18 - Esophageal Gastric Flashcards
Esophageal Cancer - Epi
8th most common cause of cancer
6th leading cause of cancer death
Epithelial: Squamous cell (ESCC) Adenocarcinoma (EAC) Small Cell Other
ESCC (Squamous Cell) - Epi
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
Esophageal Squamous Cell Carcinoma - Risk Factors
Environmental: Smoking Alcohol History of caustic ingestion Betel nut chewing HPV?!
Associated medical conditions:
Achalasia
Tylosis
Plummer-Vinson Syndrome
Esophageal Adenocarcinoma - Epi
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
Esophageal Adenocarcinoma - Risk Factors
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)
Barrett’s Esophagus
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!!
Barrett’s Esophagus - Epi
1 - 2% of general population
5 - 10% of GERD patients
White people get it more than anyone else
Barrett’s Esophagus - Progression to Cancer
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%
Barrett’s Esophagus - Risk factors for progression
Difficult to study due to low rate of progression Male sex and older age Biomarkers: p53, aneuploidy None yet prospectively validated
Barrett’s Esophagus - Management
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
High grade dysplasia - Endoscopic treatment
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
Esophageal Cancer - Clinical Features
Frequently no symptoms until advanced disease Dysphagia GI Bleeding: Overt - Hematemesis Occult - Iron deficiency anemia Weight loss
Esophageal Cancer - Staging
TNM Staging
US for T staging
FNA of suspicious nodes
Esophageal Cancer - Prognosis
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
Esophageal Cancer - Treatment
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
Gastric Cancer (adeno) - Epi
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
Gastric Cancer - Classification
Intestinal Vs Diffuse
Gastric Cancer - Intestinal
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
Gastric Cancer - Diffuse
Poorly differentiated Infiltrates the layers of the stomach Worse prognosis Genetic predisposition Stable incidence Men = Women
Gastric cancer - Risk factors
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 (-)
H. Pylori
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
H. Pylori - Mechanisms of Carcinogenesis
Induces chronic inflammation
Virulence factors - cagA, vacA, BabA2
Induction of strong TH1 response
Host immunologic factors → IL-1β
H. Pylori - Progression
H. Pylori is an early event Gastritis Chronic inflammation Atrophic gastritis Intestinal Metaplasia Dysplasia Carcinoma
Diffuse Gastric Cancer - Genetic Risk Factors - Hereditary Diffuse Gastric Cancer:
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
Diffuse Gastric Cancer - Genetic Risk Factors - Familial Adenomatous Polyposis
Mutation of APC
Colon adenomatous polyps lead to adenocarcinomas
Fundic gland polyps (Dysplasia in 40%)
Diffuse Gastric Cancer - Genetic Risk Factors - Lynch syndrome (HNPCC)
Mutation of MLH1, MSH2, MSH6, PMS1
Mismatch repair defect
Colon, endometrial, ovarian, urinary tract cancers
Diffuse Gastric Cancer - Genetic Risk Factors - Peutz Jeghers
Mutation of STK11
Hamartomatous polyps in the GI tract
Hyperpigmentation of oral mucosa, palms, soles
Diffuse Gastric Cancer - Genetic Risk Factors - Juvenile Polyposis
Mutation of BMPR1A or SMAD4
Hamartomatous polyps in the GI tract
Gastric Cancer - Screening
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
Gastric Cancer - Prevention
H. Pylori eradication
Gastric Cancer - Signs/Symptoms
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
Gastric Cancer - Diagnosis
Endoscopy and biopsy
Gastric Cancer - Staging
T - Ultrasound
N - Sample nodes
M - CT or PET CT
Laproscopic peritoneal lavage
Gastric Cancer - Prognosis
Poor Overall survival 24% TNM stage: 1 - 60 - 90% 2 - 35 - 45% 3 - 10 - 40% 4 - 5 - 15%
Superficial Gastric Cancer - Treatment
Superficial - Endoscopic submucosal dissection
Otherwise, multimodality treatment
Multimodality treatment for gastric cancer
Surgery + Adjuvant
Perioperative chemo
Neoadjuvant chemo + surgery
Lots of debate among benefits of these
Gastric Cancer Surgery
D1 (Perigastric) lymphadenectomy
D2 (Extended) lymphadenectomy
D2 had higher perioperative M&M, less downstaging, standard of care in asia
Gastric Cancer - Palliative Treatment
Chemo + Trastuzumab in patients with HER2 tumors
Gastrojejunostomy/stent to help them eat
Palliative radiation for bleeding
