September 15, 2011
UB Department of Surgery
Grand Rounds
Craig Collins MD
 Anatomy/Physiology
 Pathogenesis
 Background
 Incidence
 Risk Factors
 Diagnosis
 Management
 Prognosis
 Take Home Points
 Future
 Small Bowel ~3m
 Duodenum ~20-30cm
 Jejunum ~100-110cm
 Ileum ~ 150cm
 Blood supply based upon celiac axis and superior
mesenteric artery (SMA). Venous return via superior
mesenteric vein (SMV).
 Layers of Small Bowel
 Mucosa
 Submucosa
 Muscularis
 Serosa
 Spiral folds of mucosa and submucosa (plicae circularis)
are more prominent proximally.
 Jejunum is larger in diameter, is generally thicker, and has
more prominent mucosal folds.
 Peyer’s Patches (lymphoid tissue) found in submucosal
layer and become more prominent distally in the Ileum.
 Primary functions are digestion, absorption, and motility.
 Endocrine function (CCK, secretin, other peptides)
 Immune function via secretion of IgA from Peyer's patches.
 Small bowel accounts for 75% of GI tract length and 90% of
mucosal surface.
 Accounts for 3-6% of GI tract tumors and 1-3% of all
malignant GI tumors.
 2/3 of symptomatic GI tract tumors are malignant.
 Majority of benign lesions are asymptomatic and are
discovered at autopsy.
 Several factors thought to account for rarity of small bowel
neoplasms.
 Rapid transit time
 Liquid contents
 Neutral pH and high levels of benzopyrene hydroxylase
 Bacterial flora/load
 Increased lymphoid tissue and IgA- Immunoprotective role.
 Hodgkin’s Lymphoma first described in 1832 by Dr. Thomas
Hodgkin.
 Orderly spread of disease from one lymph node group to
another, pathologically characterized by presence of Reed
Sternberg cells.
 One of the first cancers to be cured by XRT and
subsequently by combination chemotherapy. ~93% cure
rate.
 Classified into 4 pathologic subtypes based upon Reed-
Sternberg cell morphology.
 Nodular Sclerosing
 Mixed Cellularity
 Lymphocyte rich
 Lymphocyte depleted
 Non-Hodgkin’s Lymphoma
 B-Cell*
 diffuse large cell*
 Small cell (Mantle cell and follicular)
 mixed small and large cell
 MALT Lymphoma
 Burkitt’s
 EATL (Enteropathy Associated T-Cell Lymphoma)
 Immunoproliferative small intestinal disease (IPSID)
* Most common (2/3), 70-80% High grade, 20-30% low grade
 Lymphomas can affect any lymph node station and nearly
every organ.
 Primary GI (extra-nodal) lymphomas represent ~30% of all
lymphomas.
 Gastric- 75%
 Small Bowel (including duodenum)- 9%
 Ileo-cecal region- 7%
 >1 GI site- 6%
 Rectum- 2%
 Colon- 1%
 All sub-types of nodal lymphomas may also arise in GI tract
but NHL are most common.
 Ulcerating or infiltrating.
 Colon cancer 50-60x more common than small bowel
cancers.
 Primary small bowel cancer:
 Adenocarcinoma (40%) > NET (30%) > Lymphoma (20%) >
Sarcoma/other (~10%)
 ~ 50% of small bowel neoplasms are secondary
(metastasis)*.
 Colon, stomach, pancreas, melanoma, breast, & lung.
*Direct extension, intraperitoneal seeding, hematogenous/lymphatic spread
 1.6 cases/million/year
 Steep rise in the 1980’s in correlation to AIDS
 Bimodal age distribution, 20’s-30’s and >50.
 Celiac disease
 IBD
Inflammation
 RA
 Chronic infection, poor sanitation
 HIV/AIDS with low CD4 count
 Post transplant
Immunosuppression
 Data taken as a whole do not support the hypothesis that
IBD alone is a risk factor for lymphoma.
 Suggests IBD pts. Treated with AZA and 6-MP are at
greater risk of lymphoma than general population.
 ? Regarding risk of severe or prolonged IBD compared with
less severe disease.
 Small but real increase in the risk of lymphoma in IBD
patients receiving anti-TNF-α therapy, but risk yet to be
clearly quantified.
 Undoubtedly an increased risk of malignancy in celiac
disease with regard to small bowel lymphoma and
adenocarcinoma.
 Risk of NHL may be increased 3-9 fold, but the overall risk
to celiac population is < 1 %.
 Risk diminishes over time if compliant with gluten free diet
and is equal to general population 15 years after diagnosis.
 Prospective cohort study of 637 pts with treated celiac
disease in the UK from 1978-2001. Malignancy rates
recorded.
 Risk to general population was estimated from cancer
registries.
 Median follow up was 6.6 years (2.2-14.5 yrs).
 Cancer diagnosis within 2 years of celiac disease excluded.
 No increase in overall malignancy rate in diagnosed celiac
disease in the post-diagnosis period when compared with
the general population.
 5x greater rate of NHL and 40x greater rate of small bowel
lymphoma compared with general population in the postdiagnosis period.
 Abdominal pain, weight loss, nausea, emesis, GIB, chronic
anemia.
 Median duration of symptoms- 6 months.
 Normal PE in 24%, abdominal mass in 46%.
 Often present with perforation, bleeding, or obstruction
necessitating emergent surgery (~25-50%)
 Criteria:
 Lack of peripheral or mediastinal lymphadenopathy.
 Normal WBC count and differential on peripheral smear.
 Tumor involvement primarily in GI tract.
 No involvement of liver or spleen.
 No history of previously treated nodal lymphoma.
 SBFT/Enteroclysis
 Barium Enema
 EGD/Colonoscopy
 Push Enteroscopy, Double Balloon Endoscopy
 Capsule endoscopy
 CT
 MRI
 PET/ PET CT
 Exploratory Laparotomy/Laparoscopy*
* Diagnosis in ~50% of patients
 Wide variety of radiologic manifestations- ulceration,
stricture, polypoid mass, mechanical obstruction,
intussusception, fistulas, aneurysmal bowel dilatation,
thick mucosal folds, separation of adjacent loops,
mesenteric adenopathy and mesenteric thickening.
 Clinical and radiographic challenge due to vague
symptoms, rarity of disease, and relative inaccessibility of
the small bowel.
 Physical Exam with performance status
 CBC with differential, platelets
 LDH
 Hep B testing if Rituximab contemplated
 CT Chest/Abdomen/Pelvis for staging
 Pregnancy testing in women of childbearing age if chemo
planned.
 Select cases- Bone marrow biopsy with aspirate for multifocal
disease. PET-CT, MRI, Hep C testing
Diagnosis- CT Enteroclysis
Diagnosis- CT Enteroclysis
Diagnosis- CT
Diagnosis- CT
Diagnosis- CT
Diagnosis- CT
Diagnosis- CT
 Endoscope introduced, balloon inflated, scope advanced.
Performed via oral and anal routes. Depth range from 18.8m.
 Allows for visualization
and tissue diagnosis.
 Retrospective review of 29 pts with GI lymphoma, further
examined by double balloon endoscopy.
 Sought to determine prevalence of additional GI
lymphomas.
 50% of their pts had additional GI lymphomas.
 Recommends complete evaluation of the small bowel in
any patient with GI lymphoma.
Double Balloon Endoscopy
 Low yield but superior test for small bowel
 Diagnostic impact in 57%, exclusive therapeutic decisions
in 12%
 Overall diagnostic yield for obscure GIB 58-80%
 6% were SB tumors
Staging- Ann Arbor
 Stage I- limited to intestine
 Stage II- Extension into regional nodes or infiltration of
surrounding organ
 Stage III- Involvement of lymph nodes on both sides of
diaphragm
 Stage IV- Involvement of distant organs or extra abdominal
lymph nodes
 Optimal treatment remains poorly defined but remains
surgical as a primary therapy followed by adjuvant
chemotherapy.
 Rarity of tumors, paucity of data on mgmt and
prognosis…info usually from small case series and
extrapolated from nodal lymphomas.
 Two most important factors regarding management
 Histology
 Staging
 For localized, early stage disease, surgical resection with
wide margins including node bearing mesentery is the
standard.
 For advanced, disseminated tumors which are not
resectable, surgical treatment is limited to obtaining tissue
for diagnosis and palliating complications.
 Radiation and chemotherapy.
 Stage I/II- Resection +/- chemotherapy
 Negative margins- clinical f/u Q3-6mos for 5 years then annually
thereafter
 Positive margins- chemotherapy, possible reoperation
 Multiple lymphomatous polyposis- chemo only
 Stage III/IV- Resection + Chemotherapy
 Observation
 Close clinical follow up
 Re-staging- which imaging to use?
 Neoadjuvant therapy?
 The best chemotherapy regimen depends on the
histology of the tumor.
 diffuse large B-cell lymphoma-CHOP is still the gold
standard.
 +/- Rituximab- primary therapy, combination, maintenence
 Low-grade lymphomas- indolent course- Fludarabine
alone or in combination with cyclophosphamide.
Rituximab as monotherapy.
 First Line- R+CHOP, RCVP x 6 cycles
 First line for elderly or Infirm- Rituximab + single agent
alkylator (cyclophosphamide, chlorambucil)
 Extended therapy- Rituximab maintenance x 2 years
 Fludarabine, cyclo, mitoxantrone
 Extent of therapy based upon age, performance status,
previous therapies, and extent of relapse.
 No role for radiation of the small bowel.
 Bovine and shark cartilage
 Echinacea
 Garlic
 Ginseng
 Ginger
 Perforation- median survival of 8 months
 AIDS related lymphomas
 Median survival 5-11 months
 B cell
 stage I/II- ~60-75% 5 year survival
 Stage III/IV- ~ 20-40% 5 year survival
 EATL
 5 year survival 10-20%
 Small bowel lymphoma is a rare disease with vague
symptoms initially, making timely diagnosis difficult.
 Risk factors include RA, CD, ?IBD, & immunosuppression.
 Imaging plays an integral role in diagnosis but studies
remain difficult to obtain/interpret.
 Majority of cases diagnosed at laparotomy, many present
emergently
 >50% of patients have nodal/distant mets at presentation.
 Primary therapy is surgery followed by adjuvant
chemotherapy depending on the stage and histology.
 Minimal progress in overall survival over the last 2 decades.
 Significant improvement in diagnostic modalities and
surgical care over the past 20 years but no significant
change in survival.
 Need better medical therapy
 Immunotherapy
 Gene therapy
 Chemotherapy
 Neoadjuvant therapy?
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