Primary malignant tumor of the small intestine

Abstract

Key Words: intestinal neoplasms/diagnosis; intestinal neoplasms/therapy; small intestine; survival analysis

INTRODUCTION

Primary malignant tumors of the small intestine are easy to be misdiagnosed bec ause of its low morbidity, nonspecific clinical manifestations and the limited examination methods. Most cases are already in advanced stage at the time of diagnosis, so therapeutic result is very poor. In order to have a better understanding of the clinical characteristics of malignant tumor of the small intestine, an analysis was made for the diagnosis, treatment and prognosis-influencing factors of 75 cases with their diagnoses confirmed by pathological examination from 1964 to August. 1995 in our hospital, so as to improve their early diagnosis, timely treatment and therapeutic effect.

MATERIALS AND METHODS

General data

This group consisted of 75 cases, 42 males and 33 females. The onset age ranged from 4 to 75 years with an average of 47 years. The course of disease was 1 to 99 months, averaging 47 months.

Pathological type and tumor site

The diagnoses of the 75 cases were confirmed by pathological examination, 26 were cases of leiomyosarcoma, 25 adenocarcinomas, 20 malignant lymphomas, and 4 other malignant neoplasms. The tumors were located at duodenum, jejunum and ileum in 18, 28 and 29 cases respectively (Table 1).

Table 1 Pathological types and distributions.

Type of neoplasms	Number by region
	Duodenum	Jejunum	Ileum	Total
Leiomyosarcoma	5	14
Adenocarcinoma	10	9	6	25
Malignant lymphoma	2	4	14	20
Malignant fibrous histiocytoma		1	1	2
Malignancy of neurofibroma			1	1
Malignancy of fibroma	1			1
Total	18	28	29	75

Clinical manifestations

Clinical manifestations of these malignant tumors are shown in Table 2.

Table 2 Clinical manifestations.

Symptom	Abdominal pain	Abdominal mass	Emaciation	Intestinal obstruction	Melena	Acute peritonitis	Jaundice	Fever	Anemia
Number	45	43	18	11	6	5	5	4	3
%	60	57.3	24	14.7	8	6.7	6.7	5.3	5

Preoperative diagnosis

Before the exploratory laparotomy, 33 cases were diagnosed as intestinal carcinoma, 25 cases as abdominal mass, and 17 cases were misdiagnosed as other diseases, such as intestinal perforation, acute peritonitis, ovary tumor, colon carcino ma, and intussusception of ileum to cecum, and so on.

Accessary examinations

No abnormal CEA (carcinoembryonic antigen) was detected in 10 cases. Twenty-thr ee out of 26 cases were found to have abdominal mass by B-type ultrasonography. CT (computed tomography) scans showed a clear demonstration of tumor on the dis eased region and the structures around it in 20 cases. Of the 13 cases accepted barium meal roentgenography, 11 were diagnosed as intestinal tumor, with an accu racy of 84.6%. Of the 7 cases of duodenal tumors,6 were diagnosed as duodenal tumor by fibroscopy which were confirmed by pathological examination. Barium en ema was performed in 18 cases and 8 of them were found to have tumor in their ileum.

Methods of treatment

Surgical treatment was the main therapeutic method for this group of cases. Thir ty-seven cases received radical resection, 21 palliative resection, and 10 bypass operation, 3 exploratory laparotomy and 3 direct biopsy. The operation mortal ity was 1.4%. Four cases did not receive surgical operation. 27 cases received adjuvant chemotherapy. 5-fluorouracil(5-FU), mitomycin(MMC), cyclophosphamid e (CTX) and adriamycin (ADM) were commonly used.

RESULTS

Survival rates were calculated with Life Table, and computer’s COX multivariate analysis model was used for survival analysis.

Follow-up data

Duration of follow-up ranged from 1 to 30 years, the follow-up rate was 94.2%. One-, 3- and 5-year survival rates of the 71 operated cases were 70.7%, 49.9% and 35.1% respectively (Tables 3, 4 and 5).

Table 3 Survival rate by operation type.

Operation type	n	Survival rate (%)
		1 year	3 years	5 years
Radical resection	37	87.5	68.7	48.1
Palliative resection	21	57.9	33.8	24.1
Symptom-relieving and exploratory operation	13	42.9	21.4	0.0

Table 4 Survival rate by pathological type.

Pathological type	n	Survival rate (%)
		1 year	3 years	5 years
Adenocarcinoma	25	53.9	27.9	14.0
Leiomyosarcoma	26	95.8	82.1	57.5
Malignant lymphoma	20	48.6	39.7	23.8

Table 5 Survival rate by location of tumor.

Location of tumor	n	Survival rate (%)
		1 year	3 years	5 years
Duodenum	17	69.2	38.5	0.0
Jejunum	27	81.8	59.6	50.4
Ileum	27	51.1	29.2	17.5

Prognostic factors analysis by computer’s COX multivariate analysis model

An analysis was made by COX multivariate analysis model, for the following factors which may influence prognosis such as patient sex, age, clinical course, histological type, tumor site, tumor size, gross type, lymph node metastasis, liver metastasis, invasion to adjacent organs, operation type, and chemotherapy. The critical value of alpha was 0.05. Statistical results showed that patient age, histological type, tumor site and operation type had significant influence on survival rate. But chemotherapy had no significant effect on prognosis.

DISCUSSION

General consideration

The incidence of primary malignant tumor of the small intestine is very low, accounting for 1%-3.6% of all gastrointestinal malignant neoplasms and 0.2%-0.3% of that of the whole body[1,2]. From 1964 to 1995, 75 cases of primary malignant tumor of the small intestine were admitted to our hospital, cons tituting about 1.4% of 4427 cases of malignancy of all GI tract in the same period. In China, the leiomyosarcoma, adenocarcinoma, and malignant lymphoma account for the most of the small intestine malignancies, but carcinoid is rare. However, in other countries the most frequently encountered malignancies of small intestine are in order of adenocarcinoma and carcinoid, malignant lymphoma and leiomyocarcinoma[3].

Relationship between pathology and tumor site. The predilection site of leiomyosarcoma is jejunum, ileum and duodenum. The predilection site of adenocarcinoma is in order of duodenum, jejunum and ileum, while the predilection site of malign ant lymphoma is ileum and jejunum, and is lower in duodenum[3]. The tumo r distribution rates in this group cases are consistent with those reported in t he literature (Table 1).

Tumor distribution in small intestine. Adenocarcinoma accounts for about 50%-66% of tumors in the duodenum (55.6% in this group), and followed by malignant lymphoma and leiomyosarcoma. In the jejunum, leiomyosarcoma is the most encountered (accounting for 50% in this group), the next is adenocarcinoma and malignant lymphoma. But in the ileum, malignant lymphoma constitutes about half of all malignancies (48.3% in this group), and followed by adenocarcinoma and leiomyosarcoma.

Many scholars hold that the low incidence of malignant tumors in small intestine is associated with the following factors: (1) Alkalinity in the small intestinal lumen is unfit for the growth of tumor. (2) Rapid peristalsis of small intestine is suggested to minimize the time of mucosal exposure to potential carcinogens from food, and liquid content in lumen may dilute carcinogens, which will lead to the reduction of carcinogenicity. (3) The lack of intralumenal bacterial flora obviously reduces carcinogenic agents, and these bacteria are necessary in the process of metabolism. (4) A large concentration of IgA produced mainly in the lymphoid tissue of small intestine, is protective against tumorigenesis by neutralizing virus and potential carcinogenic agents. (5) The T-lymphocyte with strong immunity, accounting for the majority of lymphocytes in collecting lymphadens of small intestines, has a strong ability and specific characteristics to protect against tumor growing. (6) Benzopyrene hydroxylase is present in large amounts in the mucosa of small intestine and may detoxify carcinogens[1].

Diagnosis

Primary malignant tumor of small intestine is easy to be misdiagnosed because of its low incidence, its vague and nonspecific clinical presentations, and the limited diagnostic methods. Misdiagnosis rate in literature reports is 40%-80%[4], and 56% in our group. We hold that following are the key point s to increase its diagnostic accuracy and to decrease its misdiagnostic rate.

A better understanding should be acquired in primary malignant tumor of small intestine. In clinics the following should be highly suspicious of the disease: unknown abdominal pain, abdominal mass, melena, and obstruction, especially when an abdominal mass is palpable.

Barium meal roentgenography is the routine method for detecting primary malignant tumor of small intestine, its diagnostic accuracy can be as high as 50%[2,5]. We think that for the patients who are suspicious of tumor in small intestine, barium meal roentgenography should be performed if possible. In our studied group, diagnoses were established by barium meal X-rays in 11 out of 13 cases with an accuracy of 84.6%. Air-barium contrast roentgenography, in which a large amounts of barium and air are injected into the duodenum lumen through a gastric tube, is suggested to be performed to visualize small intestine segment by segment, so as to increase its diagnostic accuracy rate. The distal ileu m usually is poorly visualized in upper GI series studies, but it may be demonstrated through barium enema in which contrast material from colon is refluxed into the distal small intestine through the ileocecal valve. Combination of barium meal roentgenography and barium enema can achieve a positive rate of 50%-80%.

Flexible endoscopic examination and direct biopsy are the most reliable methods to establish the diagnosis, especially in early stage of the disease. It is also helpful and reliable for diagnosis of tumors in the duodenum. In our studied group, the diagnosis was established in 6 of 7 cases by flexible endoscopic examination and were confirmed by pathological examination. In foreign countries, the flexible endoscopy for small intestine was used in clinic in 1969. But it developed very slowly because of its technical difficulties in inserting and the great suffering of patients[5].

Computed Tomography (CT) scans can show a good demonstration of the tumor-involved region and the structures around it. Furthermore, CT scan can define whether there is local or distant metastasis. Especially for those whose diagnosis ca not be confirmed by GI barium roentgenography, CT scan is an effective method[6].

Treatment

Surgical resection is so far the most effective therapeutic method for malignant tumor of small intestine. If diagnosis is established, radical resection should be performed as early as possible, which requires at least segmental resection of 10cm of the involved region, including removal of the corresponding mesentery and its lymph nodes[7]. It was reported the 5-year survival rate of radical resection is 25%-54%[1,8], which is consistent with that (48.1%) in ours tudy. For carcinoma in the duodenum, Whipples operation should be performed if possible. Tumor in the distal ileum should be treated by right hemicolonectomy. Palliative resection of tumor is somewhat valuable and should not be given up easily . Its 5-year survival rate is 0%-25% reported in literature[1], and is 24.1% in our study. Bypass operation can temporarily relieve symptoms but could not prolong the patient’s life. Reexploratory resection should be performed for recurrence if possible[9,10].

Adjuvant postoperative chemotherapy for malignant lymphoma is necessary. The unresectable malignant lymphoma of small intestine should be treated mainly by che motherapy in order to relieve symptoms and prolong life. The usual chemot herapy regimen is CHOP (CTX + VCR + ADM + Prednisone). Leiomyosarcoma of small intesti ne is partly sensitive to chemotherapeutic agents. For huge leiomyosarcoma, preoperative combination chemotherapy of ADM and CTX can minimize the size of tumor and improve resection rate. Chemotherapy has no effect on adenocarcinoma of small intestine due to its nonsensitivity to chemotherapeutic agents. In our study, 27 cases had accepted chemotherapy, but neither postoperative adjuvant nor palli ative chemotherapy is effective in prolonging the survival, which is possibly as sociated with the late stage of the disease.

Prognostic factors

It was reported that prognostic factors of primary malignant tumor of the small intestine are chiefly the operation type, histological type, tumor site and tumor size [1,7], and each of them was analyzed by monovariate analysis. Up to now there have been no reports in theworld about the prognostic factors studied by multivariate analysis model. In our study, 12 factors were analyzed by computer’s COX multivariate analysis model, including patient sex, age, clinical course, histological type, tumor site, tumor size, gross type, lymph node metastasis, live r metastasis, invasion to adjacent organs, operation type, and chemotherapy. The results showed that significant prognostic factors were histological type, operation type, patient age and tumor site in order, neither tumor size nor chemotherapy had significant effect on prognosis.