Small Bowel: Diagnosis and Staging of Cancer of the Small Bowel and Appendix
Karen M. Horton, MD and Elliot K. Fishman, MD
Neoplasms of the small bowel continue to pose a significant diagnostic challenge to both the clinician and radiologist. This is due to several factors. First, these tumors are uncommon with an annual incidence of only 0.5 to 1.0 per 100,000 people in the western hemisphere. Due to its rarity, the diagnosis of small intestinal neoplasms is often overlooked. Second, these tumors typically result in nonspecific symptoms such as abdominal pain, gastrointestinal bleeding, nausea, vomiting, and weight loss. This contributes to a delay in diagnosis. Third, most small bowel neoplasms are small, especially in the early stages . This makes detection difficult on conventional radiologic studies. Although small bowel enteroscopy may come to play a larger role in the diagnosis of small bowel tumors, this technology is still evolving and has not yet replaced more traditional radiologic examinations.
Radiologic examination of the small intestine has improved significantly over the past 20 years. Today, contrast examinations (dedicated small bowel series and enteroclysis) and computed tomography are the major radiological examinations performed for evaluation of small bowel pathology . In addition, Magnetic Resonance Imaging (MRI) may be utilized in select problem cases.
Technique:
Contrast Studies
The dedicated small bowel series is the most commonly performed radiologic examination for evaluation of suspected small bowel disease. It is a simple and noninvasive test. After a scout abdominal radiograph is obtained, the patient drinks 400 - 600cc of thin barium. Overhead radiographs are obtained at 20-minute intervals to follow the progression of contrast through the entire small bowel and into the right colon. Fluoroscopy is performed intermittently by the radiologist to observe peristalsis. Also, the radiologist uses a compression devise in order to fully evaluate the small intestine by separating overlapping loops. Spot compression films are obtained of the small bowel with attention to areas with suspected abnormalities.
Enteroclysis is a more invasive examination of the small intestine which can be performed in patients in whom there is a high suspicion of small bowel pathology. During enteroclysis, a tube is placed through the patient's nose or mouth and advanced through the esophagus, stomach, and duodenum to the ligament of Treitz. A balloon is inflated to secure the tube. Some radiologists routinely administer mild sedation to relieve patient anxiety. Next, a barium mixture is infused followed by methylcellulose. Often, a mechanical pump is utilized to administer the contrast. The goal is to fully distend the small intestine to maximize detection of a mass or obstruction. This technique results in distended small bowel loops which are coated with barium. The appearance similar to a barium thus the enteroclysis is referred to as a "small bowel enema".
The exact role of the small bowel series and enteroclysis is controversial. Most radiologists agree that because of the low prevalence of small bowel disease, the dedicated small bowel series is a good inexpensive screening test. However, in patients with a high clinical suspicion of small bowel disease, enteroclysis may be performed as the primary examination. It is more sensitive than the dedicated small bowel series and more accurate. However, it is also more invasive and more expensive. In one series comparing the dedicated small bowel series with enteroclysis, the enteroclysis demonstrated additional information in 50% of cases. In a series by Maglinte, 42 lesions were detected on enteroclysis which were not visualized by the small bowel series. The failure of the small bowel series was due to both technical and perceptive errors .The literature supports that enteroclysis is more sensitive than dedicated small bowel series for detection of small bowel malignancies.
CT
Optimal CT examination of the small intestine requires careful attention to technique. Patients should be examined after an overnight fast or should be NPO for at least six hours before the examination. Adequate opacification of the small intestine is essential, as non-distended segments may mimic or mask disease. We routinely administer 750cc of flavored hypaque 30-45 minutes prior to the study and an additional 250cc immediately prior to the start of the examination. Although high attenuation agents such as hypaque have traditionally been utilized as CT oral contrast agents, there has been recent interest in low-density agents such as water or milk . Unlike high attenuation oral contrast, these low attenuation agents do not interfere with 3D studies of the abdomen. In addition, low attenuation contrast allows better visualization of the enhancing bowel wall and may improve detection of small bowel disease and neoplasms.
To maximize the detection of small bowel pathology, the small intestine should be adequately distended. To improve small bowel distention, CT enteroclysis can be performed. This technique is a combination of enteroclysis and CT. The CT is performed after the administration of low-density contrast through a duodenal tube using a mechanical pump. This allows maximum distention of the small intestine, which is especially helpful when diagnosing low-grade obstruction or small masses. However, this examination is invasive and more research is needed to determine if CT enteroclysis will improve the detection of staging of small bowel neoplasms.
Regardless of the type of oral contrast administered, the use of intravenous contrast is essential in the detection and staging of small bowel neoplasms. Intravenous contrast is necessary to determine the presence and pattern of enhancement of small bowel neoplasms as well as to opacify adjacent vessels in order to detect encasement. In addition, intravenous contrast is necessary to detect liver metastasis. We routinely administer 120cc of Omnipaque 350 (Nycomed, Princeton NJ) at 2-3cc per second. Scanning should be performed 40 seconds after the start of the injection which allows evaluation of the liver in the portal phase of enhancement. Spiral scanning offers a distinct advantage over conventional CT by allowing rapid scanning during IV contrast administration and narrow collimation. For small bowel imaging, spiral or helical CT is optimal with 5mm collimation and a table speed of 8mm per second. Reconstruction is typically performed at 5mm intervals. Additional targeted images or delayed scans can be obtained as needed.
Adenocarcinoma
The appearance of adenocarcinoma on barium studies varies with location. In the duodenum, 75% of adenocarcinomas appear as polypoid masses. Other appearances include infiltrative or stenotic lesions with or without ulceration. The upper GI series has a reported accuracy of 70 - 80% for detection of duodenal malignancies. If substances such as glucagon are administered during the upper GI series, the accuracy can be increased to 85 - 90% by maximizing duodenal distention and decreasing peristalsis
. In a report of 67 patients with adenocarcinoma of the duodenum, the upper GI series diagnosed 88% of cases. In that study, the EGD diagnosed 89% of cases. The upper GI series is a useful complimentary study when combined with the EGD, especially if the entire duodenum is not visualized at endoscopy.
On barium studies, adenocarcinomas of the mesenteric small bowel (jejunum and ileum) classically appears as a focal area of luminal narrowing, fold destruction, and over hanging edges (apple core lesion) . The mass is typically rigid and will not compress. Ulceration may be present. If the lumen is narrowed significantly, small bowel obstruction will occur. However, not all apple core lesions in the small intestine are due to primary adenocarcinoma. Metastasis to the small bowel can have an identical appearance . Also, inflammatory diseases such as Crohn's disease can result in segmental areas of stenosis which may mimic the appearance of adenocarcinoma. Usually, however, there are other indications that Crohn's disease may be present, such as involvement of other segments of the gastrointestinal tract. Overall, lesions smaller than 2cm in diameter may be difficult to visualize with CT. These are better detected by small bowel series or enteroclysis .
In addition to the apple core appearance, adenocarcinoma may appear as a polypoid intraluminal or intramural mass, rarely resulting in intussusception. Differentiating this appearance of adenocarcinoma from other polypoid lesions can be difficult. Rarely, adenocarcinoma can appear as a subtle eccentric plaque-like lesion in the small bowel, which can be detected on enteroclysis.
On computed tomography, small bowel adenocarcinomas may demonstrate a variety of appearances . The tumor most frequently appears as eccentric or circumferential wall thickening (usually greater than 1.5cm) involving a short segment of the small bowel . This may result in an "apple core" appearance, similar to that seen with barium contrast studies. Although inflammatory diseases of the small bowel may also produce diffuse or segmental wall thickening, this usually does not exceed 1.5cm in thickness. Also, inflammatory or ischemic diseases of the small intestine can produce a halo of alternating high and low attenuation within the wall. This is characteristic of a non-neoplastic process.
In cases of adenocarcinoma of the small intestine, which produce significant wall thickening, there may be luminal narrowing and proximal obstruction. Ulceration has been reported to occur in approximately 40% of cases of small bowel adenocarcinoma. However, this is usually not as well demonstrated on CT as with barium studies. Adenocarcinomas can rarely present as polypoid masses which may result in obstruction or intussusception. On CT, adenocarcinomas may appear homogeneous in attenuation, or in cases of large tumors with ischemia and necrosis, may appear heterogeneous. Contrast enhancement of the tumor may also be demonstrated.
In addition to detecting the primary small bowel adenocarcinoma, CT may aid in tumor staging. CT is not able to resolve the individual layers of the bowel wall. However, it can delineate tumors confined to the muscular wall and distinguish these from tumors that extend into the adjacent mesenteric fat. Irregular tumor margins or stranding in the adjacent mesenteric fat are indications of local tumor invasion.. Also, obliteration of fat planes between bowel loops or between the bowel and adjacent structures are suggestive of local tumor extension. CT can detect enlarged mesenteric lymph nodes which may be involved with tumor. Based on the location of the primary tumor, the regional draining lymph nodes can be predicted. For instance, tumors involving the duodenum tend to involve the lymph nodes in the peripancreatic, gastroduodenal, pyloric, and superior mesenteric artery regions. Regional lymph node drainage for both the jejunum and the ileum occur along the superior mesenteric vessels, while the terminal ileum may drain into lymph nodes in the cecal and ileocolic regions. Typically, mesenteric nodes greater than 1cm in short axis diameter are suspicious for neoplastic involvement. However, the sensitivity and specificity of CT are limited due to the fact that even very small nodes may harbor malignancy and large nodes may simply be reactive.
CT is currently the imaging modality of choice for the detection of liver metastasis. To maximize the detection of metastasis to the liver, imaging should be performed during the portal venous phase of enhancement. This will maximize the detection of small low attenuation lesions.
Staging of small bowel adenocarcinoma is based on the TMN system(Tables 1 and 2). This classification does not apply to lymphoma, sarcoma or carcinoid tumors.
Carcinoid Tumors
The radiologic appearance of carcinoid tumors varies depending on the size and location. The ileum is the most common location for small bowel carcinoid, followed by the jejunum. Carcinoid tumors arise from the Kulchitsky cells in the crypts of Lieberkuhn. Therefore, they grow as submucosal nodules. At this stage, the small bowel series and enteroclysis are much more sensitive for detection. The CT scan may be normal when the tumors are small and confined to the submucosa. On the small bowel series or enteroclysis, submucosal carcinoid tumors appear as smooth solitary intraluminal defects, most commonly in the distal ileum. This appearance is not specific for carcinoid however other submucosal masses such as leiomyoma, lipoma or submucosal metastasis or lymphoma could have an identical appearance. When the submucosal carcinoid tumor ulcerates, this can produce the appearance of a "target legion" on the contrast studies. However, this appearance is not specific for carcinoid and can occur in other tumors such as lymphoma, melanoma, metastatic breast cancer, or Kaposi’s sarcoma. Since approximately 30% of carcinoid tumors are multicentric, the contrast study may reveal multiple submucosal nodules. As the small intestinal carcinoid grows, there may be extension and thickening of the muscular layers of the wall. On contrast studies, this appears as thickening of the wall and mucosal folds . If the tumor extends outside the bowel loop, it can infiltrate the mesentery and result in a desmoplastic reaction. On contrast studies, this will appear as angulation and tethering as well as fixation of the involved small bowel loops. Retraction of the loops toward the root of the mesentery can also be seen. If there is an extensive mesenteric component with fibrosis, the mesenteric vessels can be encased, resulting in ischemia of the loops.
Although CT scans typically cannot demonstrate the small primary mass within the wall of the small bowel, CT is an excellent modality to demonstrate the mesenteric extension of tumors. Carcinoids which have infiltrated the mesentery demonstrate a characteristic CT appearance . On CT, this appears as an ill-defined mesenteric mass, containing calcification in up to 70% of cases . The mesenteric mass appears spiculated with a stellate pattern. CT scans with intravenous contrast nicely demonstrate the encasement or occlusion of mesenteric vessels. Thickening and ischemia of the involved small bowel loops may also be demonstrated as a result of mesenteric vessel encasement. Although the CT appearance of a mesenteric mass with calcifications and desmoplastic reaction is suggestive of carcinoid tumor, other conditions such as treated lymphoma or retractile mesenteritis can have a similar CT appearance.
In cases where there is a high clinical suspicion of carcinoid tumor but inconclusive barium studies or CT, angiography can be performed and may demonstrate the submucosal mass based on its vascularity.
CT is especially useful for evaluation of patients with suspected carcinoid tumor due to the high incidence of metastasis. Over 80% of tumors measuring greater than 2cm in diameter are associated with metastatic disease. The major site of metastasis from carcinoid tumor include the liver, nodes, bones, and lungs.
Carcinoid metastases to the liver have a characteristic CT appearance due to their vascularity. On early phase (arterial phase) imaging after the administration of intravenous contrast, these metastasis enhance brightly. On delayed imaging, these lesions may become isodense with the liver parenchyma. Therefore, if metastatic carcinoid tumor is suspected, arterial phase imaging should be performed. CT or ultrasound can be used for guidance if percutaneous biopsy is indicated.
In addition to contrast studies and CT, nuclear scintigraphy is a useful diagnostic tool in patients with carcinoid syndrome. Radionucleide scanning following the injection radioactive somatostatin analogues such as 111 Indium (or I 123) labeled octreotide or 123I-labeled metaiodobenzylguanidine (MIBG)is a sensitive noninvasive method to diagnose and localize carcinoid as well as other neuroendocrine tumors. This technique is especially useful to localize occult tumors and to detect chemically active metastases. However, scintigraphy does not provided precise anatomic detail.
Usually, contrast studies, CT and nuclear scintigraphy play a complementary role in the diagnosis and staging of patients with suspected carcinoid.
Lymphoma
Most small bowel lymphomas are of the non-Hodgkin’s cell type involving the mesenteric small bowel and rarely the duodenum. The primary tumor can often be detected with small bowel contrast studies and CT. However, CT offers the advantage of simultaneously detecting adenopathy as well as the extraluminal extent of disease.
There are four major patterns of small bowel lymphoma identified on radiographic studies. First, lymphoma can appear as multiple nodules or filling defects within the small bowel. The nodules may coalesce and result in the appearance of asymmetric wall thickening and luminal narrowing. Second, lymphoma may appear as a single polypoid lesion, which may vary in size. If small (,1-2 cm), this may not be visible on CT, but can be detected on enteroclysis. Polypoid lesions can result in complications such as intussusception, which is nicely demonstrated on CT. Third, lymphoma can be infiltrating. This will appear as thickened, destruction of the normal small bowel fold pattern and luminal narrowing. This appearance may simulate adenocarcinoma of the small bowel on contrast studies and CT. However, lymphoma usually involves a relatively longer segment of small bowel than adenocarcinoma and as opposed to adenocarcinoma, small bowel lymphoma typically does not result in obstruction. This is because the lymphoma usually weakens the muscular wall of the bowel and does not induce the typical fibrosis or desmoplastic reaction that occurs with adenocarcinoma. Also, the presence of associated significant retroperitoneal adenopathy favors the diagnosis of lymphoma over adenocarcinoma. In addition to luminal narrowing, aneurysmal dilatation of the effected bowel loops has been described in up to 50% of cases. The fourth pattern is that of a large exophytic mass that may ulcerate or fistulize to adjacent bowel loops.
The small bowel can be involved secondarily when lymphoma develops in the adjacent mesenteric lymph nodes and spreads by direct extension into small bowel loops. The small bowel loops can be displaced or completely encased by the enlarged nodes. Bulky mesenteric disease can form a mantle of nodes which envelope mesenteric vessels and small bowel loops producing the (sandwich sign) .
Leiomyosarcoma
Leiomyosarcoma is a gastrointestinal stromal tumor (GIST) which arises from smooth muscles cells in the muscularis propria. These are estimated to comprise between 10 - 16% of all intestinal neoplasms. When small, it is difficult to distinguish leiomyosarcomas from benign leiomyomas based on radiographic or even pathologic appearance. These tumors are characterized pathologically by their differentiation into smooth muscle or neural elements and are then categorized as benign, borderline, low malignant potential, or malignant.
Leiomyosarcomas are rare in the duodenum but occur with equal incidence in the jejunum and ileum. These tumors typically appear exophytic and bulky). There is often central ulceration or low attenuation compatible with necrosis. These tumors can be so large, that it becomes difficult to determine their site of origin. 3D CT imaging may be helpful in these instances. Leiomyosarcomas typically do not produce significant adenopathy. This can also help distinguish leiomyosarcomas from lymphomas on CT. CT can also detect direct invasion of adjacent organs or distant metastasis, typically involving the liver. Metastatic leiomyosarcoma to the liver classically appears cystic on CT, and should not be mistaken for benign hepatic cysts.
Metastases
Metastases can involve the small intestine by three distinct routes. Neoplasms in organs such as the pancreas or colon can grow to directly invade nearby small bowel loops (Fig 11). This can be detected on contrast studies as tethering, serosal spiculation, or mass effect indicating extrinsic involvement of the bowel. CT can demonstrate extension of the primary tumor to encase or invade adjacent bowel loops.
The small intestine may be involved by intraperitoneal seeding in primaries such as ovarian cancer or in psudomyxoma peritonei . CT can nicely demonstrate the intraperitoneal implants on the small intestine as well as implants on solid organs such as the liver or spleen.
Finally metastases may involve the small intestine by hematogenous spread in patients with cancers such as lung, breast or melanoma .
This radiographic appearance may simulate primary small bowel tumors. On contrast studies metastases to the small bowel can appear as target lesions in the submucosa, simulating lymphoma or as applecore lesions, simulating primary adenocarcinoma. On CT, metastases may appear as a focal mass or focal thickening of the small bowel, similar to the CT appearance of primary small bowel tumors.
Malignancies of the Appendix
Neoplasms of the appendix are rare, occurring in only 0.5% of appendices . The most common appendiceal malignancy is carcinoid, which comprises up to 15% of all gastrointestinal carcinoid tumors .
Since 80% of appendiceal carcinoid tumors are less than 1cm in size, the diagnosis is usually not made preoperatively on radiologic examination. Contrast studies are not usually useful in the diagnosis of primary appendiceal carcinoid, although they may demonstrate non-filling of the appendix or in some cases mass effect of the cecum. Similarly, although CT cannot usually visualize small appendiceal masses, it is useful for evaluation of possible metastasis. The primary site of metastasis is the liver. Carcinoid metastasis are hypervascular and are best visualized on scans performed with intravenous contrast and imaged in the arterial phase of liver enhancement. As with carcinoid tumors of the small intestine, if there is extension beyond the appendix into the adjacent mesenteric fat, this can be detected with CT.
Adenocarcinoma of the appendix occurs in 0.1% of appendices. Most or possibly all of appendiceal adenocarcinomas are thought to arise from preexisting adenomas. There two main types of adenocarcinoma of the appendix, the cystadenocarcinoma or the colorectal type adenocarcinoma.
Since almost 70% of patients with adenocarcinoma of the appendix present with signs and symptoms suggesting acute appendicitis, the diagnosis is usually not made until surgery or after examination of the pathologic specimen. In cases of appendiceal adenocarcinoma, the contrast enema is not usually helpful in making the diagnosis. It typically demonstrates non-filling of the appendix and possibly mass effect on the cecum. The contrast enema cannot distinguish between acute appendicitis and adenocarcinoma of the appendix. Likewise, the findings on CT can be identical, consisting of inflammation and soft tissue thickening of appendix and adjacent fat.
Cystadenocarcinomas typically demonstrate abundant extra cellular mucin. Mucocele of the appendix is a condition caused by an abnormal accumulation of mucus in a dilated appendix . The reported prevalence in appendectomy specimens is 0.2 - 0.3%. Preoperative diagnosis of mucocele of the appendix is crucial to attempt to avoid rupture at surgery. The term mucocele of the appendix is a descriptive term indicating that the appendix is distended by mucin. This can occur from hyperplasia, a benign mucinous cystadenoma or a mucinous cyst adenocarcinoma. The etiology of the mucocele is determined at pathology and cannot typically be determined on radiologic examinations.
Barium enemas in patients with mucocele of the appendix classically demonstrate extrinsic compression on the cecum or adjacent small bowel . Also, there is non-filling of the appendix. However, these findings are very nonspecific.
On CT, the normal appendix appears as a tubular structure with thin walls and should not measure more than 6mm in diameter . A mucocele of the appendix appears as a low attenuation well-defined mass in the right lower quadrant adjacent to the cecum . Mucoceles are typically retrocecal, because 65% of appendixes are retrocecal in location. The attenuation of the mass is dependent on the amount of mucin. The CT may also demonstrate mass effect. A key differential point is the lack of appendiceal inflammation. This helps distinguish mucocele from acute appendicitis. On CT, there is enhancement of the wall of the mucocele. The wall may either be thick or thin. The thickness of the wall does not help distinguish between neoplastic and non-neoplastic causes of mucocele of the appendix. The presence of an intramural nodule may help suggest the diagnosis of cystadenocarcinoma as the cause of the mucocele.
On ultrasound, a mucocele typically appears as a cystic mass in the right lower quadrant adjacent to the cecum. Ultrasound, usually demonstrates good through-transmission and posterior enhancement.The internal echoes are dependent on the amount and viscosity of the mucin. On ultrasound, mucocele wall is typically thin which helps distinguish a mucocele from appendiceal wall thickening in appendicitis.
Almost 50% of patients with cyst adenocarcinoma of the appendix will develop pseudomyxoma peritonei. This can be well visualized on CT. Pseudomyxoma peritonei appears as multiple foci of gelatinous material throughout the peritoneum . This can cause a scalloping appearance to the liver and spleen as well as gastrointestinal tract. CT is also helpful in detecting lymph node metastasis, which are noted in 25% of cases at presentation. Prognosis of adenocarcinoma of the appendix is determined by the Dukes staging and the degree of differentiation.
Metastasis to the appendix has been reported with ovarian cancer, breast cancer, stomach cancer, and lung cancer. Other malignant tumors of the appendix have been reported but are extremely rare. These include malignant lymphoma, smooth muscle tumors, nerve sheath tumors, ganglioneuromas, and Kaposi sarcoma.
Conclusions
Contrast studies and CT are the main radiologic examination performed to evaluate suspected small bowel pathology. Although neoplasms of the small bowel and appendix are rare and continue to be a diagnostic challenge to the clinician, advancements in radiologic technology such as improvement in enteroclysis techniques, the development of spiral CT, and CT enteroclysis have improved diagnosis and preoperative staging of these tumors. With the introduction of new CT oral contrast agents and faster multidetector CT scanners, the diagnosis and evaluation of patients with small bowel and appendiceal neoplasms will likely continue to improve.