Esophageal Carcinoma Flashcards

Question 1

Q

Overall survival rate of esophageal carcinoma?

A. <10%
B. 10-20%
C. 20-30%
D. >30%

Answer

A

Ans B

18.6% 5 year overall survival as per SEER website.

The 5 year survival rate for patients who have complete or near complete response after operative therapy is 40-75%.

The yearly incidence of the esophageal cancer is comparable to its yearly total of cancer related deaths.

MD ANDERSON 6E PG 355, 356.

Although present day therapeutic interventions have begun to have an impact, with statistically significant improvement in survival over the most recent 3 decades, cancer of the esophagus remains a highly lethal disease as evidenced by the case fatality rate of 90%.

Devita 10e Pg 574.

Across all races the death rate is approximately 5 times higher in men than women.

Over the past decade the death rate due to esophageal cancer has been declining at an average of 0.8% per year.

Shackleford 8e Pg 362.

Question 2

Q

which is the most common esophageal cancer in India

A. Sqaumous cell carcinoma
B. Adenocarcinoma
C. Adenosquamous
D. Lymphosarcoma

Answer

A

Ans A -

In the past squamous cell carcinoma accounted for more than 95% of cases, but in recent years adenocarcinoma arising in the backgroung of Barrett Esophagus has become increasingly more common and it now accounts for more than 75% of the esophageal cancers at most major american centers.

SCC has substantial geographic variation from 1.5-7 cases per lac in most parts of the world including USA, reaching upto 100-150 per lac in its endemic areas such as northern China, South Africa, Iran, Russia and India.

MD Anderson 6e Pg 356

Question 3

Q

Which of the following is a risk factor for development of SCC

A. Male
B. Smoking
C. Alcohol
D. Overweight

Answer

A

Ans D

Majority of the new cases are diagnosed in people over the age of 65 years-74 years, with the median age being 67 years. Overall there is a male preponderance for 7:1 for all esophageal cancer.

Risk factors of SCC -

Males have a 3-4 times higher risk than females.
Smoking and Alcohol have a synergistic effect and can increase the risk upto 44 times
Achalasia (30x risk)
Strictures resulting from lye ingestion
Zenker Diverticulum
Esophageal webs in Plummer Vinson syndrome
Prior radiation
Familial connective tissue disorder such as tylosis
Diets with Nitrates and Nitrosamines.
Fungal contamination of foodstuffs with associated aflatoxin
Deficiency of vitamin A, C and Riboflavin.

MD Anderson 6e Pg 356, 357.

90% of the squamous cell cancer can be attributed to tobacco use.
Tobacco and alcohol are independent risk factors with multiplicative effect.

Smoking has a dose-response effect. Quitting smoking leads to reduction in the risk of ESCC.

Occupational risks for ESCC -

Perchloroethylene (Dry cleaners, Metal polishers)
Combustion products
Fossil fuels
Chimney sweepers, printers, gas station attendants, asphalt and Metal workers
Silica and metal dust
Asbestos

Devita 10e Pg 574.

Current smokers have a 3-7x times the increased risk for the development of SCC and 2x increased risk of development of EAC.
Consuming more than 3 alcoholic beverages per day increases the risk of SCC.

Achalasia - increased risk of SCC due to chronic mucosal irritation caused by nitrosamines released from the bacteria in the food. 10-50x increase in relative risk. Average of 24 years after the onset of achalasia symptoms.
Achalasia is also associated with increased risk of EAC.

shackleford 8e Pg 363, 364.

Question 4

Q

which of the following is not a risk factor for the development of adenocarcinoma of the esopagus

A. Overweight
B. Male
C. Eradication of H Pylori
D. Tobacco
E. Alcohol

Answer

A

Ans E -

Typical patient for adenocarcinoma is a middle class, over weight male in his 60-70s.
The primary etiologic factors are obesity and Barrett Esophagus.
Annual incidence of malignant transformation in Barrett is approximately 0.5% per year.

Tobacco use and eradication of H pylori are also linked to the increased incidence of esophageal adenocarcinoma.

MD Anderson 6e Pg 356.

Quitting smoking does not appear to decrease risk of adenocarcinoma therefore carcinogenesis occurs early on in EAC. Smoking is also a risk factor for the development of BE.

There is no relationship b.w alcohol intake and risk of esophageal adenocarcinoma.

Devita 10e Pg 575.

Infection with H pylori particularly the cagA+ strain is inversely associated with a risj of adenocarcinoma of the esophagus.
Leads to chronic atrophic gastritis and decreased acid production.

However the concurrent presence of gastric atrophy and H pylori infection has been reported to significantly increase the risk of squamous cell carcinoma.
Atrophic gastritis may promote bacterial overgrowth and lead to intra-gastric nitrosation with the production of nitrosamines leading to increased risk of SCC.

Devita 10e Pg 576,

patients with a BMI more than or equal to 30 have a 2-3 times higher risk of developing EAC.

Shackleford 8e Pg 328.

Question 5

Q

Most common location for the development of SCC of esophagus

A. Proximal third of esophagus
B. Middle third of esophagus
C. Distal third of the esophagus
D. GEJ

Answer

A

Ans B -

20% cases of SCC involve the upper third of the esophagus, 50% involve the middle third, and the remaining 30% extend from the distal part of the esophagus to the GEJ.

SCC rarely invades the stomach and there is a discrete segment of normal mucosa between the cancer and the gastric cardia.

Nearly 97% of adenocarcinoma develop in the middle and distal esophagus.

MD Anderson 6e Pg 357.

Approximately 60% of the SCC are located in the middle third of the esophagus, whereas 30% are located in the distal and 10% arise in the proximal one third.

Devita 10e Pg 578.

Cancer of the cervical esophagus is rare.
SCC is evenly distributed between the middle and lower thoracic esophagus, whereas 75% of all EAC is located in the distal esophagus.

EGJ tumors are defined as those located between the distal 5cm of the esophagus and proximal 5cm of the gastric cardia. Siewert et al classified them as -

type I - Esophageal
type II - Cardiac
type III - Subcardiac.

Shackleford 8e Pg 363.

Question 6

Q

the most common symptom of esophageal carcinoma

A. Regurgitation
B. Chest Pain
C. Progressive dysphagia
D. Weight loss

Answer

A

Ans C -

Symptoms such as dysphagia, weight loss, regurgitation or back pain are alarming.

Most patients experience symptoms for 2-6 months before they seek medical attention.
The most common symptom is progressive dysphagia, which occurs in as many as 80-90% of patients.

MD Anderson 358

Question 7

Q

What percentage of esophageal lumen must be compromised before patient experiences dysphagia

A. 25-50%
B. 30-60%
C. 50-75%
D. 80-100%

Answer

A

Ans C -
dysphagia is a late sign because the esophageal lumen must be reduced to 50-75% of its original size before patients experience this symptom. Typically when the diameter approaches 12 to 13mm.

MD Anderson 6e 358

Question 8

Q

Which of the following is most accurate for T staging of esophageal cancer -

A. Endoscopy and Biopsy
B. EUS
C. CECT Chest
D. MRI

Answer

A

Ans B -

Endoscopic ultrasound is the most accurate in predicting depth of invasion of the primary lesion.

CT scans of the chest and abdomen should be obtained to assess the degree of any local invasion of mediastinal structures, adenopathy, or for evidence of dissemination/distant metastases, especially in the lungs.

MD Anderson 6e Pg 359

Question 9

Q

Which of the following is not true regarding EGFR expression in esophageal cancer?

A. EGFR is commonly overexpressed in early stages of esophageal cancer
B. Associated with poor prognosis
C. Associate with poor response to chemoradiotherapy
D. Associated with metastatic disease in ESCC

Answer

A

Ans D-

EGFR family of receptor tyrosine kinases -
- stimulate a number of signal transducers such as ras, raf, MEK, ERK, PI3K and AKT.

Aberrant activation of the EGFR members is crucial in esophageal carcinogenesis.

EGFR is commonly overexpressed in early stages of esophageal cancer and overexpression correlates with poor prognosis.

Increased expression of EGFR is seen in BE, EAC and ESCC.

EGFR overexpression may predict

poor response to chemoradiotherapy
decreased survival in ESCC
recurrent disease and decreased overall survival in ESCC after esophagectomy.

Devita 10e Pg 570.

Question 10

Q

which of the following is true regarding Cyclin D1

A. complexes with either CDK4 or CDK 6
B. causes de-phosphorylation of pRb tumor supressor protein and reduces its tumor supressing activity
C. Inhibits E2F family of transcription factors therefore allows progress to G1/S
D. All of the above

Answer

A

Ans A -

CDK and CDK-inhibitors (p16, p15, p21 and p27) regulate the mammalian cell cycle.

During the G1 phase -
- cyclin D1 complexes with CDK 4 and CDK 6 to phosphorylate the retinoblastoma pRB tumor supressor protein and in doing so relieves its negative regulatory effect.

this allows E2F family of transcription factor to propel the cell cycle towards the G1/S transition phase.

Devita 10e Pg 571

Question 11

Q

which of the following is true regarding cyclin D1 overexpression in esophageal cancer

A. active in premalignant lesions such as BE or squamous dysplasia
B. Majority of early stage ESCC and EAC have cyclin D1 overexpression
C. associated with poor outcomes and survival as well as poor response to chemotherapy
D. All of the above

Answer

A

Ans D -

All of the above statements are true.

Devita 10e Pg 571,

Question 12

Q

which of the following is a late change observed in ESCC

A. Cyclin D1
B. p16INK4a mutations
C. EGFR
D. Tp53

Answer

A

Ans B -

pINK4a is an early genetic alteration via promoter hypermethylation or point mutations or allelic deletion via BE and EAC, but interestingly it is a late event in ESCC.

Cyclin D1 is found in majority of early stage ESCC and EAC.

EGFR is commonly overexpressed in early stage esophageal cancer.

Tp53 mutation or loss of heterozygosity appears early in BE and EAC, and they have also been identified in 40-75% of ESCC.

Devita 10e Pg 571.

Question 13

Q

Which of the following is not seen esophageal cancer

A. Cyclin D1 overexpression
B. EGFR Overexpression
C. Rb gene mutation
D. Tp53 mutation

Answer

A

Ans C -

An Rb gene mutation is not found in either type of esophageal neoplasm but allelic loss of 13q region where the Rb gene resides has been found in 50% of patients with BE and ESCC.

Common molecular genetic alterations in Esophageal and Gastric Cancers

Oncogenes - EGFR, Cyclin D1
Tumor supressors - p16INK4a, TP53, E-Cadherin, p120Catenin
DNA mismatch repair genes - hMLH1, hMSH2 (Mismatch repair instability)

Devita 10e Pg 571.

Question 14

Q

Which of the following is associated with a response to induction chemoradiotherapy and survival after esophagectomy in ESCC and EAC

A. Cyclin D1
B. EGFR
C. TP 53
D. p16INK4a

Answer

A

Ans C -

Cyclin D1 overexpression correlates with poor outcomes and survival as well as poor response to chemotherapy.

EGFR overexpression is associated with poor prognosis, poor response to chemoradiotherapy, decreased survival in patients with ESCC.

The presence of p53 point mutation correlates with a response to induction chemoradiotherapy and predicted survival after esophagectomy in patients with either ESCC or EAC.

Devita 10e Pg 571.

Question 15

Q

The most common variant of Esophageal cancer worldwide is  - 
A. Adenocarcinoma
B. GIST
C. SCC
D. Leiomyosarcoma

Answer

A

Ans C -

In recent decades, the United states along with many other western countries has witnessed a profound increase in incidence rates of adenocarcinoma, whereas squamous cell carcinoma continues to dominate worldwide.
Devita 10e Pg 574

Question 16

Q

which of the following is not an endemic region for Esophageal carcinoma

A. Turkey
B. India
C. Northern China
D. Iran
E. South Africa
F. Spain

Answer

A

Ans F - Spain

endemic areas such as norther china, s. africa, iran, russia and india.

MD Anderson 6e Pg 356.

Highest rates for males from Calvados, France, Hong Kong and Miyagi Japan.

Highest rates for females from Bombay, Shanghai and Scotland.

Devita 10e 574.

Question 17

Q

All of the following are associated with increased risk of esophageal cancer except -

A. Vitamin A deficiency
B. Vitamin C Deficiency
C. Vitamin E Deficiency
D. Vitamin K

Answer

A

Ans D -

A number of micronutrients are associated with increased risk for esophageal cancer -

Vitamin A, C and E
Selenium,
PUFA
Vitamin D

Devita 10e POg 575.

Deficiencies of Vitamin A, E, Se and Zn are also beleived to contribute to the development of SCC.

Question 18

Q

which of the following is the single most important risk factor for the development of EAC

A. Smoking
B. Barrett’s esopagus
C. Central obesity
D. GERD

Answer

A

Ans B -

Barrett’s esophagus is the single most important risk factor for developing esophageal adenocarcinoma with a relative risk of 11.3 and an annual risk of conversion of 0.12-0.33%.

GERD has been implicated as one of the strongest risk factor for the development of adenocarcinoma of the esophagus. Chronicity of the reflux symptoms are associated with a 2 to 16 fold increased risk of adenocarcinoma of the esophagus regardless of the presence of Barrett’s esophagus.

Devita 10e Pg 576.

More so than GERD, Barrett esophagus is the most important risk factor in the development of EAC.
Risk factors for progression to EAC include - chronic GERD, hiatal hernia, advanced age, male, white, tobacco use and Obesity.
the risk of cancer also increases as the segment length of BE increases

Shackleford 8e Pg 365.

High grade dysplasia in BE is the most powerful predictor of subsequent invasive adenocarcinoma and is associated with a per year cacner incidence rate of 6%,

Devita 10e Pg 582.

Question 19

Q

which of the following statements is true regarding esophageal cancer

A. Aspirin may have protective effect against transformation to EAC
B. Tylosis is an autosomal recessive condition mapped to TOC gene.
C. Caustic injury leads to distal esophageal SCC in 10-20 years.
D. Prior upper aerodigestive tract cancers are associated with increased risk for ESCC of 4% per year

Answer

A

Ans A -

BE is associated with increased expression of COX2. Both selective and non-selective COX2 inhibitors were effective at inhibiting Barrett’s esophagus-related adenocarcinoma. NSAIDs may act as a potential chemopreventive agents.

Tylosis is a rare inherited autosomal dominant disease with hyperkeratosis of palms and soles and esophageal papillomas. They have abnormal maturation of Squamous cells and inflammation within the esophagus. It is mapped to TOC gene on 17q 25.

Caustic injury with lye ingestion leads ESCC within 40-50 years after a caustic injury in the middle third of the esophagus. These cancers are diagnosed late because the chronic dysphagia and pain caused by lye strictures masks the symptoms of esophageal cancer.

Prior aerodigestive tract cancers are associated with increased risk of ESCC at a rate of approximately 4% per year. Notably TP53 is not functioning as a tumor susceptibility gene is this setting.

Plummer Vinson syndrome or Paterson Kelly syndrome is associated with IDA + Glossitis + Cheilitis + Brittle fingernails + Splenomegaly + Esophageal webs.
10% of these individuals have hypopharyngeal or esophageal epidermoid carcinomas.

Low socioeconomic status is also associated with an increased risk for SCC.

Achalasia cardia is associated with a 16-30 fold increase in the risk of ESCC. Average duration before the development of ESCC in achalasia is 17 years.
Occurs due to prolonged irritation by the food retained in the midesophagus.

(If EAC develops it develops just below the air-fluid level in achalasia - Sabiston 20E)

HPV is associated with increased risk of ESCC in the high endemic regions of Asia and South africa. This is mediated by the E6 and E7 mediated sequestration of Rb and p53 proteins.

Devita 10e Pg 576, 577.

Question 20

Q

which of the following is the most likely to be responsible for EAC

A. EGFR overexpression
B. TP53 gene mutation
C. CDKN2A mutation.
D. NOTCH

Answer

A

ANS A

For esophageal and GEJ adenocarcinomas, amplification of certain genes rather than gene mutations are more important drivers of oncogenesis - including EGFR, ERBB2, FGF 1 and 2.
The most common affected genes by mutation though are Tp53 and CDK2NA. NOTCH is an important gene in esophageal squamous cell carcinoma.

Devita 10e Pg 577.

Question 21

Q

what is the 5 year survival rate of esophageal adenocarcinoma

A. <5%
B. <10%
C. <15%
D. <20%

Answer

A

Ans D -

Esophageal adenocarcinoma is a highly lethal disease with a survival rate of less than 20% at 5 years.

Shackleford 8e Pg 314.

The overall 5 year survival rate is estimated to be less than 18%.

Shackleford 8e Pg 368.

Question 22

Q

which malignancy has seen the highest rate of increase in the last 4 decades

A. Gastric carcinoma
B. Esophageal squamous cell carcinoma
C. Esophageal adenocarcinoma
D. Head and Neck cancers

Answer

A

Ans C -

The incidence of EAC has been climbing for more than 40 years at a rate greater than any other malignancy and with a greater than 7 times increase in the US between 1975 and 2006.

Shackleford 8e Pg 314.

Incidence amoung caucasian men increased up until the year 2000 reflecting the marked increase in the incidence of esophageal adenocarcinoma of the esophagus more than 400% in the past 2 decades.

Although the incidence of esophageal cancer is lower in caucasian females, rates of adenocarcinoma have increased in women by more than 300% during the past 20 years.

Devita 10e Pg 574.

Question 23

Q

what proportion of patients with GERD have BE

A. 2-5%
B. 5-10%
C. 10-15%
D. >20%

Answer

A

Ans C -

Depending on how it is defined and the diligence with which it is detected, BE is found in approximately 10%-15% of the patients with asymptomatic GERD.

Shackleford 8e Pg 314.

Question 24

Q

which of the following statements is false about Columnar Lined Esophagus

A. Presence of chief and parietal cells along with mucus secreting cells is suggestive of oxyntocardiac mucosa.

B. Cardiac type or junctional type of mucosa is always present in the squamo-oxyntic gap

C. Intestinalized type Columnar Mucosa, when present, is the most proximal in the squamo oxyntic gap.

D. A direct transition from esophageal squamous mucosa to oxyntic gastric mucosa does exist in some individuals without a buffer zone of cardiac epithelium.

Answer

A

Ans B -

The normal esophagus is lined by stratified squamous epithelium, whereas the normal stomach is lined by the gastric oxyntic epithelium. The former is never present in the stomach, whereas the latter is never present in the esophagus.

At the junctional zone of these two, there can be 3 types of epithelium - these can be -

pure cardiac
Oxyntocardiac
Intestinalized cardiac.

Cardiac or Junctional type of epithelium - comprises exclusively of mucus secreting cells.
Oxynto-cardiac or Gastric fundic type of epithelium comprises of mucus secreting as well as some parietal and chief cells.
Intestinalized cardiac or specialized type of epithelium containing mucus secreting cells and prominent goblet cells.

These three cell types can be detected without visible CLE in the region just distal to the GEJ as defined by proximal extent of gastric rugal folds.

When present, these epithelia always reside in the squamo-oxyntic gap.

When only one epithelium is present, such as is found only in short gaps generally less than 5mm, it is oxyntocardiac.

In longer gaps, both cardiac and oxyntocardiac mucosa can be present with cardiac mucosa being proximal to the oxyntocardiac.

When all three epithelia are present then intestinalized is the most proximal whereas cardiac lies in the middle followed by oxyntocardiac distally.
Admixing however can occur.

Cardiac mucosa is not present at the normal GEJ. A direct transition from esophageal squamous mucosa to oxyntic gastric mucosa does exist in some individuals without a buffer zone of cardiac epithelium in between.

Shackleford 8e Pg 317, 318.

Question 25

Q

which of the following is true regarding Cancers of the cardiac

A. Cancers arising in the cardia are not associated with symtomatic GERD

B. Incidence of Cancers of Cardia has increased

C. Cancers of cardia are classified as gastric cancers in the most recent staging of the AJCC

D. Cancers of cardia are not associated with intestinal metaplasia

Answer

A

Ans B -

Gastric cardia - used to denote the region of the stomach just distal to GEJ.

According to the recent theory, metaplastic cardiac epithelium has a derivation similar to metaplastic esophageal epithelium. This means that cancers of cardia are best classified as esophageal cancer and not gastric. This is consistent with the latest staging of American Joint Committee on Cancer (7th ed)

What has been called proximal stomach lined by metaplastic columnar epithelium is in fact esophagus.

Cancers arising in the cardia are associated with symptomatic GERD, although to a lesser extent when compared to EAC.

The increasing incidence of cardiac adenocarcinoma has paralleled the rise in EAC over the last four decades, while the distal stomach cancer rate has fallen.

The vast majority of cases of both EAC and Cardia adenocarcinoma are seen to occur in association with intestinal metaplasia.
The presence of dysplastic epithelium arising in cardiac or fundic mucosa is uncommon in absence of co-existing IM.

Shackleford 8e Pg 318.

there are no other immunohistochemical markers either specific for mucin or intestinalisation such as CDX2, DAS-1, Hep Par 1, Villin or MUC2 that can differentiate metaplasia occuring in the tubular esophagus from the cardia. Infact, IM arising in the proximal stomach possess immunohistochemical features similar to BE and not to IM arising in distal stomach.

Shackleford 8e Pg 319.

Question 26

Q

the risk of developing EAC increases by what percentage for every cm of BE

A. 1% per year for each cm
B. 11% over 4 years for each cm
C. 4% over 11 years for each cm
D. 4% per year for each cm

Answer

A

Ans B -

For every additional centimeter in BE length the risk of developing HGD or EAC increased by 11% over 4 years.

shackleford 8e Pg 319.

Question 27

Q

All of the following features distinguish pseudogoblet cells from goblet cells except -

A. Lack of triangular nucleus
B. Occur as row of cells in superficial epithelium
C. Both A and B
D. None of the above

Answer

A

Ans C -

Pseudogobelt cells are mucin-containing columnar cells that are difficult to distinguish from true goblet cells.

Goblet cells typically arise from single cells in a random distribution.
Pesudogoblet cells tend to occur in rows within the superficial epithelium.

Psuedogoblet cells also lack the triangular nucleus characteristic of true goblet cells.

Shackleford 8e Pg 319.

Question 28

Q

Which of the following is not true regarding Intestinal metaplasia -

A. Defined by the presence of goblet cells which normally reside in the intestine.

B. Goblet cells serve as markers for malignant potential of the metaplastic epithelium

C. Goblet cells are usually the precursor to EAC.

D. Goblet cell dynamics, goblet cells density, thoroughness of biosy can all affect the detection of Goblet cells

Answer

A

Ans C

Intestinal metaplasia is defined by the presence of goblet cells. “No goblets-No Barrett’s”

However the highly differentiated goblet cell is unlikely to be the precursor to EAC, because cancers typically arise from poorly differentiated cell lines.

The goblet cell merely serves as a marker for the malignant potential of the surrounding metaplastic epithelium.

A number of factors can affect the detection of goblet cells -

Differentiation of goblet cells from pseudogoblet cells.
Sampling error which depends on the thoroughness of the biopsies, the length of CLE, and goblet cell density.
Goblet cell dynamics.

Shackleford 8e Pg 319.

Question 29

Q

Which of the following statements is true regarding Goblet cells

A. The density of goblet cells was the highest in the distal part of the squamo-oxyntic gap.

B. The likelihood of detecting intestinal metaplasia increases with higher number of biopsies taken

C. The likelihood of detecting goblet cells does not correlate with the length of the CLE.

D. Current guidelines recommend biopsy in any one of the four quadrants every 1-2cm interval.

Answer

A

Ans B -

Intestinal metaplasia of patients with a length of CLE of 1cm or less is 56%, whereas it increases to 100% for CLE more than 5cm in length.

The likelihood of detecting goblet cells has been shown to correlate directly with number of biopsies performed at endoscopy as well as the length of CLE, and reaching 100% when more than 16 biopsies were taken.

The goblet cell density depends on the position along the length of the CLE. Highest near the SCJ and lowest in the more distal portions.

Current recommendation is to perform a four quadrant biopsy every 1-2cm along CLE, with special attention given to the regions of mucosal nodularity or irregularity.

Shackleford 8e Pg 319.

Question 30

Q

which of the following is involved in the early stages or non-intestinal type of metaplasia in BE

A. Sonic Hedgehog
B. BMP4
C. CDX2
D. both A and B

Answer

A

Ans D -

The first step in intestinalisation is mediated by upregulation of sonic hedgehog or SHH-BMP4 signalling path leading to phosphorylation of SMAD proteins.

The SHH-BMP4/pSMAD signalling pathway is responsible for the induction of genes responsible for non-intestinal type of metaplasia.

The next step is mediated by the interaction of pSMAD with CDX2 (intestine specific homeobox gene).

In the final stages of intestinal differentiation, Wnt and NOTCH signalling are also key.

Shackleford 8e Pg 319, 320.

Question 31

Q

BE affects what proportion of the general population?

A. 5%
B. 5-10%
C. 1-2%
D. 15-20%

Answer

A

Ans C -

A standard estimate is that barrett disease affects approximately 1-2% of western populations.

Recent meta-analyses including 51 studies with over greater than 450,000 patients from Asia suggests that histologically proven pooled prevalence of BE is 1.3%, and thus comparable to western estimates. This suggests that BE is not uncommon in Asian countries.

Shackleford 8e Pg 323.

Question 32

Q

which of the following statements is false regarding BE

A. Not known to occur in children less than 5 years of age

B. BE patients are slightly older than their non-BE GERD patients.

C. there is a 2:1 female to male preponderance of BE

D. The risk of BE is increased after 12 years of age.

Answer

A

Ans C

Most epidemiologic data show a 2:1 male predominance.
BE patients are also typically slightly older than non-BE GERD patients at between 50-65 years of age.

BE is rare in pediatric age group, and histologic presence of IM is approximately 0.12% in patients less than 20 years of age.

There are no reports of BE containing IM in a child under the age of 5 years.

The risk of BE is increased after 12 years of age supporting a timeline of some years before BE development.

Shackleford 8e Pg 323.

Question 33

Q

which of the following statements is true regarding BE?

A. Length of the BE correlates with the amount and duration of reflux exposure.

B. Patients with BE have more esophageal dysmotility and lower LES pressures compared to patients with GERD without BE.

C. BE patients tend to have longer exposure to gastric contents with very low pH (<2 or 3)

D. BE patients tend to have higher proportions of Hiatal hernia as compared to GERD without BE.

E. All of the above

Answer

A

Ans E -

Chronic GERD is the main cause of BE.

The risk and length of BE both correlate with the amount and duration of the reflux exposure.

The exact mechanism by which GERD leads to BE remains elusive.

Patients with BE when compared with other GERD patients have

more esophageal dysmotility
lower LES pressure
higher likelihood of hiatal hernia
longer exposure to gastric contents with lower pH (<2-3)
higher likelihood of duodenal reflux along with acid reflux.
higher frequency of episodes is associated with a 10x increased risk of BE.

notably, patient who have BE may report that their symptoms have improved in recent years, which is postulated to be relaxed to BE development and perhaps reduced esophageal sensitivity.

Shackleford 8e Pg 328.

Question 34

Q

which of the following statements is false regarding BE

A. Central visceral adiposity may be a more important risk factor for BE than BMI alone.

B. Smoking and GERD may have a synergistic effect on disease development and progression

C. Wine consumption may increase the risk of BE

D. Twin studies have suggested a nearly 30-40% heritability of BE.

Answer

A

Ans C -

Patients with a BMI more than 30 may be 2-3 times higher risk of developing EAC. There is no more than 50% increase in risk for BE with BMI more than 30.

Central visceral adiposity may be a more important risk factor for BE formation than BMI itself. Visceral adipose tissue was 1.5 times higher in patients with BE as compared to controls.
When controlling for waist-to-hip ratio, the association between BMI and BE has been shown to be almost completely attenuated.
Central obesity alters the expression levels of
- leptin
- adiponectin
- TNF Alpha
- IL6
- IGF

Leptin is upregulated in obesity and increases proliferation of EAC in vitro.
Studies have found an increased risk of BE if leptin was increased. Significant inverse relationship has also been documented with adiponectin.

Smoking -
There is a 2x increased risk of BE in patients who have ever smoked. There is a dose-response which plateaus at about 20 pack years.

Smoking and GERD may have a synergistic effect on disease development and progression.

There is no convincing data to show increased risk of BE or EAC due to alcohol consumption. On the contrary an inverse association of wine consumption and risk of BE has been reported.

Family history -
There is most probably a heritable or familial aspect for BE and EAC and this is supported by -
- Concordance in both mono- and di-zygotic twins.
- increased disease risk in patients with a positive family history
- identification of SNPs through GWAS in genes that render individuals susceptible to BE and EAC.

Twin studies have suggested a heritability of upto 30-40%.

Shackleford 8e Pg 328.

Question 35

Q

which of the following is not associated with reduced risk of BE and EAC

A. H Pylori infection
B. Aspirin
C. Atorvastatin
D. Rabeprazole.
E. Height

Answer

A

Ans D -

Height -
Height is inversely associated with risk of BE and EAC irrepective of gender, age, patient education, BMI, weight and GERD symptoms.

H pylori -
H pylori infections reduce intragastric acidity through the generation of ammonia or by causing severe corpus gastritis with concomitant decrease in gastric parietal cells, thus reducing the acid production. Infection with H. Pylori CagA+ strains has consistently been shown to reduce the risks of EAC, evidence for this effect is less consistent for BE.
This risk was reduced even when controlling for reflux symptoms, hence suggesting that the protective effect of H pylori cannot be explained by simply reduced gastric acid production.

NSAID -
Aspirin has been shown to protective in a number of cancers - Stomach, EAC, Colon and Rectum. There is a 44-58% reduction in mortality due to esophageal cancers in aspirin users. They inhibit the COX2 enzyme and this restores apoptosis and inhibits cell growth and proliferation as well as neoangiogenesis.

Statin -
Patients taking statin medications have a reduced risk of developing both BE and EAC. Statin use is significantly associated with a reduced risk of BE compared with controls.

Acid suppressive treatment with PPI failed to show any major protective effect on BE progression. PPIs are indicated for symptom relief but they are not BE chemopreventive agents.

Anti-reflux surgery -
- While several single centre studies have shown that Antireflux surgeries may be associated with BE regression this is not shown by multicentre and population data studies that have so far failed to show this occurs more frequently than expected by chance alone.

Vitamin C, A and E are also associated with decreased risk of BE, however use of anti-oxidants supplements failed to show influence over BE risk. High dietary intake of Mg significantly reduces the risk of reflux esophagitis and BE and this effect is most prominent in the setting of a low calcium:magnesium intake ratio.

Shackleford 8e Pg 330.

Question 36

Q

What is the annual cancer risk for BE ?

A. 1% per year
B. 0.5-1% per year
C. 0.1-0.5% per year
D. 2-3% per year

Answer

A

Ans C -

Low incidence rate with annual cancer risks ranging from 0.12% to 0.43%

It is currently considered that the risk of developing EAC in non-dysplastic BE is low at approximately 1 in 300-500 patients per year, and that the risk of mortality in BE patients is increased due to other causes.

Shackleford 8e Pg 331.

Upto 60% of incidence EAC cases are diagnosed within 1 year of the diagnosis of BE, indicating that they are probably missed at index endoscopy.
The Seattle protocol includes four quadrant biopsies every 1-2 cm, but even such rigorous biopsy strategies typically sample less than 5% of the Barrett epithelium, thus rendering sampling error unavoidable.

Question 37

Q

Which of the following is not a risk factor for the progression of BE to EAC

A. Male Sex
B. Age more than 50 years
C. Low waist to hip ratio 
D. Smoking
E. long duration of GERD symptoms

Answer

A

Ans C -

Men are at increased risk of developing EAC compared with women, and the M:F ratios can be upto 6:1.

Risk of EAC increases with age with the peak around 6th and 7th decade of life.

The duration of patient’s BE is also a risk factor with those having BE for more than 10 years having 2x risk of HGD and EAC compared to those less than 10 years.

Men over the age of 50 years with BE are at increased risk of developing EAC.

EAC is a cancer with one of the strongest associations with obesity.
In males increased waist-to-hip ratio and waist circumference may confer a higher risk of BE progression.

Tobacco use is a risk factor for EAC. The risk is increased for both current and former smokers. Smoking has also been found to increase the risk for progression to HGD and EAC in BE patients across all strata of smoking intensity and current smokers display the highest risk of malignant BE progression.

Longer symptoms duration - patients with 20 years or longer of reflux symptoms have 3x higher risk of EAC compared with those less than 10 years. Moreover patients who have reflux symptoms have an approximately 6 times higher risk of EAC compared with those without symptoms.

Severe long standing and frequent GERD are associated with an increased risk for EAC. Current management guidelines recommend BE patients with severe and uncontrolled symptoms of reflux require acid supressive therapy to help prevent progression.

Shackleford 8e Pg 331.

Question 38

Q

Ultra-short BE is defined as a BE of length

A. <1mm
B. <10mm
C. <15mm
D. <20mm

Answer

A

Ans B -

The risk of neoplastic progression increases with the length of the BE.
Long segment BE is more than or equal to 3cm, short segment BE is more than or equal to 1m but less than 3cm whereas ultra-short segment barrett esophagus is defined as less than 1cm.

Recent guidelines suggest that patients with greater than 3cm of BE and no dysplasia - screening endoscopy with quadrantic biopsies every 2-3 years.
SSBE with no dysplasia - screening interval can be increased to 3-5 years.

If a nodule/ulcer/stricture is present there is a high risk of malignancy irrespective of Barrett segment length and reassessment without delay is needed.

Shackleford 8e Pg 331.

Question 39

Q

the most common location for squamous cell carcinoma of esophagus is

A. Distal third of esophagus
B. Upper third of esophagus
C. Gastroesophageal junction
D. both B and C

Answer

A

Ans A -

Approximately 60% of these neoplasms arise in the middle one third of the esophagus. Whereas 30% and 10% arise in the distal third and proximal third of the intra-thoracic esophagus respectively.

Devita 10e Pg 578.

Question 40

Q

which of the following is true regarding Small cell carcinoma of the esophagus

A. Arise of Argyrophillic cells located in sub-mucosa

B. Located in the proximal one third of the esophagus

C. Produce a variety of hormones such as parathormones, secretin, GCSF

D. usually detected early due to paraneoplastic effects

Answer

A

Ans C -

Small cell carcinoma of the esophagus arises from the argyrophillic cells located in the basal layer of squamous epithelium.

They are usually located in the middle and distal one third of the esophagus

They are associated with ectopic production of parathormone, gastrin releasing peptide, secretin and GCSF.

They usually present with systemic disease.
Devita 10e Pg 579.

Question 41

Q

all of the following are common sites of metastases from Ca Esophagus except

A. Lung
B. Liver
C. Bone
D. Adrenal
E. Kidney

Answer

A

Ans E-

the lung, liver and bone are the most common sites of distant disease with the depth of tumor and lymph node involvement predictive of tumor dissemination.

Devita 10e Pg 579.

The most common metastatic sites are retroperitoneal or celiac lymph nodes, liver, lungs and adrenals.

Adenocarcinomas most frequently metastasize to intra-abdominal sites, while metastases from SCC more commonly spread to intra-thoracic and cervical locations.

Shackleford 8e Pg 368

Question 42

Q

which of the following is the most common mode of therapeutic failure in ESCC

A. Distant metastases
B. Locoregional Failure
C. Cervical Metastases
D. Both A and C

Answer

A

Ans B -

In patients with cancers of upper and middle thirds of the esophagus, which are predominantly squamous cell cancers, local-regional recurrence predominates over distant recurrence, whereas in patients with lesions of the lower third where adenocarcinomas are more located, distant recurrences are more common.

Preoperative radiotherapy and preoperative chemoradiotherapy reduce the rate of loco-regional recurrence but they have no effect on the rate of distant metastases. Addition of surgery further reduces the local failure from 45% to 32% but it does not diminish the systemic recurrence, infact it may enhance it by allowing patients to manifest distant disease because they do not succumb to local regional failure.

Devita 10e Pg 579.

Question 43

Q

typical patients with EAC is usually described with all except

A. middle or upper class 
B. Male
C. Obese
D. symptomatic GERD with history of treatment for reflux
E. none of the above

Answer

A

Ans E -

Patients with EAC tend to caucasian males from middle to upper socioeconomic classes who are overweight, have a symptomatic gastroesophageal reflux, and have been treated with anti-reflux therapy.

Devita 10e Pg 579.

Because of the influence of nutritional and socioeconomic factors, the risk of squamous cell carcinoma of esophagus increases with decreasing BMI.

Devita 10e Pg 576.

Question 44

Q

Best available marker for the assessment of risk of BE progression

A. Dysplasia confirmed by two gastrointestinal pathologists.

B. Presence of severe esophagitis or strictures

C. Duration of symptoms more than 20 years

D. Duration of BE more than 10 years

Answer

A

Ans A -

Dysplasia remains the basis for clinical decision making. The risk of EAC development is higher in patients with LGD compared to NDBE and highest for patients with HGD.
Dysplasia confirmed by two gastrointestinal pathologists is currently the best available biomarker for the assessment of risk of BE progression.

Shackleford 8e Pg 332.

Question 45

Q

which of following has shown the highest promise as a biomarker for BE progression ?

A. CDK2NA
B. EFGR
C. p53
D. ERBb2

Answer

A

Ans C -

the largest body of evidence concerns the potential utility of p53 immunohistochemistry to assess protein expression.

Addition of p53 immunohistochemistry may improve the diagnosis of dysplasia and improve patient stratification.

Shackleford 8e Pg 333.

Question 46

Q

All of the following are true regarding indefinite for dysplasia except -

A. Interim diagnosis
B. due to inflammation obscuring HPE
C. maximal acid supression is advised
D. Follow up can be liberal compared to LGD

Answer

A

Ans D -

A specimen indefinite for dysplasia is often a result of active inflammation, which precludes accurate histologic classification. This is an interim diagnosis only which requires close follow up for definitive characterisation of the histologic pattern. Acid supression therapy should be maximized and repeat biopsies obtained after a brief period to allow healing.

Shackleford 8e Pg 340.

Maximize acid supression therapy (High dose PPI with a nocturnal Histamine Blocker). Repeat EGD with surveillance biopsies after a period for healing (Weeks to months)

Shackleford 8e Pg 341 Box 33.1

Question 47

Q

which of the following is true regarding surveillance in BE

A. Endoscopic mucosal resection is indicated for mucosal abnormalities

B. Four quadrant biopsies at 2cm intervals are indicated in non-dysplastic BE at 1-2 year interval.

C. Four quadrant biopsies at 1cm interval are indicated at 6-12 month intervals in LGD

D. All of the above.

Answer

A

Ans All of the above.

The efficacy of surveillance has been questioned. But poor efficacy is likely due to excessively long interval between surveillance endoscopies and an inadequate number of biopsies to adequately evaluate Barrett Segment.

Surveillance of non-dysplastic Barrett Esophagus should include -
- use of high definition endoscopy with 4 quadrant biopsies every 2cm with separate EMR of mucosal abnormalities at an interval of 3-5 years.

If there is a history of LGD, biopsies should be obtained at every 1cm every 6-12 months.

Although increasingly patients are opting for undergoing ablation rather than continued
surveillance.

Verbeek et al have demonstrated a decreased esophageal adenocarcinoma mortality at 2 and 5 years for those adhering to surveillance protocols.

Shackleford 8e Pg 340

Question 48

Q

All of the following are correct regarding the treatment of LGD in BE except

A. repeat EGD with surveillance biopsies at 1cm intervals at 6 months

B. If there is a regression on two consecutive exams then the surveillance may be de-escalated to Non-dysplastic Barrett.

C. Aggressive reflux control is recommended with anti-reflux surgery

D. Persistent or high risk features on repeat biopsies are an indication for Esophagectomy

Answer

A

Ans D -

Low grade dysplasia -

Aggressive reflux control with recommendation for anti-reflux surgery in appropriate candidates and second opinion from expert GI pathologist.

Repeat EGD with surviellance bx in 6 months
If there is regression on two consecutive exams then surveillance may be de-escalated to non-dysplastic BE.

If there is persistence of LGD or high risk features seen on index or repeat bx then ablative therapy to reduce the risk of progression is recommended.

Shackleford 8e Pg 341, Box 33.1

Barrett esophagus and LGD on a single biopsy should undergo continued surveillance in the absence of high risk features such as mucosal irregularity, multifocal disease, long segment disease.

LGD present on a second biopsy is defined as persistent dysplasia.
When LGD is not found on second biopsy this is characterised as regressive disease. However this can be true regression or simply a sampling error or interobserver variability.

Number of endoscopies with LGD was an independent predictor for progression.

The available evidence suggests that at a diagnosis of LGD, patients should undergo management of their reflux disease, ideally with anti-reflux surgery. Repeat endoscopy and biopsies are recommended at 3-6 months and if dysplasia persists, ablation with a low risk modality such as RFA is recommended to reduce the risk of progression.

Shackleford 8e Pg 345, 346.

For LGD to be considered confirmed, guidelines recommend a second pathologist with GI expertise review the biopsies, and for a second endoscopy and biopsy after 6 months to reassess the BE and confirm the continued presence of the LGD. In this group of patients with confirmed LGD, the data for a higher risk of progression to HGD and IMC are clear. Using this definition for LGD guidelines in the US recommend endoscopic ablation to be appropriate for patients with confirmed LGD.

Shackleford 8e Pg 351.

Question 49

Q

Which of the following is not true regarding management of HGD in BE

A. Second opinion for confirmation by expert GI pathologist

B. Endoscopic resection of visible lesions

C. Ablation of Barrett mucosa

D. none of the above

Answer

A

Ans D -

High grade dysplasia or intra-mucosal adenocarcinoma -

second opinion from expert GI pathologist must be sought.
Endoscopic resection of visible lesions must be undertaken
ablation of Barrett mucosa must be undertaken.

Shackleford 8e Pg 341. Box 33.1

EMR has recently gained favor - it is safe, effective and less invasive. Also allows for more definitive histological examination for diagnosis or staging and is curative in nearly all patients when the disease is limited to the mucosa.

HGD must be evaluated thoroughly before intervention - review by 2 expert GI pathologists. Using high resolution endoscopes, meticulous and systematic approach to biopsies and EMR of concerning of area. Use of seattle protocol if patient cannot be referred to a high volume centre - 1cm interval four quadrant biopsies from the proximal extent of the gastric folds to the most proximal extent of intestinal metaplasia.

Non-nodular BE with HGD : ablative therapy is preferrable to both intense surveillance and surgery.

Mucosal nodularity/ulceration/irregular mucosal contour - EMR can be both diagnostic and therapeutic.
The pathologic findings from the EMR specimen should guide the next steps in the therapy.

a. LGD or HGD on EMR should undergo ablation of the remainder of the intestinal metaplasia.
b. T1a on EMR - ablation of the surrounding IM
c. T1b on EMR - consider for esophagectomy
d. non-dysplastic on EMR - continue surveillance without change.

Complete resection of T1b is also possible with ESD. However the risk of lymph node metastasis becomes significant as the tumor invades into the submucosa.

The first and most critical step in staging is endoscopic resection of the lesion and pathologic evaluation of depth of invasion, and risk factors for node metastasis -

size more than 2cm
poor differentiation
LVNI

Shackleford 8e Pg 346.

If nodules are present, there is a 2.6 times potential for progression to EAC, and if ulceration is present the risk of presence of EAC in a HGD segment has been reported to be 80%, compared with 52% if there was no ulceration.
Endoscopic resection of these abnormalities if possible offers better pathologic staging and complete resection should be performed before attempts at BE ablation.
Patients with a diagnosis of IMC that has been endoscopically completely removed will need ablation of the residual BE segment.

Shackleford 8e Pg 350.

Question 50

Q

Which of the following are indication for esophagectomy in HGD with BE

A. Long segment BE more than 8 cm
B. multifocal disease is present
C. Difficult to control reflux 
D. Poor esophageal motility or large hiatal hernias
E. All of the above

Answer

A

Ans E -

Consider esophagectomy in patients with ultra-long BE more than 8cm, when multifocal disease is present, or in patients with difficult to control or severe GERD especially in the setting of poor esophageal motility and large hiatal hernia.

Shackleford 8e Pg 341.

Although the rate of occult invasive esophageal cancer is much lower than 40%, it is not 0% and factors such as multifocal or nodular disease have been associated with increased risk. Treatment with esophagectomy in this group was recently found to have increased utility and cost effectiveness.

Patients who have a relatively low operative risk estimation based on a lack of comorbid conditions in the setting of high risk tumor features should be carefully counselled regarding the treatment options and potential outcomes.

Esophagectomy should be considered in those who fail endoscopic therapy.

Shackleford 8e Pg 347.

Question 51

Q

ASPECT trial is related to

A. Role of statins in prevention of esophageal cancer

B. role of aspirin in prevention of gastric cancer

C. Role of Aspirin and Esomeprazole in prevention of EAC

D. Role of aspirin in prevention of EAC

Answer

A

ANS C -

Aspirin in conjunction with PPI has been found to decrease the PGE2 levels in patients with either non-dysplastic Barrett or LGD. The aspirin Esomeprazole Chemoprevention Trial is currently ongoing to study this issue.

Shackleford 8e Pg 341.

Question 52

Q

which of the following statements is false regarding BE

A. PDT has been shown to reduce risk of EAC in setting of HGD.

B. Endoscopic ablative therapies can prevent the progression from non-dysplastic BE to HGD or LGD

C. Rate of recurrence after endoscopic ablation can be decreased with the use of Anti-reflux surgery

D. PDT is known to be associated with Buried Barrett glands under the neosquamous epithelium

Answer

A

Ans B -

Level 1 evidence exists for a reduced risk of adenocarcinoma with PDT in HGD and RFA in both LGD and HGD

Endoscopic ablation in the setting of non-dysplastic BE is not currently recommended as there is no convincing evidence to suggest that ablation of non-dysplastic BE decreases the risk of malignancy. There are two likely reasons -

complete ablation without recurrence has not be demonstrated with any modality.
ongoing acid exposure may sabotage the effectiveness of ablation.

The risk of recurrence was found to be significantly lower in those who underwent surgical fundoplication.

Shackleford 8e Pg 344.

At this time there is no evidence that supports the routine use of endoscopic ablative therapies for NDBE. Ablation for NDBE is not cost effective due to the low rate of progression to adenocarcinoma in this group of patients.

Shackleford 8e Pg 351

Question 53

Q

the most common endoscopic ablative technique used at present in BE

A. EMR + RFA
B. RFA alone
C. PDT
D. Argon plasma coagulation

Answer

A

ans A -

Presently the most commonly applied techniques are endoscopic resection of a focal abnormality with RFA of the residual dysplastic or non-dysplastic BE.

Shackleford 8e Pg 350.

Question 54

Q

which of the following is considered the safest technique in the setting of LGD

A. RFA
B. PDT
C. APC
D. Cryotherapy

Answer

A

Ans A -

RFA was the most safe and effective option in this group but ablation does not completely eradicate the risk of progression to either HGD or EAC.

Shackleford 8e Pg 350.

For ablation to be a realistic option in asymptomatic patients with NDBE, the treatment must be safe, be effective, have durable long term results and be cost effective. The safest and most effective treatment is RFA. Patients with NDBE who had RFA and regular follow up with treatment of residual or recurrent IM, the complete regression rate was 70% at 1 year and 92% at 5 years.
This group of patients required multiple endoscopies and more intense surveillance than recommended for non-treated NDBE. The impact of this approach on the patient’s longevity and quality of life along with the cost effectiveness is yet to be clearly determined.

With respect to cost effectiveness of BE ablation in 2004, a study examined the management of HGD comparing endoscopic surveillance, esophagectomy and endoscopic ablation using PDT. Endoablation using PDT was shown to be the most cost effective strategy. A recent review also concluded that endoscopic therapy for dysplastic BE using PDT or RFA, was cost effective compared to esophagectomy.

Shackleford 8e Pg 351.

However one single institution cohort study reported the cost of PDT to be 5 times that of RFA.

Using a markov model, assessing patients with HGD - RFA with continued surveillance is more cost effective than endoscopic surveillance and esophagectomy when a cancer develops.

Shackleford 8e Pg 351.

The most frequently used mucosal ablation technique is RFA because this procedure produces a more predictable degree of mucosal eradication and has a low side effect profile.

Shackleford 8e Pg 353.

Question 55

Q

All of the following are risk factors for progression of LGD to HGD or EAC except

A. Males
B. Obese
C. NDBE for more than 10 years
D. BE longer than 3cm
E. Persistent esophagitis
F. Multifocal disease 
G. Presence of nodules in the BE mucosa

Answer

A

Ans B -

The factors that have been associated with higher rate of progression of LGD to HGD or EAC include - 
Male gender
NDBE for more than 10 years
Length of BE more than 3cm
Persistent esophagitis
Multifocal dysplasia
Presence of nodules in the BE mucosa.

In a consensus statement from the BOBCAT group it was agreed that there was moderate evidence to support the ablation of high risk LGD group.

Shackleford 8e Pg 351.

Question 56

Q

which of the following is the most common complication of Stepwise Radical Endoscopic Resection

A. Stricture
B. Bleeding
C. Perforation
D. Buried Barrett

Answer

A

Ans A -

Following a targeted resection of the abnormal neoplastic focus, multiple resections are then performed to remove the rest of the BE segment in a piecemeal fashion.
Aims is to attempt 50-70% of circumference resection at the first session. The technique usually requires 2-3 ER sessions per patient.

In patient with HGD and IMC this technique provides Complete eliminated of the neoplastic pathology in 80-100% and complete elimination of IM in 70-100%.
At a median followup of 23 months - durability was 85-100% for dysplastic BE and 75-100% for IM.

The efficacy of SRER for complete eradication of dysplasia is nearly 95% whereas for IM is 89%.

The most common complication of SRER is stricture which occurs in nearly 23-88% cases and this is much higher compared to the EMR+RFA group.

The other complications are Perforations, Bleeding, and Buried Barrett.

Shackleford 8e Pg 352.

Question 57

Q

All of the following are disadvantages associated with the use of ESD except

A. Time consuming
B. Higher rates of Bleeding
C. Higher rates of stricture compared to SRER
D. Higher rates of perforation

Answer

A

Ans C -

ESD used in early neoplasia of stomach, esophagus and CRC. The main advantage is the ability to remove enbloc large lesions in a plane b/w submucosa and muscularis propria.

Compared to EMR, in neoplasia of stomach, esophagus and CRC, ESD was associated with better rates of enbloc removal and curative resections with less local recurrence.

However ESD is more time consuming, with higher rates of bleeding and perforation.

While ESD also has a considerably higher rate of strictures, nearly 60%, this is less compared to SRER, which has a stricture rate of upto 80%.

It also requires extra level of expertise.
Also there is no clear evidence of improved rates of CE of dysplasia with SRER or focal EMR followed by BE ablation notably using RFA.

Complete resections rates of dysplasia are 97-100%, whereas complete resections rates for IM are 60%.
Durability for eradication of dysplasia at 2 years is 92%, whereas for IM at 2 years is 75%.

Stricture is the most common complication.

Patients which may be considered for ESD are -

visible lesions
multiple lesions
lesions larger than 15mm
poorly lifting with submucosal injection

Shackleford 8e Pg 352, 353.

Question 58

Q

All of the following can decrease the efficacy of RFA at the time of first application except-

A. Large hiatal hernia
B. Longer segment of BE
C. Esophagitis 
D. Narrow esophagus
E. Esophageal webs

Answer

A

Ans E -

RFA offers the most reliable destruction of mucosa to the level of submucosa. The efficacy of this technique at the time of the first application can be reduced if there is a large hiatal hernia, longer segments of BE, esophagitis and a narrow esophagus.

Shackleford 8e Pg 353.

Question 59

Q

All of the following are predictors for poor response to RFA in BE except

A. Active reflux esophagitis
B. EMR scar regeneration with new BE
C. Esophageal lumen narrowing pre-RFA
D. Number of years of neoplasia before treatment
E. All of the above

Answer

A

Ans E -

Predictors of a poor response to RFA include active reflux esophagitis, EMR scar regeneration with new BE mucosa, esophageal lumen narrowing pre-RFA, and the number of years of neoplasia pretreatment.

Recurrence after RFA occurs in three distinct patterns -

Endoscopically invisible or Buried Barrett
Visible recurrence in the tubular esophagus
intestinal metaplasia typically seen at the GEJ.

Usually the recurrence histologic grade is no worse than the pretreatment grade.

Shackleford 8e Pg 354.

Question 60

Q

What is the decrease in likelihood of successful eradication for every 1 cm incresase in length of BE with RFA

A. 5%
B. 13%
C. 18%
D. 23%

Answer

A

Ans B -

The IM recurrence rate in 4-8 cm group was 16% compared to 23% for the longer segments.
The 3 year IM CE rates were 82% for 4-8cm group and 65% for the more than 8 cm group.
It was estimated that the potential for successful eradication of IM decreased by 13% for each extra 1cm of BE.

Shackleford 8e Pg 354.

Continued careful surveillance is necessary after patients have had RFA ablation and that the surveillance biopsies should include the cardia.

Shackleford 8e Pg 354.

Question 61

Q

which of the following is false regarding RFA in BE

A. Most common complication of RFA is stricture

B. The rate of stricture formation is higher in patients using NSAID or previous history of anti-reflux surgery

C. EMR + RFA has fewer complications compared to the SRER

D. EMR is associated with fewer treatments for presistent disease

Answer

A

Ans D

Stricture formation is the most common complication following RFA, with the incidence reported to be between 7-12%.

The predictors of higher stricture rate were the use of NSAID, previous anti-reflux surgery and history of esophagitis.

Less common complications of RFA include - GI hemorrhage, dysphagia, and transient retrosternal pain.

EMR+RFA has fewer short term complications compared to the SRER group.

Further treatments for persistent or recurrent disease was required more often following EMR compared with RFA.

Complete Eradication of dysplasia is 74% for RFA and 91% for EMR+RFA.

Complete eradication of IM is 80-90% for RFA and 78% for EMR + RFA.

Shackleford 8e Pg 355.

Question 62

Q

all of the following are the photosensitizers used in photodynamic therapy in BE except

A. Porfimer Sodium
B. Indocyanine Green
C. Aminolevulinic acid
D. meta-tetrahydroxyphenyl chlorine or mTHPC

Answer

A

Ans B -

the photosensitizing drugs used are activated by light at specific wavelengths resulting in a photodynamic reaction causing direct cytotoxicity, inflammation, and necrosis.

The drugs used include porfimer sodium, aminolvelulinic acid and meta-tetrahydroxyphenyl chlorine.

Shackleford 8e Pg 355.

Question 63

Q

which of the following is false statement regarding PDT in BE

A. Expensive, intensive and requires specialized equipment

B. ALA has a higher rate of strictures and photosensitivity compared to Porfimer sodium

C. Red light ranging from 630-635nm is used in most cases.

D. One the major drawbacks is the high rate of buried glands

Answer

A

Ans B -

There is good tissue penetration and thus a good depth of necrosis.
PDT is intensive, expensive and requires specialized equipment, and has a large side effect profile.

ALA has less photosensitivity due to its shorter half life and has a lower stricture rate due to a more limited absorption of light. While the CE of HGD is comparable in ALA and PS (47% and 40% respectively), a stricture rate of 9% versus 33% and a difference in photosensitivity of 6% versus 43%.

PS 2mg/kg is given iv 72 hours prior to the procedure, whereas ALA 30-60mg/kg can be given orally on the day of procedure.

The majority of PDT data are from red light 630-635 nm with some series using green light at 514nm.

PDT is a targeted therapy that will specifically treat the Barrett segment allowing replacement by neosquamous epithelium in 50-80%.

There is long term evidence that PDT leads to signficant reduction in HGD and in the progression to EAC compared with PPI. The risk of recurrence of HGD is upto 8% and the risk is higher if the length of BE is more than 8cm and if multiple treatments were required to eliminate the IM.

Shackleford 8e Pg 355

Question 64

Q

All of the following are side effects associated with PDT except

A. Strictures
B. Photosensitivity 
C. Pleural effusion
D. Hypotension
E. raised creatinine

Answer

A

Ans E -

The complication profile of PDT includes strictures, photosensitivity, pleural effusions, hypotension and transient liver function test abnormalities.

The rate of buried Barrett glands varies but can be as high as 48%.

Shackeford 8e Pg 356.

Answer 65

A

Ans D -

The efficacy of complete eradication of dysplasia and IM are both lower than RFA in PDT.

Complete eradication of dysplasia - 
PDT 50-80%, RFA 74%
Complete eradication of IM -
PDT 13-52%, RFA 80-100%
Durability of eradication of Dysplasia -

PDT 48%, RFA 92%

Buried glands as well as strictures occur much more frequently with PDT than RFA.

Shackleford 8e Pg 356.

Answer 66

A

Ans B -

Buried barrett is the most common complication of APC occuring in 24% patients.
Strictures occur in 9-11% patients. Other complications are less common with APC.

Shackleford 8e Pg 356.

Answer 67

A

Ans A -

Cryotherapy destroys tissues with cycles of rapid cooling and slow thawing. It is a no-contact therapy using liquid nitrogen carbon dioxide.

Failure of cellular metabolism occurs due to intracellular and extracellular ice. The cell damage leads to vascular stasis and ischemic necrosis.

A pressure of 22pounds/inch or 151.7 psi is used.

A spray catheter is used for application with multiple areas 3-5 able to be treated at once.

The liquidized gas is applied until white frost appears, and then allowed to thaw after a period of at least 45 seconds.

The dosing has varied from 3 cycles of 20 seconds to 4 cycles of 10 seconds and recently 2 cycles of 20 seconds.

A 20s application of liquid nitrogen will produce 6-7 liters of gas at room temperatures. There may be technical difficulties with frosting of the lens and applying the treatment around the decompression tube.

Shackleford 8e Pg 356.

Additionally -
the CE rate for HGD is 87-100% and CE rate for IM is 53-84%. Whereas the durability of eradication is 84-100% at two years.

the rate of recurrence is higher in BE longer than 3cm. Most of the recurrences occur at the neosquamo-columnar junction.

The procedure may be beneficial in patients with irregular or scarred areas due to the non-contact technique.

Common complications include - Stricture, perforation, chest pain and buried barrett.

Shackleford 8e Pg 357.

Answer 68

A

Ans A -

BE may be subsquamous at the squamo-columnar junction in a typical BE segment. This was found to be the case in 98% of patients who had Barrett squamous junction resected as part of the EMR for focal neoplasia.

The average subsquamous length was 3.3mm and it was present as finger like projections. The majority of these deposits were within 5mm of the neosquamo-columnar junction

The incidence of malignancy in these residual buried glands is not clear. It has been reported that neoplastic BE may be more resistant to the ablative therapies and are more likely to remain as residual segments or as buried cells. Buried glands however may regress in some patients after ablation. However there has been suggestion that there is a biologic change in the DNA of these residual segments which may relate to a lower neoplastic potential.

Buried metaplasia can also be seen in patients who have not had any ablative therapy, with theories that this is a result of extensive biopsy sampling and subsequent healing. This has been documented in 20-25% of patients.
The reported incidence of buried metaplasia is the lowest after RFA.

Shackleford 8e Pg 357

Answer 69

A

Ans 2 -

When assessing the efficacy, the incidence of sustained eradication, ease of application, consistency of outcomes and safety profile, RFA is the superior method for eradication of BE segments.

For visible lesions the combination of EMR and RFA is the gold standard.

SRER removes the whole segment but has been restricted to shorter BE segments, has a similar incidence of persistent or recurrent IM compared to RFA, and although relatively safe, there is a high stricture rate.

For BE the role of ESD is not clear.

PDT has disappointing results with respect to long term CE rates, requires specific expertise and has a high complication profile that includes high rates of stricture formation and photosensitivity.

APC - easy to apply but the durability of CE is disappointing, with recurrence occuring in long term studies. The results from APC can be dependent on the operator, energy settings, APC mode and the distance of the catheter from the mucosa and time of energy transmission.
For longer segments of Barrett the procedure can be very time consuming.

Cryo has not shown equivalent durability when compared to RFA.

Cryo and APC may be reasonable alternative therapies if a patient had recurrence following previous RFA therapy.

Shackleford 8e Pg 358.

Answer 70

A

Ans D -

The overall incidence of esophageal cancer has declined in the US over the last 1 decade at a rate of 1.4% per year.

However, EAC is now the most common esophageal cancer in US and Europe. Whereas SCC remains the predominant type in the world.

EAC has grown at the highest rate of all known malignancies in the last 4 decades, while SCC at the same time has shown a steady decline.

The esophageal cancer belt with the highest incidence nof ESCC runs from the Middle East to the Northeast China.

Shackleford 8e Pg 362.

Answer 71

A

Ans D -

A positive association has been found between risk of EAC and the use of sphincter relaxing medications such as

nitroglycerines
anticholinergics
Beta-adrenergic agonists
aminophyllines
BZDs
calcium channel blockers

After adjusting for reflux symptoms, the positive association almost disappeared and therefore promotion of reflux is the mechanism behind this association.

Shackleford 8e Pg 365

Answer 72

A

Ans E-

American college of GE 2016 guidelines recommend endoscopic screening for BE in men with

chronic or frequent symptomatic GERD
with 2 or more risk factors for EAC (White, Age >50 years, Central obesity, Current or past tobacco user, family history of BE or EAC in first degree relative)

In women they recommend screening consideration on a case-to-case basis.

In patients with BE surveillance is recommended every 3-5 years in the absence of dysplasia, with more frequent intervals in the setting of dysplasia.

Shackleford 8e Pg 365.

Answer 73

A

Ans F -

Clinical stage or pretreatment stage is the extent of disease by diagnostic studies such as

physical examination
imaging tests
Endoscopic examination
biopsies of primary tumor
surgical exploration without resection of the affected area

The pathologic stage is defined by the same diagnostic studies used for clinical staging supplemented by findings from the surgical resection and histological examination of the surgically removed tissues.

Shackleford 8e Pg 369.

Answer 74

A

Ans B -

GX : Grade cannot be assessed
G1 : Well differentiated
G2 : Moderately differentiated
G3 : Poorly differentiated
G4 : Undifferentiated

Both G3 and G4 are considered high grade.

Shackleford 8e Pg 370

Answer 75

A

Ans C -

The TNM staging for all solid tumors was devised by Pierre Denoix between 1943 and 1952. Currently it is maintained and developed by - American Joint Committee on Cancer and Union for international cancer control.
The TNM staging is updated every 6-8 years.

Shackleford 8e Pg 370

Answer 76

A

Ans C -

UICC stands for Union for International Cancer Control

AJCC stands for American Joint committee on cancer.

Answer 77

A

Ans B -

N1: 1-2 nodes
N2: 3-6 nodes
N3: 7 or more nodes

there is no agreement on the ideal number of nodes to be resected for optimal staging.

Data suggests that the number of lymph nodes recovered, rather than their location, is an independent predictor of survival after esophagectomy.

SEER database shows, that when more than 12 nodes are examined there is significant reduction in mortality compared to no lymph node evaluation.

Moreover, patients who had more than 30 nodes examined had a significantly lower mortality than any other group.

There is general agreement that a 2 field LN dissection should be done in an invasive cancer.

Shackleford 8e Pg 370.

Answer 78

A

Ans B -

A Bronchoscopy should be reserved for patients with tumors in the upper and middle esophagus to rule out invasion of the membranous trachea and possible tracheo-esophageal fistula, although an EUS is now the procedure of choice to identify these unusual manifestations.

Devita 10e Pg 580.

Answer 79

A

Ans A -

EUS is superior to CT scans in both T and N staging of esophageal cancer. The overall accuracy for T staging is 85% and for N staging is approximately 75%.

The accuracy of determining lymph node involvement has been increased to 85-100% with the use of linear array EUS with a channel that allows for passage of a needle to perform tissue aspiration for cytology.

The accuracy of FDG PET scans in assessing regional lymph nodes falls somewhere between the low and high accuracy of CT and EUS respectively.

Devita 10e Pg 580

EUS is probably the most accurate means currently available for determining T and N status. Overall accuracy for depth of invasion is 76 to 90%, overall accuracy in predicting resectability is approximately 90-100% for adenocarcinoma and 75-80% for SCC.

studies comparing EUS and CT scanning generally agree that EUS is superior in determination of overall T status and assessment of regional lymph nodes (70-86% accuracy)

MD Anderson 6e Pg 360

Answer 80

A

Ans A -

In the detection of distant metastases, an FDG-PET scan is superior to CT, with a sensitivity, specificity and accuracy all in the range of 80-90%.
PET scans in combination with CT scans further improve specificity and accuracy of non-invasive staging.

PET-CT leads to detection of unsuspected metastatic disease or Upstaging in 15% of patients, which leads to alteration of the intended treatment plan in atleast 20% of patients. PET therefore has a role that is complementary to other staging procedures although it should supplant them.

Shackleford 8e Pg 580.

Answer 81

A

Ans D -

the sixth edition defined regional nodes N1 as those in the peri-esophageal, mediastinal and perigastric areas. But cervical and celiac nodes were regarded as distant metastases and designated as M1a disease.

In the 7th edition a regional node was redefined to include any para-esophageal node extending from the thoracic inlet to the celiac axis.

Shackleford 8e Pg 370

Answer 82

A

Ans D

In squamous cell carcinoma, tumors in the upper and middle thoracic esophagus have a poorer prognosis compared to those in the lower thoracic esophagus.

Also, tumor grade G1 has a better prognosis, whereas grade 2,3 and 4 are grouped together as worse prognosis.

therefore G1 tumor in the lower thoracic esophagus has the best prognosis - stage Ib

whereas a G2-4 tumor in the upper and middle thoracic esophagus has the worst prognosis. Stage IIb

on the other hand, a G1 tumor in the upper or middle thoracic esophagus or a G2-4 tumor in the lower esophagus has intermediate prognosis - Stage IIa.

For adenocarcinoma however only the tumor differentiation is of significance, and G1 and G2 are grouped together as better prognosis and G3 is considered worse prognosis.

Shackleford 8e Pg 371.

Answer 83

A

Ans B -

Siewert classification for GEJ tumors - Location of the tumor is defined by its epicentre or where 2/3 of its mass is located.

type I - epicentre of the tumo r is identified within 1-5cm above the anatomic EGJ.

type II - Cardia - the epicentre is identified within 1cm above or 2cm below the EGJ.

type III - cardial carcinoma - the epicentre is identified between 2cm and 5cm below the EGJ, infiltrating the EGJ and the distal esophagus from below.

Shackleford 8e Pg 372.

As per the AJCC 8th edition, the Siewert I and II are considered as esophageal cancers and Siewert III tumor, (more than 2cm below the GEJ even if involving the EGJ proximally) are considered as gastric cancers.

TNM classification - AJCC licensed app.

Answer 84

A

Ans A -
As per AJCC 8th edition, Siewert I and II - tumors with epicenter within distal esophagus, or upto 2cm below the esophagus are considered as esophageal cancers, whereas those with epicenter more than 2 cm below the esophagus are staged as gastric cancer even if the tumor progresses proximally and involves the EGJ.

TNM staging - AJCC licensed.

In the revised AJCC 7th edition, tumors whose midpoint are in the lower thoracic esophagus, EGJ or within proximal 5cm of the stomach that extend into the EGJ/esophagus are classified as adenocarcinoma of the esophagus for the purpose of staging.

All other cancers whose midpoint is more than 5cm distal to the EGJ, or those within 5cm of EGJ but not extending into the EGJ or esophagus (Siewert Type III) are staged using the gastric cancer staging system.

Shackleford 8e Pg 372.

Answer 85

A

Ans A -

The diagnostic yield approaches 100% when six or more samples are obtained using a standard endoscopic biopsy protocol.

Shackleford 8e Pg 374.

Answer 86

A

Ans C -

SCCs were found to highly accumulate FDG at the primary tumor.

Adenocarcinomas demonstrate more limited FDG accumulation. 
Non-avid tumors are often - 
 - Poorly differentiated
 - non-intestinal growth type
 - mucus containing tumor type

Shackleford 8e Pg 374.

Answer 87

A

Ans C -

PET has poor spatial resolution which renders it insufficient to separate the primary tumor from juxta-tumoral lymph nodes secondary to the interference from the primary tumor. The sensitivity of PET is poor in identification of lymph node involvement ranging from 38-82%.
This is especially true for nodes in the middle and lower mediastinum.
Sensitivity of PET for cervical nodes was 78%, for upper thoracic nodes was 82% and for abdominal nodes was 60%, but it was only 38% and 0% for the mid and lower mediastinum.
PET scan specificity is much better compared to the sensitivity. The main utility of PET scanning is in its ability to indentify the presence of distant metastasis. It has a accuracy of 84% in detecting metastases compared to 63% with CT. The accuracy of PET in detecting locoregional nodes is only moderate. EUS-FNA is more accurate in this regard. However PET is clearly more accurate for identifying distant nodal and visceral metastases.

Shackleford 8e Pg 375.

The accuracy of PET scans in assessing regional lymph nodes falls somewhere between the low and high accuracy of CT and EUS, respectively. In the detection of distant metastases, an FDG PET scan is superior to CT, with a sensitivity, specificity and accuracy all in the rang of 80-90%. PET scans in combination with CT further improves specificity, and accuracy of non-invasive imaging.

Devita 10e Pg 580

Although CT is probably the most widely used non-invasive staging modality worldwidem its accuracy is quite limited. Overall accuracy in determining resectability and T status have been estimated at 60-70% whereas accuracy in determining N status is less than 60%. Accuracy in detection of metastatic disease is somewhat better estimated at 70-90% for lesions greater than 1%. The used of combined imaging with PET-CT has improved the accuracy of both tests. Studies with this technique have reported overall accuracy levels of nearly 60% to detect locoregional nodal metastases and 90% to detect distant disease.

MD Anderson 6e Pg 360.

Answer 88

A

Ans A -

An esophageal wall thickness greater than 5mm on CT scan is generally considered abnormal.

Shackleford 8e Pg 375.

Answer 89

A

Ans C -

A CT scan cannot reliably distinguish between the various T stages, T1 and T2 lesions generally show a esophageal wall thickness between 5 and 15mm and T3 lesions have a wall thickness greater than 15mm, but this is far from accurate.

Shackleford 8e Pg 375.

Answer 90

A

Ans A -

The sensitivity of detecting abdominal and mediastinal nodes is sub-optimal with CT because size alone is used as a diagnostic criterion.

intrathoracic and abdominal nodes greater than 1cm are considered enlarged
Supra-clavicular nodes with a short axis greater than 0.5cm are considered enlarged
retrocrural nodes greater than 0.6cm are considered enlarged.

Sensitivity and specificity of CT for detecting nodal involvement in 50% and 83% respectively.

Large nodes may be inflammatory and not metastatic, whereas small nodes may be metastatic.

Shackleford 8e Pg 376.

Answer 91

A

Ans B -

Obliteration of the fat plane between esophagus and aorta/trachea/bronchi/pericardium is suggestive of invasion, but the paucity of fat makes this assessment unreliable.

Thickening or indentation of normally flat membranous trachea and left main bronchus also is suggestive of invasion but is should always be confirmed with bronchoscopy.

When the area of contact between the esophagus and aorta exceeds beyond 90 degree of the circumference, an 80% accuracy of infiltration is reported.

shackleford 8e Pg 375.

accuracy of CT for detecting aortic involvement or tracheobronchial invasion exceeds 90%.

Devita 10e Pg 580.

Answer 92

A

Ans A

CT scanning is inferior to laparoscopy in detecting peritoneal metastases.

Shackleford 8e Pg 375.

Overall accuracy of laparoscopy in staging and determination of resectability of esophageal carcinoma is as high as 90-100% and invasive procedures can avoid un-necessary surgical resection in as many as 20% patients.
Prospective comparisons with CT and EUS have suggested that laparoscopy and laparoscopic ultrasonography have superior overall accuracy in staging particularly for lymph nodes and metastatic disease.

MD Anderson 6e Pg 361.

Minimally invasive surgical techniques are being used for the staging of both local-regional and distant disease. Performing laparoscopy as the initial procedure at the time of a planned esophagectomy allows for detection of unsuspected distant metastases which spares the morbidity of laparotomy in 10-15% of cases.

Devita 10e Pg 581.

Small volume intraperitoneal metastases can be difficult to diagnose non-invasively by either CT or PET scans. Laparoscopic or thoracoscopic assessment can help identify occult intra-peritoneal or intrathoracic distant metastases as well as sampling regional lymph nodes.

A change in the stage originally assigned by CT and EUS occurred in 32.1% of patients with adenocarcinoma of the esophagus.

CALGB trial - Thoracoscopy and laparoscopy identified nodes or metastatic disease missed by CT in 50%, by MRI in 40% and by EUS in 30% cases. Although no deaths were involved, it did involve use of GA, one-lung anesthesia, median operating time of 3.5 hours and a hospital stay of 3 days.

Currently diagnostic thoracoscopy is not used except in highly selective cases where other staging studies suggest metastatic disease. Many consider diagnostic laparoscopy in patients with EAC with extensive gastric involvement or in patients with suspicious CT and PET findings.

Laparoscopy can be of use in diagnosing abdominal mets, such as peritoneal mets or unsuspected cirrhosis which is a relative contraindication for resection. Value of laparoscopy is minimal for proximally located tumors.

Following CT and EUS, laparoscopy can upstage nodal status in upto 20% and downstage it in 4-19% cases. Change in management can occur in upto 20% patients. Laparoscopic assessment is indicated in cases where liver mets or peritoneal mets are suspected and confirmation is required.

Shackleford 8e Pg 377, 378.

Answer 93

A

Ans E -

The modified criteria (Four standard EUS criteria plus EUS identified celiac nodes, >5 LN or EUS T3/4 tumor)

were more accurate than standard criteria (Hypoechoic, smooth border, round or width >5 to 10mm) at identifying malignant lymph nodes.

Compared to HPE, the sensitivity, specificity and accuracy of EUS/FNA for locoregional lymph nodes are all over 85%.

The sensitvity is highest for -

cervical and upper thoracic
infra-carinal
left paratracheal
recurrent laryngeal nodes.

EUS/FNA was more sensitive than CT and more accurate than CT or EUS for nodal staging.

Shackleford 8e Pg 376.

Answer 94

A

Ans D -

SCCs were found to highly accumulate FDG at the primary tumor site, in contrast to adenocarcinoma which demonstrated more limited FDG accumulation.
Shackleford 8e Pg 374

Overall accuracy of EUS in predicting resectability is approximately 90-100% for adenocarcinoma but decreases to 75-80% for SCC

MD Anderson 6e Pg 360

EUS accuracy is operator dependent and inter-observer reliability was found to be influenced by experience and tumor stage. Agreement among experienced endosonographers for both T and N stage was good, except for T2 tumors in which agreement was poor. There is a tendency to overstage T2 due to peritumoral inflammation.

Shackleford 8e Pg 376.

Answer 95

A

Ans D -

EBUS has a greater accuracy in evaluating tracheobronchial invasion by esophageal neoplasia when compared with conventional bronchoscopy, CT and EUS.

Sensitivity and specificity of tracheal involvement were 92% and 83% respectively, compared with 50-60% for CT and 70-80% for MRI.

EBUS diagnosis of tracheobronchial invasion was based on interruption in the most external hyperechoic layer of the tracheobronchus (Corresponding to its adventitia).

Shackleford 8e Pg 377

Answer 96

A

Ans A -

MUNICON Trial examined PET scan response during induction chemotherapy (Not chemoradiotherapy) in patients with GEJ adenocarcinoma.

PET scan non-responders assessed after 2 weeks of induction CTx were referred for immediate surgery rather than continuining with full 3-month course of CTx.
Survival in these non-responding patients was found to be equivalent to the survival in non-responding patients in a preceding trial who continued the full 3 months of CTx prior to surgery.
This study indicated that discontinuation of ineffective therapy and referral for earlier surgery did not compromise the outcome.

Survival in non-responders was inferior to PET non-responding patients compared with the PET responders.

Therefore MUNICON trial only established that ineffective therapy can be discontinued after 2 weeks in non-responders. It however does not explain whether such patients should be referred to alternative chemotherapy or chemoradiation.

Devita 10e Pg 580.

Two recent systematic reviews of the current available literature that addressed the evaluation of tumor response by PET scan to neoadjuvant therapy concluded -
- although PET scans are the best imaging imaging modality to assess response, the current data do not support routine use of PET scans to guide therapeutic decisions.

Alliance Intergroup randomized phase II trial is designed to answer this question in currently ongoing - T3/4 or N1 esophageal adenocarcinoma undergo PET Scan pretreatment –> induction chemo with either Modified Folfox6 or Carboplatin/paclitaxel –> PET scan at day 36-42 –> PET responders continue the initial chemo with concurrent 50.4 Gy RT or crossover to alternative Chemo with concurrent 50.4Gy RT.

Devita 10e Pg 581.

Answer 97

A

Ans D -

Decreased FDG uptake significantly correlated with pathologically confirmed response in patients treated with induction chemotherapy before esophagectomy. A prospective validation study confirmed that a decrease in the standard uptake value of 35% or more during preoperative chemotherapy may predict histologic response and is associated with improved survival and decreased recurrence.

Similar results have also been shown in SCC of esophagus.

Devita 10e Pg 580

Answer 98

A

Ans A -

T stage is now listed as high grade dysplasia that includes all non-invasive neoplastic epithelium which was formerly called carcinoma in situ.
Carcinoma in situ is a diagnosis that is no longer used for columnar mucosa anywhere in the GIT.

Devita 10e Pg 581.

Answer 99

A

Ans A -

Figure 36.8 shackleford 8e Pg 379.

Dysphagia or weight loss –> Upper endoscopic biopsy (Barium swallow if EGD not available) –> CANCER –> Contrast CT with or without PET –> if regional disease then EGD+EUS with or without FNA.

Answer 100

A

Ans D -

Changes between the 7th and 6th AJCC guidelines are -
- Tumor location is now defined by the position of the proximal edge of the tumor and is designated as upper, middle or lower esophagus

The Tis stage is now listed as high grade dysplasia that includes all non-invasive neoplastic epithelium which was formerly called carcinoma in situ
T1 tumors are now subclassified as T1a - tumor invades lamina propria/muscularis mucosae and T1b - invades submucosa.
T4 tumors are now subclassified as T4a (Resectable - pleura, pericardium and diaphragm) and T4b (unresectable - Aorta, vertebral body, trachea, etc)
N stage is determined by the presence of involved regional lymph nodes and is now subclassified according to the number of regional lymph nodes.
M1a subclassification based on distant lymph node involvement is no longer used.

The current AJCC

Devita 10e Pg 582.

Answer 101

A

Ans B -

Although older literature advocated for surveillance, patients with confirmed HGD should now be referred for treatment. Without intervention the progression risk from flat HGD to EAC is high ranging from 6-19% per year. Patients with visible lesions, such as nodular esophagus have a much higher risk of progression (40-70%). There is also a risk of concomitant adenocarcinoma in patients diagnosed with HGD. In one study patients who underwent esophagectomy for HGD, actually harbored invasive cancer in approximately 50% of the resected specimen. But other more recent studies using better endoscopic techniques and superior equipment suggest that the rate of undiagnosed cancer may be as low 11%.

Surveillance should be reserved for those who are unable or unwilling to undergo therapy. In these cases
- endoscopy every 3 months, with random 4 quadrant biopsies every 1cm with focused biopsies on any mucosal irregularity.

Shackleford 8e Pg 383.

it is important to note that the extent of HGD does not predict the presence of occult adenocarcinoma identified at esophagectomy, and therefore cannot be applied to a subjective quantification of disease.

Devita 10e Pg 583.

Answer 102

A

Ans A -

EMR is the preferred diagnostic and therapeutic tool for patients with nodular BE or early EAC. EMR is capable of removing small or moderate sized mucosal and superficial submucosal lesions.

It is superior to EUS for the assessment of depth invasion because the depth is determined by histologic examination.

Studies that compared EMR with EGD-EUS report that the pathologic staging was changed by EMR in 30-48% cases.

Shackleford 8e Pg 384.

EUS maintains a limited role for the evaluation of patients with HGD and early EAC. The accuracy of EUS staging in these disease categories is modest at best.

The sensitivity of EUS staging for mucosal tumors was 90%, whereas for submucosal tumors was 46%, which was not significantly different from the sensitivity of high resolution endoscopy in experienced hands.

Shackleford 8e Pg 383.

Answer 103

A

Ans C -

RFA detroys tissue through heat energy applied to the esophageal mucosa. Mucosal ablation is performed under endoscopic guidance, followed by immediate debridement of the ablated area, and the ablation treatment is then immediately repeated in the same area.

The depth of ablation is typically between 500 and 1000 um. This will typically ablate through the epithelium and into the lamina propria layer of esophageal mucosa.
Multiple endoscopic treatments may be required to attain complete eradication of dysplasia. Treatments are usually performed every 2-3 months, after which surveillance is continued.

Shackleford 8e Pg 384.

Answer 104

A

Ans A -

Poor response to RFA is defined as less than 50% regression of BE 3 months after circumferential RFA.
Predictive factors for a poor response included the presence of active reflux esophagitis, regeneration of Barrett at the ER scar, relative esophageal narrowing prior to RFA, and number of years with dysplastic changes before RFA.

Shackleford 8e Pg 384.

Note - persistent chest pain lasting less than 1 week after RFA may be the most common adverse effect after RFA.

Answer 105

A

Ans B =

In patients diagnosed with HGD the main goal of Endoscopic resection is to resect visible lesions within the esophagus. Solitary nodules, areas of nodularity and superficial ulcers are all high risk areas for concurrent, unrecognized carcinoma or progression to invasive disease.

Shackleford 8e Pg 386.

Answer 106

A

Ans B -

Stricture may occur, and this depends on previous pathology in the individual patient and the extent of circumferential resection. Removing more than 50% circumference significantly increases the risk of stricture.

Complete circumferential resections can be performed, but we typically like to stage procedures that will require circumferential resections into several episodes. Single session circumferential resection is associated with high grade stenosis and therefore stenting at the time of resection should be considered.

Shackleford 8e Pg 388.

Answer 107

A

Ans B -

LVI is the most important prognostic determinant of outcome for resected early stage cancer.
In current surgical literature the risk of nodal involvement has been estimated to increase from 2-3% for T1a lesion without LVI to 60% for T1b lesion with LVI. Size of tumor and differentiation are other factors that have been shown to be independent prognostic variables in some studies, in which lesions less than 2cm and well to moderately differentiated tumors are less likely to harbor concurrent lymphadenopathy.

Shackleford 8e Pg 388.

The need for cross sectional imaging is debated in small T1a lesions given the low risk of regional or distant metastasis, and is not at all indicated for patients with dysplasia only.

Patients at higher risk for regional and distant disease such as those with larger lesions, or those patients with LVI should undergo imaging every 4-6 months and consider EUS to screen for regional disease.

Shackleford 8e Pg 388

Answer 108

A

Ans D -

An Ivor Lewis MIE has been compared to the open procedure, 
the patients who underwent MIE had comparatively - 
 - Shorter ICU stay
 - Shorter Hospital stay
 - comparable R0 resection rate
 - Comparable stage specific survival
 - comparable lymph node retrieval
 - decreased blood loss. 
 - decreased pulmonary infections
 - comparable 30 day mortality
 - comparable in-hospital mortality

However the Operative times were significantly longer with the minimally invasive techniques.

Although minimally invasive esophagectomies have been applied to treatment of all stages of esophageal carcinoma, until their oncologic equivalency is established they would seem most applicable in the management of premalignant and early stage disease.

Devita 10e Pg 584.

Answer 109

A

ANs C - Rates of complete pathological response are usually higher in SCC in patients recieving Neoadjuvant CRT.

The majority of esophageal cancer patients will ultimately die of metastatic disease. Even in patients with seemingly localised disease successfully managed operatively, death from metastasis is a common occurence.

Shackleford 8e Pg 391

Taken together the bulk of evidence to date demonstrates improved local control following neoadjuvant CRT compared with surgery alone as evidenced by
- significant clinical and pathological response rate
- significant reduction in LN disease burden within the mediastinum
- improved R0 resection rate.
This benefit was however more pronounced in SCC compared with EAC.

For CRT in EAC the pCR rate hovers around a consistent 20-25% irrespective of the chemotherapy regimen and amount of radiotherapy. However in patients who do respond to neoadjuvant therapy, this improved local control translates into improved survival.

Shackleford 8e Pg 398.

Collectively the data demonstrate that when given in perioperative setting, chemotherapy effectively reduced tumor burden, facilitate curative resection and impart a significant survival benefit in patients with SCC or EAC locally advanced cancers. Chemotherapy provides a benefit in both SCC and EAC. The benefits of chemotherapy with respect to survival did not differ according to histology as per the MRC/OE2 trial. Thus effective chemotherapy may be considered in esophageal cancer patients in addition to surgery, regardless of histology.

Shackleford 8e Pg 394

Answer 110

A

Ans B -

A standard two field lymphadenectomy (abdominal and lower mediastinal) can be readily achieved and for that matter if the surgeon is so inclined a radical enbloc resection can be performed via the transhiatal approach as described by Bumm et al.

Devita 10e Pg 585.

Benefit of CRT in patients with earlier stage disease (Stage I and II) is less clear. Mariette et al - compared NA-CRT in patients with stage I and II esophageal cancer with surgery alone.

R0 resection : comparable
pCR rate : higher in NA-CRT
lymph node positive : lower in NA-CRT
downstaging of tumor : higher in NA-CRT
locoregional control : better in NA-CRT

But,

no difference in distant recurrence and OS
increased in-hospital mortality in NA-CRT group.

Taken together the data demonstrates that an oncologic benefit for NA-CRT in patients with locally advanced esophageal cancer, is not maintained in patients with earlier stage disease.

Shackleford 8e Pg 397,398.

The favorable results of the cross trial were not confirmed in a recently completed French randomized trial comparing nCRT with surgery to surgery alone in stage I and II esophageal cancer patients. No differences in 3 year overall survival and radical resection rates were found. We caution to conclude that patients with early stage esophageal cancer should not undergo nCRT. We beleive that in absence of high quality evidence on the specific effect of nCRT on early stage tumors, the result from CROSS trial (which included stage II cancers) should be leading.

Shackleford 8e Pg 411.

Overall the main drawback of definitive chemoradiation is a prohibitive rate of local failure, even in a seemingly complete responsder it is in the range of 40-60%. Thus the current standard in many centres is to reserve definitive chemoradiation for poor surgical candidates, a strategy that is best suited for SCC histology, given the poorer response rate of adenocarcinoma to radiotherapy.

Shackleford 8e Pg 400.

Taken together the results suggest that in locally advanced SCC, defnitive CRT and CRT with Surgery offer equivalent survival results, with a reduction in treatment-associated morbidity and mortality in the definitive CRT arm. Although local control was improved in patients subject to surgery, subgroup analysis suggests that surgery is rescuing patients who do not demonstrate adequate response to CRT, thus providing local control because of CRT failure. This can be evidenced by the survival rates observed in patients who responded to treatment versus those who did not.

Shackleford 8e Pg 401.

For patients with SCC, neoadjuvant CRT provides excellent results and represents standard therapy. That being said, excellent results with NA-CT alone have been reported and this remains an acceptable standard in appropriate situations where R0 resection is possible.

Shackleford 8e Pg 402.

Answer 111

A

Ans D -

The stomach is considered by most surgeons as the replacement conduit of choice for the resected esophagus. A segment of colon usually based on the ascending branch of the IMA is an effective esophageal subsitute if stomach is deemed unsuitable.

Devita 10e Pg 585.

In the far majority of patients undergoing resection for esophageal cancer, reconstruction is performed using a gastric conduit.

Shackleford 8e Pg 407.

The stomach is mobilised by dividing all vascular attachments while preserving the Rt. GE artery and Rt. Gastric artery on whose pedicle the reconstructive conduit will be based.

The duodenum is fully mobilized by a Kocher Maneuvre.

Pyloric drainage procedure is performed which has been demonstrated in prospective randomized trials to reduce gastric stasis and minimize pulmonary complications such as aspirations.

Devita 10e Pg 585.

Answer 112

A

Ans C -

Advantages attributed to the transhiatal approach include avoidance of a thoracotomy incision which thereby minimizes pain, and subsequent post-operative pulmonary complications, elimination of lethal complications of mediastinitis associated with an intra-thoracic anastomotic leak; and a shorter duration of operation, which results in decreased morbidity and mortality.

Limitations and disadvantages of transhiatal esophagectomy include -
poor visualisation of upper and middle thoracic esophageal tumors, increased anastomotic leak rate with subsequent stricture formation, the possibility of chylothorax, and the possibility of RLN injury.

Devita 10e Pg 585.

THE was associated with shorter operation time, less pulmonary complications, lower postoperative mortality.
On the other hand anastomotic leaks and recurrent nerve palsies occurred more frequently after THE than after TTE.
Lymph node yield was higher after TTE. Two british high volume centers showed similar long term survival benefit after THE and TTE for patients with SCC or EAC, and this advantage in short term recovery after THE over TTE without jeopardizing oncologic outcome was also confirmed in a recent meta-analysis of 52 studies.

Shackleford 8e Pg 410.

Answer 113

A

Ans C-

Pulmonary complications including pneumonia and atelectasis are among the most common complicaitons occuring in 57% of TTE and 27% of THE respectively. These complications can be minimized by early ambulation and careful attention to adequate pain control. Prevention of aspiration can be achieved by keeping the patient constantly in the semi-upright position and by meticulous attention to maintaining a functioning nasogastric tube.

Shackleford 8e Pg 410.

Answer 114

A

Ans B -

The transthoracic esophagectomy is the most common surgical approach and it is also the standard surgical procedure against which all other techniques are measured.

A right thoracotomy combined with an upper midline laparotomy or the Ivor Lewis esophagectomy is the technique most commonly used.

Devita 10e Pg 586.

Answer 115

A

Ans C -

The abdominal portion of the procedure is the same as the THE with mobilisation of the stomach, abdominal lymphadenectomy and pyloromyotomy with placement of feeding jejunostomy.

A muscle sparing right lateral thoracotomy is performed through the fifth or sixth intercostal space.

A peritumoral or two field lymphadenectomy is possible using this approach.

Enbloc resection of middle and distal esophageal tumors is possible.

Devita 10e Pg 585, 586.

Answer 116

A

Ans D -

The transthoracic approach provides direct visualisation and exposure of the intrathoracic esophagus, facilitating a wide dissection to achieve a more adequate radial margin around the primary tumor, more thorough node dissection and more sound cancer operation.

In patients with significant comorbid conditions, the combined effects of an abdominal and thoracic incision may compromise cardiorespiratory function. An intrathoracic anastomotic leak can lead to mediastinitis, sepsis and death. Esophagitis in the non-resected thoracic esophagus may occur secondary to bile reflux.

Devita 10e Pg 586.

Rindani et al -

perioperative mortality higher in TTE
THE had higher rates of anastomotic leak, stricture and RLN injury
5yr survival was similar

Hulscher et al - review of studies

postoperative mortality higher in TTE
pulmonary complications higher in TTE
5 yr survival not different

Metanalysis upto 2010

inhospital and 30 day mortality higher in TTE
pulmonary complications higher in TTE
length of stay higher in TTE
anastomotic leak, stricture and RLN palsy higher in THE
no difference in 5 yr survival

Hulscher et al - phase III trial

number of LN retrieved higher in TTE
pulmonary complications, ICU stay and hospital stay longer in TTE
no survival advantage at 5 years.

Devita 10e Pg 587.

Answer 117

A

Ans C -

Two concepts guide extended esophagectomy

En-bloc resection
Systematic LN dissection either two field or three field.

Most of the techniques described encompass both these components.

An enbloc esophagectomy involves -

resection of middle and lower esophageal tumors
mediastinal pleura laterally
pericardium anteriorly
azygous vein and thoracic duct posteriorly

along with the surrounding peri-esophageal tissue and lymph nodes. For tumors traversing the hiatus, a cuff of diaphragm is also resected.

In addition a thorough mediasitnal LN dissection extending from tracheal bifurcation to the esophageal hiatus, and an upper abdominal LN dissection incorporating LN along portal vein, CHA, Celiac Trunk, LGA, Splenic Artery (As included in the two field lymphadenectomy)

Devita 10e Pg 587.

Answer 118

A

ANS B -

A Three field lymphadenectomy extends the lymphadenectomy to superior mediastinum, including nodes along the course of the right and left recurrent laryngeal nerves, and through a separate collar incision in the neck the removal of the lower cervical nodes including the deep external and lateral cervical nodes.

Devita 10e Pg 587.

Answer 119

A

Ans B -

Hagen et al - 100 patients - enbloc esophagectomy with 2 field Lymphadenectomy.

perioperative mortality 6%
Pneumonia (19%)
Subphrenic abscess (13%)
respiratory failure (9%)
anastomotic leak (10%)
5 year survival 52% overall, for stage III 25%.

Altorki et al - 128 patients - 61% received enbloc esophagectomy.

in-hospital mortality 5.1%
Respiratory events (24%)
anastomotic leak (12.8%)
4 year survival 41.5% for enbloc
4 year survival for Stage III 34.5%.

Devita 10e Pg 588.

Answer 120

A

Ans C -

The body of evidence confirms that extended resections improve staging and may enhance local-regional control, however there is no reliable data confirming a survival benefit for these procedures.

Devita 10e Pg 588.

Extended enbloc TTE with extensive 2 field lymphadenectomy attempts to increase the local regional control by increasing the radicality of resection. It is established that extensive lymphadenectomy provides the benefit of more accurate staging, but its beneficial effect on survival is still unclear.

Shackleford 8e Pg 405.

Placement of appropriate retractors through the widened esophageal hiatus allows for the enbloc dissection of all fatty tissue and lymph nodes surrounding the lower thoracic esophagus under visual control as far as possible. Under normal circumstances, this can be done upto the level of inferior pulmonary veins.

Shackleford 8e Pg 407.

Answer 121

A

Ans C -

Advanced age alone should not be considered a contraindication for esophagectomy. The increased mortality risk in >70 years of age is due to medical comorbidities.
When operative mortality is excluded, long term survival after resection in elderly is similar to younger population.

Strong association with smoking and alcohol in esophageal cancer (Esp. SCC) means that all patient should be carefully screened for cardiovascular, pulmonary and hepatic dysfunction regardless of their age.

20-30% patients with esophageal cancer will have evidence of cardiovascular disease if carefully screened. This evaluation should atleast consist of ECG for all patients.

FEV1 <1L are at increased risk of respiratory complications.

Child Pugh A alone is not a contraindication.

Patients who are planned for NA-CRT or NA-CT should be screened for renal insufficiency.

Shackleford 8e Pg 405.

Answer 122

A

Ans B -

Once the tumor has penetrated the submucosal layer or T1b - upto one half of patients have nodal metastases.

More than 80% of patients with invasion of the muscularis propria (T2) will have atleast one involved lymph node.

In the presence of transmural invasion (T3) nodal involvement will be present in >85%.

Shackleford 8e Pg 407.

Answer 123

A

Ans C -

When a cervical anastomosis is performed, the procedure starts with a thoracotomy followed by the abdominal part.

Whereas in case of a thoracic anastomosis the laparotomy is performed prior to the thoracic phase.

Thoracic dissection includes the removal of azygous vein (with associated nodes), thoracic duct, paratracheal nodes, subcarinal nodes, paraesophageal and parahiatal nodes in continuity with the resected esophagus.

Nodes in the aortopulmonary window are removed separately.

The pleura cranial to the azygous arch is saved to create a pedicled flap to cover the subsequent anastomosis.

The pericardium should only be removed when the tumor is adherent.

Shackleford 8e Pg 406.

Answer 124

A

Ans A -

In case of intrathoracic anastomosis the esophagus is divided above the level of the azygous arch.

Shackleford 8e Pg 407.

Answer 125

A

Ans C -

The major disadvantage of using the stomach include the almost complete lack of peristaltic activity and the tendency for persistent reflux into the remaining cervical esophagus and in long term survivors this can result in the development of intestinal metaplasia (Barrett) in the cervical remnant.
The need to preserve length may also result in more limited margins especially for large or very distal tumors.

Shackleford 8e Pg 408.

Answer 126

A

False -

Despite the increased rate of recurrent laryngeal nerve damage, leakage or possible stricture formation some surgeons prefer the cervical anastomosis during TTE, because of a longer proximal tumor free margin and a THEORETICALLY reduced morbidity in case of anastomotic leak. The latter is founded on the assumption that leakage of a cervical anastomosis is more likely to be confined to the neck instead of leaking into the pleural cavity or mediastinum.

However a meta-analysis on this topic did not show differences in pulmonary complications and tumor recurrence which suggests that a cervical anastomosis after TTE does not decrease the risk of thoracic complications compared with an intrathoracic anastomosis.

Risk of intrathoracic manifestations due to leakage of a cervical anastomosis is significantly less in patients after THE than in patients who underwent TTE. This is probably explained by the difference in mediastinal dissection and pleural resection. After THE, the bilaterally intact parietal pleura may confine infections which prevents extension into the pleural cavity and mediastinum.

Shackleford 8e Pg 408.

NOTE - studies comparing the cervical with intra-thoracic anastomosis in the neoadjuvant era are lacking.

Answer 127

A

Ans B -

The esophagus is divided at the level of thoracic inlet and the specimen is removed via the abdomen after tying the tape to the esophagus. The cervical remnant should not be too long, thus preventing that the anastomosis will ultimately retract into the upper chest with a possibly increased risk of intrathoracic manifestation in case of leakage.

Shackleford 8e Pg 408.

Answer 128

A

Ans B -

Frequently the left colon is used in an isoperistaltic fashion. The ascending and descending colon are mobilised completely. The left segment of the colon to interposed derives its arterial supply from the ascending branch of the left colic artery and this usually corresponds to the segment extending from the mid-transverse colon to the proximal descending colon. This segment is mobilized by dissecting the middle colic artery back to its origin from the SMA where it arises as a single trunk in most patients. The MCA and MCV are then temporarily occluded to ensure adequate collateral flow through the marginal artery.

Left colon can be used in an anti-peristaltic position which is based on vascular pedicle of the middle colic artery and vein. In this way the interposed segment can be longer by making use not only of the descending colon but also some part of the sigmoid colon.

Right colon can be used including the ileocecal valve in an isoperistaltic position and again based on the middle colic vessels. The advantage of this technique is that the ileocecal valve acts as an antireflux mechanism at the proximal anastomosis.

Shackleford 8e Pg 409.

Answer 129

A

Ans B - the first successful esophagectomy was performed by Franz Torek in 1913.

Sabiston 20E Pg 1036.

Answer 130

A

Ans C -

Radiotherapy was the first treatment modality used in treatment of esophageal cancer.

Shackleford 8e Pg 1036.

Answer 131

A

Ans B -

Unless the tumor extends into the stomach, reconstruction is performed with a greater curvature gastric tube.

Schwartz 10e Pg 1011.

Through a midline incision the stomach is mobilized by dividing all vascular attachments while preserving the right gastroepiploic and right gastric vessels on whose pedicle the reconstructive conduit will be based.

Devita 10e 587.

Short gastric vessels should be divided as close as possible to the spleen to preserve as many collateral vessels to the fundus as possible.

Shackleford 8e Pg 407.

Answer 132

A

Ans A -

Cardiac complications are seen in 26% TTE and 16% THE patients, with the development of atrial fibrillation accounting for majority of these complications.

The shift of body fluids and the extensive mediastinal dissection that causes a systemic inflammatory response likely play a role in the pathogenesis. Although these are generally self limiting, they do require cardiac monitoring and treatment, which can prolong the ICU stay.
Atrial fibrillation can also be caused by anastomotic dehiscence with secondary mediastinitis or by mechanical irritation by a chest tube.

Shackleford 8e Pg 410.

Answer 133

A

Ans D -

Long term survival following esophagectomy depends on the following

Age
Gender
Histologic type
depth of tumor invasion or T3
Radicality of resection
Number of involved lymph nodes

A high total number of lymph nodes resected is an independent prognostic factor of survival after primary surgery.
The optimal threshold for survival benefit was removal of 23 nodes and the operation most likely to achieve this was found to be an enbloc transthoracic resection.

Shackleford 8e Pg 410.

Answer 134

A

Comment -

The results of all the meta-analysis that have been done in this regard suffer from two main disadvantages -

patients that underwent THE were more likely to be frail.
whereas patients with more advanced tumors were likely to be treated transthoracically.

This produced a selection bias.
Proponents of the THE approach explain differences in survival by stage that have been consistently reported as being due to stage migration, this occurs when positive nodes in the extended part of dissection increase pN stage in patients with more favorable prognosis as compared with patients with the same number of nodes after a limited dissection during THE.

Altorki et al.
reported outcome in only T3N1-3 patients and they showed that enbloc dissection was associated with 35% survival at 4 years whereas THE was associated with 11% survival at 4 years.

Hulscher et al -
On ventilator time, pulmonary complications and hospital stay were shorter for THE.
But in hospital mortality were comparable between THE and TTE.
More extended TTE was associated with a higher percentage of tumor free resection margins, whereas median number of lymph nodes removed was 2x higher after TTE than after THE. This high lymph node yield however did not result in a significantly better survival.

However in a subgroup analysis of patients with Siewert I tumors and lymph nodes 1-8 positive, an improved long term survival was found in TTE.
The effect of stage migration on improved survival after TTE cannot be excluded. Also the results were unclear for SCC.

TTE is the preferred technique in Siewert type I
THE is adequate in siewert type II and in patients with poor performance status without clinically suspected nodes at or above the level of carina.

Shackleford 8e Pg 410, 411.

In the patients after primary surgery from the CROSS trial, the total number of resected nodes and the number of resected positive nodes were positively correlated. However this positive association completely disappeared in patients who underwent nCRT.
Also, after surgery alone the total number of nodes removed correlated positively with OS. This positive correlation was also absent after nCRT.
These results question the necessity of maximizing surgical lymph node dissection after nCRT, both for prognostication and therapeutic purposes.

Shackleford 8e Pg 412.

Answer 135

A

Ans A

As a time honored operation there is no doubt that enbloc Ivor Lewis esophagectomy is the standard to which less radical techniques must be compared.

Schwartz 10e Pg 1011.

Answer 136

A

Ans C -

SANO refers to surgery as needed in esophageal cancer patients approach. This approach explores the feasibility of active surveillance strategy in patients with a clinically complete response (cCR) after nCRT. Surgical resection would only be offered to patients in whom residual disease is highly suspected or proven after nCRT.

Shackleford 8e Pg 411.

Answer 137

A

ans D -

Improved surgical and oncologic outcomes are usually achieved after 35-40 cases. A recent British general consensun reported that the appropriate learning curve to perform MIE is estimated to include between 20 and 50 cases.

Shackleford 8e Pg 415.

Answer 138

A

Ans C -

MIE minimizes post operative pain, allows for a faster recovery, decreases the risk of wound infection, cardiopulmonary complications, blood loss and length of hospital stay.
Pulmonary complication rate - pneumonia and ARDS - decreases with MIE due to smaller incision, avoiding rib spreading, minimized retraction of right lung. Occasionally single lung ventilation can also be avoided by using a prone position.

In a recent metanalysis MIE was associated with significantly longer operative times but significantly shorter hospital stay, mortality and overall morbidity.

Most of the morbidity advantage with MIE was attributable to pulmonary and cardiovascular complications which were significantly lower for MIE, whereas gastrointestinal complications, anastomotic leaks and recurrent laryngeal nerve injury were similar in both groups.

Shackleford 8e Pg 419.

In some cases a higher lymph node harvest has been reported with MIE and this might be explained by a magnified visualization using the laparoscopic and thoracoscopic camera.

The adequacy of resected margins is still a controversial topics with no definitive results.

Most of the studies showed that there is no difference in the ability to achieve R0 resections and similar survival outcomes.

MIE is feasible and safe, and although technically challenging it can offer reduced mortality, faster recovery, improved short term quality of life yet with similar oncologic results to the open approach.

Shackleford 8e Pg 419.

Answer 139

A

Ans D -

Vagal preservation minimizes dumping, diarrhea and depending on the type of reconstruction early satiety and reflux symptoms.

The technique for a vagal sparing esophagectomy with gastric pull up allows preservation of the left gastric artery and branches to the pylorus and this improves the perfusion of the proximal portion of the graft and may reduce anastomotic leaks and stenosis.

Shackleford 8e Pg 421.

Vagal sparing procedure is only applicable to patients with intramucosal tumors, and no evidence of lymphadenopathy since preserving the vagus precludes the ability to perform an adequate lymphadenectomy along the left gastric artery and in the peri-esophageal mediastinal tissues.

shackleford 8e Pg 421

Answer 140

A

Ans D -

A vagal sparing procedure should be considered in any patient with a benign process such as end stage achalasia cardia or GERD, in patients with high grade dysplasia in squamous mucosa or BE and in patients with esophageal cancer limited to the mucosa.

Importantly vagal sparing procedure is only applicable to patients with a intramucosal tumor and no evidence of lymphadenopathy since preserving the vagus precludes the ability to perform an adequate lymphadenectomy along the left gastric artery and in the peri-esophageal mediastinal tissues.

Submucosal tumors have a significant risk of lymph node metastases and tumor invasion into this layer is a contraindication.

Shackleford 8e Pg 421.

Vagal sparing approach may be specifically considered in intramucosal esophageal carcinoma with advanced complicated reflux disease - since the severe alterations of esophageal function make preservation of the esophagus by EMR a less attractive option in these patients - due to the severe foreshortening and refractory esophageal strictures.

Answer 141

A

Ans B -

Vagal sparing procedure is only applicable to patients with intramucosal tumors and no evidence of lymphadenopathy since preserving the vagus nerves precludes the ability to perform an adequate lymphadenectomy along the left gastric artery and in the periesophageal mediastinal tissues.
Therefore a biopsy showing cancer in an area of nodularity or ulceration requires initial endoscopic resection to confirm the tumor is confined to the mucosa. Submucosal tumors have a significant risk for lymph node metastases and tumor invasion in this layer is a contraindication for vagal sparing approach.

Relative contraindications to a vagal sparing esophagectomy include the presence of

an esophageal stricture
history of caustic injury to the esophagus
prior antireflux or esophageal surgery.

Since in these circumstances mediastinal scarring may prohibit safe stripping of the esophagus or may lead to vagal disruption even if the stripping is accomplished safely.

Diabetes or evidence of impaired gastric empyting should be considered a relative contraindication for a vagal sparing procedure using a colon interposition to the intact stomach.

Prior gastric surgery such as a pyloroplasty may preclude an advantage to preserving the vagal nerves, although even in this setting avoidance of post-vagotomy diarrhea may be a sufficient reason to spare the vagus nerves if possible.

Shackleford 8e Pg 421.

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