TUMORS OF THE 1)IGESTIVE TRACT

CHARLES F. GERCHICKTER, M.D.

(lhai the Burgiccil Pathologiccil Lciborcitory, Uepnrtrrirnt of S?rryer?j Johns Ilopk~nsLlo c1711l zl7liVersif?J)

The digestive tract is continuous with the mucous membranes of ectodermal origin in the mouth and at the anus. The pharynx, although of entodermal origin is lined by epidermal tissue, and tumors of this portion of the tract are more conveniently considered with other epi- dermal tumors of the oral and intra-oral membranes. of the remainder of the digestive tract will be considered together. The most frequent tumors in this region, except for those in the esophagus, which loses its digestive during embryonic life, are mid . These growths arise from the glandular portion of the mucosa throughout the digestive tract.. The incidence of benign is approximately one-sixteenth that of . Adenocarcinoma and its mucoid, fibrous, and anaplastic vari- ants are more common in the , large bowel, and rectum, and relatively rare in the esophagus and small intestine. Primary mucoid mrcinoma is uncommon, but is similar in distribution to adenocar- cainoma. Squamous-cell caiicer is the predominating form in the esopha- gus and may invade the cardiac end of the stomach. It is also found in the rectum and anal margin, but is exceedingly unusual elsewhere in the gastro-intestinal tract. Sarcoma is not common in the alimentary canal. Lympliosarcoma, myosarcoma, and sarcoma of the nerve sheath are the leading forms. These growths comprise approximately 4 per cerit of the malignimt tumors in the present series.

BENIGNTUMORS With the exception of polypoid adenomas and so-called carciiioids, 1)criign tumors are relatively rare in the gastro-intestinal tract. My- omas, angiomas, and other new growths of the supporting wall of the digestive tube occur. They are not peculiar to this region, however, aiitl are omitt ed from the present discussion. The distribution and calassification of benign tumors in this series are as shown in Table I.

Adcizomatous Polyps Adc.nomiltons polyps arc single or multiple. The multiple type may rarely give a familial history, several mcmbers of a single family being aflcctcd. Tho distribution of these growths in the digestive tmct in the present study was as shown in Table I and Fig. 1. 130 TUMORS OF THE DIGESTIVE TRACT 131

While reduplication of the epithelial layers of the mucosa at the margin of traction diverticula may occur, benign are rarely observed in the esophagus. Ginsburg has reported a case of multiple ptipillomas of the esophagus which the patient related to swallowing of ammonia twenty years previously. Patterson, in a review of 61 cases of benign tnmors of the esophagus iii the literature between the years I71 7 and 1932, found only 3 adenomas. Recently Moersch and Broders have reported the fourth case. In geiieral, the incidence of these be- itign growths in the digestive tract increases from above downwvud, approximately 60 per cent occurriiig in the rectum. The tumors are often multiple. Stewart reports 56 cases of gastric polyps ancl 127 oc- curring in the large bowel; 23 of the gastric cases were multiple, arid 57

T4nm I: Rrnigrb Titmors of tliP Di,yr,\tave Tract (178 Cases)

...... NOlW

...... 10

...... 36 cases

...... 10

...... 5

...... 1

Small iritc+t int1 ...... Itectiun ...... s tomac~ll ...... of the coloiiic cases. He estimated that 5 per cent of of the stomach are related to pre-existing benign polyps, whereas 36 per cent of eancei's in tlir large bowel have such an origin. Some observers, in- c*lutiing Fitzgihhon ancl Rankiii, believe that practically all cai.cinomas of the large bowel originate iii polypoid adenomas. These tumors project into the lumcii of the digestive tube causing o1,structioii or 1)lcccling. Young adults are usnally affected. With qowths iii the iwtnm or stomach fraiik hemorrhage may occur, whereas those ill thci lwrgc bowel tiiitl intestiiie are manifested by tarry stools or anemia. (Figs. '3, 1ant1 6.) tut.y 111 dfiplr polyposis occurred twice in the preseiit series. ln one of these cases malignant change occurred. This patient, a male 132 CHAHLES F. GESCHICKTEB aged fifty-two, was admitted for acute diarrhea, distention, aiid a,- dominal tenderness. Examination showed multiple polyps in the rec- tum and failure of the rectum aiid sigmoid region to fill by barium enema. A firm abdominal mass was palpated in the region of the left colori which at operation proved to be an inoperable . The patient stated that a fatal form of intestinal trouble had affected his family. A brother had died, supposedly from intestinal tuberculosis. Rchilliiig has reviewed the literature on this phase of the disease. Males are usually affected. The entire tract from the stomach to the

FIG.1. CIIAET SHOWINGTHE DISTR~BUTIONOF BENIGN ADENOMAS IN THE DIGESTIVETRACT rectum is involved, and in 50 per cent of the cases malignaricy super- venes in one or more of the polyps. As many as six members in one family have been affected. Although the disease is hereditary, it is usually not seen until after the twentieth year. lIistologically polypoid adenomas, whether solitary, multiple, or hereditary, are composed of single or reduplicated layers of columnar epithelium, lying on delicate stalks of connective tissue (Figs. 3 and 5). The presence of secretory epithelium varies with the portion of the howti1 tiffectetl. The smaller growths show an orderly arrangement of epithelium, while the larger growths exhihit marlied , vari- ation in the nuclei, and a tendency to invade the surrounding mucosa FIG.2. POLYPOID ADENONAOF THE STODZACH This tunior showed early malignant change. Path. No. 19901.

FIG. 3. LOW-POWERPIIOTOMICROGRAPH OF ONE OF SEVERAL BENIGN POLYPOID ADENOMASOF TIIE STOMACH. PATH. NO. 45290

FIQ.4. POLYPOID ADENOMAOF THE DUODENUM Microscopically this tumor showed evidences of early malignant change. Path. No. 46597. From Raiford, T. S.: Arch. Surg. 25: 140, 1933. 133 134 CHARLES I?. GESCHICKTEE and sti-oma. With such invasion it is difficult to distinguish benign adenomns from early adciiocnrcinoma. Solitary polyps in the rectum may hc treated hy excision 01’ fulg~ux- tioii. Elsewhere in the tract resection is the treatmeiit of choice. The possi1)ility of multiplicity cziid of malignant change must bc borne in mind wlieii treatmeiit is undertaken.

FIG.5. PHOTOMICROGRAPHOF TYPICAL BENION POLYPOID ADENOMA OF THE ILEUM Thc tumor ocrurrcd in a child of seven months and produced intussusccption. Path. No. 38963. Prom Haiford, T. 8.: Arch. Surg. 25: 157, 1932.

8ince the studies of Huebscliamm and Masson, which related the car- cinoids of the appendix to the chromaffin system, over 400 such tumors have been described in the literature. Thc older term carciiioid ~vas used because of the histologic resemblaiice of these relatively benign growths to cancer. Approximately 300 of these nrgeiitaffiiie tumors have occurred in the appendix and 100 in the small intestine, with scatteretl instaiices in the stomach, largc bowel, and rectum. In the present TUMORS OF THE DIGESTIVE TRACT 135 series 2% of these tumors occurred in the appendix, 10 in the small in- testine, 2 in the large bowel, aid one iii the stomach. Adults are iisiially affeded, the age limits hing twelve and sixty-six years in this series. Symptoms appear early in the appendix hecause of the small size of the lumen, aiid suggest appendicitis. At operation a bulbous en- largement is found near the tip of the organ. When the tumor occurs

FIG.6. POLYPOIDADENONA OF THE RYWTVX. PATH.No. 29916 in the intestine, diarrhea. without melena (produced by incomplete ob- strnction) is the major symptom. Although the majority of these growths are henigii and run a chronic course, some 20 per cent undergo malignant change. Eight of the cases studied showed secondary de- posits in the lymph nodes. Even where such secondary deposits occur a cure may he affected. On microscopic study the tumor cells are found growing in islands or strands surrountled by dense bands of connective tissue. The cells are epithelial in nature, of moderate size, and tend to form a syncytium. The small, more deeply staining cells may show rosette formation. These epithelial cells may be impregnated by silver, hence the term argentaffiiie tumor (Fig. 7). Aberrant Pancreatic Rests These tumors are glandular misplacements which form small sub- mucous grayish white nodules in the wall of the bowel, rarely exceed- ing a centimeter in diameter. They are usually asymptomatic and are discovered only at autopsy. One of the 6 cases in the present series produced an intussusception of the ileum. Microscopically, character- istic paiicreatic tissue is present. The cells are arranged in acini and have a granular basophilic cytoplasm (Fig. 8). In addition, there are islaiids of Langerhaiis and small numbers of pancreatic ducts. ac- cording to Warthin these growths arise from the lateral buds of the pancreatic ducts as they pass through the intestinal wall of the embryo. They are thus segregated and carried up or clown the digestive tract tlnring the process of fetal growth. 136 CHARLES F. GESCHICKTER

niucrtirula mid Ederic I>ivei*ticulilill the gasti.o-iiitcstiiia1 tritcat of the embryo are observed most commonly between the tluodenum aiid the terminal ileum but may occur also in other portions of the tract (Lewis and Thyrig). These knob-like protrusions may disappear or they may persist and give rise to diverticulosis (multiple outpouchings of the intestine), single diver- ticnla, or enteric cysts. The enteric cysts are formed from diverticnla

FIG. 7. PHOTOMICROGRAPH OF A OR ARGENTAFFINETuiaon OF THE ILEUM Path. No. 6739. From Raiford, T. S.: Arch. Surg. 25: 166, 1938. which have lost their communication with the intestinal lumen. Ves- tiges of the so-called post-anal gut, which in the embryo connects tlie central canal of the spinal cord with the invaginating portion of the primitive anus, may also form cysts of this character. (The pulsion and traction diverticula of the esophagus are attributed to weakness in the muscular wall rather than to congenital outpouchings such as are found in the intestinal tract.) Diverticulitis complicatirig corigenital diverticula of the gastro-in- TTJMORS OF THE DIGESTIVE TRACT 137 testinal tract is most common in the region of the sigmoid, in elderly patients. The symptoms include intermittent attacks of pain, fever, t enderness, rigidity, and a recurrently disappearing mass in the region of the sigmoid. This condition is distinguished from carcinoma of the large bowel by the absence of blood in the stool and by the character- istic appearance of the outpoachings in the roentgenogram. Meckel’s diverticulum is usnally connected with the ileum. It rep- resents the remains of the omphalomesclnteric or vitelline duct found

FIQ.8. LOW-POWERPHOTOMICROGRAPH OF AN ABERRANT PANCREATIC REST OF THE DUODENUM The tissue resembles normal . Path. No. 10579. From Raiford, T. 5.: Arch. Surg. 25: 170, 1932. in the emhryo. Twisting of a loop of 1)owel at this site may produce acute obstruction. Myomas, cysts and carcinomas have been reported in this vestige (Fig. 9). McGlannan has reported a large cystic tumor of Meckel’s diverticulum with myosarcoma in the wall and has cited similar cases. 1i:nteric cysts may he found within the mesentery, arising from diverticula which have lost their cwnmunication with the iiitcstine. Such cysts have been reported arising from the duodenum (Crardner and Hart). The majority have been ileocecal in location and FIG. 9. PHOTOMICROGKAPH OF AN ANAPLASTIUCARCINONA ARISINGIN MECKEL'S DIVERTIC- ULUM. PATII.No. 43336

FIG. 10. Pl~OTOiHICROGKAPI~OF THE WALL OF AN ENTERIC CYS'T OCCURRING IN A BOY 08' TWO AND ONE-RALF YEARS. PATH. NO. 52506

138 TUMORS OF THE DIGESTIVE TRACT 139 are attributed to remnants of Meckel’s diverticulum. They have been reported at all ages. Histologically they are composed of all the nor- mal layers of the digestive tract, the epithelial lining varying with the location of the cyst (Fig. 10). The retroperitoneal enteric cysts aris- ing from remnants of the post-anal gut show a mucous membrane char- acteristic of the large bowel. They are more common in infants and are found anterior to the sacrum or coccyx. Typical columnar arid goblet cells are fourid in the lining. Serous or muscular coats may be seen in the cyst wall. The cysts are benign and may be shelled out. Hallantyrie, however, has reported a carciiioma arising from a remnant of the post-anal gut in a female of thirty-eight years. Muworele of the Appeiadiz Gelatinous material is occasionally encountered in the region of the cecum in patients operated upon for appendicitis. There were 5 such cases of mucocele in the present series arid in 2 of these mucoid ear- cirioma of the bowel was suspected even after frozen sections had been made. In one of these cases the condition was secondary to a rieuri- iioma of the appericliceal wall (B’ig. 11 ). Loveri has reported a case of mucocele of the appendix complicating ail argentaffine tumor. He was able to collect 150 cases of mucocele of the appendix from the literature. IIe believed that these cysts arise from iriflammatory strictures. The appeiidix is distended with gelati- 11ous material, or appendiceal fistula lined hy mucosa identical with that of the appendix may communicate with the peritoneal cavity. Numer- ous omeiital deposits consisting of small sacs distended with mucus and lined by uoblet cells and cyliiidrical epithelium may be found where rupture of”, the primary appendiceal, sac has occurred. Indefinite dis- tress and abtlomiiial distention accompany peritoneal involvement. The tumors are definitely benign, but the outlook is grave in the eases with peritoneal transplants.

MALIGNANT TUMORS OF THE IhGESTIVE TRACT Carcinoma of the digestive tract is responsible for the greatest iium- her of cancer deaths. The majority of these growths are not diagnosed in time for effective treatment, approximately 50 per cent being beyond operative measures at the time of their clinical recognition. In fre- quency, carcinoma of the stomach equals or exceeds the total number of caricers in the remainder of the tract (esophagns, small intestine, appendix, coloii arid rectum). The distribution in the present series (Pig. 12) was as follows : Esophagus ...... 80 Stomach ......

Rectum ...... FIG.11. MCCOCELEOF TIIE AXTENDIS (ABOVE) AND A POHTION OF THE MASS XEMOVRD 17 THE MCJCOCELE(BELOW) Gelatiiioucl niaterial was found along ttic mesentcric border of the cecum. B’ibroiicwrc tous tissue was found in tho appendiccal wall and occluding the lumen. Path. No. 36267.

140 TUMORS OF THE DIGESTIVE TRACT 141

TABLE : Microsczopic. C/ussijicution of Mulignunt Cr~stro-intratisicxlTumors

Adenocarcirzonju ...... 538 cases Esophagus ...... 4 Stomach ...... 212 Small intestiiic ...... 11 Appendix ...... 1 Colon ...... 100 Rectum ...... 210

Muco-arlenoc.arciizoi~lcl...... 123 cases Esophagus ...... 2 Stomach ...... Small intestine ...... 2 Colon ...... Rectum ...... Appendix ...... 1

Fibrocarcinomn (Srirrkoris) ...... 58 cases Esophagus ...... Stomach ...... Small intestine ...... Colon ...... 16 Rectum ...... 25

Anaplustic Cawinomti (Medidlary) ...... ,. . 71 cases Stomach ...... 65 Colon ...... 5 Rectum ...... 0 Small intestine ......

Primary M'ucoid Ctrwiiioma ( Kiynet-Ring-Cell Cuiacw) ...... 32 cases Stomach ...... 18 Colon ...... 7 Rectum ...... 7

Squamous-Cell Curcinowu ...... 88 cases Esophagus ...... 74 Colon ...... 1 Rectum ...... 12 Stomach ...... 1

Lymphosnrcowui ...... 38 cases Stomach ...... 4 Small intestine ...... 20 COlOll ...... 12 Rectum ...... 2

Other Forms of Surr.omtr, Myosnrcoma urkd Nprve SIirutlr Strrcom!n ...... 14 cases Total ...... 962 cases

The percwitage of surgical cures increases f rorn above downward, being approximately zero in the esophagus, 2 per cent in the stomach, 5 per cent in the small intestine, 15 per cent in the colon, and 30 per cent in the i.ectum. In general, these growths arc not radiosensitive. 142 CHARLES F. GESCIIICKTEIL

Curr iw 111 a of t h P l$s011 hug us Cancer occurs usually in the lower third of the esophagus in males between the ages of fifty and sixty years. The disease usually termi- nates fatally within a year of its clinical recognition. Forty per cent

FIG. 12. CHAKT SHOWING THE ~~ISTIlIllIJTION03’ CARC’INOMA IN THE DIGESTIVETRACT Oper. =- operable c:~s~B.Cures :-fire gear survivalcr. of the 80 cases studied were in the lower portion of the esophagus, 4 involving the cardiac end of the stomach as well. The average dura- tion of symptoms was five months (excluding 6 cases in wliicli the trouble extended beyond a year). Difficulty in swallowing, increasing rapidly to the point where liquids oiily can be retained, is tlic out- standing clinical feature. This was present in all but 4 cases. Pain substernally or in the region of the dorsal spine is the symptom next in frequency. In 6 cases in this series the initial symptom was dyspnea caused hy compression or invasion of the trachea or main bronchi. Loss of weight and weakness occur early. A gradual onset, with symptoms beginning three to eighteen years previously, was recorded in 4 cases in the present series. Two of the patients complained of unusual sensations in swallowing, which they attributed to chronic indigestion. Such chronic symptoms suggest that TTJMORS OF THE DIGESTIVE TRACT 143 benign leukoplakia or small diverticula of the esophagus have prececled the development of cancer. The visualization of a zone of coilstriction iii the roentgenogram is an important aid to diagnosis (Fig. 13). Biopsy with the esophagoscope furnishes confirmatory evidence. Palliative treatment in esophageal caiicer consists in gradual dila-

I!’IG. 13. ROENTGENOGRAMSHOWING A STRICTURE OF THE ESOPHAGUSPRODUCED BY CARCINOMA AT THE .JUNCTIONOF’ THE MIDDLEAND LOWERTIIIRDS. PATII. NO. 52268

k’lG. 14. LOW-POWERAND IIIGH-POWER PIIOTOMICROGKAPHS OF THE SQIJAMOUS-CELL CARCI- NONA OF TIIE ESOPHAGUS DEI’I(’TED IN FIG. 13 tatioii with bougies or irradiation. Where the obstruction cannot be thus relieved, gast rostomy may be performed. Relief of obstruction by repeated electrocoagulation of the tumor has been reported by Hesse. Resection of the esophagus has been attempted, but cures are seldom effected. All of the cases in the present series proved fatal. 144 C€IhlII~ESP. GESCHICKTEK

Clarciiioma of the esophagus is usually of the squamous-cell type with or without ltert~tiiiiztitioii (Fig. 14). This form of lesion cst ends longitudinally or around the esophageal wall, giving rise to constriction or comprcssioii before ulceration occurs. Adeiiocarciiioma arid hasnl- cell cwiicer are rarely found in this location (Fig. 15).

FIG.13. PHOTOMICI~OGKAPHOF A CYSTIC BASAL-CELLCANCER OF THE ESOPIIAQUS This form is cxtrciricly rarc in the euophagus. Path. No. 14092.

Carcinoma of the Stowach Carcinoma of the stomach leads in caiicer mortality, and surpasses in frequency the combined total of for the remainder of the gastro-intestinal tract. In a small proportion of cases (5 to 10 per cent), the disease may have its origin in a preceding gastric ulcer or benign , but more often it arises without any demonstrable preceding pathology. Males are affected more often than females, three to one in our series. The highest iiiciderice is in the age period forty-five to sixty years, but some 4 per cent of the cases occur between twenty-eight arid thirty-nine years. The disease has been recorded in infancy. In approximately 400 cases in which the site of the tumor was charted, 200 were in the pyloric region, 100 along the lesser curva- ture, 50 in the distal half of the body, aiiti the remainder elsewhere in the stomach. In two-thirds of the cases the disease begins abruptly with hemorrhage, pain, distention, or vomiting. This group of pa- tients is usually symptom-free from three to ten months prior to con- sulting a physician. Those with the shortest duration of symptoms have the poorest prognosis. Loss of weight arid anemia may be promi- iieiit if tlie lesion is advanced. In rare instances a blood picture rc- TUMORS OF THE DIGESTIVE TRACT 145 sembliiig leukemia has been recorded. In approximately one-third of the cases the disease is insidious in onset, with dyspepsia that suggests gastric or duodenal ulcer. Pain in relation to meals, relieved by alkali or foods, and eructations are prominent symptoms in this group. These cases are emphasizecl hy advocates of the theory that carcinoma. of the stomach begins in ulcer.

FIGS.16 AND 17. ROENTQENOGRAMSOF CARCINOMA OF STOIIACII Fig. 16 (Path, No. 37894) shows a filling defect at the pyloric end of the stoiriacli caused by carcinoma occupying the pylorus and greater eurvaturc. Fig. 17 (Path. No. 37396) shows constriction of thc pylorus and dilatation of the stoniach productd by adenocarcinoma.

B'IG. 18. ('ONTRA(T1ON OF THE ENTIRESECOND HALFOF THE STOMACH PRODUCED BY INFIL- TRATING SCIRRHOUSCARCINOMA. PATH. No. 28109

On clinical cxamiiiat ioii the principal findings are a palpable mass in the region of the epigastrium (present in ahout 50 per cent of the cases), signs of retention of gastric coiiteiits, and anacidity upon gastric analysis. High values for combined acids in the absence of free hydro- cliloric acid arc evidciice in favor of pyloric obstruction or decreased 146 CHARLES F. GESCHICKTER gastric motility, wliicli is most often due to gastric carcinoma. Lactic acid or the Boas-Oppler bacillus may be found on gastric analysis. Iiitragastric photography, estimation of soluble albumin in the gastric coiiteiits, arid the clemoiistration of pi~~teolyticciizymes are among the aids to diagnosis. The most important mcaiis of diagnosis is tlic roentgeiiogrum. Dc-

E'IG. 19. ADENOCARCINOMB OF THE STOMACH SHOWING CONSTRICTION OF THE PYLOKUS. PATH. KO. 40,568 formitp in the gastric lumen aiid changes in gastric motility following barium intake arc outstanding features (Fip 16, 17, and IS). Large growths protr*ucleinto tlie lumeii aid ulccratioris arc preseiit as ;I mar- ginal or ceiitral defect. Normal gastric rugae arc smootlied or ef'faeccl. ("aiicer in tlie mid-portion of the stomach may produce an hour-glass defect. Abseiice of gastric peristalsis is the most commoii chaiigc in motility. Obstruction is present in 60 per cent of cases aiid is denoted by a residue after six hours or by delayed emptying under tlic fluoro- scope. If obstruction is iiot preseiit, the pylorus is gaping. Lesioiis of the cardiac end are difficult to demoiistrate arid are best seen hy exerting pressure from below on tlie barium-filled stomach dnriug fluoroseopic examination. Defects caused by cancer arc persistent mid remaiii coiistaiit in location in successive roentgenograms, and in spite of the admiriistratioii of antispasmodic drugs. Alultiple small defects in the film usually signify beiiigii lesions. Gastric syphilis may rc- semble carcinoma but produees no palpable tumor. In distinguishing cancer from gastric ulcer iii the rociitgciiogram the following points are helpful: Cancer has a raised edge aiid usually exceeds 2.5 em. in diameter. Absence of gastric spasm aid obliteratioii of surrounding rugac favor . TUMORS OF THE DIGESTIVE TRACT 147

130th cliiiical adroeiitgenologic factors must he weighed iii distiii- gnishing operable from inoperable cases. Cardiac cancer is not resect- able in most instances. ("aiicfer in the second half of the stomach, oc- cupying most of this region and extending beyond the iiicisura is seldom operable. Fixatioii of tlie stomach is also unfavorable for resection. Metastases to the lungs or bones, which may be visualized

RTORIAC'H.

]+'I<;. 20s. TAOW-POWER AND HIGH-POWEEPHOTOMICROOKAPHS OF I'RIMAKY MUCOIDCAR('IN0hlA OF THE STOMACHSHOWN IN FIG.20h in the x-ray film, to the rectal shelf, to the supraclavicular nodes, and to the ahdominal wall are all signs of inoperability. Free fluid in the :ibdominal cavity is also an uiifavorable sign. On exploration, exten- sion of the disease to the iieighboriiig lymph nodes, involvement of the omeiitum aid liver, aiid fisatioii of tlie mass to adjoining strnctures preclude further surgery. FIG.21. MARKEDLYTHICKENED WALL OF THE STOMACH IN A CASE OF LINITISPLASTICA. PATH.No. 46080

FIG.23. PHOTOMICROGRAPHSHOWING INFILTRATING CAKCINONA CELLS IN A CASE OF LINITIS PLASTICA. PATH. NO. 43336

FIG. 23. GROSS SPECIMEN AND PHOTOMICROGRAPH OF ANAPLASTICCARCINOMA OF THE f$PO&fACIi. PATH.NO. 39822

148 TUMORS OF THE DIGESTIVE TRACT 149 Bulky, polypoid growths, protruding into the gastric cavity (Fig. lY), are usually found on microscopic examination to be adenocarci- iioma, occasioiially with mucoid or gelatinous changes (Table 11). Primary mucoid carcinoma also produces a bulky tumor (Figs. 20A and B). Sessile, ulcerating carcinoma infiltrates the gastric wall to a variable degree. It may prove microscopically to be Grade 4 adeno- carciiioma (aiiaplastic or so-called medullary cancer) or scirrlious car- cinoma (Figs. 23 aiid 24). Diffuse iiifiltration of the entire stomach wall with scattered nests of malignant cells and thickening oi the mus- cular walls is known as linitis plastica (Figs. 21 aiid 22).

PIG.24. PHOTOMICROGRAPHOF SCIRRHOIJS CAR(’INOMA OF THE STOMACH.PATH. No. 16270 Of 650 carcinomas of the stomach seen in the surgical wards of the .Johns Hopkiiis Hospital during the last‘forty-five years, oiily 135, or 20 per cent, were resectable. Thirteen patients lived beyond the five- year period, 5 others beyond the three-year period, aiid 4 died of the disease four or more years after operation.

Iiatestinal Cancer Carcinoma of the small iiitestirie comprises from 3 to 10 per cent of all gastro-intestinal cancers according to the various reports in the literature (Raiford). In the present series there were 16 cases, 7 in the duodenum, 4 in the jejunum, arid 5 in the ileum (slightly over 1 per cent of the total). The age iiicideiice ranged between thirty-three and sixty-eight years. 150 C HAItlJCS P. GESCHIC ICTEI:

Carcinomas of this region are adcnocarciiiomas arid are usually of the constricting and infiltrating form. Occasiorially polypoitl ade- noma with malignant change occurs, or adenocarciiioma with mucoid

FIGS. 25h AND B. ROENTGENOGEAUAND PIIOTOMICKOQRAPII OF CABCINOMA OF THE JEJUNUM The tumor produced complete obstruction of tho lumen and jejunum with marked dilata- tion of the proxinial bawel. The roentgenogram shows dilatation of the lumen. The photo- niicrogrsph (Raiford, T. B. : Ann. Burg. 25: 134, 1932) shows adenocarcinorna infiltrating the submucosa and muscularis. Path. No. 26196. degeneration. The symptoms are due to obstruction of gradually in- creasiiig severity or to sudden and complete blockage following intus- susceptioii (Figs. 25 A-D). Pain, distention, and nausea are produced by carcinomas occurring in the duodenum. Obstruction produces con- stipation, sometimes alternating with diarrhea. Sudden obstruction is accompaiiied by pain, distention, vomiting, and shock. or occult blood in the stool is a common finding in cliroiiic cases. A dis- appearing palpable tumor is suggestive of of the small intes- tine. With the exception of duodenal growths arid those in the region of the terminal ileum, these masses are visualized with difficulty in the roentgenogram. The prognosis for malignant disease in this region is relatively poor. In the present series there was oiily one cure. Appeiadiceal Tumors Only two carcinomas of the appendix are recorded in this series, although 5 mucocelcs and 22 were fouiicl in this location. Failure to distinguish carciiioid or argcntaffine tumors from cancer, and the confusion of mucoceles or pseudo-mucinous cays ts with colloid car- ciiioma are responsible for the relative f requeiicy with which maligiiitiit tumors of the appendix were formerly reported. Adeiiocarciiioma of the appeiidix is extremeIy rare (Fig. 36) ; one case has been reported by Montgomery. In tlic two cases of adeno- TUMORS OF THE DIGESTIVE TRACT 151 carcinoma recorded in this laboratory the patients were operated upon for appendicitis. In one case the appendix was much enlarged, aiid in the other multiple peritoiieal nodules were present. Histologically

J?IG. 25c. GROSS SPEC’IIIFN OF TT‘MOR IN FIGS.83A AND B, SIIOWING OBSTRUCTION OF THE JEJ UPI‘TJX WI’PH PROXIhIAL 1)ILATATION

FIG.23D. CROSS-SECTION OF INVOLVEDBOWEL SHOWIXG ANNULAR NATURE OF TUMORSHOWN IN B’IGY. 2.5-4, I3 AND C Froin Kaiford, T. S.: Arch. Swg. 23: 131, 1932. these adeiiocarciiiomas resemble those found elsewhere in the gastro- iiitestirial tract. In one of the cases studied mucoid changes occurred (Fig. 27). FIG.26. PHOTOMIPKOGKAPIIOF ADENO('AR( INONA OF WE APPENDIX The tumor slron~sdcfinitc. glandular rlciiiciits infiltrating tho fibrous tissuc. Path. No. 29498.

$'I(:. 27. PITOTOIMICROGRAPII OF A MTJcO-ADENO('AlU ISOIilA OF THE APPENDIX. PATTI. NO. 101 12

152 TUMORS OF THE DIGESTIVE TRACT 153

Camw of the Colon Tumors of the colon approximate those of the rectum in frequency and are about one-half as common as those of the stomach. Males are affected twice as often as females. The peak of incidence is in the fifth and sixth clecades. The earliest symptoms are vague iiidigcstioii and change in the c*l~arilct(~rof tlie stool. The outstanding feature is obstruction, accom- panied by constipation, diarrhea or flatulence, and distention. Hemor- rhage may be manifested by anemia, tarry stools, or occult blood on chemical t cst. Increasingly severe indigestion with iiausea and vomit- ing is a relatively late sign. Perforation with acute abdominal pain aiid cachexia associated with widespread metastases are relatively uncommon.

h’IG. 28. ROENTGENOGRAM SHOWING FILLINGDEFECTS IN THE REGIONOF TItE CECUM, FOL- LOWING A HARItJN ENENAIN A CASE OF ADENOCARCINOMA 0% THE *4SCENDING COLON. PATII.KO. 43726

A mass or muscle spasm may be found at the tumor site on physical examinat ion. A filling defect in the roentgenogram following a barium enema is the most important diagnostic fiiiding (Fig. 28). Three f ourtiis of carcinomas of tlie colon are located in the asceiidiiig 01’ descending colon (Figs. 29 and 31). The remainder are approxi- mately eveiily distributed between the hepatic flexure, the transverse colon, and the splenic flexure. The symptomatology varies with the location of the tumor. Anemia is an outstanding feature of carci- nomiis of the ascending colon axid hepatic flexure. In the transverse colon the tumors show a tendency to extend to the stomach, giving rise to gastric distress, nausea, vomitiiig, aiid other forms of severe indi- gestion. Obstructive sips develop relatively early in this portion of the ho\vel. In tlic spleiiic flexure and descending colon obstruction and tarry stools are tlie outstanding features. 154 C€€AI?LES F. GESCIIICIITEIL

Operability, the mode of t reatmelit, and the prognosis vary with the location of the carcinoma. In the right or ascending colon resection of the entire bowel is the treatment of choice. Over 50 per cent of car-

FIG.29. BULKY ADENO(’ARCIN0MA OF THE COLON PRODUCING PARTIAL OHSTKUCTION. PATH. NO. 4,7348

FIG. 30. PIIOTO~IICROURAPH OF THE ADENOCAR(’INOMASHOWN IN 1”IU. 8!) Thc tumor is undergoing early muroid change.

cinomas in this region are operable, and approximately 40 per cent of the patients remain well more than five years following resection. Tn the hepatic and splenic flexures less than 50 per cent of the cases are operable. The outlook is extrcmely grave, and permanent cures are less than 10 per cent. In the transverse colon approximately 85 per cent of the carcinomas are resectable, but the tendency for tumors at this site to involve the stomach and mcsciitery reduces the number of TUMORS OF THE DIQESTIVE TRACT 155 permanent cures to approximately 25 per cent. In the descending colon and sigmoid the operability and prognosis are similar to those of tumors of the ascending colon. Approximately 50 per cent of these

FIG. 31. BULKYADENOCARCINOMA OF THE CECUM PRODUCING COMPLETE OBSTRUCTION AND INFILTRATION OF THE ABDOMINALWALL. PATH. NO. 28918

FIG.32. PHOTOMICROQRAPII OF AN EARLYCARCINOMATOUS LESION IN THE MUCOSAOF THE BOWELAT THE SPLENICFLEXURE There is 110 evidence that this tumor originated in a benign polyp. Path. No. 35962. tlimors are resectable, aiid 10 1)er cwlt of the patients so treated survive the five-year period. End-to-end anastomosis is preferable following resection in the 156 CHARLES F. GESCHICKTER transverse and descending colon, since there is difficulty in mobilizing the bowel in tlicsc regions after. adequate resection. Leading causes of operative mortality are peritonitis, shock, obstruction, pneumonia, and embolus. In tlie ascending, descending and transverse colon the operative mortality varies from 20 to 25 per cent, while that for tllc flexures appiwximates 30 per cent. Adenocarciiioma is the predominant histologic type of cancer of the colon (Figs. 30 and 32). This microscopic form and its variant muco- adeiiocarcinoma comprise 80 per cent of all the malignant tumors in this region (Table 11). The rare forms are squamous, medullary, scirrhous and primary mucoid cancer. All of these tumors are highly malignant with the exception of scirrhous carcinoma, which compares favorably with muco-adeiiocarciiioma or adenocarcinoma in curability.

FIa. 33. PIlOTOMICROCIRAPH OF AN ANAPLASTICCARCINOMA OF THE 8IGMOXD The speciInen was rcmoved at exploratory laparotomy, the growth proving inoperable. 1’8th. No. 29388. The percentage of metastases is greatest for tumors of the right ~01011, approximating 60 per cent. 111 the descending or left colon only 35 per cent of the tumors show to the regional lymph nodes and to distant structures.

Rectal Carcinoma Carcinoma in the rectum is somewhat higher in frequency than in the remainder of the large bowel. Males are twice as often affected as females, aiid tlie patients are slightly older (sixth and seventh decades) thali those with carcinoma elsewhere in the gastro-intestinal tr;wt. Paill at stool (tencsmus) aiid the passage of blood and mucus are the outstaliding symptoms. Ohsti*uction is observed as a rule only in the higher gro~7thstoward tlie rectosigmoid junction. Invasion of the prostate, vagina, and bladder, with involvement of the lumbar sacral TUMORS OF THE DIGESTIVE TRACT 157 plexus, occurs in advaiiced cases. HemorrllnFe is accompanied by mild anemia. Palpation of the tumor by the examiiiiiig finger is possible in a majority of the ~ases. Visualization with tlie proctoscope and re- moval of a piece of tissue for hiopsy make diagnosis certain. l’he polypoid tumors (low-grade adeiiocarc*inoma) produce ulceration or constriction (Fig. 34). Histologically 75 per cent of these growths are adenocarcinoma or muco-adenocarcinoma (Figs. 35 and 36). Fibrous carcinoma (scirrhous cancer) is present in 15 per cent of the cases. Hquamous-cell and primary mucoid cancer are more common here than in the remainder of the large bowel (Fig. 37). I~~xtensionand metastasis from rectal cancer are more frequent than with malignant tumors of the colon. In approximately one-third of the

FIG. 34. ADENOCARCINOMAOCCURRISG SIX C’ENTIMETEKS ABOVE THE AKALMARGIX. PATH.No. 37692 cases the sui~omidixigstructures are invaded and in another third the lymph nodes, liver, or distant orgaiis are irivolved by metastases. Re- cause of the spread of the disease at the time of its recognition, combined operation from above and below (abdominoperineal resection) is the treatment of choice. Miles prefers doing both abdominal and perineal approaches at one stage. Rankin does the abdominal procedure in the first stage, with the formation of a permanent colostomy, followed by u lapse of several weeks before attempting the perineal resection. Such ti preliminary abdominal procedure makes it possible to determine the extent and operability of the growth, reduces peritonitis by extraperi- toiiealizing the growth, and lessens shock. The mortality approsi- mates 5 per cent in the two-stage operation in expert hands. The av- erage mortality approaches 20 per cent. A few growths near the anus 158 CHARLES F. GESCHICKTER can be removed by perineal dissection alone, with restoration (usually incomplete) of sphincteric control, but recurrence is frequent with this procedure.

FIQS.35 AND 36. PHOTOMICROQRAPHS OF CARCINOMAOF THE RECTUM Fig. 35 (left) is a typical adonocarcinoma (Path. No. 45528). Fig. 36 is an adcnocarei- noma with mucoid change (Path. No. 43485).

FIG. 37. LOW-POWERAND IIIQII-POWEEPHOTOMICROGRAPHS OF AN EPIDERMOID CARCINOMA OF THE RECTUMORIQINATINQ IN A SMALL PAPILLOMA "lie tumor was successfully resected with restoration of continuity of the bowel. Path. No. 43948.

In the series of 370 patients with rectal cancer seen at the Johns Hopkins Hospital over a period of forty-five years, 53 per cent were in- operable; 10 per cent refused treatment; 37 per cent were operated upon TUMORS OF THE DIGESTIVE TRACT 159 with an immediate mortality of 22 per cent. Only 10 per cent of the patients were living and only 5 per cent cured for a period of five years or over. In the more recent cases (in the past decade) operability has

FIG. 38A. LYNPROSARC'OMA OF THE COLON. PATH. NO. 29605 reached 65 per cent, the mortality 10 per cent, and cures 36 per cent (Raiford). Sarcoma of the Digestive Tract Sarcoma of the gastro-intestinal tract comprises about 3 per cent of malignant growths in this region. The major form is lymphosar- coma. The stomach is affected more frequently than the small or large bowel. 1)'Aunoy et al. found 335 gastric sarcomas in the literature, of which 63 per cent were either lymphosarcoma or round-cell sarcoma. Fourteen per cent were myosarcoma or fibrosarcoma, the fibrosarcomas probably including tumors of neurogenic or myomatous origin. Stamm- ler, in 1924, collected 394 cases of sarcoma of the small and large in- testine, 218 of which "ere localized in the small intestine. Of the 218, 34 were in the duodenum. Dvorak was able to collect only 30 verified cases of sarcoma of the esophagus; these were of the round-cell or spindle type, probably lymphosarcomas and myosarcomas. In the present series of cases there were 46 lymphosarcomas, 13 in the stomach, 20 in the ileum, and 10 in the cecum (Figs. 38A and R). There were two in the rectum and sigmoid and one in the duodenum. The lymphosarcomas produce obstruction relatively late and give a prolonged history of dull, dragging pain, of loss of weight, weakness and anemia. Nausea is intermittent and bleeding is rare. A slight rise in temperature is common. Intussusception may occur when the small bowel is affected. Ihsemeyer estimates that 10 per cent of in- tussusception is caused by sarcoma. These growths may dilate the in- testinal tract rather than constrict it, giving rise to a diffuse infiltration which stiffens the u7all of the digestive tube so that it resembles a gar- den hose. The lesions are radiosensitive and permanent cures have hen recorded with such therapy. The more localized growths have been cured by resection. 160 CHARIAES F. GESCHICKTEE

Only 4 myosarcomtts were fouiicl iii this series, 2 in the stomiicli, and oiic each iii the ileum and iii the rectum. Although bc~iiigiimyomus are relatively commoii in the digestive tube, maligntint tumors of this type are exceedingly rare. The stomach aiitl small iiitcstiiic are more often ai'fected than the colon and rectum. These lesions produw large, solid growths which metastasize relatively late to the liver and lungs.

FIG. 380. PITOTOMICROGRAPII 0% ~dYMPHOSARCOMA OF TIIE COLON SIIOTVN IX FIG. 38.i From Raiford, T. S.: Arch. Surg. 26: 822, 1933.

Ten sarcwmas of the nerve sheath were studied, 4 in the rectum, 3 in the stomach, and 3 in the small intestine. Microscopically they re- semble the more commoii neurogenic sarcomas of the peripheral nerves. One of the cases in the small intestine was associated with multiple subcutaneous nerve sheath tumors of the voii Rccklinghauscn type. All of the cases terminated fatally.

BIIII~IOGHAPHY BALLANTYNE,EL M. : Sacrocoecygral tumors; adeiiocarcinonia of a cystic coiigrriital ern- bryonal remnant, Arch. Path. 14: 1, 1932. D'AUNOY,R., AND ZOmLER, A.: Sarcoma of the stomach, Am. J. Surg. 9: 444, 1930. DVORAK,11.: Stircoma of the esophagus, Arch. Surg. 22: 794, 1931. FITZG~BBON,G., AND RANKIN,F. W.: Polyps of the large intestine, Surg. Gynrc. & Obst. 52: 1136, 1931. GARDNER,C. E., AND I~ART,D.: Enlerogenous cysts of the duodenum, J. A. M. A. 104: 1809, 1935. GINSBURG, L. : Multiple papillomas of the esophagus, Arch. Otol. 14: 570, 1931. TUMORS OF THE DIGESTIVE TRACT 161

HESSE,W. : Beitrag zur Beharidlung des Oesophaguskarzinoms, Folia otol. laryng. 33 : 98, 1930. HUEBSCHAMW,P. : Sur le carcinoine primitif cle Yappendice vcrmiculare, Rev. m6d. de la Suisse rom. 31: 317, 1910. KASEMEYER,E. : Tumoriiivagiiiatioii drs Ilarms, Ileutsche Ztschr. f. Chir. 118 : 205, 1912. LEWIS, D., AND UESCHICKTER, C. F’.: Tumors of the sympathetic nervous system, Arch. Surg. 28: 16, 1934. LEWIS, F. T., AND THYNG,F. W.: Regular occurrerice of intestinal diverticula in the embryo of the pig, rabbit and man, Am. J. Anat. 7: 505, 1907. LOVEN,K. A. : Grosse Psrudomyxozyste in der Apperitlix auf der Grundlage einer Kar- zinoidstriktur, Acta chir. Scandiiiav. 69 : 99, 1931. MASSON,P.: Contribution to the study of the sympathetic nerves of the appendix, Am. J. Path. 6: 217, 1930. nfCGLAh’NAN, A. : Meckel’s diverticulum, Surg. Gynec & Obst. 35 : 142, 1922. MOERMCH,H. J., AND BRODERS,A. C. : Adenoma of the esophagus, Arch. Otolaryng. 21 : 168, 1935. MONTGOMERY,J. G., AND JOHNSOY,E. T.: Primary carcinoma and carcinoid of the ap- pendix, J. Missouri State M. A. 28: 215, 1931. PATTERSON,E. J. : Beiiign neoplasms of thc esophagus : report of a case of myxofibroma, Ann. Otol., Rhinol. & Laryng. 41 : 942, 193‘2. RAIBORD,T. S.: Tumors of the small intestine, Arch. Surg. 25: 122; 321, 1932. RAIFORD,T. S.: Caremomas of the large bowel, Ann. Surg. 101: 863; 1042, 1935. RAXICIN,3’. W.: Surgical treatmerit of carcinoma of the colon, Surg. Gynec. & Obst. 53: 229,1931. SCHILLING,H., AND BERNER,0. : Om ii €-’olyposis iritestini,” Norsk. mag. f. laegevidenik. 92: 602, 1931. SIMPSON,TV. i\l. : Aberrant pancreatic ti5sue; analysis of one hundred arid fifty human cases with rrport of new caw, in: Contributions to Medical Science, Dedicated to Aldred Scott Warthin, Ann Arbor, Mich., George Wahr, p. 435, 1927. ST4MMLER, M. : Ilie Neubildungen des Darms, Neue Deutsche Chirurgie h’o. 33a, 1924. STEWART,M. J. : Precancerous lesions of alimentary tract, Lancet 2 : 669, 1931. WARTHIN,A. S.: Cited by Simpson.