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Multiple primary malignant neoplasms of the rectum and sigmoid colon
MULTIPLE PRIMARY MALIGNANT NEOPLASMS OF THE RECTUM AND SIGMOID COLON REPORT
OF FIVE ADDITIONAL
HARRY E. BACON, M.D.
AND
CASES
ORVILLE
C.
GASS,
M.D.
Assistant in Proctology, Tempk University MedicaI SchooI
Professor and Head of Department of Proctology, TempIe University Medical School PHILADELPHIA,
PENNSYLVANIA
I
N 1939, the authors1*2 reported seven cases of muItipIe primary maIignant tumors occurring in the rectum or sigmoid and other parts of the human organism, and three contact growths. It is our purpose to present five additional cases that have been encountered on our service during the ensuing five-year period : CASE REPORTS CASE I. R. F., a white femaIe, aged fiftytwo, was seen in consuItation August 4, 1944. She stated that she had been bIeeding for seven or eight years, but since May there occurred a change in the character of the blood. Previously the bIood was bright red in color, sparse in amount and was noted on the stool or foIIowing an evacuation. On May 3, 1944, a hemorrhoidectomy had been performed, but shortly thereafter she experienced five or six evacuations daiIy. She had been constipated for many years and required Iaxatives. The stooIs were usuaIIy of the constipated type except when excess Iaxatives were resorted to. RecentIy the evacuations consisted of a “pinkish liquid” and “gas” which Ieft her with a feeIing of incompIeteness and fuIIness. The first movement each day occurred when she first arose in the earIy morning, but frequentIy she had an incompIete evacuation during the night. During the day the patient usuaIIy passed a fairIy we11 formed stoo1 which was accompanied by bright red bIood; the sense of fuIIness was reIieved temporariIy. No weight Ioss was cited. The patient had had a thyroidectomy fourteen years previousIy and recently had been hospitaIized for hypertension. Her famiIy history was irrelevant. Proctoscopy reveaIed a cauliflower-Iike growth at a distance of 12 cm. invoIving the anterior and IateraI phases of the rectosigmoid.
The process presented nodularity, uIceration and eversion of the edges. Biopsy made of the lesion was reported adenocarcinoma of the rectum grade III. The patient was hospitalized August 9, 1944, and on the fifteenth a one-stage abdominoperinea1 proctosigmoidectomy without the establishment of an abdominal coIostomy and with preservation of the sphincter muscles was performed. ApproximateIy 40 cm. of rectum and sigmoid were resected. After compIetion of the operation the specimen was opened and it was found to contain an additiona Iesion. Description of the specimen was as foIIows: “Specimen of bowel measures 40 cm. in length; 15 cm. from dista1 end there is a large fungoid tumor mass which measures 6 cm. in diameter. It occupies the major portion of the wall circumference. The centra1 portion is ulcerated and the base indurated. The tumor penetrates the entire thickness of the wall to inyade the subserosa1 fat, but no enlarged nodes are paIpated. Ten cm. above this lesion there is a papiIIoma measuring I cm. in diameter and 4 cm. in Iength. Sections taken from the Iarge tumor mass show it to be adenocarcinoma. Sections taken from the dista1 end of the poIypoid growth show it to be undergoing papiIIary proIiferation with earIy malignant change. Diagnosis: Carcinoma of rectosigmoid and maIignant papiIIoma of proximal sigmoid.” The patient had an uneventful recovery and was discharged on the fifteenth postoperative day. CASE II. A. T., a white maIe, aged sixtyseven, was referred because of abdomina1 pain and recta1 bIeeding. For a period of six months the patient had experienced pain in the lower abdomen which was partiaIIy relieved by defecation. An occasiona pain was experrenccd in the rectum at the time of bowel movement. Three months previousIy the patient had passed considerabIe red bIood with
240
NF.WSERIESVOL.LXVIII,NO.~
Bacon,
Gass-Sigmoid
each bowe1 movement. The patient stated that he had always been constipated. He had no early morning diarrhea; two stooIs daily were incomplete and unsatisfactory. A frequent desire for evacuation was cited; usuahy flatus and debris were expelled. He had Iost approximateIy three to four pounds during his illness. The past history was irrelevant. On digita examination a cauIifIower-like mass presenting fixation, noduIarity and eversion of the edges was noted. Proctosigmoidoscopy revealed a circumferentia1, crater-like process. Biopsy made was reported adenocarcinoma of the rectum grade III. On June IS, 1943, a one-stage abdominoperineal proctosigmoidectomy without the establishment of an abdominal coIostomy and with preservation of the sphincter muscIes was performed. Fifteen cm. of the rectum and lower sigmoid coIon were removed. The process penetrated the entire waI1 of the gut to cause puckering of the overlying serosa and there was enlargement of regional lymph nodes. No metastasis to the liver was demonstrable. The patient’s postoperative course was uneventful and he was discharged from the hospital on his twelfth day. In March 1944, nine months following operation, his famiIy physician discovered a smaI1 lesion on the right side of his tongue. A biopsy was made by a IocaI surgeon and a diagnosis of epithelioma made. On hlay 5, 1944, the patient was operated upon for his second malignant Iesion by Dr. J. Blady. CASE III. Mrs. M. M., white, aged sixtynine, was referred July 12, 1943, because of rectal bleeding. For a period of three weeks she had noticed bright red bIood after each bowel movement. The bIood was sparse in amount and there was no history of frequent stools or early morning diarrhea. The movements were compIete and satisfactory, however, the patient experienced a sense of fullness in the lower part of the abdomen after each defecation. Her weight was seventy-two pounds. Two years previousIy the patient had been operated upon for cancer of the right breast. There was no evidence of metastasis at this time. Her father died of cancer of the stomach. On proctosigmoidoscopy a papiIIary adenocarcinoma was noted at a distance of 14 cm. The tumor was located in the Ieft IateraI quadrant and invoIved approximately onequarter of the circumference of the rectum. A biopsy made at this time was sent to the
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AmericanJournalof Surgery
241
TempIe University Hospital and reported as foIIows: “The sections show these fragments of tissue to consist of adenocarcinoma. The ceIIs are of the taI1 cylindrical type which one expects to see in a primary carcinoma of the Diagnosis: Adenocarcinoma of the rectum. rectum.” The treatment in this case was determined by the patient’s poor physical condition and refusa1 of the famiIy for any surgica1 procedure. Electrofulguration was instituted JuIy I 9, 1943, through a sigmoidoscope and thereafter at weekly intervals. Some gain in weight was experienced and three months later there was cIinicaIIy no evidence of malignancy. The patient returned for re-examination after a period of eight weeks and recurrence was noted. Again a palliative double-barreled colostomy with implantation of radon from above and from below was advised but refused. CASE IV. Mrs. F. W. C., white, femaIe, aged fifty, was seen in consultation October 29, 1943. The patient’s symptoms began three months previousIy with a bearing-down sensation and a frequent desire for defecation. The bowel movements were incomplete and unsatisfactory. Often when the patient had the urge for a bowel movement only Batus and smaI1 amounts of fecal material mixed with bIood would be expelled. The blood was sparse in amount, bright red in coIor and occurred onIy with evacuation. The patient was uncertain whether or not she had lost any weight. Past and famiIy history were irrelevant. Digital examination revealed thickening of the upper portion of the rectovaginal septum. Upon advancing the finger a large mass approximately the size of an orange was encountered. The mass was hard and circumferentially placed; it presented fixation, nodularity and eversion of its edges. Vagina1 examination discIosed a serosanguineous discharge. A malignant type of erosion of the cervix was noted. The uterus itself did not seem to be fixed, but infiltration existed in the vauIt. Biopsies of the cervica1 and recta1 lesions were reported adenocarcinoma grade II of the rectum and squamous ceI1 carcinoma grade III of the uterine cervix. On November 9, 1943, an abdominoperinea1 proctosigmoidectomy without the estabIishment of an abdomina1 colostomy and with preservation of the sphincter muscIes was performed. The report of the operative specimen examined and recorded by Dr. A. L. Pietrolango
242
American
Journal
of Surgery
Bacon,
Gass-Sigmoid
read as follows: “The specimen is a piece of bowe1 measuring approximately 18 cm. in length. In the centraI portion there is an ulcerative tumor mass which compIeteIy surrounds the Iumen. The edges are raised, robed and firm. The ffoor is deepIy ulcerated with necrotic tissue. Examination of the subserosal fat fails to show any evidence of enlarged lymph nodes. The tumor apparentIy inIiItrates the entire thickness of the bowel wall. Numerous anaplastic gIanduIar structures are found diffusely infiltrating the wall. A chronic infIammatory reaction accompanies the process. Diagnosis: Adenocarcinoma of colon, grade II.” The cervical lesion was treated with radium by Dr. W. Steel, the referring physician. CASE v. Miss M. M., a white femaIe, age thirty-eight, was operated upon for carcinoma of the cecum in October, 1941. The operation consisted of an ileocolostomy foIlowed by resection. The growth removed by Dr. J. L. Summey was reported as adenocarcinoma. She was symptom free thereafter. On December 20, 1944, she was referred to us with the diagnosis of carcinoma of the rectosigmoid junction. The history revealed that she began to pass mucus streaked with blood some eighteen months after her first operation. Later she experienced sharp pains in the Ieft Iower quadrant becoming more constant and relieved onIy by reclining. The stooIs were described as smal1 and often bIack in coIor. The pain forced her to consult her physician who by doubIe contrast enema found a spacetaking Iesion at the rectosigmoida1 region. Further examination reveaIed a circumferentia1 cancerous process, adenocarcinoma grade II. The patient was admitted to our clinic and on December 27, 1944, was operated upon for her second primary malignancy. A sigmoidectomy was performed using the aseptic technic and a temporary transverse coIostomy estabIished proximal to the primary anastomosis. The Ieft tube and ovary were enmeshed in the cancerous bowel and removed. There was no evidence of metastasis. Gross description of the specimen was as foIIows: “The specimen is a segment of large bowe1 about 24 cm. in length to the serosal surface of which a tube and ovary are attached. In the center of the bowel a large uIcer 4 cm. in diameter is found on the mucosa1 surface. The uIcer base contains necrotic tissue. Its edges are firm but proliferative. The mucosal surface in the immediate vicinity has become
Colon
lL1AY, lg.&s
involved in the neopIastic process as is demonstrated by poIypoid masses which are really part of the advancing tumor edges. The tumor has penetrated the entire thickness of the bowel and the tube and ovary are cIosely adherent at this point. GrossIv no definite evidence of tumor penetration ‘is seen. The ovary contains follicular and hemorrhagic TABLE I DOVRLE MALIGNANCYIN THE ANUS, RECTUM AND
SIGMOID
COLON
Author
Graham (3). ................. Kraske (4). .................. Bargen & Rankin (5). .......... Morton (6). ................... Bargen & Rankin (5). Bargen & Rankin (5). Bargen & Rankin (5). Bargen & Rankin (5) Bargen & Rankin (5). IIochenegg (7), Robson & Knaggs (8). Abe1 (9)................ Abel (9). Lockhart-Mummery (IO). Lockhart-Mummerv (IO) Norbury (I I). .... .“. .... : ....... Miller (12) (101). .............. Morgan (I 3) ................... PaDin (14). .................... Rotter ‘( 1-5) Rotter (I 5) . Rotter (15). . . Rotter (15). Rotter (15). Graham (3) ,,....
.I Rectum .I Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Rectum
Graham (3).
Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectosigmoid Rectum
Cole (16).
Rectum
Kirshbaum & ShiveIy (17). Kirshbaum & ShiveIy (17). Schweiger & Bargen (18). Schweiger & Bargen (18). Schweiger & Bargen (18).
Rectum Rectum Rectum Rectum Rectum
Schweiger 81 Bargen (18).
Rectum
Schweiger & Bargen Schweiger & Bargen Schweiger & Bargen Schweiger & Bargen Schweiger & Bargen Silvers (19). Bacon (I) (2). Bacon (I) (2). .
Rectum Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum
(18) (18). (18). (18), (18).
-I
Rectum Anus Sigmoid Siamoid Sigmoid Rectum Rectum Sigmoid Sigmoid Rectum Rectum Pelvic coIon Rectum Sigmoid Sigmoid Rectum Sigmoid Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid Rectosigmoid PeIvic sigmoid Sigmoid Sigmoid Sigmoid Rectum Rectosigmoid Sigmoid coIon Rectum Rectum Sigmoid Sigmoid Sigmoid Sigmoid Rectum Rectum
NEWSERIESVOL.LXVIII,NO.~
Bacon,
Gass-Sigmoid
cysts. Diagnosis: Adenocarcinoma of sigmoid, grade II, with ovarian capsular invasion.” The patient’s postoperative course was satisfactory. She will return to the hospital at the end of a six weeks period for closure of the transverse colostomy. A review of the Iiterature of proved cases is appended in TabIes I to VI. TABLE THREE
Site
Rectum Rectum Rectum Rectum
.’
: .I
American
bIe for its separate To this MercantorP quaIifIcation: “that
Journnl
243
of Surgery
group of metastases. added the folIowing if after remova] of two
carcinomas the patient remains free from the disease, the two growths must have been independent eIse there shouId have been other metastasis.” It is evident that in carcinomas arising from the intestinal II
OR MORE MALIGNANT
Author
Lane (20). Norbury (I I). _. Dowden (21). _. Maingot (22). Bargen & Rankin (5) Bargen & Rankin (5) Schmidt (23). Angevine (24). Zimmerman (25). Doering (26), WuIf (27). Miller (12) (101). Bunting (28). Getting (29). v. Mielecki (30). Jentzer (31). Bargen & Rankin (5). Lauds (32). Goetze (33). Bargen & Rankin (5). KIingenstein (34). Schweiger & Bargen (18). Litchman (35). Whigham (36). Bargen, J. R. (37). Mayo, C. W. (38). Kretschmer (I I I). Smith (112) ._.. ,, ,. Bacon (I) (2).
Colon
~
LESIONS
Site
Site
I
Site
~Siamoid I Sjgmoid -
Breast ~ I Transverse coIon Slgmoid Small Intestine Anus Sigmoid Three separate carcinomas of the rectum and sigmoid Rectosigmoid 1Rectum Rectum I Rectum RectumSigmoid Rectum Rectum Anus Rectum Left Adrenal Sigmoid Rectum Rectum Hepatic Flexure Hepatic Flexure Rectum Splenic Flexure Rectum Hepatic Flexure Transverse colon Siamoid i Cecum IIeum Rectum Larynx Stomach Rectum L arynx Stomach Rectum Orbit Stomach SpIenic FIexure Uterus (sa.) Sigmoid Ascending colon Esophagus BiIe duct TonsiI Rectum Prostate Colon Rectum Stomach Transverse colon Spienic Aexure Sigmoid Cecum Transverse colon Uterus Sigmoid Ascending colon Sigmoid Sigmoid Sigmoid Cecum Rectum Sigmoid Prostate Rectum Cecum Descending colon Cecum Rectosigmoid Cecum Descending coIon i Sigmoid Prostate Sigmoid Bladder Sigmoid Descending colon Cecum I Rectum 1Sigmoid Rectum
I The postuIates Iaid down by BilIroth,87 which must be fuIHIed before multiple carcinoma can be identified as independent lesions, are we11 known because they have been mentioned by virtualIy every writer on the subject, but here again they bear repetition: (I) The two growths shouId differ histologicaIIy which must be so pronounced as to excIude the possibiIity that they are of the same origin, but in different stages of deveIopment; (2) each growth must spring from its parent epitheIium; and (3) each growth must be heId responsi-
epitheIium the first of these postuIates cannot we11 be satisfied because as Thompsons9 has said, “since carcinomatous degeneration of multiple intestina1 poIypi is entirely IikeIy, it seems that this postulate need not be fuIfiIIed in identifying muItipIe independent carcinomas of the intestine.” As a matter of fact, BuntingZs is of the opinion that these postuIates were intended to appIy onIy to maIignant growths arising in different organs. It is admitted that the limitations of these criteria are too strict because a
244
Amcricnn
Journ~~I of Surgrry
Bacon,
Gass-Sigmoid
faIseIy low incidence has resulted. What then are the criteria which one is to empIoy? The fundamental probIem is “what constitutes muItipIe primary maIignancy?” Tumors arising independently of ante-
Author
Site
Junghanns (39). Kuster (40). Lockhart-Mummery (10). Lockhart-Mummery (IO). Norbury(r~)............ Warren & Gates (41). Norbury (I I) Handford
(42).
EIiot (43) Bargen & Rankin Bargen & Rankin
(5). (5).
Abe1 (9). Karsner
61 Clark (44).
Behrend
(45).
Lockhart-Mummery Littlewood
(46).
Littlewood
(46).
Cokkins
(47).
Cokkins
(47).
Cokkins
(47).
MALIGNANCIES
(IO).
Goriainowa & Schabad (102). Hauser (49). Pemberton & Waugh (50). Hauser (49). Orr (51). _. _. _. Rau (52). . Judd & PhiIIips (53) .
.\lAY, ,<&$j
malignant growth occurring independentI>in the same individual. For this there are excellent examples such as polyposis of the large bowel and stomach, lyfnphosarcoma and multiple myeloma. But It is said that
TABLE DUAL
Colon
OF THE
III GASTROINTESTINAL
Site
TRACT
Author
( Rectum , Rectum
Colon Colon Rectum Colon Rectum Colon Rectum CoIon Rectum Colon Rectum Transverse colon Rectum SpIenic IIexure Sigmoid Splenic Aesure Rectum Cecum Sigmoid Ascending coIon Pelvic Descending coIon coIon Sigmoid Descending colon Rectum Ascending coIon Rectum Transverse coIon Rectum SpIenic Aexure Rectum Ascending colon PeIvic Transverse sigmoid coIon Pelvic Descending sigmoid colon RectoTransverse 1 sigmoid coIon Srgmoid Stomach Sigmoid Stomach Sigmoid Stomach Rectum Stomach Rectum Stomach Rectum 1Stomach Rectum Stomach
Site
Feilchenfeld (54). Hanlon (55). v. Hansemann (56). Orr (51). Lockhart-Mummery (IO). Kroger (57). Devic & GaIIavardin (58). Robson & Knaggs (8). Lockhart-Mummery (IO) de Vries (59). Deetz (60). Brandt & Jekabson (61). Nicholls (62). MuIIer (63). Maingot (100) Stalker, Phillips, Pembertor (64). Kirshbaum, ShiveIy (I 7). Kirshbaum, ShiveIy (17). Schweiger & Bargen (18). Schweiger & Bargen (18). ,
Rect urn Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid
Stomach Stomach Stomach Stomach Stomach Stomach Pylorus Jejunum Pylorus Stomach GaIIbIadde r Pancreas Pancreas Pancreas Stomach
Sigmoid Sigmoid Sigmoid Rectum Sigmoid
Schweiger
& Bargen
(18)
Schweiger Schweiger Schweiger
& Bargen & Bargen & Bargen
(18). (18). (18).
Schweiger
& Bargen
(18)
Rectosigmoid Sigmoid Rectum Rectosigmoid Rectum
Cecum Stomach Stomach Colon Ascending colon Transverse coIon Cecum Cecum Cecum
Schweiger Saltzstein,
& Bargen (18). Kelly (65).
HeIlendaII (66) Herrlin, Mersheimer Danes ( I 03) BuII (I IO). BuII (IIO).............. Bacon (I) (2). Bacon (I) (2).
(67)
Rectum Rectosigmoid Sigmoid Sigmoid Rectum Sigmoid Sigmoid Rectum Rectum
Ascending coIon Cecum Transverse coIon pF;;dix e Pylorus Stomach Stomach Stomach Stomach
cedent tumor growth are known as primary tumors. Whereas a mutation for tumor usuaIIy occurs in a singIe group of ceIIsunicentric origin, it cannot be denied that it does occur occasionaIIy in severa groups of ceIIs-muIticentric or pIuricentric origin. This is understood to mean more than one
muItipIe maIignancy superimposed on an existent intestina1 poIyposis, whiIe a disis not considered in this tinct entity, discussion. The question arises, shouId these growths be histoIogicaIIy distinct and heterogeneous? It is generaIIy agreed that two tumors
Bacon,
NEwSERIESVOL_LXV~I~.N~.~
Gass-Sigmoid
which are distinctIy different histoIogicaIIy are independent, but it does not necessariIy folIow that histoIogic simiIarity represents one parent tumor from which the other has sprung. We know that sarcoma and carcinoma or the mixed type of carcinoma sarcomatodes, early stressed by Virchow, does occur. ProbabIy this is the resuIt of some abnorma1 stimuIus acting on the epitheIia1 and mesoderma1 eIements for which there is some evidence. The TABLE w MCLTLPLE
MALItiNANCY TRACT
AND
OF
THE
GENITO-URINARY
Author
BiIz(68)....................... Hanlon (55) Lockhart-Mummery (69). Fried (70) _. _. Warren Br Gates (41). Warren & Gates (41). HanIon (55). ScharIieb (71). GouiIlioud (48). Rau (52). Tanberg (72). HanIon(55)...........,,....,.. HanIon(55)._...........,...... BiIz(68)....................... HanIon (55). HanIon (ii), HanIon (55). Junghanns (39). MuIIer (63). Hanlon (55). HanIon (55). Nehrkorn (73)..,........,....._ Stalker, PhiIIips, Pemberton Kirshbaum, ShiveIy (17).
LOWER
Site
.
INTESTINAL
SYSTEM
Sigmoid Sigmoid Rectum Anus Rectum Rectum Rectum Rectum
Sigmoid Rectum Rectum Rectum Sigmoid Rectum ,’ Rectum Rectum Anus Rectum Sigmoid Rectum Sigmoid Anus (64) Sigmoid Rectum
Site
Uterus Uterus Uterus Cervix Cervix Cervix FaIIopian tube Both ovaries Ovary Ovary Kidney Kidney Kidney Kidney Kidney Kidney Prostate Prostate Prostate Penis Penis BIaddcr ; Uterus ’ Kidney
investigations of EhrIich and ApoIantgn which resuIted in the production of a typica sarcoma foIlowing the repeated inocuIation of mice with a typical adenocarcinoma are worthy of mention, also those of RusseIgl who succeeded in obtaining a pure sarcoma after continuous growth of an adenocarcinoma of the breast in a mouse. These experiments were confirmed by FouIds.g2 Others have cited their investigations. 106,106*107 HaaIand,g3 too, propa-
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Amcricun
J~,urnal of Surgery
245
gated a slow-growing adenocarcinoma in a mouse which exhibited sarcomatous change. According to Major g4 this change is conTABLE v MISCELLANEOUSCASES Author
Junghanns (39). Bile110 & Montanini Carnevale-Ricci (75) OphuIs (76). Rau (52). _. Rau (52). _. Rau (52). Kaufmann (104). HanIon (55). _. KIebs (77). ., de Besche (78). ..... HanIon (55). ....... de Vries (59). ...... Gottstein (79). HeIIendaII (6.5). EIiot (43). Lockhart-Mummery Norhury (I I). Norbury (I I). Kesteven (80). Lockhart-Mummery Eliot (43). IIanIon (55). Williams (81). Seecof (82). Lockhart-Mummery rviuller (63). v. Volkmann (83).
Site
(69)
(IO).
(IO).
Warren & Gates (41). Hibshman (84). Stalker, PhiIIips, Pembcrton Kirshbaum, Kirshbaum, Kirshbaum,
Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Anus Rectum Rectum Rectum Rectum Rectum Rectum Rectum
74)
ShiveIy (17). ShivcIy (17). ShiveIy (17).
Litchman (35). Bacon (I). Bacon (I). ......... Bacon (I). ......... Bacon (I). ................... Bacon (I). ...................
.
(64)
Rectum Rectum Sigmoid
.
Sigmoid Rectum Rectum Rectum Sigmoid Sigmoid Rectum Rectum Rectum
Site
Esophagus Esophagus Esophagus Esophagus Esophagus Esophagus Esophagus Orbit Face EyeIid Lip Lip Tongue Tongue Breast Breast Breast Breast Breast Breast Breast Breast Breast Breast Lung Bronchus Bronchus Skin of buttocks Skin Tongue Both breasts TonsiI Hepatic Gal1 bladder Lung 1Lie Esophagus Nose Tongue Gal1 bIadder
troIIed aImost entireiy by t le time element, inasmuch as where the transpIanted carcinoma is removed early and transmitted to another anima1 of the same species, carcinoma results; but if the transpIanted carcinoma is permitted to grow unti1 it becomes sarcoma, then a11 animaIs injected
246
American Journal oFSurgery
Bacon,
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deveIop a pure sarcoma. One may recall the case cited by Kidnerg5 in which a carcinoma deveIoped in the operative scar after remova of a sarcoma. There has been much discussion as to whether one maIignant growth has an inhibitory influence on the deveIopment of another primary neopIasm in the same individuaI. According to Lockhart-MummerylO there seems to be sufficient cIinica1 evidence to show that one maIignant growth does inhibit such deveIopment and Dukesgfi has cited some interesting experiments in
CoIon
MAY, I()45
reason why more than one glandular organ shouId not be exposed to the exciting cause of carcinoma, whatever that may be, either at about the same time or many years Iater.” So far as metastases are concerned a11 wouId tend to produce those of the same type but in different Iocations. The opinion is fairIy universa1 that taking al1 phases into consideration, the various factors point to some genera1 change as the predisposing cause of muItipIicity. SIaughterg8 in a recent articIe expresses the opinion that the etiologic factor of malig-
TABLE VI SARCOMA
AND
CARCINOMA
IN
DIFFERENT
SYSTEVS
Author
Warren & Gates (41). Landau (99). Werner (85). Nehrkorn (73). Dijkstra (86). Bergen 81 Rankin (3). (cited also in TabIe I).
Adenocarcinoma, rectum Carcinoma, rectum Adenocarcinoma, rectum Melanotic sarcoma, rectum S pm d1e cell sarcoma, rectum Adenocarcinoma, sigmoid
animaIs in an attempt to prove that transpIantation of a part of the origina maIignant tumor to heaIthy tissue eIsewhere in the body, tends to cause disappearance of the primary neopIasm. Others are equaIIy firm in their belief that immunity is not conferred, or that one primary maIignant growth does not inhibit the deveIopment of another. As to the occurrence of these growths, statistics show that they are more common in organs unreIated by any system. By means of breeding experiments on mice, Maud SIyeg’ has shown that spontaneous cancer is inherited as a MendeIian dominant. Indeed, her work is impressive in that there is probabIy a susceptibiIity to tumor formation in individuaIs deveIoping muItipIe maIignant growths and because these are not Iimited to any organ or portion of the human body. There seems to be Iittle significance as to the distinction between synchronous and metachronous growths. As EIiot43 has said “there is no
Lymphosarcoma, rectum Fibrosarcoma, breast Fibromyosarcoma, uterus Carcinoma, uterus Carcinoma, gallbIadder Sarcoma, uterus
Osteoma,
jaw
nancy acts on a11 tissues of one type and may produce muItipIe lesions. MuItipIe tumors occurring in different organs suggest a tumor diathesis inasmuch as they occur more frequentIy than couId be expected on the basis of chance aIone. Secondary tumor formation was accredited to the existence of a continuous network in the submucosa of the bowe1, but this since has been disproved. The occasiona1 transmission of cancer by retrograde venous emboIism has been cited also. Even though they may appear simiIar, secondary growths should not be confused with multipIe primary maIignancy. It is recognized that an impIantation type of cancer does exist, many authentic cases of which have been reported.22,‘06s l’)*,log Such may occur from one labia to the other or from one side of the anus to the other as recentIy encountered by the writers. Growths limited to a smaI1 portion of the bowe1 such as the sigmoid or rectum may occur by direct contact, a detached
NEW SERIESVOL.LXVIII,NO. 2
Bacon,
Gass-Sigmoid
fragment of the primary lesion being engrafted onto another portion of the mucous membrane. In such, a marked variation in the histologic appearance would not be expected inasmuch as they arise from the same type of epithelium. It is obviously difficult to determine their exact status. Where the aboral growth is the younger or where the two tumors are situated out of contact with each other or possibly when a prolonged period of time separates the appearance of the two neopIasms, they must be considered both primary neoplasms. In order to obviate a falsely low incidence of multiple primary malignancy, there has been a tendency to liberalize the origina requirements. Those suggested by Warren and Gates seem logical and are must here cited, “each of the tumors present a definite picture of malignancy; each must be distinct, and the possibility of one being a metastasis of the other must be excluded.” In other words as CokkinP has said a good rule to follow is that if two malignant tumors co-exist, or follow each other, and it can be definitely established that one is not a metastasis of the other, they must be regarded as primary growths.
Colon
American
possibility of multiple kept in mind.
Journal
of Surgery
neopIasms
The literature on the occurrence of multiple primary malignancies has been reviewed. An effort has been made to bring to date the total of such cases in which one or more lesions were located in the anus, rectum, or sigmoid coIon. Additiona cases have been presented in which there would seem to be no doubt of their multicentric origin. The conclusion is reached that (I) although it is by no means easy to establish evidence of muIticentric origin in a11 cases of multiple malignancy, severa cases are found and reported each year. (2) The rate of reported cases is 8.8 per year when the cases are Iimited to the involvement of anus, rectum and sigmoid colon. (3) It is evident that one malignancy does not confer immunity against another. (4) The
should be
REFERENCES
BACON, H. E. MultipIe malignant tumors with invoIvement of the lower bowel. Am. J. Surg., 35 : 243~ 1939. 2. BACON, H. E. MuItipIe maIignancy of the Iower bowel with report of muItipIe primary and contact growths. Tr. Am. hoc. Sot., p. 236, I.
1938.
3. GRAHAM, S. Communication 4.
6.
7. 8.
9.
IO.
to author (Dec.
IO)
1937. KRASKE, P. Ueber die Entstehung sekundarer Krebsgeschwure durch Impfung. Zentralhl. f. Cbir., I L: 801, 1884. BARGEN, J. A. and RANKIN, F. W. MuItipIe carcinomata of the Iarge intestine. Ann. Surg., 91: 583, 1930. MORTON, C. A. A case of multipIe adenomatous poIypi of the Iarge intestine associated with carcinoma both in the sigmoid IIexure and lower end of rectum. Lancet, I : I 245, I 895. HOCHENEGG, J. Bestrebungen zur Kontinzerzielung bei Wegen Mastdarkrebses operierten. Wien. med. Wcbnscbr., May, 1900. ROBSON, A. W. and KNAGGS, R. L. Two cases of double maIignant tumors of the intestines. Lancet, I : 640, 1905. ABEL, A. L. Three cases of doubIe carcinomata of the coIon and rectum. Proc. Roy. Sot. Med., 22:
1330,1928. LOCKHART-MUMMERY, J. P. Proc. Roy. Sot. Med.,
24: 198, 1930. I I. NORBURY, L. E. MuItipIe primary malignant growths. Proc. Roy. Sot. Med., 24: 6, 1930. maIignant foci in 12. MILLER. R. T. Multiple . primarv _ cancer of the colon. Ann. Surg., 80: 456, 1924. ‘3. MORGAN, C. W. Proc. Roy. Sot. Med., 24: 207, 1
SUMMARY
247
_
r 930.
14. ‘5.
16. 17. 18.
‘9. 20. 21. 22. 23.
POPIN,F. Gas. bebd. d. SC. med. Bordeaux, 52: 41, 1931. ROTTER, J. Im. Hanbuch der prakt. chir. Bergmann & Bruns. 3: 580, 1903. Polyposis rectiadenoma malignurn. Spontanheilung. Arch. f. klin. Cbir., 58: 357, 1899. COLE, P. P. IntramuraI spread o recta1 cancer. Brit. M. J., I: 431, 1913. KIRSHBAUM, J. D. and SHIVELY, F. S. MuItipIe primary malignant tumors. J. Lab. FY C/in. Med., 24: 283, 1938. SCHWEIGER, L. R. and BARGEN, J. R. MuItipIe primary malignant Iesions of the large bowe1. Arch. Int. Med., 66: 133r, 1940. SILNERS,H. I. MuItipIe intestinal carcinomata appearing simuItaneousIy. Am. J. Digest. Dia., 6: 25, 1939. LANE, W. A. Cancer of the colon, its causation and treatment. Lancet, 2: I 184, 1920. DOWDEN. J. W. Carcinoma of peIvic colon. Edinburgh M. J., 19: 181, 1917. MAINGOT, R. Multiple carcinomata of the rectum. Tr. Med. Sot. London, 50: 121, 1927. SCHMIDT. Bon veirfschem Darmkrebs. Inaug. Diss., KieI, 1901.
248
Americnn
Journal
uf Surgery
Bacon,
Gass-Sigmoid
24. ANGEVIUE, D. )vl. Three primary malignant epithehal tumors of anorectal region occurring in one person. Canad. M. A. J., 23: 38, 1930. 25. ZIMMERMAN,R. Canad. J. Med. SC., 7: 390, 1882. 26. DOERING, H. Die Polyposis intestini und ihre Beziehung zur carcinomatosen Degeneration. Arcb.J. klin. Cl&., 83: 194, 1907. 27. WULF, L. Inaug. Diss. KieI, 1892. 28. BUNTNG, C. H. Multiple primary carcinomata of the ileum. Bull. Johns Hopkins Hosp., 15: 389, 1904. 29. GOTTING, G. Zur MuItiplicitat primarer Carcinome. Zischr. f. Krebsforscb., 7: 675, 1909. 30. MIELECKI, W. Anatomisches una Kritisches zu 560 Obduktionen, bei denen sick bosartige GessbiwuIste fandrn. Ztsch~. j. KrebsJororscb,13: 505. ‘9’3. 31. JENTZER,A. Multiple tumors; 4 cases. Rea. med. de la Suisse Rom., 40: 236, 1920. 32. LAUDA, E. Wien. med. Wcbnscbr., 75: 1890, 1925. 33. GOETZE, 0. Beruerkungen uber Multiplezitat primarer Carcinome in AnIehung an einen Fall van dreifachen carcinoma. Zfscbr. J. KrebsJorsch., 13: 281, 1913. 34. KLENGENSTEIN, P. MuItipIe carcinomata of the coIon. PartiaI coIectomy for carcinoma of the transverse coIon; of the sigmoid and of the ascending colon. Ann. Surg., 102: 1079, 1935. 35. LrrcHhrAN, A. L. and MCDONALD, J. R. Fecal IistuIa. Surg., Cynec. ey Obst., 78: 449, 1944. 36. WHI~HAM, J. R. M. Persona1 communication, April, 1943. 37. BARGEN, J. A. Causes of colonic cancer. South. M. J., 32: 627, 1939. 38. MAYO, C. W. Multiple primary maIignant lesions of the colon with resection. Proc. .!?a$ Meet., Mayo Clinic., 15 : 465, 1940. 39. JUNGSHANNS, H. Eine Krebsstatistik uber 35 Jahre (4192 Carcinome bei 36408 Leichenoffnungen). Ztscbr. f. Krebsforscb., 29: 623, 1929. 40. KUSTER. Ein chirurgisch Triennium, p. 161, 1882. Ueber Neubildungen der Niere und ihre Behandlung. Centralbl. J. Krankb. d. Hum. ser. Org., 8: 583, 1897. 41; WARREN, S. and GATES, 0. MuItipIe primary malignant tumors. Am. J. Cancer, 16: 1358, 1932. 42. HANDFORD, H. Disseminated polypi of the Iargc intestine becoming malignant strictures (maIignant adenoma) of the rectum and of splenic flcxure. Tr. Parb. Sot. London, 4’: 133, 1890. 43. ELIOT, E. Recurrence versus metastatis in carcinoma. Tr. Am. Surg. Ass., 40: 115, 1922. 44. KARSR.EK, H. T. and CLARK, B. AnaIysis of 104 cases of carcinoma of the large intestine. Am. J. Cancer, 16: 958, 1932. 45. BEHREND, M. Carcinoma of coIon. Treatment depending on location of lesions. Surg., Gynec. &+Obst., 65: 505, 1937. 46. LITTLEWOOD.Cited by Yeomans. 47. COKKINS, A. J. MuItipIe carcinoma of the colon with four original cases. Brtt. J. Surg., 21: 570, 1934. 48. GO~ILLIOUD, C. Krebs des Eierstocks in Verlaufe van Krebsen des Magens, dcs Darmes und der Gallenivegc. Zentralbl. f. Gyniik., 31: 1426, ,907.
49
50.
5’. 52. 53.
54. 55. 56.
57, 58. 59. 60.
6r.
62.
63.
64.
65-
66. 67. 68. 69. 70. 71. 72. 73.
Colon
MAY. 194~
I IAWSER, G. Das Cylinderepithelcarcinom des Magens und Dickdarms, Jena, 189o. Geibt es primare zur Geschwulslbildung fubrende Epithelerkrankung? Beitr. R. path. Anat. u. z. allg. Patb., 33: I, 1903. PEMBERTON,J. DEJ. and WAUGH, J. hl. Primary carcinomas of the stomach and sigmoid Ilexure occurring simuItaneousIy in the same individua1. Surgery, 2: 21 I, 1937. ORR, J. W. MuItipIe malignant neoplasms. J. Path. u Bact., 33: 283, 1930. RAU, W. Ztscbr. J. Krebsforscb., 18: 141, 1922. JUDD, E. S. and PHILLIPS, J. R. Independent carcinoma of the coIon occurring six years after carcinoma of the stomach. Surg. Cl&. North America, 14: 525, 1934. FEILCHENFELD.Inaug. Diss., Berl., 1904. HANLON, F. R. Multiple primary carcinoma. Am. J. Cancer, 15: 2001, ‘93’. HANSEMANN, V. Das gIeichzeitige Voskommen verschiedenarliger GeschwaIste bei derseIben Person. Ztscbr. ,J. Krebsforscb., I : 183, 1904. KROGER, C. Cited by Rieder (Arch. J. klin. Cbir., ‘35: 179, 1925). DEVIC, E. and GALLOVARDIN. Bull. Sot. med. d. bBp. de L_von., 2: 242, 1903. DEVRIES. Zentralbl. J. ges. inn Med. u. Grenzgeb., vol. I, 1912. DEETZ, E. Vier weitere FaIIe von PIattenepitheIKrebs der GaIlenbIase. Arch. J. palb. anat., 64: 381, Igor. BRAN~T, M. and JEKARSON, K. Eine Krebsstatistik uber, 30 Janre fur das I. Rigasche Stadtkrankenhaus. Ztscbr. ,f. Krebsforscb., 32: 280, 1930. NICHOLLS, A. G. Multiple primary tumors in the stomach and mamma. Montreal M. J., 32: 326, ‘903. MULLER, R. F. Ueber multipIe Nichtsystematisierte Primare Carcinome und ihre Haufigkeit. Zrscbr. f. Krebsforscb., 3 I : 339, ‘930. STALKER, L. K. PHILLIPS, R. B. and PEMBERTON, J. DE J. MuItipIe primary maIignant lesions: Surg., Gynec. &+Obst., 68: 595. 1939. SALTZSTEIN,H. C. and KELLY, J. Some complications in the surgical handhng of carcinoma of the left colon and rectum. Surg., Gynec.
NEWSER~ESVOL.LXVIII, No. 2
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74. BILELLO, A. and MONTANINI, N. PIuricita di tumori maligni nello stesso soggetto. Tumori, 5: 369, 1931. 71;. CARNEVALE-RICCI. F. Evoluzione clinica ed anatomo pathologica dei fibomi rinofaringei trattati con la diathermocoaguIazione. Arch. ital. di otol., I: 221, 1931. 76. OPHCLS, W. A statistical survey of 3ooo autopsies. Stanford Unniu.Press, p. 316, 1926. 77. KLEBS, E. T. Handbucb der parb. anat., 2: 190, I 869. 78. BESCHE, A. Multiple kancere. Norsk. Mag. ,f. Laegeitidensk, 5: 533, 1908. 79. GOTTSTEIN, A. Quoted by Warren and Gates. 80. KESTEVEN, W. B. Case of cancer of the breast. Tr. Clin. Sot. London, 9: 77, 1876. 8 I. WILLIAMS, C.: Multiple primary carcinoma. Virginia Med. Montbly, 58: 24, 1931. 82. SEECOF, D. P. MuItipIe primary malignant neoplasms; report of case of carcinoma of lung each producing and carcinoma of rectum, metastases. Cancer Research, 8: 2I3, 1924. 83. VOLKMANN, R. Beitr. z. klin. cl&., 1875. 84. HIBSHMAN, H. Z. Personal communication. 85. WERNER, J. L. Rectal carcinoma associated with uterine sarcoma. Tr. Am. Proc. Sot., p. 64, 1937. 86. DIJKSTRA, 0. H. Nederl. Tydscbr. u. genneesk., 70: 270, 1926. 87. BILLROTH, T. Die AIIegemeina Chirurgie Pathologie u. Therapie. P. 908. Berlin, 1889. Reimer. 88. MERCANTON, F. Des carcinomes primaires muItiples. These de Lausanne, 1893. Rep. med. de la Suisse, Rom., 13: 173, 1893. 89. THOMPSON, J. W. Secondary resections in recurring carcinoma of the colon. J. A. M. A., 107: 1688, 1936. 90. ERHLICH, P. and APOLANT. Zur Kenntnis der SarkomentwickeIung bei Carcinomtransplantationen. Centralb1.f. ally. Patb. u. path. Anut., I7: 513, 1906. 01. RUSSEL. B. R. Sarcoma deveIooment occurrinz during the propagation of a hemorrhagic adenocarcinoma of the mamma of the mouse. J. Parb. Ed Bact., 14: 34, 1809. 92. FOULDS, L. Tenth Scientific Rep. Imp. Cancer Res. Fund., p. 21, 1932. 93. I~AALAND, M. Third Scientific Report, Imp. Cancer Res., p. 175, 1908. I,
3
Colon
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Journal
of Surgery
249
94. MAJOR, R. H. Multiple primary malignant tumors. Bull. Jobn Hopkins Hosp., 29: 332, 1918. 95. KIDNER, F. C. Sarcoma and carcinoma in the same patient. Boston M. @ S. J., 158: 836, 1908. 96. DUKES, C. The heredity factor in polyposis intestini or multipIe adenomata. Cancer Rev., 5: 241, 1930. 97. SLYE, M. Relation of inbreeding to tumor production; studies in incidence and inheritabiIity of spontaneous tumors in mice. J. Cancer Res., 5: 53. 192o. Relation of heredity to cancer occurrence as shown in strain 73. Am. J. Cancer Res., 18: 535. ‘933. of origin of 98. SLAUGHTER, D. P. The multiplicity malignant tumors. Surg., GJrnec. P’* Obsr., 79: 89, 1944. 99. LANDAC, H. Krebs und Sarkom am gleichen Menschen. Miincben. med. Wcbnscbr., 650, 1905, R. Primarv carcinomas of the stomach IO”. MAINGOT, and sigmoid coIon occurring simuItaneousIy. Bril. M. J., I: I 18, 1938. MILLER, R. T. Cancer of the colon. Tr. Am. Surg. Ass., 49: 54, ‘923. SCHABAD, L. M. and GORIAINOWA, R. W. Zur Frage der Todesursachen bei Krebskranken. Zrscbr. J. h’rebsforscb., 33: 594, 1931. 103. DAVIS. Quoted by Krakiewicz. des primaren 104. KAC.I;MAKN, C. Ueber Multiplicitat Carcinoms. Vircbow’s Arch. f. pub. anat., 75: 317. 1879. reaction to 105. BASHFORD, E. F. The immunity cancer. Proc. Roy. Sot. Med., p. 165, 1909. I 06. FENCER, C. DoubIe carcinoma of the colon. J. A. M. A., 2. 606, 1888. of tumors. J. Med. 107. LOEB, L. On transpIantation Research, 6: 28, 1901. I 08. BORRMAP\;,R. Deutscbe Ztscbr. f. Cbir., 76: 404, ‘905. 109. HOCHE, L. Du cancer gastrique secondaire. Presse mLd., I: 67, 1901. I IO. BULL, M. P. Bull. et mkm. Sot. Natl. d. cbir., 58: 1338, 1932. primary cancers. III. KRETSCHMER, H. L. Multiple J. Ural., 40: 421, 1938. of three primary 112. SMITH, C. FI. Surgical remova carcinomas of the colon. Proc. Sta$ Meet., Ma_vo Clin., 13: 122, 1938. 1’3. JENSEN, C. 0. Centralb1.f. Bakt., 34: 122, 1903,
OF FIVE ADDITIONAL
HARRY E. BACON, M.D.
AND
CASES
ORVILLE
C.
GASS,
M.D.
Assistant in Proctology, Tempk University MedicaI SchooI
Professor and Head of Department of Proctology, TempIe University Medical School PHILADELPHIA,
PENNSYLVANIA
I
N 1939, the authors1*2 reported seven cases of muItipIe primary maIignant tumors occurring in the rectum or sigmoid and other parts of the human organism, and three contact growths. It is our purpose to present five additional cases that have been encountered on our service during the ensuing five-year period : CASE REPORTS CASE I. R. F., a white femaIe, aged fiftytwo, was seen in consuItation August 4, 1944. She stated that she had been bIeeding for seven or eight years, but since May there occurred a change in the character of the blood. Previously the bIood was bright red in color, sparse in amount and was noted on the stool or foIIowing an evacuation. On May 3, 1944, a hemorrhoidectomy had been performed, but shortly thereafter she experienced five or six evacuations daiIy. She had been constipated for many years and required Iaxatives. The stooIs were usuaIIy of the constipated type except when excess Iaxatives were resorted to. RecentIy the evacuations consisted of a “pinkish liquid” and “gas” which Ieft her with a feeIing of incompIeteness and fuIIness. The first movement each day occurred when she first arose in the earIy morning, but frequentIy she had an incompIete evacuation during the night. During the day the patient usuaIIy passed a fairIy we11 formed stoo1 which was accompanied by bright red bIood; the sense of fuIIness was reIieved temporariIy. No weight Ioss was cited. The patient had had a thyroidectomy fourteen years previousIy and recently had been hospitaIized for hypertension. Her famiIy history was irrelevant. Proctoscopy reveaIed a cauliflower-Iike growth at a distance of 12 cm. invoIving the anterior and IateraI phases of the rectosigmoid.
The process presented nodularity, uIceration and eversion of the edges. Biopsy made of the lesion was reported adenocarcinoma of the rectum grade III. The patient was hospitalized August 9, 1944, and on the fifteenth a one-stage abdominoperinea1 proctosigmoidectomy without the establishment of an abdominal coIostomy and with preservation of the sphincter muscles was performed. ApproximateIy 40 cm. of rectum and sigmoid were resected. After compIetion of the operation the specimen was opened and it was found to contain an additiona Iesion. Description of the specimen was as foIIows: “Specimen of bowel measures 40 cm. in length; 15 cm. from dista1 end there is a large fungoid tumor mass which measures 6 cm. in diameter. It occupies the major portion of the wall circumference. The centra1 portion is ulcerated and the base indurated. The tumor penetrates the entire thickness of the wall to inyade the subserosa1 fat, but no enlarged nodes are paIpated. Ten cm. above this lesion there is a papiIIoma measuring I cm. in diameter and 4 cm. in Iength. Sections taken from the Iarge tumor mass show it to be adenocarcinoma. Sections taken from the dista1 end of the poIypoid growth show it to be undergoing papiIIary proIiferation with earIy malignant change. Diagnosis: Carcinoma of rectosigmoid and maIignant papiIIoma of proximal sigmoid.” The patient had an uneventful recovery and was discharged on the fifteenth postoperative day. CASE II. A. T., a white maIe, aged sixtyseven, was referred because of abdomina1 pain and recta1 bIeeding. For a period of six months the patient had experienced pain in the lower abdomen which was partiaIIy relieved by defecation. An occasiona pain was experrenccd in the rectum at the time of bowel movement. Three months previousIy the patient had passed considerabIe red bIood with
240
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Gass-Sigmoid
each bowe1 movement. The patient stated that he had always been constipated. He had no early morning diarrhea; two stooIs daily were incomplete and unsatisfactory. A frequent desire for evacuation was cited; usuahy flatus and debris were expelled. He had Iost approximateIy three to four pounds during his illness. The past history was irrelevant. On digita examination a cauIifIower-like mass presenting fixation, noduIarity and eversion of the edges was noted. Proctosigmoidoscopy revealed a circumferentia1, crater-like process. Biopsy made was reported adenocarcinoma of the rectum grade III. On June IS, 1943, a one-stage abdominoperineal proctosigmoidectomy without the establishment of an abdominal coIostomy and with preservation of the sphincter muscIes was performed. Fifteen cm. of the rectum and lower sigmoid coIon were removed. The process penetrated the entire waI1 of the gut to cause puckering of the overlying serosa and there was enlargement of regional lymph nodes. No metastasis to the liver was demonstrable. The patient’s postoperative course was uneventful and he was discharged from the hospital on his twelfth day. In March 1944, nine months following operation, his famiIy physician discovered a smaI1 lesion on the right side of his tongue. A biopsy was made by a IocaI surgeon and a diagnosis of epithelioma made. On hlay 5, 1944, the patient was operated upon for his second malignant Iesion by Dr. J. Blady. CASE III. Mrs. M. M., white, aged sixtynine, was referred July 12, 1943, because of rectal bleeding. For a period of three weeks she had noticed bright red bIood after each bowel movement. The bIood was sparse in amount and there was no history of frequent stools or early morning diarrhea. The movements were compIete and satisfactory, however, the patient experienced a sense of fullness in the lower part of the abdomen after each defecation. Her weight was seventy-two pounds. Two years previousIy the patient had been operated upon for cancer of the right breast. There was no evidence of metastasis at this time. Her father died of cancer of the stomach. On proctosigmoidoscopy a papiIIary adenocarcinoma was noted at a distance of 14 cm. The tumor was located in the Ieft IateraI quadrant and invoIved approximately onequarter of the circumference of the rectum. A biopsy made at this time was sent to the
CoIon
AmericanJournalof Surgery
241
TempIe University Hospital and reported as foIIows: “The sections show these fragments of tissue to consist of adenocarcinoma. The ceIIs are of the taI1 cylindrical type which one expects to see in a primary carcinoma of the Diagnosis: Adenocarcinoma of the rectum. rectum.” The treatment in this case was determined by the patient’s poor physical condition and refusa1 of the famiIy for any surgica1 procedure. Electrofulguration was instituted JuIy I 9, 1943, through a sigmoidoscope and thereafter at weekly intervals. Some gain in weight was experienced and three months later there was cIinicaIIy no evidence of malignancy. The patient returned for re-examination after a period of eight weeks and recurrence was noted. Again a palliative double-barreled colostomy with implantation of radon from above and from below was advised but refused. CASE IV. Mrs. F. W. C., white, femaIe, aged fifty, was seen in consultation October 29, 1943. The patient’s symptoms began three months previousIy with a bearing-down sensation and a frequent desire for defecation. The bowel movements were incomplete and unsatisfactory. Often when the patient had the urge for a bowel movement only Batus and smaI1 amounts of fecal material mixed with bIood would be expelled. The blood was sparse in amount, bright red in coIor and occurred onIy with evacuation. The patient was uncertain whether or not she had lost any weight. Past and famiIy history were irrelevant. Digital examination revealed thickening of the upper portion of the rectovaginal septum. Upon advancing the finger a large mass approximately the size of an orange was encountered. The mass was hard and circumferentially placed; it presented fixation, nodularity and eversion of its edges. Vagina1 examination discIosed a serosanguineous discharge. A malignant type of erosion of the cervix was noted. The uterus itself did not seem to be fixed, but infiltration existed in the vauIt. Biopsies of the cervica1 and recta1 lesions were reported adenocarcinoma grade II of the rectum and squamous ceI1 carcinoma grade III of the uterine cervix. On November 9, 1943, an abdominoperinea1 proctosigmoidectomy without the estabIishment of an abdomina1 colostomy and with preservation of the sphincter muscIes was performed. The report of the operative specimen examined and recorded by Dr. A. L. Pietrolango
242
American
Journal
of Surgery
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Gass-Sigmoid
read as follows: “The specimen is a piece of bowe1 measuring approximately 18 cm. in length. In the centraI portion there is an ulcerative tumor mass which compIeteIy surrounds the Iumen. The edges are raised, robed and firm. The ffoor is deepIy ulcerated with necrotic tissue. Examination of the subserosal fat fails to show any evidence of enlarged lymph nodes. The tumor apparentIy inIiItrates the entire thickness of the bowel wall. Numerous anaplastic gIanduIar structures are found diffusely infiltrating the wall. A chronic infIammatory reaction accompanies the process. Diagnosis: Adenocarcinoma of colon, grade II.” The cervical lesion was treated with radium by Dr. W. Steel, the referring physician. CASE v. Miss M. M., a white femaIe, age thirty-eight, was operated upon for carcinoma of the cecum in October, 1941. The operation consisted of an ileocolostomy foIlowed by resection. The growth removed by Dr. J. L. Summey was reported as adenocarcinoma. She was symptom free thereafter. On December 20, 1944, she was referred to us with the diagnosis of carcinoma of the rectosigmoid junction. The history revealed that she began to pass mucus streaked with blood some eighteen months after her first operation. Later she experienced sharp pains in the Ieft Iower quadrant becoming more constant and relieved onIy by reclining. The stooIs were described as smal1 and often bIack in coIor. The pain forced her to consult her physician who by doubIe contrast enema found a spacetaking Iesion at the rectosigmoida1 region. Further examination reveaIed a circumferentia1 cancerous process, adenocarcinoma grade II. The patient was admitted to our clinic and on December 27, 1944, was operated upon for her second primary malignancy. A sigmoidectomy was performed using the aseptic technic and a temporary transverse coIostomy estabIished proximal to the primary anastomosis. The Ieft tube and ovary were enmeshed in the cancerous bowel and removed. There was no evidence of metastasis. Gross description of the specimen was as foIIows: “The specimen is a segment of large bowe1 about 24 cm. in length to the serosal surface of which a tube and ovary are attached. In the center of the bowel a large uIcer 4 cm. in diameter is found on the mucosa1 surface. The uIcer base contains necrotic tissue. Its edges are firm but proliferative. The mucosal surface in the immediate vicinity has become
Colon
lL1AY, lg.&s
involved in the neopIastic process as is demonstrated by poIypoid masses which are really part of the advancing tumor edges. The tumor has penetrated the entire thickness of the bowel and the tube and ovary are cIosely adherent at this point. GrossIv no definite evidence of tumor penetration ‘is seen. The ovary contains follicular and hemorrhagic TABLE I DOVRLE MALIGNANCYIN THE ANUS, RECTUM AND
SIGMOID
COLON
Author
Graham (3). ................. Kraske (4). .................. Bargen & Rankin (5). .......... Morton (6). ................... Bargen & Rankin (5). Bargen & Rankin (5). Bargen & Rankin (5). Bargen & Rankin (5) Bargen & Rankin (5). IIochenegg (7), Robson & Knaggs (8). Abe1 (9)................ Abel (9). Lockhart-Mummery (IO). Lockhart-Mummerv (IO) Norbury (I I). .... .“. .... : ....... Miller (12) (101). .............. Morgan (I 3) ................... PaDin (14). .................... Rotter ‘( 1-5) Rotter (I 5) . Rotter (15). . . Rotter (15). Rotter (15). Graham (3) ,,....
.I Rectum .I Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Rectum
Graham (3).
Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectosigmoid Rectum
Cole (16).
Rectum
Kirshbaum & ShiveIy (17). Kirshbaum & ShiveIy (17). Schweiger & Bargen (18). Schweiger & Bargen (18). Schweiger & Bargen (18).
Rectum Rectum Rectum Rectum Rectum
Schweiger 81 Bargen (18).
Rectum
Schweiger & Bargen Schweiger & Bargen Schweiger & Bargen Schweiger & Bargen Schweiger & Bargen Silvers (19). Bacon (I) (2). Bacon (I) (2). .
Rectum Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum
(18) (18). (18). (18), (18).
-I
Rectum Anus Sigmoid Siamoid Sigmoid Rectum Rectum Sigmoid Sigmoid Rectum Rectum Pelvic coIon Rectum Sigmoid Sigmoid Rectum Sigmoid Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid Rectosigmoid PeIvic sigmoid Sigmoid Sigmoid Sigmoid Rectum Rectosigmoid Sigmoid coIon Rectum Rectum Sigmoid Sigmoid Sigmoid Sigmoid Rectum Rectum
NEWSERIESVOL.LXVIII,NO.~
Bacon,
Gass-Sigmoid
cysts. Diagnosis: Adenocarcinoma of sigmoid, grade II, with ovarian capsular invasion.” The patient’s postoperative course was satisfactory. She will return to the hospital at the end of a six weeks period for closure of the transverse colostomy. A review of the Iiterature of proved cases is appended in TabIes I to VI. TABLE THREE
Site
Rectum Rectum Rectum Rectum
.’
: .I
American
bIe for its separate To this MercantorP quaIifIcation: “that
Journnl
243
of Surgery
group of metastases. added the folIowing if after remova] of two
carcinomas the patient remains free from the disease, the two growths must have been independent eIse there shouId have been other metastasis.” It is evident that in carcinomas arising from the intestinal II
OR MORE MALIGNANT
Author
Lane (20). Norbury (I I). _. Dowden (21). _. Maingot (22). Bargen & Rankin (5) Bargen & Rankin (5) Schmidt (23). Angevine (24). Zimmerman (25). Doering (26), WuIf (27). Miller (12) (101). Bunting (28). Getting (29). v. Mielecki (30). Jentzer (31). Bargen & Rankin (5). Lauds (32). Goetze (33). Bargen & Rankin (5). KIingenstein (34). Schweiger & Bargen (18). Litchman (35). Whigham (36). Bargen, J. R. (37). Mayo, C. W. (38). Kretschmer (I I I). Smith (112) ._.. ,, ,. Bacon (I) (2).
Colon
~
LESIONS
Site
Site
I
Site
~Siamoid I Sjgmoid -
Breast ~ I Transverse coIon Slgmoid Small Intestine Anus Sigmoid Three separate carcinomas of the rectum and sigmoid Rectosigmoid 1Rectum Rectum I Rectum RectumSigmoid Rectum Rectum Anus Rectum Left Adrenal Sigmoid Rectum Rectum Hepatic Flexure Hepatic Flexure Rectum Splenic Flexure Rectum Hepatic Flexure Transverse colon Siamoid i Cecum IIeum Rectum Larynx Stomach Rectum L arynx Stomach Rectum Orbit Stomach SpIenic FIexure Uterus (sa.) Sigmoid Ascending colon Esophagus BiIe duct TonsiI Rectum Prostate Colon Rectum Stomach Transverse colon Spienic Aexure Sigmoid Cecum Transverse colon Uterus Sigmoid Ascending colon Sigmoid Sigmoid Sigmoid Cecum Rectum Sigmoid Prostate Rectum Cecum Descending colon Cecum Rectosigmoid Cecum Descending coIon i Sigmoid Prostate Sigmoid Bladder Sigmoid Descending colon Cecum I Rectum 1Sigmoid Rectum
I The postuIates Iaid down by BilIroth,87 which must be fuIHIed before multiple carcinoma can be identified as independent lesions, are we11 known because they have been mentioned by virtualIy every writer on the subject, but here again they bear repetition: (I) The two growths shouId differ histologicaIIy which must be so pronounced as to excIude the possibiIity that they are of the same origin, but in different stages of deveIopment; (2) each growth must spring from its parent epitheIium; and (3) each growth must be heId responsi-
epitheIium the first of these postuIates cannot we11 be satisfied because as Thompsons9 has said, “since carcinomatous degeneration of multiple intestina1 poIypi is entirely IikeIy, it seems that this postulate need not be fuIfiIIed in identifying muItipIe independent carcinomas of the intestine.” As a matter of fact, BuntingZs is of the opinion that these postuIates were intended to appIy onIy to maIignant growths arising in different organs. It is admitted that the limitations of these criteria are too strict because a
244
Amcricnn
Journ~~I of Surgrry
Bacon,
Gass-Sigmoid
faIseIy low incidence has resulted. What then are the criteria which one is to empIoy? The fundamental probIem is “what constitutes muItipIe primary maIignancy?” Tumors arising independently of ante-
Author
Site
Junghanns (39). Kuster (40). Lockhart-Mummery (10). Lockhart-Mummery (IO). Norbury(r~)............ Warren & Gates (41). Norbury (I I) Handford
(42).
EIiot (43) Bargen & Rankin Bargen & Rankin
(5). (5).
Abe1 (9). Karsner
61 Clark (44).
Behrend
(45).
Lockhart-Mummery Littlewood
(46).
Littlewood
(46).
Cokkins
(47).
Cokkins
(47).
Cokkins
(47).
MALIGNANCIES
(IO).
Goriainowa & Schabad (102). Hauser (49). Pemberton & Waugh (50). Hauser (49). Orr (51). _. _. _. Rau (52). . Judd & PhiIIips (53) .
.\lAY, ,<&$j
malignant growth occurring independentI>in the same individual. For this there are excellent examples such as polyposis of the large bowel and stomach, lyfnphosarcoma and multiple myeloma. But It is said that
TABLE DUAL
Colon
OF THE
III GASTROINTESTINAL
Site
TRACT
Author
( Rectum , Rectum
Colon Colon Rectum Colon Rectum Colon Rectum CoIon Rectum Colon Rectum Transverse colon Rectum SpIenic IIexure Sigmoid Splenic Aesure Rectum Cecum Sigmoid Ascending coIon Pelvic Descending coIon coIon Sigmoid Descending colon Rectum Ascending coIon Rectum Transverse coIon Rectum SpIenic Aexure Rectum Ascending colon PeIvic Transverse sigmoid coIon Pelvic Descending sigmoid colon RectoTransverse 1 sigmoid coIon Srgmoid Stomach Sigmoid Stomach Sigmoid Stomach Rectum Stomach Rectum Stomach Rectum 1Stomach Rectum Stomach
Site
Feilchenfeld (54). Hanlon (55). v. Hansemann (56). Orr (51). Lockhart-Mummery (IO). Kroger (57). Devic & GaIIavardin (58). Robson & Knaggs (8). Lockhart-Mummery (IO) de Vries (59). Deetz (60). Brandt & Jekabson (61). Nicholls (62). MuIIer (63). Maingot (100) Stalker, Phillips, Pembertor (64). Kirshbaum, ShiveIy (I 7). Kirshbaum, ShiveIy (17). Schweiger & Bargen (18). Schweiger & Bargen (18). ,
Rect urn Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid
Stomach Stomach Stomach Stomach Stomach Stomach Pylorus Jejunum Pylorus Stomach GaIIbIadde r Pancreas Pancreas Pancreas Stomach
Sigmoid Sigmoid Sigmoid Rectum Sigmoid
Schweiger
& Bargen
(18)
Schweiger Schweiger Schweiger
& Bargen & Bargen & Bargen
(18). (18). (18).
Schweiger
& Bargen
(18)
Rectosigmoid Sigmoid Rectum Rectosigmoid Rectum
Cecum Stomach Stomach Colon Ascending colon Transverse coIon Cecum Cecum Cecum
Schweiger Saltzstein,
& Bargen (18). Kelly (65).
HeIlendaII (66) Herrlin, Mersheimer Danes ( I 03) BuII (I IO). BuII (IIO).............. Bacon (I) (2). Bacon (I) (2).
(67)
Rectum Rectosigmoid Sigmoid Sigmoid Rectum Sigmoid Sigmoid Rectum Rectum
Ascending coIon Cecum Transverse coIon pF;;dix e Pylorus Stomach Stomach Stomach Stomach
cedent tumor growth are known as primary tumors. Whereas a mutation for tumor usuaIIy occurs in a singIe group of ceIIsunicentric origin, it cannot be denied that it does occur occasionaIIy in severa groups of ceIIs-muIticentric or pIuricentric origin. This is understood to mean more than one
muItipIe maIignancy superimposed on an existent intestina1 poIyposis, whiIe a disis not considered in this tinct entity, discussion. The question arises, shouId these growths be histoIogicaIIy distinct and heterogeneous? It is generaIIy agreed that two tumors
Bacon,
NEwSERIESVOL_LXV~I~.N~.~
Gass-Sigmoid
which are distinctIy different histoIogicaIIy are independent, but it does not necessariIy folIow that histoIogic simiIarity represents one parent tumor from which the other has sprung. We know that sarcoma and carcinoma or the mixed type of carcinoma sarcomatodes, early stressed by Virchow, does occur. ProbabIy this is the resuIt of some abnorma1 stimuIus acting on the epitheIia1 and mesoderma1 eIements for which there is some evidence. The TABLE w MCLTLPLE
MALItiNANCY TRACT
AND
OF
THE
GENITO-URINARY
Author
BiIz(68)....................... Hanlon (55) Lockhart-Mummery (69). Fried (70) _. _. Warren Br Gates (41). Warren & Gates (41). HanIon (55). ScharIieb (71). GouiIlioud (48). Rau (52). Tanberg (72). HanIon(55)...........,,....,.. HanIon(55)._...........,...... BiIz(68)....................... HanIon (55). HanIon (ii), HanIon (55). Junghanns (39). MuIIer (63). Hanlon (55). HanIon (55). Nehrkorn (73)..,........,....._ Stalker, PhiIIips, Pemberton Kirshbaum, ShiveIy (17).
LOWER
Site
.
INTESTINAL
SYSTEM
Sigmoid Sigmoid Rectum Anus Rectum Rectum Rectum Rectum
Sigmoid Rectum Rectum Rectum Sigmoid Rectum ,’ Rectum Rectum Anus Rectum Sigmoid Rectum Sigmoid Anus (64) Sigmoid Rectum
Site
Uterus Uterus Uterus Cervix Cervix Cervix FaIIopian tube Both ovaries Ovary Ovary Kidney Kidney Kidney Kidney Kidney Kidney Prostate Prostate Prostate Penis Penis BIaddcr ; Uterus ’ Kidney
investigations of EhrIich and ApoIantgn which resuIted in the production of a typica sarcoma foIlowing the repeated inocuIation of mice with a typical adenocarcinoma are worthy of mention, also those of RusseIgl who succeeded in obtaining a pure sarcoma after continuous growth of an adenocarcinoma of the breast in a mouse. These experiments were confirmed by FouIds.g2 Others have cited their investigations. 106,106*107 HaaIand,g3 too, propa-
Colon
Amcricun
J~,urnal of Surgery
245
gated a slow-growing adenocarcinoma in a mouse which exhibited sarcomatous change. According to Major g4 this change is conTABLE v MISCELLANEOUSCASES Author
Junghanns (39). Bile110 & Montanini Carnevale-Ricci (75) OphuIs (76). Rau (52). _. Rau (52). _. Rau (52). Kaufmann (104). HanIon (55). _. KIebs (77). ., de Besche (78). ..... HanIon (55). ....... de Vries (59). ...... Gottstein (79). HeIIendaII (6.5). EIiot (43). Lockhart-Mummery Norhury (I I). Norbury (I I). Kesteven (80). Lockhart-Mummery Eliot (43). IIanIon (55). Williams (81). Seecof (82). Lockhart-Mummery rviuller (63). v. Volkmann (83).
Site
(69)
(IO).
(IO).
Warren & Gates (41). Hibshman (84). Stalker, PhiIIips, Pembcrton Kirshbaum, Kirshbaum, Kirshbaum,
Rectum Rectum Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Rectum Rectum Sigmoid Rectum Rectum Rectum Rectum Anus Rectum Rectum Rectum Rectum Rectum Rectum Rectum
74)
ShiveIy (17). ShivcIy (17). ShiveIy (17).
Litchman (35). Bacon (I). Bacon (I). ......... Bacon (I). ......... Bacon (I). ................... Bacon (I). ...................
.
(64)
Rectum Rectum Sigmoid
.
Sigmoid Rectum Rectum Rectum Sigmoid Sigmoid Rectum Rectum Rectum
Site
Esophagus Esophagus Esophagus Esophagus Esophagus Esophagus Esophagus Orbit Face EyeIid Lip Lip Tongue Tongue Breast Breast Breast Breast Breast Breast Breast Breast Breast Breast Lung Bronchus Bronchus Skin of buttocks Skin Tongue Both breasts TonsiI Hepatic Gal1 bladder Lung 1Lie Esophagus Nose Tongue Gal1 bIadder
troIIed aImost entireiy by t le time element, inasmuch as where the transpIanted carcinoma is removed early and transmitted to another anima1 of the same species, carcinoma results; but if the transpIanted carcinoma is permitted to grow unti1 it becomes sarcoma, then a11 animaIs injected
246
American Journal oFSurgery
Bacon,
Gass-Sigmoid
deveIop a pure sarcoma. One may recall the case cited by Kidnerg5 in which a carcinoma deveIoped in the operative scar after remova of a sarcoma. There has been much discussion as to whether one maIignant growth has an inhibitory influence on the deveIopment of another primary neopIasm in the same individuaI. According to Lockhart-MummerylO there seems to be sufficient cIinica1 evidence to show that one maIignant growth does inhibit such deveIopment and Dukesgfi has cited some interesting experiments in
CoIon
MAY, I()45
reason why more than one glandular organ shouId not be exposed to the exciting cause of carcinoma, whatever that may be, either at about the same time or many years Iater.” So far as metastases are concerned a11 wouId tend to produce those of the same type but in different Iocations. The opinion is fairIy universa1 that taking al1 phases into consideration, the various factors point to some genera1 change as the predisposing cause of muItipIicity. SIaughterg8 in a recent articIe expresses the opinion that the etiologic factor of malig-
TABLE VI SARCOMA
AND
CARCINOMA
IN
DIFFERENT
SYSTEVS
Author
Warren & Gates (41). Landau (99). Werner (85). Nehrkorn (73). Dijkstra (86). Bergen 81 Rankin (3). (cited also in TabIe I).
Adenocarcinoma, rectum Carcinoma, rectum Adenocarcinoma, rectum Melanotic sarcoma, rectum S pm d1e cell sarcoma, rectum Adenocarcinoma, sigmoid
animaIs in an attempt to prove that transpIantation of a part of the origina maIignant tumor to heaIthy tissue eIsewhere in the body, tends to cause disappearance of the primary neopIasm. Others are equaIIy firm in their belief that immunity is not conferred, or that one primary maIignant growth does not inhibit the deveIopment of another. As to the occurrence of these growths, statistics show that they are more common in organs unreIated by any system. By means of breeding experiments on mice, Maud SIyeg’ has shown that spontaneous cancer is inherited as a MendeIian dominant. Indeed, her work is impressive in that there is probabIy a susceptibiIity to tumor formation in individuaIs deveIoping muItipIe maIignant growths and because these are not Iimited to any organ or portion of the human body. There seems to be Iittle significance as to the distinction between synchronous and metachronous growths. As EIiot43 has said “there is no
Lymphosarcoma, rectum Fibrosarcoma, breast Fibromyosarcoma, uterus Carcinoma, uterus Carcinoma, gallbIadder Sarcoma, uterus
Osteoma,
jaw
nancy acts on a11 tissues of one type and may produce muItipIe lesions. MuItipIe tumors occurring in different organs suggest a tumor diathesis inasmuch as they occur more frequentIy than couId be expected on the basis of chance aIone. Secondary tumor formation was accredited to the existence of a continuous network in the submucosa of the bowe1, but this since has been disproved. The occasiona1 transmission of cancer by retrograde venous emboIism has been cited also. Even though they may appear simiIar, secondary growths should not be confused with multipIe primary maIignancy. It is recognized that an impIantation type of cancer does exist, many authentic cases of which have been reported.22,‘06s l’)*,log Such may occur from one labia to the other or from one side of the anus to the other as recentIy encountered by the writers. Growths limited to a smaI1 portion of the bowe1 such as the sigmoid or rectum may occur by direct contact, a detached
NEW SERIESVOL.LXVIII,NO. 2
Bacon,
Gass-Sigmoid
fragment of the primary lesion being engrafted onto another portion of the mucous membrane. In such, a marked variation in the histologic appearance would not be expected inasmuch as they arise from the same type of epithelium. It is obviously difficult to determine their exact status. Where the aboral growth is the younger or where the two tumors are situated out of contact with each other or possibly when a prolonged period of time separates the appearance of the two neopIasms, they must be considered both primary neoplasms. In order to obviate a falsely low incidence of multiple primary malignancy, there has been a tendency to liberalize the origina requirements. Those suggested by Warren and Gates seem logical and are must here cited, “each of the tumors present a definite picture of malignancy; each must be distinct, and the possibility of one being a metastasis of the other must be excluded.” In other words as CokkinP has said a good rule to follow is that if two malignant tumors co-exist, or follow each other, and it can be definitely established that one is not a metastasis of the other, they must be regarded as primary growths.
Colon
American
possibility of multiple kept in mind.
Journal
of Surgery
neopIasms
The literature on the occurrence of multiple primary malignancies has been reviewed. An effort has been made to bring to date the total of such cases in which one or more lesions were located in the anus, rectum, or sigmoid coIon. Additiona cases have been presented in which there would seem to be no doubt of their multicentric origin. The conclusion is reached that (I) although it is by no means easy to establish evidence of muIticentric origin in a11 cases of multiple malignancy, severa cases are found and reported each year. (2) The rate of reported cases is 8.8 per year when the cases are Iimited to the involvement of anus, rectum and sigmoid colon. (3) It is evident that one malignancy does not confer immunity against another. (4) The
should be
REFERENCES
BACON, H. E. MultipIe malignant tumors with invoIvement of the lower bowel. Am. J. Surg., 35 : 243~ 1939. 2. BACON, H. E. MuItipIe maIignancy of the Iower bowel with report of muItipIe primary and contact growths. Tr. Am. hoc. Sot., p. 236, I.
1938.
3. GRAHAM, S. Communication 4.
6.
7. 8.
9.
IO.
to author (Dec.
IO)
1937. KRASKE, P. Ueber die Entstehung sekundarer Krebsgeschwure durch Impfung. Zentralhl. f. Cbir., I L: 801, 1884. BARGEN, J. A. and RANKIN, F. W. MuItipIe carcinomata of the Iarge intestine. Ann. Surg., 91: 583, 1930. MORTON, C. A. A case of multipIe adenomatous poIypi of the Iarge intestine associated with carcinoma both in the sigmoid IIexure and lower end of rectum. Lancet, I : I 245, I 895. HOCHENEGG, J. Bestrebungen zur Kontinzerzielung bei Wegen Mastdarkrebses operierten. Wien. med. Wcbnscbr., May, 1900. ROBSON, A. W. and KNAGGS, R. L. Two cases of double maIignant tumors of the intestines. Lancet, I : 640, 1905. ABEL, A. L. Three cases of doubIe carcinomata of the coIon and rectum. Proc. Roy. Sot. Med., 22:
1330,1928. LOCKHART-MUMMERY, J. P. Proc. Roy. Sot. Med.,
24: 198, 1930. I I. NORBURY, L. E. MuItipIe primary malignant growths. Proc. Roy. Sot. Med., 24: 6, 1930. maIignant foci in 12. MILLER. R. T. Multiple . primarv _ cancer of the colon. Ann. Surg., 80: 456, 1924. ‘3. MORGAN, C. W. Proc. Roy. Sot. Med., 24: 207, 1
SUMMARY
247
_
r 930.
14. ‘5.
16. 17. 18.
‘9. 20. 21. 22. 23.
POPIN,F. Gas. bebd. d. SC. med. Bordeaux, 52: 41, 1931. ROTTER, J. Im. Hanbuch der prakt. chir. Bergmann & Bruns. 3: 580, 1903. Polyposis rectiadenoma malignurn. Spontanheilung. Arch. f. klin. Cbir., 58: 357, 1899. COLE, P. P. IntramuraI spread o recta1 cancer. Brit. M. J., I: 431, 1913. KIRSHBAUM, J. D. and SHIVELY, F. S. MuItipIe primary malignant tumors. J. Lab. FY C/in. Med., 24: 283, 1938. SCHWEIGER, L. R. and BARGEN, J. R. MuItipIe primary malignant Iesions of the large bowe1. Arch. Int. Med., 66: 133r, 1940. SILNERS,H. I. MuItipIe intestinal carcinomata appearing simuItaneousIy. Am. J. Digest. Dia., 6: 25, 1939. LANE, W. A. Cancer of the colon, its causation and treatment. Lancet, 2: I 184, 1920. DOWDEN. J. W. Carcinoma of peIvic colon. Edinburgh M. J., 19: 181, 1917. MAINGOT, R. Multiple carcinomata of the rectum. Tr. Med. Sot. London, 50: 121, 1927. SCHMIDT. Bon veirfschem Darmkrebs. Inaug. Diss., KieI, 1901.
248
Americnn
Journal
uf Surgery
Bacon,
Gass-Sigmoid
24. ANGEVIUE, D. )vl. Three primary malignant epithehal tumors of anorectal region occurring in one person. Canad. M. A. J., 23: 38, 1930. 25. ZIMMERMAN,R. Canad. J. Med. SC., 7: 390, 1882. 26. DOERING, H. Die Polyposis intestini und ihre Beziehung zur carcinomatosen Degeneration. Arcb.J. klin. Cl&., 83: 194, 1907. 27. WULF, L. Inaug. Diss. KieI, 1892. 28. BUNTNG, C. H. Multiple primary carcinomata of the ileum. Bull. Johns Hopkins Hosp., 15: 389, 1904. 29. GOTTING, G. Zur MuItiplicitat primarer Carcinome. Zischr. f. Krebsforscb., 7: 675, 1909. 30. MIELECKI, W. Anatomisches una Kritisches zu 560 Obduktionen, bei denen sick bosartige GessbiwuIste fandrn. Ztsch~. j. KrebsJororscb,13: 505. ‘9’3. 31. JENTZER,A. Multiple tumors; 4 cases. Rea. med. de la Suisse Rom., 40: 236, 1920. 32. LAUDA, E. Wien. med. Wcbnscbr., 75: 1890, 1925. 33. GOETZE, 0. Beruerkungen uber Multiplezitat primarer Carcinome in AnIehung an einen Fall van dreifachen carcinoma. Zfscbr. J. KrebsJorsch., 13: 281, 1913. 34. KLENGENSTEIN, P. MuItipIe carcinomata of the coIon. PartiaI coIectomy for carcinoma of the transverse coIon; of the sigmoid and of the ascending colon. Ann. Surg., 102: 1079, 1935. 35. LrrcHhrAN, A. L. and MCDONALD, J. R. Fecal IistuIa. Surg., Cynec. ey Obst., 78: 449, 1944. 36. WHI~HAM, J. R. M. Persona1 communication, April, 1943. 37. BARGEN, J. A. Causes of colonic cancer. South. M. J., 32: 627, 1939. 38. MAYO, C. W. Multiple primary maIignant lesions of the colon with resection. Proc. .!?a$ Meet., Mayo Clinic., 15 : 465, 1940. 39. JUNGSHANNS, H. Eine Krebsstatistik uber 35 Jahre (4192 Carcinome bei 36408 Leichenoffnungen). Ztscbr. f. Krebsforscb., 29: 623, 1929. 40. KUSTER. Ein chirurgisch Triennium, p. 161, 1882. Ueber Neubildungen der Niere und ihre Behandlung. Centralbl. J. Krankb. d. Hum. ser. Org., 8: 583, 1897. 41; WARREN, S. and GATES, 0. MuItipIe primary malignant tumors. Am. J. Cancer, 16: 1358, 1932. 42. HANDFORD, H. Disseminated polypi of the Iargc intestine becoming malignant strictures (maIignant adenoma) of the rectum and of splenic flcxure. Tr. Parb. Sot. London, 4’: 133, 1890. 43. ELIOT, E. Recurrence versus metastatis in carcinoma. Tr. Am. Surg. Ass., 40: 115, 1922. 44. KARSR.EK, H. T. and CLARK, B. AnaIysis of 104 cases of carcinoma of the large intestine. Am. J. Cancer, 16: 958, 1932. 45. BEHREND, M. Carcinoma of coIon. Treatment depending on location of lesions. Surg., Gynec. &+Obst., 65: 505, 1937. 46. LITTLEWOOD.Cited by Yeomans. 47. COKKINS, A. J. MuItipIe carcinoma of the colon with four original cases. Brtt. J. Surg., 21: 570, 1934. 48. GO~ILLIOUD, C. Krebs des Eierstocks in Verlaufe van Krebsen des Magens, dcs Darmes und der Gallenivegc. Zentralbl. f. Gyniik., 31: 1426, ,907.
49
50.
5’. 52. 53.
54. 55. 56.
57, 58. 59. 60.
6r.
62.
63.
64.
65-
66. 67. 68. 69. 70. 71. 72. 73.
Colon
MAY. 194~
I IAWSER, G. Das Cylinderepithelcarcinom des Magens und Dickdarms, Jena, 189o. Geibt es primare zur Geschwulslbildung fubrende Epithelerkrankung? Beitr. R. path. Anat. u. z. allg. Patb., 33: I, 1903. PEMBERTON,J. DEJ. and WAUGH, J. hl. Primary carcinomas of the stomach and sigmoid Ilexure occurring simuItaneousIy in the same individua1. Surgery, 2: 21 I, 1937. ORR, J. W. MuItipIe malignant neoplasms. J. Path. u Bact., 33: 283, 1930. RAU, W. Ztscbr. J. Krebsforscb., 18: 141, 1922. JUDD, E. S. and PHILLIPS, J. R. Independent carcinoma of the coIon occurring six years after carcinoma of the stomach. Surg. Cl&. North America, 14: 525, 1934. FEILCHENFELD.Inaug. Diss., Berl., 1904. HANLON, F. R. Multiple primary carcinoma. Am. J. Cancer, 15: 2001, ‘93’. HANSEMANN, V. Das gIeichzeitige Voskommen verschiedenarliger GeschwaIste bei derseIben Person. Ztscbr. ,J. Krebsforscb., I : 183, 1904. KROGER, C. Cited by Rieder (Arch. J. klin. Cbir., ‘35: 179, 1925). DEVIC, E. and GALLOVARDIN. Bull. Sot. med. d. bBp. de L_von., 2: 242, 1903. DEVRIES. Zentralbl. J. ges. inn Med. u. Grenzgeb., vol. I, 1912. DEETZ, E. Vier weitere FaIIe von PIattenepitheIKrebs der GaIlenbIase. Arch. J. palb. anat., 64: 381, Igor. BRAN~T, M. and JEKARSON, K. Eine Krebsstatistik uber, 30 Janre fur das I. Rigasche Stadtkrankenhaus. Ztscbr. ,f. Krebsforscb., 32: 280, 1930. NICHOLLS, A. G. Multiple primary tumors in the stomach and mamma. Montreal M. J., 32: 326, ‘903. MULLER, R. F. Ueber multipIe Nichtsystematisierte Primare Carcinome und ihre Haufigkeit. Zrscbr. f. Krebsforscb., 3 I : 339, ‘930. STALKER, L. K. PHILLIPS, R. B. and PEMBERTON, J. DE J. MuItipIe primary maIignant lesions: Surg., Gynec. &+Obst., 68: 595. 1939. SALTZSTEIN,H. C. and KELLY, J. Some complications in the surgical handhng of carcinoma of the left colon and rectum. Surg., Gynec.
NEWSER~ESVOL.LXVIII, No. 2
Bacon,
Gass-Sigmoid
74. BILELLO, A. and MONTANINI, N. PIuricita di tumori maligni nello stesso soggetto. Tumori, 5: 369, 1931. 71;. CARNEVALE-RICCI. F. Evoluzione clinica ed anatomo pathologica dei fibomi rinofaringei trattati con la diathermocoaguIazione. Arch. ital. di otol., I: 221, 1931. 76. OPHCLS, W. A statistical survey of 3ooo autopsies. Stanford Unniu.Press, p. 316, 1926. 77. KLEBS, E. T. Handbucb der parb. anat., 2: 190, I 869. 78. BESCHE, A. Multiple kancere. Norsk. Mag. ,f. Laegeitidensk, 5: 533, 1908. 79. GOTTSTEIN, A. Quoted by Warren and Gates. 80. KESTEVEN, W. B. Case of cancer of the breast. Tr. Clin. Sot. London, 9: 77, 1876. 8 I. WILLIAMS, C.: Multiple primary carcinoma. Virginia Med. Montbly, 58: 24, 1931. 82. SEECOF, D. P. MuItipIe primary malignant neoplasms; report of case of carcinoma of lung each producing and carcinoma of rectum, metastases. Cancer Research, 8: 2I3, 1924. 83. VOLKMANN, R. Beitr. z. klin. cl&., 1875. 84. HIBSHMAN, H. Z. Personal communication. 85. WERNER, J. L. Rectal carcinoma associated with uterine sarcoma. Tr. Am. Proc. Sot., p. 64, 1937. 86. DIJKSTRA, 0. H. Nederl. Tydscbr. u. genneesk., 70: 270, 1926. 87. BILLROTH, T. Die AIIegemeina Chirurgie Pathologie u. Therapie. P. 908. Berlin, 1889. Reimer. 88. MERCANTON, F. Des carcinomes primaires muItiples. These de Lausanne, 1893. Rep. med. de la Suisse, Rom., 13: 173, 1893. 89. THOMPSON, J. W. Secondary resections in recurring carcinoma of the colon. J. A. M. A., 107: 1688, 1936. 90. ERHLICH, P. and APOLANT. Zur Kenntnis der SarkomentwickeIung bei Carcinomtransplantationen. Centralb1.f. ally. Patb. u. path. Anut., I7: 513, 1906. 01. RUSSEL. B. R. Sarcoma deveIooment occurrinz during the propagation of a hemorrhagic adenocarcinoma of the mamma of the mouse. J. Parb. Ed Bact., 14: 34, 1809. 92. FOULDS, L. Tenth Scientific Rep. Imp. Cancer Res. Fund., p. 21, 1932. 93. I~AALAND, M. Third Scientific Report, Imp. Cancer Res., p. 175, 1908. I,
3
Colon
American
Journal
of Surgery
249
94. MAJOR, R. H. Multiple primary malignant tumors. Bull. Jobn Hopkins Hosp., 29: 332, 1918. 95. KIDNER, F. C. Sarcoma and carcinoma in the same patient. Boston M. @ S. J., 158: 836, 1908. 96. DUKES, C. The heredity factor in polyposis intestini or multipIe adenomata. Cancer Rev., 5: 241, 1930. 97. SLYE, M. Relation of inbreeding to tumor production; studies in incidence and inheritabiIity of spontaneous tumors in mice. J. Cancer Res., 5: 53. 192o. Relation of heredity to cancer occurrence as shown in strain 73. Am. J. Cancer Res., 18: 535. ‘933. of origin of 98. SLAUGHTER, D. P. The multiplicity malignant tumors. Surg., GJrnec. P’* Obsr., 79: 89, 1944. 99. LANDAC, H. Krebs und Sarkom am gleichen Menschen. Miincben. med. Wcbnscbr., 650, 1905, R. Primarv carcinomas of the stomach IO”. MAINGOT, and sigmoid coIon occurring simuItaneousIy. Bril. M. J., I: I 18, 1938. MILLER, R. T. Cancer of the colon. Tr. Am. Surg. Ass., 49: 54, ‘923. SCHABAD, L. M. and GORIAINOWA, R. W. Zur Frage der Todesursachen bei Krebskranken. Zrscbr. J. h’rebsforscb., 33: 594, 1931. 103. DAVIS. Quoted by Krakiewicz. des primaren 104. KAC.I;MAKN, C. Ueber Multiplicitat Carcinoms. Vircbow’s Arch. f. pub. anat., 75: 317. 1879. reaction to 105. BASHFORD, E. F. The immunity cancer. Proc. Roy. Sot. Med., p. 165, 1909. I 06. FENCER, C. DoubIe carcinoma of the colon. J. A. M. A., 2. 606, 1888. of tumors. J. Med. 107. LOEB, L. On transpIantation Research, 6: 28, 1901. I 08. BORRMAP\;,R. Deutscbe Ztscbr. f. Cbir., 76: 404, ‘905. 109. HOCHE, L. Du cancer gastrique secondaire. Presse mLd., I: 67, 1901. I IO. BULL, M. P. Bull. et mkm. Sot. Natl. d. cbir., 58: 1338, 1932. primary cancers. III. KRETSCHMER, H. L. Multiple J. Ural., 40: 421, 1938. of three primary 112. SMITH, C. FI. Surgical remova carcinomas of the colon. Proc. Sta$ Meet., Ma_vo Clin., 13: 122, 1938. 1’3. JENSEN, C. 0. Centralb1.f. Bakt., 34: 122, 1903,