Chapter 17: Congenital Disorders and Neoplasms of the ESO Flashcards
1
Q
What are the 4 types of congenital abnormalities of the esophagus?
A
- Obstruction
- Achalasia
- Esophagitis
- Neoplasms
2
Q
The GI tract is a common site of developmental abnormalities. In these cases, defects of what other organ should be considered?
A
defects of other organs that develop in the same embryonic period should be sought
3
Q
__________ are structural developmental anomalies that disrupt normal GI transit and typically present early in life.
A
Atresia and fistulae
4
Q
Intestinal atresias are _____ common than esophageal atresias but often involve the _____.
A
less
duodenum
5
Q
____________ is the most common form of congenital intestinal atresia, while the
__________ is the most common site of fistulization.
A
- Imperforate anus
- Esophagus
6
Q
Imperforate anus is a result of what embryologically?
A
Cloacal diaphragm does not involute
7
Q
When are atresia, fistula and duplications of the esophagus discovered?
Treated?
A
- Shortly after birth, due to regurg when eating.
- W/o surgery, cannot live.
8
Q
What is esophageal atresia?
A
- Incomplete development of the esophagus.
- Thin, non-canalized cord replaces part of esophagus and causes mechanical obstruction.
9
Q
What is the most common form of esophageal atresia?
A
Atresia with associated fistula at/near birfurcation of trachea
- Upper segment of esophagus is blind
- Fistula b/w lower segment and trachea, most commonly at or near bifurcation of trachea
*Figure B is most common
10
Q
Are a fistula & atresia always present together?
A
No (C) is just a fistula
(A) is just atresia.
11
Q
Fistulas of the esophagus can lead to what sxs?
A
- Aspiration
- Suffocation
- Pneumonia
- Severe fluid/electrolyte imbalances
12
Q
_____________ an incomplete form of atresia where lumen is narrow d/t fibrous
thickening of the wall, causing partial or complete obstruction.
Most often involves what parts of the GI tract?
A
Stenosis
-ESO and SI
13
Q
Developmental abnormalities of the the esophagus are associated with what other defects?
A
- Congenital heart defects
- GU malformation
- Neurologic disease
14
Q
When congenital GI disorders are present, what other associations should we consider?
A
VACTERL associations
- Vertebral
- Anal anomalies
- Cardiac
- TE fistula
- Renal anomalies
- Limb anomalies
15
Q
Diaphragmatic hernia occurs when?
If severe, what happens?
A
- Incomplete formation of the diaphragm allows the abdominal viscera to herniate into the thoracic cavity.
- When severe, can cause pulmonary hypoplasia => incompatible with life
16
Q
Difference between omphalocele and gastroschisis?
A
- Omphalocele: abdominal musculature does not close completely, abdominal viscera herniates outside of abdomen into ventral membranous sac.
- Gastroschisis is similar, but involves ALL layers of abdominal wall (peritoneum => skin) = all organs exposed
17
Q
What is the most frequent site of ectopic gastric mucosa and what is it referred to here?
May result in what problems?
A
- Upper 1/3 of esophagus (Inlet patch)
- Dysphagia, esophagitis, Barrett esophagus, or rarely, adenocarcinoma
18
Q
What are examples of ectopia seen within the GI tract?
A
- Ectopic pancreatic tissue: in stomach or esophagus
- Gastric heterotropia: patches of ectopic gastric mucosa in the small bowel or colon
19
Q
Gastric heterotropia may present with what signs/symptoms?
A
Occult blood loss due to peptic ulceration of adjancent mucosa
20
Q
What is the most common true diverticulum and where does it occur?
A
- Meckel diverticulum
- Ileum
21
Q
Cause of Meckel Diverticulum?
A
Failed involution of vitelline duct
22
Q
What is the rule of 2’s in regards to Meckel Diverticulum?
A
- 2% of population
- 2x more common in males
- Symptomatic by age 2 (only 4% are ever symptomatic!)
- Present within 2 ft of ileocecal valve
- 2 in. long
23
Q
What may be present in a Meckel Diverticulum that causes symptoms and what are these symptoms?
A
- Mucosal lining of Meckel diverticula can resemble the NL SI.
- However, ectopic pancreatic and gastric tissue can be present, which will secrete acid and cause peptic ulceration of adjancent SI tissue –> occult bleeding or abdominal pain resembling appendicitis or obstruction.
24
Q
Which sex is most commonly affected by congenital hypertrophic pyloric stenosis?
A
M (3-5x more likely)
25
Which _genetic disorders_ are associated with an increased risk of **Pyloric Stenosis**?
1. **Turner syndrome**
2. **Trisomy 18**
26
Which _enviornmental factors_ have been linked to an increased risk of developing **pyloric stenosis?**
**Erythromycin** or **azithromycin** exposure, orally or via mother's milk in **first 2 weeks of life**
27
When and how does **congenital hypertrophic pyloric stenosis** typically present?
- Between **3rd - 6th weeks of life**
- New onset regurgitation w/ **projectile, NON-bilious vomiting** after eating w/ frequent demands of re-feeding
28
What is found on PE with a **congenital hypertrophic pyloric stenosis**?
What is tx?
- Firm, ovoid, **1-2 cm abdominal mass**
- Tx = **myotomy (splitting of muscle)** is curative
29
What is **Hirschsprungs disease (megacolon)?**
* **Absence of** **ganglion cells,** derived from NC, **in the colon** that begins at the rectum =\> extends proximal, causing
* proximal dilation
* functional obstruction of the bowel
* loss of coordinated peristatlic contractions.
30
* What causes the absence of ganglion cells in **Hirschsprungs disease** (congenital megacolon)?
* Affects proximal and distal intestinal segment how?
* - Migration of NCC from cecum to rectum is arrested prematurely
* - OR when ganglion cells undergo premature death
* - **Proximal segment:** dilated
* **- Distal segment**: lack both the Meissner submucosal and Auerbach myenteric plexus
31
Which genetic abnormality can account for the majority of familial cases of **Hirschsprung disease?**
**LOF mutation of RET** (receptor tyrosine kinase)
32
How does **Hirschsprung disease** typically present?
1. **Failure to pass meconium** in the immediate postnatal period.
2. =\> **Obstruction** or **constipation**
3. =\> **Abdominal distension** and **bilous vomitting**
33
What are the major threats to life in regards to **Hirschsprung disease**?
1. **Enterocolitis**
2. **Fluid/electrolye imbalance**
3. **Perforation**
4. **Peritonitis**
34
Diagnosis of **Hirschsprung diseas**e requires what?
Which stain can be used?
- Documenting absence of ganglion cells within affected segment
- Immunohistochemical stains for **acetylcholinesterase** for ganglion cells
35
Which part of the colon is ALWAYS affected in **Hirschsprung Disease**?
**Rectum**
36
What are some causes of **acquired megacolon?**
Which is associated with loss of ganglion cells and which aren't?
* **Chagas disease** ---\> Trypanosoma cruzi (Reduviid bug) = loss of ganglion cells
* Other causes that are NOT associated w loss of ganglion cells
* ulcerative colitis
* inflammatory stricture
* obstruction by neoplasm
37
* **Esophagus** is a tube that delivers digested food and fluids to the stomach.
* _Structural (mechanical) obstruction_ or _functional obstruction_ can prevent this. How functional obstruction prevent delivery of food & fluids to stomach?
**Discruption** of **coordinated peristaltic contractions** that occur after we swallow.
38
\_\_\_\_\_\_\_\_\_\_ allows us to categorize 3 types of **esophageal dysmotility.**
What are they?
1. **Nutcracker esophagus**
2. **Diffuse esophageal spasm**
3. **Hypertensive lower esophageal sphincter (LES)**
39
What is **nutcracker esophagus?**
**Long, high amplitude contraction**s in the **distal esophagus** that are cause some loss of NL coordination (NL coordination in proximal).
40
What is **diffuse esophageal spasm**?
* **Diffuse, uncoordinated contractions** (repetitive and simultantous) of the esophagus (corkscrew)
* On manometry: no high pressure
41
On Barium swallow, which esophageal obstruction looks like a **corkscrew**?
**Diffuse esophageal spasm**
42
What do the following show on **Esophageal manometry?**
* - Nutcracker ESO
* - Diffuse esophageal spasm
* - Hypertensive LES
* **Nutcracker ESO:** high pressure at baseline, but relaxes normally
* **Diffuse esophageal spasm**: LES function is NL
43
What is **hypertensive lower esophageal sphincter?**
1. **High resting pressure of LES**
2. **Incomplete relaxation**
**W/O** alterations in the patterns of esophageal contraction.
44
How can **hypertensive LES** be differentiated from **achalasia**?
**Achalasia**: ↓ esophgeal peristaltic contractions
45
**Esophageal dysmotility** causes \_\_\_\_\_\_\_\_\_\_\_, which can result in the formation of \_\_\_\_\_\_\_\_\_\_\_.
* **↑ wall stress**
* **small diverticulae,** primarily the epiphrenic divertiulum, located above the LES.
46
What can form a **Zenker diverticulum?**
Impaired relaxation and spasm of the cricopharyngeaus muscle after swallowing =\> increased pressure in distal pharynx =\> **Zenkers diverticulum.**
47
Where does **Zenkers diverticulum** (\_\_\_\_\_\_\_\_\_ diverticulum) form?
* Pharyngoesophageal diverticulum
* RIGHT above the **upper esophageal sphincter**
48
When do **Zenker Diverticulae** most commonly develop (age)?
What symptoms do they cause when small vs large?
* **50s**
* **Small** (asymptomatic); **large** (accumulate food and cause regurg and halitosis)
49
What are causes of **mechanical obstruction** of the esophagus?
How does it present?
* **Strictures/stenosis** or **cancer**
* **Progressive dysphagia** that begins with inability to swallow **solids** =\> **liquids**. However, because it happens slowly, patients may *subconsciously* *change their diet to favor soft foods* and *not notice it until obstruction is almost complete.*
50
Fibrous thickening of the submucosa, causing **lumen of esophagus to narrow** most often due to inflamation/scarring due to GERD, irradiation or caustic injury.
* Muscularis propia begins to atrophy and there is secondary epithelial damage.
**Esophageal stenosis** (benign)
51
How can we differentiate **functional obstruction/ benign strictures** vs. **malignant strictures?**
* Functional obstruction/ benign strictures: can maintain weight and appetitie
* Malignant strictures: WL
52
How are **esophageal mucosal webs** and **esophageal rings (Schatzki rings)** different?
* **Esophageal mucosal webs** are ledge-like semi-circumferential protrusions of fibrovascular CT and overlying epithelium.
* _MC_: proximal or mid ESO
* **Schatzki rings** are circumferential, thicker and include [mucosa, submucosa and hypertrophic muscularis propria].
* _MC_: distal ESO
53
**Esophageal mucosal webs** most often occur in whom?
Associated with what other diseases?
- **Woman \>40 yo**
- **GERD**, **chronic GVHD**, or **blistering skin diseases**
54
What are the characteristic findings in **Plummer-Vinson syndrome**?
- **Esophageal mucosal webs** in the upper esophagus
- **Iron-deficiency anemia**
- **Glossitis** (beefy red tongue)
- **Cheilosis** (cracking of corners of mouth)
55
**Esophageal rings** located _____________ are called **A rings**; whereas those located ________________ are called **B rings**.
* A rings = above GE junction
* B rings = at the squamocolumnar junction
56
What type of mucosa are **A** and **B Schatzki rings** covered by?
* **A rings** = squamous mucosa
* **B rings** = gastric cardia type of mucosa
57
**Esophageal webs** causes **\_\_\_\_\_\_\_\_\_\_\_ dysphagia.**
**Non-progressive** dysphagia associated w/ **incompletely chewed food**
58
When we swallow, what normally allows LES to relax?
1. **Inhibitory neurons** release **NO** and **vasoactive intestinal polypeptides**
2. **Normal cholinergic signaling** is interrupted.
59
What is the triad of **Achalasia**?
* 1. Incomplete LES relaxation
* 2. Increased LES tone
* 3. Aperistalsis of esophagus
60
**Achalasia** causes _______ dysphagia and...
1. **Progressive/gradual** dysphagia for **solids + liquids**
2. **Hard time burping**
3. **Chest pain**
61
**Primary achalasia** is the result of what?
What nerve/nucleus may be affected?
- Degeneration of the inhibitory neuronal (ganglion cells) in ***distal esophagus***
- **Extraesophageal vagus n.** and **dorsal motor nucleus** may also undergo degenerative changes
62
**Secondary achalasia** may arise in relation to infection by what bug?
What are the characteristics of this type of achalasia?
**Chagas disease (Trypanosoma cruzi), causing**
1. Destruction of myenteric plexus (duodenal, colonic and uteric)
2. Failure of peristalsis
3. Esophageal dilation
63
Linkage of **achalsia** to which immune disorders suggest that achalasia may also be driven by immune-mediated destruction of inhibitory esophageal neurons?
1. HSV1 infection
2. Immunoregulatory gene polymorphisms
3. Sjorgen syndrome
4. Autoimmune thyroid disease
64
What are 3 treatment options for both **primary** and **secondary achalasia**?
1) **Surgery** (Laparoscopic myotomy)
2) **Pneumatic balloon dilation**
3) **↓ LES pressure** (BOTOX injection, to inhibit LES cholinergic neurons)
65
1. Complete absence of NL peristalsis
2. Incomplete LES relaxation w swallowing.
**Achalasia**
66
\_\_\_\_\_\_\_\_\_ can result from **chemical** or **infectious mucosal** **injury**.
**Infection** is most common in \_\_\_\_\_\_\_\_\_\_\_\_\_.
* **Esophagitis**
* **Immunocompromised**
67
What are the 2 main sx related to pathology of **GI tract**?
1. **Abdominal pain**
2. **GI hemorrhage**
68
\_\_\_\_\_ blood loss of the GI tract is a medical MRGC.
**Acute blood loss**
69
**Which are more common:** UGI bleeds or LGI bleeds?
**UGIB**
70
ID the source of bleeding based on the character of blood:
## Footnote
**Vomiting bright red blood (hememesis)**
If GI, most likely **proximal to the ligament of Trietz.**
71
ID the source of bleeding based on the character of blood:
## Footnote
**Black, tarry stool (melena)**
**Upper GI bleed**
72
ID the source of bleeding based on the character of blood:
## Footnote
**Bright, red blood in rectum (hematochezia)**
**Lower GI bleed** (or very rapid UGI bleed)
73
**Esophageal** causes of **vomitting of bright red blood (hematemesis)**
74
**Mallory-Weiss tears** are what?
* **Longitudinal, incomplete mucosal tears** (only mucosa and submucosa) on the gasdtric side of the GE junction, which may extend to the distal ESO.
75
**Mallory-Weiss tears** are most commonly associated/caused by what?
1. **Severe retching** (i.e., bulimia)
2. **Vomiting secondary to acute alcohol intoxication**
76
What is **Boerhaave syndrome** and how does it compare to Mallory-Weiss tears?
- Much less common, but **MORE severe**
- **Transmural** tearing and rupture of the **distal esophagus**
77
What occurs in patients suffering from **Boerhaave Syndrome** and how do they present?
The pt presentation often includes what other differential dx?
- **Severe mediastinitis** (air in mediastinum 2' to perf. Esophagus)
- Severe **chest pain,** **tachypnea**, and **shock**\*\*
- **Subcutaneous emphysema**
- Initial diff dx usually includes an MI
78
Which is considered a **catastrophic event**: Mallory-Weiss syndrome or Boerhaaves syndrome?
What do we hear on ausculatation?
* **Boerhaaves syndrome**
* **Hamman's signs:** crunching sound due to pneumomediastinum
79
Chemical or **infectious esophagitis** can cause what symptoms?
**Range from**: Odynophagia =\> hemorrhage, stricture or perforation.
80
What are causes of **chemical esophagitis** in kids vs adults?
* **Kids**: ingestion of household cleaning products
* **Adults**: attempted suicide, causing severe damage
* Other: pills, alkalis, acids
81
What is **pill-induced esophagitis?**
**Less severe chemical injury** to the esophageal mucosa that occurs when pills lodge and dissolve, instead of going into stomach.
82
**Infectious esophagitis** in healthy individuals in ***UNCOMMON*** and most often due to \_\_\_\_\_\_\_\_\_\_\_.
**HSV**
83
**Viral esophagitis** caused by **Herpes virus** is distinguished by what morphological characteristics?
- **Punched-out ulcers**
- **Nuclear viral inclusions**
84
**Infectious esophagitis** in *debilitated/immunospressed* is MORE common and caused by what?
1. **HSV**
2. **CMV**
3. **Fungus**
85
**Viral esophagitis** caused by **CMV** is distinguished by what morphological characteristics?
- **Shallow ulcers**
- Nuclear and cytoplasmic inclusions (**characteristic**)
86
Which **fungi** are the most common causes of **esophagitis**?
1. - **Candidiasis** (most common)
2. - **Mucormycosis**
3. - **Aspergillosis**
87
**_Esophagitis_** caused by what organism is characterized morphologically by **gray-white, pseudomembranes** composed of **densely matted fungal hyphae** and inflammatory cells covering the esophageal mucosa?
**Candidiasis**
88
What is the most common viral cause of esophagitis?
**Herpes simplex**
89
Pt presents with **apoptosis** of basal epithelial cells, **atrophy** of mucosa and **fibrosis** of submucosa of esophagus **WITHOUT** signifiant acute inflammatory infiltrates on histology. What is this?
**Esophageal GVHD**
90
What are causes of **LES relaxation**?
* **1. Vagal mediated pathways**
* **2. ↑ intra-abdominal pressure**
* **3. Obesity**
* **4. Hiatal hernia**
* **5. Delayed gastric emptying (gastroparesis)**
* **6. Idiopathic.**
91
What is the most common cause of **esophagitis** and the most common outpatient GI diagnosis?
**Reflux esophagitis** into the lower esophagus. (GERD)
92
What is the most common cause of gastroesophageal reflux?
**Transient relaxation of lower esophageal sphincter**
93
Recruitment of which immune cells are often seen morphologically with more severe injury as a result of **GERD**?
- **Eosinophils** recruited into squamous mucosa
- Followed by **neutrophils**
94
What is pathogenic of reflux esophatitis d/t GERD
**1. Eosinophils and neutrols in the squamous mucosa**
**2. Elongation of papilla in the lamina propria that ends to the upper 1/3**
**3. Basal zone hyperplasia**
95
What are some of the complications that may result from **reflux esophagitis?**
1. - Ulceration
2. - Hematemesis
3. - Melena (dark sticky feces)
4. - Stricture development (ulcer -\> loss of mucosal layer --\> fibrosis)
5. - Barrett esophagus
96
What are the symptoms of **Eosinophilic Esophagitis** in both *adults* and *children*?
- **Adults** - food impaction and dysphagia
- **Children** - feeding intolerance and GERD-like sx's
97
What is the **cardinal** **histological** **feature** of **_eosinophilic esophagitis_**?
i.e., large #'s of which cells and where
Large #'s of i**ntraepithelial eosinophils**, particularly **superficially**
98
How is **eosinophilic esophagitis** different from **GERD**?
- Acid reflux is **NOT** prominent
- PPI's usually do **NOT** provide relief
99
The majority of patients with **eosinophilic esophagitis** are also what?
Many have what underlying disorders?
**Atopic:** genetic tendency to develop allergic diseases such as
* Atopic dermatitis
* Allergic rhinitis
* Asthma
* Modest peripheral eosinophilia
100
What are 2 major causes of **Esophageal Varices**?
Normal route of blood flow?
1) **Portal HTN** (cirrhosis - alcoholic liver disease): collateral channels form where portal and caval systems communicated--\> congested subepithelial and submucosal venous plexi in distal esophagus and prox. stomach
* - Left gastric vein ---\> Portal V.
2) **Hepatic schistosomiasis** - parasitic disease -\> flukes (trematodes)
101
**Variceal hemorrhage** is a medical emergency that can be treated how?
1. - Inducing splanchnic vasoCONSTRICTION
2. - Endoscopic sclerotherapy (inject thrombotic agents)
3. - Balloon tamponade
4. - Variceal ligation
102
What are the signs/symptoms of **esophaeal varices?**
* - Esophageal bleeding
* - **PAINLESS** hematemesis
103
In people with **esophageal varices**, ______ die initially and _____ recurr within a year.
**30%;**
**50%**
104
Diseases that impede what flow cause the formation of **esophageal varices**, an important cause of **esophageal bleeding.**
Venous blood from the GI tract goes through the liver via the portal vein, before going to the heart =\> systemic circulation.
105
What are symptoms of **hiatal hernia**?
* **Heartburn**
* **Regurg of gastric juices**
106
What is a complication of **chronic GERD**?
**_Barrett esophagus:_**
* Metaplasia of lower esophageal mucosa (stratified squamous epi ---\> nonciliated columnar epithelium w/ goblet cells)
107
The greatest concern in **Barrett esophagus** is that it confers an increased risk of developing?
**Esophageal adenocarcinoma**
108
Even though a vast majority of **esophageal adenocarcinomas** are associated with Barrett's esophagus, what is important to remember?
Most individuals with BE **do not** develop esophageal tumors.
(0.2-2% have dysplasia)
109
How is **Barrets esophagus** diagnosed?
**Endoscopy** and **biospy**, showing evidence of metaplastic columnar mucosa above GE junction.
110
What does **BE esophagus** look like?
Patches of **red, velvety mucosa t**he extend up from GE junction: pale squamous esophageal mucosa alternates with light brown gastric mucosa distally.
111
When [**Barretts esophagus + dysplasia],** what do we see?
1. Atypical mitosis
2. Nuclear hyperchromasia
3. Irregularly clumped chromatin
4. ↑ nuclear-to-cytoplasm ratio
5. Failure to epithelial cells to mature as they migrate to the esophageal surface
112
* **BE w/o dysplasia**
* **BE w/ low-grade dysplasia**
* **BE w/ high-grade dysplasia**
What are the chances of becoming adenocarcinoma?
* 0.5%
* 10%
* 40%
113
Which type of **esophageal cancer** is most common worldwide; which is becoming more prevalent?
- **Squamous cell carcinoma** = more common worldwide
- **Adenocarcinoma** is becoming more prevalent in the US and Western society
114
**Benign** **tumors** of the **esophagus** are usually \_\_\_\_\_\_\_\_\_\_.
**Mesenchymal**
115
Most esophageal adenocarcinomas arise from \_\_\_\_\_\_\_\_\_\_\_\_.
**Barretts esophagus**
116
What is the **most likely factor** contributing to the ↑ rates of esophageal adenocarcinoma, especially in the US?
Increased incidence of **obesity-related GERD** and **Barrett Esophagus.**
117
What is associated w/ ↓ risk of **esophageal adenocarcinoma**?
- Some types of **H. pylori**
* Cause gastric atrophy --\> ⇩ acid secretion and reflux
118
Which _ethnicity_ and _sex_ is most commonly affected by **esophageal adenocarcinoma**?
Recent increased incidence in which populations?
1. **Caucasians**
2. **Men** 7x more likely
3. Recent ↑ rates in: **Hispanic men** and **White women**
119
Progression from **Barrett Esophagus** =\> **Adenocarcinoma** occurs over a period of time in a stepwise acquisition of genetic changes, which are seen early on and later in this progression?
- **Early**: mutations of TP53 and downregulation of CDKN2A
- **Later**: amplification of EGFR, ERBB2, MET, cyclin D1 and cyclin E
120
Where in the **esophagus** does **adenocarcinoma** typically occur and where may it invade?
Major morphological characteristics?
- **Distal 1/3** of esophagus and may invade adjacent gastric cardia
- Initially flat/raised patches ---\> large masses \>5cm
- Tumor produces mucin and forms glands
121
How does a patient with an **esophageal adenocarcinoma** typically present (signs/symptoms)?
1. **Pain** or **difficulty swallowing**
2. **Progressive weight loss**
3. **Hematemesis**
4. **Chest pain**
5. **Vomiting**
122
By the time a patient presents with symptoms of **esophageal adenocarcinoma**, what has the cancer likely done?
How does this affect prognosis?
* Spread to **submucosal lymphatic vessels**
* Overall 5-year survival is \<25%
* If cancer is limited to the mucosa or submucosa the 5-year survival is closer to 80%
123
Which gender has the greatest risk for **esophageal SqCC** of the esophagus and what is the typical age?
Which race of people are at the greatest risk?
- **\>45 yo**
- **Males** 4x more
- **African Americans** 8x more affected!!!
124
Which part of the **esophagus** do the majority of **squamous cell carcinomas** begin?
**Middle 1/3** of the **esophagus**
125
**Esophageal squamous cell carcinoma** risk factors
**- Alcohol and Tobacco use (major factor)**
- **Achalasia** --\> rotting food --\> irritation
- **Tylosis** = thickening of palms and soles + white patches in mouth
- **Plummer-Vinson syndrome** --\> rotting food on ledge of web
- Frequent consumption of hot beverages
- Hx of Radiation to Mediastinum
- HPV infection --\> p16 + E6 + E7
126
**SqCC** of the **esophagus** has a very high incidence in which 5 geographic locations?
* **- Iran**
* **-China**
* **- Hong Kong**
* - Brazil
* - South Africa
127
How does **esophageal SCC** begin?
Early appearane?
Late appearance?
* Begins as in situ lesion (squamous dysplasia)
* Early: small grey-white plaque thickenings
* Late: exophytic tumor masses --\> obstruct lumen
128
Which genetic mutations play a role in the development of **squamous cell carcinoma** of the **esophagus**?
- Amplification of SOX2
- Over-expression of cyclin D1
- Loss-of-function mutations in TP53, E-cadherin, and NOTCH1
129
Which 3 structures surrounding the **esophagus do SCC's** sometimes invade and what does this lead to in each?
1) **Respiratory tree** --\> pneumonia
2) **Aorta** --\> catastrophic exsanguination
3) **Mediastinum/Pericardium**
130
Differentiate the **esophageal cancer** on the top from that on the bottom; what are the distinguishing morphological features?
- **Top**: adenocarcinoma; often organized w/ glands
- **Bottom**: SCC of the esophagus; moderately to well-differentiated w/o presence of glands
131
**_HY:_** Cancers in the upper, middle, and lower 1/3 of the esophagus will have different sites of metastasis, what are they?
* **Upper 1/3:** cervical LN's
* **Middle 1/3:** mediastinal/paratracheal/tracheobronchial LN's
* **Lower 1/3:** gastric and celiac nodes
132
What are the common signs and symptoms of someone presenting with **SCC** of the **esophagus**?
What is seen if the tumor ulcerates?
1. **Progressive dysphagia** (solids --\> liquids)
2. **Odynophagia** (painful swallowing)
3. Pt's alter diet so have impaired nutrition and prominent wt. loss
- If tumor ulcerates =\> hemorrhage or sepsis w/ sx's of iron deficiency anemia
133
What is the association of **TE fistula** and **SCC** of the esophagus?
Often, the 1st sx's of SCC are caused by **aspiration of food** via a TE fistula
134
How has endoscopic screening impacted the prognosis of **esophageal SCC?**
What is the overall prognosis in the US?
- **5-year survival** of **75%** if caught early while still superficial
- Overall in the US 5-year survival remains \<20%
135
**Tylosis** (dry hands and feet), a risk factor for esophageal SCC, is a mutation in __________ and causes \_\_\_\_\_\_\_\_\_
* **RHBDF2 mutation**
* **Howel-evans syndrome**
136
