Small bowel obstruction caused by secondary tumors

1.1. Epidemiology 

Intestinal involvement of metastatic cancer is common; with varying incidence among different malignancies, such involvement, mostly in the form of diffuse peritoneal carcinomatosis, has been reported in up to 5–10% of cases in neoplasms such as breast cancer and malignant melanoma [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. Necropsy figures are even higher [12]. Nevertheless, small bowel obstruction caused by isolated metastases to the bowel wall seems to be an extremely rare event; between 1988 and 2005, only 36 such cases have been reported. As seen in Table 1, which summarizes the main epidemiological features of these cases, the majority (47%) was associated with primary lobular breast cancer. Other leading causes of this complication were malignant melanoma and lung cancer, mostly of non-small cell histology. Most patients presented with this complication in the sixth decade of their life (mean age, 55 years) and there seems to be a slight female predominance (58%), which one could expect in light of the apparent association with breast cancer.

Table 1. Epidemiological features of patients with small bowel obstruction caused by secondary tumors

	Age (years) mean (range)		56.9 (50.1–62.8)
	Gender
	Male		21 (58.3%)
	Female		15 (41.7%)
	Primary tumor	Lobular breast cancer	17 (47.2%)
		Malignant Melanoma	3 (8.3%)
		Lung cancer	4 (11.1%)
		Renal cell carcinoma	2 (5.6%)
		Ovarian cancer	2 (5.6%)
		Osteosarcoma	2 (5.6%)
		Prostate cancer	2 (5.6%)
		Squamous cell carcinoma	1 (2.8%)
		Rectal adenocarcinoma	1 (2.8%)
		Testicular germ cell cancer	1 (2.8%)
		Metastatic liposarcoma	1 (2.8%)

1.2. Clinical presentation 

The time interval from diagnosis of the primary tumor to the development of small bowel obstruction secondary to isolated metastases to the bowel wall varies widely, from presentation with bowel obstruction to the development of such complication more than 30 years after the diagnosis of the primary malignancy, in a case of malignant melanoma [3].

The presenting symptoms are non-specific and provide no clue as to the cause of the small bowel obstruction [13]. The possibility of a metastasis in the bowel wall as a potential cause of an obstruction requires a high level of suspicion and should be considered in any patient with a history of cancer, regardless of the known activity status of his disease. The disease free interval and the type of cancer are important, as a recurrence after a very long disease free interval, such as of 10 years or more, is highly unlikely in most tumors, with the exception of breast cancer and malignant melanoma. On the other hand, presence of metastases in other sites should lead to a higher level of suspicion.

1.3. Diagnostic work-up 

Several factors make the diagnosis of secondary tumors as the cause of small bowel obstruction especially tricky. First, the rarity of the condition commonly leads to a low index of suspicion. Second, the symptoms of metastases to the bowel are often non-specific and can be easily misattributed to much more common etiologies, which in addition are frequently relevant to these patients (e.g., adhesions). Third, gastro-intestinal metastases from certain tumors, such as malignant melanoma and breast cancer can occur after many years of freedom of disease [3], [14], [15]. Lastly, metastases to the bowel wall can represent the first site of recurrence, with otherwise no evidence of active disease [2], [16]. All this factors often lead to a significant delay in the diagnosis of secondary tumors as the etiology of small bowel obstruction [16].

Definitive diagnosis of bowel obstruction caused by secondary tumors requires pathological evaluation of a biopsy or resected specimen, and these are almost invariably obtained during surgical intervention [16], [17], [18]. However, the diagnosis may well be suspected by the results of imaging studies, most commonly computerized tomography, although this usually happens in the presence of a recognized metastatic spread [18]. In 20(55%) of the reported cases, the cause of the small bowel obstruction was determined only post-mortem [12].

As a rule, the diagnostic work-up should not differ from the general work-up of small bowel obstruction, regardless of its cause. The indication for explorative laparotomy remains clinical, i.e. depending on the severity of the peritoneal signs or other alarming signs for bowel wall distress. Nonetheless, the aggressiveness of the work-up, and later on of the therapeutic interventions (see below), may be affected by the extent of the metastatic disease and its chances to respond to specific anti-cancer treatment. For example, an aggressive work-up seems questionable in a terminal patient succumbing to disseminated disease.

1.4. Pathology 

Breast cancer is the leading cause of small bowel obstruction secondary to isolated metastases to the bowel wall. This condition has several histopathological characteristics that are worth attention. First, while only 15% of patients with breast cancer have the lobular variant, these make up the majority of patients with solitary gastro-intestinal metastases, and all of the cases associated with small bowel obstruction [1], [9], [10], [14], [19]. Second, metastases of lobular carcinomas have a high potential for misinterpretation because most metastases consisted of infiltrating strands of pleomorphic cells without gland formation (Fig. 1) [11], [12]. Lastly, small bowel metastases from breast cancer are usually associated with coexisting peritoneal carcinomatosis. Several observations can be made with regard to other tumors too. The typical histological subtype in cases of small bowel obstruction secondary to metastatic lung cancer is adenocarcinoma [12], [20]. In the two cases of small bowel obstruction secondary to ovarian cancer, those metastases were microscopically made up of large, complex, papillary or cribriform glands and Psammoma bodies were noted [12]. In the cases of metasatic renal cell carcinoma, the metastases had a cear cell morphology with a sarcomatoid pattern [21], [22].

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Fig. 1. Metastasis in the small bowel, similar histology of infiltrating lobular carcinoma in primary breast tumor (case of Kaplan Medical Center).

1.5. Treatment 

Treatment of small bowel obstruction caused by secondary tumors has two targets, to solve the acute obstruction and to control the metastatic disease. Obstruction in this circumstances almost never resolves by conservative treatment and surgical intervention is almost always indicated [12], [18]. The actual type of intervention depends on several factors, some which are patient specific and other which are specific for the underlying malignant disease. Among the patient specific factors, the most important are the patient clinical condition and ability to sustain major surgery. Among the disease specific factors the most important are the extent of metastatic spread, the likelihood of a significant response to therapy and the overall prognosis. For example, in a healthy woman with hormone receptor previously untreated recurrent breast cancer the chances for long-term survival following resection of the obstructing gastro-intestinal metastases may be excellent and major surgery is clearly justified. On the other extreme, in an elderly patient with severe comorbidities and metastatic lung cancer that failed first line chemotherapy, who present with obstructing gastro-intestinal lesion, diverting procedure may be more appropriate.

Following the diagnosis of an obstructing gastro-intestinal metastasis, as the sole manifestation of systemic disease or in the presence of other sites of active disease, initiation or replacement of specific anti-cancer therapy should be considered. The goals of such therapy may be to delay or avoid another recurrence following resection of a single metastasis, or to delay progression of disease following local treatment for the obstructing lesion, in the presence of disseminated disease. The specific type of anti-cancer therapy, which can be hormonotherapy, chemotherapy or targeted biological therapy, dependes on the specific malignancy. Similarly, there is a large variability in the expected effectiveness of the treatment.

1.6. Prognosis 

The prognosis of patients who present with small bowel obstruction caused by secondary tumors varies widely [12], [16], [17]. As the chosen treatment varies according to multiple patient and disease specific factors, these factors may have a significant impact on the patient outcome too. In general, the most important prognostic factors seem to be the patient's ability to undergo surgical resection of the obstructed segment, the disease free interval prior to the diagnosis of the metastasis in the bowel, and the type and extent of the underlying malignancy and its probability for a durable response to anti-cancer therapy. The examples described in the section “treatment” demonstrate two extremes with regard to the recommended management of this condition. However, they may well represent two extremes with respect to the prognosis of this condition too.