Gastric Flashcards
Hereditary Diffuse Gastric Cancer
What is the mutation?
CDH1
E-cadherin
(same thing)
Hereditary Diffuse Gastric Cancer
what other cancer is associated?
lobular breast cancer
Hereditary Diffuse Gastric Cancer
International Gastric Cancer Linkage Consortium (IGCLC) criteria for referral to genetic testing (3)
Either:
A: 2 cases of diffuse GC in 1st or 2nd degree relative with 1 case documented before age 50
B: 3 cases of diffuse GC in 1st or 2nd degree relative regardless of age.
C: 1 case of diffuse GC before age 40
25-50% will carry a mutated CDH1 allele
Hereditary Diffuse Gastric Cancer
What is cumulative risk of GC and lobular BC?
What is average age of onset of clinically evident invasive GC?
Cumulative risk by age 80:
GC 70% in males; 56% in females
lobular BC 42% (39-52%) in females
Age of onset is 38 but varies with mutation.
Hereditary Diffuse Gastric Cancer
endoscopic surveillance?
Annual EGD with random biopsies
Starting at age 20
or
5-10 years before earliest familial case.
Hereditary Diffuse Gastric Cancer
when to do total gastrectomy?
Offer after childhood growth is complete and extensive QOL preoperative discussion. (early 20s)
Endoscopy fails to discover T1a cancers.
Hereditary Diffuse Gastric Cancer
what percentage of patients will have T1a cancer on prophylactic total gastrectomy?
85% despite minimal endoscopic findings
[Strong Annals of Surg 2016]
others report up to 92%
Hereditary Diffuse Gastric Cancer - Total Gastrectomy
What to check frozen sections for?
- Confirm tumor free
2. confirm squamous mucosa and duodenal mucosa to ensure complete removal of gastric mucosa.
Hereditary Diffuse Gastric Cancer - Total Gastrectomy
Do you need to do a D2?
No - D1 by consensus guidelines.
No evidence for D2 as lymph node mets are exceedingly rare.
Hereditary Diffuse Gastric Cancer - Total Gastrectomy
What is the trend for Wt and QOL scores?
decrease until 6-12 months post-op and then stabilize or improve.
Final Wt loss ~10%
[Strong Annals of Surg 2016]
Hereditary Diffuse Gastric Cancer
what percentage of all GC?
1-3%
Hereditary Diffuse Gastric Cancer
Who to potentially offer endoscopic surveillance?
Patients refusing or deferring total gastrectomy
Patients meeting IGCLC criteria, but cannot document a mutation.
[Lim Gastrointestinal Endoscopy 2014]
Hereditary Diffuse Gastric Cancer
What techniques might optimize endoscopic detection?
High resolution white light endoscopywith targeted and multiple random biopsies detected signet ring carcinoma in 63% of CDH1 carriers. Also used autoflourescence, but concluded it didn’t help [Lim Gastrointestinal Endoscopy 2014]
blue dye
Hereditary Diffuse Gastric Cancer
What is the histological subtype?
Signet Ring
Hereditary Diffuse Gastric Cancer
What percent of families have CDH1 mutation?
What are some other possible genetic causes?
40% of families have a CDH1 mutation (>100 known mutations)
alpha-catenin (CTNNA1) same pathway
other genetic syndromes (BRCA-2, Peutz-Jeghers)
[Hansford JAMA Oncology 2015]
What percent of gastric adenocarcinoma will have positive peritoneal cytology without gross metastatic disease?
~10%
Gastric cancer 3 year overall survival for positive peritoneal cytology and no progression after neoadjuvant therapy?
3-year OS rate of 12% versus 0% for patients who did not receive neoadjuvant therapy.
[Badgwell MDACC 18649106]
20 year risk of a gastric remnant carcinoma?
4% (2.9% in 16 years)
[Morgagni pmid 25218580]
Most important prognostic indicator of long term-survival for second operation for gastric cancer? (indicator of metachronous cancer)
Non-anaastomotic recurrence had 95% v 37% 5 year survival in one south korean study.
PMID 18080844
Endoscopic Mucosal Resection (EMR) indications
GE cancer limited to the muscularis mucosa (T1a) with <10% risk of lymph node involvement
Reccurent Esophageal Cancer
Re-resection if surgically feasible;
Consider brachytherapy for non-surgical candidate
[Wong Hee Kam, Rivera Brachytherapy 2015]
Tylosis
autosomal dominant
hyperkeratosis of palms
Esophageal SSC at age 45
Bloom Syndrome
Autosomal recessive chromosomal breakage
Leukemias
Wilm’s Tumors
Early esophageal SCC
Fanconi’s Anemia
autosomal recessive DNA repair mutation congenital malformation AML SCC of numerous locations Pancytopenia
Risk of cancer with a biopsy of high grade dysplasia with Barretts Esophagus?
10% for T1b or higher
Barretts Esophagus Surveillance
no dysplasia - every 3-5 years
low grade dysplasia - every 6-12 months
high grade dysplasia - every 3 months (or eradicate)
Treatment for esophageal cancer invading the pericardium?
Still resectable
Siewert classification
I is within 5 cm above the GE junction
II is 1 cm above or 2 cm below the GE junction
III is 5 cm below the GE junction but invades up to it (stage and treat III like gastric cancer)
Common mutation in SCC
inactivation of Notch1
What are optimal staging studies before and after neoadjuvant chemoRT for esophageal cancer?
before: EUS (better for nodes) and PET (complimentary)
after: just PET
Three classes of gastric carcinoids
Type I (>60%) - associated with chronic atrophic gastritis
Type II - associated with MEN-I
Type III - sporadic
Type I gastric carcinoids are
well differentiated and limited to the mucosa without invasion.
Work-up for type I and type II gastric carcinoids
Endoscopy and CT scan are standard
Nuclear med test exists (Somatostatin Scintigraphy)
Treatment of type I and Type II gastric carcinoids
Endoscopic removal and 6 month surveilance
Antrectomy and local resection for recurrence
(<5 tumors, all <1cm, no evidence of metastatic disease on imaging)
Type III gastric carcinoids
usually solitary
arise in normal stomach
>2cm
Treatment of Type II gastric carcinoids
Same surgical approach as gastric adeno
15% have lymph node involvement at presentation.
ACOSOG Z9001
DeMatteo trial for adjuvant imatinib for GISTs. Stopped early since results were so positive. 20% recurrence with placebo v 8% with gleevec
RTOG 0132
Good outcomes with neoadjuvant imatinib. Has been accepted without any direct comparrison
Scandinavian Sarcoma Group XVIII
1 v 3 years of imatinib trial.
three years is better, patients tend to recur once it is stopped.
Inclusion criteria for Scandinavian Sarcoma Group XVIII
At least one of the following: tumor >10cm mitotic count > 10/50hpf tumor >5 cm and mitosis > 5 tumor rupture before or during surgery
Surgery for ampullary adenocarcinoma
Whipple!
All other are investigational with inferior results. 58% v 78% OS at 2 years
[Roggin KK, Yeh JJ, Ferrone CR 2005]
What patients saw the benefit of 3 years of gleevec in SSG 18
only c-kit exon 11 mutations.
Another phrase for goblet cell tumors
mixed adeno-neuroendocrine carcinomas
Management of goblet cell tumor of the appendix
agressive; right hemicolectomy for all, unless there is metastatic disease.
systemic therapy for goblet cell tumor
FOLFOX
Management of carcinoid tumor of the appendix
Right hemicolectomy for any of the following: tumor >2cm indeterminate size involvement of the base lymphovascular invasion invasion of the mesoappendix intermediate and high grade tumors tumors with mixed histology (adeno-, goblet-)
STK11
gene for Peutz Jehgers Syndrome
Peutz Jeghers Syndrome
pigmented oral spots
GI hamartomas
numerous malignancies
Medical causes of increases Chromogranin A
PPIs H2 blockers chronic atrophic gastritis renal failure liver failure
Non-neuroendocrine tumors that can secrete Chromogranin A
pancreatic cancer
hepatocellular carcinoma
prostate cancer
What additional organ should you take out for all carcinoid tumors?
Gallbladder;
Somatostatin can cause gallstones
Median survival for mucinous appendiceal tumors
16 years
What adjuvant therapies are there after HIPEC for mucinous appendiceal tumors?
NONE;
Can consider imaging surveilance and tumor markers.
EPIC (intraperitoneal chemotherapy)
No heat
No OR
No level I data
Most common complication of HIPEC
prolonged ileus
Side effect of cisplatin HIPEC
renal failure - Give thiosulfate
survival after HIPEC for low grade mucinous appendiceal tumors
80% at 20 years
survival after HIPEC for high grade mucinous appendiceal tumors
45% at 20 years
