Chapter 53 Esophageal Cancer Flashcards
What percentage of esophageal cancer diagnosed are curable?
Less than 15%
What percentage of esophageal cancer diagnoses are presented with unresectable or metastatic disease?
approximately half of patients
Length of oesophagus
25 cm
Lining of esophagus
Stratified keratinized squamous epithelium, extending from the cricopharyngeus muscle at the level of the cricoid cartilage superiorly to the gastroesophageal junction inferiorly. The lower one-third (5 to 10 cm) of the esophagus may contain glandular elements.
What is Barrett’s esophagus?
Replacement of the stratified squamous epithelium with columnar epithelium is referred to as Barrett’s esophagus, often occurring in the lower one-third.
What is Z-line in esophagus?
Endoscopically visible junction of the squamous and glandular epithelium
Describe layers of esophageal wall
3 layers: mucosa, submucosa,muscularis propria mucosal layer epithelium(M1), lamina propria(M2), muscularis mucosae(M3) submucosal layer inner (SM1), middle (SM2), and outer (SM3) musclaris propria circular inner layer and longitudinal outer layer The adventitia (periesophageal connective tissue) lies directly on the muscularis propria No serosa is present, facilitating extraesophageal spread of disease.
Describe 4 regions of esophagus(AJCC)
cervical upper thoracic midthoracic lower thoracic
Extension of cervical esophagus
begins at the cricopharyngeus muscle (approx. C7 level or 15 cm from the incisors) extends to the thoracic inlet (approx. T3 level or at approx. 20 cm from the incisors, at the level of the suprasternal notch), and therefore lies within the neck
Extension of thoracic esophagus
extends from approx. level of T3 (beginning at about 20 cm) to T10 or T11
Extension of upper thoracic esophagus
superiorly by the thoracic inlet and inferiorly by the lower border of the azygos vein extending from approx. 20 to 25 cm
Extension of middle thoracic esophagus
extends from the lower border of the azygos vein to the inferior pulmonary veins extending from approx. 25 to 30 cm
Extension of lower thoracic esophagus
extends from the inferior pulmonary veins and to the stomach and is inclusive of the gastroesophageal junction, typically extending from approximately 30 to 40 cm.
Define GE junction
Endoscopically, defined as the point where the first gastric fold is encountered, although this may be a “theoretical” landmark. Location of the GE junction can be accurately defined histologically as the squamocolumnar junction.
Recent AJCC staging system, subsites staged as an adenocarcinoma of the esophagus vs stomach cancer
epicenter in the lower thoracic esophagus gastroesophageal junction within the proximal 5 cm of the stomach (i.e., cardia) and extending up to the GE junction or esophagus vs epicenter is >5 cm distal to the gastroesophageal junction or within 5 cm of the gastroesophageal junction but does not extend to the junction/esophagus
Useful landmarks in reference to endoscopy Carina GE junction
Carina ∼25 cm from the incisors GE junction ∼40 cm from the incisors
Siewert et al. tumor characterization involving GE junction according to location of tumor
Type I adenocarcinoma of the distal esophagus : located >1 cm up to 5 cm above GE junction (Z-line) Type II : within 1 cm cephalad to 2 cm caudad to the GE junction, it is classified as type II. Type III : >2 cm below the GE junction However, locally advanced/ bulky tumors can make it difficult to accurately distinguish where tumors originated in relationship to the GE junction
Lymphatic drainage of esophagus
1.Longitudinal interconnecting system of lymphatics. 2.Lymphatic network is primarily located within the submucosa; however channels are also present within the lamina propria, facilitating spread of even superficial cancers of the esophagus involving the mucosa. 3.Intramural lymphatics may traverse the muscularis propria, facilitating tumor spread to regional lymphatic channels and paraesophageal nodes. 4.Autopsy series have demonstrated a relatively high incidence of directly draining channels extending from the submucosa lymphatics into the thoracic duct facilitating systemic spread. 5.Lymph can travel the entire length of the esophagus before draining into lymph nodes and thus the entire esophagus is at potential risk for lymphatic involvement 6.Up to 8 cm or more of ‘normal’ tissue can exist between gross tumor and micrometastases “skip areas” secondary to this extensive lymphatic network. 7.As many as 71% of frozen tissue sections scored as margin negative by conventional histopathology show involvement by lymphatic micrometastases with immunohistochemistry. 8.Lymphatics of the esophagus drain into nodes that usually follow arteries, including the inferior thyroid artery, the bronchial and esophageal arteries, and the left gastric artery (celiac axis)
What percentage of esophageal carcinoma accounts for GI malignancy?
6%
Ratio M:F esophageal cancer
4:1
Which countries have highest incidence of Esophageal carcinoma?
Linxian, China, Russia, and the Caspian region of Iran
Major risk factors of esophageal cancer
1.Alcohol and Tobacco 2.Diets of scant amounts of fruits, vegetables, and animal products 3.Plummer-Vinson (Paterson-Kelly) syndrome characterized by iron-deficiency anemia and low riboflavin levels 4.Nitrate rich foods 5.Achalasia and tylosis 6.Barrett’s esophagus 7.Obesity
Amount of consumption of alcohol and tobacco leading to RR of 155:1 esophageal cancer
>30 g/day of tobacco along with 121 g/day of alcohol
Which cancers are at an increased risk with Plummer-Vinson (Paterson-Kelly) syndrome?
oral cavity hypopharyngeal esophageal cancer
What percentage of incidence of SCC is associated with Achalasia and tylosis(long duration 25 years)?
5%
Patients with tylosis (hyperkeratosis of the palms and soles and papilloma of the esophagus) have what percentage of a reported risk in developing esophageal cancer at a mean age of 45 years.
38%
Name some nitrate compounds and nitrate rich foods
1.nitrosamines, nitrosamides, and N-nitroso compounds 2.nitrate-rich foods include pickled vegetables, alcoholic bever-ages, cured meats, and fish
What is the cause of Barrett’s Oesophagus?
Severe and long-standing gastroesophageal reflux
Barrett’s Oesophagus has which-fold increased risk of having Adenocarcinoma?
44-fold
Smokers have what-fold increased risk of having Adenocarcinoma Oesophagus than non-smokers?
2-3 folds
How long does relative risk of esophageal adenocarcinoma persists in contrast to a significant decline in similar patients with squamous cell carcinoma?
3 decades
What fold risk of Oesophageal adenocarcinoma is related with Obesity? Why?
3-4 folds Due to increased risk of reflux
What percentage of middle-aged patient with Barrett’s esophagus has a risk of developing esophageal adenocarcinoma during his or her lifetime?
10-15%
Genetic abnormalities involved in the genesis of SCCA esophageal cancer
-p53 mutations -multiple allelic losses at 3p and 9q, with amplification of cyclin D1 and epidermal growth factor receptor(EGFR)
Genetic abnormalities involved in the genesis of Adenocarcinoma esophageal cancer
-overexpression of p53 -multiple allelic losses at 17p, 5q, and 13q -amplification and overexpression of EGFR and human epidermal growth factor receptor 2 (HER-2)
Squamous cell carcinoma is characterized by extensive local growth and proclivity to lymph node metastases. Because the esophagus has no covering serosa, direct invasion of contigu-ous structures may occur early. Lesions in the upper esopha-gus can impinge on or invade the recurrent laryngeal nerves, carotid arteries, and trachea. If extraesophageal extension occurs in the mediastinum, tracheoesophageal or broncho-esophageal fistula may occur. Tumors in the lower one-third of the esophagus can invade the aorta or pericardium, resulting in mediastinitis, massive hemorrhage, or empyema.
A
Incidence of lymph node metastases with depth of penetration in Oesophageal cancer
18% of patients with spread to the submucosa had lymph node involvement
Percentage of nodal involvement in T1/T2 oesophageal cancer
T1 - 14% to 21% T2 - 38% to 60% At autopsy, lymph node metastases are found in approximately 70% of patients Distant metastasis can occur at almost any site
Factors significantly associated with nodal metastasis in oesophageal cancer
T stage tumoral length degree of differentiation
Skip metastasis (distant lymph node metastases without regional lymph node metastasis) occurred, usually in oesophageal cancer patients with?
poorly differentiated, large and deeply invasive tumors.
Anderson LL, autopsy findings SCCA Oesophagus what are the sites of distant metastasis?
Any sites (Lymph nodes,Lung,Liver,Adrenals,Diaphragm,Bronchus,Pleura, Stomach,Bone,Kidneys,Trachea,Pericardium,Pancreas)
Lower esophageal and gastroesophageal junctional ade-nocarcinomas, what percentage of patients will have nodal metastases at presentation. Factors influencing such metastasis?
70% 1.tumoral depth of penetration 2.all T3 and T4 lesions
Pathologic resection data demonstrated rates of lymphatic involvement for lower esophageal and GE junctional tumors of T2, T3, and T4 tumors
45%, 85%, and 100%
Primary direction for lymphatic flow for the lower esophagus?
The primary direction is toward the abdomen Involvement of both mediastinal and abdominal lymph nodes is common
Classification by Siewert, nodal metastases according to oesophageal tumors type I/II/III
Type I - mediastinum and abdomen Type II - preferentially spreading inferiorly and less frequently into the mediastinum Type III- almost exclusively inferiorly, toward the celiac axis
Japanese Gastric Cancer Association Classification Describe tumor stratification of esophagogastric junction carcinoma undergoing primary resection by Erlangen
AEG Type I (distal esophagus) Type II (gastric cardia) Type III (subcardia)
Japanese Gastric Cancer Association Classification Describe incidence of nodal metastasis by T-stage in esophagogastric junction carcinoma undergoing primary resection by Erlangen
Overall incidence of LN mets : 71% T1 - 17% T2 - 78% T3 - 86% T4 - 90%
University of Pennsylvania Fox Chase Cancer Center Adenocarcinoma of the esophagus and GE junction treated with surgery alone Percentage of LRR rate?
77%
Contemporary randomized trials, Esophageal cancer local failure rates with surgery alone?
32% to 45%
Recent randomized trials of esophageal cancer using “definitive” chemoradiation local failure?
Approx 50%
Clinical features of Esophageal cancer
1.Dysphagia >90% 2.Odynophagia 50% 3.Weight loss 40% to 70% of patients report loss of >5% of total body weight 4.Vague chest pain 5.Hoarseness 6.Cough 7.Glossopharyngeal neuralgia 8.Hematemesis, hemoptysis, melena 9.Dyspnea, and persistent cough secondary to tra-cheoesophageal or bronchoesophageal fistula 10.Compression or invasion of the left recurrent laryngeal nerve or the phrenic nerves can cause dysphonia or hemidiaphragm paralysis 11.SVC syndrome and Horner’s syndrome 12.Pleural effusion and exsanguination resulting from aortic communication may also be seen 13.Abdominal and back pain may occur with celiac axis nodal involvement with lower esophageal tumors
When does symptoms of esophageal cancer start?
3 to 4 months before diagnosis
Which is the best tool to diagnose and define the extent of the esophageal lesion?
Endoscopy
Advantages of endoscopy in esophageal cancer
1.Biopsies and brushings of primary site and suspicious areas harboring satellites or submucosal spread 2.RT treatment planning - accurate endoscopic measurement and characterization of tumor and gastroesophageal junction in relation to the incisors 3.Panendoscopy of the oral cavity, pharynx, larynx, and tracheo-bronchial tree in patients with squamous cell carcinomas, given the high incidence of second tumors in the head and neck and upper airways
Indication of bronchoscopy in esophageal cancer
Proximal malignancies to evaluate for the presence of tracheal or carinal invasion, patients with tumors abutting these structures on CT
Indication of CT thorax and abdomen in esophageal cancer
Identify metastases to the liver, upper abdominal nodes, or adrenals
Limitations of diagnostic CT in esophageal cancer
1.CT may not adequately assess periesophageal lymph node involvement or accurately define the true extent of the primary tumor 2.Accurately determine resectability in only 65% to 85% of cases 3.Accurately predicts T stage in approx. 70% of cases and 4.Nodal involvement in only 50% to 70% of cases
What is the diagnostic modality of choice to accurately assess periesophageal and celiac lymph node involvement and transmural extent of disease?
EUS Endoscopic Ultrasound
What is the accuracy of EUS for T and N stage in esophageal cancer?
When matched to surgical pathology 85-90% for tumor invasion (T stage) 75-80% for lymph node metastases