Transcript TOPGEAR Trial

Chapters 46 & 50
Gastric and Small Intestinal
Neoplasms
True or False: The incidence of
gastric cancer continues to be on the
rise since the 1930s, and is one of
the top ten causes of cancer-related
deaths in the United States.
Gastric Adenocarcinoma
• Incidence of gastric cancer has been stable
over the past decade, however decreased
drastically since 1930.
• Gastric cancer remains among the top 10
causes of cancer-related death in the US.
– Estimated 20,000 cases annually
Gastric Cancer
Risk factors for gastric cancer include all of the
following except?
1.
2.
3.
4.
Previous gastric surgery
Helicobacter pylori infection
Hyperplastic gastric polyps
Gastritis
True or False: The risk of gastric cancer is 2 fold in patients
that have been diagnosed with pernicious anemia for 5 or
greater years.
True or False: H. Pylori is associated with a 3-fold increase
in risk of GE junction, body, and antrum cancers.
Intestinal type gastric cancer is more commonly found in
all of the populations below except?
1.
2.
3.
4.
Women
Japanese
Older patients
Chronic atrophic gastritis
Which proto-oncogenes and tumor suppressor genes have
been involved with gastric cancer?
1.
2.
3.
4.
K-ras
HER-2 Neu
MKK4
All of the above
Risk Factors
•
•
•
•
•
Environmental
Predisposing Lesions
Gastritis
Helicobacter pylori
Prior Gastric Surgery
Risk Factors
• Environmental
– High intake of salt and nitrite-containing foods, lack of fresh
fruits and vegetables
• Predisposing Lesions
– Gastric Polyps: Adenomatous polyps (Not hyperplastic
polyps)
– Polyps related to size and number
– Risk is 10-20% and is greatest for polyps > 2 cm in size
– Surgical resection:
• Endoscopic removal for pedunculated and no evidence of invasive
cancer
• Operative excision for sessile lesions > 2 cm in size, biopsy-proven
cancer, and complicated polyps (bleeding/pain)
Risk Factors
• Gastritis
– Increased in chronic gastritis associated with pernicious
anemia
– Risk is twice age-matched controls for patients diagnosed
with pernicious anemia for more than 5 years
– Characterized by fundic mucosal atrophy, loss of parietal
and chief cells, hypochlorhydria, hypergastrinemia
– Endoscopic surveillance is not needed
• Helicobacter pylori
• Prior Gastric Surgery
Risk Factors
• Helicobacter pylori
– Three-fold increase in gastric cancer risk in patients
who are seropositive for H. Pylori
– Childhood acquisition of H. Pylori is frequent in areas
of high gastric cancer risk.
– H. Pylori is not associated with increased GE junction
tumors – ( increased by Barrett’s Esophagus)
– Pathophysiology related to: chronic inflammation 
atrophic gastritis  metaplasia  cancer
• Prior Gastric Surgery
Risk Factors
• Prior Gastric Surgery
– Risk increases typically 15 to 25 years post partial
gastrectomy
– Patients who have partial gastrectomy
– Pathophysiology related to:
• Decreased luminal pH, bacterial overgrowth, reflux of bile acids
into stomach
• Possible increased in microsatellite instability (MSI-H)
phenotype, whish is associated with lack of expression of hMLH1
and hMSH2 DNA mismatch repair genes
– Survival for gastric remnant cancers is poor 7-33% 5 year
survival
Clinical Features
Diagnosis and Screening
• Endoscopy with endoscopic biopsy
– 95% accuracy with multiple biopsies
– Use of endoscopic ultrasound
– Findings: Ulcer w/ irregular border and
necrotic
• Barium contrast studies
– Double contrast studies: Air and
barium
– Findings: Ulceration, mass, loss of
mucosal detail
• CT
• PET/CT
– Systemic staging
– Locally advanced tumors or when
neoadjuvant therapy is being
considered
Pathology
• Gastric Adenocarcinoma:
– Intestinal
• Malignant cells form glands
• More likely associated with gastric atrophy, chronic atrophic
gastritis, dysplasia
• More common in high risk populations: Japanese, men,
older patients
– Diffuse
• No glandular formation, instead loose sheets of cells
• Lymphatic invasion common
• More common in younger patients, women, populations
with low incidence
A T3 tumor invades which layer of the gastric wall?
1.
2.
3.
4.
Mucosa
Lamina propria
Muscularis propria
Serosa
Staging
Operative resection is indicated for all
adenomatous polyps except?
1. Sessile polyps > 2 cm in size
2. Polyps demonstrating invasive carcinoma
on endoscopic biopsy
3. Symptomatic polyps
4. Polyps endoscopically excised without
evidence of invasive cancer
True or False: Intra-operative peritoneal washings are
used in staging patients undergoing surgical resection
for gastric cancer.
Patients with tumors of the gastric proximal body
require which surgical resection for oncologic cure?
1.
2.
3.
4.
Proximal gastrectomy
Total gastrectomy
Antrectomy
Distal gastrectomy
What proximal margin distance is desired for complete
gastric resection?
1.
2.
3.
4.
2 cm
4 cm
6 cm
10 cm
Treatment
•
•
•
•
Surgical Resection is the mainstay
Staging Laparoscopy
Peritoneal cytology
Surgical options: (Based on location of cancer)
– Distal subtotal gastrectomy (Antrum and distal stomach)
– Total gastrectomy
– Esophagogastrectomy (GE junction)
• Margins:
– Proximal margin 6 cm
– Distal margin 3-6 cm
• Outcomes related to center volume
• Recurrence risk related to:
– Positive margins (including histologic positivity)
• Lymphadenectomy:
– D0/1/2/3
Treatment
Removal of the para-aortic nodal basin consists of
which type of lymphadenectomy?
1.
2.
3.
4.
D0
D1
D2
D3
What is the minimum number of lymph nodes
expected to be removed during a
lymphadenectomy for gastric cancer?
1.
2.
3.
4.
10
12
14
15
Japanese Studies demonstrate: 10% improvement Stage per
Stage for D2/D3 lymphadenectomies
- Additional benefits: Accurate Staging of tumors
- US studies advocate # of nodes : 15 nodes
True or False: Multi-modality therapy for gastric
cancer is superior to surgery alone.
Multimodality Therapy
Intergroup 70
MAGIC 71
• US Intergroup Trial
• Use of Adjuvant 5FU,
Leukovorin, and XRT
• Median F/U 5 years: Improved
Disease Free (30 vs 19 mo)
• Improved Overall Survival (36
vs 27 mo)
• Criticism: < D1
lymphadenectomy performed
in 54% of patients, 1/3 of
patients were unable to
complete adjuvant therapies
due to post op complications
• (Medical Research Council
Adjuvant Gastric Infusional
Chemotherapy Trial)
• Perio-operative chemotherapy
Epirubisin/Cisplatin/FU versus
Sx alone
• Improved 5 year survival 36%
vs 23%
• Criticism: only 42% completed
full course of chemotherapy
TOPGEAR Trial
True or False: Post-operative mortality has been shown
to be affected by the volume of the center.
Treatment of a Mucosa-associated lymphoma consists
of which of the below?
1.
2.
3.
4.
Systemic chemotherapy
Surgical resection
Antibiotic therapy
All of the above
Gastric Lymphoma
• Most common organ involved in extranodal
lymphomas
• Patient considered to have gastric lymphoma
if initial symptoms are gastric and the stomach
is exclusively involved
• Peak incidence is 6th-7th decade of life
• Low-grade: Mucosal associated Lymphoma
(MALT)
• High-grade: Lymphoma
MALT
• Low-grade lymphoma
• Pathophysiology: Development of lymphoid
tissue resembling small intestinal Peyer’s
patches within the gastric submucosa in
response to infection with H. Pylori
• Treatment: H. Pylori Treatment
• H. Pylori treatment leads to 70-100%
eradication following 5 months of treatment
• Salvage therapy: Chemotherapy and XRT
Non-MALT Lymphomas
• Historically total gastrectomy was treatment
of choice
• Chemotherapy or Chemoradiation therapy has
been shown to be successful and surgery is
reserved for local palliation/control
• 5% risk of hemorrhage or perforation
Which type of gastric carcinoid is NOT associated with
hypergastrinemia?
1.
2.
3.
4.
Type I
Type I
Type III
None of the above
Gastric Carcinoids
•
•
•
•
1 % of all gastric neoplasms
10-30% of all carcinoids
Diagnosis with endoscopic biopsy
Pathophysiology: Arise from enterochromaffin cells  secretion of
histamine  stimulates hypergastrinemia
• Type:
– Type I: Most common, associated with atrophic gastritis and
pernicious anemia, hypergastrinemia
– Type II: Occur with ZE syndrome and MEN I, hypergastrinemia
– Type III: Solitary larger lesions associated with normal gastrin level
– Type IV: large, solitary lesions associated with parietal cell hyperplasia
• 5 yr survival:
– Type I and II: 81%
– Type III and IV: 33%
Which the Tyrosine Kinase receptors is associated
with GIST tumors?
1.
2.
3.
4.
Bcl-2
Bax
Her2-Neu
C-Kit
Which of the following below is false regarding
gastric GIST tumors?
1. Risk of recurrence is related to tumor size and
mitotic index
2. Imatinib is an adjuvant therapy used for the
treatment of GIST tumors
3. Lymphadenectomy is routine in the surgical
treatment of GIST
4. Only Microscopically negative margins are
needed for the surgical treatment of GIST
tumors
GIST
• Arise form interstitial cells of Cajal – intestinal pacemaker in
the myenteric plexus of the bowel wall
• 50% are found within the stomach
• 95-99% express DC117 (c-KIT) – Tyrosine Kinase inhibitor
• Treatment:
– Surgical resection without lymphadenectomy
– Goal is negative microscopic margin
– Neoadjuvant Imatinib/Gleevec (tyrosine kinase inhibitor) – 80%
response
• Prognosis:
– Increased risk of recurrence related to tumor size > 2 cm and
mitotic index > 5-10 mitoses/HPF
True or False: Small bowel malignancies comprise 30% of
all GI malignancies.
Small Bowel Neoplasms
• Account for 1-3% of all GI malignancies
• Predilection of adenocarcinomas for the
duodenum: 80% of all small bowel tumors
occur in duodenum or proximal jejunum
• Overall increase in incidence due to improved
imaging modalities.
• Increased incidence in 6-7th decade of life.
Which of the following conditions predisposes patients to
small bowel cancers?
1.
2.
3.
4.
Celiac Sprue
Familial Adenomatous Polyposis
Inflammatory Bowel Disease
All of the above
Small Bowel Neoplasms
• Risk Factors:
– Crohn Disease:
• 10-12 fold increased risk of developing small-bowel adenocarcinoma
• Predilection for the ileum
– Familial Adenomatous Polyposis
• Close to 100% of FAP patients will develop adenomatous polyps in the
duodenum
• 300-fold increased risk of duodenal adenocarcinoma over that of the general
population
• Need endoscopic surveillance and frequent polypectomy
– Celiac Sprue
• Increased risk of intestinal lymphoma
– Peutz-Jeghers
• Hamartomas have a risk of malignant transformation to adenocarcinoma
– Immunosuppression (cyclosporine): Post Transplant
Lymphoproliferative Disorder: Treatment is reduction in
immunosuppression
Small Bowel Neoplasms
Diagnostic Studies
• CT Scan
– SB wall > 1.5 cm
– Discrete mesenteric lymph nodes
– Masses > 1.5 cm
– SB intussusception: ileocolic, jejunoilieal
• Endoscopy for duodenal lesions
• Video Capsule Endoscopy
• Double Balloon Enteroscopy
Small Bowel Neoplasms
Benign
• Hamartomas
• Lipomas
• Adenomas
Malignant
• Adenocarcinoma
• GIST
• Leiomyosarcoma
• NHL
• Carcinoid
True or False: Asymptomatic small Intestinal lipomas <
2cm in size can be observed.
True or False: The most common location of small bowel
adenocarcinoma is the Ileum.
Small Bowel Adenocarcinoma
• 30% of all small bowel tumors
• Predilection for the duodenum
• 80% of tumors are located in the duodenum or
proximal jejunum
• Slight male predominance
• Predisposing factors:
– Villous and tubulovillous adenomas
– Crohns Disease
• Treatment: Surgical resection and
Lymphadenectomy +/- Chemo (5 FU)
Non-Hodgkins Lymphoma most commonly occurs in which
location of the Gastrointestinal tract?
1.
2.
3.
4.
Stomach
Ileum
Appendix
Colon
Non-Hodgkin Lymphoma
• 4-20 % of all NHLs
• Stomach > SB > Colon
• Typically spare the duodenum, equal frequency in
jejunum and ileum
• For diagnosis there must be no evidence of lymphoma
outside of the GI tract
• Majority of primary intestinal lymphomas are B-cell
type
• B-Cell lymphomas have better prognosis then T-Cell
lymphomas
• Treatment: Surgery vs Systemic therapy
Gastrointestinal Carcinoids occur most frequently in which
location?
1.
2.
3.
4.
Appendix
Stomach
Ileum
Colon
True or False: Carcinoid syndrome is best diagnosed by
measuring serum 5-HIAA.
Which of the chemotherapeutic agents below is used
to treat intestinal carcinoids?
1. Herceptin
2. Streptozocin
3. Adriamycin
4. Gleevec
Carcinoid
•
•
•
•
•
•
•
•
•
Enterochromaffin cells at the base of the crypts of Lieberkuhn
APUD (Amine Precursor Uptake and Decarboxylation) system
Appendix > SB > Stomach
Presentation: Abdominal pain, Intussusception
Prognosis: Related to size, Tumors > 2 cm have 80% risk of nodal
involvement, 50% risk of liver metastasis
Carcinoid Syndrome: Related to 5 Ht, Kallikrein, Bradykinin,
Prostaglandins, signifies disease outside bowel (bypass monoamine
oxidase in liver)
Dx: 24 hr urinary exretion of 5HIAA
Sx: Flushing and Diarhea, Right heart failure, right heart valve
lesions
Treatment: Surgical resection, tumor debulking, 5Ht analogues
(somatostatin), Chemotherapy (Streptozocin)