Neoplasms of the Small Intestine

Alan Cohen, MD,*t Donald McNeill, MD,*$ Jose J. Terz, MD and Walter Lawrence, Jr, MD

Our experience with small intestinal neoplasms at the Medical College of Virginia has been reviewed. There were 78 benign and malignant neoplasms observed in our surgical pathology laboratory over a 20-year period. There were 34 benign small-bowel tumors, but the majority of these lesions were asymptomatic inci- dental findings at the time of surgery for other conditions. There were 21 patients with malignant neoplasms of the small bowel and 23 patients with carcinoid, a potentially malignant lesion. Clinical observations and the results of treatment are reviewed.

A wide range of b o t h b e n i g n a n d mal ig- nan t t umors has been desc r ibed in the smal l bowel in a n u m b e r of exce l l en t re- views (1, 2, 4, 9-13), b u t th is p o r t i o n of the in tes t ine does a p p e a r to be r e l a t ive ly im- m u n e to neop las ia , w h e n c o m p a r e d to the s tomach a n d the large bowel . T h e f requen- cy of ben ign t umors is va r i ab le , a l t h o u g h u n i f o r m l y low, a n d m a l i g n a n t neop la sms of the smal l bowel gene ra l ly r ep re sen t on ly I - 5 % of a l l cancers of the ga s t ro in t e s t i na l tract. T h e inc idence of t u m o r s in each of the r e p o r t e d series also bears some r e l a t i o n to the m e t h o d of i d e n t i f y i n g them, e i t he r by surgery or by au topsy e x a m i n a t i o n . F o r this reason, this rev iew was ca r r i ed o u t us ing the surgical p a t h o l o g y a n d c l in ica l records of pa t i en t s a t the Med ica l Col lege

From the Divisions of Surgical Ontology and Surgical Pathology of the Medical College of Vir- ginia (Health Sciences Division of Virginia Com- monwealth University), Richmond, Va.

Address for reprint requests: Walter Lawrence, Jr, MD, Division of Surgical Oncology, Medical Col- lege of Virginia, Richmond, Va 23219.

*Clinical Fellows of the American Cancer Society. J'Current address: LCDR, MC, USNR, Naval

Hospital, Quonset Point, RI. $Current address: Major, MC, Department of

Pathology, DeWitt Army Hospital, Fort Belvoir, Va.

of V i r g i n i a Hosp i t a l s ; these records demon- s t ra te the b e n i g n o r m a l i g n a n t t umors of the smal l bowe l d u r i n g the 20-year pe r iod , 1950-1969. Since mos t au topsy reviews con- sist m a i n l y of a s y m p t o m a t i c neoplasms , i t was h o p e d tha t this c l in ica l s tudy w o u l d include" e n o u g h s y m p t o m a t i c lesions to re- veal the i m p o r t a n t fea tures of c l in i ca l ly s igni f icant smal l -bowel tumors .

MATERIALS

All primary benign and malignant small-bowel neoplasms from the duodenum, jejunum and ileum were included in this analysis except for primary neoplasms of the ampulla of Vater. This study in- cluded 78 individual tumors from the files of the Division of Surgical Pathology of the Medical Col- lege of Virginia, all carefully reviewed pathological- ly by one of us (DM) for confirmation of diagnosis at the time of this review. There were 34 benign tumors, the largest single group, followed by 23 carcinoids, which are potentially malignant lesions, and 21 malignant small-bowel tumors. The ileum was the favored site, even after exclusion of all carcinoids. There were 44 tumors of the ileum (in- cluding seven localized at the ileocecal valve), 21 in the duodenum, and 13 in the jejunum. Except for an unusually high proportion of carcinoid tumors (29.5%), the proportion of benign to malig- nant neoplasms was really not dissimilar to that in other reviews.

Digestive Diseases, Vol. 16, No. 9 (September 1971) 815

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Table 1. Age Distribution of Patients with Small-Bowel Tumors

Small-bowel tumors

Malig- Age (yr) Benign nant Carcinoid Total

0-10 4 1 0 5 11-20 0 0 0 0 21-30 2 2 0 3 31-40 0 1 2 3 41-50 5 1 6 12 51-60 4 4 4 12 61-70 9 6 7 22 71-80+ 10 6 4 18

Total 34 21 23 75

R E S U L T S

C l i n i c a l F i n d i n g s

Although each o f the various categories of small-bowel neoplasms should be con- sidered separately, there were a number of features ,in the clinical presentat ion that were common to the total series. For ex- ample, the preponderance of both benign and mal ignant lesions was found in the seventh and eighth decades, a l though the age range of the entire series extended from neonate to 81 years (Table 1). Sex distribu- tion was approximate ly equal for the entire series, as well as for most of the groups of specific lesions.

In the entire series, there were 32 lesions that produced symptoms prior to their sur- gical identification, nine of these being benign, fifteen malignant , and eight were carcinoids. Of 32 asymptomatic lesions in this series, 28 proved to be benign, while only four were malignant. Most asympto- matic tumors were found at the time of laparotomy which was carried out for other indications. T h e presence or absence of significant symptoms in the remaining 14 patients was too poorly documented for specific observations to be made regarding symptomatology.

An a t tempt was made to relate specific symptoms to the benign or mal ignant char- acter of the tumors. Except for a frequent history of weight loss in the group with mal ignant tumors, there was no other dif- ferentiat ing point in the clinical histories that was helpful in separating benign from mal ignant tumors (Table 2).

In patients in this entire series, the dura- tion of symptoms ranged from 2 days to 4 years. T h e most frequent symptoms at all sites were abdominal pain, nausea and vomiting, or occasionally, gastrointestinal blood loss. The re was generally a shorter symptomat ic interval for lesions of t h e duodenum (3 months) than for those of the j e junum (8.8 months) and ileum (7.3

Table 2. Symptoms and Signs of Pathology and Anatomic Location

Nausea Pathology and Weight and Obstr uc- Abdomi-

anatomic location Pain Bleeding loss vomit ing tion Anemia nal mass

Pathology Benign 2 3 2 4 2 1 1 Carcinoid 5 1 2 2 4 1 1 Mal ignant 11 3 10 10 2 3 7

Anatomic location Duodenum 5 3 3 6 1 1 0 Jejunum 4 2 4 5 2 2 3 I leum 9 2 7 5 5 2 6

Total 18 7 14 16 8 5 9

816 Digestive Diseases, Vol. 16, No. 9 (September 1971)

NEOPLASMS OF THE SMALL INTESTINE

months). It was also noteworthy that proxi- mal lesions produced symptoms more fre- quently than did lesions of the distal small intestine.

Physical and Laboratory Findings

The commonest positive physical findings in the overall group were those abdominal findings associated with intestinal obstruc- tion, and the presence of an abdominal mass. There were nine palpable masses, eight of which were associated with malig- nant tumors. Six of the 9 patients with palpable abdominal masses had lesions in the ileum. Th e only positive laboratory finding in this series was. anemia, which was noted in 5 patients. Radiographic study by upper gastrointestinal and small-bowel series was rarely diagnostic, although seven lesions in the duodenum or proximal jeju- num were identified by this method.

Clinicopatholofiic Correlations

Benign neoplasms. Histologic type and anatomic location of the 34 benign lesions encountered are shown in Table 3. These patients ranged in age from new- born to 81 years, but the preponderance o[ lesions was in the elderly. Only 12 of these patients had symptoms of any kind, and despite the surgical nature of this series,

22 tumors were incidental findings at the time of surgery for unrelated conditions. Benign lesions of the duodenum were more likely to be symptomatic than were more distal lesions, but five of the symptomatic lesions were only indirectly symptomatic by virtue of a possible relationship to gas- tric hypersecretion and peptic ulcer (islet cell tumors).

Physical and laboratory findings were generally unimpressive in this group of pa- tients with benign lesions. Only 1 patient had an abdominal mass, and 1 patient had significant anemia. Correct radiographic diagnosis was made in 6 patients prior to surgery, however. All of these lesions were located in the duodenum.

There were ten adenomas and eight leio- myomas, the benign lesions most frequently observed. Th e five islet cell adenomas of tile duodenum and four lipomas of the ileum were next in frequency; there were a few lesions arising from other mesoder- real tissues (two adenomas of Brunner 's glands, two hemangiomas, one lymphangi- oma and one fibroma).

There were 9 patients with adenomas presenting as polyps, and their mean age was 53 years. Five polyps were located in the ileuln, three in the jejunum, and one at the ileocecal valve. Three of these lesions

Table 3. Benign Small-Bowel Neoplasms

I leum and Benign neoplasms Duodenum Jejunum ileocecal valve Total

Adenomas Islet cell 5 0 0 5 Brunner's gland 2 0 0 2 Adenoma 1 3 6 10

Leiomyomas 3 3 2 8 Hemangiomas 0 1 ] 2 Lymphangiomas 0 1 0 1 Fibromas 0 0 1 1 Lipomas 1 0 4 5

Total 12 8 14 34

Digestive Diseases, Vol. 16, No. 9 (September 1971) 817

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were symptomatic, with some degree of obstruction (two jejunal and one ileal), and two of the lesions actually caused intussus- ception. T h e symptomatic ileal polyp was associated with Peutz-Jegher's syndrome. In addition to these nine adenomas, there was one papillary adenoma of the duodenum which appeared to arise from heterotopic pancreatic ductal tissue. This lesion pro- duced upper gastrointestinal bleeding, and was identified by radiographic study prior to surgery.

Leiomyomas occurred in 8 patients with a mean age of 76 years. Half of these pa- tients were male and half were female. Only two of these lesions were symptomatic, one arising in the duodenum and the other in the je junum. In each instance, symptoms were obstructive in nature, and there was also evidence of gastrointestinal bleeding in each case.

All five of the islet cell adenomas were duodenal, and all were associated with pep- tic ulcer disease. The re were 3 males and 2 females in this group, the mean age being 52 years. All patients were treated by sur- gical resection of the adenoma. One ade- noma was excised from a duodenal stump, one excised with retained antrum, and one removed with a duodenal stomal ulcer at the time of concomitant vagotomy. Another adenoma was resected at the time of antrec- tomy for peptic ulcer disease, and the fifth patient underwent excision of the adenoma at the time of subtotal gastric resection. One year later, this patient required total gastrectomy for documented Z-E syndrome; this was the only patient of the 5 in whom the relationship between the tumor and the ulcer disease was actually established.

In this series, there were five neoplasms that were lipomas. Of these five, three were actually incidental findings in the region of the ileocecal valve, but the other two le- sions (1 in the duodenum and the other in the ileum) were symptomatic.

Both patients with Brunner 's gland ade- nomas had unusually large lesions (4.5 and 5 cm). One was in a 42-year-old male, arid the other, in a 68-year-old female; both were symptomatic lesions. The clinical pres- entation was upper gastrointestinal bleed- ing in one case and duodenal obstruction in the other. Both were identified radio- graphically. They were successfully treated by surgical resection.

Carclnoids. T h e next largest group of small-bowel neoplasms were the 23 carci- noids representing 29.5% of the entire series. They were found in the ileum (18 patients) and duodenum (5 patients). There were 11 females and 12 males, and the mean age at the time of diagnosis was 56 years.

Of the 23 patients with carcinoid tumors, 8 had symptoms which could be associated with their tumors; these included nausea, vomiting and abdominal pain which were experienced by all 8. Three patients also described weight loss. Two of these patients had abnormal urinary levels of 5-HIAA prior, to surgery. One of these died on the second postoperative day, and she Was found, at autopsy, to have endocardial fibrosis of the-right heart.

T h e physical examinat ion and the radio- logic presentation in 6 of these 8 patients indicated partial or complete bowel ob- struction, with a palpable abdominal mass in one instance. Obstruction in 3 of these patients with small-bowel carcinoid actu- ally led to bowel perforation prior to sur- gical intervention. T h e prognostic impor- tance of the presence of symptoms in the patient with carcinoid is shown by the fact that 4 of the 8 symptomatic patients have died as a result of their tumor.

All extra-appendiceal carcinoids should probably be considered potentially malig- nant; the size of the lesion and the depth of invasion have generally been considered

818 Digestive Diseases, Vol. 16, No. 9 (September 1971)

NEOPLASMS OF THE SMALL INTESTINE

significant features of this determinat ion (5, 8). Seven (30%) of the lesions were lo- calized to the mucosa, and six (26%) of them extended through all layers of the bowel wall but without evidence of lym- phatic spread or distant metastasis. All of these 13 patients without metastatic spread have remained well or have died due to completely unrelated causes. I t would ap- pear that carcinoid tumors without meta- stasis to lymph nodes at the time of resec- tion have a very favorable prognosis.

Of the 23 patients with carcinoid tumors, 10 demonstrated metastases to regional lymph nodes (9 cases) and /o r to distant organs (6 cases). One patient died post- operatively, and 4 others died subsequently as a result of progression of tumor growth. One patient who was lost to followup un-

derwent abdominal paracentesis for pre- sumed recurrent disease 1 year after surgi- cal resection, and he has probably died. One patient is alive 2 years after segmental resection, and another, 4 years after resec- tion of the bowel carcinoid and a solitary hepatic metastasis. A third patient is alive and well 14 years after segmental bowel resection, but there is clinical hepatomeg- aly. In view of the poor results obtained when lymphatic spread has occurred, it would appear that this feature of the tumor is the most important prognostic factor in the treatment of carcinoid tumors (Table 4).

Th e presence of other primary neoplasms in patients with carcinoid tumor has fre- quently been commented upon (3, 6, 8). Of the 23 patients in this series of carcinoid patients, 4 (17.4%) had malignant tumors

Table 4. Results of Treatment for Carcinoid Tumors with Metastases

Patient Site of tumor Metastasis Treatment Followup

AS Duodenum Lymph node, pancreas, Pancreatoduodenectomy Died at 6 years (unknown liver (duodenum) cause)

LM Ileum Lymph node Resection of terminal Died at 6~ years with i leum and right colon disease for Duke's B ca of cecum

KF Ileum Lymph node, Segmental resection Living at 14 years, peritoneal implants asymptomatic

(hepatomegaly) HB Ileum Lymph node Segmental resection Living at 1 year (lost to

further fol lowup) EP Ileum Tuboovarian and hepatic Segmental resection Died at 5 months with

disease FJ Ileum Lymph node, liver Segmental resection Died at 3 years with

disease BJ Ileum Lymph node, liver Segmental resection Postoperative death

peritoneal implants AS Ileum Lymph node Segmental resection Living 2 years, no evidence

and right colectomy of disease for Duke's C ca of colon

MH Ileum Lymph node, liver Segmental resection Living 4 years, no evidence and excision of of disease hepatic metastasis

OG Ileum Lymph node Segmental resection Living 2 years, no evidence of disease

Digestive Diseases, Vol. 16, No. 9 (September 1971) 819

COHEN ET AL

of other sites. These included: adenocarci- noma of the sigmoid colon, adenocarci- noma of the cecum, adenocarcinoma of the ampul la of Vater and cyl indroma of the anus. I t was also of interest that there was heterotopic pancreatic tissue in the small bowel in 5 of the patients in this series of 23 carcinoid tumors.

Table 5. Malignant Small-Bowel Neoplasms

Malignant Duo- Jeju- Ileum neoplasms denum num + Total

Adenocarcinoma 2 3 5 10 Leiomyosarcoma - - 2 3 5 Lymphosarcoma 2 0 4 6

Totals 4 5 12 21

Carcinoid 5 18 23

Grand Total 9 5 30 44

Malignant tumors. T h e most com- mon mal ignant tumor in this series was adenocarcinoma (10 patients), the ileum, with five cases, being the most common site. Next in frequency were lymphosarcomas, with six cases, and leiomyosarcomas, with five (Table 5).

Eight of the adenocarcinomas were ses- sile neoplasms, and two were carcinomas developing in polyps of the ileocecal valve. Three of the sessile lesions were in the ileum, three in the j e junum and two in the duodenum. Of these 8 patients, all but l had symptoms related to their neoplasm. Obstructive symptoms occurred in 6, and gastrointestinal bleeding occurred in one ileal and in two jejunal lesions. T h e mean age of these patients was 58 years.

Surgical t reatment of the adenocarcinoma varied according to its location. T h e carci-

Table 6. Results of Treatments for Adepocarcinoma

Patient Site Invasion or metastasis Treatment Followup

DH Duodenum Invasion of pancreas Pancreatoduodenectomy Postoperative death and common duct

MS Duodenum Invasion of pancreas Pancreatoduodenectomy Living 16 years (no evidence of disease)

ML Ileocecal None Right colectomy, Died at 4 years (no valve (in sigmoid colectomy evidence of disease) a polyp) for colon Ca

AH Ileoceal None Right colectomy for valve (in Duke's C Ca a polyp)

OT Ileum Lymph node Segmental resection

EW Ileum None Segmental resection

TP Ileum None Segmental resection

LJ Jejunum Lymph nodes, pancreas, Segmental resection and two liver nodules gastrojejunostomy

JH Jejunum Mesenteric lymph Segmental resection node

CB Jejunum None Segmental resection

Died at 5 years (no evidence of disease)

Died at 4 years (unknown cause)

Died at 4 years (adenocarcinoma of uterus)

Living 3 years (with proven metastasis)

Died at 2 months

Died at 18 years of metastatic prostatic Ca

Living 6 years (no evidence of disease)

820 Digestive Diseases, Vol. 16, No. 9 (September 1971)

NEOPLASMS OF THE SMALL INTESTINE

nomatous polyps of the ileocecal valve were removed at the time of surgical resection of colon cancers presenting simultaneously. Both ileal carcinomas and two of three jejunal carcinomas were segmentally re- sected. A palliative gastroenterostomy was performed in the other pat ient with je junal carcinoma, and both carcinomas of the duodenum were subjected to pancreatoduo- denectomy.

Results of surgical t reatment of these 10 patients with adenocarcinoma are sum- marized in Tab le 6. One pat ient with car- cinoma of the duodenum died postopera- tively, and tile other is living and well 16 years after resection. Of the 3 patients with jejunal carcinoma, 1 is living and free of tumor 6 years postoperatively, and one died of an unrelated cause (metastatic pro- static cancer) 18 years after resection. T h e third patient with je junal carcinoma was treated only palliatively and survived for 2 months. One of the patients with carci- noma of the i leum died as a result of a second pr imary cancer (uterus) 4 years after resection, and another died of unknown cause after 4 years. T h e third pat ient with carcinoma of the i leum is alive 3 years after resection, but metastasis to an axillary lymph node has been detected. T h e 2 pa- tients with carcinoma in a polyp died with- out evidence of recurrent or metastatic dis- ease 4 and 5 years after resection. Of the 10 patients with carcinoma (1 duodenal , 2 jejunal and 1 ileocecal valve), 4 are known to have lived for more than 5 years wi thout recurrence or metastasis. Of the 6 deaths which occurred before the 5-year interval, 3 were not due to further growth of the small-bowel cancer. However, only 2 of the 10 patients are alive and free of cancer (6 and 14 years). In 2 patients, cancer is known to have recurred, but other causes of death in 6 of the 10 patients make evaluation of surgical t reatment difficult.

Pr imary lymphosarcoma occurred in 6 pa- t i e n t s - i n the i leum in 4 patients and in the duodenum in 2. T h e mean age for this group was 67 years. T h e histologic classifi- cation was re t iculum cell type in 5 patients, and lymphocytic type in the other. All but 1 pat ient had symptoms which were related to the presence of their neoplasm. Both duodenal patients presented with nausea and vomit ing due to part ial obstruction, and 1 had upper gastrointestinal bleeding as well. T h r e e of the 4 patients with ileal lesions had obstruction or gastrointestinal bleeding, and 1 with both symptoms had a palpable mass.

T r e a t m e n t by resection was difficult to evaluate in this small group. One of the patients with lymphosarcoma of the duode- n u m survived for 9 months after resection, but died as a result of metastatic cancer of the colon. T h e other pat ient with a duo- denal lesion survived 5 ~ years before being lost to followup, but he did require irradia- tion therapy for axillary involvement that developed subsequent to surgical resection of the pr imary site. One with ileal lympho- sarcoma succumbed to hemorrhage f rom lymphosarcoma involving the stomach 1 year after ileal resection, and 1 pat ient is alive with disseminated disease 21 months after intestinal resection. Followup is in- complete for the other 2 patients with ileal lymphosarcoma.

Of the five leiomyosarcomas in this series, two were located in the j e junum and three, in the ileum. These were found in 4 fe- males and 1 male whose mean age was 50 years. Obstructive symptoms were common as in the other groups discussed, and 1 pat ient with a je junal lesion presented with symptoms of anemia and a hemoglobin de- terminat ion of 6 g%. Followup on this group of patients was too incomplete to be meaningful , but 1 pat ient survived for 11 years, before death due to liver metastasis.

Digestive Diseases, Vol. 16, No. 9 (September 1971) 821

D I S C U S S I O N

T h e relative infrequency of small intes- tinal tumors is attested to by this series of 78 primary tumors which occurred over a 20-year period in a surgical pathology lab- oratory with approximately 10,000 acces- sions yearly. T h e anatomic distribution and the histologic types of small-bowel neo- plasms in this series are similar to others reported. It has been stated that in autopsy series, benign lesions ou tnumber malignant varieties, while the latter are more common in clinical series (2). I f carcinoids are in- cluded with the malignant group, the ratio of malignant to benign tumors in this series is 44:34, but it is striking that benign tu- mors ou tnumber malignant lesions if we segregate the carcinoids as a difficult group to classify. This large group of benign le- sions in a clinical series (43.6%) is undoubt- edly due to the fact that a number of these lesions were actually incidental findings at the time of surgery for other conditions.

T h e diagnosis of small-bowel neoplasms is hampered by a number of factors. They arise more frequently from the distal small bowel, and symptoms are nonspecific, re- gardless of the tumor type or anatomic loca- tion. Symptoms are often chronic and are dismissed or treated symptomatically unless they are progressive, as might occur with malignant lesions. As expected, malignant lesions do give rise to symptoms much more frequently than benign tumors. T h e findings of an abdominal mass was infre- quent (9 of 78 patients), and all but 1 of these patients had a malignant neoplasm. Lastly, the radiologist is not often able to make the diagnosis of small-bowel tumor unless the lesion is in the duodenum, proximal j e junum or ileocecal area. Unfor- tunately, there were no useful clues to the diagnosis of smaU-bowel tumors, that were developed as a result of this study.

The re is a large variety of benign tu-

COHENETAL

mors reported in the world literature, and the more common types are represented in this series. At the Mayo Clinic (8), the most common benign lesions were leiomyoma, lipoma and adenomatous polyp. In our series, these histologic types were also the most common, with the exception of five islet cell adenomas occurring in the duo- denum. Although all five occurred in pa- tients with peptic ulcer disease, only one was associated with a clear-cut clinical pic- ture of the Zollinger-Ellison syndrome.

T h e carcinoid tumor is an unusual lesion with malignant potential and a wide range of prognostic features. If the lesion is symp- tomatic, rather than an incidental finding, it is more likely to have metastasized. Moer- tel et at (8) state that 93% of symptomatic carcinoids in their series had metastasized, while only 9% of asymptomatic carcinoids had done so. In our small series, of the 23 patients only 8 (35%) had symptoms which were related to the carcinoid tumor, and 5 of these patients had metastases demon- strated at the time of surgery. Of the 15 asymptomatic patients, 5 also had meta- static disease, so the significance of symp- tomatology seems less striking in our series.

T h e presence or absence of metastases was clearly related to the size of the pri- mary carcinoid in Moertel's study, which ranged from less ~than 2% for lesions small- er in size than 1 cm to 80% for lesions over 2 cm (8). MacDonald considered depth of invasion of the bowel wall to be another impor tant factor (5). Lymphatic spread almost never occurred in his series in the absence of muscularis invasion, and usually not without serosal involvement; however, of 16 patients in our series with invasion of the entire bowel wall, there were 6 who did not have regional or distal metastatic disease. T h e presence or absence of meta- stases is of great prognostic significance as shown by the fact that all 13 patients in

822 Digestive Diseases, Vol. 16, No. 9 (September 1971)

NEOPLASMS OF THE SMALL INTESTINE

this series, wi thout lymphat ic or distant spread at the t ime of resection, have re- mained well from the s tandpoint of their carcinoid tumor. Of the 10 patients with metastases who underwent segmental re- section, 2 are alive less than 5 years after- wards, 1 is alive with significant hepato- megaly 14 years afterwards, and the others are all dead.

T h e endocrine features of carcinoid tu- mors have intrigued clinicians since the carcinoid syndrome was first described; five physiologic substances have been shown to be secreted by funct ioning carcinoids (9): serotonin, 5-hydroxytryptol0han, kallikrinin, histamine and A C T H . T h e diagnosis of car- cinoid syndrome by the finding of 5-HIAA in the urine of patients with intestinal carcinoid is uncommon, is always associated with liver metastasis, and is uniformly in- dicative of incurability. Mart in (6) recently reported 7 of 59 patients with gastrointes- tinal carcinoid who had an increase in urinary 5-HIAA or symptoms of the syn- drome, and all died due to their tumor. T w o of the patients in this series had clear- cut manifestations of the syndrome, and neither survived.

T h e presence of other pr imary cancers in patients with carcinoid is unusually high, with reports of 29% by Moertel (8), 25% by Martin (6), and 32% by Kuiper (3), while the incidence of second p r imary can- cers with other mal ignant neoplasms is in the 5 -7% range (7, 14). In this series, there are only 4 of the 23 patients with carcinoid known to have other cancers (17.4%), but all 4 were associated with carcinoid tumors arising in the ileum. I t is also of interest that all 4 of the second pr imary cancers originated in the gastrointestinal tract.

Of the mal ignant small-bowel tumors (other than carcinoid), adenocarcinoma is always considered the most frequent, fol- lowed in incidence by leiomyosarcoma and

lymphosarcoma. Th i s distr ibution was simi- lar in our series of 21 patients with malig- nant lesions, but the usual preponderance of adenocarcinomas in the duodenum was not observed. As with the carcinoid tumors, there did seem to be a higher incidence of second pr imary cancers with adenocarci- noma of the small bowel. The re were 2 patients with associated carcinoma of the colon, and 1 each with carcinoma of the uterus and carcinoma of the prostate. T h e results of t rea tment of all of the noncarci- noid mal ignant tumors of the small bowel have been disappointing, but there are a few long-term survivors.

R E F E R E N C E S

1. Botsford TW, Crowe P, Crocker DW: Tu- mors of the small intestine: a review of experience with 115 cases including a re- pork of a rare case of malignant hemangio- endothelioma. Amer J Surg I03:35B, 1962

2, Colcock BP, Braasch JW: Surgery of the small intestine in the adult, Major Prob- lems in Clinical Surgery. Vol VII. Philadel- phia, WB Saunders Company, 1968, p 66

3. Kuiper DH, Gracie WA Jr, Pollard HM: Twenty years of gastrointestinal carcinoids. Cancer 25:1424, 1970

4. McPeak C J: Malignant tumors of the small intestine. Amer J Surg 114:402, 1967

5. MacDonald RA: A study of 356 carcinoids of the gastrointestinal tract. Amer J Med 21:867, 1956

6. Martin RG: Management of carcinoid tu- mors. Cancer 26:547, 1970

7. Moertel CG, Dockerty MB, Baggenstoss AH: Multiple Primary Neoplasms. Cancer 14:221, 1961

8. Moertel CG, Sauer G, Dockerty MB, et al: Life history of the carcinoid tumor of the small intestine. Cancer 14:901, 1961

9. Oates JA, Butler TC: Pharmacologic and endocrine aspects of carcinoid syndrome. Advances Pharmacol 5:109, 1967

Digestive Diseases, Vol. 16, No. 9 (September 1971) 823

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10. Pagtalunan RJ, Mayo CW, Dockerty MB: Primary malignant tumors of the small intestine. Amer J Surg 108:13, 1964

11. River L, Silverstein J, Tope JW: Collective Review: benign neoplasms of the small intestine, a critical comprehensive review with reports of 20 new cases. Int Abst Surg 102:1, 1956

12. Rochlin DB, Longmire WP: Primary tu- mors of the small intestine. Surgery 50: 586, 1961

13. Sethi G, Hardin CA: Primary malignant tumors of the small bowel. Arch Surg 98: 659, 1969

14. Watson TA: Incidence of mult iple cancer. Cancer 6:365, 1953

824 Digestive Diseases, Vol. 16, No. 9 (September 1971)