Chapter 17: Congenital Disorders and Neoplasms of the ESO Flashcards
What are the 4 types of congenital abnormalities of the esophagus?
- Obstruction
- Achalasia
- Esophagitis
- Neoplasms
The GI tract is a common site of developmental abnormalities. In these cases, defects of what other organ should be considered?
defects of other organs that develop in the same embryonic period should be sought
__________ are structural developmental anomalies that disrupt normal GI transit and typically present early in life.
Atresia and fistulae
Intestinal atresias are _____ common than esophageal atresias but often involve the _____.
less
duodenum
____________ is the most common form of congenital intestinal atresia, while the
__________ is the most common site of fistulization.
- Imperforate anus
- Esophagus
Imperforate anus is a result of what embryologically?
Cloacal diaphragm does not involute
When are atresia, fistula and duplications of the esophagus discovered?
Treated?
- Shortly after birth, due to regurg when eating.
- W/o surgery, cannot live.
What is esophageal atresia?
- Incomplete development of the esophagus.
- Thin, non-canalized cord replaces part of esophagus and causes mechanical obstruction.
What is the most common form of esophageal atresia?
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
Are a fistula & atresia always present together?
No (C) is just a fistula
(A) is just atresia.
Fistulas of the esophagus can lead to what sxs?
- Aspiration
- Suffocation
- Pneumonia
- Severe fluid/electrolyte imbalances
_____________ 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?
Stenosis
-ESO and SI
Developmental abnormalities of the the esophagus are associated with what other defects?
- Congenital heart defects
- GU malformation
- Neurologic disease
When congenital GI disorders are present, what other associations should we consider?
VACTERL associations
- Vertebral
- Anal anomalies
- Cardiac
- TE fistula
- Renal anomalies
- Limb anomalies
Diaphragmatic hernia occurs when?
If severe, what happens?
- Incomplete formation of the diaphragm allows the abdominal viscera to herniate into the thoracic cavity.
- When severe, can cause pulmonary hypoplasia => incompatible with life
Difference between omphalocele and gastroschisis?
- 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
What is the most frequent site of ectopic gastric mucosa and what is it referred to here?
May result in what problems?
- Upper 1/3 of esophagus (Inlet patch)
- Dysphagia, esophagitis, Barrett esophagus, or rarely, adenocarcinoma
What are examples of ectopia seen within the GI tract?
- Ectopic pancreatic tissue: in stomach or esophagus
- Gastric heterotropia: patches of ectopic gastric mucosa in the small bowel or colon
Gastric heterotropia may present with what signs/symptoms?
Occult blood loss due to peptic ulceration of adjancent mucosa
What is the most common true diverticulum and where does it occur?
- Meckel diverticulum
- Ileum
Cause of Meckel Diverticulum?
Failed involution of vitelline duct
What is the rule of 2’s in regards to Meckel Diverticulum?
- 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
What may be present in a Meckel Diverticulum that causes symptoms and what are these symptoms?
- 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.
Which sex is most commonly affected by congenital hypertrophic pyloric stenosis?
M (3-5x more likely)
Which genetic disorders are associated with an increased risk of Pyloric Stenosis?
- Turner syndrome
- Trisomy 18
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
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
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
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.
- 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
Which genetic abnormality can account for the majority of familial cases of Hirschsprung disease?
LOF mutation of RET (receptor tyrosine kinase)
How does Hirschsprung disease typically present?
- Failure to pass meconium in the immediate postnatal period.
- => Obstruction or constipation
- => Abdominal distension and bilous vomitting
What are the major threats to life in regards to Hirschsprung disease?
- Enterocolitis
- Fluid/electrolye imbalance
- Perforation
- Peritonitis
Diagnosis of Hirschsprung disease requires what?
Which stain can be used?
- Documenting absence of ganglion cells within affected segment
- Immunohistochemical stains for acetylcholinesterase for ganglion cells
Which part of the colon is ALWAYS affected in Hirschsprung Disease?
Rectum
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
-
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.
__________ allows us to categorize 3 types of esophageal dysmotility.
What are they?
- Nutcracker esophagus
- Diffuse esophageal spasm
- Hypertensive lower esophageal sphincter (LES)
What is nutcracker esophagus?
Long, high amplitude contractions in the distal esophagus that are cause some loss of NL coordination (NL coordination in proximal).
What is diffuse esophageal spasm?
-
Diffuse, uncoordinated contractions (repetitive and simultantous) of the esophagus (corkscrew)
- On manometry: no high pressure
On Barium swallow, which esophageal obstruction looks like a corkscrew?
Diffuse esophageal spasm
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
What is hypertensive lower esophageal sphincter?
- High resting pressure of LES
- Incomplete relaxation
W/O alterations in the patterns of esophageal contraction.
How can hypertensive LES be differentiated from achalasia?
Achalasia: ↓ esophgeal peristaltic contractions
Esophageal dysmotility causes ___________, which can result in the formation of ___________.
- ↑ wall stress
- small diverticulae, primarily the epiphrenic divertiulum, located above the LES.
What can form a Zenker diverticulum?
Impaired relaxation and spasm of the cricopharyngeaus muscle after swallowing => increased pressure in distal pharynx => Zenkers diverticulum.
Where does Zenkers diverticulum (_________ diverticulum) form?
- Pharyngoesophageal diverticulum
- RIGHT above the upper esophageal sphincter
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)
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.
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)
How can we differentiate functional obstruction/ benign strictures vs. malignant strictures?
- Functional obstruction/ benign strictures: can maintain weight and appetitie
- Malignant strictures: WL
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
Esophageal mucosal webs most often occur in whom?
Associated with what other diseases?
- Woman >40 yo
- GERD, chronic GVHD, or blistering skin diseases
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)
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
What type of mucosa are A and B Schatzki rings covered by?
- A rings = squamous mucosa
- B rings = gastric cardia type of mucosa
Esophageal webs causes ___________ dysphagia.
Non-progressive dysphagia associated w/ incompletely chewed food
When we swallow, what normally allows LES to relax?
- Inhibitory neurons release NO and vasoactive intestinal polypeptides
- Normal cholinergic signaling is interrupted.
What is the triad of Achalasia?
- Incomplete LES relaxation
- Increased LES tone
- Aperistalsis of esophagus
Achalasia causes _______ dysphagia and…
- Progressive/gradual dysphagia for solids + liquids
- Hard time burping
- Chest pain
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
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
- Destruction of myenteric plexus (duodenal, colonic and uteric)
- Failure of peristalsis
- Esophageal dilation
Linkage of achalsia to which immune disorders suggest that achalasia may also be driven by immune-mediated destruction of inhibitory esophageal neurons?
- HSV1 infection
- Immunoregulatory gene polymorphisms
- Sjorgen syndrome
- Autoimmune thyroid disease
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)
- Complete absence of NL peristalsis
- Incomplete LES relaxation w swallowing.
Achalasia
_________ can result from chemical or infectious mucosal injury.
Infection is most common in _____________.
- Esophagitis
- Immunocompromised
What are the 2 main sx related to pathology of GI tract?
- Abdominal pain
- GI hemorrhage
_____ blood loss of the GI tract is a medical MRGC.
Acute blood loss
Which are more common: UGI bleeds or LGI bleeds?
UGIB
ID the source of bleeding based on the character of blood:
Vomiting bright red blood (hememesis)
If GI, most likely proximal to the ligament of Trietz.
ID the source of bleeding based on the character of blood:
Black, tarry stool (melena)
Upper GI bleed
ID the source of bleeding based on the character of blood:
Bright, red blood in rectum (hematochezia)
Lower GI bleed (or very rapid UGI bleed)
Esophageal causes of vomitting of bright red blood (hematemesis)
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.
Mallory-Weiss tears are most commonly associated/caused by what?
- Severe retching (i.e., bulimia)
- Vomiting secondary to acute alcohol intoxication
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
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
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
Chemical or infectious esophagitis can cause what symptoms?
Range from: Odynophagia => hemorrhage, stricture or perforation.
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
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.
Infectious esophagitis in healthy individuals in UNCOMMON and most often due to ___________.
HSV
Viral esophagitis caused by Herpes virus is distinguished by what morphological characteristics?
- Punched-out ulcers
- Nuclear viral inclusions
Infectious esophagitis in debilitated/immunospressed is MORE common and caused by what?
- HSV
- CMV
- Fungus
Viral esophagitis caused by CMV is distinguished by what morphological characteristics?
- Shallow ulcers
- Nuclear and cytoplasmic inclusions (characteristic)
Which fungi are the most common causes of esophagitis?
- Candidiasis (most common)
- Mucormycosis
- Aspergillosis
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
What is the most common viral cause of esophagitis?
Herpes simplex
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
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.
What is the most common cause of esophagitis and the most common outpatient GI diagnosis?
Reflux esophagitis into the lower esophagus. (GERD)
What is the most common cause of gastroesophageal reflux?
Transient relaxation of lower esophageal sphincter
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
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
What are some of the complications that may result from reflux esophagitis?
- Ulceration
- Hematemesis
- Melena (dark sticky feces)
- Stricture development (ulcer -> loss of mucosal layer –> fibrosis)
- Barrett esophagus
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
What is the cardinal histological feature of eosinophilic esophagitis?
i.e., large #’s of which cells and where
Large #’s of intraepithelial eosinophils, particularly superficially
How is eosinophilic esophagitis different from GERD?
- Acid reflux is NOT prominent
- PPI’s usually do NOT provide relief
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
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)
Variceal hemorrhage is a medical emergency that can be treated how?
- Inducing splanchnic vasoCONSTRICTION
- Endoscopic sclerotherapy (inject thrombotic agents)
- Balloon tamponade
- Variceal ligation
What are the signs/symptoms of esophaeal varices?
- Esophageal bleeding
- PAINLESS hematemesis
In people with esophageal varices, ______ die initially and _____ recurr within a year.
30%;
50%
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.
What are symptoms of hiatal hernia?
- Heartburn
- Regurg of gastric juices
What is a complication of chronic GERD?
Barrett esophagus:
- Metaplasia of lower esophageal mucosa (stratified squamous epi —> nonciliated columnar epithelium w/ goblet cells)
The greatest concern in Barrett esophagus is that it confers an increased risk of developing?
Esophageal adenocarcinoma
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)
How is Barrets esophagus diagnosed?
Endoscopy and biospy, showing evidence of metaplastic columnar mucosa above GE junction.
What does BE esophagus look like?
Patches of red, velvety mucosa the extend up from GE junction: pale squamous esophageal mucosa alternates with light brown gastric mucosa distally.
When [Barretts esophagus + dysplasia], what do we see?
- Atypical mitosis
- Nuclear hyperchromasia
- Irregularly clumped chromatin
- ↑ nuclear-to-cytoplasm ratio
- Failure to epithelial cells to mature as they migrate to the esophageal surface
- 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%
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
Benign tumors of the esophagus are usually __________.
Mesenchymal
Most esophageal adenocarcinomas arise from ____________.
Barretts esophagus
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.
What is associated w/ ↓ risk of esophageal adenocarcinoma?
- Some types of H. pylori
- Cause gastric atrophy –> ⇩ acid secretion and reflux
Which ethnicity and sex is most commonly affected by esophageal adenocarcinoma?
Recent increased incidence in which populations?
- Caucasians
- Men 7x more likely
- Recent ↑ rates in: Hispanic men and White women
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
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
How does a patient with an esophageal adenocarcinoma typically present (signs/symptoms)?
- Pain or difficulty swallowing
- Progressive weight loss
- Hematemesis
- Chest pain
- Vomiting
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%
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!!!
Which part of the esophagus do the majority of squamous cell carcinomas begin?
Middle 1/3 of the esophagus
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
SqCC of the esophagus has a very high incidence in which 5 geographic locations?
- - Iran
- -China
- - Hong Kong
- Brazil
- South Africa
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
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
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
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
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
What are the common signs and symptoms of someone presenting with SCC of the esophagus?
What is seen if the tumor ulcerates?
- Progressive dysphagia (solids –> liquids)
- Odynophagia (painful swallowing)
- 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
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
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%
Tylosis (dry hands and feet), a risk factor for esophageal SCC, is a mutation in __________ and causes _________
- RHBDF2 mutation
- Howel-evans syndrome
