Esophageal cancer

Esophageal cancer

Overview

Esophageal cancer is cancer that develops in the esophagus, the food channel that connects the throat to the stomach. Swallowing difficulties and weight loss are common symptoms. Other symptoms include swallowing discomfort, hoarseness, swollen lymph nodes around the collarbone, a dry cough, and perhaps coughing up or vomiting blood.

Among gastrointestinal cancers, esophageal cancer has a dismal prognosis. Although esophageal squamous cell carcinoma is the most common kind, Western countries have experienced a significant increase in the prevalence of esophageal adenocarcinoma, which coincides with the obesity pandemic. Early detection efforts have been problematic due to the fact that dysplasia and early cancer are often asymptomatic.

 

Esophageal cancer definition

Esophageal cancer definition

The majority of esophageal malignancies are classified histologically as squamous cell carcinoma (SCC) or adenocarcinoma. In the United States, the incidence of these carcinomas has been falling (less than 30%) and growing (more than 60%) over the last three decades. The incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) continues to rise significantly as a result of Barrett's esophagus.

 

Epidemiology

With an estimated 16,940 instances per year in the United States, esophageal cancers are the fifth most prevalent gastrointestinal cancer and the sixth most common cancer globally. The highest-risk area, known as the "esophageal cancer belt," encompasses parts of northern Iran, southern Russia, central Asian nations, and northern China, where squamous cell cancers account for 90 percent of all cases.

Esophageal carcinoma is the fourth most prevalent cause of cancer in this risk group. In contrast, the United States is considered a low-risk area, with an increase in the incidence of esophageal adenocarcinoma, mostly owing to an increase in obesity and GERD, and a consistent drop in squamous cell carcinoma due to long-term cigarette and alcohol usage reductions. Adenocarcinoma is primarily a disease of white men. In contrast, blacks and Asians have the greatest incidences of esophageal squamous cell carcinoma.

 

Causes of esophageal cancer

Nearly 90% of esophageal squamous cell carcinomas in the United States are caused by a history of smoking, alcohol intake, and a diet poor in fruits and vegetables. In poorer nations, risk factors for esophageal squamous cell carcinoma are less definite, however they may include poor nutritional status, a low consumption of fruits and vegetables, and consuming hot drinks.

Human papillomavirus (HPV) infection has been linked to an increase in the incidence of upper esophageal squamous cell carcinoma. Achalasia, caustic strictures, gastrectomy, and atrophic gastritis are all related with an increased risk of esophageal squamous cell carcinoma. A patient's present or prior squamous cell carcinoma of the aerodigestive tract may be associated with synchronous or metachronous esophageal squamous cell carcinoma.

The majority of esophageal adenocarcinomas in the United States are caused by Barrett's metaplasia, which is caused by a history of smoking, a high body mass index, gastroesophageal reflux disease (GERD), and a poor fruit and vegetable diet. Alcohol use has not been linked to adenocarcinoma.

Barrett's esophageal metaplasia has been linked to epidermal growth factor polymorphisms, Helicobacter pylori infection, and other diseases that enhance esophageal acid exposure, such as diabetes (e.g., Zollinger-Ellison syndrome, scleroderma, lower esophageal sphincter relaxing drugs, or procedures). Familial Barrett's esophagus is related with uncommon autosomal inherited dominant susceptibility alleles and should be suspected in a patient with esophageal/GEJ adenocarcinoma, especially if he is Caucasian, has GERD, and is older than 40 years.

Although a high cereal diet, antioxidants, fruits and vegetables, folate, vitamin C, proton-pump inhibitors, and NSAIDs can protect against the formation and progression of Barrett's esophagus and hence esophageal cancer, none has been proven to be a preventative strategy.

 

Pathophysiology

Pathophysiology of esophageal cancer

Esophageal squamous cell carcinoma develops from tiny polypoid excrescences, denuded epithelium, and plaques, which are most typically found in the middle of the esophagus. To differentiate normal squamous epithelium carrying glycogen from malignant squamous glycogen-deprived cells, tissue staining with Lugol's iodine should be performed to distinguish normal squamous epithelium containing glycogen from malignant squamous glycogen-deprived cells.

Advance lesions are ulcerated, circumferential, infiltrate the submucosa, and spread cephalad. The lymphatic system spreads the cancer to regional lymph nodes, but one-third of patients will develop distant metastases to the liver, lung, and bone, including invasion of malignant cells into the bone marrow.

Approximately 60% of distal esophageal adenocarcinoma and, more commonly, GEJ cases develop from Barrett's esophageal metaplastic epithelium. Surveillance utilizing upper endoscopy and biopsy to evaluate tissue for signs of dysplasia is the standard treatment for people with Barrett's esophagus. Adenocarcinoma incidence is 1.0 case per 1000 person-years in individuals without dysplasia; however, discovery of low-grade dysplasia on the index endoscopy is related with an adenocarcinoma incidence rate of 5.1 cases per 1000 person-years.

 

Symptoms of esophageal cancer

Symptoms of esophageal cancer

Progressive solid food dysphagia owing to locally advanced malignancy generating blockage and dysphagia to liquid occurs in advanced stages of both esophageal adenocarcinoma and squamous cell carcinoma. Cachexia and significant weight loss are symptoms of dysphagia, which may be severe illness, causing many patients to be incapacitated at the time of diagnosis. Subtle non-specific symptoms, such as retrosternal pain or a burning feeling, may have preceded.

 Symptoms of hematemesis, melena, and anemia may be present at the time of the first diagnosis as part of overt or occult gastrointestinal bleeding. Regurgitation is also possible, but aspiration pneumonia is uncommon. Fistulas caused by tracheobronchial wall invasion might appear clinically as laryngeal nerve paralysis, cough, and/or post-obstructive pneumonia.

Unless the cancer has spread to the neck nodes or the liver, physical examination results in individuals with esophageal cancer are often benign. Lymphadenopathy in the laterocervical or supraclavicular region, as well as the presence of hepatomegaly, are frequently signs of unresectable illness.

 

Diagnosis

Diagnosis of esophageal cancer

The importance of a clinical examination focusing on lymph nodes in the supraclavicular and axillary areas cannot be overstated. On patients with clinical suspicion, clinicians may opt to begin with barium tests, but upper endoscopy with minimally invasive biopsy should be performed to confirm the diagnosis. Multiple biopsies should offer enough histology material to provide a proper diagnosis with greater precision. There is no evidence of in vivo staining with Lugol's iodine.

CT scans of the chest and abdomen should be conducted to determine the size of the main tumor and to look for probable liver metastases and celiac lymphadenopathy. CT, on the other hand, is ineffective at differentiating tumor depth, has low lymph node sensitivity, and occasionally fails to identify tiny metastases, particularly inside the peritoneum.

Endoscopic ultrasonography (EUS) has become the gold standard of therapy for locoregional staging, with up to 90% accuracy in detecting tumor depth and involvement of locoregional and mediastinal lymph nodes. Furthermore, EUS enables for a tiny needle aspiration biopsy of questionable lymph nodes (greater than 1 cm) to confirm the existence of lymph node metastases, which is critical for accurate staging.

One disadvantage of EUS is that it cannot detect tumor stenosis, which is clinically observed in one-third of instances and can result in an underestimated tumor. EUS can be used after neoadjuvant therapy to restage local disease before surgery, but it lacks the sensitivity to determine full response.

Positron emission tomography CT (PET/CT) has become a common element of the preliminary diagnostic workup for evaluating distant metastases. Adenocarcinoma typically metastasizes to the abdomen, whereas squamous cell carcinoma usually metastasizes to the lungs. PET enables for the detection of occult locations of distant metastatic dissemination, sparing the patient the morbidity of intensive local-regional therapy when it is unneeded in up to 20% of instances. PET/CT scans may be clinically beneficial in patients following induction treatment for locally advanced illness to assist exclude people from subsequent surgery if metastatic disease is discovered. This happens to 8% of patients.

Diagnostic laparoscopy for resectable illness remains contentious and is not regularly suggested. Prior tumor, node, and metastasis (TNM) staging distinguished between esophageal squamous cell carcinoma and adenocarcinoma, but the eighth edition in 2017 regrouped them.

Siewert et al. divide EGJ into three types based on the distance to the anatomic junction: type I (less than 1 cm), type II (1 to 2 cm), and type III (more than 2 cm), with the latter occurring in more than 66 percent of instances. Location is less essential than the quantity of lymph nodes. Regardless of histology, half of the patients will have locally progressed or metastatic disease at the time of presentation.

Bronchoscopy is used to rule out invasion of the trachea or bronchi in malignancies of the middle and upper third of the thoracic esophagus (tumor at or above carina). It should only be done if the patient has no signs of M1 illness. In staging regional nodes, laparoscopy and thoracoscopy had higher than 92 percent accuracy.

 

Treatment for esophageal cancer

Treatment of esophageal cancer varies according to stage locoregional (stages I-III) versus metastatic cancer (stage IV) and  histologic subtype squamous cell carcinoma (SCC) versus adenocarcinoma.

Recommendations for esophageal cancer include the following:

  • Endoscopic therapy (endoscopic mucosal excision, endoscopic submucosal dissection, and/or ablation) is preferable for high-grade dysplasia (HGD) or T1a tumors larger than 2 cm; ablation alone is an option for individuals with HGD.
  • If multifocal HGD is found elsewhere in the esophagus, further ablation may be required following ER, although it may not be necessary for tumors that are entirely removed.
  • Esophagectomy is indicated for patients with extensive HGD or pT1a adenocarcinoma with nodular disease that is not adequately controlled by ER with or without ablation; a transhiatal, transthoracic, or minimally invasive approach may be used; gastric reconstruction is preferred; and feeding jejunostomy is preferred to gastrostomy for postoperative nutritional support.
  • Preoperative chemoradiation (for non-cervical esophageal cancers), definitive chemoradiation (recommended for cervical esophagus tumors), or esophagectomy are the primary therapeutic choices for patients with SCC T1b, N+ tumors, and locally advanced resectable tumors (T2-T4a, any regional N) (for non-cervical esophagus tumors).
  • Preoperative chemoradiation is preferred for patients with adenocarcinoma T1b, N+ tumors and locally advanced resectable tumors (T2-T4a, any regional N); definitive chemoradiation is indicated only for non-surgical patients; esophagectomy is an option for patients with low-risk, 2 cm, well-differentiated lesions.
  • Tumors in the submucosa (T1b) or deeper may be treated with esophagectomy.
  • For patients with SCC, no postoperative treatment is indicated if no residual disease is present at surgical margins (R0 resection).
  • For patients with adenocarcinoma who have not received preoperative therapy, postoperative fluoropyrimidine-based chemoradiation (following R0 resection) is indicated for all patients with Tis, T3-T4 tumors, node-positive T1-T2 tumors, and selected patients with T2, N0 tumors with high-risk features.
  • Chemotherapy following R0 resection is indicated for all patients with adenocarcinoma, irrespective of the nodal status.
  • Chemoradiation may be offered to all patients with residual disease at surgical margins (R1 and R2 resections).
  • Definitive chemoradiation is preferred for all T4b (unresectable) tumors.
  • Fluoropyrimidine- or taxane-based regimens are indicated for preoperative and definitive chemoradiation.
  • Two-drug cytotoxic regimens are preferred for patients with advanced disease because of lower toxicity.
  • Trastuzumab should be added to first-line chemotherapy (category 1 for combination with cisplatin and fluoropyrimidine; category 2B for combination with other chemotherapy agents) for patients with HER2-overexpressing advanced or metastatic adenocarcinoma (a tumor immunohistochemistry [IHC] score of  3+ or 2+ with the evidence of HER2 amplification by fluorescent in situ hybridization [FISH]).
  • Ramucirumab, either as a single agent or in combination with paclitaxel, was approved in 2014 by the US Food and Drug Administration (FDA) for the treatment of patients with advanced esophagogastric junction (EGJ) adenocarcinoma refractory to or progressive following first-line therapy with platinum- or fluoropyrimidine-based chemotherapy.

 

Surgical Indications and Contraindications

Surgery remains the cornerstone of treatment for esophageal cancer. Indications for surgery include the following:

  • Esophageal cancer in a patient who is a candidate for surgery
  • High-grade dysplasia in a patient with Barrett esophagus that cannot be adequately treated endoscopically  

 

Contraindications to surgery include the following:

  • Metastasis to N2 nodes (ie, cervical or supraclavicular lymph nodes) or solid organs (eg, liver, lungs); the treatment of patients with celiac lymph node involvement remains controversial 
  • Invasion of adjacent structures (eg, the recurrent laryngeal nerve, tracheobronchial tree, aorta, pericardium)

Furthermore, the existence of severe concomitant illnesses (e.g., cardiovascular disease, pulmonary disease) might reduce a patient's odds of surviving an esophageal resection. As a result, heart and respiratory performance must be thoroughly assessed prior to surgery. Relative contraindications to the surgery include a forced expiratory volume in 1 second of less than 1.2 L and a left ventricular ejection fraction of less than 0.4.

 

Esophagectomy

Esophageal resection (esophagectomy) is still an important part of multimodality therapy for patients with malignancies of any stage. Endoscopic mucosal resection is an investigational treatment for individuals with T1a disease or high-grade dysplasia that is only available at a few sites and is only done under strict procedure. Because different treatment techniques for dysphagia have become available, esophagectomy is no longer employed for symptom relief.

An esophagectomy can be done by an abdominal and cervical incision, with blunt mediastinal dissection into the esophageal hiatus, or with an abdominal and right thoracic incision.

THE has the benefit of not requiring a chest incision, which can cause extended pain and worsen the condition of patients with reduced respiratory function. Following esophageal removal, the stomach is frequently used to restore gastrointestinal tract continuity.

Transthoracic esophagectomy

There are two types of TTE, as follows:

  • Ivor Lewis esophagectomy (right thoracotomy and laparotomy)
  • McKeown esophagectomy (right thoracotomy followed by laparotomy and cervical anastomosis) 

The patient is positioned supine on the operating table for TTE. A central venous catheter, an arterial line, a Foley catheter, and a dual-lumen endotracheal tube are inserted. Antibiotics are given before to surgery. An incision is created in the upper midline.

The stomach is mobilized after the peritoneal cavity is explored for metastatic illness (if metastases are identified, the surgery is terminated). The right gastric and right gastroepiploic arteries are left intact, while the short gastric vessels and the left gastric artery are severed.

The gastroesophageal junction is then mobilized, and the esophageal hiatus is expanded. A pyloromyotomy is done, and a feeding jejunostomy is inserted to provide nutritional assistance postoperatively.

The patient is moved in the left lateral decubitus posture after the abdominal incision is closed, and a right posterolateral thoracotomy is done in the fifth intercostal region.

The azygos vein is split to facilitate complete esophageal mobilization. The stomach is brought into the chest via the hiatus and then separated 5 cm below the gastroesophageal junction.

At the apex of the right chest cavity, an anastomosis (hand-sewn or stapled) is done between the esophagus and the stomach. The chest incision is then closed.

McKeown esophagectomy, which involves an anastomosis in the cervical area, is similar in procedure but has the benefit of being applicable to malignancies of the upper, middle, and lower thoracic esophagus.

 

Transhiatal esophagectomy

The preoperative details for THE are identical to those for TTE, except that a single-lumen endotracheal tube is utilized instead of a double-lumen endotracheal tube. In the operating room, the neck is being readied.

The abdominal portion of the procedure is comparable to the TTE; however, esophageal dissection is conducted through the expanded esophageal gap without entering the right chest. In this manner, the esophagus is moved all the way to the thoracic inlet.

A 6-cm incision is then made on the left side of the neck. The carotid artery and internal jugular vein are retracted laterally, and the esophagus is found and isolated posterior to the airway. No mechanical retractors are employed to retract the trachea to avoid harm to the left recurrent laryngeal nerve.

After the proximal stomach and thoracic esophagus have been resected, the remaining stomach is pushed up through the posterior mediastinum until it meets the residual esophagus at the cervical level. The anastomosis is then hand-sewn, and a tiny drain is put in the neck beside the anastomosis. The wounds in the abdomen and neck have been closed.

 

Survival rate of esophageal cancer

Survival rate of esophageal cancer

Because most patients come with advanced illness, the prognosis of esophageal cancer is often poor. The illness has already advanced by the time the initial symptoms (such as trouble swallowing) occur. In the United States, the overall five-year survival rate (5YSR) is roughly 15%, with the majority of patients dying within the first year after diagnosis. According to the most recent survival data for England and Wales (patients diagnosed in 2007), just one out of every 10 persons survives esophageal cancer for at least ten years.

Individualized prognosis is heavily influenced by stage. Those with cancer that is fully limited to the esophageal mucosa have a 5YSR of around 80%, but submucosal involvement reduces this to less than 50%. Extending into the muscularis propria (muscle layer of the esophagus) predicts a 20% 5YSR, whereas extending into tissues next to the esophagus predicts a 7% 5YSR. Patients with distant metastases (who are ineligible for curative surgery) had a 5YSR of less than 3%.

 

Conclusion 

The overall incidence of esophageal squamous cell carcinoma is decreasing, whereas the incidence of adenocarcinomas is quickly increasing, most likely due to lifestyle changes. Selected individuals may be offered curative surgery or endoscopic resection. The conventional treatment for locally advanced resectable esophageal cancer is tri-modality therapy (chemoradiation followed by surgery).

Although adjuvant therapy following neoadjuvant therapy is not standard of care, it is frequently administered to high-risk patients. In non-surgical candidates, definitive chemoradiation therapy can be a viable therapeutic option, particularly for individuals with esophageal squamous cell carcinoma.

Squamous cell carcinoma and adenocarcinoma account for more than 95 percent of esophageal malignancies, with a poor prognosis and a high death rate. Nonindustrialized nations have a higher prevalence of squamous cell carcinoma, and key risk factors include smoking, alcohol consumption, and achalasia.

 

In industrialized countries, the most common kind of esophageal cancer is adenocarcinoma, and key risk factors include chronic gastroesophageal reflux disease, obesity, and smoking. Although esophageal cancer is generally asymptomatic in the early stages, dysphagia alone or in combination with unintended weight loss is the most prevalent presenting symptom. If any symptoms are present, physicians should have a low threshold for recommending endoscopy.

If cancer is found, combined positron emission tomography and computed tomography should be performed to do preliminary staging. Endoscopic ultrasonography should be done to establish tumor depth and nodal involvement if no distant metastases are discovered.

Endoscopic mucosal resection can be used to treat localized cancers, whereas esophagectomy, neoadjuvant chemotherapy, chemoradiotherapy, or a combination of modalities can be used to treat regional tumors. Palliative care is used to treat nonresectable cancers or malignancies with distant metastases. There are no guidelines for esophageal cancer screening, and no specific preventative techniques have been validated.