Tumors of the Small Bowel

1
Tumors of the Small Bowel

• Hematology Grand Rounds
• Washington University School of Medicine
• Tom Fong
• May 4, 2007

2
Case Presentation

• 37 yo female with cystic fibrosis s/p B lung
  transplant 2002 who presents with recurrent
  abdominal pain and nausea, KUB c/w SBO, s/p ex
  lap/small bowel resection.
• Path c/w adenocarcinoma of distal ileum, staging
  w/u stage II (T3, N0, M0) disease
• Now recovered from surgery, no symptoms, good PS
• Meds include prednisone, tacrolimus for I/S
• Exam unremarkable, abdomen non-tender
• Labs with normal chemistries and blood counts
• Onc consult further recommendations?

3
Tumors of the Small Bowel

• Rare disorder 6000 new cases, 1000 deaths in
  2006 from small bowel malignancies
• Comprise 2 of GI malignancies, lt0.4 of all
  cancers
• Incidence 1 per 100,000
• Slight male predominance
• Median age of presentation 57
• Known disease associations Peutz-Jeghers,
  Crohns disease, FAP, Gardners syndrome,
  autoimmune diseases, immune deficiency states,
  immune suppresion

4
Tumors of the Small Bowel

• Histologies
• Adenocarcinoma 45
• Carcinoid 30
• Lymphoma 15
• Sarcoma 10

5
Tumors of the Small Bowel

• Why are they so rare?
• Putative factors
• Rapid transit of intestinal contents less
  carcinogen exposure
• Liquid bowel contents less mucosal irritation
• Lower bacterial load than colon less conversion
  of bile acids into carcinogens by organisms
• Increased lymphoid tissue/IgA may be protective

6
Tumors of the Small Bowel

• Risk factors
• Diet (i.e. red meat, salt-cured foods)
• Tobacco (cigarette smoking)
• Alcohol use
• Impaired GI motility
• Other disease states Peutz-Jeghers, Crohns
  disease, Gardners syndrome, FAP, celiac sprue,
  immune deficiency states (AIDS, post-transplant),
  autoimmune diseases

7
Tumors of the Small Bowel

• Clinical Presentation
• Non-specific symptoms including abdominal pain
  (dull, cramping), weight loss/anorexia,
  anemia/occult bleeding, palpable mass, small
  bowel obstruction, rare bowel perforation
• Often advanced disease by the time patients
  present with symptoms

8
Tumors of the Small Bowel

• Diagnosis
• HP, CBC, CMP urine 5-HIAA if carcinoid
  suspected
• No clear role for CEA or other tumor markers
• Imaging
• No single standard preferred method
• Choices include CT, MRI, upper GI with SBFT, and
  enteroclysis (double contrast study), octreotide
  or MIBG scan (carcinoid sx)
• Diagnostic procedures
• GI procedures include capsule endoscopy, upper
  endoscopy (standard to duodenum), upper
  endoscopy with push enteroscopy (visualize most
  of small bowel)
• Exploratory laparotomy particularly if
  indicated for complete SBO, bowel perforation,
  bleeding, etc.

9
Tumors of the Small Bowel

• Adenocarcinoma
• Most common histology (up to 50)
• Most common in 50s-60s, MgtF
• Highest incidence in duodenum, except in Crohns
  disease (ileum)
• 2/3 are resectable at time of diagnosis
• Stage at presentation predicts prognosis

10
Tumors of the Small Bowel

• Adenocarcinoma
• 5 year survival by stage
• Stage I 100
• Stage II 52
• Stage III 45
• Stage IV 0
• 5 year survival by resectability
• 54 in resected, 0 in unresected
• Curative-intent resection performed in 61
• (Barnes et al., Ann Surg Oncol 1994 173
  retrospective analysis of 67 pts, MD Anderson)

11
Adenocarcinoma of Small Bowel

• Retrospective review of 217 patients
• Median age 55, male predominant (61)
• Stage I (4), II (20), III (39), IV (35)
• Site of origin Duodenum 52, jejunum 25, ileum
  13
• Curative-intent surgery in 67 (Whipple done in
  17)
• Mode of Dx
• lt1998 Surgery 39, Upper GI 36, EGD 14
• gt1998 EGD 28, Surgery 26, Upper GI 22, CT 18
• Mode of Dx (by location)
• Duodenum EGD 42, Upper GI 24, CT 16, Surgery
  15
• Ileum Surgery 57, Upper GI 21, CT 7, Phys
  exam 7
• (MD Anderson, Dabaja et al., Cancer 2004
  101518)

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Adenocarcinoma of Small Bowel

• (217 pts _at_ MD Anderson Dabaja et al., Cancer
  2004 101518)

Overall Survival
Overall Survival by Stage
Median OS 20 months 5-yr OS rate 26

13
Adenocarcinoma of Small Bowel
(217 pts _at_ MD Anderson Dabaja et al., Cancer
2004 101518)
Overall survival by node status
Overall survival by treatment
Only lymph node involvement and
curative-intent surgery were independent
predictors of overall survival in multivariate
analysis
14
Adenocarcinoma of Small Bowel

• So what about adjuvant therapy?
• (217 pts _at_ MD Anderson Dabaja et al., Cancer
  2004 101518)

Adjuvant chemotherapy after a Whipple procedure
or resection did not appear to significantly
affect the survival curve (P 0.49) (Table 7)
15
Adenocarcinoma of Small Bowel

• So, what about adjuvant therapy?
• Halfdanarson et al., ASCO 2006 Abstract 4127
• - Retrospective review of 491 pts with
  adenocarcinoma of SB _at_ Mayo
• - Stage distribution I (7), II (27), III
  (28), IV (33)
• - Median OS 20.7 months, 5-yr OS 26
• - OS not better with adjuvant chemoRT or 5-FU
  based chemo
• - RR 1.17, p0.45 (n40 for CRT, n33 for
  5-FU)
• - Adjusted for age, sex, LN, grade, tumor
  location

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Adenocarcinoma of Small Bowel

• Role of adjuvant therapy?
• Limited data, no prospective trials
• No proven benefit in retrospective trials
• Adjuvant regimens used in colon cancer are often
  employed in clinical practice
• Role of adjuvant therapy remains undefined, as
  benefits remain unknown

17
Adenocarcinoma of Small Bowel

• Adenocarcinoma Chemo in advanced disease
• No standard chemotherapy regimen
• Regimens used include
• 5-FU, doxorubicin, mitomycin C (FAM)
• RR 18, OS 8 months (39 pts Gibson et al.,
  Oncologist 2005 10132)
• 5-FU cisplatin or carboplatin or oxaliplatin
• RR 21, OS 14 months (20 pts Locher et al.,
  Oncology 2005 69290)
• Gemcitabine and irinotecan, 5-FU based regimens
• RR 36 palliative chemo predicts OS HR 0.47, p
  0.035
• (113 pts reviewed, 44 pts received chemo Fishman
  et al., Am J Clin Oncol 2006 29225)
• 5-FU based chemotherapy
• Median OS 15.3 mos v. 3.1 mos (BSC)
• (491 pts reviewed, ? received chemo Halfdanarson
  et al., ASCO 2006 Abstract 4127)
• Chemo appears active prospective trials lacking

18
Tumors of the Small Bowel

• Carcinoid
• Roughly 30 of small bowel tumors
• Originate from Kulchitsky cell, an
  enterochromaffin cell in crypts of Lieberkuhn
• Most commonly found in ileum
• Often secrete serotonin and other bioactive
  products including histamine, prostaglandins,
  polypeptides such as VIP, gastrin, glucagon, etc.
• In addition to abdominal symptoms, may present
  with symptoms related to secretory products
  (carcinoid syndrome) watery diarrhea, flushing,
  sweating, dyspnea, facial edema, tachycardia,
  hypotension, etc.
• Metastatic disease present in 90 of symptomatic
  pts

19
Tumors of the Small Bowel

• Carcinoid
• If suspected, diagnostic tests include
• 24 hr urine for 5-HIAA (serotonin by-product)
• Also consider other biochemical tests (urine
  5-HT, serum 5-HT, serum chromogranin A, etc.)
• Octreotide scan - 90 sensitivity if carcinoid sx
• MIBG scan (radiolabeled iodine, taken up by tumor
  and stored in granules) 50-60 sensitive

20
Carcinoid Tumors

• Management
• Surgery is treatment of choice if localized
• Appendiceal carcinoids appendectomy
• Second GI malignancies common
• Endoscopy recommended prior to surgery
• Rx for advanced disease/carcinoid syndrome
• Octreotide (somatostatin analogue)
• Hepatic regional therapy (RFA, cryotherapy,
  chemoembolization, etc.)
• Interferon
• Chemotherapy/clinical trial

21
Tumors of the Small Bowel

• Lymphoma of the small bowel
• 15 of small bowel tumors
• Small percentage of GI lymphomas
• Stomach 75, small bowel 9, ileocecal 7
• Most common in ileum
• Risk factors autoimmune diseases, immune
  deficiency or immune suppression, Crohns dz

22
Tumors of the Small Bowel

• Lymphoma of the small bowel
• Histologies include
• Extranodal marginal zone B-cell lymphoma of MALT
  type (MALToma)
• Marginal zone lymphoma
• Burkitts lymphoma
• Immunoproliferative small intestinal disease
  (IPSID) common in Middle East

23
Lymphoma of the Small Bowel

• Treatment
• Surgical Resection
• Locoregional Radiation Therapy
• Chemotherapy for advanced disease
• Treatment per histologic subtype of NHL
• MALToma follicular lymphoma-like regimens
• MCL, Burkitts more aggressive regimens

24
Tumors of the Small Bowel

• Sarcoma
• Account for 10 of small bowel tumors
• Most in jejunum or ileum
• Majority are leiomyosarcoma (75)
• Then fibrosarcoma, liposarcoma, angiosarcoma
• Enlarge extraluminally may grow extensively
  without causing obstruction
• Similar histologically to benign counterparts
• Leiomyosarcoma leiomyoma liposarcoma lipoma
• Criteria for malignancy number of mitoses,
  nuclear atypia, cellularity, presence of necrosis

25
Tumors of the Small Bowel

• Small bowel sarcoma
• Treatment
• Surgical resection is mainstay of therapy
• Incomplete resection may still palliate symptoms
• Chemotherapy may be considered
• Limited data for sarcoma regimens for SB sarcoma

26
Case Presentation

• 37 yo female with CF s/p bilateral lung
  transplant 5 yrs ago with stage II (T3, N0)
  adenocarcinoma presenting with SBO, s/p partial
  resection of small bowel (negative margins).
• So, our decision?

27
Case Presentation

• Presented options
• Observation
• Adjuvant chemotherapy
• Oral capecitabine (X-ACT trial for colon cancer)
• FOLFOX (MOSAIC trial for colon cancer)

28
Case Presentation

• Patient chose oral capecitabine.