Gastroesophageal junction tumors

Overview and updates

Dr. Mahmoud W. Qandeel

 Outlines

• Epidemiology
• Definition and classification
• Risk factors
• Presentation
• Diagnosis and staging
• Treatment

Dr. Mahmoud W. Qandeel

 Epidemiology

• Cancers of the esophagus and stomach are among the most prevalent
malignancies globally and are a major cause of cancer-related mortality.
• Overall approximately 1.4 million new cases of cancers of the esophagus and
stomach arise worldwide each year.
• Gastroesophageal junction tumors refer to tumors that arise close to the
gastroesophageal junction.
• This subset of tumors has increased in prevalence in the past decade, increasing
by approximately 10% over the past 40 years.
• Overwhelmingly the most common histology is adenocarcinoma, accounting for
more than 90% of all gastroesophageal tumors
• Epidemiological shift?
Dr. Mahmoud W. Qandeel
 Definition and classification

• The most commonly used classification system to define a

gastroesophageal tumor was created by Jorg Rudiger Siewert, a German
surgeon who created a classification system for gastroesophageal
junction tumors based on the location of the epicenter of the given
tumor.

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel
Dr. Mahmoud W. Qandeel
 Risk factors
• Gastroesophageal reflux disease
• Barrett esophagus,
– Long-segment Barrett esophagus, (> or = 3 cm), has a higher risk of development of
gastroesophageal junction tumors than short-segment Barrett esophagus.
• Obesity.
• Dietary composition
– Diets high in fats and red meats have been associated with an increased incidence of
gastroesophageal cancer.
– In contrast, diets high in fruits, fish, and vegetables have been associated with a
decreased incidence of gastroesophageal tumors.
• Smoking
– When compared with never-smokers, ex-smokers have a relative risk of 1.62 and
current smokers having a relative risk of 2.32 of developing gastroesophageal cancer.

Dr. Mahmoud W. Qandeel

H. Pylori?

• A study by Wu and colleagues in 2003 revealed no association between H

pylori infection and esophagogastric adenocarcinoma.
• Two other studies showed an inverse relationship between H pylori infection
and the development of adenocarcinoma of the esophagogastric junction.

• Chow and colleagues showed that infection with H pylori imparted a 60%
decrease in the risk for developing esophageal or cardia adenocarcinoma.
• A similar study from a Swedish population demonstrated a 50% to 80%
reduced risk for esophageal adenocarcinoma with H pylori infection
 Presentation

• Most patients present with vague symptoms of dysphagia and weight loss, with an
occasional patient presenting with UGIB.
• Most patients remain asymptomatic until presenting later with locally advanced disease.
• Approximately 80% of patients with gastroesophageal junction tumors present with
locally advanced or diffuse metastatic disease.
• Many patients with gastroesophageal junction tumors also have positive lymph nodes at
the time of presentation.
• This high incidence of lymphadenopathy occurs as a result of the anatomic configuration
of the esophagus. ??

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel
 Diagnosis and Staging

• Patients who present with dysphagia should have an upper GI barium swallow as their
initial diagnostic test followed by should prompt an EGD and biopsy of the mass .
• Once a diagnosis of malignancy has been made, PET-CT scan and endoscopic
ultrasound should be performed to define the full extent of disease.
• PET-CT scan is useful to determine whether any distant disease is present, such as in
the liver or retroperitoneum.
– Although PET-CT is helpful for evaluation of distant metastases, it is less helpful in defining the
depth of tumor invasion or presence of locoregional lymph node metastases.
• Endoscopic ultrasound, however, does clearly define depth of invasion and can show
enlarged lymph nodes, which can be biopsied during endoscopic ultrasound if needed.

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel
Dr. Mahmoud W. Qandeel
AJCC 8th Edition
• Cancers involving the EGJ that have their epicenter within the
proximal 2 cm of the cardia (Siewert types I/II) are to be staged as
esophageal cancers.

• Cancers whose epicenter is more than 2 cm distal from the EGJ, even if
the EGJ is involved, will be staged using the stomach cancer TNM and
stage groupings.

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel
Dr. Mahmoud W. Qandeel
 Preoperative Treatment

• All patients with GEJ tumors should have a complete multimodality

treatment plan determined in a multidisciplinary tumor conference.
• The need for preoperative chemotherapy or radiation treatment
depends on the stage and location of the GEJ tumor.

• Early-stage GEJ tumors, which have not invaded the muscularis propria
and have no apparent lymphadenopathy, are treated with surgery.

• If there is no up-staging of disease after pathologic results are reviewed,

then surgery alone is sufficient and no adjuvant treatment is required.
Dr. Mahmoud W. Qandeel
 SURGERY

• Patients who undergo preoperative treatment are restaged after completion of

treatment.
• Regardless of the Siewert classification, the surgical management of GEJ tumors involves
resection of the esophagus and stomach with wide margins around the tumor.
• In general, it is best to achieve at least 5 cm margins both proximal and distal to the GEJ
tumor.
• This margin distance is based on numerous studies that have shown that microscopic
disease can be present centimeters away from the mass.
• One study showed that patients with GEJ tumors who had fewer than 7 positive lymph
nodes experienced increased survival when surgical margin was greater than 3.8 cm.
• Patients with 7 or more positive lymph nodes did not experience the same survival
benefit with this surgical margin.
Dr. Mahmoud W. Qandeel
• For locally advanced disease, which is defined as a T3 or T4 lesion, or a lesion
with regional lymphadenopathy, multiple trials have investigated surgery alone
compared with preoperative chemotherapy and/or radiation treatment.

• The Cancer and Leukemia Group B (CALGB) 9781 study examined patients with
lesions of the thoracic esophagus or gastroesophageal junction and showed
that the addition of chemotherapy and radiation treatment prior to surgery
increased the median survival from 1.79 years to 4.48 years.
• The overall 5-year survival rate in the same study increased from 16% to 39%.

Dr. Mahmoud W. Qandeel

• Another study, the ChemoRadiotherapy for Oesophageal cancer Followed by
Surgery Study (CROSS) trial, enrolled 366 patients and evaluated
preoperative chemoradiation therapy followed by surgery compared with
surgery alone for esophageal and gastroesophageal junction cancers 25% of
these patients had gastroesophageal junction tumors.

• Complete R0 resection was performed in 92% of patients who underwent

preoperative treatment, compared with 69% of patients who had surgery
alone.
• And 5-year survival was 47% in the chemoradiation treatment group
compared with 24% in the group who had surgery alone.

Dr. Mahmoud W. Qandeel

• The Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC)
trial investigated 503 patients with resectable cancer of the stomach, gastroesophageal
junction or lower esophagus15; 253 patients underwent surgery alone, whereas 250
patients were given 3 cycles of preoperative chemotherapy, using epirubicin, cisplatin and
5-fluorouracil, surgery, and then an additional 3 cycles of chemotherapy after surgery; 90%
of patients completed the preoperative chemotherapy, whereas only 50% of patients
completed their postoperative chemotherapy.

• The overall 5-year survival was 36% in the perioperative chemotherapy group and 23% in
the surgery alone group.
• It was also observed that down-staging occurred on pathologic examination due to
treatment response in both the primary tumor and nodal basins.
• Perioperative complication rate and mortality were similar between the groups.

Dr. Mahmoud W. Qandeel

• Recently, the role of the HER2 receptor has been investigated in patients with GEJ tumors.
• HER2 is overexpressed in approximately one-quarter of all GEJ tumors.
• Overexpression is associated with a more aggressive clinical course and an overall worse
outcome.
• Trastuzumab is, which is directed against the HER2 receptor, and its role in the clinical
management of patients with GEJ tumors is being investigated in a multi-institutional
phase III trial.
• In this trial, patients with locally advanced esophageal cancers that overexpress HER2 are
randomized to receive preoperative chemoradiation with or without trastuzumab.
• A previous study evaluating patients with unresectable esophageal cancers showed that
the addition of trastuzumab to a standard chemotherapy regimen increased survival.

Dr. Mahmoud W. Qandeel

 SESAP 16
Which of the following statements regarding GEJ adenocarcinoma is true?
A. There is a steady decrease in the incidence within the USA
B. The incidence is inversely proportional to the precence of acid reflux
C. Gastric H. Pylori is believed to be causative
D. Women have a lower incidence than men
E. Whites have a lower incidence than blacks

Dr. Mahmoud W. Qandeel

SESAP 15
A 54-year-old man presents with progressive dysphagia and 6 kg weight loss. His
albumin is 2.9 mg/dL and his serum transferrin is 11 g/dL. AN EGD is performed and
shows a mass at GE junction. Biopsy demonstrates the presence of invasive
adenocarcinoma. Based on staging with EUS and CT, the patient is scheduled for
neoadjuvant chemotherapy and radiation therapy, followed by surgical resection.
Which of the following is the preferred form of alimentation for this patient?
A. TPN
B. Enteral via NJ feeding tube
C. Enteral via PEG
D. Oral after placement of uncovered metal stent
E. Oral after placement of a covered silicone stent

Dr. Mahmoud W. Qandeel