benign and malignant tumors of small bowel

1. Tumors of Small Bowel
Presenter-
Dr. Akshay Sarraf
2nd Year Resident
Dept. of General Surgery
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2. Introduction
• Small intestine contains over 90% of the mucosal surface area of the GI
tract but only 1.1% to 2.4% of all GI malignancies.
• The incidence of small bowel cancer has increased an average of
approximately 2% each year during the past 15 years.
• The 5-year survival for localized small bowel cancer is approximately
85%(vs. 42% in distant disease).
• Mean age at presentation- 62 years for benign tumors and approximately
57 years for malignant tumors.
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3. • The incidence of small bowel cancer is particularly low in India,
Romania, and other parts of Eastern Europe.
• Most benign neoplasms are asymptomatic and often identified as an
incidental finding.
• Malignant neoplasms account for 75% of symptomatic lesions that
lead to surgery.
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4. • Stromal tumors and adenomas are the most frequent of the benign
tumors and appear to be more common in the distal small bowel.
• Adenocarcinoma is the most common malignant neoplasm.
• Neuroendocrine tumors (NETs) account for 25% to 30% of small
intestine malignant neoplasms.
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5. • Risk factors-
1. Familial Adenomatous Polyposis (FAP) 6. Prior peptic ulcer disease
2. Hereditary Nonpolyposis Colorectal Cancer 7. Cystic fibrosis
3. Peutz-Jeghers syndrome 8. Biliary diversion (i.e., previous cholecystectomy)
4. Crohn disease 9. Smoking, heavy alcohol consumption
(>80 g/day of ethanol),
5. Gluten-sensitive enteropathy (i.e., celiac sprue) 10. Consumption of red meat or salt cured
foods.
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6. • Genetics
• KRAS gene mutation.
• Deletion of 5q (APC gene), 17q (p53 gene), and 18q (DCC [deleted in colon
cancer] and DPC4 [SMAD4] genes).
• DNA mismatch gene repair is inactivated.
• Microsatellite instability (MSI-H)- typical of small bowel carcinomas
associated with celiac disease.
• Epidermal growth factor receptor and vascular endothelial growth factor
(VEGF) expression.
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7. • Presentation
• Most patients with benign neoplasms remain asymptomatic.
• Often vague and nonspecific and may include dyspepsia, anorexia, malaise,
and dull abdominal pain, often intermittent and colicky.
• Pain, most often related to obstruction, is the most frequent complaint.
• Bleeding is usually occult; hematochezia or hematemesis may occur.
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8. • Diagnosis
• High index of suspicion must be present for these neoplasms to be diagnosed.
• Correct preoperative diagnosis is made in only 50% of symptomatic patients.
• Plain X-Ray- just for confirming obstruction.
• Small bowel follow-through yields an accurate diagnosis in 53% to 83% of
patients with malignant neoplasms
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9. • CT of the abdomen can prove particularly useful in detecting extraluminal
tumors, such as GISTs.
• Ultrasonography has not proved effective for preoperative diagnosis of small
bowel neoplasms.
• CT enteroclysis appears to be a more sensitive technique, with a diagnostic
accuracy of approximately 95%.
• MRI enteroclysis has a sensitivity and specificity of 98% and 97%,
respectively.
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10. • Flexible endoscopy- duodenal lesions; the colonoscope can be advanced into
the terminal ileum for visualization and biopsy.
• Capsule endoscopy in the setting of obscure bleeding is highly sensitive and
specific.
• CT Angiography is of value in diagnosing and localizing tumors of vascular
origin.
• Diagnosis of a small bowel tumor is often achieved only at the time of surgical
exploration.
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11. Benign Tumors
• The most common benign neoplasms include benign stromal tumors,
adenomas, and lipomas.
• Adenomas are the most common benign tumors reported in autopsy
series.
• Stromal tumors are the most common benign small bowel lesions that
produce symptoms.
• At operation, a thorough search of the remainder of the small bowel is
warranted because multiple tumors are not uncommon.
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12. • Stromal Tumors-
• GIST make up 20% of all soft tissue sarcomas occurring throughout the
gastrointestinal tract
• Most prevalent in the stomach (60%) and jejunum and ileum (30%), and rarely
in duodenum (5%).
• Arise from the interstitial cell of Cajal, an intestinal pacemaker cell of
mesodermal descent.
• GISTs can be malignant tumors and nearly 20% of patients are found to have
metastatic disease, most commonly in the liver.
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13. • Median age of diagnosis is 65 years of age, no sex predilection.
• A median size of 6 cm at diagnosis; some GISTs can even be larger than 20
cm.
• Symptoms include abdominal pain, fullness, bowel obstruction, or tumor
hemorrhage resulting in anemia, melena, or hematemesis.
• The workup of GIST is often initiated with a CT scan.
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14. • An endoscopic core biopsy with immunohistochemical staining for KIT (95%)
and anoctamin-1 (98%) confirms the diagnosis.
• More than 95% of stromal tumors express CD117, and 70% to 90% express
CD34.
• Stromal tumors are firm, gray-white lesions with a whorled appearance noted
on cut surface.
• Microscopic examination demonstrates well-differentiated smooth muscle
cells.
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15. • May grow intramurally and cause obstruction.
• Sometimes achieve considerable size and eventually outgrow their blood
supply, resulting in bleeding manifestations.
• The mitotic index is classified as low (<5 mitoses/50 hpf ) or high (>5
mitoses/50 hpf ).
• Tumors larger than 5 cm, regardless of mitotic index, have higher rates of
metastasis and recurrence
• Surgical resection is necessary for appropriate treatment.
• Higher-risk GIST lesions may require adjuvant therapy after resection.
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16. • Adenomas:
• Account for approximately 15% of all benign small bowel tumors.
• Three primary types: true adenomas, villous adenomas, and Brunner gland
adenomas.
• 20% in the duodenum, 30% are found in the jejunum, and 50% are found in
the ileum.
• Are asymptomatic; most occur singly and are found incidentally at autopsy.
• most common presenting symptoms are pain, bleeding and obstruction.
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17. • Villous adenomas: rare, premalignant; are most commonly found in the
duodenum
• May be associated with the familial polyposis syndrome.
• malignant potential is reportedly between 35% and 55%.
• Endoscopic ultrasound is a useful modality in the preintervention evaluation
and may help guide management planning.
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18. • The options for treatment are endoscopic and surgical.
• In the jejunum and ileum, the treatment of choice is segmental resection.
• Surgical management has potential morbidity (20%–30%) associated with
duodenal resection by pancreaticoduodenectomy or pancreas-preserving
duodenectomy.
• Endoscopic resection (i.e., snare excision, thermal ablation, argon plasma
coagulation, or photodynamic therapy) is a safe alternative.
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19. • Lifelong risk of recurrence is approximately 50% after endoscopic treatment
• Endoscopic mucosal resection(EMR) for the treatment of duodenal adenomas
and Brunner gland tumors has a high success rate for complete removal.
• The risk of delayed bleeding a/w EMR is significant
• Invasive changes or a recurrence after polypectomy necessitates a more
definitive approach (e.g., pancreaticoduodenectomy).
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20. • Adenomas a/w FAP
• Adenomas in the duodenum can be found in 50% to 90% of cases.
• Increasing age is an independent risk factor for adenoma development.
• 5% lifetime risk for development of duodenal adenocarcinoma.
• For direct surveillance and treatment, patients are classified by the Spigelman
classification.
• Screening endoscopy is performed at regular intervals with biopsy of all
suspicious, villous, or large (>3 cm) adenomas.
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22. • Peutz-Jeghers Syndrome:
• Inherited syndrome of mucocutaneous melanotic pigmentation and
gastrointestinal hamartomatous polyps.
• Autosomal dominant, with a high degree of penetrance.
• Brown or black spots located in the circumoral region of the face, buccal
mucosa, forearms, palms, soles, digits, and perianal area.
• Hamartomas are most commonly found in the jejunum and ileum
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23. • The most common symptom is recurrent colicky abdominal pain, a palpable
mass in 1/3 patients.
• Hemorrhage as a result of autoamputation of the polyps may occurs.
• Adenomatous changes have been reported in 3% to 6% of hamartomas.
• Extracolonic cancers are common, occurring in 50% to 90% of patients (small
intestine-m/c, stomach, pancreas, ovary, lung, uterus, and breast).
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24. • Treatment is directed at bowel obstruction or persistent gastrointestinal
bleeding
• Resection should be limited to the segment of bowel that is producing
complications
• Because of the widespread nature of intestinal involvement, cure is not
possible; therefore, extensive resection is not indicated.
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25. • Hemangiomas-
• Developmental malformations consisting of submucosal proliferation of blood
vessels.
• Can occur at any level of the gastrointestinal tract; jejunum is the most
commonly affected small bowel segment.
• 3% to 4% of all benign tumors of the small bowel and are multifocal in 60% of
patients.
• A/w Osler-Weber-Rendu disease and Turner syndrome.
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26. • The most common symptom of small bowel hemangiomas is intestinal
bleeding.
• Angiography and technetium Tc-99m red blood cell scanning are the most
useful diagnostic studies.
• If a hemangioma is localized preoperatively, resection of the involved
intestinal segment is warranted.
• Intraoperative transillumination and palpation may help to identify a
nonlocalized hemangioma.
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27. Malignant Neoplasms
• Incidence of malignant neoplasms of the small intestine has increased
steadily during the past three decades.
• Neuroendocrine neoplasms (NENs) increased more than fourfold.
• 5-year survival rate is 34.9% compared to 51.5% survival rate for
colorectal cancer
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28. • Almost always produce symptoms, the most common of which are
pain and weight loss.
• Obstruction develops in 15% to 35% of patients as a result of tumor
infiltration and adhesions
• Gastrointestinal bleeding, manifested by anemia and occult blood-
positive stools or occasionally by melena or hematochezia.
• A palpable mass may be felt in 10% to 20% of patients, and
perforations develop in approximately 10%.
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29. • Neuroendocrine Neoplasms:
• Arise from enterochromaffin cells (Kulchitsky cells).
• “carcinoid” has become a misnomer, as all NENs have
malignant potential.
• Reported in a number of organs, including lungs, bronchi,
and the gastrointestinal tract.
• Median age for gastroenteric NEN of 63 years.
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30. • Divided into NETs and neuroendocrine carcinomas.
• The distinction between a G3 well-differentiated NET and a G3 poorly
differentiated NEC can be difficult and may require additional pathologic
confirmation or immunohistochemical staining. 30

31. • Midgut NETs are characterized by having high serotonin production.
• The most prominent neuropeptide- serotonin and substance P
• Almost always occur within the last 2 feet of the ileum.
• Carcinoid syndrome- cutaneous flushing (80%); diarrhea (76%);
hepatomegaly (71%); cardiac lesions, most commonly right-sided heart
valvular disease (41%–70%); and asthma (25%) and are present mostly in
those patients with hepatic metastases.
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32. • Found in five typical sites: small intestine (38%), rectum (34%), colon (16%),
stomach (11%), and unknown sites (1%).
• Are multicentric in 20% to 30% of patients.
• The malignant potential is related to location, size, depth of invasion, and
growth pattern.
• 3% of appendiceal NETs, 35% of ileal NETs are associated with metastasis.
• GI NETs of <1 cm in diameter(75%) have 2% chance of metastasis, NETs 1 to
2 cm -50% and larger than 2 cm are associated with metastasis 80% to 90% of
cases.
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34. • After invasion of the serosa, the intense desmoplastic reaction produces
mesenteric fibrosis, intestinal kinking, and intermittent obstruction.
• Larger mesenteric mass caused by nodal disease and desmoplastic invasion of
the mesentery, which is often mistaken for the primary tumor.
• Frequent coexistence of a second primary malignant neoplasm of a different
histologic type, usually a synchronous adenocarcinoma.
• As mesenteric and nodal extension progresses, local venous engorgement and,
ultimately, ischemia of the affected segment of intestine.
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35. • Rarely diagnosed preoperatively.
• Elevated urinary levels of 5-HIAA measured during 24
hours are highly specific although not sensitive.
• Chromogranin A (CgA) is elevated in more than 80% of
patients with NETs. (specificity of 95%, sensitivity 55%)
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36. • Radiologically a solid mass with spiculated borders and radiating surrounding
strands that is associated with linear strands within the mesenteric fat and
kinking of the bowel, a diagnosis of gastrointestinal NET can be made fairly
confidently.
• Scintigraphic(indium(111In)-labeled pentetreotide) localization has a higher
sensitivity than CT for delineating and localizing NETs.
• MRI can be helpful in diagnosing metastatic disease, especially in the liver.
• FDG is taken up only in highgrade NETs (e.g., high Ki-67 expression),
whereas most NETs have low Ki-67 expression
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37. • Treatment small bowel NETs is based on tumor size, location, and presence of
metastatic disease.
• primary tumors smaller than 1 cm in diameter without evidence of regional
lymph node metastasis, a segmental intestinal resection is adequate
• wide excision of bowel and mesentery- lesions >1 cm, multiple tumors, or
with regional lymph node metastasis.
• Lesions of the terminal ileum are best treated by right hemicolectomy.
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38. • Small duodenal tumors can be excised locally; however, more extensive
lesions may require pancreaticoduodenectomy.
• In cases of mesenteric disease aggressive surgical resection and debulking
achieve relief of 93% of obstruction and 83% of mesenteric vessel
encasement.
• In contrast to metastases from other tumors, there is a definite role for surgical
debulking, which often provides beneficial symptomatic relief.
• Metastasectomy (Liver) provides the most durable survival benefit compared
with other treatment modalities.
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40. • NETs have the best prognosis of all small bowel tumors.
• Resection of a NET localized to its primary site approaches a 100% survival
rate.
• Five-year survival rates are approximately 65% in patients with regional
disease and 25% to 35% in those with distant metastasis
• Tumors recur in 40% to 60% of patients.
• An elevated level of CgA is an independent predictor of an adverse prognosis.
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41. • Adenocarcinoma-
• Constitute ~40% of the malignant tumors of the small bowel.
• Median age at diagnosis is in the sixth decade of life, M>F.
• Most of these tumors are located in the duodenum and proximal jejunum.
• Those associated with Crohn disease tend to occur at a somewhat younger age,
and more than 70% arise in the ileum.
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42. • May have important gene mutations- APC, β-CATENIN, EGFR, VEGF-A,
KRAS, HER2, TP53.
• m/c familial causes include FAP, Lynch syndrome, and Peutz Jeghers
syndrome.
• Tumors of the duodenum manifest early because of the earlier presentation of
symptoms, which are usually jaundice and chronic bleeding.
• Jejunum and ileum- nonspecific symptoms like vague abdominal pain and
weight loss, Intestinal obstruction and chronic bleeding; Perforation is
uncommon.
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43. 43

44. • Treatment
• Is determined by location and stage.
• An R0 resection of the primary tumor with locoregional lymph node resection
is the only curative treatment.
• Regional lymphadenectomy of the periduodenal, peripancreatic, and hepatic
lymph nodes as well as involved vascular structures is necessary.
• Neoadjuvant chemotherapy- if there is tumor invasion into adjacent structures.
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45. • Jejunal and ileal adenocarcinomas require surgical resection with regional
lymphadenectomy and jejunojejunal or ileoileal anastomosis.
• Ileocecectomy with right hemicolectomy with ligation of the ileocolic artery
and subsequent regional lymphadenectomy for terminal ileum lesion.
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46. • Poorly differentiated cancers or those who had incomplete lymph node
resections (<10 nodes identified) should at least be considered for adjuvant
chemotherapy.
• Adjuvant fluoropyrimidine and oxaliplatin may increase overall survival in
patients with advanced disease.
• BALLAD trial- proposes adjuvant chemotherapy will result in an
improvement in disease-free survival and overall survival compared with
observation alone after potentially curative surgery for patients with stage I, II,
and III small bowel adenocarcinoma.
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47. • Metastatic disease- studies have determined that using FOLFOX (oxaliplatin,
5-FU, and leucovorin) and FOLFIRI (irinotecan, 5-FU, and leucovorin) as
first-line therapy.
• Unresectable metastatic disease may require surgical intervention for
uncontrolled bleeding, bowel obstruction, or perforation.
• Prognosis of small bowel adenocarcinoma is poor.
• Five-year survival rates are typically in the 14% to 33% range.
• Duodenal adenocarcinoma has a 5-year survival rate of 50%.
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48. • Stage III- >3 positive lymph nodes 5-year disease-free survival rate was 37%; 1 or 2
positive lymph nodes was 57%.
• Advanced age, advanced stage, ileal location, recovery of fewer than 10 lymph nodes,
and number of positive nodes are significant predictors of poor overall survival.
• Any attempts at curative resection should always include an extensive regional
lymphadenectomy.
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49. • Lymphoma-
• Primary or as a manifestation of systemic disease.
• One-third of gastrointestinal lymphomas occur in the small bowel, accounts
for 5% of all lymphomas.
• 25% of small bowel malignant tumors in the adult; most common intestinal
neoplasm in children younger than 10 years.
• Most commonly found in the ileum, d/t greatest concentration of gut-
associated lymphoid tissue.
• Primary small bowel lymphomas was associated with celiac disease and
immunodeficient states (e.g., AIDS).
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50. • Usually large, with most greater than 5 cm and may extend beneath the
mucosa.
• There is often diffuse infiltration of the intestinal wall.
• Symptoms include pain, weight loss, nausea, vomiting, and change in bowel
habits.
• Perforation may occur in up to 25% of patients.
• Fever is uncommon and suggests systemic involvement.
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51. 51

52. • Treatment
• A combination of surgery, chemotherapy, and radiation therapy is used for all
small bowel tumors.
• In the absence of symptoms, small bowel lymphomas are often chemo
responsive and do not require surgery.
• B-cell lymphomas are more chemosensitive have high remission rates with or
without surgery.
• T-cell lymphomas are traditionally more resistant to therapy and will progress
to symptoms of obstruction or perforation if not resected.
• Five-year survival of 50% to 60% can be expected and is dictated by response
to systemic therapy.
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53. • GIST-
• Constitute about 20% of malignant neoplasms of the small bowel.
• More common in the jejunum and ileum.
• Typically are diagnosed in the fifth and sixth decades of life with slight male
predilection.
• Larger than 5 cm at the time of diagnosis in 80% of patients.
• Mostly arise from the muscularis propria and generally grow extramurally.
• Most common indications for surgery include bleeding and obstruction, free
perforation as a result of hemorrhagic necrosis in large tumor masses.
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54. • Invade locally or spread by direct extension into adjacent tissues and
hematogenously to the liver, lungs, and bone; lymphatic metastases are
unusual
• The treatment regimen is based on localized versus metastatic disease.
• Surgical management includes complete resection of localized GISTs
• If capsule rupture occurs, patients should receive adjuvant therapy
• A laparoscopic approach in patients with large tumors is strongly discouraged.
• Radiologic criteria for unresectability include infiltration of the celiac trunk,
superior mesenteric artery, or portal vein.
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55. • Current guidelines suggest that patients with high-risk disease should receive 3
years of adjuvant treatment with imatinib.
• Imatinib- Tyrosine kinase inhibitor that blocks the unregulated mutant c-kit
tyrosine kinase and inhibits the BCR-ABL and PDGF tyrosine kinases.
• Not recommended for low-risk patients after an R0 resection.
• Neoadjuvant imatinib should be considered for patients requiring extensive
surgery to allow for tumor shrinkage prior to resection.
• Deletions affecting exon 11, codon 557/558 of the c-kit gene, and D842V
PDGFRα mutations have a higher risk of recurrence within the first 3 to 4
years after surgery.
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56. 56

57. • Nilotinib is a second-generation tyrosine kinase inhibitor active in chronic
myeloid leukemia and has an inhibitory effect on ckit and PDGF
• Phase 3 trials have shown minimal differences between this drug and imatinib
or sunitinib.
• Sorafenib is a VEGF, c-kit, PDGFR, and BRAF inhibitor and has been
effective in imatinib- and sunitinib-resistant tumors.
• The combination of imatinib and doxorubicin has shown some benefit in
patients with wild-type GISTs.
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58. Metastatic Neoplasm
• Much more common than primary neoplasms.
• usually arise from other intraabdominal organs, including the uterus
cervix, ovaries, kidneys, stomach, colon, and pancreas.
• By direct extension or implantation of tumor cells.
• May be found in patients with adenocarcinoma of the breast and
carcinoma of the lung.
• Cutaneous melanoma is the most common extraabdominal source
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59. • Common symptoms of metastatic disease include anorexia, weight
loss, anemia, bleeding, and partial bowel obstruction.
• Palliation to relieve symptoms or, occasionally, a bypass if the
metastatic tumor is extensive and not amenable to resection.
• Nonoperative palliation includes endoscopic or radiologic placement
of self-expandable metal stents.
• Gastrostomy and jejunostomy tubes also may be placed to provide
decompression when other palliative methods are not possible.
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60. References
1. Bailey & Love’s Short Practice of Surgery, 28th Edition.
2. Sabiston Textbook of Surgery, 21st Edition.
3. Schwartz’s Principles of Surgery, 11th Edition.
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61. THANK YOU
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