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Esophageal Cancer

Disease Details

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Description: Esophageal cancer is a malignant tumor that forms in the tissues lining the esophagus, the muscular tube through which food passes from the throat to the stomach.
Type: Esophageal cancer is a type of malignancy that occurs in the esophagus, the tube that carries food from the throat to the stomach. It primarily comes in two forms: squamous cell carcinoma and adenocarcinoma. The type of genetic transmission for esophageal cancer is generally sporadic, meaning most cases are not inherited. However, some rare hereditary conditions, like Tylosis with esophageal cancer (TOC) and familial Barrett's esophagus, can increase the risk and involve genetic mutations. These conditions typically follow an autosomal dominant pattern of inheritance.
Signs And Symptoms: Prominent symptoms usually do not appear until the cancer has infiltrated over 60% of the circumference of the esophageal tube, by which time the tumor is already in an advanced stage. Onset of symptoms is usually caused by narrowing of the tube due to the physical presence of the tumor.The first and the most common symptom is usually difficulty in swallowing, which is often experienced first with solid foods and later with softer foods and liquids. Pain when swallowing is less usual at first. Weight loss is often an initial sign in cases of squamous-cell carcinoma, though not usually in cases of adenocarcinoma. Eventual weight loss due to reduced appetite and undernutrition is common. Pain behind the breastbone or in the region around the stomach often feels like heartburn. The pain can frequently be severe, worsening when food of any sort is swallowed. Another sign may be an unusually husky, raspy, or hoarse-sounding cough, a result of the tumor affecting the recurrent laryngeal nerve.
The presence of the tumor may disrupt the normal contractions of the esophagus when swallowing. This can lead to nausea and vomiting, regurgitation of food and coughing. There is also an increased risk of aspiration pneumonia due to food entering the airways through the abnormal connections (fistulas) that may develop between the esophagus and the trachea (windpipe). Early signs of this serious complication may be coughing on drinking or eating. The tumor surface may be fragile and bleed, causing vomiting of blood. Compression of local structures occurs in advanced disease, leading to such problems as upper airway obstruction and superior vena cava syndrome. Hypercalcemia (excess calcium in the blood) may occur.If the cancer has spread elsewhere, symptoms related to metastatic disease may appear. Common sites of spread include nearby lymph nodes, the liver, lungs and bone.Liver metastasis can cause jaundice and abdominal swelling (ascites). Lung metastasis can cause, among other symptoms, impaired breathing due to excess fluid around the lungs (pleural effusion), and dyspnea (the feelings often associated with impaired breathing).
Prognosis: In general, the prognosis of esophageal cancer is quite poor, because most patients present with advanced disease. By the time the first symptoms (such as difficulty swallowing) appear, the disease has already progressed. The overall five-year survival rate (5YSR) in the United States is around 15%, with most people dying within the first year of diagnosis. The latest survival data for England and Wales (patients diagnosed during 2007) show that only one in ten people survives esophageal cancer for at least ten years.Individualized prognosis depends largely on stage. Those with cancer restricted entirely to the esophageal mucosa have about an 80% 5YSR, but submucosal involvement brings this down to less than 50%. Extension into the muscularis propria (muscle layer of the esophagus) suggests a 20% 5YSR, and extension to the structures adjacent to the esophagus predict a 7% 5YSR. Patients with distant metastases (who are not candidates for curative surgery) have a less than 3% 5YSR.
Onset: Esophageal cancer typically has an insidious onset, meaning it develops gradually and may not cause early symptoms. When symptoms do appear, they can include difficulty swallowing (dysphagia), unintentional weight loss, chest pain, indigestion, and coughing. The disease is often diagnosed at a more advanced stage due to the lack of early warning signs.
Prevalence: Esophageal cancer is relatively rare, with variations in prevalence depending on the region. Globally, it accounts for about 1% of all cancers, but it is more common in certain areas, such as Eastern Asia and parts of Africa. The prevalence is lower in Western countries. The two main types are squamous cell carcinoma and adenocarcinoma, each with different risk factors and geographical distribution.
Epidemiology: Esophageal cancer is the eighth-most frequently-diagnosed cancer worldwide, and because of its poor prognosis, it is the sixth most-common cause of cancer-related deaths. It caused about 400,000 deaths in 2012, accounting for about 5% of all cancer deaths (about 456,000 new cases were diagnosed, representing about 3% of all cancers).ESCC (esophageal squamous-cell carcinoma) comprises 60–70% of all cases of esophageal cancer worldwide, while EAC (esophageal adenocarcinoma) accounts for a further 20–30% (melanomas, leiomyosarcomas, carcinoids and lymphomas are less common types). The incidence of the two main types of esophageal cancer varies greatly between different geographical areas. In general, ESCC is more common in the developing world, and EAC is more common in the developed world.The worldwide incidence rate of ESCC in 2012 was 5.2 new cases per 100,000 person-years, with a male predominance (7.7 per 100,000 in men vs. 2.8 in women). It was the common type in 90% of the countries studied. ESCC is particularly frequent in the so-called "Asian esophageal cancer belt", an area that passes through northern China, southern Russia, north-eastern Iran, northern Afghanistan and eastern Turkey. In 2012, about 80% of ESCC cases worldwide occurred in central and south-eastern Asia, and over half (53%) of all cases were in China. The countries with the highest estimated national incidence rates were (in Asia) Mongolia and Turkmenistan and (in Africa) Malawi, Kenya and Uganda. The problem of esophageal cancer has long been recognized in the eastern and southern parts of Sub-Saharan Africa, where ESCC appears to predominate.In Western countries, EAC has become the dominant form of the disease, following an increase in incidence over recent decades (in contrast to the incidence of ESCC, which has remained largely stable). In 2012, the global incidence rate for EAC was 0.7 per 100,000 with a strong male predominance (1.1 per 100,000 in men vs. 0.3 in women). Areas with particularly high incidence rates include northern and western Europe, North America and Oceania. The countries with highest recorded rates were the UK, Netherlands, Ireland, Iceland and New Zealand.
Intractability: Esophageal cancer can be challenging to treat, particularly if diagnosed at an advanced stage. Early-stage esophageal cancer may be treated with surgery, radiation, and chemotherapy, potentially leading to better outcomes. However, advanced esophageal cancer often spreads to other parts of the body and can be more difficult to manage. Treatment options for advanced stages focus on palliative care to manage symptoms and improve quality of life but are generally less likely to result in a cure.
Disease Severity: Esophageal cancer is a serious condition with a variable prognosis depending on several factors, including the stage at diagnosis, location of the tumor, patient’s overall health, and response to treatment. Generally, it is associated with a high mortality rate due to late-stage diagnosis and significant complications. Early-stage esophageal cancer has a better prognosis and may be treated effectively with surgery, chemotherapy, and/or radiation therapy. Advanced stages often involve more complex treatment and lower survival rates.
Healthcare Professionals: Disease Ontology ID - DOID:5041
Pathophysiology: Esophageal cancer primarily starts in the cells lining the esophagus and can be categorized into two main types: squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma arises from the flat cells lining the esophagus, frequently in the upper and middle parts. Adenocarcinoma originates in glandular cells, typically starting in the lower part near the stomach.

The pathophysiology involves chronic irritation of the esophageal mucosa leading to cellular mutations. Risk factors include smoking, heavy alcohol consumption, gastroesophageal reflux disease (GERD), Barrett's esophagus (a condition where the normal tissue lining the esophagus changes due to acid reflux), obesity, dietary factors, and exposure to certain carcinogens.

Over time, these mutations result in the uncontrolled growth of abnormal cells. These cells can penetrate deeper layers of the esophageal wall, invade nearby structures, and spread (metastasize) to other parts of the body through the lymphatic system and bloodstream. The progression from dysplasia (abnormal cells) to carcinoma (cancer) marks the transition from a potentially reversible state to malignant disease.
Carrier Status: Carrier status does not apply to esophageal cancer, as it is not an inherited condition caused by a single gene mutation that can be passed from one generation to another. Instead, esophageal cancer typically results from a combination of genetic, environmental, and lifestyle factors.
Mechanism: Esophageal cancer occurs when malignant cells form in the tissues of the esophagus. The primary mechanism involves the uncontrolled growth and division of these cells, typically leading to the formation of a tumor. There are two main types of esophageal cancer: squamous cell carcinoma, which occurs in the flat cells lining the esophagus, and adenocarcinoma, which originates in glandular cells usually found in the lower esophagus.

Molecular mechanisms of esophageal cancer include:

1. **Genetic Mutations**: Mutations in genes like TP53, which codes for the tumor suppressor protein p53, can lead to loss of cell cycle regulation and uncontrolled cell proliferation.

2. **Oncogene Activation**: Activation of oncogenes such as HER2 and EGFR can lead to increased cell growth and survival signals.

3. **Tumor Suppressor Genes Inactivation**: Loss or inactivation of tumor suppressor genes such as CDKN2A (p16) can contribute to malignant progression.

4. **Epigenetic Changes**: DNA methylation and histone modifications can alter gene expression without changing the DNA sequence, affecting genes involved in cell growth, apoptosis, and DNA repair.

5. **Inflammation and Oxidative Stress**: Chronic inflammation, often due to factors like gastroesophageal reflux disease (GERD) or exposure to carcinogens like tobacco and alcohol, can cause DNA damage and promote tumorigenesis.

6. **Signal Transduction Pathways**: Aberrations in signaling pathways such as the PI3K/AKT, MAPK, and Wnt pathways can lead to increased proliferation, survival, and metastasis of cancer cells.

Understanding these molecular mechanisms is crucial for developing targeted therapies and improving treatment outcomes for patients with esophageal cancer.
Treatment: Treatment for esophageal cancer typically depends on the stage and location of the cancer, as well as the patient's overall health. Common treatment options include:

1. **Surgery:** To remove the tumor and part of the esophagus, sometimes including nearby lymph nodes.
2. **Radiation Therapy:** Using high-energy rays to kill cancer cells or shrink tumors.
3. **Chemotherapy:** Using drugs to kill cancer cells or stop their growth.
4. **Targeted Therapy:** Using drugs that target specific molecules involved in cancer cell growth.
5. **Immunotherapy:** Using the body's immune system to fight cancer.
6. **Endoscopic Treatments:** Such as endoscopic mucosal resection or ablation for early-stage cancers.
7. **Palliative Care:** To relieve symptoms and improve quality of life when the cancer is advanced.
Compassionate Use Treatment: Compassionate use treatment for esophageal cancer typically involves accessing experimental drugs or treatments that are not yet approved for general use. This can include new chemotherapeutic agents, targeted therapies, or immunotherapies that are still in clinical trials.

Off-label treatments for esophageal cancer might involve using FDA-approved drugs for other types of cancers or conditions in a manner that they are not specifically approved for in the context of esophageal cancer. Examples could include certain targeted therapies or immunotherapies like pembrolizumab (Keytruda) or nivolumab (Opdivo), which are approved for other cancers but might be used off-label based on emerging evidence.

Experimental treatments can refer to ongoing clinical trials testing new drugs, combinations of existing drugs, advanced surgical techniques, or novel radiation therapy protocols. These treatments are part of research studies and are aimed at finding more effective ways to treat esophageal cancer.

Patients interested in these options should consult their oncologist to explore available clinical trials and discuss the potential risks and benefits of experimental or off-label treatments.
Lifestyle Recommendations: For esophageal cancer, lifestyle recommendations often include:

1. **Quit Smoking and Limit Alcohol**: Tobacco and heavy alcohol use are significant risk factors.
2. **Healthy Diet**: Consume a diet rich in fruits, vegetables, and whole grains. Avoid highly processed foods and those with high fat content.
3. **Maintain a Healthy Weight**: Obesity is a risk factor, so maintaining a healthy weight through diet and exercise is advised.
4. **Safe Eating Practices**: Avoid consuming very hot liquids and foods, which can damage the esophageal lining.
5. **Manage Acid Reflux**: If you have gastroesophageal reflux disease (GERD), manage it effectively with diet changes and medication if necessary.
6. **Regular Check-Ups**: Especially if there are risk factors present like Barrett's esophagus or a family history of esophageal cancer.

These recommendations can help reduce the risk of developing esophageal cancer and improve overall health.
Medication: For esophageal cancer, the treatment plan often includes various medications as part of chemotherapy, targeted therapy, and immunotherapy. Specific drugs used can vary based on the individual's condition and the cancer's stage. Common chemotherapy drugs include cisplatin, carboplatin, and 5-fluorouracil (5-FU). Targeted therapies might involve drugs like trastuzumab for HER2-positive cancer. Immunotherapy options include pembrolizumab or nivolumab. Always consult with an oncologist to determine the appropriate medication regimen tailored to the patient's specific situation.
Repurposable Drugs: For esophageal cancer, there are several drugs that are being explored for repurposing. Some of these include:

1. **Metformin**: Originally used for type 2 diabetes, it has shown potential in inhibiting cancer cell growth.
2. **Aspirin**: Known for its anti-inflammatory properties, it has been studied for its ability to reduce cancer risk and progression.
3. **Statins**: Used to lower cholesterol, these drugs might have a role in decreasing cancer cell proliferation and improving survival rates.

Research is ongoing to verify the effectiveness and safety of these drugs in treating esophageal cancer.
Metabolites: Esophageal cancer can be associated with specific metabolites that may serve as biomarkers for the disease. These metabolites include:

1. **Amino acids** - Altered levels of certain amino acids, such as glutamine and glutamate, can be observed.
2. **Lipids** - Changes in lipid profiles, such as increased levels of phosphatidylcholines and decreased levels of sphingomyelins, may occur.
3. **Glucose and related metabolites** - Alterations in glucose metabolism, including increased lactate production due to the Warburg effect, can be seen.
4. **Nucleotides** - Variations in nucleotide levels, such as uridine and adenosine derivatives, may be significant.

These metabolites can be measured in various biological samples, including blood and tissue, providing potential diagnostic and prognostic information for esophageal cancer.
Nutraceuticals: Nutraceuticals, which are food-derived products believed to provide health benefits, have been studied for their potential roles in the prevention and treatment of esophageal cancer. While evidence for their effectiveness is still emerging, some nutraceuticals showing promise include:

1. **Curcumin**: Found in turmeric, curcumin has anti-inflammatory and antioxidant properties that may inhibit cancer cell growth.
2. **Green Tea Polyphenols**: These contain catechins, particularly epigallocatechin gallate (EGCG), which may reduce tumor growth and metastasis.
3. **Resveratrol**: Present in grapes and red wine, resveratrol has been indicated to have anticancer properties, potentially through mechanisms related to apoptosis and cell cycle regulation.
4. **Omega-3 Fatty Acids**: Found in fish oil, these may have anti-inflammatory effects that could contribute to cancer prevention.
5. **Vitamins and Minerals**: Vitamins such as A, C, and E and minerals like selenium may help in preventing esophageal cancer due to their antioxidant properties.

It is important to note that while these nutraceuticals show potential, more clinical trials and research are needed to confirm their efficacy and safety in the treatment or prevention of esophageal cancer. Always consult with a healthcare provider before starting any new supplement regimen.
Peptides: In the context of esophageal cancer, peptides can serve several roles, including being used as therapeutic agents or in vaccine development to stimulate an immune response against tumor cells. Nano (nanotechnology) approaches are being explored for targeted drug delivery, imaging, and diagnostic purposes. Nanoparticles can enhance the delivery of chemotherapeutic agents directly to the tumor site, potentially reducing side effects and improving treatment efficacy.