Primary Tumors of the Small Bowel Terry A. Treadwell, MD, Temple, Texas Raleigh Ft. White, III, MD, Temple, Texas
Primary tumors of the small bowel are uncommon lesions, comprising less than 6 per cent of all gastrointestinal neoplasms [I] and less than 2 per cent of all malignant gastrointestinal tumors [2,3]. This rate seems surprisingly low when the length and surface area of the small bowel are considered and compared with those of the remainder of the gastrointestinal tract. These tumors are uncommon possibly because of some inherent protective resistance in the small bowel [4,5]. Tumors of the small bowel may be difficult to diagnose because of their infrequent occurrence and protean manifestations. The diagnosis of a malignant lesion is usually delayed until the disease is widespread and the patient’s prognosis is often dismal regardless of the mode of therapy. Our experience with 140 primary tumors of the small bowel is reviewed to encourage awareness and earlier diagnosis of these lesions. Material and Methods A twenty-five year survey of the clinical records at Scott and White Memorial Hospital and Temple’s Veterans Administration Center from 1946 to 1971 revealed 140 primary tumors of the small bowel in 133 patients. Fifty-two lesions were benign (Figure 1) and eightyeight were malignant (Figure 2). Thirty periampullary tumors diagnosed during the period of the survey were excluded from this study. The youngest patient in the series was two months old and the oldest was eighty years. At the time of diagnosis, the average age of the patients with benign tumors was 56.9 years and of those with malignant tumors, 55.9 years. Six of the 140 lesions (4.3 per cent) were in children fourteen years of age or younger (three of the eighty-eight malignant lesions [3.4 per cent] and three of the fifty-two benign lesions [5.8 per cent]).
From the Department of Surgery, Scott and White Clinic, Temple, Texas. Reprint requests should be addressed to Terry A. Treadwell. MD, Scott and White Memorial Hospital. Temple, Texas 76501. Presented at the Twenty-Seventh Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 21-24, 1975.
Volume 130, December 1975
The sex distribution of the 133 patients was almost equal, with sixty-six males and sixty-seven females, but the incidence of malignant lesions was slightly higher in the males in a ratio of 1.3:1. Symptoms were present for more than six months before a diagnosis was made in 63.3 per cent of patients with benign tumors and 47.6 per cent of patients with malignant lesions. (Table I.) The presenting complaints varied with the type of tumor. (Figure 3.) Bleeding was the most common presenting symptom in patients with benign lesions (52.9 per cent), but obstructive symptoms predominated in patients with malignant lesions (50.6 per cent). Symptoms of obstruction were the initial complaints in only 4.8 per cent of patients with benign lesions. Only one patient with a malignant tumor had a clinical picture of obstructive jaundice. Although 21.6 per cent of the benign lesions were incidental findings at surgery, only 3.6 per cent of the malignant tumors were incidental findings. One carcinoid tumor was diagnosed preoperatively because of symptoms typical of the carcinoid syndrome. Most of the benign lesions were located in the proximal small bowel (duodenum, 34.6 per cent; ileum, 11.5 per cent), but most of the malignant lesions were located distally (duodenum, 17 per cent; ileum, 61.4 per cent). (Figure 4.) Twenty-five per cent of the benign lesions involved multiple areas of the small bowel. Carcinoid tumor was the only malignant lesion involving multiple areas of the small bowel, occurring in three of nineteen patients. The adenomas and polyps were the only benign lesions that were clustered in a particular location (eight of nine adenomas and five of eight polyps were located in the duodenum). (Figure 5.) Hemangiomas tended to be multiple, involving both the jejunum and ileum in twelve of twenty-two patients. Malignant lesions were frequently -found in specific locations in the small bowel. (Figure 6.) Sarcomas and carcinoids occurred more often in the ileocecal area. Adenocarcinomas were clustered in the duodenum (nine of twenty-seven) and ileum (twelve of twenty-seven). Thirty-nine of the 133 patients (29.3 per cent) had a palpable mass (36.8 per cent of the malignant tumors and 14 per cent of the benign tumors). Radiographs pointed to the small bowel as the site of the disease in 43.7 per cent of the patients with malignant lesions and
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Figure
TABLE
10
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20
25
30
25
Figure 2. Malignant tumors.
I. Benign tumors.
I Duration
of Symptoms Lesions Malignant
Duration
Number
1 year Total
9 8 27 18 22 84
Per Cent 10.7 95 32.2 21.4 26.2
Benign Number 1 2 15 7 24 49
Per Cent 2 4.1 30.6 14.3 49
32 per cent of those with benign lesions. The correct diagnosis was made preoperatively in 41 per cent of the patients with benign tumors, but despite numerous examinations only 26.5 per cent of those with malignant tumors had a correct preoperative diagnosis.
Results The method of treatment was based on the type of small bowel tumor. Excision was curative in all but three of the patients with benign lesions: two patients with multiple hemangiomas and one with the Peutz-Jeghers syndrome continued to have symptoms related to their widespread disease. The prognosis was dismal for the eighty-eight patients with malignant lesions regardless of the method of treatment used. The average period of survival after diagnosis was 5.03 years. The average survival for patients with adenocarcinoma was 3.6 years; with lymphoma, 1.3 years; with carcinoid, 6.8 years; and with leiomyosarcoma, 8.3 years. (Figure 7.) Potentially curative surgical procedures were possible in only 51.1 per cent of the patients with malignant tumors: the lowest number of potentially curative procedures was performed in patients with adenocarcinoma (39.3 per cent). (Table II.)
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Adjunctive radiation therapy and chemotherapy were used during the later years of the study; 46.8 per cent of the patients with lymphoma, leiomyosarcoma, and adenocarcinoma received radiation therapy, chemotherapy, or a combination of both. (Table III.) Patients with lymphoma who lived more than one week postoperatively received radiation therapy (70.8 per cent). Regardless of the method of treatment, the average five year survival rate was only 30.7 per cent. (Table IV.) Although the survival rate was somewhat lower for patients with lymphoma (25 per cent) and adenocarcinoma (25 per cent), 47.4 per cent of patients with carcinoid tumors survived five years and 31.6 per cent survived ten years. Thirty per cent of the patients with leiomyosarcoma survived five years. The location of the lesion influenced the survival rate; 37 per cent of patients with ileal lesions but only 6.7 per cent of patients with duodenal lesions lived five years. (Table V.) Fifty-seven of the 133 patients (42.9 per cent) had a second primary neoplasm determined from the case history or detected during the follow-up period. Comments Primary tumors of the small bowel are usually discovered in patients in the sixth and seventh decades 131. R ecently, the average age of patients at the time of diagnosis was 62.2 years for those with benign lesions [6] and from fifty-three years [7] to 56.8 years [6] for those with .malignant lesions. These findings correlate with the age of patients at the time of diagnosis in our series (average age of patients with benign lesions was 56.9 years and for those with malignant lesions, 55.9 years). Our series contained an unusual number of lesions in children under fourteen years of age (6 of 140 lesions or 4.3 per cent). In the survey by
TheAmorkan
Journal of Surgery
Tumors of Small Bowel
60% 1
cl
MALIGNANT
MALIGNANT
I
BENIGN
BENIGN
DUODENUM
ILEUM
JEJUNUM
MULTIPLE
UNKNOWN
0DUODENUM Figure 4. Location of tumor.
Ffgure 3. Presentlng symptoms.
1
15
: :
IO
:
0
q JEJUNUM q ILEUM n JEJUNUM
(L ILEUM
Figure 5. Location of benign lesions.
Figure 6. Specific location of malignant lesions of small bowel. TABLE II
Surgical Treatment Cure
Tumor
o
.
.
.
.
DUODENUM
q JEJUNUM n ILEUM
;
.
.
-
-
,h
YEARS
Lymphoma Leiomyosarcoma Adenocarcinoma Carcinoid AngiosarFoma Fibroneurosarcoma Melanoma Total
Patients
Number
24 10 28 19 4 2 1 88
11 5 11 12 4 1 1 45
Palliation Per Cent
45.8 50 39.3 63.2 100 50 100 51.1
Number
Cent
13 5 17 7
54.2 50 60.7 36.8
1
Per
50
43
Flgure 7. Average survival with malignant lesions.
Rivers, Silverstine, and Tope [S] of 1,399 benign lesions of the small bowel, 122 (5.9 per cent) were in patients less than ten years old. The delay in the diagnosis of a primary small bowel tumor is often related to the vague and nonspecific symptoms that these tumors produce. In 1961 Rochlin and Longmire [9] reported that 40 per cent of their patients had symptoms for at least ten months before the diagnosis was made. In a more recent study, 60 per cent of patients with
Volume
130.
December
1975
malignant tumors and 50 per cent of patients with benign tumors had symptoms for more than six months [6]. In our series, 47.6 per cent of patients with malignant tumors and 63.3 per cent of patients with benign tumors had symptoms for more than six months. The most consistent symptoms produced by small bowel tumors are poorly localized abdominal pain, symptoms of recurrent obstruction, weight loss, and weakness secondary to anemia [3,10,11].
751
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TABLE
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III
Radiation
and Chemotherapy Lvmphoma
Leiomvosarcoma
(24) Radiation (alone) Chemotherapy (alone) Both forms of therapy Total
TABLE
IV
Malignant
-
14 (58.3%)
1 (10%)
3 (12.5%) 17 (70.8%)
1 (10%) 2 (20%)
Lesions (SB Patients) Survival
Tumor
Patients
Lymphoma Leiomyosarcoma Adenocarcinoma Carcinoid Angiosarcoma Fibroneurosarcoma Melanoma Total
TABLE
V
24 10 28 19 4 2 1 88
Location
Five Years
Ten Years
6 3 7 9 1 0
2 2 4 6 1 0
(25%) (30%) (25%) (47.4%) (25%)
1 (100%) 27 (30.7%)
of Lesion Correlated
(8.3%) (20%) (14.3%) (31.6%) (25%)
1 (100%) 16 (18.2%)
with
Survival
Survival Location Duodenum Jejunum Ileum
Number 15 19 54
Five Years
Ten Years
1 (6.7%) 6 (31.6%) 20 (37%)
0 2 (10.5%) 14 (25.9%)
Because benign small bowel tumors are usually asymptomatic, 60 to 75 per cent of the symptomatic tumors are malignant [3]. When benign lesions cause symptoms, obstruction, pain, and bleeding are the most common findings. In a col: lected series of 1,047 benign tumors, 56 per cent of the patients had symptoms of obstruction, 38 per cent had pain, and 30 per cent had bleeding [12]. In our series of patients with benign tumors, bleeding occurred in 52.9 per cent, obstruction in 9.8 per cent, and pain in 15.7 per cent. This high incidence of bleeding as a presenting symptom is due to the large number of hemangiomas (42.3 per cent of the fifty-two benign tumors). In the collected series, only 12.9 per cent of the benign lesions were hemangiomas. In a collected series of 808 malignant lesions, the most frequent presenting symptoms were weight loss (39 per cent), obstruction (30 per cent), bleeding (23 per cent), and pain (20 per cent) [ 71. In the present study, 50.6 per cent of the patients with malignant lesions had symptoms of obstruction when they were first observed, 22.9 per cent had pain, and 20.7 per cent had bleeding.
752
iio)
Adenocarcinoma
Total
(62)
(28) 7 2 1 10
(25%) (7.1%) (3.6%) (35.7%)
22 2 2:
(46.8%)
O’Brien [3] reports that benign tumors of the small bowel increase in frequency as the ileocecal area is approached. Wilson et al [12] confirmed this observation in their collective review. However, in our series, 34.6 per cent of the benign lesions were located in the duodenum and only 11.5 per cent were in the ileum. The preponderance of malignant lesions in the distal small bowel has been substantiated by a large collected series in which most of the malignant tumors were in the ileum (48.8 per cent) as compared with 22.6 per cent in the duodenum and 28.5 per cent in the jejunum [7]. In our series, 61.4 per cent of the malignant lesions were found in the ileum and 17 per cent in the duodenum. The lack of physical findings and the inaccessibility of the small bowel to clinical investigation cause delays in diagnosis. The presence or absence of a palpable mass varies considerably, occurring in 7 per cent [2] to 63 per cent [9] of patients, but a mass is more likely to accompany a malignant lesion. In our series, a palpable mass was found in 29.3 per cent of the patients, 14 per cent with benign tumors and 36.8 per cent with malignant tumors. Silberman, Crichlow, and Caplan [6] reported a palpable mass in 3 per cent of patients with benign lesions and 22 per cent of patients with malignant tumors. Patients with leiomyosarcoma were more likely to have a mass (72 per cent) than were patients with lymphoma (66 per cent), carcinoma (36 per cent), or carcinoid (15 per cent)
[W.
The most reliable radiologic study for diagnosing small bowel tumors is an upper gastrointestinal series with small bowel follow-through. This study has provided a positive diagnosis for 63 per cent of the small bowel lesions in two series [6,10]. The probability of detecting a tumor is better if it is located in the proximal portion of the small bowel. Vuori [IO] reported a positive diagnosis for 70 per cent of duodenal lesions compared with a positive diagnosis for 53 per cent of jejunal and ileal lesions. The types of tumors encountered in the small bowel are similar to those found elsewhere in the
The American Journal of Surgery
Tumors of Small Bowel
gastrointestinal tract. In a collected series of 1,721 benign small bowel tumors, the most common types of tumors were leiomyoma (22.1 per cent), lipoma (17.5 per cent), adenoma (14.2 per cent), polyp (14.2 per cent), and bemangioma (12.3 per cent) [12]. In our series, the most common types of benign tumors were hemangioma (42.3 per cent), adenoma (17.3 per cent), polyp (15.4 per cent), and leiomyoma (15.4 per cent). Our series included only one lipoma. Other benign tumors of the small bowel are uncommon [3,8]. In a collected series of 2,144 malignant small bowel tumors, the most frequently encountered tumors were adenocarcinoma (50 per cent), carcinoid (39 per cent), and leiomyosarcoma (11 per cent) [7]. Malignant lymphoma was reported in 19 per cent of patients with malignant small bowel tumors in another large study [13]. The most common malignant tumors in our series were adenocarcinoma (30.7 per cent), lymphoma (27.3 per cent), carcinoid (21.6 per cent), and leiomyosarcoma (11.4 per cent). Other malignant lesions,of the small bowel such as angiosarcoma, neurofibrosarcoma, and melanoma, rarely occur [3].
Survival
The low five year survival rate reported in most series of malignant small bowel tumors seems universal. The delay in making the diagnosis results in widespread disease at the time of surgical treatment. Ebert and Zuidema [2] reported that 69 per cent of their patients had metastases at the time of surgical intervention. Curative procedures were attempted in 51.1 per cent of the patients in our series. These procedures were possible in only 39.3 per cent of the patients with adenocarcinoma, because many of these tumors (nine of twenty-seven) were located in the duodenum; the lesions were infiltrating and locally metastasizing by nature and the closeness of vital structures in this area made a “cancer operation” impossible. Rochlin and Longmire [?I reported that 40 per cent of their patients had curative surgery; however, only two of seven duodenal lesions could be resected. Curative procedures were attempted in 78 per cent of Silberman, Crichlow, and Caplan’s patients 161, but only 28 per cent of the malignant lesions in the duodenum could be removed. The inability to remove duodenal lesions is reflected in the five year survival rate when the location of the tumors is considered. In our series, 37 per cent of patients with malignant lesions in the
Volume 130, December 1975
ileum but only 6.7 per cent of patients with malignant lesions in the duodenum lived five years. The reported five year survival rates for patients with duodenal lesions range from 0 [6] to 30 per cent [IO]. From 29 [IO] to 33 per cent [14] of patients with ileal lesions have survived five years. Pancreaticoduodenectomy is the procedure of choice for potentially curable duodenal lesions [6,7,9]. For patients with malignant lesions in other locations, wide resection and lymph node dissection should be attempted if a cure seems possible [IO]. When curative resection is impossible, palliative resection or bypass procedures are indicated [9]. A patient’s prognosis after diagnosis of any malignant lesion of the small bowel is guarded despite a combination of therapeutic maneuvers. In our series, the average five year survival rate for all malignant tumors was 30.7 per cent. The five year survival rate for patients with various types of tumors ‘ranged from a low of 25 per cent in patients with malignant lymphoma and adenocarcinoma to a high of 47.4 per cent for those with carcinoid tumors. These survival rates are comparable to those reported in other studies [3,10,13]. In patients with tumors of the small bowel, radiotherapy and chemotherapy are of questionable benefit. Most authorities agree that chemotherapy is not useful [7,9,15,16]. Radiotherapy has been considered unsuccessful when used for all types of tumor except lymphoma. Weaver and Batsakis [17] have questioned the benefit obtained from the use of radiotherapy in patients with gastrointestinal lymphomas, except in those with incompletely removed lesions. It is our clinical impression that patients with gastrointestinal lymphoma are provided a prolonged disease-free period and some palliation with this form of treatment. This view is supported by others [3,7].
Etiology
The cause of primary small bowel tumors eludes the investigators. Some benign lesions, such as ectopic pancreatic adenomas in the duodenum, may result from a congenital developmental defect. Heredity plays a role in some of these lesions. The Peutz-Jeghers syndrome is inherited as a Mendelian dominant trait. The Rendu-Osler-Weber syndrome (multiple hereditary telangiectasis) is thought to be inherited as a Mendelian dominant trait with variable penetrance. For the most part, however, the cause of benign small bowel tumors is unknown.
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Theories have been advanced concerning the cause of malignant small bowel tumors. Bone and Wright [18] offer a purely mechanical theory by noting that small bowel mucosal cells are proliferating so rapidly that growth of a clone of malignant cells is inhibited. The fluid nature and the alkalinity of the small intestinal contents are thought to protect the small bowel to some degree [4,8]. The rapid transit time of intestinal contents through the small bowel may decrease potential carcinogenic contact with the mucosa [4]. The amount of potential carcinogen that can be formed from bile and other products by bacterial metabolism is reduced because of the “less sophisticated” bacterial population of the small bowel [4]. Enzymes that are known to detoxify certain potential carcinogens are reported to be more abundant in the small bowel [19]. It is the clinical impression of Renshaw and McCrae [5] that patients who received an extract of whole mucosa of the small intestine for treatment of rheumatic diseases had fewer carcinomas develop in all parts of the body than did patients not receiving the extract. The growth of metastatic lesions was inhibited in patients who had colonic cancer with known metastases when treatment was begun. This theory suggests that some humoral factor may be present in the small bowel and that this factor may act as a protective mechanism. High concentrations of IgA that have been found in the small bowel [7] may help explain the observations of Renshaw and McCrae and may be the basis for the paucity of malignant lesions of the small bowel. Lowenfels [4] found that an inordinate number of primary and metastatic malignant lesions of the small bowel have been reported in patients whose immunologic status was being suppressed for other reasons [4]. Patients who have one small bowel neoplasm are more likely to have a second neoplasm. The reported incidence of a second primary neoplasm ranges from 17.7 [14] to 74 per cent [20]. Of the 133 patients in our series, fifty-seven (42.9 per cent) had a second neoplasm as determined either by history or during the follow-up period. This incidence is much higher than the 0.33 per cent incidence of second neoplasms in the general population [4]. This observation further implicates some basic immunologic problem in patients in whom primary small bowel tumors develop. Summary Primary tumors of the small bowel are uncommon, representing less than 6 per cent of all gastrointestinal tumors and less than 2 per cent of all
754
malignant gastrointestinal tumors. This report concerns a twenty-five year survey of our clinical records from 1946 to 1971 which revealed 140 primary small bowel tumors, excluding periampullary tumors. Fifty-two of the neoplasms (37 per cent) were benign; eighty-eight (63 per cent) were malignant and included twenty-eight adenocarcinomas (31.8 per cent), twenty-four lymphosarcomas (27.3 per cent), nineteen carcinoids (21.6 per cent), and ten leiomyosarcomas (11.4 per cent), The average age at the time of diagnosis was 56.9 years for patients with benign tumors and 55.9 years for those with malignant tumors. The illusive and obscure nature of small bowel tumors is illustrated by the fact that 63.3 per cent of patients with benign lesions and 47.6 per cent of those with malignant lesions had symptoms for more than six months before the diagnosis was made. Bleeding was the most common presenting complaint in patients with benign neoplasms (52.9 per cent) whereas patients with malignant lesions more often had symptoms of obstruction (50.6 per cent). Most of the benign lesions were located proximally in the small bowel (duodenum, 34.6 per cent; ileum, 11.5 per cent), and most of the malignant lesions were located distally (duodenum, 17.0 per cent; ileum, 61.4 per cent). Treatment of patients with malignant lesions was radical excision whenever possible. Adjunctive radiation therapy was used for those with lymphoma. A second benign or malignant tumor occurred in 42.9 per cent of the patients with primary small bowel tumors. The average period of survival after diagnosis of a malignant small bowel tumor was 5.03 years: for patients with adenocarcinoma, 3.6 years; lympho6.8 years; and sarcoma, 1.3 years; carcinoid, leiomyosarcoma, 8.3 years. References 1. Broders AC Jr, Hightower NC, Hunt WH III, Stinson JC. While RR, Laurens HF: Primary neoplasms of the small bowel. Arch Surg 79: 753, 1959. 2. Ebert PA, Zuidema GD: Primary tumors of the small intestine. Arch Surg 91: 452, 1965. 3. O’Brien TF: Primary tumors and vascular malformations, p 959. Gastrointestinal Disease (Sleisenger MH. Fordtran JS, ed). Philadelphia, WB Saunders, 1973. Lowenfels AB: Why are small bowel tumours so rare? Lancet 1: 24, 1973. Renshaw A. McCrae JS: Why are small bowel tumours so rare? Lancet 1: 425, 1973. Silberman H, Crichlow RW, Caplan HS: Neoplasms of the small bowel. Ann Surg 180: 257. 1974. Wilson JM. Melvin DB, Gray GF, Thorbjamarson B: Primary malignancies of the small bowel. Ann Surg 180: 175. 1974. 8. River L, Silverstine J, Tope JW: Benign neoplasms of the
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small bowel. Int Absh Surg 102: 1, 1956. 9. Rochlin DB, Longmire WP Jr: Primary tumors of the small bowel. Surgery 50: 586, 1961. 10. Vuori JVA: Primary malignant tumors of the small intestine. Acta Chir Stand 137: 555, 1971. 11. Cohen A. McNeil1 D, Terz JJ, Lawrence W Jr: Neoplasms of the small intestine. AmJDigDis 16: 815, 1971. 12. Wilson JM, Melvin DB, Gray G, Thorbjarnarson B: Benign small bowel tumor. Ann Surg 181: 247, 1975. 13. Paztaluman RJ, Mayo CW, Docherty MB: Primary malignant tumors of the small intestine. Am J Surg 108: 13, 1964. 14. Reyes EL, Talley RW: Primary malignant tumors of the small intestine. Am J Gastroenterol54: 30, 1970. 15. Griffin WO Jr: Benign and malignant small intestinal tumors: Mechel’s diverticulum, p 901. Textbook of Surgery (Sabiston DC Jr, ed). Philadelphia, WB Saunders, 1972. 16. Storer EH: Small intestlne, p 1095. Principles of Surgery (Schwartz SI, ed). New York, McGraw-Hill, 1974. 17. Weaver DK. Batsakis JG: Primary lymphomas of the small intestine. Am J Gastroenterol42: 620, 1964. 18. Bone G, Wright NA: The rarity of small bowel tumours: an al-, ternative hypothesis. Lancet 1: 618, 1973. 19. Wattenberg LW: Carcinogen-detoxifying mechanisms in the gastrointestinal tract. Gastroenterology 51: 932, 1966. 20. Alexander JW, Altemeir WA: Associated neoplasm of the small intestine with other neoplestic growths. Ann Surg 167: 958, 1968.
VOllmw130. December 1975
Discussion Raymond C. Read (Little Rock, AR): The tumors that the authors report are symptomatic compared with autopsy series. They have a higher incidence of bleeding in the benign tumors. The main interest of this paper is to draw our attention again to why the small bowel, all twenty-two feet of it, is so immune to cancer, not only epidermal cancer but also mesodermal cancer. We all know that cancer of the stomach stops sharply at the duodenum. Why is it that cancer cells do not enjoy the milieu in the small intestine? Studies in the future will analyze patients who do have immune mechanisms, weeding out malignant transformations. Terry A. Treadwell (closing): The high incidence of bleeding in our series of benign tumors is directly related to the number of hemangiomas. We had twenty-two hemangiomas. In a series of more than 1,000 cases of benign tumor (121, the incidence of hemangioma was only 12 per cent. For this reason I feel that our incidence of bleeding as a presenting symptom in patients with benign tumors was spuriously high.
755
Primary tumors of the small bowel are uncommon lesions, comprising less than 6 per cent of all gastrointestinal neoplasms [I] and less than 2 per cent of all malignant gastrointestinal tumors [2,3]. This rate seems surprisingly low when the length and surface area of the small bowel are considered and compared with those of the remainder of the gastrointestinal tract. These tumors are uncommon possibly because of some inherent protective resistance in the small bowel [4,5]. Tumors of the small bowel may be difficult to diagnose because of their infrequent occurrence and protean manifestations. The diagnosis of a malignant lesion is usually delayed until the disease is widespread and the patient’s prognosis is often dismal regardless of the mode of therapy. Our experience with 140 primary tumors of the small bowel is reviewed to encourage awareness and earlier diagnosis of these lesions. Material and Methods A twenty-five year survey of the clinical records at Scott and White Memorial Hospital and Temple’s Veterans Administration Center from 1946 to 1971 revealed 140 primary tumors of the small bowel in 133 patients. Fifty-two lesions were benign (Figure 1) and eightyeight were malignant (Figure 2). Thirty periampullary tumors diagnosed during the period of the survey were excluded from this study. The youngest patient in the series was two months old and the oldest was eighty years. At the time of diagnosis, the average age of the patients with benign tumors was 56.9 years and of those with malignant tumors, 55.9 years. Six of the 140 lesions (4.3 per cent) were in children fourteen years of age or younger (three of the eighty-eight malignant lesions [3.4 per cent] and three of the fifty-two benign lesions [5.8 per cent]).
From the Department of Surgery, Scott and White Clinic, Temple, Texas. Reprint requests should be addressed to Terry A. Treadwell. MD, Scott and White Memorial Hospital. Temple, Texas 76501. Presented at the Twenty-Seventh Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 21-24, 1975.
Volume 130, December 1975
The sex distribution of the 133 patients was almost equal, with sixty-six males and sixty-seven females, but the incidence of malignant lesions was slightly higher in the males in a ratio of 1.3:1. Symptoms were present for more than six months before a diagnosis was made in 63.3 per cent of patients with benign tumors and 47.6 per cent of patients with malignant lesions. (Table I.) The presenting complaints varied with the type of tumor. (Figure 3.) Bleeding was the most common presenting symptom in patients with benign lesions (52.9 per cent), but obstructive symptoms predominated in patients with malignant lesions (50.6 per cent). Symptoms of obstruction were the initial complaints in only 4.8 per cent of patients with benign lesions. Only one patient with a malignant tumor had a clinical picture of obstructive jaundice. Although 21.6 per cent of the benign lesions were incidental findings at surgery, only 3.6 per cent of the malignant tumors were incidental findings. One carcinoid tumor was diagnosed preoperatively because of symptoms typical of the carcinoid syndrome. Most of the benign lesions were located in the proximal small bowel (duodenum, 34.6 per cent; ileum, 11.5 per cent), but most of the malignant lesions were located distally (duodenum, 17 per cent; ileum, 61.4 per cent). (Figure 4.) Twenty-five per cent of the benign lesions involved multiple areas of the small bowel. Carcinoid tumor was the only malignant lesion involving multiple areas of the small bowel, occurring in three of nineteen patients. The adenomas and polyps were the only benign lesions that were clustered in a particular location (eight of nine adenomas and five of eight polyps were located in the duodenum). (Figure 5.) Hemangiomas tended to be multiple, involving both the jejunum and ileum in twelve of twenty-two patients. Malignant lesions were frequently -found in specific locations in the small bowel. (Figure 6.) Sarcomas and carcinoids occurred more often in the ileocecal area. Adenocarcinomas were clustered in the duodenum (nine of twenty-seven) and ileum (twelve of twenty-seven). Thirty-nine of the 133 patients (29.3 per cent) had a palpable mass (36.8 per cent of the malignant tumors and 14 per cent of the benign tumors). Radiographs pointed to the small bowel as the site of the disease in 43.7 per cent of the patients with malignant lesions and
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25
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Figure 2. Malignant tumors.
I. Benign tumors.
I Duration
of Symptoms Lesions Malignant
Duration
Number
1 year Total
9 8 27 18 22 84
Per Cent 10.7 95 32.2 21.4 26.2
Benign Number 1 2 15 7 24 49
Per Cent 2 4.1 30.6 14.3 49
32 per cent of those with benign lesions. The correct diagnosis was made preoperatively in 41 per cent of the patients with benign tumors, but despite numerous examinations only 26.5 per cent of those with malignant tumors had a correct preoperative diagnosis.
Results The method of treatment was based on the type of small bowel tumor. Excision was curative in all but three of the patients with benign lesions: two patients with multiple hemangiomas and one with the Peutz-Jeghers syndrome continued to have symptoms related to their widespread disease. The prognosis was dismal for the eighty-eight patients with malignant lesions regardless of the method of treatment used. The average period of survival after diagnosis was 5.03 years. The average survival for patients with adenocarcinoma was 3.6 years; with lymphoma, 1.3 years; with carcinoid, 6.8 years; and with leiomyosarcoma, 8.3 years. (Figure 7.) Potentially curative surgical procedures were possible in only 51.1 per cent of the patients with malignant tumors: the lowest number of potentially curative procedures was performed in patients with adenocarcinoma (39.3 per cent). (Table II.)
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Adjunctive radiation therapy and chemotherapy were used during the later years of the study; 46.8 per cent of the patients with lymphoma, leiomyosarcoma, and adenocarcinoma received radiation therapy, chemotherapy, or a combination of both. (Table III.) Patients with lymphoma who lived more than one week postoperatively received radiation therapy (70.8 per cent). Regardless of the method of treatment, the average five year survival rate was only 30.7 per cent. (Table IV.) Although the survival rate was somewhat lower for patients with lymphoma (25 per cent) and adenocarcinoma (25 per cent), 47.4 per cent of patients with carcinoid tumors survived five years and 31.6 per cent survived ten years. Thirty per cent of the patients with leiomyosarcoma survived five years. The location of the lesion influenced the survival rate; 37 per cent of patients with ileal lesions but only 6.7 per cent of patients with duodenal lesions lived five years. (Table V.) Fifty-seven of the 133 patients (42.9 per cent) had a second primary neoplasm determined from the case history or detected during the follow-up period. Comments Primary tumors of the small bowel are usually discovered in patients in the sixth and seventh decades 131. R ecently, the average age of patients at the time of diagnosis was 62.2 years for those with benign lesions [6] and from fifty-three years [7] to 56.8 years [6] for those with .malignant lesions. These findings correlate with the age of patients at the time of diagnosis in our series (average age of patients with benign lesions was 56.9 years and for those with malignant lesions, 55.9 years). Our series contained an unusual number of lesions in children under fourteen years of age (6 of 140 lesions or 4.3 per cent). In the survey by
TheAmorkan
Journal of Surgery
Tumors of Small Bowel
60% 1
cl
MALIGNANT
MALIGNANT
I
BENIGN
BENIGN
DUODENUM
ILEUM
JEJUNUM
MULTIPLE
UNKNOWN
0DUODENUM Figure 4. Location of tumor.
Ffgure 3. Presentlng symptoms.
1
15
: :
IO
:
0
q JEJUNUM q ILEUM n JEJUNUM
(L ILEUM
Figure 5. Location of benign lesions.
Figure 6. Specific location of malignant lesions of small bowel. TABLE II
Surgical Treatment Cure
Tumor
o
.
.
.
.
DUODENUM
q JEJUNUM n ILEUM
;
.
.
-
-
,h
YEARS
Lymphoma Leiomyosarcoma Adenocarcinoma Carcinoid AngiosarFoma Fibroneurosarcoma Melanoma Total
Patients
Number
24 10 28 19 4 2 1 88
11 5 11 12 4 1 1 45
Palliation Per Cent
45.8 50 39.3 63.2 100 50 100 51.1
Number
Cent
13 5 17 7
54.2 50 60.7 36.8
1
Per
50
43
Flgure 7. Average survival with malignant lesions.
Rivers, Silverstine, and Tope [S] of 1,399 benign lesions of the small bowel, 122 (5.9 per cent) were in patients less than ten years old. The delay in the diagnosis of a primary small bowel tumor is often related to the vague and nonspecific symptoms that these tumors produce. In 1961 Rochlin and Longmire [9] reported that 40 per cent of their patients had symptoms for at least ten months before the diagnosis was made. In a more recent study, 60 per cent of patients with
Volume
130.
December
1975
malignant tumors and 50 per cent of patients with benign tumors had symptoms for more than six months [6]. In our series, 47.6 per cent of patients with malignant tumors and 63.3 per cent of patients with benign tumors had symptoms for more than six months. The most consistent symptoms produced by small bowel tumors are poorly localized abdominal pain, symptoms of recurrent obstruction, weight loss, and weakness secondary to anemia [3,10,11].
751
Treadwell
TABLE
and White
III
Radiation
and Chemotherapy Lvmphoma
Leiomvosarcoma
(24) Radiation (alone) Chemotherapy (alone) Both forms of therapy Total
TABLE
IV
Malignant
-
14 (58.3%)
1 (10%)
3 (12.5%) 17 (70.8%)
1 (10%) 2 (20%)
Lesions (SB Patients) Survival
Tumor
Patients
Lymphoma Leiomyosarcoma Adenocarcinoma Carcinoid Angiosarcoma Fibroneurosarcoma Melanoma Total
TABLE
V
24 10 28 19 4 2 1 88
Location
Five Years
Ten Years
6 3 7 9 1 0
2 2 4 6 1 0
(25%) (30%) (25%) (47.4%) (25%)
1 (100%) 27 (30.7%)
of Lesion Correlated
(8.3%) (20%) (14.3%) (31.6%) (25%)
1 (100%) 16 (18.2%)
with
Survival
Survival Location Duodenum Jejunum Ileum
Number 15 19 54
Five Years
Ten Years
1 (6.7%) 6 (31.6%) 20 (37%)
0 2 (10.5%) 14 (25.9%)
Because benign small bowel tumors are usually asymptomatic, 60 to 75 per cent of the symptomatic tumors are malignant [3]. When benign lesions cause symptoms, obstruction, pain, and bleeding are the most common findings. In a col: lected series of 1,047 benign tumors, 56 per cent of the patients had symptoms of obstruction, 38 per cent had pain, and 30 per cent had bleeding [12]. In our series of patients with benign tumors, bleeding occurred in 52.9 per cent, obstruction in 9.8 per cent, and pain in 15.7 per cent. This high incidence of bleeding as a presenting symptom is due to the large number of hemangiomas (42.3 per cent of the fifty-two benign tumors). In the collected series, only 12.9 per cent of the benign lesions were hemangiomas. In a collected series of 808 malignant lesions, the most frequent presenting symptoms were weight loss (39 per cent), obstruction (30 per cent), bleeding (23 per cent), and pain (20 per cent) [ 71. In the present study, 50.6 per cent of the patients with malignant lesions had symptoms of obstruction when they were first observed, 22.9 per cent had pain, and 20.7 per cent had bleeding.
752
iio)
Adenocarcinoma
Total
(62)
(28) 7 2 1 10
(25%) (7.1%) (3.6%) (35.7%)
22 2 2:
(46.8%)
O’Brien [3] reports that benign tumors of the small bowel increase in frequency as the ileocecal area is approached. Wilson et al [12] confirmed this observation in their collective review. However, in our series, 34.6 per cent of the benign lesions were located in the duodenum and only 11.5 per cent were in the ileum. The preponderance of malignant lesions in the distal small bowel has been substantiated by a large collected series in which most of the malignant tumors were in the ileum (48.8 per cent) as compared with 22.6 per cent in the duodenum and 28.5 per cent in the jejunum [7]. In our series, 61.4 per cent of the malignant lesions were found in the ileum and 17 per cent in the duodenum. The lack of physical findings and the inaccessibility of the small bowel to clinical investigation cause delays in diagnosis. The presence or absence of a palpable mass varies considerably, occurring in 7 per cent [2] to 63 per cent [9] of patients, but a mass is more likely to accompany a malignant lesion. In our series, a palpable mass was found in 29.3 per cent of the patients, 14 per cent with benign tumors and 36.8 per cent with malignant tumors. Silberman, Crichlow, and Caplan [6] reported a palpable mass in 3 per cent of patients with benign lesions and 22 per cent of patients with malignant tumors. Patients with leiomyosarcoma were more likely to have a mass (72 per cent) than were patients with lymphoma (66 per cent), carcinoma (36 per cent), or carcinoid (15 per cent)
[W.
The most reliable radiologic study for diagnosing small bowel tumors is an upper gastrointestinal series with small bowel follow-through. This study has provided a positive diagnosis for 63 per cent of the small bowel lesions in two series [6,10]. The probability of detecting a tumor is better if it is located in the proximal portion of the small bowel. Vuori [IO] reported a positive diagnosis for 70 per cent of duodenal lesions compared with a positive diagnosis for 53 per cent of jejunal and ileal lesions. The types of tumors encountered in the small bowel are similar to those found elsewhere in the
The American Journal of Surgery
Tumors of Small Bowel
gastrointestinal tract. In a collected series of 1,721 benign small bowel tumors, the most common types of tumors were leiomyoma (22.1 per cent), lipoma (17.5 per cent), adenoma (14.2 per cent), polyp (14.2 per cent), and bemangioma (12.3 per cent) [12]. In our series, the most common types of benign tumors were hemangioma (42.3 per cent), adenoma (17.3 per cent), polyp (15.4 per cent), and leiomyoma (15.4 per cent). Our series included only one lipoma. Other benign tumors of the small bowel are uncommon [3,8]. In a collected series of 2,144 malignant small bowel tumors, the most frequently encountered tumors were adenocarcinoma (50 per cent), carcinoid (39 per cent), and leiomyosarcoma (11 per cent) [7]. Malignant lymphoma was reported in 19 per cent of patients with malignant small bowel tumors in another large study [13]. The most common malignant tumors in our series were adenocarcinoma (30.7 per cent), lymphoma (27.3 per cent), carcinoid (21.6 per cent), and leiomyosarcoma (11.4 per cent). Other malignant lesions,of the small bowel such as angiosarcoma, neurofibrosarcoma, and melanoma, rarely occur [3].
Survival
The low five year survival rate reported in most series of malignant small bowel tumors seems universal. The delay in making the diagnosis results in widespread disease at the time of surgical treatment. Ebert and Zuidema [2] reported that 69 per cent of their patients had metastases at the time of surgical intervention. Curative procedures were attempted in 51.1 per cent of the patients in our series. These procedures were possible in only 39.3 per cent of the patients with adenocarcinoma, because many of these tumors (nine of twenty-seven) were located in the duodenum; the lesions were infiltrating and locally metastasizing by nature and the closeness of vital structures in this area made a “cancer operation” impossible. Rochlin and Longmire [?I reported that 40 per cent of their patients had curative surgery; however, only two of seven duodenal lesions could be resected. Curative procedures were attempted in 78 per cent of Silberman, Crichlow, and Caplan’s patients 161, but only 28 per cent of the malignant lesions in the duodenum could be removed. The inability to remove duodenal lesions is reflected in the five year survival rate when the location of the tumors is considered. In our series, 37 per cent of patients with malignant lesions in the
Volume 130, December 1975
ileum but only 6.7 per cent of patients with malignant lesions in the duodenum lived five years. The reported five year survival rates for patients with duodenal lesions range from 0 [6] to 30 per cent [IO]. From 29 [IO] to 33 per cent [14] of patients with ileal lesions have survived five years. Pancreaticoduodenectomy is the procedure of choice for potentially curable duodenal lesions [6,7,9]. For patients with malignant lesions in other locations, wide resection and lymph node dissection should be attempted if a cure seems possible [IO]. When curative resection is impossible, palliative resection or bypass procedures are indicated [9]. A patient’s prognosis after diagnosis of any malignant lesion of the small bowel is guarded despite a combination of therapeutic maneuvers. In our series, the average five year survival rate for all malignant tumors was 30.7 per cent. The five year survival rate for patients with various types of tumors ‘ranged from a low of 25 per cent in patients with malignant lymphoma and adenocarcinoma to a high of 47.4 per cent for those with carcinoid tumors. These survival rates are comparable to those reported in other studies [3,10,13]. In patients with tumors of the small bowel, radiotherapy and chemotherapy are of questionable benefit. Most authorities agree that chemotherapy is not useful [7,9,15,16]. Radiotherapy has been considered unsuccessful when used for all types of tumor except lymphoma. Weaver and Batsakis [17] have questioned the benefit obtained from the use of radiotherapy in patients with gastrointestinal lymphomas, except in those with incompletely removed lesions. It is our clinical impression that patients with gastrointestinal lymphoma are provided a prolonged disease-free period and some palliation with this form of treatment. This view is supported by others [3,7].
Etiology
The cause of primary small bowel tumors eludes the investigators. Some benign lesions, such as ectopic pancreatic adenomas in the duodenum, may result from a congenital developmental defect. Heredity plays a role in some of these lesions. The Peutz-Jeghers syndrome is inherited as a Mendelian dominant trait. The Rendu-Osler-Weber syndrome (multiple hereditary telangiectasis) is thought to be inherited as a Mendelian dominant trait with variable penetrance. For the most part, however, the cause of benign small bowel tumors is unknown.
753
Treadwell and White
Theories have been advanced concerning the cause of malignant small bowel tumors. Bone and Wright [18] offer a purely mechanical theory by noting that small bowel mucosal cells are proliferating so rapidly that growth of a clone of malignant cells is inhibited. The fluid nature and the alkalinity of the small intestinal contents are thought to protect the small bowel to some degree [4,8]. The rapid transit time of intestinal contents through the small bowel may decrease potential carcinogenic contact with the mucosa [4]. The amount of potential carcinogen that can be formed from bile and other products by bacterial metabolism is reduced because of the “less sophisticated” bacterial population of the small bowel [4]. Enzymes that are known to detoxify certain potential carcinogens are reported to be more abundant in the small bowel [19]. It is the clinical impression of Renshaw and McCrae [5] that patients who received an extract of whole mucosa of the small intestine for treatment of rheumatic diseases had fewer carcinomas develop in all parts of the body than did patients not receiving the extract. The growth of metastatic lesions was inhibited in patients who had colonic cancer with known metastases when treatment was begun. This theory suggests that some humoral factor may be present in the small bowel and that this factor may act as a protective mechanism. High concentrations of IgA that have been found in the small bowel [7] may help explain the observations of Renshaw and McCrae and may be the basis for the paucity of malignant lesions of the small bowel. Lowenfels [4] found that an inordinate number of primary and metastatic malignant lesions of the small bowel have been reported in patients whose immunologic status was being suppressed for other reasons [4]. Patients who have one small bowel neoplasm are more likely to have a second neoplasm. The reported incidence of a second primary neoplasm ranges from 17.7 [14] to 74 per cent [20]. Of the 133 patients in our series, fifty-seven (42.9 per cent) had a second neoplasm as determined either by history or during the follow-up period. This incidence is much higher than the 0.33 per cent incidence of second neoplasms in the general population [4]. This observation further implicates some basic immunologic problem in patients in whom primary small bowel tumors develop. Summary Primary tumors of the small bowel are uncommon, representing less than 6 per cent of all gastrointestinal tumors and less than 2 per cent of all
754
malignant gastrointestinal tumors. This report concerns a twenty-five year survey of our clinical records from 1946 to 1971 which revealed 140 primary small bowel tumors, excluding periampullary tumors. Fifty-two of the neoplasms (37 per cent) were benign; eighty-eight (63 per cent) were malignant and included twenty-eight adenocarcinomas (31.8 per cent), twenty-four lymphosarcomas (27.3 per cent), nineteen carcinoids (21.6 per cent), and ten leiomyosarcomas (11.4 per cent), The average age at the time of diagnosis was 56.9 years for patients with benign tumors and 55.9 years for those with malignant tumors. The illusive and obscure nature of small bowel tumors is illustrated by the fact that 63.3 per cent of patients with benign lesions and 47.6 per cent of those with malignant lesions had symptoms for more than six months before the diagnosis was made. Bleeding was the most common presenting complaint in patients with benign neoplasms (52.9 per cent) whereas patients with malignant lesions more often had symptoms of obstruction (50.6 per cent). Most of the benign lesions were located proximally in the small bowel (duodenum, 34.6 per cent; ileum, 11.5 per cent), and most of the malignant lesions were located distally (duodenum, 17.0 per cent; ileum, 61.4 per cent). Treatment of patients with malignant lesions was radical excision whenever possible. Adjunctive radiation therapy was used for those with lymphoma. A second benign or malignant tumor occurred in 42.9 per cent of the patients with primary small bowel tumors. The average period of survival after diagnosis of a malignant small bowel tumor was 5.03 years: for patients with adenocarcinoma, 3.6 years; lympho6.8 years; and sarcoma, 1.3 years; carcinoid, leiomyosarcoma, 8.3 years. References 1. Broders AC Jr, Hightower NC, Hunt WH III, Stinson JC. While RR, Laurens HF: Primary neoplasms of the small bowel. Arch Surg 79: 753, 1959. 2. Ebert PA, Zuidema GD: Primary tumors of the small intestine. Arch Surg 91: 452, 1965. 3. O’Brien TF: Primary tumors and vascular malformations, p 959. Gastrointestinal Disease (Sleisenger MH. Fordtran JS, ed). Philadelphia, WB Saunders, 1973. Lowenfels AB: Why are small bowel tumours so rare? Lancet 1: 24, 1973. Renshaw A. McCrae JS: Why are small bowel tumours so rare? Lancet 1: 425, 1973. Silberman H, Crichlow RW, Caplan HS: Neoplasms of the small bowel. Ann Surg 180: 257. 1974. Wilson JM. Melvin DB, Gray GF, Thorbjamarson B: Primary malignancies of the small bowel. Ann Surg 180: 175. 1974. 8. River L, Silverstine J, Tope JW: Benign neoplasms of the
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Tumors of Small Bowel
small bowel. Int Absh Surg 102: 1, 1956. 9. Rochlin DB, Longmire WP Jr: Primary tumors of the small bowel. Surgery 50: 586, 1961. 10. Vuori JVA: Primary malignant tumors of the small intestine. Acta Chir Stand 137: 555, 1971. 11. Cohen A. McNeil1 D, Terz JJ, Lawrence W Jr: Neoplasms of the small intestine. AmJDigDis 16: 815, 1971. 12. Wilson JM, Melvin DB, Gray G, Thorbjarnarson B: Benign small bowel tumor. Ann Surg 181: 247, 1975. 13. Paztaluman RJ, Mayo CW, Docherty MB: Primary malignant tumors of the small intestine. Am J Surg 108: 13, 1964. 14. Reyes EL, Talley RW: Primary malignant tumors of the small intestine. Am J Gastroenterol54: 30, 1970. 15. Griffin WO Jr: Benign and malignant small intestinal tumors: Mechel’s diverticulum, p 901. Textbook of Surgery (Sabiston DC Jr, ed). Philadelphia, WB Saunders, 1972. 16. Storer EH: Small intestlne, p 1095. Principles of Surgery (Schwartz SI, ed). New York, McGraw-Hill, 1974. 17. Weaver DK. Batsakis JG: Primary lymphomas of the small intestine. Am J Gastroenterol42: 620, 1964. 18. Bone G, Wright NA: The rarity of small bowel tumours: an al-, ternative hypothesis. Lancet 1: 618, 1973. 19. Wattenberg LW: Carcinogen-detoxifying mechanisms in the gastrointestinal tract. Gastroenterology 51: 932, 1966. 20. Alexander JW, Altemeir WA: Associated neoplasm of the small intestine with other neoplestic growths. Ann Surg 167: 958, 1968.
VOllmw130. December 1975
Discussion Raymond C. Read (Little Rock, AR): The tumors that the authors report are symptomatic compared with autopsy series. They have a higher incidence of bleeding in the benign tumors. The main interest of this paper is to draw our attention again to why the small bowel, all twenty-two feet of it, is so immune to cancer, not only epidermal cancer but also mesodermal cancer. We all know that cancer of the stomach stops sharply at the duodenum. Why is it that cancer cells do not enjoy the milieu in the small intestine? Studies in the future will analyze patients who do have immune mechanisms, weeding out malignant transformations. Terry A. Treadwell (closing): The high incidence of bleeding in our series of benign tumors is directly related to the number of hemangiomas. We had twenty-two hemangiomas. In a series of more than 1,000 cases of benign tumor (121, the incidence of hemangioma was only 12 per cent. For this reason I feel that our incidence of bleeding as a presenting symptom in patients with benign tumors was spuriously high.
755
