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Small intestine cancer
Small intestine cancer
Small intestine cancer
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Small intestine cancer
Other namesSmall bowel cancer, cancer of the small bowel
Picture of a carcinoid tumour that encroaches into lumen of the small bowel. Pathology specimen. The prominent folds are plicae circulares, a characteristic of small bowel.
SpecialtyGastroenterology, general surgery, oncology
Symptomsvomiting blood, blood in the stool

Small intestine cancer is a cancer of the small intestine. It is relatively rare compared to other gastrointestinal malignancies such as gastric cancer (stomach cancer) and colorectal cancer.[1][2]

Small intestine cancer can be subdivided into duodenal cancer (the first part of the small intestine) and cancer of the jejunum and ileum (the latter two parts of the small intestine). Duodenal cancer has more in common with stomach cancer, while cancer of the jejunum and ileum have more in common with colorectal cancer. Five-year survival rates are 65%.[3]

Experts[which?] believe that small intestine cancer develops much like colorectal cancer. It first begins as a small growth on the inner lining of the intestine (polyp), which over time becomes cancer.[4]

Approximately 50% of adenomas of the small intestine arise in the duodenum even though this location comprises only 4% of the length of the small intestine. These adenomas occur mainly close to the ampulla of Vater, the outlet of the common bile duct from which bile acids are released.[5] This area is also closely associated with the pancreas, so they are treated as pancreatic cancer.

The small intestine works by mixing food and gastric juices into a thick fluid in the stomach and then emptied into the small intestine. It then continues to break down and absorb the nutrients. Although it is referred to as the small intestine, it is the longest section of the GI tract being approximately 20 feet long. The length of the small intestine comprises 75% of the length of the entire gastrointestinal tract[6]

There are three parts of the small intestine. The duodenum is the 1st section of small intestine and only about a foot long. The jejunum and ileum make up most of the small intestine. Most of the nutrients in food are absorbed into the bloodstream in these two parts.[4]

Histopathologic types

[edit]
Relative incidence of histopathologic types of small intestine cancers, and their prognoses[7]

Subtypes of small intestine cancer include:[4]

Most small intestine cancers (especially adenocarcinomas) develop in the duodenum. Cancers developed in the duodenum are often found at the ampulla of Vater.

  • Adenocarcinoma
    Adenocarcinoma
  • Carcinoid
    Carcinoid

Risk factors

[edit]
Endoscopic image of adenocarcinoma of duodenum seen in the post-bulbar duodenum

Risk factors for small intestine cancer include:[8][9]

  • Age: Cancer risk increases with age. The average age diagnosis is 65.(Cleveland Clinic, 2022)
  • Race: In the U.S., small intestine cancer is slightly more common among people who identify as African Americans. Although lymphoma is more common among people who identify as white.(Cleveland Clinic, 2022)
  • HIV/AIDS: treatments like radiation therapy may weaken your immune system and make you more susceptible to small intestine cancer. Drugs that suppress your immune system may also increase your risk.(Cleveland Clinic, 2022)
  • Sex: Males are 25% more likely to develop the disease.(Cleveland Clinic, 2022)
  • Diet: Various research has suggested that diets high in red meat and salted or smoked foods may raise the risk of small intestine cancer.(Cleveland Clinic, 2022). A human prospective study observed a markedly elevated risk for carcinoid tumors of the small intestine associated with dietary intake of saturated fat[10]
  • Crohn's disease
  • Celiac disease
  • Radiation exposure
  • Hereditary gastrointestinal cancer syndromes: familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz–Jeghers syndrome
  • Cholecystectomy, which alters the flow of bile to the small intestine, increases the risk of small intestinal adenocarcinomas,[11] and this risk declines with increasing distance from the common bile duct.

Additional images

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References

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Small intestine cancer

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Small intestine cancer, also known as small bowel cancer, is a rare that arises from uncontrolled cell growth in the tissues of the , the longest segment of the —measuring about 20 feet in adults—that connects the to the and is essential for digesting food, absorbing nutrients, and supporting immune function. Although rare, its incidence has been increasing in recent years. This cancer typically begins as a polyp or abnormal growth on the inner lining of the , most commonly in the (the first section), and can spread to nearby tissues or distant organs if not detected early. , it represents fewer than 1 in 10 of all gastrointestinal cancers, with an estimated lifetime risk of approximately 0.3% for both men and women. The small intestine consists of three main parts—the duodenum, jejunum, and ileum—each of which can be affected by different histological subtypes of this cancer. The primary types include , which originates in the glandular cells lining the intestine and accounts for about one-third of cases; neuroendocrine tumors (such as tumors), which are often slow-growing and hormone-producing; lymphomas, which develop from cells in the intestinal wall; and sarcomas, including gastrointestinal stromal tumors (GISTs) that arise from connective or supportive tissues. These subtypes vary in behavior, with adenocarcinomas being more aggressive and neuroendocrine tumors potentially remaining localized for longer periods. Symptoms of small intestine cancer are often nonspecific and may mimic other gastrointestinal disorders, delaying diagnosis until the disease has advanced. Common signs include crampy abdominal pain (especially after eating), unexplained weight loss, fatigue, blood in the stool (which may appear dark or tarry), jaundice (yellowing of the skin and eyes if the tumor blocks the bile duct), nausea, vomiting, watery diarrhea, and skin flushing in cases of neuroendocrine tumors. Risk factors encompass inherited genetic conditions such as Lynch syndrome and familial adenomatous polyposis (FAP), chronic inflammatory bowel diseases like Crohn's disease and celiac disease, impaired immune function (e.g., from HIV or organ transplants), and lifestyle elements including a diet high in red and processed meats or alcohol and low in fiber. Despite its rarity, early detection through imaging, endoscopy, or biopsy can improve outcomes, with treatment typically involving surgery to remove the tumor, often combined with chemotherapy, targeted therapies, or radiation depending on the stage and type.

Clinical presentation

Symptoms

Small intestine cancer often presents with nonspecific symptoms that can mimic other gastrointestinal disorders, leading to delayed . The most common patient-reported complaints include , unexplained , , , and . Abdominal pain is frequently the initial symptom, typically described as crampy and intermittent, often worsening after eating and located in the mid-. For tumors in the , pain may be centered in the upper mid-, while ileal involvement can cause discomfort in the lower . Unexplained and fatigue are also prevalent, with the latter sometimes associated with from occult . and occur commonly, and changes in bowel habits—such as or —may develop as the tumor progresses, along with dark-colored stools due to . In late stages, symptoms often intensify due to intestinal obstruction, manifesting as , , and severe cramping . The onset of these symptoms is typically insidious, developing gradually over several months, with an average delay of 6 to 12 months from initial presentation to diagnosis owing to their vague nature.

Signs

Small intestine cancer often manifests with objective clinical signs detectable during , reflecting tumor location, size, and complications such as obstruction or bleeding. Abdominal tenderness upon may be elicited, particularly in the presence of local or partial caused by the tumor. Jaundice, presenting as yellowing of the skin and sclerae, arises from biliary obstruction in periampullary tumors located near the . In advanced disease with peritoneal dissemination, ascites may accumulate, leading to and fluid wave on examination. Cachexia, evident as profound involuntary accompanied by muscle wasting and general debility, commonly appears in progressive or metastatic cases. Chronic blood loss from tumor ulceration frequently results in , manifesting as of the skin and mucous membranes along with due to compensatory increased . , a potential complication, yields hyperactive bowel sounds in early or partial stages due to proximal , progressing to diminished or absent sounds in complete obstruction with paralytic . A palpable abdominal mass is identified in approximately 25% of cases overall, occurring more commonly with sarcomas such as gastrointestinal stromal tumors that tend to grow exophytically and attain larger sizes.

Risk factors and etiology

Genetic and inherited factors

Small intestine cancer arises from a combination of inherited and sporadic genetic alterations. (FAP), an autosomal dominant disorder caused by germline mutations in the gene on chromosome 5q21-22, significantly elevates the of small bowel , particularly in the . Individuals with FAP face a lifetime of 3-5% for small bowel , representing a increase of over 300-fold compared to the general population. These mutations lead to truncated proteins that disrupt the regulation of β-catenin, promoting uncontrolled cell proliferation through aberrant activation of the , which drives polyp formation and progression to . Peutz-Jeghers syndrome (PJS), an autosomal dominant condition due to germline mutations in the gene on chromosome 19p13.3, is associated with hamartomatous polyps throughout the and a markedly increased risk of small bowel , with a lifetime risk estimated at 13% ( >500-fold). These mutations impair the LKB1 protein's role in regulating cell growth and polarity, leading to polyp formation and heightened malignant transformation. Lynch syndrome, another autosomal dominant condition resulting from germline defects in genes such as MLH1, MSH2, MSH6, and PMS2, is associated with increased incidence of small bowel and, to a lesser extent, lymphomas. The lifetime risk of small bowel in Lynch syndrome carriers is estimated at 1-4%, conferring a of over 100-fold relative to the general population. These mutations impair , leading to and accumulation of somatic mutations that contribute to tumorigenesis, often presenting at younger ages and with a higher frequency of multiple primary cancers. In sporadic cases, which comprise the majority of small intestine cancers, somatic mutations play a central role. Adenocarcinomas frequently harbor alterations in KRAS (approximately 42% of cases), TP53 (54%), and APC (11%), which activate oncogenic signaling and disrupt tumor suppression, facilitating tumor initiation and progression. For neuroendocrine tumors of the small intestine, common genetic changes include chromosomal losses, notably of (observed in up to two-thirds of cases); these alterations are thought to influence tumor growth and , though their precise functional roles remain under investigation.

Environmental and lifestyle factors

Environmental and lifestyle factors play a role in the development of small intestine cancer, particularly through modifiable exposures that promote chronic or cellular damage. Dietary patterns, such as high consumption of animal fats and proteins, have been associated with increased of small bowel , with correlations observed between these dietary components and cancer incidence (r = 0.61 for fats, r = 0.75 for proteins). Similarly, red and intake is linked to a 2- to 3-fold elevated for small intestine cancers, potentially due to carcinogenic compounds formed during processing or cooking. In contrast, low-fiber diets may exacerbate by impairing gut health, while high fiber intake appears protective against . Chronic inflammatory conditions triggered by diet, such as celiac disease, substantially raise the of small intestine by 10- to 13-fold through persistent mucosal and immune dysregulation. Lifestyle behaviors further contribute to susceptibility. is associated with a 1.5- to 2-fold higher risk of small bowel , with current smokers showing a of 1.77 compared to never smokers in large cohort studies. Alcohol consumption demonstrates a weak positive with risk, with a of approximately 1.5 for heavy drinkers. Occupational exposures also pose risks, particularly for neuroendocrine tumors; workers in metal preparation and have shown elevated rates, with odds ratios up to 4.3 for structural metal workers developing tumors. , often exacerbated by environmental triggers like diet and , increases risk by 20- to 60-fold via chronic , with standardized incidence ratios reaching 34.9 in affected individuals. Demographic factors intersect with these exposures to heighten vulnerability. Small intestine cancer incidence is higher in males, with a male-to-female ratio of 1.3:1, and predominantly affects individuals over 60 years of age, with a diagnosis age of 66. emerges as an additional modifiable factor, conferring a of about 1.3 for small intestine cancers, particularly through abdominal adiposity that promotes and . These environmental and lifestyle elements can interact with genetic predispositions to amplify overall risk, though their effects are largely acquired rather than inherited.

Histopathologic classification

Adenocarcinoma

Adenocarcinoma is the most common histologic subtype of small intestine cancer, arising from glandular epithelial cells and accounting for approximately 30-40% of all small bowel malignancies. It predominantly occurs in the , representing about 50% of cases, followed by the at around 30%, with the being less frequently affected at 20%. This subtype is histopathologically similar to colorectal but exhibits distinct molecular features that differentiate it from other gastrointestinal cancers. Macroscopically, small bowel adenocarcinomas often present as annular constricting lesions that lead to intestinal obstruction, particularly in the and , while duodenal tumors may appear more exophytic and polypoid. These growth patterns contribute to early symptoms such as and due to partial or complete blockage. Microscopically, these tumors display tubular or mucinous architectural patterns, characterized by complex glandular structures embedded in a desmoplastic stromal reaction. They can be further subclassified into intestinal-type (expressing CDX-2, MUC2, and CD10) or gastric-type (expressing MUC5AC and MUC6) phenotypes, with poorly differentiated forms being more common than in colorectal counterparts. The molecular profile of small bowel adenocarcinoma includes frequent inactivating mutations in APC (seen in 7-27% of cases), activating mutations in KRAS (approximately 42-54%), and alterations in SMAD4 (10-17%), which drive tumorigenesis and progression similar to but less pronounced than in colorectal cancer. HER2 (ERBB2) amplification occurs in 8-13% of tumors, particularly those in the duodenum, offering potential for targeted therapies. Additional common alterations involve TP53 (around 58%) and PIK3CA (16%), with microsatellite instability in about 8% and high tumor mutational burden in 10%. Clinically, small bowel adenocarcinoma demonstrates aggressive local invasion into surrounding tissues and is associated with metastasis at diagnosis in 30-40% of patients, most commonly to the liver and . Compared to neuroendocrine tumors, it carries a poorer , with 5-year overall survival rates of approximately 71%. Patients with underlying conditions such as face an elevated risk for this subtype.

Neuroendocrine tumors

Neuroendocrine tumors (NETs), formerly referred to as tumors, account for approximately 40% of all small intestine malignancies and are the most common subtype. These neoplasms arise from enterochromaffin cells within the diffuse neuroendocrine system of the gut mucosa. They predominantly originate in the , comprising about 60% of small bowel NETs, with the remainder occurring in the or . While most are well-differentiated (grades 1 or 2), poorly differentiated neuroendocrine carcinomas represent a more aggressive subset with higher proliferative activity. A notable feature of small bowel NETs is their multifocality, observed in up to 30% of cases, which underscores the need for thorough evaluation of the entire during . In patients with advanced disease, particularly those with liver metastases, 10-20% develop , manifesting as episodic flushing, diarrhea, and abdominal cramping due to excessive serotonin secretion by the tumor. This syndrome highlights the functional endocrine capacity of these tumors, distinguishing them from non-hormone-producing small bowel cancers. Histologically, small bowel NETs are characterized by nests or trabeculae of uniform polygonal cells with finely granular, salt-and-pepper and inconspicuous nucleoli. Immunohistochemical is typically positive for neuroendocrine markers such as chromogranin A and , aiding in confirmation of the . These tumors generally exhibit indolent growth patterns, but 30-50% present with metastases at , often to regional lymph nodes or the liver. Tumor grading relies on the Ki-67 proliferation index, where grade 1 tumors have a low index of less than 3%, indicating slower proliferation and better differentiation. Some small bowel NETs are associated with inherited syndromes like ().

Lymphomas

Lymphomas account for approximately 15-20% of small intestine malignancies, with the vast majority being non-Hodgkin lymphomas, particularly and, less commonly, . These tumors arise from the lymphoid tissue within the intestinal mucosa and are characterized by their potential association with underlying conditions such as , including in patients with . A notable link exists with celiac disease, which predisposes to specific subtypes like , though B-cell variants predominate overall. These lymphomas most frequently originate in the , comprising 60-65% of cases, often involving the Peyer's patches, which are aggregates of lymphoid follicles in the intestinal wall. A distinctive variant, immunoproliferative small intestinal disease (IPSID), is prevalent in Mediterranean and Middle Eastern regions and typically affects the proximal , presenting as a low-grade linked to chronic infection with . Histologically, lymphomas feature dense lymphoid infiltrates that efface the normal mucosal architecture, with the majority showing CD20-positive B-cells indicative of B-cell lineage origin. These infiltrates often extend transmurally and may include a component in IPSID cases. In terms of behavior, these tumors exhibit rapid growth, particularly in high-grade forms like , with such as fever, night sweats, and weight loss occurring in 20-30% of patients. Extranodal spread is frequent, commonly involving mesenteric lymph nodes or adjacent structures, contributing to their aggressive clinical course.

Sarcomas

Sarcomas represent rare mesenchymal tumors arising from the s of the , accounting for approximately 10-20% of all small bowel malignancies. These tumors originate from , stromal cells, or other mesenchymal elements and are distinct from epithelial or lymphoid neoplasms due to their non-hematopoietic, connective tissue derivation. The primary subtypes include gastrointestinal stromal tumors (GISTs), which are the most common form of small intestine sarcoma, leiomyosarcoma, and less frequently liposarcoma. GISTs arise from interstitial cells of Cajal and are characterized by activating mutations in the KIT gene, leading to c-kit protein expression. Leiomyosarcomas typically develop from smooth muscle layers. Liposarcomas, though rarer in the small bowel, originate from adipose tissue precursors. These tumors predominantly occur in the jejunum and ileum, with the ileum being a favored site for leiomyosarcomas and both jejunum and ileum commonly affected by GISTs. GISTs in the small intestine are typically c-kit positive on immunohistochemical staining, aiding in their identification. Histologically, leiomyosarcomas consist of spindle-shaped cells with atypical nuclei, eosinophilic cytoplasm, and a high mitotic rate that correlates with aggressive behavior. In contrast, GISTs often display epithelioid or spindle cell morphology, with epithelioid variants showing rounded cells and prominent nucleoli; a elevated mitotic rate further indicates malignancy potential. Sarcomas of the are often diagnosed at a large size, with an tumor of about 10 cm, contributing to their insidious presentation. They exhibit aggressive behavior through hematogenous spread, with to the liver occurring in approximately 40% of cases at diagnosis or recurrence.

Diagnosis

Imaging studies

studies play a crucial role in the initial detection, localization, and characterization of cancers, often prompted by symptoms such as or obstruction. These non-invasive modalities help identify tumor masses, assess bowel wall involvement, and evaluate for regional or distant spread, guiding subsequent diagnostic steps. Computed tomography (CT) enterography is the preferred initial test for suspected small intestine cancer due to its high resolution and ability to evaluate the entire bowel. It involves oral contrast to distend the small bowel loops, allowing detection of masses greater than 1 cm with a sensitivity of 80-90%, particularly for identifying circumferential wall thickening, luminal narrowing, and associated . This modality excels in delineating features like shouldering of the bowel wall and mesenteric involvement, as well as complications such as obstruction or . Magnetic resonance (MR) enteroclysis provides detailed evaluation and is particularly useful in younger patients to minimize , offering an alternative to CT for comprehensive bowel assessment. By using oral and intravenous contrast with bowel distension, it achieves high accuracy (up to 96.6%) in detecting small bowel neoplasms, superior for characterizing tumor margins, vascular involvement, and multifocal lesions without . It is especially beneficial for neuroendocrine tumors, where it highlights hypervascularity and desmoplastic reactions. Positron emission tomography-computed tomography (PET-CT) is primarily employed for staging, particularly in neuroendocrine tumors using imaging (e.g., 68Ga-DOTATATE PET-CT) to detect primary lesions and metastases with high sensitivity due to receptor overexpression. For aggressive subtypes like or , 18F-FDG PET-CT aids in identifying metabolically active disease and occult metastases, improving staging accuracy over CT alone, though it is not routine for initial detection. Ultrasound has a limited role in small intestine cancer evaluation due to acoustic shadowing from bowel gas, but it can detect secondary signs such as , , or peritoneal spread with moderate sensitivity (around 50%). (EUS) is more targeted for duodenal lesions, providing high-resolution images of the bowel wall layers to assess depth of invasion and guide , with utility in preoperative planning for ampullary or proximal tumors.

Endoscopic and biopsy procedures

Endoscopic procedures provide direct visualization and tissue sampling of the , often guided by prior abnormalities such as masses or wall thickening identified on CT or MRI. Upper , also known as (EGD), is the primary method for evaluating duodenal tumors in small intestine cancer. This procedure involves inserting a flexible through the mouth to examine the , , and , allowing for real-time visualization and targeted of suspicious lesions. Biopsies obtained during EGD enable pathologic confirmation of , including adenocarcinomas. Capsule endoscopy offers a non-invasive means to visualize the entire small bowel mucosa, particularly useful for detecting tumors in the jejunum or ileum that are beyond the reach of standard EGD. Patients swallow a small capsule containing a camera that transmits images as it traverses the digestive tract, providing comprehensive assessment of mucosal lesions with a sensitivity of approximately 80% for small bowel tumors. However, this modality lacks the ability to obtain biopsies, necessitating follow-up procedures for tissue confirmation if abnormalities are detected. Double-balloon enteroscopy extends diagnostic and sampling capabilities deeper into the , targeting the and for tumors not accessible by conventional . This technique uses an with two balloons—one on the scope tip and one on a transparent overtube—that are alternately inflated to pleat the intestinal wall, advancing the scope while minimizing loops; it can be performed via oral (anterograde) or rectal (retrograde) routes. The procedure achieves total in about 86% of cases and facilitates in the majority of targeted lesions, with a diagnostic yield superior to for small or submucosal tumors. Biopsy specimens from these endoscopic procedures undergo cytologic and histologic analysis to confirm and classify the tumor type. examination reveals characteristic features such as glandular formations in adenocarcinomas, with playing a key role in subtyping; for instance, small bowel adenocarcinomas may show cytokeratin 7 (CK7) positivity, aiding differentiation from other gastrointestinal malignancies.

Staging

TNM classification

The TNM classification system, developed by the American Joint Committee on Cancer (AJCC), is used to stage small intestine cancers, primarily adenocarcinomas, based on the extent of the (T), involvement of regional lymph nodes (N), and presence of distant (M). This system, as outlined in the AJCC 8th edition (effective January 2018), provides a standardized framework for assessing disease progression and guiding clinical management. The T category reflects the depth of tumor invasion into the small bowel wall. T1 tumors are confined to the or (with T1a limited to the lamina propria and T1b to the ). T2 tumors invade the muscularis propria. T3 tumors extend through the muscularis propria into the subserosa or nonperitonealized perimuscular tissue (such as the ) without penetrating the serosa. T4 tumors perforate the visceral peritoneum or directly invade adjacent organs or structures, such as the or in duodenal cases. The N category indicates regional lymph node involvement, with regional nodes including mesenteric and perigastric nodes for the . N0 denotes no regional . N1 indicates in 1 to 2 regional s. N2 signifies in 3 or more regional s. The M category assesses distant spread. M0 indicates no distant . M1 denotes distant , commonly to sites such as the liver or . For neuroendocrine tumors of the (primarily jejunal and ileal), the AJCC 8th edition adapts the TNM with modifications based on tumor size and node burden, while incorporating histologic grade (G1 to G3, determined by mitotic rate and Ki-67 index) as a prognostic factor that influences overall staging and outcomes, though grade is not directly integrated into the core T, N, or M descriptors. In this context, T1 tumors invade the or and are ≤1 cm; T2 tumors invade the muscularis propria or are >1 cm; T3 tumors extend through the muscularis propria into subserosal tissue without penetrating the serosa; and T4 tumors invade the serosa or adjacent structures. N1 involves fewer than 12 regional nodes, while N2 involves 12 or more regional nodes and/or extensive mesenteric masses (>2 cm).

Prognostic groupings

Prognostic groupings for small intestine cancer integrate the TNM classification elements into stage categories that predict patient outcomes, primarily for , the most common . These groupings, defined by the American Joint Committee on Cancer (AJCC), stratify disease based on tumor invasion depth (T), regional involvement (N), and distant (M), providing a framework for and treatment planning. For adenocarcinoma, the 5-year relative survival rates based on SEER data (2015–2021) are approximately 86% for localized disease (Stages I and II), 80% for regional disease (Stage III), and 47% for distant disease (Stage IV). The following table summarizes the AJCC prognostic stage groups for small intestine adenocarcinoma:
StageTNM CombinationDescription
IT1-2 N0 M0Tumor invades submucosa or muscularis propria; no regional lymph nodes or distant metastasis.
IIAT3 N0 M0Tumor invades subserosa; no regional lymph nodes or distant metastasis.
IIBT4 N0 M0Tumor perforates serosa or invades adjacent structures; no regional lymph nodes or distant metastasis.
IIIAAny T N1 M0Any T stage with metastasis to 1-2 regional lymph nodes; no distant metastasis.
IIIBAny T N2 M0Any T stage with metastasis to 3 or more regional lymph nodes; no distant metastasis.
IVAny T Any N M1Distant metastasis present.
Note that staging systems differ for other subtypes: lymphomas typically use the Lugano classification, while sarcomas, including gastrointestinal stromal tumors (GISTs), use AJCC staging for sarcomas or specific GIST criteria. Neuroendocrine tumors of the use a distinct AJCC staging system, often simplifying to localized (no ), regional (nodal involvement), and metastatic categories, with 5-year exceeding 90% for localized disease but dropping to around 54% for metastatic cases. Tumor grade is integrated into these groupings, as high-grade (poorly differentiated) tumors adversely affect across stages, often leading to upstaging equivalent to advanced disease due to aggressive behavior.

Treatment

Surgical interventions

Surgical interventions represent the cornerstone of treatment for localized small intestine cancer, aiming to achieve complete tumor removal while preserving intestinal function. For resectable disease, the primary approach involves of the affected bowel segment, including the tumor and a margin of surrounding healthy tissue, accompanied by to address regional involvement. This procedure typically includes removal of at least 8-10 s for adequate staging and oncologic clearance. In cases of duodenal , a more extensive (Whipple procedure) is often required due to the tumor's proximity to the and , incorporating resection of the , head of the , and adjacent structures. Surgical margins of at least 5 cm proximally and distally are recommended to minimize local recurrence risk. For neuroendocrine tumors of the , surgery focuses on curative intent for localized lesions through or right hemicolectomy for ileal tumors, with mesenteric to resect involved nodes and desmoplastic reactions that may cause . In advanced cases with liver metastases, which occur in 50-75% of at , cytoreductive is performed to alleviate symptoms from hormone excess, such as , particularly when hepatic tumor burden exceeds 50-90%. Liver resection, including hemihepatectomy or wedge resections, is feasible in approximately 20-50% of metastatic cases, depending on tumor distribution and fitness, often combined with techniques for multifocal . Palliative surgical options are employed for unresectable or advanced disease causing complications like intestinal obstruction or bleeding. Bypass procedures, such as gastrojejunostomy for duodenal lesions or enteroenterostomy for jejunal/ileal blockages, divert intestinal contents around the tumor to restore patency without attempting curative resection. For duodenal obstructions, endoscopic stenting with self-expandable metal stents provides an alternative to , offering faster symptom relief and shorter hospital stays in select patients. Oncologic outcomes of surgical resection vary by and , with R0 resection (negative margins) achieved in 50-70% of cases for primary small bowel tumors, correlating with improved local control. Postoperative complication rates range from 20-45%, including anastomotic leaks (5-10%), infections, and prolonged , with higher risks in extensive procedures like . Morbidity is influenced by patient comorbidities and nutritional status, but overall 30-day mortality remains low at 2-5% in specialized centers.

Systemic and targeted therapies

Systemic therapies for small intestine cancer encompass , targeted agents, and , tailored to the histologic subtype such as , , gastrointestinal stromal tumors (GIST), or neuroendocrine tumors (NETs). These approaches are primarily used in adjuvant settings following or for metastatic disease, aiming to control tumor growth, alleviate symptoms, and improve survival. Selection of therapy depends on tumor biology, patient , and molecular features like microsatellite instability (MSI) status. For small bowel adenocarcinoma, the most common epithelial malignancy, systemic chemotherapy is a cornerstone. In adjuvant settings for locally advanced disease, regimens such as (fluorouracil, leucovorin, and ) or CAPEOX ( and ) are recommended for 6 months to reduce recurrence risk. In metastatic cases, first-line or CAPEOX yields objective response rates of approximately 45-50%, with median around 7 months. (fluorouracil, leucovorin, and ) serves as a second-line option, achieving response rates of about 20%. may be added to these fluoropyrimidine-based regimens to enhance efficacy in advanced disease. Primary lymphomas of the , often diffuse large B-cell type, respond well to immunochemotherapy. The R-CHOP regimen (rituximab, , , , and ), administered in 21-day cycles for 6-8 cycles, is the standard, achieving complete remission rates of 60-70% in aggressive non-Hodgkin lymphomas, including gastrointestinal subtypes. This combination targets B-cell proliferation and has demonstrated superior outcomes over CHOP alone in improving event-free survival. Targeted therapies address specific molecular drivers in small intestine sarcomas and NETs. For GIST, which arises from , mesylate—a — is first-line at doses of 400-800 mg daily, inhibiting KIT or PDGFRA mutations present in over 80% of cases. Clinical trials report partial response rates of 50-70%, with many patients achieving stable disease and prolonged exceeding 2 years. For well-differentiated small intestine NETs, analogs such as or provide symptomatic relief from by suppressing hormone secretion; they are administered as long-acting formulations monthly, stabilizing tumor growth in NETs as shown in the PROMID trial. For progressive disease, (an inhibitor) is recommended, with peptide receptor radionuclide therapy (PRRT) using lutetium Lu 177 dotatate for receptor-positive tumors, and (a multi-tyrosine kinase inhibitor) as a recent option for advanced gastroenteropancreatic NETs per NCCN guidelines version 1.2025. Emerging immunotherapy options target immune checkpoints in select cases. Approximately 5-10% of small bowel adenocarcinomas exhibit MSI-high (MSI-H) status due to mismatch repair deficiency, rendering them responsive to PD-1 inhibitors like or nivolumab. In MSI-H advanced gastrointestinal cancers, including small bowel subtypes, these agents yield objective response rates of 30-50%, with durable responses in refractory settings as evidenced by KEYNOTE-158 and trials. Such therapies are typically reserved for later lines after failure.

Prognosis

Survival outcomes

The 5-year relative for small intestine cancer is 71.1% overall, based on diagnoses from 2015 to 2021. rates vary markedly by at , with 86% for localized disease confined to the , 80% for regional involvement of nearby lymph nodes or structures, and 47% for distant , according to recent Surveillance, Epidemiology, and End Results (SEER) Program data as of 2025. These outcomes differ substantially across histological subtypes. Neuroendocrine tumors generally exhibit the most favorable , with 5-year rates of 80-90%, reflecting their often indolent behavior and responsiveness to targeted therapies. In contrast, adenocarcinomas, the most aggressive epithelial malignancies in the , have 5-year rates of 30-50%, influenced by late presentation and limited systemic options. lymphomas achieve 64% 5-year with regimens like CHOP, particularly when combined with for localized disease (based on Canadian data). Sarcomas, including gastrointestinal stromal tumors (GISTs), show 79% 5-year following resection and therapy such as (based on Canadian data). Survival has improved notably in recent decades, with increases in 5-year relative rates since 2000, attributable to enhanced for earlier staging and multidisciplinary treatment approaches.

Influencing factors

Several tumor-related characteristics significantly influence the of small intestine cancer, particularly , the most common histological subtype. High-grade tumors, characterized by poor differentiation, are associated with worse outcomes due to increased aggressiveness and metastatic potential. Tumor location also plays a critical role, with duodenal adenocarcinomas exhibiting the poorest —median overall as low as 20 months—compared to ileal tumors, which show better outcomes owing to earlier detection and easier surgical access. Additionally, resection margin status is a key determinant; R1 resections (microscopically positive margins) are linked to significantly diminished relative to R0 (negative margins) resections by promoting local recurrence. Patient-specific factors further modulate beyond tumor . Advanced age, particularly over 70 years, correlates with reduced 5-year , attributed to diminished physiological reserve and higher burden, as evidenced by SEER data showing progressively lower relative in older cohorts. Poor , defined as Eastern Cooperative Oncology Group (ECOG) score greater than 2, independently predicts inferior overall due to limited tolerance for aggressive therapies. Comorbid conditions, such as , exacerbate outcomes in small bowel , yielding 5-year rates around 30%—notably lower than in de novo cases—stemming from chronic and diagnostic delays. Treatment-related variables can favorably alter when optimized. Achieving complete (R0) resection improves 5-year survival to 42% in localized , reflecting effective local control and reduced recurrence risk. Evidence for adjuvant in node-positive cases is limited, with non-randomized studies showing no clear survival benefit. Biomarkers offer prognostic and therapeutic insights, particularly microsatellite instability-high (MSI-H) status, present in 18-35% of small bowel . MSI-H tumors predict superior responses to , with objective response rates of 30-50% and prolonged in responders, contrasting with stable tumors that show limited benefit.

Epidemiology

Incidence and prevalence

Small intestine cancer is a rare , accounting for less than 1% of all cancer diagnoses worldwide. Globally, an estimated 64,477 new cases were reported in 2020, corresponding to an age-standardized incidence rate (ASR) of 0.60 per 100,000 population. This represents approximately 3.5% of all gastrointestinal cancers. , projections for 2025 estimate about 13,920 new cases.00816-8/fulltext) The disease exhibits geographic variation, with higher incidence rates in high-income Western countries compared to regions in . In very high human development index (HDI) countries, which include many Western nations, the ASR reaches 1.0 per 100,000, while in low HDI regions such as parts of , it is approximately 0.3 per 100,000. remains low overall, with an estimated 89,327 individuals living with small intestine cancer in the United States as of 2022. The condition predominantly affects older adults, with a peak incidence in the 60-70 age group and a median age at of around 66 years. There is a slight predominance, with a -to-female incidence of approximately 1.2:1.00816-8/fulltext) Histologically, small intestine cancers comprise a diverse group of subtypes, with neuroendocrine tumors (including carcinoids) and being the most common. The approximate distribution of major types based on recent population data is shown below:
TypePercentage
32%
Neuroendocrine tumors41%
14%
(including GIST)14%
This distribution underscores the heterogeneity of the disease, with more frequently occurring in the duodenum and neuroendocrine tumors in the ileum.00105-1/fulltext) The incidence of small intestine cancer has shown a consistent upward trend worldwide over the past several decades, with age-standardized rates (ASRs) increasing in most regions due to improved detection, changes in risk factors, and shifts in histological subtypes such as neuroendocrine tumors. , the ASR rose from 1.02 per 100,000 in 1975 to 2.93 per 100,000 in 2022, representing an overall increase of approximately 118% from 1975 to 2018, based on Surveillance, Epidemiology, and End Results (SEER) Program data. Globally, an estimated 64,477 new cases occurred in 2020, with an ASR of 0.60 per 100,000, and average annual percent changes (AAPCs) ranging from 2.20% to 21.67% across countries, reflecting a broad pattern of rising burden particularly in high-income nations. Demographic variations highlight disparities in incidence by , age, and race/. Men experience higher rates than women, with U.S. ASRs of 2.61 per 100,000 for men and 1.92 per 100,000 for women from 2000 to 2019, and a similar global pattern showing male ASRs of 0.73 versus 0.49 per 100,000 in 2020; men accounted for 53.10% of U.S. cases during this period. Incidence increases markedly with age, peaking in the 80–84 age group and with a age of 66 years, though the 55–69 age group comprises the largest proportion of cases (38.08%) in the U.S. Racial disparities are evident, with non-Hispanic Black individuals showing the highest ASRs, such as 4.25 per 100,000 among Black men, compared to lower rates among (who represent 69.07% of cases); Black men have rates 42% higher than White men, and Black women 46% higher than White women. Geographic variations underscore higher incidence in developed regions, with North America and Western Europe reporting ASRs up to 1.4–1.5 per 100,000 (e.g., highest country-specific rates in Norway and French Guiana), compared to lower rates in Asia (e.g., 0.7 per 100,000 in Japan) and sub-Saharan Africa (0.12 per 100,000). In the U.S., from 2000 to 2020, annual incidence rose from 1.54 to 2.78 per 100,000, with AAPCs of 2.01% for men and 2.12% for women through 2019, though a temporary 8.94% decline occurred in 2020 likely due to COVID-19 disruptions in screening. Histopathological subtypes also vary in trends, with neuroendocrine carcinomas being the most common (54.26% of U.S. cases), showing steeper increases than adenocarcinomas or gastrointestinal stromal tumors (GISTs).00105-1/fulltext)

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