Small Intestine Tumors

Robert R. Cima, MD, MA

Associate Professor of SurgeryConsultant, Colon and Rectal Surgery

Vice-Chair, Quality and Safety, Department of Surgery

Rochester, MN

Small Intestine Tumors

Robert R. Cima, MD, MA

Associate Professor of SurgeryConsultant, Colon and Rectal Surgery

Vice-Chair, Quality and Safety, Department of Surgery

Rochester, MN

Disclosure

• No financial or commercial relationships

Epidemiology

• Rare and diverse group of tumors• 3,104,173 cancers in the SEER database (1973-2004)

• 20.4% are gastrointestinal (small intestine and colo-rectal malignancies)• ~ 90% are large intestine adeno-carcinomas

• Small intestine (SI) accounts for 80% of intestinal length and 90% of absorptive area• SI malignancies represent 3.1% of intestinal malignancies• Appendiceal cancers represent 0.7%

Epidemiology

• Malignant SI neoplasms• NETs (neuroendocrinetumors) 36.5%• Adenocarcinomas 30.9%• Lymphomas 18.7%• Sarcomas/GISTs 10.0%• Non-specified 3.9%

• Metastatic disease• Melanoma• Breast • Lung Gustafsson et al. 2008

Epidemiology

• Colon malignancies • NETs 0.6%• Adenocarcinomas 93%• Lymphomas 0.4%• Sarcomas/GISTs 0.1%• Non-specified 5.9%

Gustafsson et al. 2008

Epidemiology

• Incidence of SI tumors has been increasing over the last three decades

Gustafsson et al. 2008

Presentation

• Symptoms are vague and non-specific• Abdominal pain (often chronic)• Nausea / Vomiting• Bloating• Diarrhea / Constipation

• Delay in diagnosis often leads to locally advanced disease

• Results in uniformly poor outcomes

Neuroendocrine Tumors (NETs)

• Cells of the diffuse neuroendocrinecell system (DNES)

• Entrochromaffin, enterochromaffin- like, gastrin, etc

• Present in GI, bronchopulmonary, and urogenital system

• Originally termed “Carcinoid” in 1907• Not a uniform cell type tumor but

rather each tumor is comprised of an individual specific cell type of the DNES• Subtypes each exhibit distinct disparate

clinical and biological behavior

NETs

• SI-NETs represents 24.3% of all NETs

• Represents a 4.4-fold increased incidence since 1973

• Majority of SI-NETs (60%) are diagnosed when the disease is no longer localized or metastatic to the liver

• Diagnosis is delayed on average 5 years

• 33% of SI-NETs are multi-centric • 18% of patients present with

“carcinoid” syndrome

Carcinoid Syndrome

• Protean symptomatology• Episodic skin flushing, diarrhea,

bronchoconstriction, sweating, abdominal cramping

• Symptoms related to over-production of vaso- active compounds• Symptom control with long acting

somatostatin (SST) analogs, no impact on survival

• 50% of individuals present with cardiac valve disease related to tumor by-products

NETs

• Surgical resection is the primary treatment

• Survival has steadily increased over the last three decades

• Overall 5 year survival for local disease is 71.8%

• 5 yrs survival with hepatic disease 40% Gustafsson et al. 2008

SI-Adenocarcinoma

• 30.9% of all SI tumors• Duodenum ~50%• Jejunum ~20%• Ileum ~15%

• Peak incidence in 6th

decade• Male predominance• Abdominal pain (67%),

obstruction (40%), bleeding/anemia (24%)

• 5 yr survival poor (~20%)

SI-AdenocarcinomaCrohn’s Disease

• Increased risk of SI adenocarcinoma(x12)

• Associated with sites of chronic inflammation

• Often “watched” as sites of “stable” CD activity

• Survival no worse than idiopathic SI-CA

SI-Adenocarcinoma

• Mayo Clinic series of 491 patients (1970-2005)

• Median survival 20.1 months

• Adjuvant chemotherapy not associated with increased survival (p=0.44)

Halfdanarson et al. 2010

Lymphoma

• Categorized by cell type; broadly grouped by Hodgkin’s and Non-Hodgkin’s

• Commonly present with abdominal pain, weight loss, bleeding, perforation, palpable mass

• Survival tied to cell type• Surgery reserved for

treatment of complications

Sarcomas/Gastrointestinal stromaltumors (GISTs)

• Derived from mesenchymal cells• GISTs are KIT (CD117) positive cells

thought to originate from interstitial cells of Cajal

• 10% of SI tumors• Usually present with bleeding which

can be significant, then obstruction• In a series of 288 GISTs, 69%

detected due to symptoms, 21% incidental findings at surgery, 10% found at autopsy

• Correct histologic type of GIST essential as tyrosine kinase inhibitor agents improve survival in KIT positive cell types

Other tumors of the SI

• Usually metastatic disease

• Melanoma• Breast• Lung

• Common presentation• Anemia• Abdominal pain• Obstruction• Perforation

• Surgery for complications of the disease

Summary• Small intestine malignancies are rare GI

tumors but incidence is increasing• Associated with higher mortality when

compared to colo-rectal malignancies• Non-specific symptoms, difficult to diagnose,

delayed presentation is associated with advanced disease stage

• Surgery primary treatment for symptoms and potential cure

• Current chemotherapy regimens not very effective (exception is KIT+ GISTs)

References

• Gustafsson et al. Int J Oncol. 2008;33:1121• Halfdanarson et al. Am J Surg. 2010;199:797• Qubaiah et al. Cancer Epidemiol Biomarkers

Prev. 2010;19:1908• Ruffolo et al. J Gastrointest Surg. Published

online 14 July 2010• Han et al. World J Gastroenterol. 2010;16:1527• Trikudanathan et al. Expert Opin Pharmacother.

2010:11:1695