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Small Bowel Cancer


Small Bowel Cancer

Article Author:
Gisela Ocasio Quinones
Article Editor:
Andrew Woolf
Updated:
7/13/2020 7:58:51 AM
For CME on this topic:
Small Bowel Cancer CME
PubMed Link:
Small Bowel Cancer

Introduction

Small Bowel Cancer encompasses a series of malignant lesions that may be identified throughout the small intestine (SI). The small bowel lies between the stomach and the large intestine (LI/Colon) and is encompassed by three different sections, the duodenum, jejunum, and ileum to the level of the ileocecal valve which provides the terminal transition point between the SI and the LI. While there are both benign and malignant lesions that can be identified throughout the SI, the overall incidence of small bowel neoplasms is extremely low when compared to lesions noted in other portions of the gastrointestinal tract. This article will focus on the overall characteristics, diagnostics, treatment and prognosis of malignant lesions. Majority of these lesions cause multiple non specific symptoms which very often lead to delay in diagnosis and therefore delay in early intervention with available treatment strategies. Common clinical features include abdominal pain, anorexia, gastrointestinal bleeding, and weight loss. More advanced processes can present with perforation, small bowel obstruction, or obstructive jaundice. Diagnosis can be variable based on location of the lesion under investigation and generally consists of laboratory studies, radiographic imaging and endoscopic evaluation. Malignant lesions overall include lymphomas, neuroendocrine tumors (carcinoids), adenocarcinomas and stromal tumors. [1]

Etiology

Over time, national registries have found that the incidence of certain types of malignant SI neoplasms vary based on location. While all of the previously mentioned malignancies can be found throughout the SI, studies have shown that these can be seen in higher incidence in certain portions of the SI. For example, adenocarcinoma is considered the most common neoplasm of the duodenum while neuroendocrine tumors are more common in the ileum. It appears that sarcomas and lymphomas occur in equal rates throughout the SI.[2] Each type of small bowel cancer has been found to have a particular set of hereditary conditions that pose a higher risk of developing such cancerous processes. The basis for each malignancy is dependent on genetics and mutations that occur resulting in malignant transformation of the cells.[3] The 5 main types and cells of origin include:

  • Sarcoma- generally classified as leiomyosarcoma and primarily arises from muscle tissue and it is most commonly found in the ileum, but can be found throughout the SI. 
    • GIST or Gastrointestinal Stromal Tumors- thought to arise from the Interstitial Cells of Cajal. These particular tumors are considered soft tissue sarcomas. 
  • Adenocarcinoma- usually develops through the malignant transformation of glandular cells of the SI. 
  • Neuroendocrine tumors- Also known as carcinoid tumors and are generally derived from hormone-producing cells and therefore are generally associated with secretory cells that cause particular clinical features. 
  • Lymphoma- derived from the lymphatics associated with the small intestine.

Risk Factors:

Full details regarding epidemiology and rates of occurrence have been delineated below. There have been certain cancer syndromes and underlying medical conditions that may predispose patients to certain types of small bowel neoplasms. 

Celiac Disease: 

  • Longstanding Celiac Disease has been found to be an independent risk factor for the development of high-grade lymphomas of the small bowel. Primarily noted to consist of Non Hodgkin Lymphoma subtypes. Although rare, patients with Type II refractory Celiac Disease have been found to have increased risk of Enteropathy Associated T Cell Lymphoma (often referred to as EATL). High index of suspicion should be considered for patients with severe Celiac Disease with significant issues consistent with recurrent obstruction or evidence of steatorrhea. Despite this primarily being noted through observational studies, some suggest that the diagnosis of EATL usually is heralded by a clinical relapse after the patient is found to have adequate response to abstinence from gluten.  

Inflammatory Bowel Disease:

  • Most specifically, Crohn’s Disease, has been found to carry an increase of small bowel cancer. Studies have shown that patients with Crohn’s Disease can have up to a 60 fold increase in risk of developing Adenocarcinoma of the small bowel.[4] 

Hereditary Cancer Syndromes: 

  • Cancer syndromes that carry increased risk of Cancer development in the Colon can often carry an increased risk of cancer of the small bowel. Examples of such syndromes include Familial Adenomatous Polyposis (FAP), Hereditary Nonpolyposis Colorectal Cancer (HNPCC/Lynch Syndrome), Peutz- Jeghers Syndrome (PJS), MUTYH- ASsociated Polyposis, as well as Cystic Fibrosis. All of the syndromes noted above carry an increased risk of Adenocarcinoma. The risk of developing Small Bowel Cancer often carries high mortality rates in patients with such diagnoses despite often undergoing prophylactic colectomy. For example, individuals who have undergone colectomy for Colon Cancer prevention in the setting of known diagnosis of FAP still require surveillance of upper GI tract with serial upper endoscopy at intervals that vary depending on polyp burden and initial screening pathology results.[5]

Epidemiology

The rate of incidence of small intestine cancer is very low in the United States with SI Cancer only accounting for approximately 3-5% of all gastrointestinal tract malignancies. The rate of incidence is proportionally extremely low when one considers that the SI accounts for approximately 90% of the surface area of the GI tract as a whole. [6] In contrast, Colon Cancer accounts for the third most common cause of cancer related death in the USA. The exact epidemiology and rate of incidence varies with each type of malignancy. 

  • Sarcoma:
    • Most common type are GIST tumors. Higher incidence rates in individuals around age 65 with reported male predominance. Sarcomas overall, however, are most commonly found in children as an oncologic process. [7]
  • Adenocarcinoma: 
    • Generally present in patient’s ages 50-70 years old with male predominance identified. [8] Certain conditions such as Inflammatory Bowel Disease, mainly Crohn’s Disease, and hereditary cancer syndromes such as FAP and HNPCC carry a higher risk and can present at younger ages. [9]
  • Neuroendocrine tumors:
    • Generally present in patient’s ages 50-70, with the majority of cases presenting in patients >65 years old. Studies have shown no gender predilection for NETs of the small intestine or rectum, but NETs of the stomach, appendix, and colon affected women more commonly than men. [10]
  • Lymphoma: 
    • Out of all Gastrointestinal tract lymphomas, small bowel accounts for approximately 9-10% of cases in total. Majority of the patients are between 60-70 years of age with a strong male predominance (60% vs 40%). [11] 

History and Physical

Majority of small bowel cancers have similar clinical presentations with the exception of neuroendocrine tumors which can present with symptoms that are specific to the products that are secreted from the neurosecretory granules contained within the malignant cells. Non specific mid abdominal pain, unexplained weight loss, and gastrointestinal bleeding are three of the most common presenting clinical symptoms. The abdominal pain is generally described as intermittent and crampy in nature with a small percentage of cases having associated nausea and vomiting. Larger neoplastic lesions can present with more severe conditions such as acute small bowel obstruction or perforation, with obstruction presenting more commonly than perforation. [12] The ambiguity of the presenting symptoms often causes a delay in diagnosis. Physical exam findings are often variable depending on the degree of disease involvement or presenting symptoms. [13]

Neuroendocrine tumors that have metastasized to the liver can present with a constellation of symptoms that occur as a result of secretion of bioactive products from the primary tumor. Therefore, workup of such lesions includes testing of biomarkers to confirm the etiology of patient’s non specific symptoms. The most common symptoms associated with carcinoid syndrome include cutaneous flushing, diarrhea (carries broad differential diagnosis), as well as less common symptoms such as venous telangiectasias and recurrent respiratory symptoms due to bronchospasms.

Evaluation

Evaluation and diagnostic process of Small Bowel Cancer consist of laboratory, Imaging, and endoscopic evaluations. Unfortunately, the diagnosis is often delayed due to the nonspecific nature of presenting symptoms and low index of suspicion in the course of evaluation of generalized abdominal pain for small bowel cancer. 

Laboratory Studies Evaluation

Initial workup generally includes an evaluation with complete blood cell count and differential, chemistry studies and liver function tests. Depending on the location of the lesion, patients may present with evidence of anemia due to fecal occult blood loss. Neuroendocrine tumors require further workup that includes an assessment of markers to determine the functionality of such lesions and to establish diagnosis of carcinoid syndrome. Minimum workup to be completed once other common causes of noted symptoms have been ruled out include measuring 4-hour urinary excretion of 5-HIAA, Chromogranins level, and blood serotonin level.

Imaging

The pathway to arriving at the diagnosis of small bowel cancer includes significant variability in the order in which tests are completed. There are multiple radiographic as well as endoscopic evaluations that are available to assist in the process of diagnosis and due to the low incidence of such malignant lesions, patients undergo multiple evaluations and imaging studies before a diagnosis is established. 

Computer tomography scan (CT scan): It is estimated that CT scan can help note abnormalities in about 70-80% of patients with small bowel cancer, however, these rates of detection can be quite variable based on the location of the lesion. [14] This modality is often utilized when determining if there is evidence of metastatic spread of disease to distal sites or regional lymph nodes. CT tomography enterography involves evaluation of the small bowel with the addition of a contrast agent that enhances images by causing distention of the small bowel and allowing for better visualization of more occult malignant lesions. [15]

Upper GI series with Small Bowel follow through vs Enteroclysis: Involves the administration of barium which in turn coats the lining of the GI tract and follow up XRs are obtained. The contrast allows for an outline of the esophagus, stomach, and small intestines to be visualized which in turn can assist in evaluation of mucosal abnormalities from neoplastic processes. [16] This particular study does not allow for visualization of smaller lesions and does not assist with staging. [17]

Enteroclysis is a similar imaging study which involves X ray imaging as the main modality however, it has been found to have higher sensitivity than standard upper GI series as it involves the administration of barium into the small intestine via nasogastric tube. While more invasive than an Upper GI series, this particular study does provide higher sensitivity as mentioned previously. 

Endoscopic Evaluation:  Endoscopic evaluation of small bowel cancers helps in identifying mucosal lesions that may not be identified on routine imaging modalities. It can assist in the diagnosis of lesions that are up to the proximal duodenum. Push enteroscopy can help access the GI tract beyond the ligament of Treitz using push or double balloom enteroscopy techniques. This allows for the traditional scope to visualize a more extensive portion of the small bowel which can help in identifying more distal lesions. Wireless video capsule endoscopy can also be utilized to evaluate the distal small bowel, however, it only allows for tissue visualization and no tissue sampling which in turn requires more invasive procedures for final diagnosis to be established. [18]

Treatment / Management

Sarcoma: Small bowel sarcomas include GIST and non-GIST tumors. The management of such lesions varied on the specific type that is identified. GISTs in particular have been found to have activating mutations that involve the KIT protooncogene and therefore therapy has been designated to target this pathway. KIT inhibitors have become first line, most specifically Imatinib.[19] A distinct difference in management for GIST and non-GIST tumors involves node resection which is widely not recommended for such lesions as they rarely metastasize to regional lymph nodes. Surgical resection, therefore, involves resection of the primary lesion with particular consideration placed on ensuring there is no spillage of the resected tissue intraoperatively. 

Adenocarcinoma: Localized small bowel adenocarcinoma is primarily managed with wide segmental surgical resection. The involved mesentery is removed at the time of surgical removal of the tumor. At the time of surgical resection, nodes are also resected as this helps determine the need for adjuvant chemotherapy. If the tumor is large and involves the first and second portions of the small bowel, a Whipple’s procedure may be considered. [20][21]

Neuroendocrine tumors: It has been previously noted that the majority of NETs arise in the jejunum and ileum and are typically well differentiated. They have been noted to be indolent in nature in most cases, however, the do carry metastasis potential. For this reason, resection of the tumor with resection the adjacent mesentery and lymph nodes is generally recommended. This applies to patients with localized disease [22],[23]. Patients with evidence of advanced disease (symptoms consistent with carcinoid syndrome), curative surgery is unlikely to be an option and therefore surgical intervention is generally reserved for debulking/palliative purposes.

Lymphoma: Majority of lesions in the GI tract that are identified as Lymphoma consist of Non-Hodgkin Lymphoma. Majority of SB Lymphoma is managed with surgical resection and adjuvant chemotherapy dependending on the histological subtype of NHL. Adjuvant radiation therapy is a less preferred option due to the many complications that follow radiation to the abdominal cavity considering that studies have not proven the benefits to outweigh the long term complications. 

Differential Diagnosis

The most common presenting signs and symptoms of different small bowel cancers are generally vague in nature. As discussed above, majority of these neoplastic processes include chronic or recurrent abdominal pain, nausea, vomiting, weight loss, or signs consistent with further complications from the cancerous lesions that may include gastrointestinal bleeding or obstructive-type symptoms. Patients who have NETs may have more unique symptoms that may help increase the clinician’s index of suspicion and lead to earlier diagnosis. This is primarily due to the fact that certain NET tumors are associated with carcinoid syndrome and the associated products of the tumor can cause a series of symptoms that are otherwise not seen with small bowel cancers. The differential diagnosis therefore includes Irritable Bowel Syndrome, Peptic Ulcer Disease, Esophagitis, Inflammatory Bowel Disease, Lipomas, Hemangiomas, Functional Abdominal Pain, Adenomas.

Medical Oncology

Small bowel cancer is one of the least commonly identified cancers of the gastrointestinal tract and therefore the number of studies completed to guide therapy is overall limited when compared to other cancers of the GI tract. Each type and case is evaluated on a case by case basis as well as considering the patient’s comorbidities and limitations to tolerate certain therapeutic agents. Most commonly used agents include  Capecitabine, Oxaliplatin, 5-FU, , Leucovorin and Irinotecan.

Staging

The most commonly used staging system for the majority of small bowel cancers  is the TNM staging system. Adenocarcinoma in particular includes a prognostic stage grouping that is utilized as part of the staging process. Small bowel lymphoma is further staged with the use of the Ann Arbor staging system which takes into consideration the number of tumor sites and location.

Prognosis

  • Sarcoma: Prognosis is heavily dependent on location of the tumor, size and resectability when based on surrounding structures with average five year survival rates of approximately 80% if the lesions are resectable. [24]
  • Adenocarcinoma: Prognosis is dependent on staging. Overall, small bowel adenocarcinoma has been found to have higher mortality rates than equivalent staged colon cancers [25]. As expected, nodal involvement is one of the most important prognostic factors that should be considered. One particular study noted that node positive disease vs node negative diseased carried a difference in approximately 40% percent five year survival rate. [26] Distant metastasis carries a much higher mortality rate and therefore significantly reduced five year prognostic value. 
  • Neuroendocrine tumors: Prognosis of neuroendocrine tumors is often more complex than other gastrointestinal malignant lesions as it is also dependent on the tumor burden, type of product secreted, evidence of carcinoid syndrome vs no carcinoid syndrome, and extent of nodal involvement/distal metastasis. Generally, tumors without evidence of carcinoid syndrome carry high survival rates, at times up to 90%. [27]
  • Lymphoma: Prognosis and evaluation of follow up and surveillance is generally under the guidance of the Ann Arbor staging scale. Resectable lesions carry high survival rates, however, the overall prognosis is affected and noted to be variable due ot high rates of recurrence.

Complications

Due to the delay in diagnosis that occurs with small bowel cancer diagnosis, patient's often presents with complications that occur later in the course of the disease for their initial evaluation. The most common complications noted include Upper and Lower Gastrointestinal Bleeding, Small Bowel Obstruction, Small Bowel Perforation and subsequent peritonitis. 

Consultations

Depending on the location of the lesion, General Surgery is often involved in the care of these patients to assist with surgical interventions that may be offered. Medical Oncology as well as Gastroenterologists are key specialists in the diagnosis and treatment of Small Bowel Cancer.

Deterrence and Patient Education

Small Bowel Cancer overall includes a series of malignant lesions that although rare, can be found throughout the small bowel. Education for clinicians should be focused on ensuring this is considered when ruling out causes for non specific gastrointestinal symptoms as this may lead to earlier diagnostic imaging and diagnosis. Patients should be educated on alarm features or signs of complications that may arise once the diagnosis has been established. Depending on the prognosis the patient is expected to have based on the identified lesion, supportive care should be provided by the involvement of the palliative care team and support groups. 

Enhancing Healthcare Team Outcomes

Initial diagnosis and management of small bowel cancer require interdisciplinary efforts to help coordinate diagnostic studies as well as treatment plans. Diagnosis is often delayed due to low index of suspicion by the initial evaluating physician. Once the diagnosis is made patient's outcomes will be significantly improved if the care is well-coordinated between the primary team, general surgeon, gastroenterologist, and medical oncologist. If the patient has evidence of advanced disease, early involvement of the palliative care team may significantly help the patient's quality of life long term and help provide early support for further goals of care discussions. 


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