Esophageal cancer

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. 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. 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). ==Causes==

The two main types (i.e. squamous-cell carcinoma and adenocarcinoma) have distinct sets of risk factors. Tobacco is a risk factor for both types. Squamous-cell carcinoma The two major risk factors for esophageal squamous-cell carcinoma are tobacco (smoking or chewing) and alcohol. Some data suggest that about half of all cases are due to tobacco and about one-third to alcohol, while over three-quarters of the cases in men are due to the combination of smoking and heavy drinking. and ingestion of caustic substances. Physical trauma may increase the risk. This may include the drinking of very hot drinks. This imbalance may be related to the characteristics and interactions of other known risk factors, including acid reflux and obesity. At a mechanistic level, in the esophagus there is a small HOXA13 expressing compartment that is more resistant to bile and acids as the normal squamous epithelium and that is prone to both intestinal differentiation as well as oncogenic transformation. Following GERD this HOXA13-expressing compartment outcompetes the normal squamous compartment, leading to the intestinal aspect of the esophagus and increased propensity to the development of esophageal cancer. Having symptomatic GERD or bile reflux makes Barrett's esophagus more likely, which in turn raises the risk of further changes that can ultimately lead to adenocarcinoma. The risk of developing adenocarcinoma in the presence of Barrett's esophagus is unclear, and may in the past have been overestimated. Abdominal obesity seems to be of particular relevance, given the closeness of its association with this type of cancer, as well as with both GERD and Barrett's esophagus. The biological explanation for a protective effect is unclear. Decreasing rates of H. pylori infection in Western populations over recent decades, which have been linked to less overcrowding in households, could be a factor in the concurrent increase in esophageal adenocarcinoma. • History of radiation therapy for other conditions in the chest is a risk factor for esophageal adenocarcinoma. • Achalasia (i.e. lack of the involuntary reflex in the esophagus after swallowing) appears to be a risk factor for both main types of esophageal cancer, at least in men, due to stagnation of trapped food and drink. • Plummer–Vinson syndrome (a rare disease that involves esophageal webs) is also a risk factor. The relationship is unclear. Possible relevance of HPV could be greater in places that have a particularly high incidence of this form of the disease, as in some Asian countries, including China. • There is an association between celiac disease and esophageal cancer. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancy. Moreover, in some cases the detection of celiac disease is due to the development of cancer, whose early symptoms are similar to some that may appear in celiac disease. ==Diagnosis==

Clinical evaluation Although an occlusive tumor may be suspected on a barium swallow or barium meal, the diagnosis is best made with an examination using an endoscope. This involves the passing of a flexible tube with a light and camera down the esophagus and examining the wall, and is called an esophagogastroduodenoscopy. Biopsies taken of suspicious lesions are then examined histologically for signs of malignancy. Additional testing is needed to assess how much the cancer has spread (see , below). Computed tomography (CT) of the chest, abdomen and pelvis can evaluate whether the cancer has spread to adjacent tissues or distant organs (especially liver and lymph nodes). The sensitivity of a CT scan is limited by its ability to detect masses (e.g. enlarged lymph nodes or involved organs) generally larger than 1 cm. Positron emission tomography is also used to estimate the extent of the disease and is regarded as more precise than CT alone. PET/MR as a novel modality has shown promising results in preoperative staging with fair feasibility and good correlation in comparison to PET/CT. It can enhance tissue differentiation with lowering the radiation dose to the patient. Esophageal endoscopic ultrasound can provide staging information regarding the level of tumor invasion, and possible spread to regional lymph nodes. The location of the tumor is generally measured by the distance from the teeth. The esophagus (25 cm or 10 in long) is commonly divided into three parts for purposes of determining the location. Adenocarcinomas tend to occur nearer the stomach and squamous cell carcinomas nearer the throat, but either may arise anywhere in the esophagus. File:Barretts esophagus.jpg|Endoscopic image of Barrett esophagus – a frequent precursor of esophageal adenocarcinoma File:Mid esophageal mass.jpg|Endoscopy and radial endoscopic ultrasound images of a submucosal tumor in the central portion of the esophagus File:Tumor Esophagus.JPG|Contrast CT scan showing an esophageal tumor (axial view) File:Tumor Esophagus2.JPG|Contrast CT scan showing an esophageal tumor (coronal view) File:EsoCaSagMark.png|Esophageal cancer File:Esophageal adenocarcinoma - intermed mag.jpg|Micrograph showing histopathological appearance of an esophageal adenocarcinoma (dark blue – upper-left of image) and normal squamous epithelium (upper-right of image) at H&E staining Types Esophageal cancers are typically carcinomas that arise from the epithelium, or surface lining, of the esophagus. Most esophageal cancers fall into one of two classes: esophageal squamous-cell carcinomas (ESCC), which are similar to head and neck cancer in their appearance and association with tobacco and alcohol consumption—and esophageal adenocarcinomas (EAC), which are often associated with a history of GERD and Barrett's esophagus. A rule of thumb is that a cancer in the upper two-thirds is likely to be ESCC and one in the lower one-third EAC. Rare histologic types of esophageal cancer include different variants of squamous-cell carcinoma, and non-epithelial tumors, such as leiomyosarcoma, melanoma, rhabdomyosarcoma and lymphoma, among others. Staging Staging is based on the TNM staging system, which classifies the amount of tumor invasion (T), involvement of lymph nodes (N), and distant metastasis (M).). File:Diagram showing T1,T2 and T3 stages of oesophageal cancer CRUK 277.svg|T1, T2, and T3 stages of esophageal cancer File:Diagram showing stage T4 oesophagus cancer CRUK 271.svg|Stage T4 esophageal cancer File:Diagram showing oesophageal cancer in the lymph nodes (N staging) CRUK 174.svg|Esophageal cancer with spread to lymph nodes ==Prevention==

Prevention includes stopping smoking or chewing tobacco. According to a 2022 umbrella review, calcium intake could be associated with lower risk. According to the National Cancer Institute, "diets high in cruciferous (cabbage, broccoli/broccolini, cauliflower, Brussels sprouts) and green and yellow vegetables and fruits are associated with a decreased risk of esophageal cancer." Dietary fiber is thought to be protective, especially against esophageal adenocarcinoma. There is no evidence that vitamin supplements change the risk. and may receive regular endoscopic screening for the early signs of cancer. Because the benefit of screening for adenocarcinoma in people without symptoms is unclear, ==Management==

Treatment is best managed by a multidisciplinary team covering the various specialties involved. Adequate nutrition must be assured, and appropriate dental care is essential. Factors that influence treatment decisions include the stage and cellular type of cancer (EAC, ESCC, and other types), along with the person's general condition and any other diseases that are present. Otherwise, curative surgery of early-stage lesions may entail removal of all or part of the esophagus (esophagectomy), although this is a difficult operation with a relatively high risk of mortality or post-operative difficulties. The benefits of surgery are less clear in early-stage ESCC than EAC. There are a number of surgical options, and the best choices for particular situations remain the subject of research and discussion. The likely quality of life after treatment is a relevant factor when considering surgery. Surgical outcomes are likely better in large centers where the procedures are frequently performed. Esophagectomy is the removal of a segment of the esophagus; as this shortens the length of the remaining esophagus, some other segment of the digestive tract is pulled up through the chest cavity and interposed. This is usually the stomach or part of the large intestine (colon) or jejunum. Reconnection of the stomach to a shortened esophagus is called an esophagogastric anastomosis. However, a meta-analysis in 2017 failed to demonstrate that anthracyclines such as epirubicin improved survival. Therefore in metastatic cancer, a two drug combination is now standard. Most recently with the addition of immune checkpoint inhibitors such as nivolumab or pembrolizumab which prolongs disease-free survival after neoadjuvant chemoradiotherapy and surgery in patients with residual locally advanced esophageal squamous cell carcinoma, they are increasingly being incorporated into combined treatment strategies and are under investigation in both neoadjuvant and chemoradiation regimens. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible. Cisplatin and fluorouracil were most commonly used a, however the REAL-2 trial confirmed that oxaliplatin and capecitabine were non-inferior and potentially more convenient. Radiotherapy is given before, during, or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localized disease but contraindications to surgery, "radical radiotherapy" may be used with curative intent. Other approaches Forms of endoscopic therapy have been used for stage 0 and I disease: endoscopic mucosal resection (EMR) and mucosal ablation using radiofrequency ablation, photodynamic therapy, Nd-YAG laser, or argon plasma coagulation. Laser therapy is the use of high-intensity light to destroy tumor cells while affecting only the treated area. This is typically done if the cancer cannot be removed by surgery. The relief of a blockage can help with pain and difficulty swallowing. Photodynamic therapy, a type of laser therapy, involves the use of drugs that are absorbed by cancer cells; when exposed to a special light, the drugs become active and destroy the cancer cells. File:Diagram showing internal radiotherapy for cancer of the oesophagus CRUK 162.svg|Internal radiotherapy for esophageal cancer File:SEMS endo.jpg|Self-expandable metallic stents are sometimes used for palliative care Follow-up Patients are followed closely after a treatment regimen has been completed. Frequently, other treatments are used to improve symptoms and maximize nutrition. ==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%, and most people die 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. ==Epidemiology==

rate) in 2022 Esophageal cancer is the eighth most frequently diagnosed cancer worldwide, In general, ESCC is more common in the developing world, and EAC is more common in the developed world. It was the common type in 90% of the countries studied. 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. 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. The National Cancer Institute estimated that there were about 18,000 new cases and more than 15,000 deaths from esophageal cancer in 2013; the American Cancer Society estimated that during 2014, about 18,170 new esophageal cancer cases would be diagnosed, resulting in 15,450 deaths. Esophageal cancer incidence and mortality rates for African Americans continue to be higher than the rate for Causasians. However, incidence and mortality of esophageal cancer has significantly decreased among African Americans since the early 1980s, whereas with whites it has continued to increase. Between 1975 and 2004, incidence of the adenocarcinoma type increased among white American males by over 460% and among white American females by 335%. == Society and culture ==

Notable cases Humphrey Bogart, actor, died of esophageal cancer in 1957, aged 57. Billy Strayhorn, American jazz composer, pianist, lyricist, and arranger, who collaborated with bandleader and composer Duke Ellington, died of esophageal cancer in 1967 at age 51. John Thaw, actor, died of esophageal cancer in 2002, at the age of 60. Christopher Hitchens, author and journalist, died of esophageal cancer in 2011, aged 62. Morrissey in October 2015 stated he has the disease and has described his experience when he first heard he had it. Mako Iwamatsu, voice actor for Avatar: The Last Airbender as General Iroh and Samurai Jack as Aku, died of esophageal cancer in 2006, aged 72. Robert Kardashian, attorney and businessman, died of esophageal cancer in 2003, aged 59. Traci Braxton, singer and reality TV star, died of esophageal cancer in 2022, aged 50. Andrew Bonar Law resigned as Prime Minister of the United Kingdom in 1923 and died of throat cancer shortly after aged 65. Ed Sullivan, host of the prominent self-titled television program The Ed Sullivan Show, died of esophageal cancer in 1974 at the age of 73. Lynn Yamada Davis, chef YouTube star, died of esophageal cancer in 2024, aged 67. Richard Dawson, comic, actor, panelist on Match Game, host of Family Feud, and civil rights activist died of esophageal cancer at 79. Mike Rinder, former senior executive in the Church of Scientology and noted critic of the organization, died of esophageal cancer in 2025. ==Research directions==

The risk of esophageal squamous-cell carcinoma may be reduced in people using aspirin or related NSAIDs, but in the absence of randomized controlled trials the current evidence is inconclusive. with heterogeneity within the tumor micro-environment. == See also ==