Malignant Tumors of the Small Intestine

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Gastrointestinal and Hepatobiliary Malignancies

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Malignant Tumors of the Small Intestine Richard G. Martin, M.D. *

The small intestine comprises the duodenum, the jejunum, and the ileum. Although its total length is much greater than that of the remaining gastrointestinal tract, this area develops fewer tumors. In our series of 11,438 cases of gastrointestinal tumors seen between 1944 and 1982 at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, there were only 280 cases of tumors located in the small intestine (Table 1). The reason for this is not known; however, there are several theories. One is that because the transit time is rapid the intestinal contents do not stay in this portion of the gastrointestinal tract for any substantial length of time. However, the transit time through the esophagus is also rapid, and it produces more tumors than does the small intestine. Another theory is that because the contents are rapidly absorbed, going to the liver for assimilation, the by-products do not stay in this area. Also, the small intestine is relatively free of bacteria that may take part in the breakdown of certain substances within the bowel content, causing carcinogenic agents to be formed. Included in the aforementioned series of 280 small-bowel tumors are 63 ampulla of Vater lesions. The reason these were included is that they were categorized with the small-bowel tumors in our registry. It is very difficult at times to decide whether such lesions develop from the bile ducts or from the lining of the duodenum in the area of the ampulla of Vater. However, these 63 patients will not be considered in detail. Therefore, this review is based on a series of 217 small bowel malignancies. All the tumors in this series were classified by our pathologist. Table 2 lists the number of cases in each location, with Table 3 showing the distribution of the various histologic types within the small intestine. All the sarcoma cases were classified as leiomyosarcoma except for two cases ofliposarcoma arising in the ileum. It is interesting to note that the majority of the adenocarcinoma lesions occur in the duodenum and the jejunum and *Professor of Surgery, Department of General Surgery, The University of Texas M. D. Anderson Hospital and Tumor Institute, Houston, Texas

Surgical Clinics of North America-Vol. 66, No.4, August 1986

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Table 1. Percentage of Gastrointestinal Tumors by Specific Site LOCATION

PER CENT

Esophagus Stomach Small Intestine Large Intestine Rectum Total

10.8 16.4 2.4

48.7 21.6 100.0

that the sarcoma, carcinoid, and lymphoma lesions are located mostly in the ileum. The male:female ratio is fairly even except that the male patients predominate in the adenocarcinoma category, and although the numbers are small, all the lymphoma patients are male (Table 4). Also of interest is the predominance in this series of the number of white patients over the number (17) of black patients. All of these tumors appeared in the second decade of life or later, except for two lymphomas occurring in pediatric patients. Small bowel tumors occur most frequently in the fourth, fifth, and sixth decades of life (Table 5). Associated conditions that might be risk factors are Crohn's disease or ileitis and multiple polyposis. We had in this series two cases that had associated Crohn's disease. It is still difficult to determine whether longTable 2. Number of Small-Bowel Tumors by Specific Site LOCATION

NUMBER OF CASES

45 42 87

Duodenum Jejunum Ileum Not specified Total

~

217

Table 3. Histologic Types of Tumors by Specific Sites in the Small Intestine CASES IN DUODENUM

HISTOLOGY

Adenocarcinoma Sarcoma Carcinoid Lymphoma Totals

CASES IN JEJUNUM

CASES IN ILEUM

CASES IN UNSPECIFIED SITE

10 6 25 ~

35 3 7

25 6

17 15 51

~

~

...1

45

9

42

87

43

Table 4. Sex Distribution of Small-Bowel Tumors HISTOLOGY

Adenocarcinoma Sarcoma Carcinoid Lymphoma Totals

MALE

FEMALE

57 18 48

30 15 41

~

~

131

86

781

MALIGNANT TUMORS OF THE SMALL INTESTINE Table

AGE IN YEARS

<20 20--29 30--39 40-49 50--59 60--69 70-79 ;=: 80 Totals

5. Small Bowel Tumors by Specific Type and Patient Age ADENO· CARCINOMA

SARCOMA

0 3 6 23

0 1 1

6 9 7 8

25

22 7 ~

86

J

33

CARCINOID

LYMPHOMA

0 0 7 24 20 29 9

2 0 0 1

2 2

~

1 Q

89

8

standing Crohn's disease is a precursor for malignancy of the small intestine. 12 Some electron microscopy studies have been done to see if this could be proven. 3 Multiple polyposis, of course, is a risk factor in the development of carcinoma of the colon; however, cases have been reported,5. 11 including one in our series, in which polyps developed in other areas of the gastrointestinal tract in patients having polyposis coli, and these may be associated with malignant growths in the small bowel. A black woman lived for over 20 years with polyposis of the colon, having had a total colectomy. Later she developed polyps in the stomach and duodenum, which were removed and showed dysplasia but no malignant changes. She then developed polypoid lesions in the ileum, which developed into adenocarcinoma of the ileum before her death.

SIGNS AND SYMPTOMS OF SMALL-BOWEL MALIGNANCY The signs and symptoms of small-bowel malignancy are very vague and often are present for a number of months or even 1 to 2 years before the diagnosis is made. These may be divided into chronic and acute signs and symptoms (Table 6). The chronic signs and symptoms may include melena, anemia, malaise, and fatigue. These are frequently present. Often the stomach and the colon are studied thoroughly for the cause of anemia but the small bowel is overlooked. Whenever anemia is present without known cause, and there is blood in the stool, a small-bowel barium followthrough study must be done to determine the possibility of malignancy in Table

6. Chronic and Acute Signs and Symptoms of Small-Bowel Malignancies CHRONIC SIGNS AND SYMPTOMS

Melena, anemia Vague pain Obstruction Malaise Weight loss Diarrhea Jaundice Mass

ACUTE SIGNS AND SYMPTOMS

Hemorrhage Pain Obstruction Perforation

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this area. Pain may be very vague or it may be acute. Obstruction is quite frequently chronic, but this also may become acute. Rarely, a mass is felt in the abdomen. Weight loss is another symptom that is quite frequently present, along with malaise. Epigastric or abdominal distress is quite frequent, and diarrhea may be present, as may alternating diarrhea and constipation. Jaundice can be present in malignancies of the duodenum and ampulla of Vater; it is most likely present in ampulla of Vater lesions and may wane in intensity because of the intermittent obstruction. Acute symptoms frequently bring the patient to surgery, where the diagnosis is made. Hemorrhage or severe bleeding from the gastrointestinal tract may occur, as may acute obstruction and perforation. Perforations were noted in our series in two adenocarcinomas of the small bowel and also in a lymphoma of the ileum. Barium follow-through studies are the only certain method of diagnosing small-bowel tumors. Endoscopy may be of value in diagnosing duodenal lesions. Computed tomography (CT) has not proven to be of much value unless the mass becomes quite large, extending beyond the bowel wall. In cases of carcinoid tumors, arteriograms can be of value. A selective arteriogram, in which the dye is injected directly into the superior mesenteric artery, frequently shows carcinoid tumors well. It is also helpful in determining whether the carcinoid lesions are solitary or multiple. Metastatic lesions may be the first evidence to suggest a primary small-bowel tumor. This is especially true with carcinoids; often biopsies of liver metastases or, in one case, bone metastases, gave the diagnosis of a carcinoid tumor. The primary lesion of the small intestine was found with follow-through barium studies. METASTATIC LESIONS Metastatic lesions should be mentioned as malignant lesions of the small bowel. They are not included in this series because they are not primary lesions, but it behooves one to be aware that metastases may occur in the area of the small bowel, causing the symptoms noted above. Such metastatic lesions have been known to occur in cases of melanoma, carcinoma of the cervix, and lung, breast, and soft-tissue tumors. Often these metastases to the small bowel cause bleeding and obstruction. In one case they caused an intussusception and in another an obstruction due to blockage of the lumen by the tumor itself. In a patient with a known history of malignancy, obstructive symptoms, or bleeding from the gastrointestinal tract, a metastatic lesion must be considered. Although the signs and symptoms tabulated above may be present in anyone of the categories of small-bowel malignancies, there are certain ones that stand out or are more common with specific histologic types. In the case of lymphoma, the main symptoms that occur are obstruction, chronic obstruction, malaise, and possibly bleeding. In sarcomas, it was very interesting that bleeding was the main symptom, along with pain. 1, 6, 13 Obstruction was not common in this category, mainly because the tumor more often grows out from the lumen of the bowel instead of into it as a polypoid lesion. The tumor frequently necroses in the center, causing the bleeding. Carcinoid tumors

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may often cause vague abdominal distress with obstructive symptoms. Frequently, diarrhea is a common symptom with these tUmors along with possible flushing and other characteristics of the carcinoid syndrome. When a carcinoid lesion is suspected, urinary 5-HIAA determination should be made. Adenocarcinomas frequently cause pain and obstruction, which may be intermittent. The obstruction in these cases is usually due to polypoid lesions that grow into the lumen or napkin-ring lesions that cut off the lumen. Chronic anemia is also quite often present.

TREATMENT AND PROGNOSIS The treatment of small bowel tumors is primarily surgical. The preoperative preparation of these patients depends a great deal on the presence of severe bleeding or obstruction. If obstruction is present, one must be very careful about any gastrointestinal preparation such as cathartics. In the presence of either pain or obstruction, the operation may become an emergency. Cleansing of the bowel is not as important for these lesions as for colon lesions; however, it is good to have the colon well prepared if at all possible. The treatment of choice is segmental resection of the small bowel. As much of the ileum as possible should be preserved at the time of resection to prevent postoperative diarrhea and the loss of vitamin B12 absorption. Ileal lesions may require a right hemicolectomy. All regional lymph nodes are resected with the primary lesion. If the lesion is in the third or fourth portion of the duodenum, a segmental resection is frequently possible. However, if the lesion is of significant size and has extended into the pancreas, a pancreatoduodenectomy or Whipple procedure may be indicated. Tumors arising in the third and fourth portions of the duodenum may ulcerate into the superior mesenteric vessels, causing hemorrhage. The vessels also may cause difficulty when proximal jejunal lesions near the ligament of Treitz are rejected. The prognosis for small-bowel tumors, as in other areas of the gastrointestinal tract, depends on the extension of tumors through the bowel wall and the number of lymph nodes positive for metastasis. Perforation of a lesion usually causes peritoneal seeding. In cases of nonresectable lesions, a sidetracking procedure should be performed to establish continuity of the lumen of the bowel to permit oral nutrition. For lymphomatous lesions, chemotherapy frequently may be used as an adjunct to surgery or, at certain times, in place of surgery. Radiation therapy may be indicated also for these lesions. Adjunctive therapy for adenocarcinoma and sarcoma lesions is of little value at this time. Liver embolization or infusion may be useful in controlling carcinoid syndrome symptoms due to liver metastases. Aggressive surgical attack upon solitary metastatic lesions of the liver, lung, or other locations should be carried out. Pre- and postoperative intubation for decompression usually can be accomplished by using a sump-type nasogastric tube. Rarely is it necessary to use a long intestinal tube, which is very difficult to place properly. The 5-year survival rates for the various categories of small-bowel lesions in this series do not differ greatly from those that have been reported

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Table 7. Survival Rates for Small-Bowel Turrwrs by Specific Types MORTALITIES AFTER 5 YEARS

MORTALITIES AFTER 10 YEARS

MORTALITIES

5-YEAR

HISTOLOGY

MORTALITIES AFTER 3 YEARS

AFTER 20 YEARS

SURVIVAL RATE

Lymphoma Sarcoma Carcinoid Adenocarcinoma

<3 27 44 69

1 4 32 10

1 1 12 8

3 1 1 0

62.5% 18.2% 50.5% 20.6%

in the literature. 2 , 4, 7, 8, 9, 10 Table 7 tabulates the 5-year survival rates for the various categories of tumors: lymphomas, approximately 62.5 per cent; sarcomas, 18.2 per cent; and carcinoid tumors, 50.5 per cent, with patients in the last group quite frequently surviving for long periods of time with a considerable volume of disease, often in the liver and other areas of the body, including the bone. For adenocarcinoma tumors, our 5-year survival rate was 20.6 per cent. A large number of our patients in all of these categories, when they succumbed to their disease, did so in the first 3 years after diagnosis. The low survival rate for small-intestinal malignant tumors is most likely influenced by the long prediagnosis period, allowing for the increased stage of disease when diagnosed.

SUMMARY The four main histologic categories of malignant small intestine tumors are (1) adenocarcinoma, (2) sarcoma, (3) carcinoid, and (4) lymphoma. Signs and symptoms may be chronic or acute and include bleeding, obstruction, pain, and weight loss. When chronic, the symptoms are so vague that early diagnosis is difficult. Often the diagnosis is made only at the time of surgery. Treatment is segmental resection of intestine with adequate margin of the tumor and resection of the regional lymph nodes. Prognosis is evaluated by tumor extension through the bowel wall and lymph node metastasis. The 5-year survival rates are low except for carcinoid and lymphomatous lesions.

REFERENCES 1. Akwari, O. E., Dozois, R. R., Weiland, L. H" et al.: Leiomyosarcoma of the small and large bowel. Cancer, 42:1375-1384, 1978. 2. Arthaud, J. B., and Guinee, V. F.: Jejunal and ileal adenocarcinoma. Am. J. Gastroenterol., 72:638-646, 1979. 3. Balazs, M.: Electron microscopic study of adenocarcinoma of the small bowel associated with Crohn's disease. Exp. Pathol., 23:53-62, 1983. 4. Barclay, T. H. c., and Schapira, D. V.: Malignant tumors of the small intestine, Cancer, 51:878-881, 1983. 5. Bussey, H. J. R., Veale, A. M. 0., and Morson, B. C,: Genetics of gastrointestinal polyposis. Gastroenterology, 74:1325-1330, 1978. 6. Chiotasso, P. J. P., and Fazio, V. W.: Prognostic factors of 28 leiomyosarcomas of the small intestine. Surg. Gynecol. Obstet., 155:197-202, 1982.

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7. Colcock, B. P., and Braasch, J. W.: Surgery of the Small Intestine in the Adult. Philadelphia, W. B. Saunders Company, 1968, pp. 66--88. 8. Coutsoftides, T., and Shibata, H. R.: Primary malignant tumors of the small intestine. Dis. Colon Rectum, 22:24-26, 1979. 9. Garvin, P. J., Herrmann, V., Kaminski, D. L., et al.: Benign and malignant tumors of the small intestine. Curro Prabl. Cancer, 3:1-46, 1979. 10. Goel, I. P., Didolkar, M. S., and Elias, E. G.: Primary malignant tumors of the small intestine. Surg. Gynecol. Obstet., 143:717-719, 1976. 11. Jarvinen, H., Nyberg, M., and Peltokallio, P.: Upper gastrointestinal tract polyps in familial adenomatosis coli. Gut, 24:333-339, 1983. 12. Weedon, D.D., Shorter, R. G., Iistrup, D. M., et al.: Crohn's disease and cancer. N. Engl. J. Med., 289:1099-1102, 1973. 13. Wood, David, A.: Tumors of the Intestines: Atlas of Tumor Pathology, Section VI-Fascicle 22. Washington, National Academy of Sciences, National Research Council, 1967. Department of Surgery M.D. Anderson Hospital and Tumor Institute Texas Medical Center 6723 Bertner Avenue Houston, Texas 77030