Gastro 41 Esophageal cancer

Definition -In some patients, long-standing acid (and perhaps alkaline) reflux is associated with a histologic change of the distal esophageal mucosa from its normal squamous epithelium to a columnar configuration. This histologic alteration is called intestinal metaplasia or Barrett esophagus.

• Diagnosis –
• Endoscopy - esophagus appears as velvety-red “tongues” of mucosa that extend cephalad from the GEJ. Based on endoscopic measurements, it can be classified into long segment (≥3 cm) and short segment (<3 cm).
• Biopsy - multiple biopsy specimens should be taken to histologically establish the diagnosis and to determine the presence of dysplasia.  Incidence of adenocarcinoma in patients with Barrett esophagus is about 40 times greater than that in the general population.

• Treatment –
• - Antireflux operation - cause regression of intestinal metaplasia or decrease the rate of dysplasia and cancer.
• - High-dose PPIs

• Most common worldwide - squamous cell carcinoma (SCC)
• Most common in united States - adenocarcinoma

• Risk factors for SCC -
• Tobacco and alcohol are strong risk factors
• More common in men
• Higher among African Americans
• HPV
• Intrinsic disorders of esophagus - Plummer-Vinson syndrome and achalasia
• Tylosis and Fanconi anemia
• History of caustic ingestion

• Risk factors for Adenocarcinoma
• Barrett esophagus
• Smoking
• Obesity

• SCC - majority arise in the proximal and middle esophagus
• Adenocarcinomas - arise in the distal esophagus or GEJ.

• Dysphagia - progressive dysphagia, beginning with an initial episode after eating solid food. After the initial episode of dysphagia, many patients will adapt by chewing more thoroughly, avoiding hard foods, or drinking liquids with swallows. Thus, it is only after the dysphagia has worsened significantly that patients seek medical attention, by which point the majority have weight loss.
• Long history of reflux symptoms including heartburn and regurgitation in patients with adenocarcinoma.
• Fatigue, retrosternal pain, and anemia
• Locally advanced tumors may be manifested with laryngeal nerve involvement causing hoarseness or with tracheoesophageal fistula.

Barium esophagram - irregular narrowing or ulceration. The classic “apple-core” filling defect is seen only if there is symmetrical, circumferential narrowing. Instead, there is often an asymmetrical bulge seen with an infiltrative appearance.

• Endoscopiy
• - friable, ulcerated masses, but the endoscopic appearance can be varied.
• - Multiple biopsies should be performed for any suspicious lesions.
• - During endoscopy, the location of the tumor relative to the incisors and GEJ should be noted, as well as the length of the tumor and degree of obstruction. The most proximal extent and circumferential extent of any Barrett esophagus should also be noted according to the Prague criteria.

For T1a tumors, EMR without additional staging.

For larger lesions - staging with a CECT scan of the chest and abdomen and PET/CT to evaluate for distant metastatic disease. If there is no evidence of distant metastatic disease, EUS should be performed to assess T stage and regional lymph nodes. EUS is superior to CT or PET for assessment of both T and N stage.

Bronchoscopy should also be performed for tumors above the carina to assess for direct tracheal invasion.

• It is still widely accepted for mapping of Barrett esophagus with high-grade dysplasia.
• This involves four quadrant biopsies at 1-cm intervals along the entire length of Barrett esophagus in addition to targeted biopsies of all visible lesions.

The PET/CT scan may demonstrate distant metastatic disease, eliminating the need for the patient to undergo EUS. The PET/CT scan may also identify a suspicious lymph node that can be specifically examined and sampled during the EUS procedure.

• Tis High-grade dysplasia
• T1 Tumor invades the muscularis mucosa (T1a) or submucosa (T1b)
• T2 Tumor invades into but not beyond the muscularis propria
• T3 Tumor invades the adventitia
• T4a Tumor invades adjacent structures that are usually resectable (diaphragm and pericardium)
• T4b Tumor invades unresectable structures

• N1 Metastasis in 1-2 regional lymph nodes
• N2 Metastasis in 3-6 regional lymph nodes
• N3 Metastasis in ≥7 regional lymph nodes

M1 Distant metastasis

• Histologic Grade
• GX Grade cannot be assessed—stage grouping as G1
• G1 Well differentiated
• G2 Moderately differentiated
• G3 Poorly differentiated
• G4 Undifferentiated—stage grouping as G3 squamous

The cervical esophagus (15 to 20 cm from the incisors) - begins at the hypopharynx and extends to the thoracic inlet,which is the level of the sternal notch.  

Upper thoracic esophagus (20 to 25 cm from the incisors)  - begins at the thoracic inlet and extends to the azygos vein. 

Mid thoracic esophagus (25 to 30 cm from the incisors) - from the lower border of the azygos vein to the inferior pulmonary vein.

Lower thoracic esophagus (more than 30 cm from the incisors) - distal to the lower border of the inferior pulmonary vein to the GEJ.

• T1a tumors - EMR.
• T1N0M0 lesions - Esophagectomy  with lymph node dissection
• T2N0 - Esophagectomy  with lymph node dissection / CROSS trial 
• T2N₊,T3,T4a, with/without nodal disease - Neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy
• Stage IV disease - systemic or palliative therapy

• Endoscopic radiofrequency ablation (RFA) and Cryotherapy - limited depth of penetration, lack of definitive pathologic analysis
• Endoscopic mucosal resection - for lesions confined to the mucosa (T1a)
• Esophagectomy

• 1. Radiation therapy.
• 2. Chemotherapy - Systemic chemotherapy has the potential to target micrometastatic deposits
• 3. Chemoradiation alone -
• 4. Chemoradiation and surgery

1. Cervical esophageal cancer – Neoadjuvant chemotherapy followed by surgery. Surgery includes one-stage, three-phase operation requires cervical, abdominal, and thoracic incisions, and a permanent terminal tracheostomy. Restoration of gastrointestinal tract continuity is accomplished with a gastric pull-up and anastomosis to the pharynx.

2. Thoracic cancer - require a total esophagectomy because of the risk of submucosal skip lesions. The transhiatal, Ivor-Lewis (transthoracic), and tri-incisional esophagectomy procedures are the most commonly performed esophagectomies.

A. Transhiatal esophagectomy (Orringer) - It is performed through an upper midline laparotomy incision and a left neck incision, typically without a thoracotomy. No thoracotomy, Neck anastomosis, Minimal mortality & morbidity

B. Ivor-Lewis transthoracic esophagectomy - can be used to resect cancers in the lower third of the esophagus but is not the optimal approach for cancers located in the middle third because of the limited proximal margin that can be achieved. This procedure combines a laparotomy with a right thoracotomy and an intrathoracic esophagogastric anastomosis.

C. Modified Ivor-Lewis transthoracic esophagectomy - a left thoracoabdominal incision with a gastric pull-up and an esophagogastric anastomosis in the left chest.

• D. Tri-incisional esophagectomy (Mckeon/En Bloc) - A right posterolateral thoracotomy or a thoracoscopy is performed first to assess resectability and exclude local invasion of contiguous structures. The abdomen is explored to exclude metastatic disease, and the stomach is mobilized in preparation for the construction of the gastric conduit. Left neck incision is preferred for the esophagogastric anastomosis, since this approach reduces the risk of injury to the recurrent laryngeal nerve (RLN) . The left RLN recurs lower (around the aortic arch) than the right RLN, which recurs around the subclavian artery and is therefore more likely to be injured from a right neck approach. 
• In McKeown approach esophago gastric anastomosis is in neck. Leakage in neck has low mortality.

3. Esophagogastric junction cancer

Either an esophagectomy with partial gastrectomy or an extended gastrectomy, with or without thoracotomy. Regardless of the approach, complete (R0) resection, a 4 cm (distal) gastric margin, a 5 cm esophageal margin, and resection of at least 15 nodes in basins appropriate for the primary tumor location is necessary. 

•Patients with Siewert type I tumors are not appropriate candidates for a purely transabdominal approach to surgical resection. The standard surgical approach is a transthoracic en bloc esophagectomy and partial gastrectomy with two-field lymphadenectomy.

•For the majority of Siewert type II and III tumors, total gastrectomy with a transabdominal/transhiatal resection of the distal esophagus with lymphadenectomy of the lower mediastinum and the abdominal D2 nodal compartment is adequate




These figures represent the Siewert classification for tumors arising at the esophagogastric junction (EGJ) and the extent of the surgical resection for an EGJ adenocarcinoma, including regional lymph nodes, based upon the Siewert classification.


Type I adenocarcinoma is located in the distal esophagus and is resected by a subtotal gastrectomy, subtotal esophagectomy, and regional lymphadenectomy.

Type II adenocarcinoma arises from the cardia or the EGJ and is resected by a total gastrectomy, distal esophagectomy, and regional lymphadenectomy.

Type III adenocarcinoma originates in the subcardial gastric location, infiltrates the EGJ and distal esophagus from below, and is resected by a total gastrectomy, distal esophagectomy, and regional lymphadenectomy.

• Two-field lymphadenectomy
• - mediastinal, upper abdomen   

• Three-field lymphadenectomy
• - mediastinal, abdominal and cervical nodes
• - commonly practiced in Asian countries for upper thoracic esophageal cancers

• First abdomen is opened, to see for liver metastasis
• Stomach is mobilised
• Pyloromyotomy done and abdomen closed. Pt positioned and Rt postero-lateral thoracotomy done
• Esophagus mobilised
• Tumour with adeqate esophagus resected
• Anastomosis done between stomach and esophagus

• Pitfalls
• - Long procedure and anesthesia time
• - Intrthoracic anastomosis
• - Morbidity

• Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial. 
• Study population - T_2-3N₊M₀
• Compared neoadjuvant chemoradiation followed by surgery versus surgery alone for esophageal and GEJ cancer.
• The chemoradiation regimen consisted of a 5-week course of carboplatin and paclitaxel administered concurrently with radiation therapy at a dose of 41.4 Gy given in 23 fractions 5 days a week. Esophagectomy was performed within 5 weeks in the treatment group and immediately after randomization in the control group.
• The completeness (R0) of resection was higher in the trimodality group than in the surgery-alone group.
• Patients receiving the trimodality therapy had significantly longer median overall survival. [@ 555]

To releive dysphagia in unresectable cancer of esophagus or if there is fistula with respiratory tract,  esophagus can be bypassed using left colon, Stomach or jejunum.

• Disadvantages
• - Risks of G.A. and major operation
• - Morbidity and mortality

Simple and effective methods (Intubation by tubes or stents or laser therapy) are available now

• ●Dilation
• ●Laser therapy
• ●Endoscopic injection therapies
• ●Photodynamic therapy
• ●Argon plasma coagulation
• ●Cryospray ablation
• ●Placement of prosthetic tubes (stenting)
• ●Brachytherapy

• Stenting is preferable therapy for patients with a malignant stricture and/or fistula.
• In the absence of a fistula, optimal therapy remains controversial. The choice of endoscopic palliative method should be based upon anatomical features, patient preferences, and available expertise

• Pain relief - Cancer esophagus or its treatment may cause pain.This needs pain killers –oral syrups or tablets, injectable drugs mainly non narcotic medicines, in severe pain narcotics are used

• Nutrition - Pt may not be able to eat due to obstruction, poor appetite, vomiting or diarrohea (due to Chemo or radiotherapy) Diet is modified accordingly- liquid diet, through feeding tube or IV hyperalimenta tion

• Psychological support- Patient is anxious and worried and needs lot of moral and mental support by family, friends, councilors and psychiaterist