18 - Esophageal Gastric Flashcards

1
Q

Esophageal Cancer - Epi

A

8th most common cause of cancer
6th leading cause of cancer death

Epithelial:
Squamous cell (ESCC)
Adenocarcinoma (EAC)
Small Cell
Other
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2
Q

ESCC (Squamous Cell) - Epi

A

Worldwide most common cell type
Incidence declining in Western countries
Probably due to decrease in smoking
Incidence of Adenocarcinoma higher now

Male predominance
African American > Caucasian in USA

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3
Q

Esophageal Squamous Cell Carcinoma - Risk Factors

A
Environmental:
Smoking
Alcohol
History of caustic ingestion
Betel nut chewing
HPV?!

Associated medical conditions:
Achalasia
Tylosis
Plummer-Vinson Syndrome

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4
Q

Esophageal Adenocarcinoma - Epi

A

Rise began in 1960s

Reasons unclear
Decreasing rates of H. Pylori infection
Increasing prevalence of GERD
Increasing rates of obesity

Low incidence in developing nations

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5
Q

Esophageal Adenocarcinoma - Risk Factors

A
Male Sex (>5:1)
White
GERD (Recurrent sx - 7.7, Long-standing severe - 43)
Smoking - 2x
Obesity - 1.5 to 2x (BMI > 30)
H. Pylori - Lower risk (~0.75)
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6
Q

Barrett’s Esophagus

A

Primary precursor lesion to EAC
Development of intestinal metaplasia in distal esophagus
Abnormal healing response to erosive esophagitis
Only 8% of patients with EAC were previously diagnosed with BE, though!!

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7
Q

Barrett’s Esophagus - Epi

A

1 - 2% of general population
5 - 10% of GERD patients

White people get it more than anyone else

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8
Q

Barrett’s Esophagus - Progression to Cancer

A
No dysplasia (0.1% - 0.3% per year chance of progression)
Low grade dysplasia (0.5% - 1.5 - 2% per year chance of progression)
High grade dysplasia (5% - 10% per year chance of progression)
Cancer

New concept:
Genome doubling & Genomic catastrophes?
Lifetime risk of cancer ~ 5 - 10%

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9
Q

Barrett’s Esophagus - Risk factors for progression

A
Difficult to study due to low rate of progression
Male sex and older age
Biomarkers:
p53, aneuploidy
None yet prospectively validated
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10
Q

Barrett’s Esophagus - Management

A

Gastric acid suppression via PPIs
Less acid reflux → less esophageal inflammation → decreased risk of cancer
Clinical trial data says efficacy is lacking, though

Endoscopic surveillance
Periodic endoscopy with random biopsies
Goal: Detect dysplasia or cancer at early stages
Effective at "stage shifting"
Unclear survival benefit
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11
Q

High grade dysplasia - Endoscopic treatment

A

Endoscopic mucosal resection

Then they burn your barett’s tissue until you’re down to your submucosa again and it grows back as squamous WHATTTT

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12
Q

Esophageal Cancer - Clinical Features

A
Frequently no symptoms until advanced disease
Dysphagia
GI Bleeding:
Overt - Hematemesis
Occult - Iron deficiency anemia
Weight loss
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13
Q

Esophageal Cancer - Staging

A

TNM Staging
US for T staging
FNA of suspicious nodes

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14
Q

Esophageal Cancer - Prognosis

A

So poor
17% 5-year survival
Similar in EAC and ESCC

Why?
Rapid lymphatic spread. Esophagus has hella lymph up in thurr

After esophagectomy, you still have a high rate of local and distant recurrence

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15
Q

Esophageal Cancer - Treatment

A

Early lesions - Endoscopic mucosal resection

Advanced lesions - (>T1b, nodal involvement):
SCC - Surgery or definitive chemo
EAC - Neoadjuvant chemoradiation (Carboplatin + Paclitaxel) then surgery

Metastatic disease: Palliative chemo (HER2 testing in EAC)
Obstruction - stenting, radiation
Bleeding - Radiation

PD-L2+ in ~50% EACs → Pembrolizumab trial underway (PD-1 antibody)

High mortality rate

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16
Q

Gastric Cancer (adeno) - Epi

A

2nd Leading cause of cancer mortality worldwide
Marked decrease in incidence in US over past 50 - 60 years
Males 2:1
Age - 71 in US ~60 in Japan
Minorities, low SES
Cardia cancer incidence rising
Risk factors for cardia cancer similar to those of EAC
GE junction and cardia tumors

17
Q

Gastric Cancer - Classification

A

Intestinal Vs Diffuse

18
Q

Gastric Cancer - Intestinal

A
Glandular
Most common
Associated with classic risk factors
Regional
Type seen in areas with high-incidence
Decreasing worldwide incidence
Men > Women
Causally related to H. Pylori
Slightly better prognosis
19
Q

Gastric Cancer - Diffuse

A
Poorly differentiated
Infiltrates the layers of the stomach
Worse prognosis
Genetic predisposition
Stable incidence
Men = Women
20
Q

Gastric cancer - Risk factors

A
Environmental:
H. Pylori infection
Smoking
High salt intake
Dietary nitrites
Associated medical conditions:
Prior gastric surgery (especially bilroth for PUD)
Pernicious anemia
Obesity (cardia tumors)
Gastric ulcers (+), Duodenal Ulcers (-)
21
Q

H. Pylori

A

Spiral-shaped gram negative bacterium (technically still a rod, not a spirochete)
Acquired in childhood
Colonizes >50% of the world’s population
Decreasing prevalence in the US

22
Q

H. Pylori - Mechanisms of Carcinogenesis

A

Induces chronic inflammation
Virulence factors - cagA, vacA, BabA2
Induction of strong TH1 response
Host immunologic factors → IL-1β

23
Q

H. Pylori - Progression

A
H. Pylori is an early event
Gastritis
Chronic inflammation
Atrophic gastritis
Intestinal Metaplasia
Dysplasia
Carcinoma
24
Q

Diffuse Gastric Cancer - Genetic Risk Factors - Hereditary Diffuse Gastric Cancer:

A

CDH1 gene codes for E-Cadherin
Mutation truncates it
AD gene with high penetrance (80% lifetime risk)
Also associated with lobular breast cancer
Prophylactic gastrectomy shows multiple foci of intramucosal cancer

25
Q

Diffuse Gastric Cancer - Genetic Risk Factors - Familial Adenomatous Polyposis

A

Mutation of APC
Colon adenomatous polyps lead to adenocarcinomas
Fundic gland polyps (Dysplasia in 40%)

26
Q

Diffuse Gastric Cancer - Genetic Risk Factors - Lynch syndrome (HNPCC)

A

Mutation of MLH1, MSH2, MSH6, PMS1
Mismatch repair defect
Colon, endometrial, ovarian, urinary tract cancers

27
Q

Diffuse Gastric Cancer - Genetic Risk Factors - Peutz Jeghers

A

Mutation of STK11
Hamartomatous polyps in the GI tract
Hyperpigmentation of oral mucosa, palms, soles

28
Q

Diffuse Gastric Cancer - Genetic Risk Factors - Juvenile Polyposis

A

Mutation of BMPR1A or SMAD4

Hamartomatous polyps in the GI tract

29
Q

Gastric Cancer - Screening

A

Performed in much of East Asia (Endoscopy, advanced imaging)

Not routine in US (low incidence, not cost efective)

Patients who might benefit from screening:
Dysplasia
Gastric adenomatous polyps
History of gastric surgery (especially Bilroth II)
Genetic - Family history of GC, FAP, HNPCC, Peutz-Jeghers, Juvenile polyposis

30
Q

Gastric Cancer - Prevention

A

H. Pylori eradication

31
Q

Gastric Cancer - Signs/Symptoms

A
Weight loss
Early satiety
Pain
Vague GI Symptoms - Nausea, indigestion
GI bleeding - Melena or hematemesis

Sister Mary Joseph Node
Virchow’s nodes
Ascites
Krukenberg Tumor

Cutaneous Paraneoplastic Manifestations:
Acanthosis nigricans
Seborrheic Keratoses
Tripepalms
Trousseau's syndrome
32
Q

Gastric Cancer - Diagnosis

A

Endoscopy and biopsy

33
Q

Gastric Cancer - Staging

A

T - Ultrasound
N - Sample nodes
M - CT or PET CT

Laproscopic peritoneal lavage

34
Q

Gastric Cancer - Prognosis

A
Poor
Overall survival 24%
TNM stage:
1 - 60 - 90%
2 - 35 - 45%
3 - 10 - 40%
4 - 5 - 15%
35
Q

Superficial Gastric Cancer - Treatment

A

Superficial - Endoscopic submucosal dissection

Otherwise, multimodality treatment

36
Q

Multimodality treatment for gastric cancer

A

Surgery + Adjuvant
Perioperative chemo
Neoadjuvant chemo + surgery

Lots of debate among benefits of these

37
Q

Gastric Cancer Surgery

A

D1 (Perigastric) lymphadenectomy

D2 (Extended) lymphadenectomy

D2 had higher perioperative M&M, less downstaging, standard of care in asia

38
Q

Gastric Cancer - Palliative Treatment

A

Chemo + Trastuzumab in patients with HER2 tumors
Gastrojejunostomy/stent to help them eat
Palliative radiation for bleeding