster overlying atransplanted carcinoma of the colon. Note thethickening of the epithelium, increase in mitoses,and loss of cellular polarity.

Volume 150 POLYPOSIS AND CARCINOMA OF THE COLON 495Number 3

factors contributing to the development ofcarcinoma of the colon and the hypotheticalstimulating factor which is suggested bythe above observations may apply to onlyone form of neoplasia in the colon.

Discussion and Speculation

Diversion of the fecal stream by colos-tomy is followed on occasion by reductionin the size of distally located carcinomas.Very rarely such carcinomas have disap-peared completely without other treatmentor following supplementary irradiation.There is evidence that complementary pre-operative irradiation may favorably affectthe five-year salvage in carcinoma of therectum. Congenital polyps of the colonmay regress in the rectum following sub-total colectomy and ileorectal anastomosis.Such regressions have been complete asfar as gross identification of polyps areconcerned. Histologic study of the mucosalsurface of the bowel, however, may showislands of hyperplastic mucosa which per-sist despite resolution of the polypoidchanges. Finally, areas of epithelial hyper-plasia in the cheek pouch of the hamsterhave developed following the heterotrans-plantation of a carcinoma of the colon. Thistype of hyperplasia has not been observedby us in any other tumor transplantation.These facts raise the following questions:

(1) May there not be a factor whichleads to polyposis and carcinogenesis whichis either produced by the mucosa of thecolon or activated by it, and which is re-moved or deactivated by diversion of thefecal stream and partial or subtotalcolectomy?

(2) Does the colonic mucosa itself pro-duce a factor which stimulates hyperplasialeading to polyposis or carcinogenesis? Maynot this factor be transplantable with thecarcinoma?

(3) Whatever the exact mechanism, doesnot the evidence suggest that diversion ofthe fecal stream may have a specific anti-

tumor effect and, therefore, be of value inpreparing the bowel for cancer surgery?

(4) Is the greater frequency of carci-nomatous implantation at the suture linein recent years attributable in part to thefact that, with improved methods for pre-paring the bowel, preliminary colostomy isseldom used today?

(5) Should subtotal colectomy be morewidely employed in the treatment of carci-noma or multiple polyps on the groundsthat it may eliminate a substance whichstimulates the formation of polyps orcarcinoma?

(6) May not preoperative irradiation af-fect the growth potential of carcinoma ofthe colon and rectum so that it is less likelyto be disseminated at the time of operation?

ConclusionDefinitive answers to the above questions

cannot be given at this time. However, itis evident that a controlled study of theeffects of preliminary colostomy and pre-operative irradiation on carcinoma of therectum and colon is indicated. In additionto comparing survival, the presence of tu-mor cells in the portal blood and in wash-ings from the bowel and peritoneal cavityat the time of colostomy should be com-pared with the findings at the time of thedefinitive resection. The available evidencesuggests that such a study might provemore fruitful that the present investigationof the effects of chemotherapy as an adjunctto operative resection of neoplasms of thelarge intestine.

References1. Cade, Sir Stanford: Personal communication.2. Daland, E.: In Case Records of the Massa-

chusetts General Hospital, No. 40411. NewEngland J. Med., 251:660, 1954.

3. Dunphy, J. E.: Some Observations on theNatural Behavior of Cancer in Man. NewEngland J. Med., 242:167, 1950.

4. Dunphy, J. E.: The Surgical Significance andManagement of Metastatic and RecurrentCancer of the Colon and Rectum. Dis. Col.& Rect., 2;77, 1959.

496 DUNPHY, PATTERSON AND LEGG September 1959

5. Everson, T. C. and W. Cole: SpontaneousRegression of Cancer. Preliminary Report.Ann. Surg., 144:366, 1956.

6. Ferguson, J. 0. and B. M. Black: Disappear-ance, Probably Spontaneous, of Locally In-operable Carcinoma of Descending Colon.Report of Case. Proc. Staff Meet. MayoClin., 29:407, 1954.

7. Hoelzel, F. and F. DaCosta: ExperimentalProduction of Polyposis of Colon in Rats.Am. J. Digest. Dis. and Nutrition, 4:23,1937.

8. Henshke, U. K.: Radiation Therapy of Cancerof the Colon and Rectum. Dis. Col. & Rect.,2:84, January-February, 1959.

9. Hubbard, T. B., Jr.: Familial Polyposis of theColon. The Fate of the Retained RectumAfter Colectomy in Children. Am. Surgeon,23:577, 1957.

10. Hubbard, T. B., Jr.: Personal communication.11. Todd, I.: Discussion of papers by Mark

Ravitch. Ann. Surg., 144:764, 1956.12. Turnbull, R.: Personal communication.

DISCUSSION

DR. JAY L. ANKENEY: Mr. President, Membersand Fellow Guests: I rise to discuss this very in-teresting paper of Dr. Dunphy's on behalf of Drs.William Holden and Jack Cole of the WesternReserve Department of Surgery. Dr. Holden andDr. Cole reported two interesting cases of disap-pearing polyps following subtotal colectomy withileoproctostomy at the Central Surgical Societyin February. Several studies were made in thesecases, which we would like to present at this time.May we have the first slide, please?

(Slide) This is the gross specimen from thefirst patient that was resected. As you can see,there are numerous polyps in the distal portionof the colon and very few in the ascending por-tion. This patient had a very difficult postopera-tive course and it was six weeks before he couldbe taken back to surgery for proctoscopy. Muchto Dr. Cole's amazement, the residual rectal polypshad markedly reduced in size and number; there-fore, he withheld his hand and merely took asmall biopsy which was studied cytochemically.

(Slide) This is a photograph taken througha proctoscope of the same patient eighteen monthslater. As you can see, the rectum is perfectlyclear. In these two cases, no attempt whatsoeverwas made to clear the rectum of these tumors. Thepolyps were allowed to regress spontaneously.They noted that the polyps began to disappear atthe anastomotic site, and the last polyps to disap-pear were those near the dentate line.

(Slide) The material that was obtained bysmall periodic biopsies from these polyps wasstudied cytochemically, and the following obser-vations were made: In the top part of this graph,you see the normal desoxyribose nucleic acid(DNA) content. This is the number of cellscounted and this is an arbitrary figure on theabscissa indicating the amount of DNA present.This is the amount of DNA observed in the"active" polyp, and this is the amount of DNAobserved in the regressing polyp. Notice there isa tendency for the DNA content to return towardnormal as the polyp regresses.

(Slide) Dr. Leuchtenberger, a cytochemistformerly in our Department of Pathology, has ob-served DNA cytoplasmic inclusion bodies in polypsof the colon. The presence of these inclusionbodies implies that polyps may be due to a virus,because a similar type of inclusion body is seenin viral infestations. These inclusions were infre-quent in regressing polyps.

(Slide) Dr. Cole and Dr. Holden have ob-served that residual rectal polyps disappear usuallywithin the first eight to ten months of obser-vation, and the possible reasons for this disap-pearance they have proposed are as follows: Per-haps the ileum and the ileal contents play somepart in preventing the formation of polyps, sincethe ascending colon in these patients containedvery few polyps. Perhaps the ileal contents bath-ing the rectum after colectomy account for thedisappearance of these tumors.

There is also the possibility that perhaps thecolon stimulates the formation of polyps in therectum and the removal of this organ, or at leastthe partial removal of this organ, removes thisstimulus and therefore polyps disappear. Dr.Holden and Dr. Cole are continuing the studiesin this field at the cellular level and hope to havemore information at a later date. Thank you.

DR. JAMEs D. HARDY: I arise to mention onemore case in which residual polyps in the distalrectum disappeared following ileoproctostomy.

I would like to call attention to the fact thatthe granular cell myoblastoma of the tonguecauses an hyperplasia of the surrounding epithe-lium which an inexperienced pathologist may in-terpret as squamous cell carcinoma.

I enjoyed the paper very much. Thank you.DR. FREDERICK GORDON KERGIN: Dr. Dunphy

has already implicated me in the case he hasreported and I really have little to add except toconfirm his observations.

I fell into the error, which perhaps othermembers of the Association have fallen into, ofattributing the favorable progress of this patientto the treatment I was carrying out. I even won-