This document provides information about esophageal cancer, including: - Key symptoms include dysphagia and weight loss. Squamous cell carcinoma and adenocarcinoma are the main types. - Risk factors include smoking, alcohol, obesity, and Barrett's esophagus. Cancer spreads locally through direct invasion and lymphatically. - Staging involves endoscopy, CT, PET, and EUS. Treatment depends on staging and includes surgery, chemotherapy, radiation, or palliative care. Prognosis depends on stage, with a 5-year survival rate of 19% on average.

1. Esophageal cancer
Data collected by : Ruwida M.S.Ashour

2. It would be so delicious just
for those who can taste and
swallow it !

3. By the end of this session , I hope you can
remember the following key points ...
What’re the symptoms and signs of esophageal
cancer ?
What’s the main pathologic type of esophageal
cancer?
How can we design the treatment according the
staging of esophageal cancer?

4. Clinical Anatomy
• Hollow muscular tube 25 cm in length
• spans from the cricopharyngeus at the
cricoid cartilage to gastroesophageal
junction (Extends from C7-T10).
• Has 4 constrictions-
• At starting(cricophyrangeal junction)
• crossed by aortic arch(9’inch)
• crossed by left bronchus(11’inch)
• Pierces the diaphragm(15’inch)
• Histologically 4 layers:
mucosa, submucosa, muscular &
fibrous layer.

5. Four regions of the
esophagus:
• Cervical = cricoid cartilage to
thoracic inlet (15–18 cm from
the incisor).
• Upper thoracic = thoracic inlet
to tracheal bifurcation (18–24
cm).
• Mid-thoracic = tracheal
bifurcation to just above the GE
junction (24–32 cm).
• Lower thoracic = GE junction
(32–40 cm).

6. Lymphatic Drainage
• The submucosal plexus
drains into the regional lymph nodes
in the cervical, mediastinal ,
paraesophageal, left gastric, and
celiac axis regions

7. Epidemiology
• Esophageal cancer is the 7th
leading cause of cancer
deaths.
• In some regions, such as
areas of northern Iran,
southern Russia, and
northern China, the
incidence reaches 800 per
100,000 population.
• The incidence rises steadily
with age, reaching a peak in
the 6th to 7th decade of life.
• Male : Female = 3.5 : 1

8. • Worldwide SCC responsible for
most of the cases , usually
occurs in the middle 3rd of the
esophagus
• Adenocarcinoma now accounts
for over 50% of esophageal
cancer in the USA, due to
association with GERD ,
Barretts’s esophagus & obesity ,
Which is most common in the
lower 3rd of the esophagus,
accounting for over 65% of
cases.
• (the ratio of upper : middle :
lower is 15 : 50 : 35).

9. Can it be a place of secondary's ?
• Secondary esophageal carcinoma occurs in about 3%
of patients dying with carcinoma
• Esophageal invasion by secondary carcinoma produces
obstruction mimics a benign stricture or primary
esophageal carcinoma.
• Fifteen cases of secondary esophageal tumor were
found. The primary site was lung in seven, breast in
four, and one each in the kidney (hypernephroma),
pancreas, cervix (squamous cell), and bladder
(transitional cell).
Autopsy and surgical pathology files at Stanford University Hospital were reviewed for cases of
secondary esophageal tumor occurring during a 6 year period.

10. Risk Factors : Squamous Cell Carcinoma
• Smoking and alcohol (80% - 90%)
• Dietary factors
• N-nitroso compounds (animal carcinogens)
• Pickled vegetables and other food-products
• Toxin-producing fungi
• Betel nut chewing
• Ingestion of very hot foods and beverages (such as tea)
• Underlying esophageal disease (such as achalasia and caustic
strictures, Tylosis)
• Genetic abnormalities:
• p53 mutation, loss of 3p and 9q alleli, amp. Cyclin D1 & amp. EGFR

11. Risk Factors: Adenocarcinoma
• Associated with Barretts’s esophagus, GERD &
hiatal hernia.
• Obesity (3 to 4 fold risk)
• Smoking (2 to 3 fold risk)
• Increased esophageal acid exposure such as
Zollinger-Ellison syndrome.
Barrett’s esophagus is a
metaplasia of the esophageal epithelial lining. The
squamous epithelium is replaced by columnar
epithelium,with 0.5% annual rate of neoplastic
transformation.

12. CAN HUMAN PAPILLOMA VIRUS BE
THE CAUSE ?
• HPV associated with the previously mentioned
risk factors tripled the esophageal cancer risk .
• Vaccine-preventable HPV-16 and HPV-18 are
the most commonly identified HPV types.

13. Pathophysiology

15. Pattern of spread
• No serosal covering, direct invasion of contiguous structures occurs early.
• Commonly spread by lymphatics (70%)
• Lymph node involvement increases with T stage.
• T1 – 14 to 21%
• T2 – 38 to 60%
• 25% - 30% hematogenous metastases at time of presentation.
• Most common site of metastases are
• lung, liver, pleura, bone, kidney & adrenal gland
• Median survival with distant metastases – 6 to 12 months

16. Clinical Features
• Dysphagia, the most common presenting
symptom of esophageal cancer, is initially
experienced for solids but eventually progresses to
include liquids.
• Weight loss - This is the second most common
symptom,occurs in more than 50% of dx cases.
• Bleeding - Patients may experience bleeding from
the tumor
• Pain - Pain may be felt in the epigastric or
retrosternal area; pain over bony structures
indicates metastatic disease
• Hoarseness - This is caused by invasion of the
recurrent laryngeal nerve
• Respiratory symptoms - These can be caused by
aspiration of undigested food or by direct invasion
of the tracheobronchial tree by the tumor; the
latter is also a sign of unresectability

17. Approach
consideration
Early disease
CT & PET Are optional
Locoregionalized
PET & CT Rcomended
without metastatic disease
endoscopic ultrasonography
recommended to improve the
accuracy of staging
small, discrete nodules or areas
of limited dysplasia
endoscopic ultrasonography,
endoscopic mucosal resection
should be considered as a
diagnostic/staging tool
locally advanced (T3/T4)
adenocarcinoma
laparoscopy is
recommended
flexible endoscopy
The primary diagnostic
method

18. 18
Pathology diagnosis - Upper endoscopy

19. Early, superficial
cancer
Circumferential ulceration
esophageal cancer
Malignant stricture
of esophagus

20. Barium swallow:
is very sensitive for detecting strictures and intraluminal masses, but does not allow
staging and biopsy.
it may be helpful for studying the distal anatomy in obstructive tumors that are inaccessible
by endoscopy.
Barium swallow demonstrating an
endoluminal mass in the mid
esophagus
Barium swallow demonstrating
stricture

21. •Staging:
• CT chest and abdomen: Essential for staging because it can identify extension beyond
the esophageal wall, enlarged lymph nodes and visceral metastases.
Figure Esophageal cancer with tracheal invasion. CT scan shows circumferential wall
thickening of the proximal esophagus (arrowheads), which shows irregular interface with
the posterior wall of the trachea (arrows), indicating direct extension into the lumen

22. Endoscopic Ultrasonography
• Endoscopic ultrasonography (EUS) is the most sensitive test
for determining the depth of tumor penetration (T staging)
and the presence of enlarged periesophageal lymph nodes
(N staging)
• Resolution of EUS permits the distinction of T1, T2, T3,
and T4 tumors. Esophageal carcinoma appears as a
hypoechoic lesion disrupting the normal
circumferential layers.
• At this time, only EUS is useful in distinguishing T1 and T2 lesions.

24. PET Scan
• most recently, proven to be valuable staging tool
• can detect up to 15–20% of metastases not seen on CT and EUS
• low accuracy in detecting local nodal disease compared to CT / EUS
• addition of PET to CT can improve specificity and accuracy of non-
invasive staging
Figure Distant lymph node metastases of esophageal cancer detected by integrated CT PET. A, Integrated CT
PET demonstrates para-aortic lymph node metastases showing increased FDG uptake (arrowheads). B,
Corresponding CT image shows lymph nodes (arrowheads) measuring 5 to 8 mm in diameter. Based on size
criteria, these lymph nodes may be considered benign on CT scan

25. Imaging and prognosis
• Recent studies found that a higher initial standardized uptake
value (PET) scanning is associated with poorer overall survival
among patients with esophageal or gastroesophageal
carcinoma receiving chemoradiation.

26. 26
Other regular tests
TNM stage

27. T stage (Tumor)
Tis
T1
T2
T3
T4
Mucosa

28. Staging
z a: Includes nodes
previously labeled as
“M1a”
z b : “M1a” designation is no
longer recognized in the
7th edn. of the AJCC
system

29. Staging : Squamous cell carcinoma

30. Staging : Adenocarcinoma
Group T N M Grade
0 Tis (HGD)
N0
M0
1, X
IA T1 1-2, X
IB T1 3
T2 1-2, X
IIA T2 3
IIB T3
Any
T1-2 N1
IIIA T1-2 N2
T3 N1
T4a N0
IIIB T3 N2
IIIC T4a N1-2
T4b Any
Any N3
IV Any Any M1

31. Prognosis
• Survival in patients with
esophageal cancer
depends on the stage of
the disease. Squamous
cell carcinoma and
adenocarcinoma, stage-
by-stage, appear to have
equivalent survival rates.
• In 2001-2007, the
overall 5-year survival
rate for esophageal
cancer was 19%

32. KIAA0101
• KIAA0101 is emerging as a meaningful marker for poor
prognosis in EC, such as early recurrence and short
survival.
• study shows that KIAA0101 upregulates cell mitosis via
an increase in cyclins A and B, resulting in enhanced cell
resistance to cisplatin. These data may provide
mechanistic evidence for the reduced chemosensitivity to
cisplatin-based therapy seen in EC.

33.  How to design the treatment
plan ?
Staging ,whether the cancer has invaded nearby
structures , whether the cancer has spread to lymph
nodes or other organs
where the cancer is located within the esophagus
The general health of patient

34. Regimen
• Endoscopic Mucosal Resection(EMR)
• Surgery
• Chemotherapy
• Radiotherapy
• Combined-modality therapy
• Palliative Therapy

35. Endoscopic Mucosal
Resection(EMR)
• Indication of EMR
Tis or T1a (defined as tumor involving the mucusa but not
involving submucosa)
---------------------------------------------------------------------------------
A population-based study of 1618 patients with grade Tis, T1a, or
T1b esophageal cancer found that overall survival times and
esophageal-cancer-specific survival times with endoscopic
therapy were similar to those with surgery, after adjustment for
patient and tumor factors

36. Endoscopic Therapy for Localized
Disease
o endoscopic therapy is a safe, less invasive, and effective therapy for very early
esophageal cancer.
o The candidates are Stage 1 patients with tumors invading into the lamina
propria (T1 mucosal) or submucosa (T1 submucosal) that do not have regional
or distant metastasis. Patients with carcinoma in-situ or high-grade dysplasia
can also be treated with endoscopic therapy.
o The two forms of endoscopic therapy that have been used for Stage 0 and I
disease are endoscopic mucosal resection (EMR) and mucosal ablation using
photodynamic therapy , Nd-YAG laser, or argon plasma coagulation.
o The prognosis after treatment with endoscopic mucosal resection is comparable
to surgical resection

37. The strip biopsy of EMR
• After marking the lesion border
with an electric coagulator, saline
is injected into the submucosa
below the lesion to separate the
lesion from the muscle layer and
to force its protrusion
• The grasping forceps are passed
through the snare loop. The
mucosa surrounding the lesion is
grasped, lifted, and strangulated
and resected by electrocautery

38. • The endoscopic double-snare polypectomy indicated for
protruding lesions. Using a double-channel scope, the lesion is grasped
and lifted by the first snare and strangulated with the second snare for
complete resection.
• Endoscopic resection with injection of concentrated saline and
epinephrine is carried out using a double-channel scope. The lesion
borders are marked with a coagulator. Highly concentrated saline and
epinephrine are injected (15–20 ml) into the submucosal layer to swell
the area containing the lesion and elucidate the markings. The mucosa
outside the demarcated border is excised using a high-frequency scalpel
to the depth of the submucosal layer. The resected mucosa is lifted and
grasped with forceps, trapping and strangulating the lesion with a snare,
and then resected by electrocautery.

39. • the use of a clear cap and
prelooped snare inside the cap.
After insertion, the cap is placed on the
lesion and the mucosa containing the
lesion is drawn up inside the cap by
aspiration. The mucosa is caught by the
snare and strangulated, and finally
resected by electrocautery. This is
called the "band and snare" or "suck
and cut" technique.
• The resulting "ulcer" heals within 3
weeks

40. • The major complications of endoscopic mucosal resection include
postoperative bleeding and perforation and stricture
formation.
• It is important to administer acid-reducing medications to prevent
postoperative hemorrhage.
• Perforation may be prevented with sufficient saline injection to raise the
mucosa containing the lesion. The "non-lifting sign" and complaints of
pain when the snare strangulates the lesion are contrainidications of
EMR.
• When perforation is recognized immediately after a procedure, the
perforation should be closed by clips. Surgery should be considered in
cases of endoscopic closure failure. The incidence of complication range
from 0–50% and squamous cell recurrence rates range from 0–8%.

41. Photodynamic Therapy
• It involves application of
photosensitizer drug which has a
preferential localization in high
concentration in the dysplastic and
malignant tissue.
• In the presence of oxygen, laser
light at a specific wavelength
activates the drug and results in a
photochemical reaction that leads
to selective tissue destruction.
• Some patients have experienced
dysrhythmias as well as nausea
,photosensitivity and stricture
formation (which, in most cases,
have responded to endoscopic
dilation).

42. Radiotherapy for
CA esophagus

43. Chemoradiotherapy
• While the radiotherapy acts locally at the tumor site, the chemotherapy acts on tumor cells that
have already spread. This combination therapy is usually administered over a 45-day period;
esophageal resection is performed after an interval of approximately 4 weeks.
• Chemotherapy and radiotherapy for esophageal cancer are delivered preoperatively , to reduce
the bulk of the primary tumor before surgery to facilitate higher curative resection rates and to
eliminate or delay the appearance of distant metastases.
• No survival benefit is obtained when radiation and chemotherapy are administered
postoperatively
• British investigators found that preoperative chemotherapy with cisplatin and fluorouracil
resulted in a 5-year survival rate of 23.0%, compared with 17.1% for surgery alone.
• Definitive chemoradiotherapy using fluorouracil plus leucovorin and oxaliplatin (FOLFOX) is an
easier, less toxic, and cheaper option than chemoradiotherapy with fluorouracil and cisplatin, the
researchers note
• ----------------------------------------------------------------------------------------
• Median overall survival with chemoradiation therapy followed by surgery was 49.4 months,
compared with 24.0 months with surgery alone.
• Overall recurrence rates were 35% for CRT plus surgery and 58% for surgery alone.

44. Surgery

45. • Prerequisite for surgery
• disease should be 5 cm beyond cricophyrangeus.
• Surgery indications
• Lower 1/3 rd oesophageal ds involving GE junction.
• Tumor size <5 cm .
• palliative surgery
• (no significant difference between surgical techniques
according to results of 2 meta-analyses)

46. Contraindications of operation
• Metastasis to N2 nodes or solid organs
• Invasion of adjacent structures (eg, the recurrent laryngeal nerve,
tracheobronchial tree, aorta, pericardium)
In addition, the presence of severe, associated comorbid conditions (eg,
cardiovascular disease, respiratory disease) can decrease a patient's
chances of surviving an esophageal resection.
46

47. Types of Surgery
• Transhiatal esophagectomy: for tumors anywhere in esophagus or gastric
cardia. No thoracotomy. Blunt dissection of the thoracic esophagus. Left with
cervical anastomosis. Limitations are lack of exposure of midesophagus and
direct visualization and dissection of the subcarinal LN cannot be performed.
• Right thoracotomy (Ivor-Lewis procedure): good for exposure of mid to
upper esophageal lesions. Left with thoracic or cervical anastomosis.
• Left thoracotomy: appropriate for lower third of esophagus and gastric cardia.
Left with low-to-midthoracic anastomosis.
• Radical (en block) resection: for tumor anywhere in esophagus or gastric
cardia. Left with cervical or thoracic anastomosis. Benefit is more extensive
lymphadenectomy and potentially better survival, but increased operative risk.

48. Transhiatal esophagectomy
• Transhiatal esophagectomy is most frequently
performed and recommended for early esophageal
cancers of the middle (below the level of carina) and
lower third of esophagus (type I and II tumors of
esophagogastric junction).
• However, transhiatal esophageal resection may be
feasible in upper esophageal carcinomas in some cases.
• Transhiatal esophageal resection is also performed for
advanced esophageal cancers in patients who are not
fit to undergo a thoracotomy.

49. Transhiatal esophagectomy
Incisions and mobilization of the
stomach. Mobilization of Stomach

50. Widening of hiatus Cervical Incision

51. Exposure of Cervical
esophagus.
Mobilization of
Cervicothoracic esophagus.

52. Esophageal mobilization on
anterior aspect.
Esophageal mobilization on
posterior aspect.

53. Transection of Cervical
Esophagus Creation of Stomach tube.

54. Stomach tube
Stomach tube pushed through
hiatus towards the neck.

55. Esophagogastric Anastomosis
with a Linear Cutting Stapler.
Completion of the
esophagogastric anastomosis.

56. Postoperative Care and Follow-up
• feeding through the feeding jejunostomy begins on postoperative day1.
• On postoperative day 6, a swallow study is performed to check for
anastomotic leakage. If no leak is present, patients start oral feedings. If a
leak is present, the drainage tubes are left in place and nutrition is
provided entirely through the feeding jejunostomy until the leak closes
spontaneously.
• Patients are seen by the responsible surgeon at 2 weeks and 4 weeks
after discharge from the hospital and subsequently every 6 months by an
oncologist. Most patients return to their regular level of activities within 2
months.

57. Complications
Respiratory complications
Atelectasis, in 3% of cases, ,may progress to pneumonia in
some cases which may prolong patient’s stay in ICU.
Pleural effusion
Postoperative hemorrhage may be mediastinal or
intraperitoneal. Source of bleeding include a tear in the
azygos vein, large prevertebral collateral veins, or spleen.
Chylothorax (1%) is a rare complication and is managed
conservatively

58. Recurrent laryngeal nerve injury
The recurrent laryngeal nerve innervates the upper
esophageal sphincter
Injuries occur in 1%-3% of cases. It causes vocal
cord paresis and dysphagia ,aspiration,
Placement of a metal retractor alongside the
tracheoesophageal groove during the cervical
dissection of esophagus should also be avoided. The
surgeon should handle the trachea, thyroid, and
cervical esophagus with fingers, when possible
Hoarseness due to recurrent laryngeal nerve injury
may resolve spontaneously, but cord medialization
procedures may be required for persistent vocal cord
paresis.

59. Cervical esophagogastric anastomotic leak
may lead to stricture formation.
Use of a side-to-side stapled cervical esophagogastric anastomosis has reduced the
incidence of anastomotic leak.
• Mangement
by opening the neck wound at the bedside and local wound packing until healing by
secondary intent occurs.
 Patient may be put on jejunal feeds until the anastomotic leak is controlled.
 For fistula due to anastomotic leak, early bedside esophageal anastomotic dilatation
(with 36F, 40F, and 46F dilators) within 1 week is very helpful and results in early
closure of the fistula by allowing preferential flow of swallowed esophageal contents
down the true lumen rather than through the leak.
 Stent placement can also facilitate fistula closure and is perhaps the preferred
avenue when an anastomotic leak is encountered.

60. • Gastroesophageal reflux
• Performing an anastomosis about 3-5 cm below the highest
point on the anterior wall of the stomach in the neck and
creating an acute angle of entry of the esophagus into the
stomach leaves some retroesophageal stomach to distend with
air and may provide some type of antireflux mechanism
• A pyloroplasty or pyloromyotomy ensures adequate gastric
emptying and is performed routinely in some centers,avoiding
the pyloromyotomy protects from the occurrence of severe
complications, such as dumping syndrome, diarrhea, or leakage
from the myotomy

61. •Delayed gastric emptying
• is rare if pyloromyotomy is performed,; most of these patients can be managed
with prokinetic agents. However, endoscopic balloon dilatation of the pylorus is
occasionally required.
• early removal of the drain from the cervical wound may result in formation of
cervical abscess. A closed suction drain should be left for a sufficient period, and
oral feeding should be delayed if an anastomotic leak is suspected.]Cervical
abscess should be promptly treated, as it may lead to tracheogastric fistula.

62. Palliative care
• In patients who are not candidates for surgery, treatment focuses
on control of dysphagia.
• The most appropriate method is determined for each patient
individually, depending on tumor characteristics, patient
preference, and the specific expertise of the physician.
• The following treatment modalities are available to help achieve
this goal:
• Chemotherapy
• Radiotherapy
• Laser therapy
• Stents[68]

63. • CHEMOTHERPAY
• Studies found that no consistent benefit with any specific chemotherapy
regimen,Cisplatin, 5-fluorouracil (5-FU), paclitaxel, and anthracyclines
had promising response rates and tolerable toxicity.
• Radiotherapy
• Radiation therapy is successful in relieving dysphagia in approximately
50% of patients
• In a study, Folkert et al found that high-dose-rate (HDR) endoluminal
brachytherapy was well tolerated in medically inoperable patients with
superficial primary or recurrent esophageal cancer.

64. Laser therapy
• Laser therapy (Nd:YAG laser) can help to achieve temporary relief
of dysphagia in as many as 70% of patients.
• The photosensitizer porfimer (Photofrin) is FDA approved for
palliation of patients with completely obstructing esophageal
cancer or partially obstructing cancer that cannot be satisfactorily
treated with Nd:YAG laser therapy.

65. Stents
• Patients may be intubated
with expandable metallic
stents, which can be
deployed by endoscopy
under fluoroscopic guidance
and can keep the esophageal
lumen patent.
• Stents are particularly useful
for patients with a
tracheoesophageal fistula.

66. Figure: A proposed treatment
algorithm for esophageal cancer.

67. Conclusion
• Esophageal cancer is the 7th leading cause of cancer deaths.
• Adenocarcinoma now accounts for over 50% of esophageal cancer in the
USA, due to association with GERD & obesity.
• Dysphagia and weight loss are the two most common presentations in
patients with esophageal cancer.
• Endoscopic ultrasound (EUS) is necessary to accompany a complete
workup for proper staging and diagnosis of esophageal cancer.
• Surgery is the standard of care for early-stage esophageal cancer.
• The hand-sewn anastomosis technique leads to more leaks, while stapled
anastomosis leads to more strictures
• Preoperative chemotherapy and radiation is the standard option for locally
advanced esophageal cancer in surgically eligible patients.

68. Thanks for your attention